1
00:00:05,357 --> 00:00:06,891
 SO WELCOME BACK TO DAY 2 OF

2
00:00:06,891 --> 00:00:10,295
 THE PAIN IN ANIMALS WORKSHOP

3
00:00:10,295 --> 00:00:11,696
 MEETING.

4
00:00:11,696 --> 00:00:15,400
 TODAY IS DEDICATED TO

5
00:00:15,400 --> 00:00:22,874
 SUGGESTIONS ON MERVE SURING 

6
00:00:22,874 --> 00:00:24,409
 OUTCOMES IN CLINICAL

7
00:00:24,409 --> 00:00:25,043
 APPROACHES.

8
00:00:25,043 --> 00:00:29,214
 THE FIRST UP IS JENNIFER

9
00:00:29,214 --> 00:00:30,682
 GEWANDTER FROM THE UNIVERSITY

10
00:00:30,682 --> 00:00:32,617
 OF ROCHESTER AND WILL TALK TO

11
00:00:32,617 --> 00:00:36,888
 US ABOUT APPROACHES TO 

12
00:00:36,888 --> 00:00:38,022
 DEFINING CLINICALLY MEANINGFUL

13
00:00:38,022 --> 00:00:48,500
 CHANGE IN TRIAL OUTCOME

14
00:00:58,943 --> 00:00:59,577
 MEASURES.

15
00:00:59,577 --> 00:01:01,179
 >> OKAY, THANKING THE

16
00:01:01,179 --> 00:01:02,580
 ORGANIZERS FOR INVITING ME TO

17
00:01:02,580 --> 00:01:04,315
 SPEAK TODAY AND THANK YOU TO

18
00:01:04,315 --> 00:01:05,784
 YOU ALL FOR COMING TO THE

19
00:01:05,784 --> 00:01:06,785
 EARLY-MORNING SESSION.

20
00:01:06,785 --> 00:01:09,120
 SO A LITTLE OVERVIEW OF MY

21
00:01:09,120 --> 00:01:10,255
 TALK TODAY.

22
00:01:10,255 --> 00:01:12,023
 AS MENTIONED, I WILL BE

23
00:01:12,023 --> 00:01:14,526
 TALKING ABOUT HOW WE IDENTIFY

24
00:01:14,526 --> 00:01:16,060
 PAIN OUTCOMES IN HUMANS AND I

25
00:01:16,060 --> 00:01:19,364
 WILL ALSO TOUCH A LITTLE ON A

26
00:01:19,364 --> 00:01:20,865
 COUPLE OTHER TOPICS INCLUDING

27
00:01:20,865 --> 00:01:23,067
 WHY WE WANT TO DO THIS AND

28
00:01:23,067 --> 00:01:25,203
 LIMITATIONS ON DOING THIS,

29
00:01:25,203 --> 00:01:28,773
 WANT TO MENTION BRIEFLY

30
00:01:28,773 --> 00:01:32,310
 UNINTENDED CONSEQUENCES OF

31
00:01:32,310 --> 00:01:34,379
 APPLYING THESE CUTOFFS AND

32
00:01:34,379 --> 00:01:44,956
 APPLICATION OF THESE IDEAS TO

33
00:01:56,468 --> 00:01:56,701
 ANIMALS.

34
00:01:56,701 --> 00:01:57,235
 OKAY, SORRY.

35
00:01:57,235 --> 00:02:04,909
 SO FIRST THE APPROACHES, OF

36
00:02:04,909 --> 00:02:08,112
 MEANINGFUL DIFFERENCE.

37
00:02:08,112 --> 00:02:18,223
 THE FIRST THING I WILL TALK ON

38
00:02:18,223 --> 00:02:21,092
 IS THE PUBLISHED RESOURCE OF

39
00:02:21,092 --> 00:02:22,360
 INCORPORATING CLINICAL OUTCOME

40
00:02:22,360 --> 00:02:24,729
 ASSESSMENTS IN ENDPOINTS FOR

41
00:02:24,729 --> 00:02:25,930
 REGULATORY DECISION-MAKING.

42
00:02:25,930 --> 00:02:28,132
 AND THERE ARE TWO CUTOFFS,

43
00:02:28,132 --> 00:02:31,336
 THIS IS CALLED THE ANCHOR

44
00:02:31,336 --> 00:02:32,937
 BASED METHOD.

45
00:02:32,937 --> 00:02:35,240
 THERE ARE TWO OUTCOMES WE USE

46
00:02:35,240 --> 00:02:37,242
 PRIMARILY FOR TRIALS AND

47
00:02:37,242 --> 00:02:40,044
 COMPARE IT TO ANCHOR BASED

48
00:02:40,044 --> 00:02:44,048
 OUTCOMES THAT ARE PLAINLY

49
00:02:44,048 --> 00:02:45,850
 UNDERSTOOD, EASIER TO

50
00:02:45,850 --> 00:02:48,987
 UNDERSTAND FOR THE OUTCOME

51
00:02:48,987 --> 00:02:57,161
 ITSELF AND IT SHOULD BE A

52
00:02:57,161 --> 00:02:59,130
 TARGETED OUTCOME.

53
00:02:59,130 --> 00:03:01,933
 SO THE PATIENT GLOBAL

54
00:03:01,933 --> 00:03:03,301
 IMPRESSION OF CHANGE, THEY

55
00:03:03,301 --> 00:03:04,536
 WOULD ASK PEOPLE AT THE

56
00:03:04,536 --> 00:03:08,540
 BEGINNING OF THE STUDY HOW

57
00:03:08,540 --> 00:03:10,008
 WELL YOUR OVERALL BEING OR

58
00:03:10,008 --> 00:03:13,444
 PAIN HAS CHANGED AND WE HAVE

59
00:03:13,444 --> 00:03:15,713
 THESE ANCHORS INCLUDING VERY

60
00:03:15,713 --> 00:03:19,150
 MUCH IMPROVED, MUCH IMPROVED,

61
00:03:19,150 --> 00:03:20,485
 MINIMALLY IMPROVED, NO CHANGE

62
00:03:20,485 --> 00:03:22,453
 OR OF COURSE IT COULD HAVE GOT

63
00:03:22,453 --> 00:03:24,188
 TEN WORSE AS WELL.

64
00:03:24,188 --> 00:03:26,791
 THEN THERE IS THE PATIENT

65
00:03:26,791 --> 00:03:28,626
 GLOBAL IMPRESSION OF SEVERITY

66
00:03:28,626 --> 00:03:31,162
 WHICH HAS ANCHORS FOR NOT

67
00:03:31,162 --> 00:03:32,730
 PAINFUL, MILDLY PAINFUL,

68
00:03:32,730 --> 00:03:34,265
 MODERATELY PAINFUL, VERY

69
00:03:34,265 --> 00:03:36,935
 PAINFUL OR EXTREMELY PAINFUL.

70
00:03:36,935 --> 00:03:38,703
 SO FOR OUTCOMES, WE HAVE THESE

71
00:03:38,703 --> 00:03:41,940
 ANCHORS TO MOVE PATIENTS FROM

72
00:03:41,940 --> 00:03:44,309
 ONE BUCKET TO ANOTHER AND OF

73
00:03:44,309 --> 00:03:45,944
 COURSE IT CAN CHANGE BUT THIS

74
00:03:45,944 --> 00:03:48,746
 IS HOW IT WORKS IN GENERAL.

75
00:03:48,746 --> 00:03:53,451
 SO THIS EXAMPLE, A PAPER BY

76
00:03:53,451 --> 00:03:57,555
 Dr. JOHN FARER, THEY TOOK

77
00:03:57,555 --> 00:04:00,058
 MULTIPLE PAIN STUDIES OF

78
00:04:00,058 --> 00:04:07,398
 PEOPLE AND PLOTTED THE PERCENT

79
00:04:07,398 --> 00:04:12,971
 CHANGE IN THE NOS SCORE VERSUS

80
00:04:12,971 --> 00:04:14,372
 THE MUCH IMPROVED, AND AS YOU

81
00:04:14,372 --> 00:04:16,674
 CAN SEE THE PAIN IS HIGHLY

82
00:04:16,674 --> 00:04:22,313
 COORDINATED WITH THESE

83
00:04:22,313 --> 00:04:24,649
 ANCHORS.

84
00:04:24,649 --> 00:04:25,216
 NOTE/FARRAR.

85
00:04:25,216 --> 00:04:26,117
 >> SO I WILL DRAW YOUR

86
00:04:26,117 --> 00:04:28,286
 ATTENTION TO THE BOTTOM HERE,

87
00:04:28,286 --> 00:04:29,687
 THIS IS A PERCENT DATA.

88
00:04:29,687 --> 00:04:32,190
 AND YOU CAN SEE WHEN USING

89
00:04:32,190 --> 00:04:36,294
 DATA AND DID R OC ANALYSIS TO

90
00:04:36,294 --> 00:04:39,163
 IDENTIFY THE CUTOFF THAT WOULD

91
00:04:39,163 --> 00:04:43,101
 GIVE THE BEST SPECIFICITY OF

92
00:04:43,101 --> 00:04:45,069
 SOMEONE WHO IS VERY MUCH

93
00:04:45,069 --> 00:04:47,905
 IMPROVED MORE THAN ANYTHING

94
00:04:47,905 --> 00:04:50,308
 ELSE, THEIR CUTOFF WAS 46.51

95
00:04:50,308 --> 00:04:54,112
 SO IF YOU USE THE IMPROVEMENT

96
00:04:54,112 --> 00:04:56,414
 OF 46.51 YOU COULD PRETTY MUCH

97
00:04:56,414 --> 00:04:59,684
 BUCKET PEOPLE ON WHETHER THEY

98
00:04:59,684 --> 00:05:00,718
 WERE MUCH IMPROVED.

99
00:05:00,718 --> 00:05:05,256
 AND FOR VERY MUCH IMPROVED

100
00:05:05,256 --> 00:05:12,530
 THAN ANYONE ELSE, THE CUTOFF

101
00:05:12,530 --> 00:05:13,264
 IS 46.51.

102
00:05:13,264 --> 00:05:14,732
 THIS IS THE ANALYSIS THAT

103
00:05:14,732 --> 00:05:16,267
 WOULD SUPPORT THOSE

104
00:05:16,267 --> 00:05:18,269
 CONCLUSIONS AND THESE TYPES OF

105
00:05:18,269 --> 00:05:19,737
 STUDY HAVE BEEN REPEATED

106
00:05:19,737 --> 00:05:21,305
 MULTIPLE TIMES WITH PRETTY

107
00:05:21,305 --> 00:05:23,775
 SIMILAR RESULTS BUT THIS IS

108
00:05:23,775 --> 00:05:29,213
 THE METHOD WHICH WE USE O

109
00:05:29,213 --> 00:05:31,916
 IDENTIFY TO -- TO IDENTIFY

110
00:05:31,916 --> 00:05:33,618
 WHAT THE CUTOFFS SHOULD BE.

111
00:05:33,618 --> 00:05:36,254
 THE OTHER WAY WE DO THIS IS TO

112
00:05:36,254 --> 00:05:39,157
 JUST ASK PEOPLE SO I WILL GO

113
00:05:39,157 --> 00:05:41,826
 BACK TO FARRAR AND WHAT HIS

114
00:05:41,826 --> 00:05:42,927
 GROUP IS CURRENTLY WORKING ON

115
00:05:42,927 --> 00:05:44,796
 AND THIS IS AN ACUTE PAIN

116
00:05:44,796 --> 00:05:47,131
 SETTING AND I WILL GIVE A

117
00:05:47,131 --> 00:05:48,499
 GENERAL EXAMPLE OF HOW THEY

118
00:05:48,499 --> 00:05:50,802
 USE THE STOP WATCH METHOD.

119
00:05:50,802 --> 00:05:52,603
 IN THIS CASE, FOR EXAMPLE, YOU

120
00:05:52,603 --> 00:05:54,205
 CAN INCLUDE PATIENTS WHO ARE

121
00:05:54,205 --> 00:05:57,642
 GETTING A THIRD MOLAR

122
00:05:57,642 --> 00:05:59,477
 EXTRACTION AND YOU ASK WHAT IS

123
00:05:59,477 --> 00:06:02,113
 YOUR PAIN RIGHT NOW AND THE

124
00:06:02,113 --> 00:06:04,649
 SCALE IS HERE, AND THEY SAY A

125
00:06:04,649 --> 00:06:07,852
 7 AND YOU SAY AS SOON AS YOU

126
00:06:07,852 --> 00:06:11,155
 CAN FEEL ANY PAIN YOU NOTICE,

127
00:06:11,155 --> 00:06:14,225
 HIT YOUR STOP WATCH AND THEY

128
00:06:14,225 --> 00:06:19,397
 DO THAT AND IT IS A 7.

129
00:06:19,397 --> 00:06:22,500
 SO THAT IS A 40 PERCENT

130
00:06:22,500 --> 00:06:23,334
 IMPROVEMENT.

131
00:06:23,334 --> 00:06:27,238
 AND THEN THEY ASK IT AGAIN AND

132
00:06:27,238 --> 00:06:29,340
 YOU CAN EASE THESE OUTCOMES TO

133
00:06:29,340 --> 00:06:31,042
 SEE WHAT PERCENT IMPROVEMENT

134
00:06:31,042 --> 00:06:32,410
 WOULD BE MINIMALLY IMPORTANT

135
00:06:32,410 --> 00:06:36,347
 TO PEOPLE OR CLINICALLY

136
00:06:36,347 --> 00:06:38,382
 MEANINGFUL TO PEOPLE AND YOU

137
00:06:38,382 --> 00:06:41,652
 CAN GET A SIMILAR R OC

138
00:06:41,652 --> 00:06:42,587
 ANALYSIS TO CONSIDER WHAT

139
00:06:42,587 --> 00:06:45,790
 WOULD BE THE CUTOFF IN AN

140
00:06:45,790 --> 00:06:47,825
 ANALYSIS FOR ACUTE PAIN

141
00:06:47,825 --> 00:06:48,159
 SETTING.

142
00:06:48,159 --> 00:06:49,594
 AND YOU COULD DO SOMETHING

143
00:06:49,594 --> 00:06:52,296
 SIMILAR IN THE CHRONIC PAIN

144
00:06:52,296 --> 00:06:56,400
 SETTING WHERE YOU COULD SAY 

145
00:06:56,400 --> 00:07:00,037
 SINCE A CHILD, DO YOU HAVE

146
00:07:00,037 --> 00:07:00,938
 MEANINGFUL PAIN RELIEF.

147
00:07:00,938 --> 00:07:04,809
 AND BECAUSE THIS IS ANCHOR

148
00:07:04,809 --> 00:07:08,379
 BASED, YOU LOSE SOME

149
00:07:08,379 --> 00:07:11,816
 PARTICIPATION WITH THE

150
00:07:11,816 --> 00:07:12,383
 ANCHORS.

151
00:07:12,383 --> 00:07:13,851
 ANOTHER WAY TO DETERMINE

152
00:07:13,851 --> 00:07:16,287
 WHETHER IT IS MORE HELPFUL IS

153
00:07:16,287 --> 00:07:17,722
 THE PATIENT INTERVIEW METHOD

154
00:07:17,722 --> 00:07:19,490
 AND THIS IS JUST ASKING THEM

155
00:07:19,490 --> 00:07:21,425
 WHAT THEY CONSIDER MEANINGFUL

156
00:07:21,425 --> 00:07:21,793
 AND WHY.

157
00:07:21,793 --> 00:07:23,327
 THIS IS VERY IMPORTANT BECAUSE

158
00:07:23,327 --> 00:07:25,029
 YOU CAN GET RICH DATA AND THAT

159
00:07:25,029 --> 00:07:27,064
 IS GOOD ON THE LEVEL.

160
00:07:27,064 --> 00:07:29,167
 THE LIMITATIONS IS YOU ARE

161
00:07:29,167 --> 00:07:31,302
 ASKING PEOPLE ABOUT

162
00:07:31,302 --> 00:07:32,036
 HYPOTHETICAL SITUATIONS SO YOU

163
00:07:32,036 --> 00:07:33,271
 WOULD SAY SOMETHING LIKE LAST

164
00:07:33,271 --> 00:07:36,107
 TIME YOU TOOK YOUR PAIN

165
00:07:36,107 --> 00:07:38,242
 MEDICINE, DID IT IMPROVE YOUR

166
00:07:38,242 --> 00:07:42,880
 PAIN, WAS IT MEANINGFUL TO

167
00:07:42,880 --> 00:07:46,184
 YOU, BUT SINCE YOU ARE TALKING

168
00:07:46,184 --> 00:07:51,189
 ABOUT THE PAST, IT COULD BE

169
00:07:51,189 --> 00:07:51,656
 NONANALOGOUS.

170
00:07:51,656 --> 00:07:55,860
 THESE ARE SMALL SAMPLE SIZES

171
00:07:55,860 --> 00:07:56,661
 SO GENERALIZABILITY IS AN

172
00:07:56,661 --> 00:08:00,665
 ISSUE AND IT COULD BE

173
00:08:00,665 --> 00:08:02,466
 DIFFICULT TO DIRECTLY

174
00:08:02,466 --> 00:08:04,335
 TRANSLATE THE RESULTS YOU GET.

175
00:08:04,335 --> 00:08:07,772
 BUT THESE COULD BE USED IN A

176
00:08:07,772 --> 00:08:09,340
 QUANTITATIVE SURVEY THAT COULD

177
00:08:09,340 --> 00:08:12,210
 BE USED TO GET MORE

178
00:08:12,210 --> 00:08:13,377
 QUANTITATIVE NUMBERS.

179
00:08:13,377 --> 00:08:16,814
 SO THOSE ARE THE TWO METHODS

180
00:08:16,814 --> 00:08:20,151
 WE USE TO OBTAIN MININGFUL

181
00:08:20,151 --> 00:08:20,484
 CUTOFFS.

182
00:08:20,484 --> 00:08:22,520
 SO NOW I WILL SHIFT AND TALK

183
00:08:22,520 --> 00:08:24,522
 ABOUT WHY WE WANT TO DO THIS

184
00:08:24,522 --> 00:08:26,591
 IN HUMANS AND FOR THOSE OF YOU

185
00:08:26,591 --> 00:08:28,025
 WHO DON'T THINK ABOUT THIS A

186
00:08:28,025 --> 00:08:29,694
 LOT, WE WANT TO DO THIS

187
00:08:29,694 --> 00:08:32,897
 BECAUSE IT WILL HELP RESPONDER

188
00:08:32,897 --> 00:08:36,100
 ANALYSIS OR ANALYSIS THAT

189
00:08:36,100 --> 00:08:37,368
 COMPARE THE PROPORTION OF

190
00:08:37,368 --> 00:08:39,337
 PARTICIPANTS WHO HAVE A

191
00:08:39,337 --> 00:08:40,838
 MEANINGFUL OUTCOME BETWEEN THE

192
00:08:40,838 --> 00:08:43,908
 TWO GROUPS AND THESE ARE

193
00:08:43,908 --> 00:08:45,443
 EASIER TO INTERPRET BETWEEN

194
00:08:45,443 --> 00:08:45,776
 PEOPLE.

195
00:08:45,776 --> 00:08:47,278
 SO IF YOU ARE CONSIDERING THE

196
00:08:47,278 --> 00:08:50,481
 PAIN OF I DON'T YOU ARE

197
00:08:50,481 --> 00:08:53,217
 GRANDMOTHER WHO -- PAIN OF

198
00:08:53,217 --> 00:08:57,088
 YOUR GRANDMOTHER WHO IS ON

199
00:08:57,088 --> 00:08:58,623
 PAIN MEDICATION, YOU CAN TRY

200
00:08:58,623 --> 00:09:05,229
 THIS AND THIS IS SOMETHING

201
00:09:05,229 --> 00:09:07,498
 WHERE PEOPLE CAN WRAP THEIR

202
00:09:07,498 --> 00:09:10,902
 HEAD AROUND THE DIFFERENCE 

203
00:09:10,902 --> 00:09:12,937
 WITH A DRUG.

204
00:09:12,937 --> 00:09:19,277
 AND ANOTHER METHOD IS TO ASK

205
00:09:19,277 --> 00:09:20,511
 ABOUT THE LIMITATIONS.

206
00:09:20,511 --> 00:09:22,446
 SO IS IT REALLY THAT

207
00:09:22,446 --> 00:09:23,614
 STRAIGHTFORWARD?  AND I WANT

208
00:09:23,614 --> 00:09:25,549
 TO ARGUE A LITTLE FOR

209
00:09:25,549 --> 00:09:26,450
 DISCUSSION PURPOSES, MAYBE NOT

210
00:09:26,450 --> 00:09:27,919
 AND I THINK WHAT IS REALLY

211
00:09:27,919 --> 00:09:29,887
 IMPORTANT TO CONSIDER IS THERE

212
00:09:29,887 --> 00:09:33,491
 IS A LOT OF VARIABILITY IN

213
00:09:33,491 --> 00:09:34,959
 WHAT IS MEANINGFUL AND IT CAN

214
00:09:34,959 --> 00:09:36,861
 CHANGE FOR A LOT OF THINGS.

215
00:09:36,861 --> 00:09:38,496
 SO BROAD THINGS FOR EXAMPLE IS

216
00:09:38,496 --> 00:09:38,930
 THE TREATMENT.

217
00:09:38,930 --> 00:09:43,434
 THE TREATMENT IS RISKY IF IT

218
00:09:43,434 --> 00:09:44,268
 CAN CAUSE IRREPUTABLE DAMAGE,

219
00:09:44,268 --> 00:09:46,437
 CAUSE YOUR JOINTS TO BE

220
00:09:46,437 --> 00:09:49,073
 REPLACED IF YOU THINK ABOUT A

221
00:09:49,073 --> 00:09:51,709
 DRUG RECENTLY PUT UP FOR

222
00:09:51,709 --> 00:09:53,177
 APPROVAL.

223
00:09:53,177 --> 00:09:54,545
 OR CONSIDERING NAUSEA,

224
00:09:54,545 --> 00:09:56,080
 VOMITING, THESE MAY BE

225
00:09:56,080 --> 00:09:58,482
 REVERSIBLE BUT FOR PEOPLE TO

226
00:09:58,482 --> 00:10:00,351
 CONSIDER CONTINUING TO TAKE A

227
00:10:00,351 --> 00:10:02,453
 DRUG, IT MAY HAVE TO BE

228
00:10:02,453 --> 00:10:04,555
 CONSIDERED TO WHETHER THE DRUG

229
00:10:04,555 --> 00:10:05,957
 IS MEANINGFUL FOR THEM OR

230
00:10:05,957 --> 00:10:06,657
 WORTH IT.

231
00:10:06,657 --> 00:10:08,726
 AND THEN TALKING ABOUT

232
00:10:08,726 --> 00:10:09,994
 SURGERY, THINGS THAT COST A

233
00:10:09,994 --> 00:10:12,563
 LOT OF MONEY TO THE PATIENTS

234
00:10:12,563 --> 00:10:13,798
 AND SOCIETY AT LARGE, YOU

235
00:10:13,798 --> 00:10:17,101
 WOULD EXPECT TO SEE A BIGGER

236
00:10:17,101 --> 00:10:20,705
 DIFFERENCE IN WHETHER IT IS

237
00:10:20,705 --> 00:10:21,939
 CLINICALLY MEANINGFUL.

238
00:10:21,939 --> 00:10:29,246
 ON THE FLIP SIDE OF THAT, YOU

239
00:10:29,246 --> 00:10:30,881
 HAVE THE CHRONIC PAIN AND IF

240
00:10:30,881 --> 00:10:32,850
 YOU CAN FIND ANYTHING THAT

241
00:10:32,850 --> 00:10:34,485
 MIGHT MOVE THE NEEDLE A LITTLE

242
00:10:34,485 --> 00:10:36,754
 BIT, THAT MIGHT BE MEANINGFUL

243
00:10:36,754 --> 00:10:37,121
 FOR THEM.

244
00:10:37,121 --> 00:10:39,190
 THERE ARE A LOT OF DRUGS THEY

245
00:10:39,190 --> 00:10:41,926
 COULD TRY THAT COULD GIVE THEM

246
00:10:41,926 --> 00:10:43,227
 A MODERATE MOVEMENT IN THEIR

247
00:10:43,227 --> 00:10:43,527
 PAIN.

248
00:10:43,527 --> 00:10:47,465
 AND THEN THERE IS THE

249
00:10:47,465 --> 00:10:48,132
 IDEOSYNCRACY BETWEEN PEOPLE.

250
00:10:48,132 --> 00:10:50,668
 I WILL TELL YOU A STORY OF A

251
00:10:50,668 --> 00:10:54,105
 TRIAL I AM DEVELOPING AT MY

252
00:10:54,105 --> 00:10:56,107
 SITE AND A WOMAN CAME IN AND

253
00:10:56,107 --> 00:10:57,708
 TOLD MY COORDINATORS THIS ONLY

254
00:10:57,708 --> 00:11:00,544
 WORKS FOR ME FOR ONE HOUR BUT

255
00:11:00,544 --> 00:11:04,548
 WORKS WELL FOR ME FOR ONE HOUR

256
00:11:04,548 --> 00:11:07,618
 AND ALLOWS ME TO WALK MY DOG

257
00:11:07,618 --> 00:11:10,921
 AND THAT IS A GOOD THING FOR

258
00:11:10,921 --> 00:11:11,489
 ME.

259
00:11:11,489 --> 00:11:14,458
 SO TWO HOURS OUT OF 24, MY

260
00:11:14,458 --> 00:11:16,327
 PAIN IS STILL A 5 THE OTHER

261
00:11:16,327 --> 00:11:17,962
 TIMES SO THAT WOULDN'T REALLY

262
00:11:17,962 --> 00:11:19,397
 CHANGE ON THE NRS.

263
00:11:19,397 --> 00:11:22,299
 SO FOR HER, A TINY IMPROVEMENT

264
00:11:22,299 --> 00:11:25,236
 ON THE NRS MIGHT BE HAVING A

265
00:11:25,236 --> 00:11:27,338
 HUGE IMPACT ON HER LIFE SO WE

266
00:11:27,338 --> 00:11:31,142
 TRY TO GET IT TOWN TO ONE --

267
00:11:31,142 --> 00:11:33,644
 DOWN TO ONE NUMBER AND THEN

268
00:11:33,644 --> 00:11:35,746
 SAY WELL, NOT ALL THE PEOPLE

269
00:11:35,746 --> 00:11:39,283
 RESPONDED, WE HAVE TO CONSIDER

270
00:11:39,283 --> 00:11:41,152
 THE CUTOFFS IN OUR ABILITY TO

271
00:11:41,152 --> 00:11:47,158
 TREAT PEOPLE AND MAKE THAT 

272
00:11:47,158 --> 00:11:47,725
 CLEAR.

273
00:11:47,725 --> 00:11:49,794
 SO ONE THING TO CONSIDER WHEN

274
00:11:49,794 --> 00:11:51,429
 YOU ARE DOING PAPERS OR

275
00:11:51,429 --> 00:11:52,963
 PRESENTING DATA, THIS IS A

276
00:11:52,963 --> 00:11:54,365
 LITTLE COMPLICATED AND I WILL

277
00:11:54,365 --> 00:11:57,635
 TRY NOT TO FUMBLE THROUGH IT

278
00:11:57,635 --> 00:12:03,941
 BUT WHAT YOU SAW ON THE Y AXIS

279
00:12:03,941 --> 00:12:06,777
 IS THE PROPORTION OF

280
00:12:06,777 --> 00:12:10,714
 PARTICIPANTS AND ON THE X

281
00:12:10,714 --> 00:12:12,283
 AXIS, THE MINIMUM PERCENT

282
00:12:12,283 --> 00:12:13,017
 IMPROVEMENT IN PAIN.

283
00:12:13,017 --> 00:12:16,253
 SO WHEN YOU GET TO ABOUT

284
00:12:16,253 --> 00:12:17,021
 10 PERCENT IMPROVEMENT IN

285
00:12:17,021 --> 00:12:19,657
 PAIN, YOU SEE A HIGHER

286
00:12:19,657 --> 00:12:21,292
 PROPORTION OF PEOPLE IN THE

287
00:12:21,292 --> 00:12:23,260
 ACTIVE GROUP RESPONDING ALL

288
00:12:23,260 --> 00:12:24,962
 THE WAY UP TO 75 PERCENT OF

289
00:12:24,962 --> 00:12:25,696
 PAIN.

290
00:12:25,696 --> 00:12:28,065
 SO YOU LOOK AT THESE AT ANY

291
00:12:28,065 --> 00:12:29,667
 CUTOFF YOU CONSIDER

292
00:12:29,667 --> 00:12:30,734
 MEANINGFUL, THERE IS A

293
00:12:30,734 --> 00:12:32,136
 SEPARATION WHERE THIS OCCURS

294
00:12:32,136 --> 00:12:34,538
 SO REGARDLESS OF THE CUTOFF,

295
00:12:34,538 --> 00:12:37,441
 THIS DRUG CAN LOOKS REALLY

296
00:12:37,441 --> 00:12:37,842
 MEANINGFUL.

297
00:12:37,842 --> 00:12:39,376
 AND IN THIS CASE THERE IS

298
00:12:39,376 --> 00:12:41,112
 REALLY A BIG SEPARATION

299
00:12:41,112 --> 00:12:43,414
 BETWEEN THE PROPORTION OF

300
00:12:43,414 --> 00:12:45,449
 PARTICIPANTS WHO SAY THEY ARE

301
00:12:45,449 --> 00:12:47,651
 20 PERCENT IMPROVED OVER THE

302
00:12:47,651 --> 00:12:49,220
 ACTIVE PLACEBO GROUP BUT

303
00:12:49,220 --> 00:12:50,654
 ANYTHING OVER 25 PERCENT IS

304
00:12:50,654 --> 00:12:52,957
 ALMOST ON TOP OF EACH OTHER.

305
00:12:52,957 --> 00:12:55,459
 SO YOU LOOK AT THIS AND SAY

306
00:12:55,459 --> 00:12:57,328
 WELL I DON'T KNOW, THIS ISN'T

307
00:12:57,328 --> 00:12:57,795
 REALLY USEFUL.

308
00:12:57,795 --> 00:13:00,264
 BUT IF YOU LOOK AT THE DATA

309
00:13:00,264 --> 00:13:02,967
 THIS WAY AND NOT LOOKING AT A

310
00:13:02,967 --> 00:13:05,436
 SINGLE CUTOFF BUT ALL THE

311
00:13:05,436 --> 00:13:08,472
 CUTOFFS, YOU CAN SEE THE

312
00:13:08,472 --> 00:13:10,875
 DIFFERENCE IN THE TREATMENT.

313
00:13:10,875 --> 00:13:15,312
 SO ONE MORE, THIS IS MY SOAP

314
00:13:15,312 --> 00:13:16,981
 BOX PAPER, I SEE THIS ALL THE

315
00:13:16,981 --> 00:13:19,583
 TIME, AS A REVIEWER, I SEE

316
00:13:19,583 --> 00:13:22,419
 THIS AND I WANT TO SAY THIS AS

317
00:13:22,419 --> 00:13:26,790
 MUCH AS POSSIBLE. 

318
00:13:26,790 --> 00:13:28,425
 A CLINICAL MEANINGFUL

319
00:13:28,425 --> 00:13:38,936
 DEFINITION OF A PATIENT IS

320
00:13:39,303 --> 00:13:40,471
 USEFUL FROM BASELINE.

321
00:13:40,471 --> 00:13:45,376
 AND IT IS NOT EQUAL TO THE

322
00:13:45,376 --> 00:13:45,976
 GROUP DIFFERENCE.

323
00:13:45,976 --> 00:13:47,545
 THERE IS A LOT OF VARIABILITY

324
00:13:47,545 --> 00:13:49,213
 IN RESPONSE AND THERE IS A

325
00:13:49,213 --> 00:13:50,581
 PLACEBO GROUP AND WE DON'T

326
00:13:50,581 --> 00:13:54,585
 HAVE THE TOOL TO DO MECHANISM

327
00:13:54,585 --> 00:13:56,220
 BASED DEVELOPMENT WHERE

328
00:13:56,220 --> 00:13:57,721
 EVERYONE IS RESPONDING

329
00:13:57,721 --> 00:13:58,122
 ACCORDINGLY.

330
00:13:58,122 --> 00:14:00,057
 AND WE REALLY WILL LIMIT THE

331
00:14:00,057 --> 00:14:01,192
 ABILITY TO IDENTIFY TREATMENTS

332
00:14:01,192 --> 00:14:02,826
 THAT ARE ACTUALLY MEANINGFUL

333
00:14:02,826 --> 00:14:04,328
 FOR PATIENTS THAT THEY CAN TRY

334
00:14:04,328 --> 00:14:06,263
 IN THE REAL WORLD IF WE HOLD

335
00:14:06,263 --> 00:14:08,098
 OURSELVES TO THE STANDARD OF

336
00:14:08,098 --> 00:14:10,434
 HAVING TO SEE A 2-POINT

337
00:14:10,434 --> 00:14:11,502
 DIFFERENCE IN GROUPS.

338
00:14:11,502 --> 00:14:14,205
 AND IF YOU THINK OF DRUGS FOR

339
00:14:14,205 --> 00:14:17,241
 PAIN, NONE OF THEM WILL GIVE

340
00:14:17,241 --> 00:14:18,542
 YOU THE 2 PERCENT DIFFERENCE

341
00:14:18,542 --> 00:14:20,411
 IN A CLINICAL TRIAL SO IT IS

342
00:14:20,411 --> 00:14:22,780
 REALLY IMPORTANT THAT WE DON'T

343
00:14:22,780 --> 00:14:26,984
 USE THIS WAY WHEN WRITING

344
00:14:26,984 --> 00:14:29,920
 PAPERS. 

345
00:14:29,920 --> 00:14:33,557
 THE CHALLENGE IS'BECOMES -- IT

346
00:14:33,557 --> 00:14:35,826
 BECOMES REALLY DIFFICULT WHEN

347
00:14:35,826 --> 00:14:42,600
 ASKING PATIENTS OF THE

348
00:14:42,600 --> 00:14:44,101
 MEANINGFUL BASELINE, WHEN

349
00:14:44,101 --> 00:14:45,002
 ASSESSING DRUGS.

350
00:14:45,002 --> 00:14:49,907
 TO SAY YOUR PAIN WILL BE FROM 

351
00:14:49,907 --> 00:14:52,810
 A 6 TO 3 AND THEY SAY WELL, IT

352
00:14:52,810 --> 00:14:56,547
 IS ACTUALLY 6 TO 4.

353
00:14:56,547 --> 00:14:58,682
 SO THE SIGNIFICANT DIFFERENCE,

354
00:14:58,682 --> 00:15:00,985
 THESE ARE ACTUAL IMPROVEMENTS

355
00:15:00,985 --> 00:15:03,420
 OVER THE ACTIVE GROUP WITH

356
00:15:03,420 --> 00:15:04,688
 PLACEBO AND THEN THE CHANGES

357
00:15:04,688 --> 00:15:07,124
 SHOULD BE LOOKED AT FOR EACH

358
00:15:07,124 --> 00:15:09,193
 ONE. 

359
00:15:09,193 --> 00:15:11,795
 SO TO CONCLUDE, IF ANY OF THIS

360
00:15:11,795 --> 00:15:13,664
 IS USEFUL FOR ANIMAL RESEARCH,

361
00:15:13,664 --> 00:15:18,902
 WHAT I JUST SAID TO YOU, AND

362
00:15:18,902 --> 00:15:27,211
 AS AN APOCK HREUPZ --

363
00:15:27,211 --> 00:15:28,612
 APOCALYPSE, YOU CAN'T ASK

364
00:15:28,612 --> 00:15:30,547
 ANIMALS WHAT IS IMPORTANT OR

365
00:15:30,547 --> 00:15:34,551
 MEANINGFUL TO THEM BUT IF THEY

366
00:15:34,551 --> 00:15:38,222
 ARE A PET OWNER, YOU COULD

367
00:15:38,222 --> 00:15:48,432
 DETERMINE THAT. 

368
00:15:48,432 --> 00:15:55,673
 AND THEN WHAT IS THE HOLISTIC

369
00:15:55,673 --> 00:15:58,375
 OUTCOMES OF AN EQUIVALENT

370
00:15:58,375 --> 00:16:01,879
 ANCHOR BASED METHOD IN

371
00:16:01,879 --> 00:16:02,212
 ANIMALS?

372
00:16:02,212 --> 00:16:06,483
 THE RELATIONSHIPS BETWEEN 

373
00:16:06,483 --> 00:16:11,488
 TYPICAL INDUCED PAIN OUTCOMES

374
00:16:11,488 --> 00:16:13,791
 NEED HOLISTIC OUTCOMES WITH

375
00:16:13,791 --> 00:16:14,491
 CLEARLY DIFFERENTIATED

376
00:16:14,491 --> 00:16:16,527
 CATEGORIES AND THAT CAN COME

377
00:16:16,527 --> 00:16:19,163
 FROM PEOPLE WHO KNOW MORE

378
00:16:19,163 --> 00:16:21,899
 ABOUT ANIMALS THAN I DO AND

379
00:16:21,899 --> 00:16:24,501
 THEN I WONDER THAT FROM A

380
00:16:24,501 --> 00:16:25,369
 PRECLINICAL PERSPECTIVE, I

381
00:16:25,369 --> 00:16:31,308
 WOULD THINK THE GOAL WOULD BE

382
00:16:31,308 --> 00:16:34,478
 TO TO IDENTIFY CLINICALLY

383
00:16:34,478 --> 00:16:37,014
 MEANINGFUL THRESHOLDS IN

384
00:16:37,014 --> 00:16:39,717
 ANIMALS TO INCREASE SUCCESSFUL

385
00:16:39,717 --> 00:16:42,252
 TRANSLATION TO CLINICAL

386
00:16:42,252 --> 00:16:42,820
 TRIALS.

387
00:16:42,820 --> 00:16:44,588
 SO MEDICALLY, THERE IS A

388
00:16:44,588 --> 00:16:46,724
 DIFFERENCE BETWEEN HUMANS AND

389
00:16:46,724 --> 00:16:49,593
 THE ANCHOR BASED METHODS WHEN

390
00:16:49,593 --> 00:16:52,763
 ASKING PEOPLE ABOUT THEIR

391
00:16:52,763 --> 00:16:53,230
 EXPERIENCE.

392
00:16:53,230 --> 00:16:55,199
 IT IS VARIABLE AMONG PEOPLE SO

393
00:16:55,199 --> 00:16:57,634
 WE NEED TO USE CAUTION WHEN WE

394
00:16:57,634 --> 00:16:59,837
 PRESENT THEM TO THE WORLD AND

395
00:16:59,837 --> 00:17:02,172
 THEN MCI D FOR AN INDIVIDUAL

396
00:17:02,172 --> 00:17:03,474
 PATIENT OR ANIMAL SHOULD NOT

397
00:17:03,474 --> 00:17:06,310
 BE USED TO INFORM

398
00:17:06,310 --> 00:17:13,350
 INTERPRETATION OF WHAT IS

399
00:17:13,350 --> 00:17:16,720
 CLINICALLY MINGFUL --

400
00:17:16,720 --> 00:17:17,921
 MEANINGFUL DIFFERENCES BETWEEN

401
00:17:17,921 --> 00:17:21,325
 GROUPS AND TRANSLATION OF

402
00:17:21,325 --> 00:17:23,026
 THESE CONCEPTS WILL REQUIRE

403
00:17:23,026 --> 00:17:23,794
 CREATIVITY.

404
00:17:23,794 --> 00:17:28,932
 SO WITH THAT, I WOULD LIKE TO

405
00:17:28,932 --> 00:17:32,703
 THANK MY COLLEAGUES AND

406
00:17:32,703 --> 00:17:36,073
 DOCTORS FARRAR AND Dr.

407
00:17:36,073 --> 00:17:39,143
 LANGFORD WHO HELPED ME THINK

408
00:17:39,143 --> 00:17:41,412
 ABOUT MY RESEARCH.

409
00:17:41,412 --> 00:17:41,779
 [APPLAUSE]

410
00:17:41,779 --> 00:17:42,546
 >> EXCELLENT
PRESENTATION,

411
00:17:42,546 --> 00:17:44,948
 THANK YOU VERY MUCH AND THE

412
00:17:44,948 --> 00:17:46,884
 PERFECT SEGUE TO THE NEXT

413
00:17:46,884 --> 00:17:49,520
 PRESENTATION, IT IS MY

414
00:17:49,520 --> 00:17:54,825
 PLEASURE TO INTRODUCE MY

415
00:17:54,825 --> 00:17:56,560
 FRIEND JOHN INNES WHO IS FROM

416
00:17:56,560 --> 00:17:58,595
 UNIVERSITY OF LIVER POOL AND

417
00:17:58,595 --> 00:18:09,173
 ENDED UP OPENING UP A PRACTICE

418
00:18:13,076 --> 00:18:13,911
 IN MOVEMENT REFERRALS.

419
00:18:13,911 --> 00:18:15,779
 JOHN HAS COME OVER FROM THE UK

420
00:18:15,779 --> 00:18:19,216
 AND MAY HAVE A BUG IN HIS

421
00:18:19,216 --> 00:18:20,584
 POWERPOINT THAT HE BROUGHT

422
00:18:20,584 --> 00:18:22,786
 OVER FROM THE UK SO WE WILL

423
00:18:22,786 --> 00:18:29,960
 JUST HOOK UP HIS COMPUTER

424
00:18:29,960 --> 00:18:30,494
 DIRECTLY.

425
00:18:30,494 --> 00:18:36,834
 AND JOHN CAN TALK ABOUT THE

426
00:18:36,834 --> 00:18:39,803
 MCI D FOR TWO OUTCOME BASED

427
00:18:39,803 --> 00:18:43,173
 MEASURES HE HAS BEEN INVOLVED

428
00:18:43,173 --> 00:18:45,876
 IN DEVELOPING FOR LOAD.

429
00:18:45,876 --> 00:18:46,677
 >> THANK YOU, REALLY NICE
TO

430
00:18:46,677 --> 00:18:49,213
 BE HERE AND LIKE TO THANK THE

431
00:18:49,213 --> 00:18:51,014
 ORGANIZING COMMITTEE AND

432
00:18:51,014 --> 00:18:52,649
 STAKEHOLDER SPONSORS FOR

433
00:18:52,649 --> 00:18:54,051
 PUTTING THIS MEETING TOGETHER,

434
00:18:54,051 --> 00:18:55,152
 IT IS REALLY IMPORTANT AND

435
00:18:55,152 --> 00:19:02,893
 GREAT TO BE HERE.

436
00:19:02,893 --> 00:19:06,530
 SO JENNIFER'S TALK JUST NOW

437
00:19:06,530 --> 00:19:09,933
 WAS A PERFECT SEGUE FOR THIS

438
00:19:09,933 --> 00:19:11,335
 TALKING ABOUT THINGS DONE WITH

439
00:19:11,335 --> 00:19:13,170
 ANIMALS AND I WILL TALK WITH

440
00:19:13,170 --> 00:19:14,905
 THINGS THAT HAVE BEEN DONE

441
00:19:14,905 --> 00:19:17,107
 THAT ARE RELEVANT TO WHAT SHE

442
00:19:17,107 --> 00:19:20,844
 IS TALKING ABOUT.

443
00:19:20,844 --> 00:19:23,447
 THE MINIMAL CLINICALLY

444
00:19:23,447 --> 00:19:28,185
 IMPORTANT KITCHENS FOR LOAD

445
00:19:28,185 --> 00:19:29,586
 AND THIS IS MOVEMENT REFERRALS

446
00:19:29,586 --> 00:19:32,022
 FROM UNIVERSITY OF LIVER POOL.

447
00:19:32,022 --> 00:19:34,758
 PATIENT HISTORY IS HUGE WITH

448
00:19:34,758 --> 00:19:39,196
 MEDICINE AND WE USE DIFFERENT

449
00:19:39,196 --> 00:19:45,569
 TERMS FOR ANIMALS AND CLINICAL

450
00:19:45,569 --> 00:19:48,372
 METROLOGY AND WHEN I SAY THAT,

451
00:19:48,372 --> 00:19:52,342
 PEOPLE LOOK AT ME BLANKLY ON

452
00:19:52,342 --> 00:19:57,648
 WHAT THESE MEANS SO THE CLIENT

453
00:19:57,648 --> 00:20:00,784
 REPORTED OUTCOME MEASURES

454
00:20:00,784 --> 00:20:03,620
 RELATE TO PATIENT OUTCOMES.

455
00:20:03,620 --> 00:20:13,130
 AND ARE NOT ALWAYS EXPLICIT. 

456
00:20:13,130 --> 00:20:20,437
 HUMAN OUTCOMES ARE OFTEN MORE

457
00:20:20,437 --> 00:20:23,707
 MEANINGFUL IF THEY HAVE

458
00:20:23,707 --> 00:20:27,144
 REPORTED OUTCOMES, FOR EXAMPLE

459
00:20:27,144 --> 00:20:31,381
 IN ENGLAND, A HIP OR KNEE

460
00:20:31,381 --> 00:20:34,284
 REPLACEMENT IS NOT COUNTED IF

461
00:20:34,284 --> 00:20:38,822
 THERE IS NO REPORTED UTCOME --

462
00:20:38,822 --> 00:20:39,222
 OUTCOME.

463
00:20:39,222 --> 00:20:42,793
 SO THERE WAS A TALK YESTERDAY

464
00:20:42,793 --> 00:20:45,929
 ON THIS TALKING ABOUT CROM

465
00:20:45,929 --> 00:20:47,164
 VALUE VALIDATION PROCESS AND

466
00:20:47,164 --> 00:20:48,732
 THESE HAVE BEEN COMPARED TO

467
00:20:48,732 --> 00:20:52,970
 EACH OTHER AND ALSO TO

468
00:20:52,970 --> 00:20:54,605
 OBJECTIVE MEASURES THAT WE

469
00:20:54,605 --> 00:20:57,908
 HAVE SOME MEASURE THE CRITERIA

470
00:20:57,908 --> 00:21:00,010
 AND ACCEPTED GOLD STANDARD.

471
00:21:00,010 --> 00:21:01,612
 BUT I JUST THOUGHT I WOULD

472
00:21:01,612 --> 00:21:03,246
 HOPEFULLY SHOW YOU A COUPLE OF

473
00:21:03,246 --> 00:21:03,580
 VIDEOS.

474
00:21:03,580 --> 00:21:05,682
 THIS IS THE REAL WORLD,

475
00:21:05,682 --> 00:21:06,283
 REALLY.

476
00:21:06,283 --> 00:21:10,087
 I USED TO BE IN ACADEMIA,

477
00:21:10,087 --> 00:21:12,990
 SPENT 22 YEARS THERE, DESCRIBE

478
00:21:12,990 --> 00:21:17,494
 MYSELF AS A RECOVERING A

479
00:21:17,494 --> 00:21:20,097
 ACADEMIC NOW AND I GO TO A

480
00:21:20,097 --> 00:21:23,834
 MEETING EVERY FEW WEEKS TO

481
00:21:23,834 --> 00:21:27,838
 TALK TO OTHERS IN ACADEMICS

482
00:21:27,838 --> 00:21:29,640
 BUT IT IS THE REAL WORLD WHEN

483
00:21:29,640 --> 00:21:31,508
 IT COMES TO CLINICAL TRIALS.

484
00:21:31,508 --> 00:21:33,210
 I GUESS JUST WATCH THIS VIDEO

485
00:21:33,210 --> 00:21:36,747
 FOR A SECOND AND THIS IS NOT

486
00:21:36,747 --> 00:21:43,654
 PARTICULARLY VALID FOR THIS

487
00:21:43,654 --> 00:21:48,592
 DOG, JUST ASSESS THIS DOG'S

488
00:21:48,592 --> 00:21:54,698
 MOBILITY AND WE SPENT ABOUT A

489
00:21:54,698 --> 00:21:57,200
 HALF DAY GETTING THE SCORE ON

490
00:21:57,200 --> 00:22:02,305
 ITS LIMBS AND TELLING US AN

491
00:22:02,305 --> 00:22:04,541
 OBJECTIVE MEASURE OF MOBILITY

492
00:22:04,541 --> 00:22:07,244
 WHERE THE OWNER GAVE A LOWER

493
00:22:07,244 --> 00:22:07,544
 SCORE.

494
00:22:07,544 --> 00:22:09,079
 AND COMPARE THAT DOG TO THIS

495
00:22:09,079 --> 00:22:11,515
 ONE AND YOU IMMEDIATELY SEE A

496
00:22:11,515 --> 00:22:11,915
 DIFFERENCE.

497
00:22:11,915 --> 00:22:14,518
 AND YESTERDAY WE HAD A TALK

498
00:22:14,518 --> 00:22:17,688
 THAT MENTIONED THE FATIGUE OF

499
00:22:17,688 --> 00:22:21,224
 CHRONIC PAIN IN HUMANS AND SO 

500
00:22:21,224 --> 00:22:27,431
 I THINK THESE DOGS SHOW

501
00:22:27,431 --> 00:22:30,100
 FATIGUE OF CHRONIC PAIN IN

502
00:22:30,100 --> 00:22:35,238
 THIS DOG, 15.2 SO THIS DOG IS

503
00:22:35,238 --> 00:22:37,107
 LESS LAID BUT THE LOAD SCORE

504
00:22:37,107 --> 00:22:40,043
 IS 23 AND YOU MAY KEEP IN YOUR

505
00:22:40,043 --> 00:22:44,815
 OWN MIND WHICH DOG HAS MORE

506
00:22:44,815 --> 00:22:45,982
 MOBILE WILT ISSUES.

507
00:22:45,982 --> 00:22:48,485
 THE LOAD SCORE IS OBJECTIVE

508
00:22:48,485 --> 00:22:51,722
 AND NOT ALWAYS THE TRUTH, IF

509
00:22:51,722 --> 00:22:52,089
 YOU WILL.

510
00:22:52,089 --> 00:22:54,691
 SO WE SEE THE DEVELOPMENT IN

511
00:22:54,691 --> 00:22:56,660
 THIS REVIEW AND THAT

512
00:22:56,660 --> 00:23:00,564
 INSTRUMENTS CAN BE USED IN

513
00:23:00,564 --> 00:23:01,665
 DOGS WITH OSTEOARTHRITIS BUT

514
00:23:01,665 --> 00:23:04,034
 THERE WAS FURTHER WORK TO DO

515
00:23:04,034 --> 00:23:06,670
 AND WE DIDN'T HAVE CLINICALLY

516
00:23:06,670 --> 00:23:08,071
 IMPORTANT DIFFERENCES FOR LOAD

517
00:23:08,071 --> 00:23:09,473
 OR OTHER INSTRUMENTS FOR THAT

518
00:23:09,473 --> 00:23:10,107
 MATTER.

519
00:23:10,107 --> 00:23:13,744
 SO IN THIS STUD STUDY WE

520
00:23:13,744 --> 00:23:16,446
 PUBLISHED LAST YEAR WITH A

521
00:23:16,446 --> 00:23:18,749
 COLLEAGUE OF MINE, MARK

522
00:23:18,749 --> 00:23:25,055
 MORTON, WE LOOKED AT THE

523
00:23:25,055 --> 00:23:26,690
 CLINICALLY IMPORTANT

524
00:23:26,690 --> 00:23:29,292
 DIFFERENCES IN THE LIVER POOL

525
00:23:29,292 --> 00:23:34,498
 AS YO ARTHRITIS IN DOGS AND

526
00:23:34,498 --> 00:23:35,866
 CANINE ORTHOPEDIC INDEX AND

527
00:23:35,866 --> 00:23:38,468
 THERE WERE OUTCOMES WITH THAT.

528
00:23:38,468 --> 00:23:41,571
 SO AS JENNIFER DESCRIBED, THE

529
00:23:41,571 --> 00:23:43,807
 SCORE RECEIVED BY THE CLIENT

530
00:23:43,807 --> 00:23:51,515
 CAN BE SEEN AS BENEFICIAL COME

531
00:23:51,515 --> 00:23:52,816
 FIRED THOSE WHO RECEIVE NO

532
00:23:52,816 --> 00:23:56,820
 CHANGE AND WE NEED TO KNOW

533
00:23:56,820 --> 00:23:58,288
 THIS ESTIMATE BECAUSE THEY ARE

534
00:23:58,288 --> 00:24:03,593
 USED IN CLINICAL TRIALS AND

535
00:24:03,593 --> 00:24:04,561
 REGULAR LAKES CLINICAL TRIALS

536
00:24:04,561 --> 00:24:08,331
 THAT CAN BE USED AS A

537
00:24:08,331 --> 00:24:10,901
 THRESHOLD OR NOT THRESHOLD AND

538
00:24:10,901 --> 00:24:13,637
 CAN BE USED IN THE CLINIC IN

539
00:24:13,637 --> 00:24:15,272
 RESPONSE TO INTERVENTION AND

540
00:24:15,272 --> 00:24:17,874
 AS JENNIFER STRIPED, WE CAN

541
00:24:17,874 --> 00:24:20,443
 USE ANCHOR OR DISTRIBUTION

542
00:24:20,443 --> 00:24:22,712
 BASED METHODS BASED ON THE

543
00:24:22,712 --> 00:24:23,280
 UNDERLYING STATISTICAL

544
00:24:23,280 --> 00:24:24,681
 FEATURES OF THE GROUP.

545
00:24:24,681 --> 00:24:29,686
 NOW, WE TOOK A OPPORTUNITY

546
00:24:29,686 --> 00:24:40,263
 WITH THE RCVS KNOWLEDGE CANINE

547
00:24:41,798 --> 00:24:47,237
 CRUCIATE REGISTRY, WE HAVE THE

548
00:24:47,237 --> 00:24:51,675
 NATIONAL PROGRAM THERE AT THE

549
00:24:51,675 --> 00:24:54,578
 COLLEGE TO IMPROVE OUTCOMES

550
00:24:54,578 --> 00:24:57,848
 AND THIS INCLUDES PATIENTS WHO

551
00:24:57,848 --> 00:25:07,624
 SIGN UP THEIR CANINE CRUCIATES

552
00:25:07,624 --> 00:25:10,360
 TO GET DATA AND THERE ARE NOW

553
00:25:10,360 --> 00:25:12,429
 THOUSANDS OF CLIENTS

554
00:25:12,429 --> 00:25:13,396
 SUBMITTING DATA TO THAT

555
00:25:13,396 --> 00:25:14,965
 PROGRAM AND WITHIN THE

556
00:25:14,965 --> 00:25:16,867
 REGISTRY, THE TWO INSTRUMENTS

557
00:25:16,867 --> 00:25:22,405
 WE USE ARE THE LOAD AND CANINE

558
00:25:22,405 --> 00:25:25,108
 ORTHOPEDIC INDEX BUT THERE IS

559
00:25:25,108 --> 00:25:27,077
 ALSO AN ANCHOR QUESTION BUILT

560
00:25:27,077 --> 00:25:29,379
 IN WHICH IS COMPARED TO

561
00:25:29,379 --> 00:25:31,448
 SURGERY, HOW IS YOUR DOG NOW

562
00:25:31,448 --> 00:25:33,083
 AND JENNIFER USED THAT

563
00:25:33,083 --> 00:25:33,583
 CONCEPT.

564
00:25:33,583 --> 00:25:35,185
 THERE ARE A RANGE OF RESPONSES

565
00:25:35,185 --> 00:25:37,053
 AND WE'RE NOT PARTICULARLY

566
00:25:37,053 --> 00:25:39,823
 INTERESTED IN THIS STUDY WITH

567
00:25:39,823 --> 00:25:42,125
 THE CRUCIATE STUDY BUT WE WILL

568
00:25:42,125 --> 00:25:44,594
 GO AROUND THE INSTRUMENT

569
00:25:44,594 --> 00:25:46,062
 PROCESSES TO ASSESS THAT.

570
00:25:46,062 --> 00:25:49,933
 I WON'T BORROW YOU WITH THE

571
00:25:49,933 --> 00:26:00,377
 DETAILS HERE, THIS IS

572
00:26:02,612 --> 00:26:03,246
 PUBLISHED IN MCI-1.

573
00:26:03,246 --> 00:26:05,448
 THERE ARE DIFFERENT METHODS TO

574
00:26:05,448 --> 00:26:08,151
 LOOK AT THE METHODS OF MCI D

575
00:26:08,151 --> 00:26:10,186
 SO WE LOOK AT THE AVERAGE

576
00:26:10,186 --> 00:26:10,954
 CHANGE CORRESPONDING TO THE

577
00:26:10,954 --> 00:26:13,189
 MEAN CHANGE IN THE SCORE OF

578
00:26:13,189 --> 00:26:15,025
 THE SOMEWHAT BETTER GROUP, WE

579
00:26:15,025 --> 00:26:18,228
 LOOK AT THE MINIMUM DETECTABLE

580
00:26:18,228 --> 00:26:19,362
 CHANGE, THE SMALLEST CHANGE

581
00:26:19,362 --> 00:26:22,666
 THAT COULD BE CONSIDERED 

582
00:26:22,666 --> 00:26:24,501
 BEYOND THE MEASUREMENT ERROR

583
00:26:24,501 --> 00:26:28,305
 WITH A 95 PERCENT CONFIDENCE

584
00:26:28,305 --> 00:26:29,773
 INTERVAL THRESHOLD.

585
00:26:29,773 --> 00:26:31,574
 THE CHANGE DIFFERENCE IS

586
00:26:31,574 --> 00:26:33,109
 DEFINED AS THE DIFFERENCE IN

587
00:26:33,109 --> 00:26:35,946
 THE AVERAGE CHANGE IN SCORE

588
00:26:35,946 --> 00:26:37,180
 BETWEEN THE SOMEWHAT BETTER

589
00:26:37,180 --> 00:26:40,617
 GROUP AND THE SAME GROUPS AND

590
00:26:40,617 --> 00:26:43,954
 THEN WE USE A OPERATING

591
00:26:43,954 --> 00:26:45,655
 CHARACTERISTIC CURVE USED TO

592
00:26:45,655 --> 00:26:46,723
 DISCRIMINATE BETWEEN THE

593
00:26:46,723 --> 00:26:51,928
 MINIMAL CHANGE AND NO CHANGE

594
00:26:51,928 --> 00:26:52,729
 GROUPS.

595
00:26:52,729 --> 00:26:55,365
 WE ALSO LOOKED AT THE

596
00:26:55,365 --> 00:26:56,866
 DISTRIBUTION METHOD, THE

597
00:26:56,866 --> 00:26:58,134
 EFFECT SIZE AND THAT IS

598
00:26:58,134 --> 00:27:00,203
 GENERALLY AGREED TO BE A SMALL

599
00:27:00,203 --> 00:27:05,542
 EFFECT SIZE SO WE CAN JUST

600
00:27:05,542 --> 00:27:08,712
 APPLY THAT TO BIGGER -- TO THE

601
00:27:08,712 --> 00:27:10,413
 STATISTICAL DATA WE HAVE AT

602
00:27:10,413 --> 00:27:10,780
 BASELINE.

603
00:27:10,780 --> 00:27:14,417
 AND THEN WE HAVE THE STANDARD 

604
00:27:14,417 --> 00:27:17,187
 ERROR OF MEASUREMENT THAT THE

605
00:27:17,187 --> 00:27:19,089
 CLIENT POINTED OUT IN THE

606
00:27:19,089 --> 00:27:20,457
 SCORE, INDEPENDENT OF THE

607
00:27:20,457 --> 00:27:22,959
 PATIENT COHORT OF THE STUDY

608
00:27:22,959 --> 00:27:24,594
 AND AN INTRINSIC PROPERTY OF

609
00:27:24,594 --> 00:27:27,797
 THE ASSESSMENT TOOL BUT TO DO

610
00:27:27,797 --> 00:27:30,333
 THAT, YOU NEED AN ASSESSMENT

611
00:27:30,333 --> 00:27:32,635
 OF RELIABILITY FOR A TOOL AND

612
00:27:32,635 --> 00:27:34,504
 TO DO THAT, THAT WAS POOH HE

613
00:27:34,504 --> 00:27:35,672
 WASLY PUBLISHED BUT WE DIDN'T

614
00:27:35,672 --> 00:27:40,176
 HAVE THAT FOR THE CANINE

615
00:27:40,176 --> 00:27:40,577
 INDECKS.

616
00:27:40,577 --> 00:27:43,113
 THIS IS THE BASELINE OF THE

617
00:27:43,113 --> 00:27:43,813
 STUDY.

618
00:27:43,813 --> 00:27:45,181
 WE HAD 125 SUBJECTS, NOT HUGE

619
00:27:45,181 --> 00:27:47,384
 NUMBERS, AND THESE ARE THE

620
00:27:47,384 --> 00:27:48,651
 PREOPERATIVE AND BASELINE

621
00:27:48,651 --> 00:27:50,253
 SCORES AND THEY WERE

622
00:27:50,253 --> 00:27:50,854
 SIGNIFICANTLY DIFFERENT.

623
00:27:50,854 --> 00:27:52,956
 THAT IS HOW THE DATA WAS

624
00:27:52,956 --> 00:27:54,491
 DISTRIBUTED ACROSS THE GROUPS

625
00:27:54,491 --> 00:27:58,161
 AND AS JENNIFER SHOWED, IT

626
00:27:58,161 --> 00:28:00,463
 CORRELATES WITH THE ANCHOR

627
00:28:00,463 --> 00:28:04,067
 CATEGORY CORRELATED WITH THE

628
00:28:04,067 --> 00:28:05,235
 MEASURES EXCEPT FOR ONE

629
00:28:05,235 --> 00:28:08,538
 INDIVIDUAL IN THE SOMEWHAT

630
00:28:08,538 --> 00:28:10,173
 WORSE CATEGORY, THOUGHT THEY

631
00:28:10,173 --> 00:28:19,049
 WERE SOMEWHAT WORSE ON BOTH

632
00:28:19,049 --> 00:28:20,417
 INMENTS BUT SCORED LITTLE

633
00:28:20,417 --> 00:28:22,152
 BETTER AND IF WE LOOK AT THE

634
00:28:22,152 --> 00:28:24,120
 SAME GROUPS AND SOMEWHAT

635
00:28:24,120 --> 00:28:25,355
 BETTER GROUPS, THERE WERE

636
00:28:25,355 --> 00:28:27,023
 SIGNIFICANT DIFFERENCES SO

637
00:28:27,023 --> 00:28:28,925
 THAT ALLOWS US TO GO ON AND

638
00:28:28,925 --> 00:28:30,693
 DESCRIBE ESTIMATES FOR

639
00:28:30,693 --> 00:28:31,361
 MINIMALLY IMPORTANT

640
00:28:31,361 --> 00:28:31,761
 DIFFERENCES.

641
00:28:31,761 --> 00:28:33,530
 SO IF YOU LOOK AT THESE

642
00:28:33,530 --> 00:28:34,931
 NUMBERS, THESE ARE THE SIX

643
00:28:34,931 --> 00:28:36,966
 DIFFERENT METHODS ACROSS THE

644
00:28:36,966 --> 00:28:41,237
 TOP, THE ANCHOR BASED AND

645
00:28:41,237 --> 00:28:42,939
 DISTRIBUTION BASED METHODS AND

646
00:28:42,939 --> 00:28:48,044
 WE GOT THOSE ASSESSMENTS FOR 

647
00:28:48,044 --> 00:28:49,879
 LOAD AND CANINE INCONNECTION

648
00:28:49,879 --> 00:28:54,217
 AND YOU CAN SEE -- INDEX AND

649
00:28:54,217 --> 00:28:57,087
 YOU CAN SEE THERE ARE SMALLER

650
00:28:57,087 --> 00:29:00,056
 LOADS AND PEOPLE ARGUE THE

651
00:29:00,056 --> 00:29:02,892
 ANCHOR BASED METHODS ARE MORE

652
00:29:02,892 --> 00:29:03,793
 CLINICALLY MEANINGFUL.

653
00:29:03,793 --> 00:29:07,230
 TO I GUESS THE SUMMARY FROM

654
00:29:07,230 --> 00:29:11,067
 THE FIRST STUDY IS WE

655
00:29:11,067 --> 00:29:13,036
 RECOMMENDED A WORKING CHANGE

656
00:29:13,036 --> 00:29:16,206
 IN LOAD OVER FOUR POINTS AND

657
00:29:16,206 --> 00:29:18,441
 FOR THE CANINE ORTHOPEDIC

658
00:29:18,441 --> 00:29:21,845
 INDEX, WE SUGGESTED A WORKING

659
00:29:21,845 --> 00:29:22,812
 MCI D OF 14.

660
00:29:22,812 --> 00:29:33,389
 AND I HAD THE OPPORTUNITY TO 

661
00:29:38,661 --> 00:29:40,597
 COLLABORATE WITH ALMP VERY

662
00:29:40,597 --> 00:29:43,433
 MUCH ORPHAN SERVE AND AGO

663
00:29:43,433 --> 00:29:46,669
 WO*RB ETCH L WILL -- WITH

664
00:29:46,669 --> 00:29:53,443
 ALVES AND HE IS WORKING WITH

665
00:29:53,443 --> 00:29:57,714
 296 DOGS WITH BILATERAL HIP

666
00:29:57,714 --> 00:30:00,416
 ARTHRITIS AND HERE WAS AN

667
00:30:00,416 --> 00:30:01,851
 OPPORTUNITY TO GENERATE MCI D

668
00:30:01,851 --> 00:30:05,421
 ESTIMATES IN A MORE RELEVANT

669
00:30:05,421 --> 00:30:07,991
 PATIENT POPULATION WHICH IS

670
00:30:07,991 --> 00:30:08,758
 OSTEOARTHRITIS.

671
00:30:08,758 --> 00:30:09,626
 AND AGAIN, I WON'T LABOR YOU

672
00:30:09,626 --> 00:30:11,427
 WITH THE NUMBERS HERE.

673
00:30:11,427 --> 00:30:13,029
 THIS WAS PUBLISHED LAST WEEK

674
00:30:13,029 --> 00:30:16,299
 IN PLUS ONE SO YOU CAN LEAD TO

675
00:30:16,299 --> 00:30:18,701
 AT YOUR LEISURE IF YOU ARE

676
00:30:18,701 --> 00:30:20,236
 HAVING PROBLEMS SLEEPING.

677
00:30:20,236 --> 00:30:25,074
 296 DOGS HERE SO A REASONABLE

678
00:30:25,074 --> 00:30:26,376
 POPULATION FOR THE STUDY AND

679
00:30:26,376 --> 00:30:28,511
 YOU SEE THE BASELINE THERE AND

680
00:30:28,511 --> 00:30:30,113
 AGAIN, THERE WERE DIFFERENCES

681
00:30:30,113 --> 00:30:32,949
 BETWEEN THE SAME GROUP AND THE

682
00:30:32,949 --> 00:30:34,918
 SOMEWHAT BETTER GROUP SO THAT

683
00:30:34,918 --> 00:30:37,887
 ALLOWED US TO GO FORWARD AND

684
00:30:37,887 --> 00:30:41,124
 GENERATE ESTIMATES FOR MCI D.

685
00:30:41,124 --> 00:30:42,125
 AND INTERESTINGLY, THE

686
00:30:42,125 --> 00:30:43,493
 ESTIMATES CAME OUT VERY

687
00:30:43,493 --> 00:30:45,628
 SIMILAR TO THE FIRST STUDY SO

688
00:30:45,628 --> 00:30:47,697
 OUR CONCLUSION IN THAT PAPER

689
00:30:47,697 --> 00:30:49,799
 THAT WAS PUBLISHED LAST WEEK

690
00:30:49,799 --> 00:30:52,435
 WAS AGAIN WE WOULD RECOMMEND

691
00:30:52,435 --> 00:30:56,706
 AT THE MOMENT AN MCI D OF 4

692
00:30:56,706 --> 00:30:59,709
 FOR LOAD AND 14 FOR CANINE

693
00:30:59,709 --> 00:31:04,280
 ORTHOPEDIC INDEX.

694
00:31:04,280 --> 00:31:08,117
 BOTH STUDIES SHOWED WITH THE

695
00:31:08,117 --> 00:31:12,121
 CURVE, IT WAS HIGHER THAN WITH

696
00:31:12,121 --> 00:31:15,091
 THE CANINE ORTHOPEDIC INDEX

697
00:31:15,091 --> 00:31:17,026
 SHOWING AN ABILITY TO

698
00:31:17,026 --> 00:31:19,162
 DISCRIMINATE BETWEEN THE SAME

699
00:31:19,162 --> 00:31:20,496
 GROUPS OR SOMEWHAT BETTER

700
00:31:20,496 --> 00:31:20,930
 GROUP.

701
00:31:20,930 --> 00:31:23,533
 THESE SHOULD BE USEFUL FOR

702
00:31:23,533 --> 00:31:26,202
 RESEARCH STUDIES INVOLVING

703
00:31:26,202 --> 00:31:28,071
 TO*GS WITH OSTEOARTHRITIS AND

704
00:31:28,071 --> 00:31:31,074
 BY REGULATORS FOR PIVOTAL

705
00:31:31,074 --> 00:31:34,043
 STUDIES AND BY CLINICIANS.

706
00:31:34,043 --> 00:31:35,078
 THERE ARE FURTHER PARAMETERS

707
00:31:35,078 --> 00:31:37,947
 THAT WOULD BE USEFUL TO HAVE

708
00:31:37,947 --> 00:31:45,154
 ESTIMATES OF SUCH AS THE

709
00:31:45,154 --> 00:31:45,888
 CLIENT ACCEPTABLE CLINICAL

710
00:31:45,888 --> 00:31:48,258
 STATE WHERE THE CLIENT IS

711
00:31:48,258 --> 00:31:51,160
 LIKELY TO DEFINE THE OUTCOME

712
00:31:51,160 --> 00:31:51,928
 AS SATISFACTORY.

713
00:31:51,928 --> 00:31:56,332
 THIS IS A PARAMETER USED IN

714
00:31:56,332 --> 00:31:57,734
 PATIENT REPORTED OUTCOMES IN

715
00:31:57,734 --> 00:31:58,768
 HUMAN MEDICINE.

716
00:31:58,768 --> 00:32:00,903
 AND THEN A SUBSTANTIAL BENEFIT

717
00:32:00,903 --> 00:32:01,804
 WOULD ALSO BE USED TO

718
00:32:01,804 --> 00:32:03,273
 UNDERSTAND AND THAT IS THE

719
00:32:03,273 --> 00:32:05,808
 CLINICAL VALUE THAT THE CLIENT

720
00:32:05,808 --> 00:32:07,510
 CONSIDERS A SUBSTANTIAL

721
00:32:07,510 --> 00:32:08,678
 IMPROVEMENT.

722
00:32:08,678 --> 00:32:10,613
 SO AGAIN, THERE'S FURTHER WORK

723
00:32:10,613 --> 00:32:13,049
 TO DO TO PROVIDE OTHER

724
00:32:13,049 --> 00:32:14,284
 FEATURES AROUND THESE

725
00:32:14,284 --> 00:32:14,817
 PARTICULAR MEASURES.

726
00:32:14,817 --> 00:32:18,955
 SO I THINK WE NOW HAVE THREE

727
00:32:18,955 --> 00:32:27,964
 CLIENT REPORTED OUTCOMES IN

728
00:32:27,964 --> 00:32:31,401
 CANINE OSTEOARTHRITIS FOR

729
00:32:31,401 --> 00:32:34,437
 REGULATED TRIALS AND THE CBPI

730
00:32:34,437 --> 00:32:40,209
 HAS BEEN USED FOR SOMETIME

731
00:32:40,209 --> 00:32:44,347
 WITH WORK ON STEROIDALS AND

732
00:32:44,347 --> 00:32:46,616
 THE OUTCOME SLIGHTLY DIFFERENT

733
00:32:46,616 --> 00:32:48,951
 THAN I MEASURED FOR YOU TODAY

734
00:32:48,951 --> 00:32:50,253
 BUT FURTHER WORK IS REQUIRED

735
00:32:50,253 --> 00:32:53,356
 TO UNDERSTAND THE FEATURES OF

736
00:32:53,356 --> 00:32:55,091
 THESE OUTCOMES IN DIFFERENT

737
00:32:55,091 --> 00:32:55,692
 CONTEXTS.

738
00:32:55,692 --> 00:32:58,361
 AND THEN OF COARSE WE NEED TO

739
00:32:58,361 --> 00:33:00,263
 DIFFERENTIATE BETWEEN PONDERS

740
00:33:00,263 --> 00:33:01,831
 AND NONRESPONDERS AS

741
00:33:01,831 --> 00:33:03,566
 ACCURATELY AS POSSIBLE FOR

742
00:33:03,566 --> 00:33:04,033
 CLINICAL TRIALS.

743
00:33:04,033 --> 00:33:07,070
 AND JUST A BIT OF REFLECTION

744
00:33:07,070 --> 00:33:09,672
 REALLY TO FINISH UP WITH OF

745
00:33:09,672 --> 00:33:14,977
 HAVE WE GOT THIS RIGHT? 

746
00:33:14,977 --> 00:33:18,481
 SO WITH CANINE BENEFITS,

747
00:33:18,481 --> 00:33:21,284
 SUCCESS CAN BE DESCRIBED AS

748
00:33:21,284 --> 00:33:28,024
 INCREASE OF 1 POINT OR MORE 

749
00:33:28,024 --> 00:33:34,230
 AND OR WITH THE PIS, IF THERE

750
00:33:34,230 --> 00:33:36,933
 IS AN INCREASE OF 2 PERCENT OR

751
00:33:36,933 --> 00:33:37,233
 MORE.

752
00:33:37,233 --> 00:33:47,076
 AND THIS IS FROM A STUDY WITH

753
00:33:47,076 --> 00:33:48,344
 DOGS WITH PLACEBOS AND YOU CAN

754
00:33:48,344 --> 00:33:52,115
 SEE THE RATE IS HIGHER AT

755
00:33:52,115 --> 00:33:52,515
 53 PERCENT.

756
00:33:52,515 --> 00:34:03,092
 YOU GO BACK TO THE STUDY THAT

757
00:34:12,135 --> 00:34:13,603
 DUNCAN LASCELLES DID,

758
00:34:13,603 --> 00:34:17,273
 TREATMENT WAS ABLE TO SHOW

759
00:34:17,273 --> 00:34:19,342
 SUCCESS IN 14 AND 28 DAYS

760
00:34:19,342 --> 00:34:23,146
 WHEREAS IN THE CANINE INDEX,

761
00:34:23,146 --> 00:34:24,213
 THE PAIN WAS DESCRIBED AS

762
00:34:24,213 --> 00:34:24,514
 NULL.

763
00:34:24,514 --> 00:34:27,650
 SO I THINK WE NEED TO REFLECT

764
00:34:27,650 --> 00:34:30,052
 ON THESE CUTOFF VALUES.

765
00:34:30,052 --> 00:34:34,791
 MY CLINICAL EXPERIENCE, WE

766
00:34:34,791 --> 00:34:39,128
 HAVE HAD THIS IN THE UK FOR 

767
00:34:39,128 --> 00:34:40,830
 ABOUT TWO YEARS NOW AND A

768
00:34:40,830 --> 00:34:42,799
 LITTLE LONGER IN THE U.S.

769
00:34:42,799 --> 00:34:44,534
 THE INITIAL RESPONSE RATE FROM

770
00:34:44,534 --> 00:34:46,702
 CLIENTS SAY THEIR T.J. IS

771
00:34:46,702 --> 00:34:48,704
 IMPROVED IN ANY DEGREE AROUND

772
00:34:48,704 --> 00:34:49,305
 18 PERCENT.

773
00:34:49,305 --> 00:34:51,941
 IN THE TYPICAL STUDY GROUP,

774
00:34:51,941 --> 00:34:54,343
 THEY RESPOND AT SAY 50 PERCENT

775
00:34:54,343 --> 00:34:59,782
 SO I THINK FOR THE MOMENT THAT

776
00:34:59,782 --> 00:35:02,218
 CDRI CUTOFF TO ME IS A LITTLE

777
00:35:02,218 --> 00:35:04,153
 BIT HARSH AND PERHAPS FURTHER

778
00:35:04,153 --> 00:35:05,922
 WORK WILL HELP US TO

779
00:35:05,922 --> 00:35:07,490
 UNDERSTAND THAT A LITTLE BIT

780
00:35:07,490 --> 00:35:07,890
 MORE.

781
00:35:07,890 --> 00:35:10,259
 SO I GUESS A PASSION OF MINE

782
00:35:10,259 --> 00:35:12,228
 NOW THAT I AM BACK IN CLINICAL

783
00:35:12,228 --> 00:35:14,497
 PRACTICE IS TO ACTUALLY EMBED

784
00:35:14,497 --> 00:35:16,265
 THESE TOOLS IN CLINICAL

785
00:35:16,265 --> 00:35:20,470
 PRACTICE, NOT JUST WITHIN THE

786
00:35:20,470 --> 00:35:20,937
 RESEARCH ARENA.

787
00:35:20,937 --> 00:35:22,505
 AND WE DEVELOPED SOME WORK IN

788
00:35:22,505 --> 00:35:24,273
 ONE OF THESE BIG CORPORATE

789
00:35:24,273 --> 00:35:26,676
 GROUPS AND ONE OF THE THINGS

790
00:35:26,676 --> 00:35:29,312
 WE DID WAS DEVELOP WORK FLOWS

791
00:35:29,312 --> 00:35:33,616
 THERE SO WE ALSO HAD A MEASURE

792
00:35:33,616 --> 00:35:34,784
 OF PATIENT REPORTED OUTCOME

793
00:35:34,784 --> 00:35:37,186
 MEASURES AND THIS IS NOT JUST

794
00:35:37,186 --> 00:35:39,355
 FOR PAIN OR ARTHRITIS BUT

795
00:35:39,355 --> 00:35:41,424
 AVAILABLE NOW FOR A RANGE OF

796
00:35:41,424 --> 00:35:43,993
 CONDITIONS WITH VETERINARY

797
00:35:43,993 --> 00:35:44,660
 MEDICINE.

798
00:35:44,660 --> 00:35:45,862
 AND VETERINARY MEDICINE IS

799
00:35:45,862 --> 00:35:48,297
 VERY MUCH IN RESPONDER MODE.

800
00:35:48,297 --> 00:35:51,100
 WE WAIT TORE A -- FOR A CLIENT

801
00:35:51,100 --> 00:35:53,569
 TO RAISE AN ISSUE AND DEAL

802
00:35:53,569 --> 00:35:55,838
 WITH THAT AND HOPE IT GOES

803
00:35:55,838 --> 00:35:58,774
 AWAY FOR THE NEXT TIME BUT

804
00:35:58,774 --> 00:36:02,545
 PERHAPS BEING MORE PROACTIVE

805
00:36:02,545 --> 00:36:04,247
 WITH MEASUREMENTS OF DATA

806
00:36:04,247 --> 00:36:05,381
 OUTCOMES TO IMPROVE OUR CARE

807
00:36:05,381 --> 00:36:07,817
 AND THERE ARE VARIOUS WAYS TO

808
00:36:07,817 --> 00:36:12,355
 DO THAT IN THE CLINIC AND I

809
00:36:12,355 --> 00:36:15,258
 PUBLISHED A PRACTICE LAST YEAR

810
00:36:15,258 --> 00:36:15,892
 ON THIS PARTICULAR TOPIC.

811
00:36:15,892 --> 00:36:19,395
 SO ONE OF THE WORK FLOWS WE

812
00:36:19,395 --> 00:36:22,765
 DEVELOPED IN MY LAST POSITION,

813
00:36:22,765 --> 00:36:24,901
 IN THE PRACTICE MANAGEMENT

814
00:36:24,901 --> 00:36:26,636
 SYSTEM, THAT WOULD TRIGGER A

815
00:36:26,636 --> 00:36:29,772
 E-MAIL TO THE CLIENT ASKING

816
00:36:29,772 --> 00:36:30,540
 THEM FOR CONSENT TO

817
00:36:30,540 --> 00:36:34,810
 PARTICIPATE IN THE SURVEYS.

818
00:36:34,810 --> 00:36:36,979
 IF THEY CONSENT, THEY REPORT

819
00:36:36,979 --> 00:36:40,616
 THE CLIENT OUTCOME MEASURES,

820
00:36:40,616 --> 00:36:42,318
 THEY HAVE CONSENTED TO THAT

821
00:36:42,318 --> 00:36:44,587
 AND THOSE WOULD COME INTO THE

822
00:36:44,587 --> 00:36:46,222
 PRACTICE SYSTEM AND DEPENDING

823
00:36:46,222 --> 00:36:48,558
 WHAT THE TREATMENT WAS, THAT

824
00:36:48,558 --> 00:36:51,093
 WOULD TRIGGER REPEAT SURVEYS

825
00:36:51,093 --> 00:36:59,068
 AT MAYBE TWO WEEKS, SIX WEEKS,

826
00:36:59,068 --> 00:37:02,705
 26 YEARS AND -- WEEKS AND THEN

827
00:37:02,705 --> 00:37:03,439
 YEARLY AFTER.

828
00:37:03,439 --> 00:37:10,980
 SO IN THIS WAY WE WERE ABLE TO

829
00:37:10,980 --> 00:37:15,518
 COLLECT ASSESSMENTS FROM THE

830
00:37:15,518 --> 00:37:15,885
 TEAM.

831
00:37:15,885 --> 00:37:18,054
 AND REPORTED OUTCOME MEASURES

832
00:37:18,054 --> 00:37:18,888
 WERE COLLECTED ACROSS THE

833
00:37:18,888 --> 00:37:23,659
 GLOBE AND THIS IS JUST A SHOT

834
00:37:23,659 --> 00:37:24,660
 OF THE PLATFORM.

835
00:37:24,660 --> 00:37:29,699
 THESE ARE DOGS THAT RECEIVED

836
00:37:29,699 --> 00:37:34,303
 ARTHROSCOPY FOR ELBOW DATA AND

837
00:37:34,303 --> 00:37:39,542
 JUST SUPPLIESD -- SPLICED AND

838
00:37:39,542 --> 00:37:42,178
 DICED THE DATA ON THAT GRAPH.

839
00:37:42,178 --> 00:37:44,914
 SO I THINK THESE TOOLS ARE

840
00:37:44,914 --> 00:37:47,283
 IMPORTANT IN CLINICAL PRACTICE

841
00:37:47,283 --> 00:37:55,524
 AND MANY HERE ARE HERE FOR

842
00:37:55,524 --> 00:37:57,727
 PRACTICE AND HOPEFULLY WE'RE

843
00:37:57,727 --> 00:37:59,028
 GETTING THERE IN THIS REGARD.

844
00:37:59,028 --> 00:38:02,298
 SO WITH THAT, I WOULD SAY

845
00:38:02,298 --> 00:38:03,899
 THANK YOU VERY MUCH AND THANK

846
00:38:03,899 --> 00:38:11,374
 YOU AGAIN FOR INVITING ME.

847
00:38:11,374 --> 00:38:11,941
 [APPLAUSE]

848
00:38:11,941 --> 00:38:13,442
 >> THANKS VERY MUCH,
JOHN,

849
00:38:13,442 --> 00:38:15,611
 THIS IS A REALLY IMPORTANT

850
00:38:15,611 --> 00:38:16,345
 CONVERSATION.

851
00:38:16,345 --> 00:38:20,816
 AS WE DEVELOP OUTCOME MEASURES

852
00:38:20,816 --> 00:38:24,153
 AND UNDERSTANDING HOW WE

853
00:38:24,153 --> 00:38:25,254
 CONVERT CHANGES INTO

854
00:38:25,254 --> 00:38:26,288
 UNDERSTANDING WHAT IS

855
00:38:26,288 --> 00:38:29,025
 MEANINGFUL AND THEN ON IN TO

856
00:38:29,025 --> 00:38:30,426
 SUCCESS FAILURE ANALYSIS AND

857
00:38:30,426 --> 00:38:34,230
 THAT BRINGS ME TO THE NEXT

858
00:38:34,230 --> 00:38:35,464
 PRESENTATION, DOTTIE BROWN,

859
00:38:35,464 --> 00:38:37,466
 BECAUSE OF A RECENT CHANGE IN

860
00:38:37,466 --> 00:38:40,670
 JOBS, NOW WORKS FOR MARS

861
00:38:40,670 --> 00:38:42,171
 HEALTHCARE, HAD A CONFLICT

862
00:38:42,171 --> 00:38:43,606
 THAT COULDN'T BE RESOLVED SO

863
00:38:43,606 --> 00:38:45,307
 SHE IS IN LONDON AT THE

864
00:38:45,307 --> 00:38:47,009
 MOMENT, COULD NOT BE HERE BUT

865
00:38:47,009 --> 00:38:47,843
 HAS RECORDED A PRESENTATION

866
00:38:47,843 --> 00:38:50,579
 AND SHE WILL TALK ABOUT HER

867
00:38:50,579 --> 00:38:53,049
 APPROACH OF DEFINING

868
00:38:53,049 --> 00:38:53,949
 SUCCESS-FAILURE ANALYSIS AND

869
00:38:53,949 --> 00:38:55,284
 REMEMBER HAVE YOUR QUESTIONS

870
00:38:55,284 --> 00:38:56,652
 READY FOR THE PANEL SESSION

871
00:38:56,652 --> 00:38:58,487
 WHEN WE WILL GET EVERYONE

872
00:38:58,487 --> 00:39:04,560
 TOGETHER AND DISCUSS THESE

873
00:39:04,560 --> 00:39:05,494
 TOPICS.

874
00:39:05,494 --> 00:39:06,629
 >> GOOD MORNING, THIS
MORNING

875
00:39:06,629 --> 00:39:10,566
 I WILL SHARE THE SUCCESS

876
00:39:10,566 --> 00:39:14,103
 PROCESS WE USE FOR THE SUCCESS

877
00:39:14,103 --> 00:39:15,771
 FAILURE ANALYSIS AND THIS WEIR

878
00:39:15,771 --> 00:39:18,007
 NARROW IS GIVEN TO THE OWNER

879
00:39:18,007 --> 00:39:19,842
 TO IDENTIFY THE SEVERITY AND

880
00:39:19,842 --> 00:39:24,947
 CHRONIC PAIN OF THEIR DOGS

881
00:39:24,947 --> 00:39:29,819
 OSTEOARTHRITIS. 

882
00:39:29,819 --> 00:39:31,487
 SO WHEN WE START LOOKING AT

883
00:39:31,487 --> 00:39:35,658
 WHAT THE CONTROLS LOOK LIKE,

884
00:39:35,658 --> 00:39:38,294
 WE SEE THE PLACEBO DATA IS IN

885
00:39:38,294 --> 00:39:40,262
 BLUE AND THE NONSTEROIDAL

886
00:39:40,262 --> 00:39:41,430
 INTERVENTION ANIMALS ARE IN

887
00:39:41,430 --> 00:39:41,764
 RED.

888
00:39:41,764 --> 00:39:45,000
 AND WE EXPECT TO SEE MORE BLUE

889
00:39:45,000 --> 00:39:47,870
 ON THE LEFTHAND SIDE OF THE

890
00:39:47,870 --> 00:39:49,905
 CURVE WHERE THERE IS

891
00:39:49,905 --> 00:39:50,973
 DETERIORATION OR MINIMAL

892
00:39:50,973 --> 00:39:52,174
 IMPROVEMENT IN CHANGE SCORE

893
00:39:52,174 --> 00:39:54,710
 AND EXPECT TO SEE MORE RED ON

894
00:39:54,710 --> 00:39:55,911
 THE RIGHTHAND SIDE OF THE

895
00:39:55,911 --> 00:39:57,813
 CURVE WHERE THERE IS

896
00:39:57,813 --> 00:39:59,215
 SIGNIFICANT IMPROVEMENT IN THE

897
00:39:59,215 --> 00:40:00,916
 CHANGE SCORE OVER TIME AND WE

898
00:40:00,916 --> 00:40:03,486
 NOTICE A LOT OF OVERLAP

899
00:40:03,486 --> 00:40:04,820
 BETWEEN THESE TWO CURVES SO WE

900
00:40:04,820 --> 00:40:07,623
 SEE A LOT OF PURPLE ON THE

901
00:40:07,623 --> 00:40:08,758
 GRAPH.

902
00:40:08,758 --> 00:40:10,025
 AND MOST COMMONLY, THIS IS HOW

903
00:40:10,025 --> 00:40:12,027
 THE DATA IS HANDLED.

904
00:40:12,027 --> 00:40:17,600
 THE DATA IS ORDINAL MEANING

905
00:40:17,600 --> 00:40:19,769
 THE ORDER OF RESPONSE OPTION

906
00:40:19,769 --> 00:40:21,804
 IS MEAN ILLFUL.

907
00:40:21,804 --> 00:40:23,539
 SO IF -- MEANINGFUL.

908
00:40:23,539 --> 00:40:27,076
 SO IF THE OWNER CHOSES A 2 AND

909
00:40:27,076 --> 00:40:29,845
 THEN A 9 LATER ON DOWN THE

910
00:40:29,845 --> 00:40:31,781
 ROAD THEY ARE IDENTIFYING MORE

911
00:40:31,781 --> 00:40:33,082
 PAIN IN THEIR DOG OVER TIME

912
00:40:33,082 --> 00:40:35,584
 BUT IT IS NOT MEANINGFUL.

913
00:40:35,584 --> 00:40:37,486
 MOVING FROM A 2 TO 4 DOES NOT

914
00:40:37,486 --> 00:40:39,622
 MEAN A DOG IS IN DEVICE AS

915
00:40:39,622 --> 00:40:41,056
 MUCH PAIN, FOR EXAMPLE.

916
00:40:41,056 --> 00:40:43,826
 AND THIS DATA IS OFTEN

917
00:40:43,826 --> 00:40:44,460
 POSITIVELY SKEWED MEANING

918
00:40:44,460 --> 00:40:48,130
 THERE IS A TAIL TO THE RIGHT 

919
00:40:48,130 --> 00:40:50,099
 AND THE MEDIAN AND MEAN AND

920
00:40:50,099 --> 00:40:53,869
 LOW DO NOT LINE UP THE WAY

921
00:40:53,869 --> 00:40:56,739
 THEY NORMAL NORMALLY WOULD IN

922
00:40:56,739 --> 00:40:59,675
 A DISTRIBUTE INPOPULATION SO

923
00:40:59,675 --> 00:41:03,045
 WE NORMALLY COMPARE SCORES

924
00:41:03,045 --> 00:41:05,114
 BETWEEN GROUPS.

925
00:41:05,114 --> 00:41:09,185
 AND THIS IS AN IDEALIZED

926
00:41:09,185 --> 00:41:10,753
 VERSION OF WHAT THE SHAPE

927
00:41:10,753 --> 00:41:12,221
 WOULD LOOK LIKE.

928
00:41:12,221 --> 00:41:13,856
 THE CURVE WOULD VARY QUITE A

929
00:41:13,856 --> 00:41:16,592
 BIT PARTICULARLY WHEN WE'RE

930
00:41:16,592 --> 00:41:19,361
 DEALING WITH RELATIVELY SMALL

931
00:41:19,361 --> 00:41:20,729
 CONCENTRATIONS OF PATIENTS AT

932
00:41:20,729 --> 00:41:21,230
 CLINICAL TRIALS.

933
00:41:21,230 --> 00:41:23,666
 WHEN YOU HAVE A OUTLIER LIKE

934
00:41:23,666 --> 00:41:25,134
 THIS, THE CONCERN IS LARGE

935
00:41:25,134 --> 00:41:26,836
 IMPROVEMENTS IN A SMALL NUMBER

936
00:41:26,836 --> 00:41:29,238
 OF DOGS WITHIN A GROUP COULD

937
00:41:29,238 --> 00:41:31,207
 POTENTIALLY MASK A LACK OF

938
00:41:31,207 --> 00:41:33,275
 IMPROVEMENT OR MINIMAL

939
00:41:33,275 --> 00:41:34,243
 IMPROVEMENT OF MANY DOGS IN

940
00:41:34,243 --> 00:41:34,677
 THAT GROUP.

941
00:41:34,677 --> 00:41:36,612
 SO THIS IS JUST ONE OF THE

942
00:41:36,612 --> 00:41:39,081
 REASONS WHY THERE MAY BE AN

943
00:41:39,081 --> 00:41:41,450
 IMTUGS TO SHIFT THE FOCUS TO

944
00:41:41,450 --> 00:41:43,519
 LOOKING AT THE DATA AT THE

945
00:41:43,519 --> 00:41:45,754
 INDIVIDUAL ANIMAL LEVEL AS

946
00:41:45,754 --> 00:41:47,022
 OPPOSED TO COMPARING OVERALL

947
00:41:47,022 --> 00:41:48,290
 DIFFERENCES BETWEEN SCORES AND

948
00:41:48,290 --> 00:41:48,757
 GROUPS.

949
00:41:48,757 --> 00:41:50,626
 SO WITH THE GOAL TO ASSIST

950
00:41:50,626 --> 00:41:55,598
 WHETHER THE TREATMENT HAS A

951
00:41:55,598 --> 00:41:57,800
 MESH MEASURABLE EFFECT FOR A

952
00:41:57,800 --> 00:41:58,968
 ANALYTIC STUDY, THE CRITERIA

953
00:41:58,968 --> 00:42:01,103
 FOR THE TREATMENT OF EACH

954
00:42:01,103 --> 00:42:03,339
 PATIENT WITH SOME SORT OF

955
00:42:03,339 --> 00:42:06,175
 CUTOFF NEEDS TO BE PREDEFINED.

956
00:42:06,175 --> 00:42:09,078
 SO THE SUCCESS OR FAILURE CAN

957
00:42:09,078 --> 00:42:10,713
 BE ASSIGNED AT THE R AT THE

958
00:42:10,713 --> 00:42:13,682
 END OF THIS STUDY AND THEN THE

959
00:42:13,682 --> 00:42:16,518
 NUMBER OF TREATMENT FAILURES

960
00:42:16,518 --> 00:42:18,287
 AND SUCCESSES IN EACH GROUP

961
00:42:18,287 --> 00:42:19,321
 CAN BE COMPARED.

962
00:42:19,321 --> 00:42:21,390
 AND AGAIN THERE ARE LOTS OF

963
00:42:21,390 --> 00:42:23,225
 DIFFERENT WAYS TO DO THIS SO I

964
00:42:23,225 --> 00:42:26,228
 AM SHARING WHAT WE DID FOR THE

965
00:42:26,228 --> 00:42:28,998
 PCBI AND IN THIS CASE, WE HAVE

966
00:42:28,998 --> 00:42:30,199
 TWO DIFFERENT DOMAINS TO

967
00:42:30,199 --> 00:42:30,566
 CONSIDER.

968
00:42:30,566 --> 00:42:33,903
 WE HAVE A CUTOFF IN THE CHANGE

969
00:42:33,903 --> 00:42:36,906
 OF THE PAIN SEVERITY SCORE AND

970
00:42:36,906 --> 00:42:38,407
 CHANGE IN THE INTERFERENCE

971
00:42:38,407 --> 00:42:40,809
 SCORE AND HOW THOSE TWO

972
00:42:40,809 --> 00:42:43,279
 CUTOFFS MAY WORK TOGETHER.

973
00:42:43,279 --> 00:42:47,383
 SO FOR THIS STUDY WE PULLED

974
00:42:47,383 --> 00:42:49,285
 TWO INDEPENDENT DATASETS

975
00:42:49,285 --> 00:42:50,552
 THROUGH CLINICAL STUDY

976
00:42:50,552 --> 00:42:50,886
 DESIGNS.

977
00:42:50,886 --> 00:42:55,357
 THESE WERE BOTH PLACEBO

978
00:42:55,357 --> 00:42:58,394
 MINIMIZED TRIALS WHERE

979
00:42:58,394 --> 00:43:08,871
 CARPROFEN WAS USED AS A 

980
00:43:11,807 --> 00:43:12,041
 CONTROL.

981
00:43:12,041 --> 00:43:19,548
 AND THE DOGS RECEIVED

982
00:43:19,548 --> 00:43:21,817
 CARPROFEN ON DAY 4 AND THEN

983
00:43:21,817 --> 00:43:23,052
 AGAIN ON DAY 14.

984
00:43:23,052 --> 00:43:29,358
 ONE WAS SETTING THE CRITERIA

985
00:43:29,358 --> 00:43:31,660
 AND DEFINING TREATMENT SUCCESS

986
00:43:31,660 --> 00:43:36,799
 AS A REDUCTION OF 1, 2 AND 3

987
00:43:36,799 --> 00:43:37,566
 FOR THOSE SCORES.

988
00:43:37,566 --> 00:43:40,769
 SO THERE IS A LOT GOING ON IN

989
00:43:40,769 --> 00:43:42,871
 THIS SLIDE BUT THE IMPORTANT

990
00:43:42,871 --> 00:43:45,507
 THING TO NOTE IS WE BROKE THE

991
00:43:45,507 --> 00:43:49,244
 DATA DOWN IN THREE POPULATIONS

992
00:43:49,244 --> 00:43:52,114
 AND EACH OF THEM HAVE A

993
00:43:52,114 --> 00:43:54,616
 SEPARATE BOX ON THE SLIDE SO

994
00:43:54,616 --> 00:43:57,152
 WITH EACH BOX, WE VARIED THE

995
00:43:57,152 --> 00:43:58,921
 SUCCESS CRITERIA FOR EACH OF

996
00:43:58,921 --> 00:44:03,826
 THE TWO GIVING SCORED.

997
00:44:03,826 --> 00:44:04,526
 SO ULTIMATELY POPULATION 1

998
00:44:04,526 --> 00:44:09,198
 WHICH IS IN THE YELLOW BOX

999
00:44:09,198 --> 00:44:12,267
 INCLUDES 137 DOGS THAT HAD A

1000
00:44:12,267 --> 00:44:13,335
 BASELINE SEVERITY OR

1001
00:44:13,335 --> 00:44:16,705
 INTERFERENCE SCORE GREATER TO

1002
00:44:16,705 --> 00:44:20,676
 OR EQUAL TO ONE.

1003
00:44:20,676 --> 00:44:25,014
 BASELINE WAS 160 DOGS WITH AN

1004
00:44:25,014 --> 00:44:26,148
 INTERFERENCE SCORE GREATER

1005
00:44:26,148 --> 00:44:29,084
 THAN OR EQUAL TO 2.

1006
00:44:29,084 --> 00:44:33,022
 AND DOGS IN THE AQUA BOX WERE

1007
00:44:33,022 --> 00:44:38,827
 87 DOGS WHICH HAD A SEVERITY

1008
00:44:38,827 --> 00:44:39,995
 SCORE OR BASELINE AT 3.

1009
00:44:39,995 --> 00:44:42,865
 AND IN EACH OF THESE CRITERIA,

1010
00:44:42,865 --> 00:44:45,267
 WE VARIED THE REDUCTION IN

1011
00:44:45,267 --> 00:44:49,838
 SCORE AS 1, 2 AND 3 FOR ONE OR

1012
00:44:49,838 --> 00:44:53,976
 BOTH OF THE SEVERITY OR PAIN

1013
00:44:53,976 --> 00:44:54,476
 MEDICATION SCORES.

1014
00:44:54,476 --> 00:44:57,012
 AND EACH POPULATION OR SUCCESS

1015
00:44:57,012 --> 00:44:59,782
 CRITERIA, THE NUMBERS WERE

1016
00:44:59,782 --> 00:45:02,017
 SUMMARIZED FOR SUCCESSES OR

1017
00:45:02,017 --> 00:45:03,852
 FAILURES WITHIN EACH TREATMENT

1018
00:45:03,852 --> 00:45:05,954
 GROUPS AND THEN THE

1019
00:45:05,954 --> 00:45:12,928
 DIFFERENCES BETWEEN THE GROUPS

1020
00:45:12,928 --> 00:45:17,900
 WERE EVALUATED FOR SUCCESS AND

1021
00:45:17,900 --> 00:45:21,770
 AGAIN THE LINE WAS CALCULATED

1022
00:45:21,770 --> 00:45:25,974
 FOR FAILURE OR SUCCESS.

1023
00:45:25,974 --> 00:45:29,511
 SO FOR BOX NUMBER 2, THESE ARE

1024
00:45:29,511 --> 00:45:31,547
 REDUCTIONS GREATER TO OR EQUAL

1025
00:45:31,547 --> 00:45:33,582
 TO 1 IN THE PAIN SEVERITY

1026
00:45:33,582 --> 00:45:34,850
 SCORE AND GREATER THAN OR

1027
00:45:34,850 --> 00:45:37,853
 EQUAL TO 2 IN THE PAIN

1028
00:45:37,853 --> 00:45:40,355
 INTERFERENCE SCORE AND THEN IN

1029
00:45:40,355 --> 00:45:42,858
 POPULATION 3, A SIMILAR

1030
00:45:42,858 --> 00:45:46,295
 SCHOOL, 64.7 WAS OBTAINED WITH

1031
00:45:46,295 --> 00:45:48,564
 THAT SAME SUCCESS CRITERIA.

1032
00:45:48,564 --> 00:45:50,265
 FOR POPULATION 3, THERE WERE

1033
00:45:50,265 --> 00:45:53,035
 SOME ALTERNATE SUCCESS

1034
00:45:53,035 --> 00:45:54,803
 CRITERIA THAT YIELDED SIMILAR

1035
00:45:54,803 --> 00:45:56,438
 OR HIGHER POWER VALUES.

1036
00:45:56,438 --> 00:45:59,174
 AND WE ALSO WANTED TO LOOK AT

1037
00:45:59,174 --> 00:46:01,977
 THE POOL DATA IN THE WAY THE

1038
00:46:01,977 --> 00:46:03,779
 ORIGINAL DATASETS WERE

1039
00:46:03,779 --> 00:46:06,081
 ANALYZED TO MAKE SURE WE WERE

1040
00:46:06,081 --> 00:46:07,783
 SEEING CONSISTENT RESULTS.

1041
00:46:07,783 --> 00:46:09,885
 SO TO EVALUATE THE SAME DATA

1042
00:46:09,885 --> 00:46:17,192
 ON THE BASIS OF MEDIAN SCORES

1043
00:46:17,192 --> 00:46:24,199
 AS DONE PREVIOUSLY, THE

1044
00:46:24,199 --> 00:46:29,538
 BASELINE OF 137 DOGS WITH

1045
00:46:29,538 --> 00:46:32,007
 CARPROFEN AND THE POPULATION

1046
00:46:32,007 --> 00:46:34,042
 1, 2 AND 3 AS CALCULATED.

1047
00:46:34,042 --> 00:46:38,113
 THE CHANGES FROM BASELINE TO 4

1048
00:46:38,113 --> 00:46:42,551
 WAS SIGNIFICANTLY DIFFERENT

1049
00:46:42,551 --> 00:46:44,720
 BETWEEN CARPROFEN AND BASEBO I

1050
00:46:44,720 --> 00:46:51,660
 WANTED KATEING THE IMPROVEMENT

1051
00:46:51,660 --> 00:46:55,364
 IN THE CARPROFEN-TREATED DOGS

1052
00:46:55,364 --> 00:46:57,232
 OVER THE PLACEBO DOGS WHICH WE

1053
00:46:57,232 --> 00:46:59,868
 WOULD EXPECT.

1054
00:46:59,868 --> 00:47:03,372
 SO OVERALL THE CHANGE IN SCORE

1055
00:47:03,372 --> 00:47:05,474
 USING CHANGE IN MEAN SCORES

1056
00:47:05,474 --> 00:47:07,075
 USED PREVIOUSLY OR BY LOOKING

1057
00:47:07,075 --> 00:47:11,914
 AT THE NUMBER OF BE A ANIMALS

1058
00:47:11,914 --> 00:47:15,350
 CATEGORIZED AS SUCCESSES BASED

1059
00:47:15,350 --> 00:47:17,586
 ON PREDEFINED PAIN SEVERITY

1060
00:47:17,586 --> 00:47:19,288
 CRITERIA AND IDENTIFYING

1061
00:47:19,288 --> 00:47:20,255
 REDUCTIONS GREATER THAN OR

1062
00:47:20,255 --> 00:47:22,057
 EQUAL TO ONE IN THE PAIN

1063
00:47:22,057 --> 00:47:23,425
 SEVERITY SCORE AND GREATER

1064
00:47:23,425 --> 00:47:26,995
 THAN OR EQUAL TO 2 IN THE PAIN

1065
00:47:26,995 --> 00:47:29,765
 INTERFERENCE SCORE YIELDED THE

1066
00:47:29,765 --> 00:47:31,500
 HIGHEST POWER FOR BOTH

1067
00:47:31,500 --> 00:47:33,735
 POPULATION 2 AND POPULATION 3.

1068
00:47:33,735 --> 00:47:37,506
 SO DOGS WITH BASELINE SCORES

1069
00:47:37,506 --> 00:47:43,812
 GREATER THAN OR EQUAL TO 3.

1070
00:47:43,812 --> 00:47:48,717
 SO THIS WAS USED IN THE CBI

1071
00:47:48,717 --> 00:47:53,789
 APPROVAL STUDY FOR GALAPRANT

1072
00:47:53,789 --> 00:47:59,995
 IN 2016 AS WELL AS THE SCORES

1073
00:47:59,995 --> 00:48:06,635
 FOR ANOTHER DRUG USED IN THE

1074
00:48:06,635 --> 00:48:08,670
 U.S.

1075
00:48:08,670 --> 00:48:09,905
 NOTE/GALLIPRANT. 

1076
00:48:09,905 --> 00:48:16,812
 SO THIS IS THE REDUCTION LINE

1077
00:48:16,812 --> 00:48:18,847
 TO DETERMINE HOW EFFECTIVE THE

1078
00:48:18,847 --> 00:48:22,818
 TKR*UG IS AND THIS HAS BEEN

1079
00:48:22,818 --> 00:48:33,328
 CARRIED FOR -- FORWARD IN

1080
00:48:33,662 --> 00:48:34,029
 FUTURE STUDIES.

1081
00:48:34,029 --> 00:48:34,396
 [APPLAUSE]

1082
00:48:34,396 --> 00:48:35,764
 >> GREAT, PLENTY OF FOOD
FOR

1083
00:48:35,764 --> 00:48:37,499
 THOUGHT THERE.

1084
00:48:37,499 --> 00:48:39,067
 HOPEFULLY WILL STIMULATE SOME

1085
00:48:39,067 --> 00:48:40,102
 GREAT QUESTIONS DURING THE

1086
00:48:40,102 --> 00:48:41,169
 PANEL DISCUSSION.

1087
00:48:41,169 --> 00:48:43,739
 WE'RE GOING TO TAKE A

1088
00:48:43,739 --> 00:48:44,506
 15-MINUTE BREAK HERE.

1089
00:48:44,506 --> 00:48:47,509
 WE WILL COME BACK AT 10:  10,

1090
00:48:47,509 --> 00:48:50,178
 SO STRETCH YOUR LEGS, GRAB

1091
00:48:50,178 --> 00:48:54,583
 SOME COFFEE, COME BACK AT

1092
00:48:54,583 --> 00:48:55,350
 10:10 A.M.

1093
00:48:55,350 --> 00:48:56,885
 WE WILL HAVE GREATER

1094
00:48:56,885 --> 00:48:58,720
 DISCUSSIONS ON SPECIES AND

1095
00:48:58,720 --> 00:49:00,289
 OUTCOME MEASURES AND EXPLORE

1096
00:49:00,289 --> 00:49:02,457
 THE AREA OF CURVE ANALYSIS

1097
00:49:02,457 --> 00:49:03,325
 APPROACH VERSUS INDIVIDUAL

1098
00:49:03,325 --> 00:49:05,327
 TIME POINTS SO SEE YOU BACK

1099
00:49:05,327 --> 00:49:10,572
 HERE IN 15 MINUTES AT 10:10 

1100
00:49:10,572 --> 00:49:14,009
 >> NEXT WE HAVE PROFESSOR
LUNA

1101
00:49:14,009 --> 00:49:17,145
 WHO WORKS AT SAN PALO IN

1102
00:49:17,145 --> 00:49:18,513
 BRAZIL AND HAS REALLY BEEN THE

1103
00:49:18,513 --> 00:49:21,416
 DRIVER OF A LOT OF WORK

1104
00:49:21,416 --> 00:49:23,351
 PARTICULARLY IN PRODUCTION

1105
00:49:23,351 --> 00:49:24,953
 ANIMALS AROUND THE ASSESSMENT

1106
00:49:24,953 --> 00:49:27,255
 OF PAIN AND DEVELOPING OUTCOME

1107
00:49:27,255 --> 00:49:37,499
 PERSONNURES AND WILL TALK TO

1108
00:49:37,499 --> 00:49:39,567
 US NOW AND HE IS WITH US OVER

1109
00:49:39,567 --> 00:49:41,269
 ZOOM, THIS IS A RECORDED

1110
00:49:41,269 --> 00:49:42,704
 PRESENTATION, HE WILL BE NOT

1111
00:49:42,704 --> 00:49:51,946
 HERE BUT WITH US FOR THE

1112
00:49:51,946 --> 00:49:52,781
 DISCUSSION FORUM.

1113
00:49:52,781 --> 00:50:01,156
 >> I WOULD LIKE TO THANK
Dr.

1114
00:50:01,156 --> 00:50:02,223
 INNES AND ORGANIZERS.

1115
00:50:02,223 --> 00:50:12,734
 ON THIS YOU WILL FIND THE

1116
00:50:13,401 --> 00:50:18,373
 SCALES USED BY USERS --

1117
00:50:18,373 --> 00:50:18,840
 [INDISCERNIBLE]

1118
00:50:18,840 --> 00:50:21,576
 I HAVE SOME INTERESTS IN

1119
00:50:21,576 --> 00:50:32,153
 RELATION TO THE PRESENTATION 

1120
00:50:36,491 --> 00:50:42,931
 AND ACTUAL COMMITTEES AS SHOWN

1121
00:50:42,931 --> 00:50:43,264
 HERE.

1122
00:50:43,264 --> 00:50:50,171
 A SUCCESSFUL SCALE IS ONE WITH

1123
00:50:50,171 --> 00:50:50,772
 THE HIGHEST SPECIFICITY.

1124
00:50:50,772 --> 00:51:01,249
 ANOTHER WAY TO IDENTIFY

1125
00:51:04,152 --> 00:51:07,922
 SUCCESS IS INTRAREPEATABILITY

1126
00:51:07,922 --> 00:51:13,595
 AND INTER-RATER RELIABILITY OR

1127
00:51:13,595 --> 00:51:14,395
 REPRODUCIBILITY.

1128
00:51:14,395 --> 00:51:22,604
 THIS CAN BE SHOWN BY THE 

1129
00:51:22,604 --> 00:51:25,573
 CUTOFF SCORE AND THE CONSENSUS

1130
00:51:25,573 --> 00:51:28,643
 BASED STANDARDS FOR SELECTION 

1131
00:51:28,643 --> 00:51:35,984
 OF HEALTH MEASUREMENT

1132
00:51:35,984 --> 00:51:39,487
 INSTRUMENT. 

1133
00:51:39,487 --> 00:51:41,823
 AFTER A REVIEW, THE PAIN SCALE

1134
00:51:41,823 --> 00:51:49,030
 HAS ALSO BEEN PUBLISHED.

1135
00:51:49,030 --> 00:51:58,339
 THIS HAS BEEN PUBLISHED FOR

1136
00:51:58,339 --> 00:52:08,917
 CATTLE, AND THE CO SMIN SCALE 

1137
00:52:12,654 --> 00:52:20,028
 WAS DEVELOPED FOR ASSESSING

1138
00:52:20,028 --> 00:52:29,037
 POSTOPERATIVE PAIN IN COWS. 

1139
00:52:29,037 --> 00:52:30,638
 THE ORIGINAL UCAPS WAS

1140
00:52:30,638 --> 00:52:38,780
 DEVELOPED AND NEXT STEP WAS TO

1141
00:52:38,780 --> 00:52:41,883
 DEVELOP CLINICAL VALIDATION IN

1142
00:52:41,883 --> 00:52:51,259
 BULLS AND IN HOSPITAL

1143
00:52:51,259 --> 00:52:52,160
 ENVIRONMENTS.

1144
00:52:52,160 --> 00:52:57,265
 BOTH WERE DEVELOPED FOR

1145
00:52:57,265 --> 00:52:59,701
 SPECIFICITY.

1146
00:52:59,701 --> 00:53:03,037
 THE UCAPS, CPS AND UNIT AND

1147
00:53:03,037 --> 00:53:13,181
 THERE WAS NO DIFFERENCE IN THE

1148
00:53:13,181 --> 00:53:18,586
 SCORES BETWEEN BREEDS. 

1149
00:53:18,586 --> 00:53:20,521
 THIS SPECIFICITY OF SHOWING

1150
00:53:20,521 --> 00:53:21,256
 PAIN.

1151
00:53:21,256 --> 00:53:23,491
 THIS COULD BE USED CLINICALLY

1152
00:53:23,491 --> 00:53:30,198
 NOT ONLY FOR PROVIDING

1153
00:53:30,198 --> 00:53:32,533
 INFORMATION ON SURGERY BUT

1154
00:53:32,533 --> 00:53:42,143
 ALSO TO MAKE SURE THAT IT IS

1155
00:53:42,143 --> 00:53:43,611
 PLAUSIBLE.

1156
00:53:43,611 --> 00:53:48,716
 SO THERE WAS PAIN ASSESSMENT

1157
00:53:48,716 --> 00:53:55,923
 IN PAIN-FREE CATTLE AND IN 

1158
00:53:55,923 --> 00:53:56,658
 OTHERS FOR SURGERY.

1159
00:53:56,658 --> 00:54:06,968
 BECAUSE SHEEP ARE USED FOR 

1160
00:54:06,968 --> 00:54:10,605
 TRANSLATIONAL MEDICINE AND USA

1161
00:54:10,605 --> 00:54:15,643
 PS USED FOR POSTOPERATIVE

1162
00:54:15,643 --> 00:54:16,477
 SURGERY IN SHEEP.

1163
00:54:16,477 --> 00:54:22,850
 IT WAS ONLY LAPAROTOMY AND

1164
00:54:22,850 --> 00:54:24,018
 FIELD CONDITIONS.

1165
00:54:24,018 --> 00:54:32,760
 PAIN SCORES INCREASED AFTER

1166
00:54:32,760 --> 00:54:34,462
 SURGERY.

1167
00:54:34,462 --> 00:54:41,169
 THE PAIN WAS SIMILAR TO THE

1168
00:54:41,169 --> 00:54:42,370
 ORIGINAL STUDY.

1169
00:54:42,370 --> 00:54:47,208
 THIS IS THE NEW PAIN SCALE

1170
00:54:47,208 --> 00:54:50,945
 COVERAGE FROM OUR GROUP.

1171
00:54:50,945 --> 00:54:55,817
 THEY SCALED FOR PEOPLE AND

1172
00:54:55,817 --> 00:55:01,089
 ABSENCE OF BEHAVIORS EXPRESSED

1173
00:55:01,089 --> 00:55:11,599
 AND FOR GOATS IS IT WORKED

1174
00:55:15,169 --> 00:55:19,440
 VERY WELL.

1175
00:55:19,440 --> 00:55:21,943
 THE BOTTOMUCATU GOAT SCORE

1176
00:55:21,943 --> 00:55:32,487
 MEASURED RESPONSIVENESS AND

1177
00:55:33,054 --> 00:55:38,159
 CONSTRUCT VALIDITY IN ZONE 3 

1178
00:55:38,159 --> 00:55:41,529
 FOR PAIN-FREE GOAT AND

1179
00:55:41,529 --> 00:55:42,263
 UNDERGOING PAIN.

1180
00:55:42,263 --> 00:55:46,968
 A NEW STUDY CLINICALLY VALUE

1181
00:55:46,968 --> 00:55:49,604
 VALIDATES THE PIG SCALE FROM

1182
00:55:49,604 --> 00:55:50,405
 NORTH CAROLINA STATE

1183
00:55:50,405 --> 00:55:53,975
 UNIVERSITY AND SHOWS A SIMILAR

1184
00:55:53,975 --> 00:55:58,112
 RESULT TO INDEX.

1185
00:55:58,112 --> 00:56:05,853
 RELIABILITY OF PAIN SYSTEM AS 

1186
00:56:05,853 --> 00:56:07,655
 SHOWN IN GOATS.

1187
00:56:07,655 --> 00:56:18,232
 THIS IS AN EFFICIENT TOOL FOR 

1188
00:56:23,304 --> 00:56:24,338
 INTEROBSERVER RELIABILITY AND

1189
00:56:24,338 --> 00:56:29,911
 USED TO MEASURE PAIN IN SWINE.

1190
00:56:29,911 --> 00:56:32,213
 THE IMPLICATIONS AND

1191
00:56:32,213 --> 00:56:36,651
 CONCLUSIONS, THE UPAPS WAS 

1192
00:56:36,651 --> 00:56:43,224
 USED TO MEASURE SENSITIVITY

1193
00:56:43,224 --> 00:56:47,094
 AND PAIN AND IN ORDER OF

1194
00:56:47,094 --> 00:56:48,262
 POURS -- IMPORTANCE.

1195
00:56:48,262 --> 00:56:52,800
 FOR EXAMPLE, IN CATTLE, PAIN

1196
00:56:52,800 --> 00:56:56,070
 WAS SHOWN IN THE WALL OF --

1197
00:56:56,070 --> 00:56:56,537
 [INDISCERNIBLE]

1198
00:56:56,537 --> 00:57:03,244
 , THE SAME TYPE OF BEHAVIOR.

1199
00:57:03,244 --> 00:57:13,688
 THE BEHAVIOR ON THE TOP IS

1200
00:57:13,688 --> 00:57:15,122
 SUFFICIENT TO 1.65.

1201
00:57:15,122 --> 00:57:22,463
 WE DID THE SAME THING WITH 

1202
00:57:22,463 --> 00:57:26,200
 SWINE AND GOATS TO BETTER

1203
00:57:26,200 --> 00:57:29,537
 UNDERSTAND THE BEHAVIORS FOR

1204
00:57:29,537 --> 00:57:32,206
 PAIN TIGERS.

1205
00:57:32,206 --> 00:57:33,908
 AND THESE GIVE US BETTER

1206
00:57:33,908 --> 00:57:37,512
 UNDERSTANDING OF IMPORTANCE OF

1207
00:57:37,512 --> 00:57:40,281
 EACH BEHAVIOR FOR PAIN

1208
00:57:40,281 --> 00:57:41,148
 DIAGNOSIS.

1209
00:57:41,148 --> 00:57:43,251
 IT IS A STEP TOWARDS AN

1210
00:57:43,251 --> 00:57:44,852
 APPLICATION CAPABLE OF

1211
00:57:44,852 --> 00:57:46,020
 AUTOMATICALLY ESTIMATING THE

1212
00:57:46,020 --> 00:57:49,190
 PROBABILITY OF ANIMAL NEEDING

1213
00:57:49,190 --> 00:57:55,796
 ANA LG ESIA OR NOT.

1214
00:57:55,796 --> 00:58:01,235
 BASED ON A PAIN RECOGNITION

1215
00:58:01,235 --> 00:58:04,672
 USING FACIAL AREA AND BODY

1216
00:58:04,672 --> 00:58:10,244
 POSTURE TO AN ACCURACY OF

1217
00:58:10,244 --> 00:58:14,348
 87 PERCENT AND FOR THE MOST

1218
00:58:14,348 --> 00:58:24,892
 RECENT MODEL, USING AI FOR 

1219
00:58:26,227 --> 00:58:27,461
 AUTHOMATIC PAIN DETECTION.

1220
00:58:27,461 --> 00:58:32,199
 WE ARE DEVELOPING NEW STUDY

1221
00:58:32,199 --> 00:58:37,305
 FOR ACCURACY OF PAIN MEASURE

1222
00:58:37,305 --> 00:58:47,848
 BASED ON THE UPAPS -- USA PS

1223
00:58:50,818 --> 00:59:01,262
 AND SHEEP FACIAL EXPRESSION

1224
00:59:01,662 --> 00:59:02,797
 FOR SCORING.

1225
00:59:02,797 --> 00:59:06,534
 MACHINE OUTPERFORMS HUMAN 

1226
00:59:06,534 --> 00:59:07,902
 EXPECT IN SHEEP PAIN

1227
00:59:07,902 --> 00:59:08,836
 VALIDATION.

1228
00:59:08,836 --> 00:59:09,770
 WHAT IS NEXT?

1229
00:59:09,770 --> 00:59:12,106
 ARE THE RESULTS PRODUCIBLE

1230
00:59:12,106 --> 00:59:15,309
 WHEN USED BY UNTRAINED

1231
00:59:15,309 --> 00:59:15,676
 SUBJECTS?

1232
00:59:15,676 --> 00:59:21,315
 WE NEED TO MODIFY THE SCALE

1233
00:59:21,315 --> 00:59:28,522
 FOR DIFFERENT AGE, SEX, OTHER 

1234
00:59:28,522 --> 00:59:33,427
 TYPES OF PAIN AND IMPLEMENT

1235
00:59:33,427 --> 00:59:33,828
 ALGORITHMS.

1236
00:59:33,828 --> 00:59:39,166
 ARTIFICIAL INTELLIGENCE CAN BE

1237
00:59:39,166 --> 00:59:42,603
 INSERTED IN APPLICATIONS FOR

1238
00:59:42,603 --> 00:59:42,970
 VET PAIN.

1239
00:59:42,970 --> 00:59:53,414
 THANKS A LOT FOR YOUR

1240
00:59:53,948 --> 00:59:54,382
 PATIENCE.

1241
00:59:54,382 --> 00:59:54,749
 [APPLAUSE]

1242
00:59:54,749 --> 00:59:55,950
 >> THANKS FOR THAT AND SO
WHAT

1243
00:59:55,950 --> 00:59:58,819
 WE HAVE HEARD SO FAR JUST AS A

1244
00:59:58,819 --> 01:00:01,022
 QUICK RECAP IS DIFFERENT

1245
01:00:01,022 --> 01:00:02,189
 APPROACHES TO DEFINING SUCCESS

1246
01:00:02,189 --> 01:00:02,990
 FAILURE.

1247
01:00:02,990 --> 01:00:04,925
 WE HAVE THE ANCHOR BASED

1248
01:00:04,925 --> 01:00:07,361
 METHOD THAT WAS DESCRIBED.

1249
01:00:07,361 --> 01:00:10,097
 A STATISTICAL APPROACH TO

1250
01:00:10,097 --> 01:00:13,100
 PAUSING PARSING OUT HOW WE

1251
01:00:13,100 --> 01:00:14,468
 SEPARATED GROUPS AND THEN

1252
01:00:14,468 --> 01:00:16,337
 PRESENTED DATA BASED ON RESCUE

1253
01:00:16,337 --> 01:00:18,139
 OR INTERVENTION SO NOW WE WILL

1254
01:00:18,139 --> 01:00:21,876
 CONTINUE THE THEME AND IT IS 

1255
01:00:21,876 --> 01:00:29,750
 MY PLEASURE TO INTRODUCE MIKE

1256
01:00:29,750 --> 01:00:31,152
 CONZEMIUS FROM THE UNIVERSITY

1257
01:00:31,152 --> 01:00:35,523
 OF MINNESOTA AND HAS DRIVEN

1258
01:00:35,523 --> 01:00:37,725
 THE REACTION FORCES IN PAIN

1259
01:00:37,725 --> 01:00:38,092
 PATIENTS.

1260
01:00:38,092 --> 01:00:40,061
 HE RECENTLY STARTED HIS OWN

1261
01:00:40,061 --> 01:00:44,532
 PRACTICE IN ARIZONA,

1262
01:00:44,532 --> 01:00:46,300
 UNFORTUNATELY LIKE PROFESSOR

1263
01:00:46,300 --> 01:00:53,541
 LUNA, UNABLE TO JOIN US

1264
01:00:53,541 --> 01:00:55,876
 PHYSICALLY SO HE IS JOINING US

1265
01:00:55,876 --> 01:00:56,644
 OVER ZOOM.

1266
01:00:56,644 --> 01:01:07,021
 MIKE, OVER TO YOU.

1267
01:01:09,056 --> 01:01:11,492
 >> IS YOUR ZOOM TURNED
UP?

1268
01:01:11,492 --> 01:01:11,859
 >> SORRY?

1269
01:01:11,859 --> 01:01:13,127
 >> WE COULDN'T HEAR YOU
FOR A

1270
01:01:13,127 --> 01:01:15,496
 SECOND BUT WE CAN HEAR YOU

1271
01:01:15,496 --> 01:01:15,763
 NOW.

1272
01:01:15,763 --> 01:01:16,464
 >> THANK YOU.

1273
01:01:16,464 --> 01:01:18,099
 THIS IS ABOUT GROUND REACTION

1274
01:01:18,099 --> 01:01:20,601
 FORCES AND MANY OF YOU MAY BE

1275
01:01:20,601 --> 01:01:22,036
 UNFAMILIAR WITH GROUND

1276
01:01:22,036 --> 01:01:23,304
 REACTION FORCES SO BRIEFLY

1277
01:01:23,304 --> 01:01:26,941
 WHEN YOU STEP ON A SCALE IT

1278
01:01:26,941 --> 01:01:27,975
 SAYS, YOU KNOW, 160 POUNDS,

1279
01:01:27,975 --> 01:01:29,343
 THAT IS A GROUND REACTION

1280
01:01:29,343 --> 01:01:29,777
 FORCE.

1281
01:01:29,777 --> 01:01:32,847
 SO WE ARE MEASURING IN DOGS,

1282
01:01:32,847 --> 01:01:36,851
 WHAT THIS TALK IS ABOUT, IN

1283
01:01:36,851 --> 01:01:41,055
 DOGS ALTHOUGH THIS COULD BE

1284
01:01:41,055 --> 01:01:42,256
 TRANSLAID -- TRANSLATED TO

1285
01:01:42,256 --> 01:01:49,430
 OTHER SPECIES WHERE WE'RE 

1286
01:01:49,430 --> 01:01:50,264
 MEASURING GROUND REACTION

1287
01:01:50,264 --> 01:01:51,165
 FORCES.

1288
01:01:51,165 --> 01:01:52,399
 SO THIS IS PARALLEL TO THE

1289
01:01:52,399 --> 01:01:55,803
 FLOOR AND VERY SENSITIVE AND

1290
01:01:55,803 --> 01:01:56,904
 COMPLICATIONAL AND YOU MEASURE

1291
01:01:56,904 --> 01:01:59,340
 A NUMBER OF OTHER THINGS OF

1292
01:01:59,340 --> 01:02:00,808
 MOTION DATA ALONG WITH THAT.

1293
01:02:00,808 --> 01:02:03,811
 SO THAT IS WHAT GROUND

1294
01:02:03,811 --> 01:02:05,546
 REACTION FORCES ARE AND WHEN

1295
01:02:05,546 --> 01:02:07,948
 -- THE REASON WE DO THAT, FOR

1296
01:02:07,948 --> 01:02:10,384
 ME, ANY WAY THE REASON I DO

1297
01:02:10,384 --> 01:02:16,023
 IT, IS ONE, IT GENERATES SOME

1298
01:02:16,023 --> 01:02:16,524
 OBJECTIVE NUMBER.

1299
01:02:16,524 --> 01:02:19,260
 AND IT IS A NUMBER GENERATED

1300
01:02:19,260 --> 01:02:22,263
 BY THE ACTUAL PATIENT OR THE

1301
01:02:22,263 --> 01:02:25,232
 STUDY SUBJECT, IF YOU WILL, AS

1302
01:02:25,232 --> 01:02:28,769
 OPPOSED TO A PERSON LOOKING AT

1303
01:02:28,769 --> 01:02:31,405
 AN ANIMAL AND GENERATING A

1304
01:02:31,405 --> 01:02:31,906
 NUMBER.

1305
01:02:31,906 --> 01:02:34,708
 DOGS I DO FOR ONE OF TWO

1306
01:02:34,708 --> 01:02:35,042
 REASONS.

1307
01:02:35,042 --> 01:02:38,746
 THEY LIMP BECAUSE A LIMB PUTS

1308
01:02:38,746 --> 01:02:43,417
 OR A -- LIMB HURTS OR A LIMB

1309
01:02:43,417 --> 01:02:44,451
 DOESN'T WORK CORRECTLY, LIKE

1310
01:02:44,451 --> 01:02:45,619
 POINTED IN THE WRONG DIRECTION

1311
01:02:45,619 --> 01:02:47,922
 OR SOMETHING LIKE THAT.

1312
01:02:47,922 --> 01:02:49,123
 SO INTUITIVELY, THERE IS AN

1313
01:02:49,123 --> 01:02:50,624
 INJURY THAT WOULD CAUSE PAIN

1314
01:02:50,624 --> 01:02:54,929
 AND THEY ARE LIMITING AND THEN

1315
01:02:54,929 --> 01:02:56,931
 I THINK WE CAN MEASURE,

1316
01:02:56,931 --> 01:03:01,669
 QUANTIFY, THAT AMOUNT OF

1317
01:03:01,669 --> 01:03:03,771
 DISCOMFORT.

1318
01:03:03,771 --> 01:03:04,405
 SO DISCLAIMER, DISCLOSURE,

1319
01:03:04,405 --> 01:03:05,940
 REALLY GOT NOTHING TO HIDE.

1320
01:03:05,940 --> 01:03:08,475
 AND SO I AM GOING TO BE

1321
01:03:08,475 --> 01:03:12,112
 SHARING THINGS FROM A PAPER WE

1322
01:03:12,112 --> 01:03:13,814
 PUBLISHED, OH, GEEZ, ABOUT A

1323
01:03:13,814 --> 01:03:16,183
 YEAR OR TWO, YEAR AND A HALF

1324
01:03:16,183 --> 01:03:19,053
 OR SO AGO OF BEST PRACTICE FOR

1325
01:03:19,053 --> 01:03:20,421
 GROUND REACTION FORCES IN THE

1326
01:03:20,421 --> 01:03:20,955
 DOGS.

1327
01:03:20,955 --> 01:03:24,124
 IT WAS MYSELF AND A SERIES OF

1328
01:03:24,124 --> 01:03:28,128
 OTHER AUTHORS THAT HAVE A LOT

1329
01:03:28,128 --> 01:03:29,763
 OF EXPERTISE USING THIS AND

1330
01:03:29,763 --> 01:03:32,032
 THE REASON WHY WE DID IT,

1331
01:03:32,032 --> 01:03:34,134
 REALLY, IS ONE, BECAUSE OF THE

1332
01:03:34,134 --> 01:03:38,439
 PAWS GROUP THAT WAS A BIT OF A

1333
01:03:38,439 --> 01:03:42,142
 MOTIVATING FACTOR, BUT ALSO

1334
01:03:42,142 --> 01:03:43,210
 BECAUSE PEOPLE START CUTTING

1335
01:03:43,210 --> 01:03:45,679
 CORNERS, TRYING TO COME UP

1336
01:03:45,679 --> 01:03:47,481
 WITH SOMETHING THAT CAN MAYBE

1337
01:03:47,481 --> 01:03:49,383
 BE SIMILAR TO THE GOLD

1338
01:03:49,383 --> 01:03:51,619
 STANDARD, IF YOU WILL, AND

1339
01:03:51,619 --> 01:03:55,256
 WHEN THEY CUT THOSE CORNERS,

1340
01:03:55,256 --> 01:03:58,959
 THEY KIND OF, LIKE ANY TOOL

1341
01:03:58,959 --> 01:04:00,527
 THAT IS REALLY GOOD, PEOPLE

1342
01:04:00,527 --> 01:04:04,131
 GET IN THE WAY OF IT.

1343
01:04:04,131 --> 01:04:07,101
 AND SO IT ADDRESSES -- THIS

1344
01:04:07,101 --> 01:04:09,103
 PAPER ADDRESSES STANDARD

1345
01:04:09,103 --> 01:04:11,005
 OPERATING PROCEDURES, QUALITY

1346
01:04:11,005 --> 01:04:16,076
 ASSURANCE, HOW YOU PICK

1347
01:04:16,076 --> 01:04:17,177
 SUBJECTS, DATA NORMALIZATION,

1348
01:04:17,177 --> 01:04:17,678
 SO FORTH.

1349
01:04:17,678 --> 01:04:19,747
 SO ONE PART OF THAT IS

1350
01:04:19,747 --> 01:04:21,015
 ACTUALLY HOW TO MEASURE THINGS

1351
01:04:21,015 --> 01:04:23,417
 AND WHAT IS QUANTIFIABLE, WHAT

1352
01:04:23,417 --> 01:04:24,585
 IS THE DIFFERENCE THAT

1353
01:04:24,585 --> 01:04:25,352
 MATTERS.

1354
01:04:25,352 --> 01:04:30,624
 SO FIRST OF ALL, WHAT GROUND

1355
01:04:30,624 --> 01:04:32,927
 REACTION FORCE DATA SHOULD BE

1356
01:04:32,927 --> 01:04:34,828
 USED AND ONE THING THAT WE

1357
01:04:34,828 --> 01:04:36,430
 WENT BACK AND FORTH ABOUT, AND

1358
01:04:36,430 --> 01:04:37,898
 THERE IS A LOT OF DATA OUT

1359
01:04:37,898 --> 01:04:40,334
 THERE IN THE LITERATURE THAT,

1360
01:04:40,334 --> 01:04:49,009
 FOR EXAMPLE, USES THIS BUT NOT

1361
01:04:49,009 --> 01:04:49,310
 THAT.

1362
01:04:49,310 --> 01:04:51,445
 AND, WELL, I THINK WHAT I AM

1363
01:04:51,445 --> 01:04:52,346
 SAYING IS WHEN YOU GET

1364
01:04:52,346 --> 01:04:54,448
 TOGETHER IN A ROOM OF EXPERTS

1365
01:04:54,448 --> 01:04:55,950
 AND DEBATE WHAT YOU HAVE TO DO

1366
01:04:55,950 --> 01:04:57,551
 OR WHAT IS THE GOLD STANDARD,

1367
01:04:57,551 --> 01:04:59,954
 SOMETIMES YOU HAVE TO GIVE UP

1368
01:04:59,954 --> 01:05:01,722
 SOME OF YOUR OWN PUBLICATIONS

1369
01:05:01,722 --> 01:05:04,091
 AND THAT IS WHAT ALL OF US HAD

1370
01:05:04,091 --> 01:05:06,994
 TO DO AT ONE POINT OR ANOTHER

1371
01:05:06,994 --> 01:05:08,662
 THROUGHOUT THIS.

1372
01:05:08,662 --> 01:05:11,765
 SO REALLY A MINIMUM AMOUNT OF

1373
01:05:11,765 --> 01:05:17,438
 DATA SHOULD BE CONSIDERED TO 

1374
01:05:17,438 --> 01:05:20,007
 INCLUDE VELOCITY,

1375
01:05:20,007 --> 01:05:21,775
 ACCELERATION, PEAK MOVEMENT

1376
01:05:21,775 --> 01:05:22,176
 AND VI.

1377
01:05:22,176 --> 01:05:28,949
 SO THIS IS USED TO GENERATE 

1378
01:05:28,949 --> 01:05:30,150
 USABLE, RELIABLE DATA.

1379
01:05:30,150 --> 01:05:31,418
 VELOCITY AND ACCELERATION ARE

1380
01:05:31,418 --> 01:05:33,020
 SUPER IMPORTANT AND THE REASON

1381
01:05:33,020 --> 01:05:35,189
 FOR THAT IS NOT EVERY PATIENT

1382
01:05:35,189 --> 01:05:43,731
 IS THE EXACT SAME SIZE AND A 

1383
01:05:43,731 --> 01:05:51,105
 PEAK VERTICAL FORCE AND VI

1384
01:05:51,105 --> 01:05:52,806
 RESPOND DIFFERENTLY TO

1385
01:05:52,806 --> 01:05:53,574
 VELOCITY.

1386
01:05:53,574 --> 01:05:57,244
 SO YOU COULD EITHER, WHEN YOU

1387
01:05:57,244 --> 01:05:59,580
 MEASURE VELOCITY, MEASURE

1388
01:05:59,580 --> 01:06:01,015
 TORSO VELOCITY OR MEASURE

1389
01:06:01,015 --> 01:06:03,050
 CONTACT TIME, HOW MUCH TIME

1390
01:06:03,050 --> 01:06:04,251
 THE FOOT IS IN CONTACT WITH

1391
01:06:04,251 --> 01:06:06,186
 THE GROUND.

1392
01:06:06,186 --> 01:06:08,389
 WELL, THOSE THINGS CHANGE

1393
01:06:08,389 --> 01:06:10,557
 DEPENDING ON HOW TALL YOU ARE.

1394
01:06:10,557 --> 01:06:12,059
 SO IF YOU CAN KIND OF IMAGINE

1395
01:06:12,059 --> 01:06:14,595
 IF I AM WALKING NEXT TO

1396
01:06:14,595 --> 01:06:16,864
 SOMEONE THAT IS HALF MY HEIGHT

1397
01:06:16,864 --> 01:06:20,434
 AND WE ARE WALKING AT THE SAME

1398
01:06:20,434 --> 01:06:23,037
 TORSO VELOCITY, OUR FEET WILL

1399
01:06:23,037 --> 01:06:24,671
 BE MOVING AT DIFFERENT

1400
01:06:24,671 --> 01:06:25,973
 VELOCITIES.

1401
01:06:25,973 --> 01:06:29,510
 SO OUR TORSO VELOCITY IS THE

1402
01:06:29,510 --> 01:06:32,079
 SAME BUT OUR FOOT VELOCITY AND

1403
01:06:32,079 --> 01:06:33,747
 CONTACT TIME WITH THE ACTUAL

1404
01:06:33,747 --> 01:06:35,649
 FLOOR IS DIFFERENT.

1405
01:06:35,649 --> 01:06:37,184
 SO REALISTICALLY WHEN I AM

1406
01:06:37,184 --> 01:06:39,219
 WALKING FAST, THE PERSON WHO

1407
01:06:39,219 --> 01:06:41,188
 IS HALF MY HEIGHT MAY ACTUALLY

1408
01:06:41,188 --> 01:06:42,589
 BE JOGGING.

1409
01:06:42,589 --> 01:06:44,925
 SO WE ACTUALLY GENERATE

1410
01:06:44,925 --> 01:06:46,693
 DIFFERENT FORCES, DIFFERENT

1411
01:06:46,693 --> 01:06:47,461
 GROUND REACTION FORCES.

1412
01:06:47,461 --> 01:06:49,963
 SO YOU HAVE TO MEASURE

1413
01:06:49,963 --> 01:06:52,199
 VELOCITY, YOU HAVE TO REPORT

1414
01:06:52,199 --> 01:06:55,569
 VELOCITY, THERE ARE WAYS TO

1415
01:06:55,569 --> 01:06:58,872
 NORMALIZE IT AND THE DETAILS

1416
01:06:58,872 --> 01:07:02,209
 WITH RESPECT TO THAT WITH OUR

1417
01:07:02,209 --> 01:07:05,946
 PATIENTS IS BY WEIGHT AND

1418
01:07:05,946 --> 01:07:08,515
 HEIGHT AND THAT IS MENTIONED

1419
01:07:08,515 --> 01:07:10,084
 IN THAT PAPER.

1420
01:07:10,084 --> 01:07:14,788
 YOU HAVE TO NOTICE PEAK

1421
01:07:14,788 --> 01:07:18,058
 VERTICAL FORCE AND VI AND THEY

1422
01:07:18,058 --> 01:07:19,893
 RESPOND DIFFERENTLY TO

1423
01:07:19,893 --> 01:07:21,195
 VELOCITY AND ACCELERATION.

1424
01:07:21,195 --> 01:07:24,298
 THERE ARE A NUMBER OF PAPERS

1425
01:07:24,298 --> 01:07:26,633
 IN THE VETERINARY LITERATURE

1426
01:07:26,633 --> 01:07:27,901
 FOR EXAMPLE, GOSH, I WOULD SAY

1427
01:07:27,901 --> 01:07:29,870
 YOU COULD PULL OUT HALF OF

1428
01:07:29,870 --> 01:07:32,039
 THEM THAT WOULD RECORD ONLY

1429
01:07:32,039 --> 01:07:35,442
 PEEK VERTICAL FORCE AND SOME

1430
01:07:35,442 --> 01:07:37,511
 OF THEM DON'T MEASURE

1431
01:07:37,511 --> 01:07:40,414
 ACCELERATION AND SOME DON'T

1432
01:07:40,414 --> 01:07:40,914
 MEASURE VELOCITY.

1433
01:07:40,914 --> 01:07:45,619
 SO IT IS KIND OF LIKE I AM

1434
01:07:45,619 --> 01:07:56,196
 GOING TO PRESCRIBE MYOCEMIA AS

1435
01:07:56,797 --> 01:08:02,102
 BROWN HAIR AS OPPOSED TO

1436
01:08:02,102 --> 01:08:06,106
 SAYING BROWN HAIR, 160 POUNDS,

1437
01:08:06,106 --> 01:08:09,109
 5'10" AND WEARING PINK ON

1438
01:08:09,109 --> 01:08:09,676
 WEDNESDAYS.

1439
01:08:09,676 --> 01:08:11,445
 NOT A RULE, JUST A RULE I

1440
01:08:11,445 --> 01:08:12,012
 FOLLOW.

1441
01:08:12,012 --> 01:08:14,381
 SO YOU HAVE SOME EXAMPLES HERE

1442
01:08:14,381 --> 01:08:25,125
 AND LOOK AT IS THE PEAK CHANGE

1443
01:08:25,125 --> 01:08:29,796
 FROM VERTICAL VELOCITY

1444
01:08:29,796 --> 01:08:31,732
 RECORDED IN A INDIVIDUAL OR

1445
01:08:31,732 --> 01:08:35,269
 GROUP OF WALKING DOGS TREATED

1446
01:08:35,269 --> 01:08:38,071
 FOR OSTEOARTHRITIS OVER TWO

1447
01:08:38,071 --> 01:08:39,239
 MONTHS CLINICALLY IMPORTANT?

1448
01:08:39,239 --> 01:08:41,742
 WELL, IF YOU PUT THOSE DATA

1449
01:08:41,742 --> 01:08:43,076
 POINTS TOGETHER AND DIVIDE BY

1450
01:08:43,076 --> 01:08:45,412
 TWO, WE HAVE A 10 PERCENT

1451
01:08:45,412 --> 01:08:47,080
 IMPROVEMENT IN GROUND REACTION

1452
01:08:47,080 --> 01:08:49,516
 FORCES AND WHAT I WOULD TELL

1453
01:08:49,516 --> 01:08:51,485
 YOU IS DEPENDING ON THE

1454
01:08:51,485 --> 01:08:53,720
 DISEASE, IF THIS WAS

1455
01:08:53,720 --> 01:08:55,923
 OSTEOARTHRITIS, THAT WOULD BE

1456
01:08:55,923 --> 01:08:59,693
 A VERY IMPRESSIVE MOVEMENT.

1457
01:08:59,693 --> 01:09:07,434
 SO LET'S LOOK AT WHAT THE PEAK

1458
01:09:07,434 --> 01:09:09,369
 VERTICAL FORCE.

1459
01:09:09,369 --> 01:09:13,640
 SO 37 TO 40 AND VI FROM 14 TO

1460
01:09:13,640 --> 01:09:14,942
 12.5, JUST THE OPPOSITE.

1461
01:09:14,942 --> 01:09:19,780
 SO IT IS ACTUALLY A DECREASE

1462
01:09:19,780 --> 01:09:20,247
 OF 10.1 PERCENT.

1463
01:09:20,247 --> 01:09:22,683
 IF YOU AVERAGE THOSE TWO, THE

1464
01:09:22,683 --> 01:09:25,118
 NET GROUND REACTION FORCE

1465
01:09:25,118 --> 01:09:25,752
 ACTUALLY DECREASED BY

1466
01:09:25,752 --> 01:09:26,353
 1 PERCENT.

1467
01:09:26,353 --> 01:09:28,522
 SO THIS IS A VERY DIFFERENT

1468
01:09:28,522 --> 01:09:30,457
 FINDING THAN WHAT OCCURRED IN

1469
01:09:30,457 --> 01:09:31,158
 THE FIRST EXAMPLE.

1470
01:09:31,158 --> 01:09:34,228
 THIS IS WHY YOU HAVE TO RECORD

1471
01:09:34,228 --> 01:09:35,128
 VELOCITY AND ACCELERATION AND

1472
01:09:35,128 --> 01:09:38,465
 WHY YOU HAVE TO REPORT GROUND

1473
01:09:38,465 --> 01:09:43,370
 REACTION FORCES TOGETHER.

1474
01:09:43,370 --> 01:09:46,373
 YOU CAN'T CARRY FORWARD AND

1475
01:09:46,373 --> 01:09:47,040
 REPORT JUST ONE.

1476
01:09:47,040 --> 01:09:48,875
 SO I FEEL LIKE WHEN YOU ARE

1477
01:09:48,875 --> 01:09:50,944
 LOOKING AT GROUND REACTION

1478
01:09:50,944 --> 01:09:52,813
 FORCES, OBVIOUSLY IT IS NOT

1479
01:09:52,813 --> 01:09:53,580
 ONLY THE SUBJECT BUT IF YOU

1480
01:09:53,580 --> 01:09:57,451
 WANT TO SAY WHAT IS A

1481
01:09:57,451 --> 01:09:58,085
 CLINICALLY MEANINGFUL

1482
01:09:58,085 --> 01:09:59,386
 DIFFERENCE, THE DISEASE

1483
01:09:59,386 --> 01:10:03,557
 MATTERS AND IF IT IS DOGS WITH

1484
01:10:03,557 --> 01:10:06,927
 A CRANIO CRUCIATE

1485
01:10:06,927 --> 01:10:09,129
 LIGAMENTMENT, LIKE A ACL TEAR,

1486
01:10:09,129 --> 01:10:11,765
 THAT IS VERY DIFFERENT THAN

1487
01:10:11,765 --> 01:10:12,232
 OSTEOARTHRITIS.

1488
01:10:12,232 --> 01:10:15,902
 SO FOR THE PURPOSES OF THIS

1489
01:10:15,902 --> 01:10:17,037
 TALK, FOCUSING ON

1490
01:10:17,037 --> 01:10:17,971
 OSTEOARTHRITIS AND CHRONIC

1491
01:10:17,971 --> 01:10:21,208
 PAIN, SO YOU NEED TO HAVE

1492
01:10:21,208 --> 01:10:26,146
 PLACEBO DATA FROM A RANDOMIZED

1493
01:10:26,146 --> 01:10:27,681
 PLACEBO CONTROLLED TRIAL.

1494
01:10:27,681 --> 01:10:30,083
 WE HAVE PRETTY GOOD

1495
01:10:30,083 --> 01:10:31,818
 INFORMATION ON OSTEOARTHRITIS

1496
01:10:31,818 --> 01:10:33,420
 AND THE PROCEDURE ON THE RIGHT

1497
01:10:33,420 --> 01:10:36,223
 WAS FROM A FDA CLINICAL TRIAL

1498
01:10:36,223 --> 01:10:39,026
 THAT WAS OBVIOUSLY A CLINICAL

1499
01:10:39,026 --> 01:10:40,427
 CONTROL TRIAL.

1500
01:10:40,427 --> 01:10:44,131
 AND THE DASH LINE ON THE TOP

1501
01:10:44,131 --> 01:10:48,201
 IS THE GROUND REACTION FORCES

1502
01:10:48,201 --> 01:10:50,203
 AND THE OTHER LINE THAT

1503
01:10:50,203 --> 01:10:52,839
 IMPROVES AND GETS BETTER AND

1504
01:10:52,839 --> 01:10:54,675
 GETS BETTER IS THE

1505
01:10:54,675 --> 01:10:55,342
 QUESTIONNAIRE.

1506
01:10:55,342 --> 01:10:58,578
 ONE BIT OF DISCLOSURE, THIS IS

1507
01:10:58,578 --> 01:11:00,347
 THE OWNER QUESTIONNAIRE USED

1508
01:11:00,347 --> 01:11:00,647
 HERE.

1509
01:11:00,647 --> 01:11:05,852
 IT IS NOT AS ANALYTICAL AS THE

1510
01:11:05,852 --> 01:11:07,621
 ONES THAT HAVE BEEN REPORTED

1511
01:11:07,621 --> 01:11:14,594
 ON TODAY, FOR EXAMPLE, LIKE

1512
01:11:14,594 --> 01:11:16,897
 THE CANINE PAIN REPORT.

1513
01:11:16,897 --> 01:11:19,232
 BUT NEVERTHELESS, THIS IS THE

1514
01:11:19,232 --> 01:11:19,700
 DATA.

1515
01:11:19,700 --> 01:11:21,835
 AND IF YOU LOOK AT THE AVERAGE

1516
01:11:21,835 --> 01:11:26,473
 DATA OF THESE PLACEBO DOGS

1517
01:11:26,473 --> 01:11:28,041
 WITH OSTEOARTHRITIS, TREATED

1518
01:11:28,041 --> 01:11:30,777
 WITH THE PLACEBO DO, NOT

1519
01:11:30,777 --> 01:11:34,281
 CHANGE OVER TIME, THE GROUND

1520
01:11:34,281 --> 01:11:36,917
 REACTION OF THE DOGS DOESN'T

1521
01:11:36,917 --> 01:11:38,051
 CHANGE.

1522
01:11:38,051 --> 01:11:39,953
 BUT THE OWNERS' INTERPRETATION

1523
01:11:39,953 --> 01:11:41,655
 OVER THE TRIAL DID CHANGE.

1524
01:11:41,655 --> 01:11:43,290
 IF YOU CATEGORIZE THINGS, ONE

1525
01:11:43,290 --> 01:11:50,197
 THING WE TRY TO DO IS SEE WHAT

1526
01:11:50,197 --> 01:11:52,132
 IS CLINICALLY DIFFERENT.

1527
01:11:52,132 --> 01:11:53,667
 SO THE MEAN DATA DID NOT

1528
01:11:53,667 --> 01:11:54,368
 CHANGE.

1529
01:11:54,368 --> 01:11:58,638
 IF THERE WAS A 12 PERCENT

1530
01:11:58,638 --> 01:12:02,709
 INCREASE IN GROUND REACTION

1531
01:12:02,709 --> 01:12:07,547
 FORCES SEEN IN DOGS AND A 5 TO

1532
01:12:07,547 --> 01:12:09,015
 10 PERCENT DECREASE IN 8.6

1533
01:12:09,015 --> 01:12:12,219
 DOGS AND THIS WAS 60 DOGS

1534
01:12:12,219 --> 01:12:14,421
 PLACEBO TREATED, ONE DOG HAD A

1535
01:12:14,421 --> 01:12:17,924
 DECREASE IN 10 PERCENT SO NO

1536
01:12:17,924 --> 01:12:21,528
 DOG IMPROVED MORE THAN 10

1537
01:12:21,528 --> 01:12:23,063
 SPERSE REALISTICALLY, IT WAS

1538
01:12:23,063 --> 01:12:23,830
 UNUSUAL.

1539
01:12:23,830 --> 01:12:27,434
 THERE CAN BE SOME WAXING AND

1540
01:12:27,434 --> 01:12:29,536
 WANING BUT IT IS UNUSUAL TO

1541
01:12:29,536 --> 01:12:30,737
 SEE IMPROVEMENT OF GREATER

1542
01:12:30,737 --> 01:12:32,439
 THAN 5 PERCENT AND RARE TO SEE

1543
01:12:32,439 --> 01:12:34,408
 AN IMPROVEMENT OF GREATER THAN

1544
01:12:34,408 --> 01:12:34,975
 10 PERCENT.

1545
01:12:34,975 --> 01:12:37,444
 SO THAT IS ONE WAY TO KIND OF

1546
01:12:37,444 --> 01:12:38,111
 LOOK AT THIS.

1547
01:12:38,111 --> 01:12:40,347
 SO IF WE CAN LOOK AT THAT THAT

1548
01:12:40,347 --> 01:12:44,518
 WAY AND THAT IS KIND OF WHERE

1549
01:12:44,518 --> 01:12:46,486
 WE SAY OH, 5 PERCENT, PRETTY

1550
01:12:46,486 --> 01:12:47,187
 IMPRESSIVE IMPROVEMENT IF YOU

1551
01:12:47,187 --> 01:12:49,523
 ARE GOING TO LOOK AT A GROUP

1552
01:12:49,523 --> 01:12:52,192
 OF DOGS.

1553
01:12:52,192 --> 01:12:53,693
 YOU CAN ALSO COMPARE AVERAGE

1554
01:12:53,693 --> 01:12:55,962
 GROUP LOOKING AT PREVIOUSLY

1555
01:12:55,962 --> 01:13:01,334
 PUBLISHED DATA WE THINK IS

1556
01:13:01,334 --> 01:13:02,669
 VERY RELIABLE.

1557
01:13:02,669 --> 01:13:07,140
 FOR EXAMPLE, WE BELIEVE

1558
01:13:07,140 --> 01:13:08,642
 ANTI-INFLAMMATORY TREATMENT

1559
01:13:08,642 --> 01:13:14,047
 FOR OSTEOARTHRITIS WORKS AND

1560
01:13:14,047 --> 01:13:19,119
 OMEGA-3 FATTY ACID DIETS

1561
01:13:19,119 --> 01:13:21,188
 SHOWING CHANGES OF IMPROVEMENT

1562
01:13:21,188 --> 01:13:25,492
 OVER TIME, THOSE STUDIES

1563
01:13:25,492 --> 01:13:31,131
 RANGING FROM 3.5 TO 6 PERCENT,

1564
01:13:31,131 --> 01:13:33,533
 AGAIN THE CHANGES IN THOSE

1565
01:13:33,533 --> 01:13:34,935
 NUMBERS, MAYBE 5 PERCENT IS

1566
01:13:34,935 --> 01:13:35,969
 THE MINIMUM.

1567
01:13:35,969 --> 01:13:39,139
 THE OTHER WAY TO ADDRESS IT IS

1568
01:13:39,139 --> 01:13:40,774
 ADDRESS THE PROBABILITY OF

1569
01:13:40,774 --> 01:13:51,318
 CHANGE IN THE PLACEBO VERSUS

1570
01:14:03,763 --> 01:14:07,067
 THE OTHER GROUP, IN DOGS WITH

1571
01:14:07,067 --> 01:14:08,835
 OSTEOARTHRITIS, A CHANGE IN

1572
01:14:08,835 --> 01:14:12,372
 BOTH PVF AND VI OVER A SHORT

1573
01:14:12,372 --> 01:14:15,642
 PERIOD OF TIME PERIOD OF

1574
01:14:15,642 --> 01:14:17,377
 3.5 PERCENT IS THE MINIMUM

1575
01:14:17,377 --> 01:14:19,713
 VALUE THAT SHOULD BE

1576
01:14:19,713 --> 01:14:20,280
 CONSIDERED CLINICALLY

1577
01:14:20,280 --> 01:14:20,647
 IMPORTANT.

1578
01:14:20,647 --> 01:14:21,915
 SO THE NUMBER OF DOGS IN EACH

1579
01:14:21,915 --> 01:14:24,985
 GROUP THAT HAVE A CHANGE IN

1580
01:14:24,985 --> 01:14:26,920
 GROUND REACTION FORCES GREATER

1581
01:14:26,920 --> 01:14:29,890
 THAN 5 PERCENT IS A GOOD

1582
01:14:29,890 --> 01:14:30,223
 MEASURE.

1583
01:14:30,223 --> 01:14:32,359
 SO THAT IS ALL I HAVE FOR YOU

1584
01:14:32,359 --> 01:14:34,194
 AND THANKS FOR YOUR TIME

1585
01:14:34,194 --> 01:14:39,900
 TODAY, REALLY APPRECIATE IT.

1586
01:14:39,900 --> 01:14:41,067
 [APPLAUSE]

1587
01:14:41,067 --> 01:14:42,536
 >> THANKS VERY MUCH,
MIKE, SO

1588
01:14:42,536 --> 01:14:44,104
 LOTS EVER FOOD FOR THOUGHT

1589
01:14:44,104 --> 01:14:47,707
 THERE, THINKING ABOUT HOW WE

1590
01:14:47,707 --> 01:14:48,675
 DEFINE CLINICALLY IMPORTANT

1591
01:14:48,675 --> 01:14:51,111
 CHANGE, HOW WE DEFINE SUCCESS

1592
01:14:51,111 --> 01:14:52,913
 FAILURE AND WE WILL BE HAVING

1593
01:14:52,913 --> 01:14:55,348
 A PANEL DISCUSSION SO LOOK

1594
01:14:55,348 --> 01:14:56,449
 FORWARD LIVELY INTERACTION

1595
01:14:56,449 --> 01:14:58,852
 THEN, WE WILL HAVE ALL THE

1596
01:14:58,852 --> 01:15:00,554
 PRESENTERS OTHER THAN Dr.

1597
01:15:00,554 --> 01:15:01,788
 BROWN AVAILABLE.

1598
01:15:01,788 --> 01:15:04,558
 SO LET'S MOVE ON TO, SORT OF A

1599
01:15:04,558 --> 01:15:06,660
 CHANGE IN DIRECTION BUT

1600
01:15:06,660 --> 01:15:09,095
 FOCUSING ON TODAY'S THEME OF

1601
01:15:09,095 --> 01:15:10,363
 LOOKING AT ANALYTICAL

1602
01:15:10,363 --> 01:15:11,531
 APPROACHES AND CAN WE ADVANCE

1603
01:15:11,531 --> 01:15:12,198
 THAT.

1604
01:15:12,198 --> 01:15:14,901
 IT IS MY PLEASURE TO INTRODUCE

1605
01:15:14,901 --> 01:15:16,136
 Dr. JIM CAMPBELL, A FRIEND

1606
01:15:16,136 --> 01:15:19,306
 AND MENTOR TO ME, A LONG

1607
01:15:19,306 --> 01:15:22,075
 CAREER AT JOHNS HOPKINS AS A

1608
01:15:22,075 --> 01:15:23,343
 NEUROSURGEON AND PAIN

1609
01:15:23,343 --> 01:15:26,313
 RESEARCHER AND HE IS NOW THE

1610
01:15:26,313 --> 01:15:31,985
 CHIEF SCIENTIFIC OFFICER AT

1611
01:15:31,985 --> 01:15:32,819
 CENTREXION THERAPEUTICS AND

1612
01:15:32,819 --> 01:15:36,089
 WILL TALK TO US ABOUT ANOTHER

1613
01:15:36,089 --> 01:15:37,157
 CONTROVERSIAL TOPIC ON WHETHER

1614
01:15:37,157 --> 01:15:39,259
 TO USE THE AREA UNDER THE

1615
01:15:39,259 --> 01:15:40,961
 CURVE AS AN ANALYSIS OR SINGLE

1616
01:15:40,961 --> 01:15:42,028
 POINTS IN TIME.

1617
01:15:42,028 --> 01:15:50,236
 JIM, TAKE IT AWAY.

1618
01:15:50,236 --> 01:15:53,673
 >> GOOD TO SIGH EVERYBODY
--

1619
01:15:53,673 --> 01:15:57,410
 SEE EVERYBODY, THANKS TO THE O

1620
01:15:57,410 --> 01:15:59,179
 ORGANIZERS AND DUNCAN FOR

1621
01:15:59,179 --> 01:16:01,348
 HAVING ME HERE AT THE MEETING.

1622
01:16:01,348 --> 01:16:03,416
 TUCK CAN AND I HAVE HAD MANY

1623
01:16:03,416 --> 01:16:04,851
 DISCUSSIONS ABOUT THE TOPIC

1624
01:16:04,851 --> 01:16:06,653
 AND ONE POINT TO MAKE HERE IS

1625
01:16:06,653 --> 01:16:10,957
 IS WE SPEND BILLIONS AND

1626
01:16:10,957 --> 01:16:12,692
 BILLIONS ON TRIALS IN ANIMALS

1627
01:16:12,692 --> 01:16:16,830
 LOOKING TO COME UP WITH BETTER

1628
01:16:16,830 --> 01:16:17,931
 THERAPY.

1629
01:16:17,931 --> 01:16:19,432
 AND RELATIVELY SPEAKING, WE

1630
01:16:19,432 --> 01:16:23,103
 SPEND VERY LITTLE ON CLINICAL

1631
01:16:23,103 --> 01:16:23,503
 TRIAL TIME.

1632
01:16:23,503 --> 01:16:26,439
 SO WE'RE LIKE GIVING A

1633
01:16:26,439 --> 01:16:29,175
 PHYSICIST A THING OR TWO BUT

1634
01:16:29,175 --> 01:16:35,181
 DON'T GIVE HIM A GOOD

1635
01:16:35,181 --> 01:16:36,483
 TELESCOPE NECESSARILY ARE OR

1636
01:16:36,483 --> 01:16:43,790
 WE DON'T TALK ABOUT THE

1637
01:16:43,790 --> 01:16:45,125
 TELESCOPE CAPITUALLY.

1638
01:16:45,125 --> 01:16:46,960
 SO THE MEASURE WE USE ARE

1639
01:16:46,960 --> 01:16:47,894
 REALLY SO IMPORTANT AND I

1640
01:16:47,894 --> 01:16:49,963
 THINK IT IS TERRIFIC TO SEE

1641
01:16:49,963 --> 01:16:51,698
 THIS MEETING BECAUSE IT REALLY

1642
01:16:51,698 --> 01:16:53,566
 BRINGS UP THE ANALYTIC TOOLS

1643
01:16:53,566 --> 01:16:56,069
 THAT WE HAVE, THAT WE USE IN

1644
01:16:56,069 --> 01:16:59,339
 CLINICAL TRIALS AND IT IS JUST

1645
01:16:59,339 --> 01:17:00,140
 SO IMPORTANT.

1646
01:17:00,140 --> 01:17:04,344
 I AM GOING TO SPEAK ABOUT A

1647
01:17:04,344 --> 01:17:09,182
 PARTICULAR ASPECT OF THIS, 

1648
01:17:09,182 --> 01:17:12,018
 NAMELY HE IS ESSAY SENSITIVITY

1649
01:17:12,018 --> 01:17:14,587
 AND THIS IS SOMETHING THAT I

1650
01:17:14,587 --> 01:17:16,456
 HAVE THOUGHT WITH QUITE A LOT

1651
01:17:16,456 --> 01:17:17,190
 OVER TIME.

1652
01:17:17,190 --> 01:17:19,259
 DUNCAN AND I HAVE HAD MANY

1653
01:17:19,259 --> 01:17:21,561
 CONVERSATIONS ABOUT THIS AND

1654
01:17:21,561 --> 01:17:24,397
 DUNCAN HAS PROMPTED ME TO DO

1655
01:17:24,397 --> 01:17:26,332
 SOME EVEN FURTHER, MORE

1656
01:17:26,332 --> 01:17:28,168
 SERIOUS THINKING ABOUT THIS,

1657
01:17:28,168 --> 01:17:32,272
 AND I DO.  TO ACKNOWLEDGE AT

1658
01:17:32,272 --> 01:17:37,177
 THE OUTSET THAT I AM INVOLVED

1659
01:17:37,177 --> 01:17:41,147
 AT CENTREXION IN MULTIPLE WAYS

1660
01:17:41,147 --> 01:17:45,051
 THAT CREATES A POTENTIAL 

1661
01:17:45,051 --> 01:17:46,486
 CONFLICT OF INTEREST.

1662
01:17:46,486 --> 01:17:48,755
 THIS SLIDE MAKES THE FURTHER

1663
01:17:48,755 --> 01:17:51,858
 POINT ABOUT THE IMPORTANCE OF

1664
01:17:51,858 --> 01:17:55,795
 ESSAY SENSITIVITY WHEN WE DO

1665
01:17:55,795 --> 01:17:57,497
 TRIALS.

1666
01:17:57,497 --> 01:17:59,733
 SO E-- ASSAY SENSITIVITY, WHAT

1667
01:17:59,733 --> 01:18:03,136
 IS IT REALLY, IT IS THE

1668
01:18:03,136 --> 01:18:04,904
 ABILITY TO DETECT EFFICACY

1669
01:18:04,904 --> 01:18:09,109
 WHEN IN FACT, IN THIS CASE, A

1670
01:18:09,109 --> 01:18:10,310
 DOCTOR, IS TRULY EFFICACIOUS.

1671
01:18:10,310 --> 01:18:12,579
 IT IS THE ABILITY TO

1672
01:18:12,579 --> 01:18:14,748
 DISTINGUISH AN ACTIVE

1673
01:18:14,748 --> 01:18:16,483
 TREATMENT FROM AN INACTIVE

1674
01:18:16,483 --> 01:18:18,418
 TREATMENT AND COULD BE SAID

1675
01:18:18,418 --> 01:18:23,323
 THAT A TRIAL THAT LACKS ASSAY

1676
01:18:23,323 --> 01:18:26,659
 SENSITIVITY LACKS INTERNAL

1677
01:18:26,659 --> 01:18:27,026
 VALIDITY.

1678
01:18:27,026 --> 01:18:34,901
 THERE ARE MANY FACTORS THAT 

1679
01:18:34,901 --> 01:18:36,669
 AFFECT ASSAY SENSITIVITY,

1680
01:18:36,669 --> 01:18:40,740
 TRIALS DESIGN AUTHORIZE RELY,

1681
01:18:40,740 --> 01:18:42,408
 TRIAL CONDUCT, SELECTION OF

1682
01:18:42,408 --> 01:18:43,576
 ENDPOINTS BUT WHAT I WANT TO

1683
01:18:43,576 --> 01:18:45,478
 FOCUS ON IN THE NEXT FEW

1684
01:18:45,478 --> 01:18:47,213
 MINUTES IS THE ANALYSIS PLAN.

1685
01:18:47,213 --> 01:18:52,752
 SO TO BEGIN, LET'S JUST LOOK

1686
01:18:52,752 --> 01:18:54,387
 AT SOME SIMULATED DATA.

1687
01:18:54,387 --> 01:19:00,193
 IN THIS CASE, MY COLLEAGUE

1688
01:19:00,193 --> 01:19:02,362
 JAMES CONNOLLY WORKED WITH ME

1689
01:19:02,362 --> 01:19:06,099
 TO PUT TOGETHER AN ARBITRARY

1690
01:19:06,099 --> 01:19:06,466
 DATASET.

1691
01:19:06,466 --> 01:19:08,568
 WE HAD 170 SUBJECTS AND

1692
01:19:08,568 --> 01:19:11,070
 IMAGINED HERE THE BLUE LINE

1693
01:19:11,070 --> 01:19:14,274
 BEING THE PLACEBO GROUP WITH

1694
01:19:14,274 --> 01:19:19,746
 170 SUBJECTS STUDY OVER A

1695
01:19:19,746 --> 01:19:22,048
 1-WEEK -- 12-WEEK PERIOD OF

1696
01:19:22,048 --> 01:19:26,219
 TIME AND THEN THE TEST COULD

1697
01:19:26,219 --> 01:19:27,754
 BE INJECTION THERAPY, A DAILY

1698
01:19:27,754 --> 01:19:29,789
 DRUG THAT IS GIVEN AND LOOKING

1699
01:19:29,789 --> 01:19:32,158
 AT THE DECREASE IN PAIN ON THE

1700
01:19:32,158 --> 01:19:34,427
 RATING SCALES AND LOOKING AT

1701
01:19:34,427 --> 01:19:36,629
 THIS OVER TIME OUT TO 12

1702
01:19:36,629 --> 01:19:37,030
 WEEKS.

1703
01:19:37,030 --> 01:19:40,400
 SO I INVITE YOU TO THINK ABOUT

1704
01:19:40,400 --> 01:19:42,702
 THIS. 

1705
01:19:42,702 --> 01:19:53,246
 IS THIS A THERAPY THAT LET'S

1706
01:19:54,214 --> 01:19:55,648
 SAY IS SAFE, IS THIS SOMETHING

1707
01:19:55,648 --> 01:19:57,250
 OF INTEREST, SOMETHING THAT

1708
01:19:57,250 --> 01:19:59,619
 SHOULD BE LOOKED AT AS A DRUG

1709
01:19:59,619 --> 01:20:07,026
 TO CARRY FORWARD AND DOES IT

1710
01:20:07,026 --> 01:20:08,294
 WORK IMPORTANTLY AND THE FACT

1711
01:20:08,294 --> 01:20:10,830
 IS THIS IS AN EXAMPLE OF A

1712
01:20:10,830 --> 01:20:11,264
 FAILED TRIAL.

1713
01:20:11,264 --> 01:20:16,502
 AND WHY IS THIS A FAILED

1714
01:20:16,502 --> 01:20:16,803
 TRIAL?

1715
01:20:16,803 --> 01:20:20,473
 BECAUSE IF YOU LOOK AT THIS,

1716
01:20:20,473 --> 01:20:22,175
 IT IS REASONABLY CONVINCING

1717
01:20:22,175 --> 01:20:23,776
 DATA AT DIFFERENT TIME POINTS

1718
01:20:23,776 --> 01:20:26,980
 BUT SEEMS THAT AT WEEK 12,

1719
01:20:26,980 --> 01:20:31,551
 THESE TWO DOGS ARE TOO CLOSE

1720
01:20:31,551 --> 01:20:33,553
 TOGETHER AND WHAT IS THE

1721
01:20:33,553 --> 01:20:34,420
 CONVENTION OF DOING THE

1722
01:20:34,420 --> 01:20:36,689
 ANALYSIS OF THE TRIAL AND

1723
01:20:36,689 --> 01:20:39,592
 SPECIFICALLY THE PRIMARY

1724
01:20:39,592 --> 01:20:40,894
 ENDPOINT IS ORDINARILY

1725
01:20:40,894 --> 01:20:46,399
 DIRECTED AT WHAT HAPPENS IN

1726
01:20:46,399 --> 01:20:48,801
 THE LAB WEEK, THE 12TH WEEK IN

1727
01:20:48,801 --> 01:20:50,436
 THIS CASE AND THIS IS REFERRED

1728
01:20:50,436 --> 01:20:56,175
 TO AS A LANDMARK ANALYSIS AND,

1729
01:20:56,175 --> 01:20:59,612
 AGAIN, IT IS WHAT THE DEVICE

1730
01:20:59,612 --> 01:21:02,348
 AT THE FDA REQUIRES OF MOST OF

1731
01:21:02,348 --> 01:21:04,183
 US IN DOING DRUG TRIALS.

1732
01:21:04,183 --> 01:21:06,552
 AND IT IS INTERESTING IN THAT

1733
01:21:06,552 --> 01:21:09,856
 WE HAVE LOTS OF DATA IN THIS

1734
01:21:09,856 --> 01:21:15,728
 TRIAL BUT IN PRINCIPLE, I

1735
01:21:15,728 --> 01:21:17,931
 MEAN, AND WE COULD LOOK AT ALL

1736
01:21:17,931 --> 01:21:19,332
 THE DATA OF COURSE BUT IN

1737
01:21:19,332 --> 01:21:22,936
 TERMS OF THE PRIMARY ENDPOINT,

1738
01:21:22,936 --> 01:21:25,371
 THE ENDPOINT ANALYSIS LARGELY

1739
01:21:25,371 --> 01:21:27,307
 IGNORES THE RICH DATASET AND

1740
01:21:27,307 --> 01:21:29,208
 FOCUSES ON THE 12TH WEEK.

1741
01:21:29,208 --> 01:21:33,012
 NOW, THIS CAN BE DONE IN

1742
01:21:33,012 --> 01:21:38,217
 ANCOVA ANALYSIS OR MORE

1743
01:21:38,217 --> 01:21:40,186
 MONTHLY, AN N MR M ANALYSIS

1744
01:21:40,186 --> 01:21:44,290
 COULD BE DONE AND THERE IS

1745
01:21:44,290 --> 01:21:45,425
 CONSIDERATION OVER OTHER TIME

1746
01:21:45,425 --> 01:21:47,360
 POINTS BUT THE PRIMARY

1747
01:21:47,360 --> 01:21:50,697
 COMPARISON IS STILL AT WEEK

1748
01:21:50,697 --> 01:21:52,265
 12.

1749
01:21:52,265 --> 01:21:53,599
 ♪/M MR M.

1750
01:21:53,599 --> 01:21:56,235
 WE COULD ASK THEREFORE, IS

1751
01:21:56,235 --> 01:22:01,808
 THERE AN ALTERNATIVE AND

1752
01:22:01,808 --> 01:22:03,309
 INTERESTINGLY, WE JUST

1753
01:22:03,309 --> 01:22:04,911
 HAPPENED TO TALK A COUPLE OF

1754
01:22:04,911 --> 01:22:06,846
 MINUTES AT THE BREAK AND HE

1755
01:22:06,846 --> 01:22:08,548
 WAS TELLING ME ABOUT THINGS HE

1756
01:22:08,548 --> 01:22:11,084
 IS DOING TO LOOK AT ACUTE PAIN

1757
01:22:11,084 --> 01:22:14,087
 AND IT TURNS OUT AN ACUTE

1758
01:22:14,087 --> 01:22:16,622
 PAIN, THE ANALYSIS IS ENTIRELY

1759
01:22:16,622 --> 01:22:17,256
 DIFFERENT.

1760
01:22:17,256 --> 01:22:21,527
 IT IS NOT A LANDMARK ANALYSIS

1761
01:22:21,527 --> 01:22:24,897
 BUT GENERALLY IS THE SO-CALLED

1762
01:22:24,897 --> 01:22:25,498
 SPID.

1763
01:22:25,498 --> 01:22:26,933
 THERE ARE THOSE THAT ARGUE A

1764
01:22:26,933 --> 01:22:28,401
 PAIN RELIEF SCALE IS MORE

1765
01:22:28,401 --> 01:22:31,137
 SENSITIVE AND I AM NOT SURE

1766
01:22:31,137 --> 01:22:36,009
 THAT THAT DISCUSSION HAS BEEN 

1767
01:22:36,009 --> 01:22:36,776
 PLAYED OUT SUFFICIENTLY.

1768
01:22:36,776 --> 01:22:39,278
 AND THERE ARE MAYBE SOME

1769
01:22:39,278 --> 01:22:40,480
 ARGUMENTS AGAINST THAT BUT I

1770
01:22:40,480 --> 01:22:44,017
 AM NOT SURE THAT THOSE

1771
01:22:44,017 --> 01:22:45,251
 ARGUMENTS ARE NECESSARILY

1772
01:22:45,251 --> 01:22:45,685
 VALID.

1773
01:22:45,685 --> 01:22:48,588
 BUT IN ANY CASE, LET'S FOCUS

1774
01:22:48,588 --> 01:22:50,523
 ON THE SPID.

1775
01:22:50,523 --> 01:22:52,425
 SO WHAT IS THIS?

1776
01:22:52,425 --> 01:22:55,628
 IT STANDS FOR SUM OF PAIN

1777
01:22:55,628 --> 01:22:58,698
 INTENSITY DIFFERENCE AND FOR

1778
01:22:58,698 --> 01:23:01,367
 EACH TIME INTERVAL, ONE

1779
01:23:01,367 --> 01:23:02,835
 SUBTRACTS THE PAIN INTENSITY

1780
01:23:02,835 --> 01:23:05,004
 AT BASELINE FROM THE PAIN

1781
01:23:05,004 --> 01:23:06,506
 INTENSITY AT THAT SPECIFIC

1782
01:23:06,506 --> 01:23:07,940
 INTERVAL AND THEN ONE CAN TAKE

1783
01:23:07,940 --> 01:23:15,648
 A SUM OF THE VALUE FOR EACH

1784
01:23:15,648 --> 01:23:21,220
 SUBJECT, TIME WEIGHTING CAN BE

1785
01:23:21,220 --> 01:23:23,022
 APPLIED TO ADJUST INTERVALS

1786
01:23:23,022 --> 01:23:28,061
 AND THEN CUMULATIVE PAIN OVER

1787
01:23:28,061 --> 01:23:30,263
 TIME AT THE ENDPOINTS FOR EACH

1788
01:23:30,263 --> 01:23:31,998
 SUBJECT AND ONE COMES UP WITH

1789
01:23:31,998 --> 01:23:34,934
 THE AREA UNDER THE CURVE

1790
01:23:34,934 --> 01:23:35,568
 ANALYSIS ESSENTIALLY.

1791
01:23:35,568 --> 01:23:37,370
 SO WHY CAN'T WE USE SIMILAR

1792
01:23:37,370 --> 01:23:39,338
 TYPE OF ANALYSIS IN CHRONIC

1793
01:23:39,338 --> 01:23:39,839
 PAIN?

1794
01:23:39,839 --> 01:23:41,507
 LET'S TALK A LITTLE MORE ABOUT

1795
01:23:41,507 --> 01:23:43,443
 AREA UNDER THE CURVE.

1796
01:23:43,443 --> 01:23:47,580
 SOMETIMES IT IS REFERRED TO AS

1797
01:23:47,580 --> 01:23:48,981
 AREA UNDER EFFECT.

1798
01:23:48,981 --> 01:23:51,084
 IF ONE LOOKS INTEREST THIS

1799
01:23:51,084 --> 01:23:53,986
 WITH REGARD IT CHRONIC PAIN

1800
01:23:53,986 --> 01:24:01,427
 TRIALS, THERE IS VERY, VERY

1801
01:24:01,427 --> 01:24:05,898
 LILLITH CHEWER --  LITTLE,

1802
01:24:05,898 --> 01:24:07,867
 LILLITH CHEWER -- LITERATURE

1803
01:24:07,867 --> 01:24:10,736
 AND IT IS STRIKING HOW LITTLE

1804
01:24:10,736 --> 01:24:14,073
 THAT HAS BEEN DISCUSSED AS AN

1805
01:24:14,073 --> 01:24:14,607
 ALTERNATIVE MEASURE.

1806
01:24:14,607 --> 01:24:16,609
 IT IS CONDITION FUSING BECAUSE

1807
01:24:16,609 --> 01:24:18,444
 WHAT ONE IN OUR FIELD

1808
01:24:18,444 --> 01:24:22,782
 GENERALLY COMES UP WITH THE

1809
01:24:22,782 --> 01:24:26,519
 AUC COMMON IN PK STUDIES, AND

1810
01:24:26,519 --> 01:24:28,654
 THAT IS VERY SIMPLY THE

1811
01:24:28,654 --> 01:24:30,189
 INTEGRAL OF THE CURVE OVER

1812
01:24:30,189 --> 01:24:30,490
 TIME.

1813
01:24:30,490 --> 01:24:33,593
 ONE CAN PLAY WITH THIS A BIT

1814
01:24:33,593 --> 01:24:36,262
 AND DO TIME WEIGHTING.

1815
01:24:36,262 --> 01:24:40,800
 ACTUALLY THIS IS PROBABLY A 

1816
01:24:40,800 --> 01:24:43,970
 NOVEL AREA FOR CONSIDERATION

1817
01:24:43,970 --> 01:24:45,905
 SO HERE WE ARE WITH OUR

1818
01:24:45,905 --> 01:24:48,708
 SIMULATED DATA AND THIS IS HOW

1819
01:24:48,708 --> 01:24:50,209
 THIS WOULD LOOK.

1820
01:24:50,209 --> 01:24:52,445
 WE HAVE RECTANGLES HERE BUT

1821
01:24:52,445 --> 01:24:56,349
 PROPERLY THESE SHOULD BE

1822
01:24:56,349 --> 01:24:57,917
 TRAPEZOIDS TO CAPTURE THE

1823
01:24:57,917 --> 01:25:07,059
 INTEREST GRASS MORE ACCURATE 

1824
01:25:07,059 --> 01:25:11,697
 -- INTEREST INTEGRALS MORE

1825
01:25:11,697 --> 01:25:12,899
 RELIABLY.

1826
01:25:12,899 --> 01:25:18,004
 IF YOU LOOK AT THE ANALYSIS AT

1827
01:25:18,004 --> 01:25:20,239
 WEEK 12 AND THIS IS JUST A

1828
01:25:20,239 --> 01:25:24,911
 SIMPLE TEA TEST BUT WE SEE

1829
01:25:24,911 --> 01:25:27,413
 HIGHLY SIGNIFICANT RESULT

1830
01:25:27,413 --> 01:25:28,781
 OUTCOMES AND QUITE

1831
01:25:28,781 --> 01:25:30,082
 SUBSTANTIALLY DIFFERENT AS

1832
01:25:30,082 --> 01:25:31,717
 OPPOSED TO WHAT HAPPENED AT

1833
01:25:31,717 --> 01:25:33,119
 WEEK 12.

1834
01:25:33,119 --> 01:25:38,191
 SO THIS IS A SIMULATED CASE,

1835
01:25:38,191 --> 01:25:39,058
 DOESN'T HAPPEN IN REAL LIFE

1836
01:25:39,058 --> 01:25:41,027
 AND I THINK IT WOULD BE VERY

1837
01:25:41,027 --> 01:25:43,196
 INTERESTING TO PURSUE LOOKING

1838
01:25:43,196 --> 01:25:46,499
 ACROSS STUDIES WHERE AUC

1839
01:25:46,499 --> 01:25:48,367
 ANALYSES ARE AVAILABLE AND TO

1840
01:25:48,367 --> 01:25:51,204
 COMPARE THESE WITH LANDMARK

1841
01:25:51,204 --> 01:25:51,571
 ANALYSES.

1842
01:25:51,571 --> 01:25:54,373
 ONE STUDY THAT STUCK IN MY

1843
01:25:54,373 --> 01:25:56,209
 MIND OVER TIME IN AN AREA OF

1844
01:25:56,209 --> 01:26:00,446
 INTEREST OF MINE AND THAT IS

1845
01:26:00,446 --> 01:26:03,950
 LOOKING AT ADJUSTING THERAPIES

1846
01:26:03,950 --> 01:26:05,451
 FOR OSTEOARTHRITIS PAIN WITH A

1847
01:26:05,451 --> 01:26:13,693
 REPORT FOR A DRUG NOW APPROVED

1848
01:26:13,693 --> 01:26:18,064
 WHICH IS A NOVEL EXTENDED

1849
01:26:18,064 --> 01:26:24,503
 RELEASE MICROSPHERE 

1850
01:26:24,503 --> 01:26:25,204
 FORMULATION OF TRIAMCINOLONE.

1851
01:26:25,204 --> 01:26:28,074
 IGNORE THE MIDDLE LINE.

1852
01:26:28,074 --> 01:26:31,244
 IT IS A DISTRACTION AT THE

1853
01:26:31,244 --> 01:26:32,845
 MOMENT AND LOOK AT THE BOTTOM

1854
01:26:32,845 --> 01:26:35,314
 LINE AND THE PLACEBO CURVE.

1855
01:26:35,314 --> 01:26:39,685
 AND AT EACH OF THESE TIME

1856
01:26:39,685 --> 01:26:42,388
 POINTS, WE SEE AN INCREASE IN

1857
01:26:42,388 --> 01:26:44,090
 PAIN BETWEEN PLACEBO AND

1858
01:26:44,090 --> 01:26:46,926
 ACTIVE BUT IT TURNS OUT THE

1859
01:26:46,926 --> 01:26:48,027
 PRIMARY ENDPOINT WAS WEEK 12.

1860
01:26:48,027 --> 01:26:51,230
 SO WHAT WAS REPORTED IN THE

1861
01:26:51,230 --> 01:26:53,599
 PRESS, FAILED TRIAL, DID NOT

1862
01:26:53,599 --> 01:26:55,968
 MEET ITS PRIMARY ENDPOINT.

1863
01:26:55,968 --> 01:26:57,770
 WHEN YOU LOOK AT THE DATA,

1864
01:26:57,770 --> 01:27:00,473
 HOWEVER, IT WAS SIGNIFICANT AT

1865
01:27:00,473 --> 01:27:03,109
 WEEK 11 AND IT WAS SIGNIFICANT

1866
01:27:03,109 --> 01:27:06,646
 AT WEEK 13 AND THEN THERE WAS

1867
01:27:06,646 --> 01:27:08,447
 A WANITTHAING EFFECT

1868
01:27:08,447 --> 01:27:10,616
 CONSISTENT WITH THE BIOLOGY

1869
01:27:10,616 --> 01:27:11,751
 AND STRO*EUD EFFECT.

1870
01:27:11,751 --> 01:27:13,586
 THEY STRIKING THAT THE COMPANY

1871
01:27:13,586 --> 01:27:18,357
 HAD TO REPORT TO INVESTORS IT 

1872
01:27:18,357 --> 01:27:20,359
 FAILED AT TRIAL.

1873
01:27:20,359 --> 01:27:22,695
 AND WE HAVE HAD SOME BITTER

1874
01:27:22,695 --> 01:27:25,598
 EXPERIENCE WITH THIS AS WELL.

1875
01:27:25,598 --> 01:27:28,868
 THIS IS A DOUBLE BLIND PLACEBO

1876
01:27:28,868 --> 01:27:31,103
 CONTROL PHASE 3 TRIAL THAT WE

1877
01:27:31,103 --> 01:27:38,544
 UNDER TOOK WITH ONE MILL GRAM

1878
01:27:38,544 --> 01:27:40,079
 OF CENTREXION INTO THE KNEE

1879
01:27:40,079 --> 01:27:42,782
 FOR PATIENTS WHO HAD MODERATE

1880
01:27:42,782 --> 01:27:44,317
 TO SEVERE ARTHRITIS PAIN.

1881
01:27:44,317 --> 01:27:48,587
 SO WE DO THE INJECTION AND

1882
01:27:48,587 --> 01:27:52,325
 LOOK AT THE RATING SCALE,

1883
01:27:52,325 --> 01:27:54,193
 DECREASE IN PAIN VERSUS THE

1884
01:27:54,193 --> 01:27:55,061
 PLACEBO.

1885
01:27:55,061 --> 01:27:57,396
 AND WE MISSED THE PRIMARY

1886
01:27:57,396 --> 01:28:00,032
 ENDPOINT WHICH AGAIN WAS WEEK

1887
01:28:00,032 --> 01:28:03,969
 12 AND SO HAPPENED BY THE WAY

1888
01:28:03,969 --> 01:28:06,138
 HAD WE DECLARED A WHICH WAS

1889
01:28:06,138 --> 01:28:10,676
 PAIN WITH WALKING ON PRIMARY

1890
01:28:10,676 --> 01:28:13,412
 ENDPOINT, IT WAS STATISTICALLY

1891
01:28:13,412 --> 01:28:14,747
 SIGNIFICANT AT WEEK 12.

1892
01:28:14,747 --> 01:28:18,451
 SO WE WERE QUITE LUCKY AND IT

1893
01:28:18,451 --> 01:28:20,286
 WAS A TOSS-UP WHETHER WE WOULD

1894
01:28:20,286 --> 01:28:23,255
 USE ONE VERSUS THE OTHER AT

1895
01:28:23,255 --> 01:28:24,623
 PRIMARY ENDPOINT.

1896
01:28:24,623 --> 01:28:29,061
 IT WAS REALLY -- THERE WAS NO

1897
01:28:29,061 --> 01:28:31,197
 COMPELLING RATIONAL TO USE ONE

1898
01:28:31,197 --> 01:28:32,331
 OVER THE OTHER.

1899
01:28:32,331 --> 01:28:38,237
 BUT WHEN YOU LOOK AT THESE

1900
01:28:38,237 --> 01:28:41,440
 DATA, PRETTY SIMILAR

1901
01:28:41,440 --> 01:28:44,076
 DIFFERENCE, EVEN OUT TO WEEK

1902
01:28:44,076 --> 01:28:46,679
 20, 25, 26, THERE IS A WANING

1903
01:28:46,679 --> 01:28:47,880
 EFFECT IN THE LAST WEEKS OF

1904
01:28:47,880 --> 01:28:48,280
 THE TRIAL.

1905
01:28:48,280 --> 01:28:49,915
 ABOUT YOUR MANY OF THESE TIME

1906
01:28:49,915 --> 01:28:52,385
 POINTS ARE IN FACT SIGNIFICANT

1907
01:28:52,385 --> 01:28:57,189
 IN THE M MR M ANALYSIS.

1908
01:28:57,189 --> 01:29:00,993
 AND WHEN WE DO A AUC ANALYSIS,

1909
01:29:00,993 --> 01:29:02,962
 SAME DATA, THIS WAS

1910
01:29:02,962 --> 01:29:05,631
 PRESPECIFIED SO THIS IS ONE OF

1911
01:29:05,631 --> 01:29:06,799
 THE DECLARED SECONDARY

1912
01:29:06,799 --> 01:29:10,669
 ENDPOINTS IN OUR STUDY, THE

1913
01:29:10,669 --> 01:29:13,072
 AREA UNDER THE CURVE FOR THIS

1914
01:29:13,072 --> 01:29:15,775
 SAME DATASET IS POSITIVE.

1915
01:29:15,775 --> 01:29:19,278
 AND THE ANALYSIS SPAN GOING

1916
01:29:19,278 --> 01:29:21,580
 FROM TIME ZERO TO WEEK 12 SO

1917
01:29:21,580 --> 01:29:24,250
 HAD THAT BEEN THE ENDPOINT, WE

1918
01:29:24,250 --> 01:29:27,052
 WOULD HAVE DECLARED THAT A

1919
01:29:27,052 --> 01:29:28,421
 SUCCESSFUL TRIAL.

1920
01:29:28,421 --> 01:29:31,690
 SO WHY THIS MIGHT NOT BE THE

1921
01:29:31,690 --> 01:29:39,799
 PRIMARY ENDPOINT IF IT HAS 

1922
01:29:39,799 --> 01:29:40,966
 BETTER ASSAY SENSITIVITY.

1923
01:29:40,966 --> 01:29:44,370
 THE WHOLE ISSUE OF THE

1924
01:29:44,370 --> 01:29:46,038
 PATIENT'S IMPRESSION OF LOCAL

1925
01:29:46,038 --> 01:29:48,841
 PAIN HAS COME UP BEFORE IN

1926
01:29:48,841 --> 01:29:50,242
 JENNIFER'S TALK AND I THINK A

1927
01:29:50,242 --> 01:29:52,011
 VERY IMPORTANT SCALE TO THINK

1928
01:29:52,011 --> 01:29:54,079
 ABOUT AND I WILL COME BACK TO

1929
01:29:54,079 --> 01:29:56,081
 THIS A LITTLE BIT MORE BUT WE

1930
01:29:56,081 --> 01:29:57,850
 ALSO DID A -- AND THERE IS

1931
01:29:57,850 --> 01:29:59,418
 SOME CONTROVERSY WHETHER YOU

1932
01:29:59,418 --> 01:30:02,822
 COULD REPEAT THE STUDY BUT WE

1933
01:30:02,822 --> 01:30:05,090
 DID THAT -- OR REPEAT THE

1934
01:30:05,090 --> 01:30:07,159
 MEASURE OVER THE COURSE OF THE

1935
01:30:07,159 --> 01:30:07,827
 TRIAL.

1936
01:30:07,827 --> 01:30:10,463
 AND WE DID THAT RIGHT ALONG.

1937
01:30:10,463 --> 01:30:12,465
 AND WE LOOKED AT THE

1938
01:30:12,465 --> 01:30:15,534
 PERCENTAGE OF SUBJECTS WHO

1939
01:30:15,534 --> 01:30:18,804
 REPORTED BEING MUCH BETTER OR

1940
01:30:18,804 --> 01:30:21,540
 VERY MUCH BETTER WHICH IS THE

1941
01:30:21,540 --> 01:30:25,110
 TOP OF THE SCALE, I WILL GO

1942
01:30:25,110 --> 01:30:31,750
 BACK, A 7-POINT SCALE WHERE 

1943
01:30:31,750 --> 01:30:33,519
 SUBJECTS CAN REPORT FEELING

1944
01:30:33,519 --> 01:30:36,222
 DIFFERENT OR WORSE AS WELL BUT

1945
01:30:36,222 --> 01:30:38,858
 THE SIGNIFICANT DATA SHOWS THE

1946
01:30:38,858 --> 01:30:40,793
 PRESPECIFIED ANALYSIS PLAN FOR

1947
01:30:40,793 --> 01:30:44,196
 DATA AT EVERY TIME APPOINTED

1948
01:30:44,196 --> 01:30:47,533
 THAT WE EXAMINED WITH VALUES

1949
01:30:47,533 --> 01:30:50,069
 GOING FROM .01 TO .05.

1950
01:30:50,069 --> 01:30:53,105
 SO ONE COULD ARGUE THAT THESE

1951
01:30:53,105 --> 01:30:57,276
 DIFFERENCES WERE CLINICALLY

1952
01:30:57,276 --> 01:31:00,746
 MEANINGFUL. 

1953
01:31:00,746 --> 01:31:02,715
 WE HAD ANOTHER PAID TRIAL THAT

1954
01:31:02,715 --> 01:31:04,683
 WAS NEARLY IDENTICAL IN STEIN

1955
01:31:04,683 --> 01:31:08,320
 AND ENDPOINTS AND ALL THE

1956
01:31:08,320 --> 01:31:12,358
 OTHER NEUTRAL COMPONENTS AND 

1957
01:31:12,358 --> 01:31:22,701
 WE HAD A SIMILAR OUTCOME AND

1958
01:31:22,701 --> 01:31:24,770
 BECAUSE THE TRIALS WERE

1959
01:31:24,770 --> 01:31:25,871
 INTEGRATED, WE COMBINED THEM

1960
01:31:25,871 --> 01:31:28,874
 SO HERE WE ARE GOING OUT TO 26

1961
01:31:28,874 --> 01:31:31,110
 WEEKS AND THIS IS THE COMBINED

1962
01:31:31,110 --> 01:31:32,044
 ANALYSIS.

1963
01:31:32,044 --> 01:31:37,149
 IN THIS CASE, THE NMRM

1964
01:31:37,149 --> 01:31:38,517
 ANALYSIS WAS APPLIED AND FOR

1965
01:31:38,517 --> 01:31:40,653
 EVERY ONE OF THE WEEKS, AND

1966
01:31:40,653 --> 01:31:41,987
 THIS IS WEEK 11 WHICH HAPPENED

1967
01:31:41,987 --> 01:31:43,956
 NOT TO BE SIGNIFICANT, ABOUT

1968
01:31:43,956 --> 01:31:45,624
 YOUR THERE WERE LATER TIME

1969
01:31:45,624 --> 01:31:48,494
 POINTS THAT WERE SIGNIFICANT,

1970
01:31:48,494 --> 01:31:51,130
 EVEN DOWN TO A POINT OF 001

1971
01:31:51,130 --> 01:31:56,101
 AND THEN PROBABLY A WANING

1972
01:31:56,101 --> 01:32:01,473
 EFFECT ONCE ONE GETS PAST WEEK

1973
01:32:01,473 --> 01:32:04,610
 20, 21. 

1974
01:32:04,610 --> 01:32:07,146
 SO THIS ANALYSIS SADLY DOESN'T

1975
01:32:07,146 --> 01:32:14,820
 APPEAR TO ACCOUNT AS A

1976
01:32:14,820 --> 01:32:16,555
 CONTRIBUTOR TO A NDA BECAUSE

1977
01:32:16,555 --> 01:32:20,960
 IT IS A COMBINATION OF TWO

1978
01:32:20,960 --> 01:32:22,561
 OTHER TRIALS.

1979
01:32:22,561 --> 01:32:27,099
 AND SO IS THIS KIND OF PAIN

1980
01:32:27,099 --> 01:32:30,903
 MEANINGFUL SO WE LOOK T AT --

1981
01:32:30,903 --> 01:32:39,878
 LOOKED AT THIS KIND OF

1982
01:32:39,878 --> 01:32:45,417
 ANALYSIS IN POINT IN TIME

1983
01:32:45,417 --> 01:32:48,721
 ANALYSIS, WEEKS 1, 2, 3 AND

1984
01:32:48,721 --> 01:32:55,961
 WHAT ONE WOULD EXPECT, AN 

1985
01:32:55,961 --> 01:32:57,096
 INJECTION OF CAPAICIN, WHEN

1986
01:32:57,096 --> 01:32:59,498
 ONE LOOKS AT THE CHANGE, THE P

1987
01:32:59,498 --> 01:33:00,799
 VALUES START TO GET MORE

1988
01:33:00,799 --> 01:33:02,601
 IMPRESSIVE IN TERMS OF THE

1989
01:33:02,601 --> 01:33:05,638
 NUMBER OF SERIOUS AND AGAIN,

1990
01:33:05,638 --> 01:33:07,473
 RACES THE QUESTION ABOUT WELL

1991
01:33:07,473 --> 01:33:15,347
 WHAT IS THE SCALE HERE THAT 

1992
01:33:15,347 --> 01:33:17,716
 HAS THE BEST ETHICAL

1993
01:33:17,716 --> 01:33:18,350
 SENSITIVITY?

1994
01:33:18,350 --> 01:33:19,685
 I HAVE ALREADY SHOWN YOU THE

1995
01:33:19,685 --> 01:33:23,088
 AREA UNDER THE CURVE MAY BE

1996
01:33:23,088 --> 01:33:24,957
 MORE RELIABLE THAN THIS IN THE

1997
01:33:24,957 --> 01:33:27,693
 FUTURE ALTHOUGH WE HAVEN'T

1998
01:33:27,693 --> 01:33:30,062
 REALLY DISCUSSED THAT THAN THE

1999
01:33:30,062 --> 01:33:33,432
 EXAMPLE I AM SHOWING YOU WITH

2000
01:33:33,432 --> 01:33:34,166
 GREATER EFFICACY.

2001
01:33:34,166 --> 01:33:36,301
 SO LET ME GO BACK TO THIS

2002
01:33:36,301 --> 01:33:38,504
 POINT BEFORE I CLOSE ABOUT

2003
01:33:38,504 --> 01:33:39,104
 GLOBAL ASSESSMENT.

2004
01:33:39,104 --> 01:33:45,210
 I THINK FOR ME IN THIS JOURNEY

2005
01:33:45,210 --> 01:33:49,381
 LOOKING AT AUC, THIS WAS A

2006
01:33:49,381 --> 01:33:52,251
 SIDE ISSUE AND WOULD I DO --

2007
01:33:52,251 --> 01:33:58,590
 JOHN'S WORK WAS REFERRED TO BY

2008
01:33:58,590 --> 01:34:01,360
 EARLIER AND SPI ID REFERRED TO

2009
01:34:01,360 --> 01:34:03,629
 AS THE GOLDEN STANDARD AND LED

2010
01:34:03,629 --> 01:34:05,397
 ME TO THINK MAYBE THIS SHOULD

2011
01:34:05,397 --> 01:34:07,599
 BE THE ENDPOINT AND IF IT IS

2012
01:34:07,599 --> 01:34:10,335
 THE GOLD STANDARD, WHY NOT USE

2013
01:34:10,335 --> 01:34:10,903
 THE GOLD STANDARD?

2014
01:34:10,903 --> 01:34:21,480
 AND THERE ARE SOME ISSUES WITH

2015
01:34:22,247 --> 01:34:22,448
 THAT.

2016
01:34:22,448 --> 01:34:24,917
 ONE IS, IS IT REALLY A MEASURE

2017
01:34:24,917 --> 01:34:27,920
 OF PAIN AND IS GLOBAL THE

2018
01:34:27,920 --> 01:34:29,888
 RIGHT WORD?

2019
01:34:29,888 --> 01:34:31,356
 [ CLEARING THROAT ]

2020
01:34:31,356 --> 01:34:32,124
 PARDON ME.

2021
01:34:32,124 --> 01:34:36,862
 I HAVE WOEFRTD IF WE SHOULD

2022
01:34:36,862 --> 01:34:39,932
 INSTEAD TALK ABOUT PATIENT

2023
01:34:39,932 --> 01:34:44,436
 CHANGE IN PAIN AND WE DO

2024
01:34:44,436 --> 01:34:46,238
 INCLUDE RECALL BUT MAYBE

2025
01:34:46,238 --> 01:34:47,740
 PATIENTS DO RECALL WHAT THEY

2026
01:34:47,740 --> 01:34:49,908
 WERE LIKE BEFORE AND HOW THEY

2027
01:34:49,908 --> 01:34:50,476
 ARE NOW?

2028
01:34:50,476 --> 01:34:53,045
 THAT OBJECTION CAN BE RAISED

2029
01:34:53,045 --> 01:34:56,515
 BY I DON'T KNOW IF IT HAS

2030
01:34:56,515 --> 01:35:01,820
 REALLY BEEN STUDIED AS A FATAL

2031
01:35:01,820 --> 01:35:02,121
 FAULT.

2032
01:35:02,121 --> 01:35:03,455
 AND WE CAN TALK ABOUT THIS

2033
01:35:03,455 --> 01:35:05,858
 LATER IF WE HAVE A CHANCE.

2034
01:35:05,858 --> 01:35:07,960
 AND WHY IN FACT DO WE

2035
01:35:07,960 --> 01:35:10,229
 NECESSARILY HAVE TO TAKE DAILY

2036
01:35:10,229 --> 01:35:11,296
 PAIN RATINGS?

2037
01:35:11,296 --> 01:35:14,166
 WE DON'T REALLY USE THE DATA

2038
01:35:14,166 --> 01:35:20,105
 NECESSARILY AND THIS ADDS TO

2039
01:35:20,105 --> 01:35:21,740
 THE COST FOR CERTAIN.

2040
01:35:21,740 --> 01:35:25,244
 SO FOR CONSIDERATION, WE COULD

2041
01:35:25,244 --> 01:35:26,812
 DO PATIENT IMPRESSION OF

2042
01:35:26,812 --> 01:35:29,548
 CHANGE IN PAIN OVER SEVERAL

2043
01:35:29,548 --> 01:35:31,884
 WEEKS INSTEAD OF DOING THESE

2044
01:35:31,884 --> 01:35:33,185
 THINGS EVERY DAY.

2045
01:35:33,185 --> 01:35:35,854
 I WILL MENTION BE A AREA UNDER

2046
01:35:35,854 --> 01:35:38,590
 THE CURVE, ANALYSIS, COULD BE

2047
01:35:38,590 --> 01:35:43,162
 MISLEADING IN A SITUATION

2048
01:35:43,162 --> 01:35:45,864
 WHERE PAIN DRUG HAS A WANING

2049
01:35:45,864 --> 01:35:49,301
 EFFECT AS MAY OCCUR, FOR

2050
01:35:49,301 --> 01:35:51,770
 EXAMPLE, AS AN OPIOID, SO WE

2051
01:35:51,770 --> 01:35:54,239
 MAY NOT WANT TO CALL THIS AUC

2052
01:35:54,239 --> 01:35:54,706
 THEN.

2053
01:35:54,706 --> 01:35:56,875
 THE WAY TO GET AROUND THIS IS

2054
01:35:56,875 --> 01:36:00,946
 AS A TOOL USED IN OTHER

2055
01:36:00,946 --> 01:36:03,482
 SITUATIONS, ECONOMIC,

2056
01:36:03,482 --> 01:36:07,286
 FINANCIAL ANALYSIS, USE A

2057
01:36:07,286 --> 01:36:09,021
 FUNCTION CALLED SUSPENSION

2058
01:36:09,021 --> 01:36:11,723
 WAITING AND THIS DESERVES TO

2059
01:36:11,723 --> 01:36:12,157
 BE CONSIDERED.

2060
01:36:12,157 --> 01:36:17,663
 SO LET ME GO TO MY COLLUSION,

2061
01:36:17,663 --> 01:36:19,631
 I WOULD SAY -- CONCLUSION, I

2062
01:36:19,631 --> 01:36:22,467
 WOULD SAY THE ENDPOINT

2063
01:36:22,467 --> 01:36:27,673
 ANALYSIS A FLAWED ENDPOINT AND

2064
01:36:27,673 --> 01:36:30,075
 ACROSS THE ANALYSIS REALLY IS

2065
01:36:30,075 --> 01:36:32,578
 A BETTER INTEGRATED TRIAL THAN

2066
01:36:32,578 --> 01:36:33,979
 UNDULY WAITING FOR THE RESULTS

2067
01:36:33,979 --> 01:36:37,583
 OVER A SINGLE WEEK.

2068
01:36:37,583 --> 01:36:40,452
 ACUTE PAIN CAN BE USED IN

2069
01:36:40,452 --> 01:36:43,755
 CHRONIC PAIN AND I WOULD SAY

2070
01:36:43,755 --> 01:36:45,490
 ACUTE PAIN UNDER THE CURVE

2071
01:36:45,490 --> 01:36:48,460
 COULD BE A PRIMARY ENDPOINT IN

2072
01:36:48,460 --> 01:36:51,296
 PAIN STUDIES BOTH IN ANIMAL

2073
01:36:51,296 --> 01:36:54,399
 AND HUMAN STUDIES AND WITH

2074
01:36:54,399 --> 01:37:02,908
 THAT, I WILL CLOSE OUT. 

2075
01:37:02,908 --> 01:37:03,375
 THANK YOU.

2076
01:37:03,375 --> 01:37:04,009
 [APPLAUSE]

2077
01:37:04,009 --> 01:37:06,478
 >> THANKS VERY MUCH, JIM,

2078
01:37:06,478 --> 01:37:07,312
 PROVOCATIVE THOUGHTS THERE.

2079
01:37:07,312 --> 01:37:08,747
 SO WE WILL MOVE TO THE PANEL

2080
01:37:08,747 --> 01:37:09,948
 DISCUSSIONS NOW AND I COULD

2081
01:37:09,948 --> 01:37:11,583
 ASK ALL THE SPEAKERS FROM THIS

2082
01:37:11,583 --> 01:37:22,127
 MORNING TO COME UP AND TAKE

2083
01:37:56,595 --> 01:37:57,129
 SEATS, PLEASE.

2084
01:37:57,129 --> 01:38:07,673
 AND JUST A VERY QUICK CHECK,

2085
01:38:08,006 --> 01:38:18,483
 MIKE, STELIO, CAN YOU HEAR US?

2086
01:38:20,819 --> 01:38:21,053
 STELIO?

2087
01:38:21,053 --> 01:38:21,486
 OKAY, GREAT.

2088
01:38:21,486 --> 01:38:22,554
 YOU WOULD THINK WITHIN FOUR

2089
01:38:22,554 --> 01:38:24,389
 YEARS OF PLAYING WITH ZOOM, WE

2090
01:38:24,389 --> 01:38:26,258
 WOULD ALMOST HAVE THIS FIGURED

2091
01:38:26,258 --> 01:38:26,525
 OUT.

2092
01:38:26,525 --> 01:38:29,861
 OKAY, ON TO QUESTIONS.

2093
01:38:29,861 --> 01:38:34,066
 ANYONE HAVE QUESTIONS FOR THE

2094
01:38:34,066 --> 01:38:36,101
 SPEAKERS? 

2095
01:38:36,101 --> 01:38:45,777
 IF NOT I CAN --

2096
01:38:45,777 --> 01:38:46,979
 [OVERLAPPING SPEAKERS]

2097
01:38:46,979 --> 01:38:49,614
 -- KICK OFF WITH ONE TO START

2098
01:38:49,614 --> 01:38:50,082
 WITH.

2099
01:38:50,082 --> 01:38:53,151
 OVER ZOOM, CAN YOU GUYS BOTH

2100
01:38:53,151 --> 01:38:56,355
 MUTE IF YOU ARE NOT SPEAKING?

2101
01:38:56,355 --> 01:38:59,791
 A LITTLE BIT OF FEEDBACK

2102
01:38:59,791 --> 01:39:00,158
 OCCURRING.

2103
01:39:00,158 --> 01:39:01,493
 GREAT, LET'S TRY THAT.

2104
01:39:01,493 --> 01:39:05,998
 SO MAYBE THIS IS AN OPEN ENDED

2105
01:39:05,998 --> 01:39:06,531
 QUESTION SO --

2106
01:39:06,531 --> 01:39:08,300
 >> I DON'T MEAN TO
INTERRUPT,

2107
01:39:08,300 --> 01:39:10,602
 I AM SORRY.

2108
01:39:10,602 --> 01:39:14,573
 SUPER FASCINATING, REALLY 

2109
01:39:14,573 --> 01:39:16,875
 ENJOYED THIS ONE, MY NAME IS

2110
01:39:16,875 --> 01:39:21,646
 SUSAN WITH THE FDA IN

2111
01:39:21,646 --> 01:39:22,114
 BIOLOGICS.

2112
01:39:22,114 --> 01:39:24,016
 COULDN'T HELP BUT NOTICE THE

2113
01:39:24,016 --> 01:39:25,650
 MEASURED REQUIREMENT IN

2114
01:39:25,650 --> 01:39:27,219
 ARTHRITIS PAIN, THE FIRST

2115
01:39:27,219 --> 01:39:30,956
 THING I THOUGHT ABOUT WAS

2116
01:39:30,956 --> 01:39:31,490
 DERMATOLOGY.

2117
01:39:31,490 --> 01:39:39,631
 I HAVE A DOG WITH AFRACTORY

2118
01:39:39,631 --> 01:39:41,933
 DERMATITIS, AND THERE IS A

2119
01:39:41,933 --> 01:39:46,371
 FOUR-PAGE OUTCOME, HOW MUCH

2120
01:39:46,371 --> 01:39:48,073
 ASK -- DOES HE ITCH, ET

2121
01:39:48,073 --> 01:39:49,808
 CETERA.

2122
01:39:49,808 --> 01:39:54,980
 SO THE QUESTION IS AS FAR AS

2123
01:39:54,980 --> 01:40:01,653
 THE PAIN KRELS -- CONTROLS IN 

2124
01:40:01,653 --> 01:40:05,257
 CLINICAL DESIGN, HAVE REPORTED

2125
01:40:05,257 --> 01:40:08,326
 OUTCOMES AS IN PETS BECAUSE I

2126
01:40:08,326 --> 01:40:13,432
 KNOW FROM MY OWN PETS THE

2127
01:40:13,432 --> 01:40:15,634
 REPORTED OUTCOME IS FOR

2128
01:40:15,634 --> 01:40:16,134
 IMPROVEMENT.

2129
01:40:16,134 --> 01:40:19,971
 >> ANYONE LIKE TO PICK
THAT

2130
01:40:19,971 --> 01:40:20,439
 UP?

2131
01:40:20,439 --> 01:40:20,705
 YES.

2132
01:40:20,705 --> 01:40:24,009
 SO I GUESS IT IS ME. 

2133
01:40:24,009 --> 01:40:28,080
 THERE ARE VALIDATED TOOLS IN

2134
01:40:28,080 --> 01:40:29,481
 EXISTENCE.

2135
01:40:29,481 --> 01:40:33,418
 I THINK WOULD CAN CHAT TO ONE 

2136
01:40:33,418 --> 01:40:35,020
 OF THE DEVELOPERS, UNIVERSITY

2137
01:40:35,020 --> 01:40:37,422
 OF BRISTOL AND I THINK THE

2138
01:40:37,422 --> 01:40:38,523
 DEVELOPER WOULD, IN AUSTRALIA

2139
01:40:38,523 --> 01:40:42,127
 AND HE HAS NO INTEREST IN THAT

2140
01:40:42,127 --> 01:40:44,262
 SCALE FOR SOME REASON.

2141
01:40:44,262 --> 01:40:50,869
 SO I AM SURE, I THINK THE RULE

2142
01:40:50,869 --> 01:40:54,473
 DISCIPLINES THAT HAVE BEEN

2143
01:40:54,473 --> 01:40:56,408
 MADE IN VETERINARY MEDICINE

2144
01:40:56,408 --> 01:41:00,545
 AND HUMAN MEDICINE SHOULD COME

2145
01:41:00,545 --> 01:41:02,914
 TOGETHER FOR BETTER CLINICAL

2146
01:41:02,914 --> 01:41:03,615
 OUTCOMES.

2147
01:41:03,615 --> 01:41:05,150
 THAT WOULD BE GREAT BECAUSE IT

2148
01:41:05,150 --> 01:41:10,288
 IS A BIT SILENT AT THE MOMENT.

2149
01:41:10,288 --> 01:41:11,990
 THERE ARE INCREASINGLY

2150
01:41:11,990 --> 01:41:15,393
 OUTCOMES OUT THERE AND COULD

2151
01:41:15,393 --> 01:41:18,029
 BE USED TO IMPROVE EACH OTHER

2152
01:41:18,029 --> 01:41:22,434
 SO I AGREE WITH THAT.

2153
01:41:22,434 --> 01:41:26,004
 >> SO COULD I INTERRUPT?

2154
01:41:26,004 --> 01:41:30,675
 DUPIXEN IS NOW VERY STRIKINGLY

2155
01:41:30,675 --> 01:41:32,978
 USEFUL THERAPY FOR ATOPIC

2156
01:41:32,978 --> 01:41:35,914
 DERMATITIS AND THERE IS A

2157
01:41:35,914 --> 01:41:39,251
 FLOOD OF THEATRES APPEAR --

2158
01:41:39,251 --> 01:41:42,053
 OTHERS THAT APPEAR TO MAYBE

2159
01:41:42,053 --> 01:41:45,891
 WORK AS WELL AND WE'RE

2160
01:41:45,891 --> 01:41:47,726
 CERTAINLY SEEING A HUGE

2161
01:41:47,726 --> 01:41:49,728
 DEVELOPMENT.

2162
01:41:49,728 --> 01:41:52,564
 IN THE CHRONIC PAIN FIELD,

2163
01:41:52,564 --> 01:41:53,798
 WE'RE LOOKING WITH ENVY ON

2164
01:41:53,798 --> 01:41:56,768
 WHAT IS HAPPENING WITH ATOPIC

2165
01:41:56,768 --> 01:41:58,970
 DERMATITIS WHICH IS HARDLY

2166
01:41:58,970 --> 01:41:59,371
 RECOMMENDED.

2167
01:41:59,371 --> 01:42:01,506
 MY WIFE IS A DERMATOLOGIST AND

2168
01:42:01,506 --> 01:42:04,309
 20 YEARS AGO THIS WAS A

2169
01:42:04,309 --> 01:42:05,977
 NUISANCE SYNDROME BUT NOW ALL

2170
01:42:05,977 --> 01:42:08,613
 OF A SUDDEN THAT THERE IS A

2171
01:42:08,613 --> 01:42:10,882
 TREATMENT, IT IS OF GREAT

2172
01:42:10,882 --> 01:42:11,249
 INTEREST.

2173
01:42:11,249 --> 01:42:13,852
 IN THE PAIN FIELD, THE

2174
01:42:13,852 --> 01:42:15,587
 FRUSTRATION HAS BEEN THAT WE

2175
01:42:15,587 --> 01:42:18,323
 HAVE REALLY NOT SEEN ANY

2176
01:42:18,323 --> 01:42:23,195
 INNOVATION FOR OVER 20 YEARS

2177
01:42:23,195 --> 01:42:27,032
 AND IT'S QUITE STRIKING WITH

2178
01:42:27,032 --> 01:42:37,509
 DRUGS WE KNOW WORK, LIKE

2179
01:42:44,683 --> 01:42:46,952
 GABAPENTON, PREABALIN, THOSE

2180
01:42:46,952 --> 01:42:48,353
 DRUGS WORK AND SOMETIMES THE

2181
01:42:48,353 --> 01:42:51,189
 HELP IT CONFERS TO A PATIENT

2182
01:42:51,189 --> 01:42:53,825
 IS CLINICALLY VERY STRIKING,

2183
01:42:53,825 --> 01:42:56,861
 ALTHOUGH OFTEN WITH SIDE

2184
01:42:56,861 --> 01:43:00,932
 EFFECTS BUT IN DOING TRIALS,

2185
01:43:00,932 --> 01:43:03,568
 IT HAS BEEN POINT OUT IN THE

2186
01:43:03,568 --> 01:43:05,870
 ANALYSIS THAT MANY OF THE

2187
01:43:05,870 --> 01:43:12,444
 TRIALS OUTRIGHT FAILED AND THE

2188
01:43:12,444 --> 01:43:13,478
 STANDARDIZED EFFECTS ARE ALL

2189
01:43:13,478 --> 01:43:16,648
 OFFER THE PLACE GOING FROM

2190
01:43:16,648 --> 01:43:18,750
 NEGATIVE TO POSITIVE IN

2191
01:43:18,750 --> 01:43:20,619
 VARIOUS LEVELS OF POSITIVITY.

2192
01:43:20,619 --> 01:43:22,887
 SO ONE REASON FOR THAT COULD

2193
01:43:22,887 --> 01:43:27,692
 BE THAT WE JUST DON'T KNOW IN

2194
01:43:27,692 --> 01:43:29,160
 CHRONIC PAIN HOW OPTIMALLY TO

2195
01:43:29,160 --> 01:43:31,963
 DO THE TRIALS AND THAT IS A

2196
01:43:31,963 --> 01:43:33,198
 REAL SHAME BECAUSE WE ARE

2197
01:43:33,198 --> 01:43:35,700
 LOOKING AT A NUMBER OF

2198
01:43:35,700 --> 01:43:38,103
 PROMISING THERAPIES AND IF WE

2199
01:43:38,103 --> 01:43:39,938
 DON'T HAVE OUR TOOLS NAILED

2200
01:43:39,938 --> 01:43:44,576
 DOWN PROPERLY, WE ARE AT RISK

2201
01:43:44,576 --> 01:43:46,878
 OF LOSING OUT ON INNOVATION

2202
01:43:46,878 --> 01:43:48,346
 BECAUSE WE WON'T APPRECIATE

2203
01:43:48,346 --> 01:43:53,285
 THAT THE DRUG TRULY WORKS FOR

2204
01:43:53,285 --> 01:43:53,618
 NOW.

2205
01:43:53,618 --> 01:43:54,986
 >> THANKS FOR THAT AND I
AM

2206
01:43:54,986 --> 01:43:56,721
 GOING TO BRING IN MIKE.

2207
01:43:56,721 --> 01:43:57,889
 MIKE, I THINK YOU HAVE

2208
01:43:57,889 --> 01:44:01,059
 SOMETHING TO SAY ABOUT THAT

2209
01:44:01,059 --> 01:44:01,793
 QUESTION?

2210
01:44:01,793 --> 01:44:03,528
 >> YES, I THINK IT IS A
GREAT

2211
01:44:03,528 --> 01:44:03,895
 QUESTION.

2212
01:44:03,895 --> 01:44:05,964
 OBVIOUSLY WE HAVE TO HAVE AN

2213
01:44:05,964 --> 01:44:06,798
 OPEN MIND.

2214
01:44:06,798 --> 01:44:08,833
 ONE THING THAT I THINK IS

2215
01:44:08,833 --> 01:44:10,468
 STARTING TO CHANGE IS, YOU

2216
01:44:10,468 --> 01:44:13,104
 KNOW, SO WHEN IT COMES TO

2217
01:44:13,104 --> 01:44:16,374
 PAIN, THE PATIENT CAN CHANGE

2218
01:44:16,374 --> 01:44:17,208
 DRAMATICALLY DEPENDING ON

2219
01:44:17,208 --> 01:44:18,343
 THEIR ENVIRONMENT THAT THEY

2220
01:44:18,343 --> 01:44:20,245
 ARE IN.

2221
01:44:20,245 --> 01:44:24,916
 AND YOU BRING A PATIENT INTO A

2222
01:44:24,916 --> 01:44:26,584
 VETERINARY HOSPITAL, YOU KNOW,

2223
01:44:26,584 --> 01:44:29,254
 IT IS QUITE COMMON FOR ME FOR

2224
01:44:29,254 --> 01:44:31,990
 EXAMPLE, FOR AN OWNER TO SAY

2225
01:44:31,990 --> 01:44:34,759
 OH, WELL LIKE I DON'T SEE MUCH

2226
01:44:34,759 --> 01:44:37,395
 VALIDITY AND THEN THEY SHOW ME

2227
01:44:37,395 --> 01:44:39,864
 A VIDEO AT HOME AND IT IS

2228
01:44:39,864 --> 01:44:40,465
 QUITE OBVIOUS.

2229
01:44:40,465 --> 01:44:42,600
 SO I DO THINK YOU HAVE TO

2230
01:44:42,600 --> 01:44:43,301
 THINK ABOUT THE ENVIRONMENT

2231
01:44:43,301 --> 01:44:46,838
 THEY ARE IN AND HOW THAT SKIS

2232
01:44:46,838 --> 01:44:49,441
 MAY OR -- DISEASE MAY OR MAY

2233
01:44:49,441 --> 01:44:52,477
 NOT BE IMPACTED BY THAT

2234
01:44:52,477 --> 01:44:53,611
 PARTICULAR ENVIRONMENT.

2235
01:44:53,611 --> 01:44:55,714
 THE ONE THING WE SHOULD WORK

2236
01:44:55,714 --> 01:44:59,050
 FOR, MANY OF US HAVE WORKED

2237
01:44:59,050 --> 01:45:00,885
 FOR, IS MEASURING THE PATIENT

2238
01:45:00,885 --> 01:45:02,253
 IN THEIR NATURAL ENVIRONMENT,

2239
01:45:02,253 --> 01:45:06,491
 WHICH IS AT HOME, VIA ACTIVITY

2240
01:45:06,491 --> 01:45:10,795
 MONITORING WHICH IS A TRICKY

2241
01:45:10,795 --> 01:45:15,066
 SCIENCE BUT THERE ARE SOME

2242
01:45:15,066 --> 01:45:17,369
 AVOCATIONS THAT HAVE COME OUT

2243
01:45:17,369 --> 01:45:18,636
 RECENTLY THAT SORT OF DESCRIBE

2244
01:45:18,636 --> 01:45:21,539
 HOW WE CAN GET TO THE END OF

2245
01:45:21,539 --> 01:45:22,674
 MEASURING THE PATIENT AT HOME

2246
01:45:22,674 --> 01:45:27,779
 WHICH I THINK TRANSLATED WELL

2247
01:45:27,779 --> 01:45:30,715
 IN MEASURING CHRONIC PAIN IN

2248
01:45:30,715 --> 01:45:31,282
 THE PATIENT'S NATURAL

2249
01:45:31,282 --> 01:45:31,850
 ENVIRONMENT.

2250
01:45:31,850 --> 01:45:33,952
 SO THAT IS MY TAKE ON ONE OF

2251
01:45:33,952 --> 01:45:36,855
 THE THINGS ABOUT

2252
01:45:36,855 --> 01:45:37,322
 QUESTIONNAIRES.

2253
01:45:37,322 --> 01:45:37,822
 >> GREAT, THANKS.

2254
01:45:37,822 --> 01:45:39,290
 LETS HE GO TO THE NEXT

2255
01:45:39,290 --> 01:45:43,995
 QUESTION OVER ON THE RIGHT

2256
01:45:43,995 --> 01:45:44,295
 HERE.

2257
01:45:44,295 --> 01:45:46,464
 >>

2258
01:45:46,464 --> 01:45:47,065
 [INDISCERNIBLE]

2259
01:45:47,065 --> 01:45:49,367
 IN HANOVER, I HAVE A QUESTION

2260
01:45:49,367 --> 01:45:51,603
 OR MAYBE COMMENT RELATED TO

2261
01:45:51,603 --> 01:45:55,140
 CAREGIVER ASSESSMENT BECAUSE

2262
01:45:55,140 --> 01:45:58,443
 WE KNOW PAIN AND ALSO THE

2263
01:45:58,443 --> 01:46:01,146
 RELATING OF PROXY, VERY

2264
01:46:01,146 --> 01:46:04,749
 DEPENDENT ON THE CULTURE, YOUR

2265
01:46:04,749 --> 01:46:05,316
 UPBRINGING.

2266
01:46:05,316 --> 01:46:10,522
 ARE THERE ANY STUDIES THAT 

2267
01:46:10,522 --> 01:46:13,825
 LOOKED AT THE INFLUKES OF

2268
01:46:13,825 --> 01:46:16,594
 THE -- INFLUENCE OF THE

2269
01:46:16,594 --> 01:46:19,864
 PATIENT ON DISEASE AND

2270
01:46:19,864 --> 01:46:20,832
 CAREGIVER ASSESSMENT?

2271
01:46:20,832 --> 01:46:23,401
 BECAUSE I THINK WHEN WE LOOKED

2272
01:46:23,401 --> 01:46:27,505
 AT THE DATA IN THE EUROPEAN

2273
01:46:27,505 --> 01:46:29,107
 UNION AND MIDWEST, THERE WAS

2274
01:46:29,107 --> 01:46:31,509
 QUITE A BIG DIFFERENCE IN THE

2275
01:46:31,509 --> 01:46:35,513
 PLACEBO EFFECT BECAUSE OF THE

2276
01:46:35,513 --> 01:46:36,481
 MUCH HIGHER PLACEBO EFFECT IN

2277
01:46:36,481 --> 01:46:40,652
 THE U.S -- I MEAN EUROPEANS,

2278
01:46:40,652 --> 01:46:42,921
 ACTUALLY SO MAYBE THE

2279
01:46:42,921 --> 01:46:51,129
 EUROPEANS ARE MORE GRUMPY AND 

2280
01:46:51,129 --> 01:46:53,932
 A LITTLE LESS EFFECTIVE AND SO

2281
01:46:53,932 --> 01:46:55,800
 THERE COULD BE A DIFFERENCE

2282
01:46:55,800 --> 01:46:58,136
 BETWEEN THE AMERICAN AND

2283
01:46:58,136 --> 01:47:01,973
 EUROPEAN CULTURE AND SO HAVE

2284
01:47:01,973 --> 01:47:04,676
 YOU NOTICED ANY DIFFERENCES

2285
01:47:04,676 --> 01:47:06,811
 WITH THE ANIMAL OR SAY A

2286
01:47:06,811 --> 01:47:07,278
 CHILD?

2287
01:47:07,278 --> 01:47:08,880
 >> GREAT QUESTION AND DO
WE

2288
01:47:08,880 --> 01:47:12,684
 NEED TO IMPLEMENT CULTURAL

2289
01:47:12,684 --> 01:47:14,552
 FAILURES OR SUCCESSES?

2290
01:47:14,552 --> 01:47:18,389
 JENNIFER, CAN YOU KICK US OFF

2291
01:47:18,389 --> 01:47:19,457
 ON THIS ONE?

2292
01:47:19,457 --> 01:47:20,258
 >> I DON'T KNOW, I MEAN,
I

2293
01:47:20,258 --> 01:47:21,826
 DON'T KNOW, I WOULD HAVE TO

2294
01:47:21,826 --> 01:47:24,963
 LOOK AT THAT BUT I THINK IT IS

2295
01:47:24,963 --> 01:47:25,930
 DEFINITELY TRUE, RIGHT, AS

2296
01:47:25,930 --> 01:47:27,932
 THERE ARE SO MANY THINGS THAT

2297
01:47:27,932 --> 01:47:31,102
 GO INTO A PLACEBO RESPONSE

2298
01:47:31,102 --> 01:47:32,737
 WITH EXPECTATIONS AND THAT

2299
01:47:32,737 --> 01:47:34,973
 WOULD BE REALLY INTERESTING TO

2300
01:47:34,973 --> 01:47:38,810
 LOOK TO SEE IF SIMILARATICALLY

2301
01:47:38,810 --> 01:47:40,645
 THERE IS A DIFFERENCE IN THE

2302
01:47:40,645 --> 01:47:42,814
 STUDY AND I THINK THE BEST WAY

2303
01:47:42,814 --> 01:47:45,750
 TO DO THAT IS AN INTERNATIONAL

2304
01:47:45,750 --> 01:47:50,188
 STUDY LOOKING AT THE SAME

2305
01:47:50,188 --> 01:47:52,590
 TYPES OF PAIN AND COMPARE

2306
01:47:52,590 --> 01:47:53,024
 THAT.

2307
01:47:53,024 --> 01:47:55,927
 >> ANYONE ELSE LIKE TO
COMMENT

2308
01:47:55,927 --> 01:47:57,529
 ON CULTURAL DIFFERENCES AND

2309
01:47:57,529 --> 01:48:01,533
 PAIN AND HOW TO COMPARE THOSE

2310
01:48:01,533 --> 01:48:01,900
 IN, MIKE?

2311
01:48:01,900 --> 01:48:07,472
 >> REAL QUICK, I CAN IT
IS --

2312
01:48:07,472 --> 01:48:09,140
 I THINK IT IS AN EXCELLENT

2313
01:48:09,140 --> 01:48:11,042
 POINT BUT A LITTLE BIT OF A

2314
01:48:11,042 --> 01:48:11,476
 RAT HOLE.

2315
01:48:11,476 --> 01:48:14,812
 I THINK IF YOU LOOK AT PLACEBO

2316
01:48:14,812 --> 01:48:16,881
 DATA, THERE ARE PUBLISHED

2317
01:48:16,881 --> 01:48:19,384
 EFFECTS WHERE THERE IS

2318
01:48:19,384 --> 01:48:20,785
 DIFFERENCES IN RELIGION, HAS

2319
01:48:20,785 --> 01:48:24,722
 AN EFFECT ON PLACEBO EFFECT,

2320
01:48:24,722 --> 01:48:27,792
 GENDER AND AGE HAVE A MACABLE

2321
01:48:27,792 --> 01:48:30,762
 BO EFFECT SO THERE ARE

2322
01:48:30,762 --> 01:48:35,500
 PUBLICATIONS THAT LOOK AT

2323
01:48:35,500 --> 01:48:38,303
 CAREGIVER PLACEBO EFFECTS AND

2324
01:48:38,303 --> 01:48:40,338
 OUTSIDE INFLUENCES, I DON'T

2325
01:48:40,338 --> 01:48:41,873
 SPECIFICALLY RECALL, YOU KNOW,

2326
01:48:41,873 --> 01:48:43,708
 WHAT COUNTRY OF ORIGIN BUT I

2327
01:48:43,708 --> 01:48:46,210
 THINK IT IS NOT ONLY COUNTRY

2328
01:48:46,210 --> 01:48:50,481
 OF ORIGIN BUT YOU KNOW FOR

2329
01:48:50,481 --> 01:48:53,651
 EXAMPLE IS AS I GET A LITTLE

2330
01:48:53,651 --> 01:48:55,219
 OLDER, COULD SAY THOSE KIDS

2331
01:48:55,219 --> 01:48:56,588
 WITH THAT ROCK AND ROLL MUSIC,

2332
01:48:56,588 --> 01:48:59,257
 THE WA I THINKEN TIPPER PAIN

2333
01:48:59,257 --> 01:49:01,125
 IN DOGS IS ALL WRONG.

2334
01:49:01,125 --> 01:49:04,495
 SO I THINK THERE'S OTHER

2335
01:49:04,495 --> 01:49:05,964
 FACTORS AS WELL SO I WOULDN'T

2336
01:49:05,964 --> 01:49:08,800
 BE SURPRISED IF THERE ARE

2337
01:49:08,800 --> 01:49:09,634
 OTHER INFLUENCING FACTORS AND

2338
01:49:09,634 --> 01:49:11,569
 ONE OF THE THINGS YOU HAVE TO

2339
01:49:11,569 --> 01:49:15,340
 ADDRESS IN YOUR STUDIES.

2340
01:49:15,340 --> 01:49:15,773
 >> OKAY.

2341
01:49:15,773 --> 01:49:19,110
 >> COULD I MAKE ONE
COMMENT?

2342
01:49:19,110 --> 01:49:25,083
 >> THEN I WILL COME TO
YOU,

2343
01:49:25,083 --> 01:49:25,583
 CELIA, ONE SECOND.

2344
01:49:25,583 --> 01:49:29,754
 >> SO CAN YOU THINK --
DUNCAN,

2345
01:49:29,754 --> 01:49:31,823
 YOU ARE VERY FAMILIAR WITH

2346
01:49:31,823 --> 01:49:33,291
 THIS, WE ARE DOING EXPLORATORY

2347
01:49:33,291 --> 01:49:35,426
 WORK IN THE U.S. AND LOOKING

2348
01:49:35,426 --> 01:49:37,829
 AT OUTCOMES FOR DOGS IN A

2349
01:49:37,829 --> 01:49:39,697
 ARTHRITIS MODEL AND WHAT WAS

2350
01:49:39,697 --> 01:49:44,335
 STRIKING WAS TO SAY THE

2351
01:49:44,335 --> 01:49:45,036
 DIFFERENCES.

2352
01:49:45,036 --> 01:49:46,938
 IT HAPPENED IN -- ONE OF THE

2353
01:49:46,938 --> 01:49:49,907
 STATES WAS RUN BY DOTTIE BROWN

2354
01:49:49,907 --> 01:49:54,712
 WHEN SHE WAS AT THE UNIVERSITY

2355
01:49:54,712 --> 01:49:57,115
 OF PENNSYLVANIA.

2356
01:49:57,115 --> 01:50:01,452
 AND THE EFFECTS SIDE,

2357
01:50:01,452 --> 01:50:02,553
 DIFFERENTIATION OF PLACEBO AND

2358
01:50:02,553 --> 01:50:05,857
 EFFECTIVE IN A BLINDED TRIAL

2359
01:50:05,857 --> 01:50:12,030
 WAS REMARKABLE AND VERY LITTLE

2360
01:50:12,030 --> 01:50:12,997
 PLACEBO WAS OBSERVED.

2361
01:50:12,997 --> 01:50:14,565
 BUT AT OTHER SITES WITHIN THE

2362
01:50:14,565 --> 01:50:17,769
 U.S., THERE WAS AN ENORMOUS

2363
01:50:17,769 --> 01:50:19,270
 PLACEBO EFFECT AND ONE WOULD

2364
01:50:19,270 --> 01:50:22,006
 NEVER BE ABLE TO SHOW THAT A

2365
01:50:22,006 --> 01:50:25,910
 DRUG TRULY WORKED OR NOT IF

2366
01:50:25,910 --> 01:50:29,180
 THE PLACEBO EFFECT IS SO LARGE

2367
01:50:29,180 --> 01:50:31,315
 THAT IT WIPES OUT THE ABILITY

2368
01:50:31,315 --> 01:50:31,883
 TO MEASURE.

2369
01:50:31,883 --> 01:50:37,221
 SO I AM NOT SCHUMER IT IS

2370
01:50:37,221 --> 01:50:38,990
 JUST -- NOT SURE IT IS JUST

2371
01:50:38,990 --> 01:50:39,457
 CULTURAL.

2372
01:50:39,457 --> 01:50:41,426
 I THINK IT IS THE

2373
01:50:41,426 --> 01:50:42,527
 SOPHISTICATION TRAINING OF THE

2374
01:50:42,527 --> 01:50:47,031
 SITE AND HOW ONE INTERACTS

2375
01:50:47,031 --> 01:50:49,934
 WITH THE CLIENT, THE OWNER OF

2376
01:50:49,934 --> 01:50:52,470
 THE PET, FOR EXAMPLE, OR IN

2377
01:50:52,470 --> 01:50:56,774
 THE CASE OF CHRONIC PAIN, THE

2378
01:50:56,774 --> 01:50:59,744
 CONDITIONS OF THE RELATIONSHIP

2379
01:50:59,744 --> 01:51:04,682
 WITH THE SUBJECTS, I THINK ARE

2380
01:51:04,682 --> 01:51:06,350
 MORE LIKELY, EVEN THOUGH --

2381
01:51:06,350 --> 01:51:09,187
 AND IT IS CHALLENGING WHETHER,

2382
01:51:09,187 --> 01:51:11,289
 IN THE UK, THEY DO SPEAK A

2383
01:51:11,289 --> 01:51:13,057
 FOREIGN LANGUAGE SO MAYBE THAT

2384
01:51:13,057 --> 01:51:13,357
 IS IT.

2385
01:51:13,357 --> 01:51:15,927
 >> I COULD CHIP IN TO SAY

2386
01:51:15,927 --> 01:51:18,763
 BRITISH ENGLISH IS DEFINITELY

2387
01:51:18,763 --> 01:51:20,198
 DIFFERENT FROM AMERICAN

2388
01:51:20,198 --> 01:51:20,798
 ENGLISH.

2389
01:51:20,798 --> 01:51:23,367
 COULD I BRING YOU IN NOW, OFF

2390
01:51:23,367 --> 01:51:28,873
 STATEMENT FOR THE PANELISTS?

2391
01:51:28,873 --> 01:51:32,510
 >> YES, SO THIS MIGHT BE
A BIG

2392
01:51:32,510 --> 01:51:37,682
 BANK BUT WE HAVE STUDIES IN

2393
01:51:37,682 --> 01:51:44,155
 FIVE LANGUAGES SO IT PROVES A

2394
01:51:44,155 --> 01:51:47,992
 POINT BUT COULD BE THAT THE

2395
01:51:47,992 --> 01:51:50,294
 EFFECTS ARE SIMILAR --

2396
01:51:50,294 --> 01:51:50,762
 [INDISCERNIBLE]

2397
01:51:50,762 --> 01:51:53,898
 >> MAYBE THAT SPEAKS TO
THE

2398
01:51:53,898 --> 01:51:56,300
 QUALITY THAT THE ASSESSMENT

2399
01:51:56,300 --> 01:51:59,904
 TOOL DOES WORK IN DIFFERENT

2400
01:51:59,904 --> 01:52:02,874
 SETTINGS. 

2401
01:52:02,874 --> 01:52:04,142
 KATHLEEN, GO AHEAD.

2402
01:52:04,142 --> 01:52:05,543
 >> KATHLEEN, UNIVERSITY
OF

2403
01:52:05,543 --> 01:52:06,644
 IOWA.

2404
01:52:06,644 --> 01:52:10,748
 EVERYBODY HAS THAT UNIQUE

2405
01:52:10,748 --> 01:52:12,583
 PERSPECTIVE, OH, WOULD HAVE

2406
01:52:12,583 --> 01:52:16,187
 BEEN MORE EFFECTIVE IF I HAD

2407
01:52:16,187 --> 01:52:18,923
 PICKED A DIFFERENT OUTCOME AND

2408
01:52:18,923 --> 01:52:20,858
 JENNIFER HAS THIS CLAUSE OF

2409
01:52:20,858 --> 01:52:24,796
 SHOULD WE PICK THE BENEFIT FOR

2410
01:52:24,796 --> 01:52:25,630
 THE OUTCOME.

2411
01:52:25,630 --> 01:52:33,204
 BUT I WONDER IF WE SHOULD

2412
01:52:33,204 --> 01:52:36,307
 COMPARE THE OUTCOME TO OUR

2413
01:52:36,307 --> 01:52:36,741
 PURPOSE?

2414
01:52:36,741 --> 01:52:39,477
 IN OTHER WORDS, IS PAIN MORE

2415
01:52:39,477 --> 01:52:42,580
 IMPORTANT OR SHOULD WE BE

2416
01:52:42,580 --> 01:52:43,915
 LOOKING AT MULTIPLE UTCOMES,

2417
01:52:43,915 --> 01:52:48,619
 AND I KNOW WE WILL TALK ABOUT

2418
01:52:48,619 --> 01:52:51,389
 THIS LATER, OR SHOULD WE MAKE

2419
01:52:51,389 --> 01:52:52,890
 OUR BEST GUESS AND THEN BE

2420
01:52:52,890 --> 01:52:55,526
 TOLD AT A CLINICAL TRIAL THAT

2421
01:52:55,526 --> 01:52:56,761
 YOU FAILED BECAUSE YOUR GUESS

2422
01:52:56,761 --> 01:52:59,764
 IS WRONG, IT IS HARSH.

2423
01:52:59,764 --> 01:53:02,133
 AND SO JENNIFER IS THE

2424
01:53:02,133 --> 01:53:03,201
 CLINICAL EXPERT AND THAT WOULD

2425
01:53:03,201 --> 01:53:05,303
 BE GREAT BUT LIKE TO GET A

2426
01:53:05,303 --> 01:53:06,904
 THOUGHT ON THIS, ARE WE

2427
01:53:06,904 --> 01:53:08,873
 LOOKING AT THINGS IN THE WRONG

2428
01:53:08,873 --> 01:53:11,375
 WAY, SHOULD WE BE THINKING

2429
01:53:11,375 --> 01:53:13,711
 ABOUT CLINICAL TRIALS AND

2430
01:53:13,711 --> 01:53:14,979
 EXPANDING ON THE METHODOLOGY

2431
01:53:14,979 --> 01:53:19,684
 IN A DIFFERENT WAY.

2432
01:53:19,684 --> 01:53:21,052
 >> JENNIFER, PLEASE?

2433
01:53:21,052 --> 01:53:23,087
 >> OH, WELL, WHAT A
QUESTION.

2434
01:53:23,087 --> 01:53:25,056
 I DON'T THINK I HAVE ANSWERS.

2435
01:53:25,056 --> 01:53:27,191
 I THINK THERE ARE SO MANY

2436
01:53:27,191 --> 01:53:29,627
 FACTORS THAT GO INTO DECIDING

2437
01:53:29,627 --> 01:53:30,795
 WHAT YOUR PRIMARY OUTCOMES

2438
01:53:30,795 --> 01:53:35,566
 SHOULD BE AND I LOVE THE IDEA 

2439
01:53:35,566 --> 01:53:38,703
 OF PERSONALIZING OUTCOMES AND

2440
01:53:38,703 --> 01:53:40,438
 ACTUALLY THINKING ABOUT THIS

2441
01:53:40,438 --> 01:53:44,675
 IN TERMS OF PAIN QUALITY,

2442
01:53:44,675 --> 01:53:46,244
 MEASURING THE ACTIVE PAIN,

2443
01:53:46,244 --> 01:53:50,548
 ASKING PEOPLE WHAT IS THE MOST

2444
01:53:50,548 --> 01:53:53,217
 IMPORTANT PAIN QUALITY TO

2445
01:53:53,217 --> 01:53:55,019
 THEM, ASSESS THE PAIN QUALITY

2446
01:53:55,019 --> 01:53:57,722
 AND I AM DOING A STUDY TO LOOK

2447
01:53:57,722 --> 01:53:58,055
 AT THAT.

2448
01:53:58,055 --> 01:53:59,857
 I THINK THERE ARE A COUPLE OF

2449
01:53:59,857 --> 01:54:00,591
 CHALLENGES.

2450
01:54:00,591 --> 01:54:02,393
 THE FIRST ONE IS IF YOU GIVE

2451
01:54:02,393 --> 01:54:03,561
 PEOPLE THE OPPORTUNITY TO

2452
01:54:03,561 --> 01:54:06,330
 CHOOSE WHAT IS IMPORTANT TO

2453
01:54:06,330 --> 01:54:08,399
 THEM AT BASELINE, THE OUTCOME

2454
01:54:08,399 --> 01:54:10,067
 HAS TO BE SOMEWHAT UNIFORM.

2455
01:54:10,067 --> 01:54:13,371
 IF IT IS MEASURED ON 0 TO 10,

2456
01:54:13,371 --> 01:54:15,373
 YOU CAN COMBINE THOSE THINGS,

2457
01:54:15,373 --> 01:54:17,074
 IF IT IS NOT, THEN YOU CAN'T

2458
01:54:17,074 --> 01:54:19,577
 AND THAT IS ONE THING TO THINK

2459
01:54:19,577 --> 01:54:19,877
 ABOUT.

2460
01:54:19,877 --> 01:54:21,913
 THE OTHER THING WITH REGARD TO

2461
01:54:21,913 --> 01:54:23,948
 BENEFIT RISKS THAT BECOMES A

2462
01:54:23,948 --> 01:54:25,116
 LITTLE MORE COMPLICATED, I

2463
01:54:25,116 --> 01:54:28,753
 THINK FOR ME, THE REASON I GOT

2464
01:54:28,753 --> 01:54:30,922
 INTO PAIN RESEARCH IS I HAD A

2465
01:54:30,922 --> 01:54:34,558
 MOM WHO WAS IN CHRONIC PAIN

2466
01:54:34,558 --> 01:54:36,427
 HER WHOLE ADULT LIFE BUT I

2467
01:54:36,427 --> 01:54:40,298
 WANTED TO MAKE IT AS EASY AS

2468
01:54:40,298 --> 01:54:42,800
 POSSIBLE TO GET DRUGS WHEN

2469
01:54:42,800 --> 01:54:44,835
 THEY DO TRULY WORK.

2470
01:54:44,835 --> 01:54:47,038
 AND WHEN YOU BRING IN BENEFIT

2471
01:54:47,038 --> 01:54:48,806
 RISK IN AN ASSESSMENT, YOU

2472
01:54:48,806 --> 01:54:50,775
 RISK BEING ARE ABLE TO SHOW IT

2473
01:54:50,775 --> 01:54:51,375
 WORKS.

2474
01:54:51,375 --> 01:54:53,945
 SO I THINK IT HELPS PEOPLE

2475
01:54:53,945 --> 01:54:56,047
 DECIDE WHICH OF THESE TWO

2476
01:54:56,047 --> 01:54:57,581
 DRUGS SHOULD I TRY FIRST OR

2477
01:54:57,581 --> 01:54:59,483
 WOULD BE BETTER FOR ME IS A

2478
01:54:59,483 --> 01:55:00,484
 GOOD OUTCOME.

2479
01:55:00,484 --> 01:55:02,520
 TO RAISE THE BAR AND SAY IN

2480
01:55:02,520 --> 01:55:04,355
 ORDER TO GET APPROVED YOU HAVE

2481
01:55:04,355 --> 01:55:07,058
 TO HAVE A HIGH BENEFIT RISK

2482
01:55:07,058 --> 01:55:11,529
 PROFILE, WE HAVE TO BE VERY

2483
01:55:11,529 --> 01:55:14,265
 CAREFUL ABOUT THAT AND THEN

2484
01:55:14,265 --> 01:55:17,001
 LOOK AT THE NEGATIVE RISK AS A

2485
01:55:17,001 --> 01:55:20,504
 BENEFIT OF THAT SO I THINK I

2486
01:55:20,504 --> 01:55:22,840
 JUST RAM BUILD A LOT OF

2487
01:55:22,840 --> 01:55:23,174
 THINGS.

2488
01:55:23,174 --> 01:55:27,178
 >> ANYONE ELSE WANT TO
COMMENT

2489
01:55:27,178 --> 01:55:28,746
 ON INDIVIDUALIZING OUTCOME

2490
01:55:28,746 --> 01:55:29,113
 MEASURES?

2491
01:55:29,113 --> 01:55:30,781
 >> MAYBE WE WILL GET INTO
THIS

2492
01:55:30,781 --> 01:55:37,888
 A LITTLE BIT WHEN WE HAVE OUR 

2493
01:55:37,888 --> 01:55:39,590
 DISCUSSIONS ABOUT COMBINING

2494
01:55:39,590 --> 01:55:41,792
 OUTCOMES AND MIGHT BE ABLE TO,

2495
01:55:41,792 --> 01:55:45,262
 WITH COME POSSIBLE COMPOSITE

2496
01:55:45,262 --> 01:55:46,797
 MEASURES, TAP INTO THIS.

2497
01:55:46,797 --> 01:55:50,601
 I THINK A COMPLEXITY IS HOW DO

2498
01:55:50,601 --> 01:55:53,104
 YOU WRITE THE LABEL AND I

2499
01:55:53,104 --> 01:55:54,638
 THINK IT'S A TERRIFIC IDEA

2500
01:55:54,638 --> 01:55:57,441
 THAT FOR ONE PERSON, PAIN IS

2501
01:55:57,441 --> 01:56:00,978
 IMPORTANT AND IN ANOTHER

2502
01:56:00,978 --> 01:56:02,646
 PERSON, MAYBE IT IS FUNCTION

2503
01:56:02,646 --> 01:56:04,815
 BUT THEN WHEN YOU ARE WRITING

2504
01:56:04,815 --> 01:56:07,585
 YOUR LABEL, HOW DO YOU WRITE

2505
01:56:07,585 --> 01:56:08,519
 THE APPROVAL?

2506
01:56:08,519 --> 01:56:13,157
 SO THIS DRUG IS APPROVED FOR

2507
01:56:13,157 --> 01:56:14,458
 IMPROVING FUNCTION AND FOR

2508
01:56:14,458 --> 01:56:17,595
 PATIENTS WHO HAPPEN TO HAVE

2509
01:56:17,595 --> 01:56:19,830
 OSTEOARTHRITIS, THAT WOULD BE

2510
01:56:19,830 --> 01:56:20,798
 OBVIOUSLY DIFFERENT THAN

2511
01:56:20,798 --> 01:56:22,733
 SAYING THE DRUG WOULD BE

2512
01:56:22,733 --> 01:56:26,370
 APPROVED AS A PAIN KRUG AND --

2513
01:56:26,370 --> 01:56:29,306
 DRUG AND YOU HAVE A SP-PBS TO

2514
01:56:29,306 --> 01:56:29,607
 THAT?

2515
01:56:29,607 --> 01:56:32,610
 >> HOW DO YOU WRITE THE
LABEL

2516
01:56:32,610 --> 01:56:35,746
 IF IT IS A TREATMENT FOR THE

2517
01:56:35,746 --> 01:56:36,380
 CONDITION?

2518
01:56:36,380 --> 01:56:41,452
 NOT A FUNCTION OF THE PAIN BUT

2519
01:56:41,452 --> 01:56:43,387
 THE CONDITION AND SO THAT IS

2520
01:56:43,387 --> 01:56:44,922
 SOMETHING WE HAVE TO WRITE

2521
01:56:44,922 --> 01:56:47,792
 WITH THEM IF WE'RE GOING TO DO

2522
01:56:47,792 --> 01:56:48,092
 THIS.

2523
01:56:48,092 --> 01:56:50,361
 AS WE ALL KNOW, ALL PEOPLE

2524
01:56:50,361 --> 01:56:55,066
 DON'T RESPOND TO OUR PRIMARY

2525
01:56:55,066 --> 01:56:57,101
 COUNCIL BUT YOU GET DIFFERENT

2526
01:56:57,101 --> 01:56:58,602
 RESPONDERS TO DIFFERENT

2527
01:56:58,602 --> 01:57:00,071
 OUTCOMES, LIKE THEY DON'T ALL

2528
01:57:00,071 --> 01:57:02,206
 RESPOND TO THE SAME OUTCOME SO

2529
01:57:02,206 --> 01:57:04,875
 I WONDER IF WE CAN CHANGE HOW

2530
01:57:04,875 --> 01:57:06,877
 THEY THINK ABOUT IT BUT THAT

2531
01:57:06,877 --> 01:57:08,245
 IS A REGULATORY IS HE AND I

2532
01:57:08,245 --> 01:57:08,679
 DON'T KNOW --

2533
01:57:08,679 --> 01:57:11,715
 >>  I THINK ANOTHER WAY
IT

2534
01:57:11,715 --> 01:57:18,222
 LOCK AT IT IS COULD THE

2535
01:57:18,222 --> 01:57:22,059
 OUTCOME CHANGE THE MEASURE AND

2536
01:57:22,059 --> 01:57:25,496
 IT MIGHT HAVE AN EFFECT ON

2537
01:57:25,496 --> 01:57:26,230
 SENSIBILITY BECAUSE THERE WILL

2538
01:57:26,230 --> 01:57:36,474
 BE A LOT OF VARIABILITY. 

2539
01:57:36,474 --> 01:57:43,280
 LIKE LETTING PEOPLE USE

2540
01:57:43,280 --> 01:57:44,849
 ASTRAMYACIN FOR CRAMPING OR

2541
01:57:44,849 --> 01:57:49,987
 PAIN AND THE MORE CONCEPTS YOU

2542
01:57:49,987 --> 01:57:50,921
 BRING IN, THE LESS SENSITIVITY

2543
01:57:50,921 --> 01:57:55,693
 YOU WILL HAVE AND I THINK FOR 

2544
01:57:55,693 --> 01:57:59,864
 A CHILD TO BALANCE FLEXIBILITY

2545
01:57:59,864 --> 01:58:03,634
 AND PAIN, AND WHAT ARE THE

2546
01:58:03,634 --> 01:58:05,603
 PLUSES AND MINUSES OF THOSE

2547
01:58:05,603 --> 01:58:06,937
 TWO THINGS.

2548
01:58:06,937 --> 01:58:09,573
 >> YEAH, I WOULD ADD THAT
A

2549
01:58:09,573 --> 01:58:12,776
 LOT OF THESE RESULTS CAN ONLY

2550
01:58:12,776 --> 01:58:16,213
 BE RESOLVED BY DOING STUDIES.

2551
01:58:16,213 --> 01:58:19,416
 SO AGAIN MY OPENING THEME IS

2552
01:58:19,416 --> 01:58:23,621
 IT IS REMARKABLE TO ME THAT WE

2553
01:58:23,621 --> 01:58:26,657
 SPENT MILLIONS IN DRUG

2554
01:58:26,657 --> 01:58:28,893
 TREATMENT AND DON'T NOTICELY

2555
01:58:28,893 --> 01:58:31,095
 KNOW WHAT THE TOOLS SHOULD BE.

2556
01:58:31,095 --> 01:58:33,964
 AND ONE WAY THIS COULD BE AN

2557
01:58:33,964 --> 01:58:35,666
 APPROACH PROBABLY WITH NIH

2558
01:58:35,666 --> 01:58:37,735
 FUNDING IS TAKE DRUGS THAT ARE

2559
01:58:37,735 --> 01:58:42,173
 KNOWN TO WORK AND THAT COULD

2560
01:58:42,173 --> 01:58:45,309
 BE GABAPENTIN WHERE IT PRETTY

2561
01:58:45,309 --> 01:58:47,611
 CLEARLY IS OPENFUL AND TEST

2562
01:58:47,611 --> 01:58:49,547
 DIFFERENT WAYS OF MEASURING

2563
01:58:49,547 --> 01:58:53,050
 OUTCOME AND LOOK AT SOME OF

2564
01:58:53,050 --> 01:58:57,655
 THESE IDEAS WITH DATA.

2565
01:58:57,655 --> 01:59:00,457
 SO I THINK WE SPEND A LOT OF

2566
01:59:00,457 --> 01:59:02,826
 TIME SPECULATING IN A LOT OF

2567
01:59:02,826 --> 01:59:04,061
 OUR JUDGMENTS ABOUT HOW TO

2568
01:59:04,061 --> 01:59:06,230
 DESIGN TRIALS AND WHAT

2569
01:59:06,230 --> 01:59:10,901
 ENDPOINTS TO USE, IS BASED ON

2570
01:59:10,901 --> 01:59:15,639
 COMMON SENSE AND DISCUSSION 

2571
01:59:15,639 --> 01:59:18,375
 BUT WE REALLY, I THINK NEED TO

2572
01:59:18,375 --> 01:59:19,910
 GET INTO EMPIRICAL DATA TO

2573
01:59:19,910 --> 01:59:21,645
 OPTIMIZE AND ADDRESS THESE

2574
01:59:21,645 --> 01:59:21,979
 ISSUES.

2575
01:59:21,979 --> 01:59:23,214
 >> THANK YOU, ALL RIGHT
LET'S

2576
01:59:23,214 --> 01:59:30,721
 MOVE ON TO ANOTHER QUESTION.

2577
01:59:30,721 --> 01:59:33,123
 >> SIMONE FROM -- JUST
READ

2578
01:59:33,123 --> 01:59:35,025
 SOME PAPERS ABOUT PAIN

2579
01:59:35,025 --> 01:59:37,761
 MANAGEMENT AND THERE ARE

2580
01:59:37,761 --> 01:59:39,430
 QUESTIONNAIRES ABOUT THIS AND

2581
01:59:39,430 --> 01:59:45,169
 PEOPLE LOOKING UP TO THE

2582
01:59:45,169 --> 01:59:46,470
 ANIMALS AS FARMERS AND FOR

2583
01:59:46,470 --> 01:59:47,738
 INSTANCE THEY SAW THIS YOU

2584
01:59:47,738 --> 01:59:50,474
 WERE YOUNGER OR OLDER THAN 24

2585
01:59:50,474 --> 01:59:52,977
 YEARS THE WAY YOU PERCEIVE

2586
01:59:52,977 --> 01:59:56,080
 PAIN IS DIFFERENT AND THEN

2587
01:59:56,080 --> 01:59:57,348
 THERE'S A DIFFERENCE TO IF YOU

2588
01:59:57,348 --> 02:00:00,851
 HAVE MORE THAN A THOUSAND

2589
02:00:00,851 --> 02:00:04,788
 PEOPLE IN YOUR STABLE OR LESS.

2590
02:00:04,788 --> 02:00:06,423
 AND THEN WE HAVE SEEN OUTCOME

2591
02:00:06,423 --> 02:00:09,526
 FROM THE U.S. THAT THEY ARE

2592
02:00:09,526 --> 02:00:12,363
 RELYING ON PERSONAL EXPERIENCE

2593
02:00:12,363 --> 02:00:14,265
 AND INTERESTINGLY WHEN I FELT

2594
02:00:14,265 --> 02:00:19,670
 WHEN THEY GOT MORE TRAINING

2595
02:00:19,670 --> 02:00:22,072
 AND EFFECTIVENESS OF THE DRUG,

2596
02:00:22,072 --> 02:00:23,941
 THE MORE TRAINING, THE LESS

2597
02:00:23,941 --> 02:00:25,109
 CONCERN ABOUT SIDE EFFECTS SO

2598
02:00:25,109 --> 02:00:27,611
 IT IS LIKE HAVING A BIAS THE

2599
02:00:27,611 --> 02:00:28,112
 OTHER WAY AROUND.

2600
02:00:28,112 --> 02:00:36,120
 SO I WAS WONDERING IF

2601
02:00:36,120 --> 02:00:37,955
 OBSTETRICIANS SAW THIS LIKE IT

2602
02:00:37,955 --> 02:00:39,490
 IS IMPLEMENTED IN FARM ANIMALS

2603
02:00:39,490 --> 02:00:44,561
 AND YOU CAN KIND OF USE IT

2604
02:00:44,561 --> 02:00:46,563
 WITHOUT HAVING TO BE OVER THE

2605
02:00:46,563 --> 02:00:49,533
 AGE OF 24?

2606
02:00:49,533 --> 02:00:50,601
 THANK YOU.

2607
02:00:50,601 --> 02:00:51,335
 >> SO STELIO, PERHAPS YOU

2608
02:00:51,335 --> 02:00:53,804
 WOULD LIKE TO COMMENT ON THAT?

2609
02:00:53,804 --> 02:00:54,905
 THERE ARE SOME STATEMENTS

2610
02:00:54,905 --> 02:01:02,813
 THERE ABOUT HOW A NUMBER OF 

2611
02:01:02,813 --> 02:01:04,248
 FACTORS CAN INFLUENCE A NUMBER

2612
02:01:04,248 --> 02:01:06,450
 OF OPTIONS AND YOU HAD A SLIDE

2613
02:01:06,450 --> 02:01:10,054
 THAT SAID AI IS BETTER THAN

2614
02:01:10,054 --> 02:01:10,654
 PEOPLE.

2615
02:01:10,654 --> 02:01:13,424
 YOU WANT TO EXPLAIN WHAT YOU

2616
02:01:13,424 --> 02:01:14,992
 MEAN BY THAT?

2617
02:01:14,992 --> 02:01:19,430
 >> WELL, AI IS BETTER
BECAUSE

2618
02:01:19,430 --> 02:01:23,033
 THE AUC, AREA UNDER THE CURVE

2619
02:01:23,033 --> 02:01:25,102
 WAS BETTER WITH INITIAL PAIN

2620
02:01:25,102 --> 02:01:29,940
 BECAUSE BASICALLY WHAT WE HAD

2621
02:01:29,940 --> 02:01:34,378
 WAS SURGERY AND AV SURGERY --

2622
02:01:34,378 --> 02:01:35,979
 AFTER SURGERY AND THERE WAS

2623
02:01:35,979 --> 02:01:44,588
 THE GROUND TRUTH OF THE SHEEP

2624
02:01:44,588 --> 02:01:47,524
 FEELING PAIN AFTER SURGERY SO

2625
02:01:47,524 --> 02:01:49,693
 THEY WERE ABLE TO SAY THEY

2626
02:01:49,693 --> 02:01:51,095
 WERE PAINFUL BETTER THAN

2627
02:01:51,095 --> 02:01:54,531
 HUMANS AND THIS IS BASED ON

2628
02:01:54,531 --> 02:01:56,066
 THE VARIOUS DISEASES USED IN

2629
02:01:56,066 --> 02:01:56,834
 THE ORIGINAL WORK.

2630
02:01:56,834 --> 02:01:59,837
 WE DID THE SAME THING WITH THE

2631
02:01:59,837 --> 02:02:03,006
 RAT BUT DIDN'T COMPARE THAT TO

2632
02:02:03,006 --> 02:02:04,408
 THE HUMAN.

2633
02:02:04,408 --> 02:02:08,846
 I THINK THE FIRST ONE IS

2634
02:02:08,846 --> 02:02:10,147
 COMPARING HUMAN VERSUS MACHINE

2635
02:02:10,147 --> 02:02:11,915
 BUT I THINK THERE IS STILL A

2636
02:02:11,915 --> 02:02:14,118
 LOT OF WORK TO DO.

2637
02:02:14,118 --> 02:02:23,460
 I STILL BELIEVE IN THE

2638
02:02:23,460 --> 02:02:24,528
 WELL-TRAINED TEST AND WHAT

2639
02:02:24,528 --> 02:02:28,399
 RELATES TO PEOPLE SO THEY CAN

2640
02:02:28,399 --> 02:02:31,935
 LEARN, ARE THEY OBSESSING IN

2641
02:02:31,935 --> 02:02:37,808
 PAIN STATE OR THEY CAN HAVE A

2642
02:02:37,808 --> 02:02:39,309
 LOT OF PAIN --

2643
02:02:39,309 --> 02:02:39,877
 [INDISCERNIBLE]

2644
02:02:39,877 --> 02:02:41,645
 -- MAKE SURE HE IS WELL

2645
02:02:41,645 --> 02:02:43,680
 TRAINED BEFORE HE STARTS DOING

2646
02:02:43,680 --> 02:02:45,816
 THE ASSESSMENT.

2647
02:02:45,816 --> 02:02:54,658
 BUT THERE ARE STUDENT FOR

2648
02:02:54,658 --> 02:03:00,831
 ASSESSMENT MAY BE FEELING PAIN

2649
02:03:00,831 --> 02:03:02,866
 IN THE STABLE, SO PAIN IS VERY

2650
02:03:02,866 --> 02:03:03,600
 IMPORTANT.

2651
02:03:03,600 --> 02:03:04,468
 >> THANK YOU FOR THOSE

2652
02:03:04,468 --> 02:03:08,572
 COMMENTS AND I MIGHT ADD SOME 

2653
02:03:08,572 --> 02:03:10,240
 MEDICAL EVENT TRAINING ITSELF

2654
02:03:10,240 --> 02:03:12,876
 ALTERS THE WAY WE SEE PAIN AND

2655
02:03:12,876 --> 02:03:15,646
 NOT NECESSARILY IN A POSITIVE

2656
02:03:15,646 --> 02:03:16,980
 DIRECTION.

2657
02:03:16,980 --> 02:03:17,714
 JOHN?

2658
02:03:17,714 --> 02:03:18,615
 >> JOHN FROM UNIVERSITY
OF

2659
02:03:18,615 --> 02:03:20,083
 PENNSYLVANIA, I THINK THAT

2660
02:03:20,083 --> 02:03:24,555
 THERE'S A KEY ISSUE HERE AND

2661
02:03:24,555 --> 02:03:26,690
 AS JIM KNOWS, I LOVE DATA AND

2662
02:03:26,690 --> 02:03:30,160
 I LOVE TO LOOK AT DATA AND I

2663
02:03:30,160 --> 02:03:31,995
 COMPLETELY AGREE YOU SHOULD BE

2664
02:03:31,995 --> 02:03:34,264
 USING MORE THAN JUST THE

2665
02:03:34,264 --> 02:03:41,638
 ENDPOINTS OF OUR TRIALS, TO

2666
02:03:41,638 --> 02:03:43,106
 UNDERSTAND WHAT IS IN THE

2667
02:03:43,106 --> 02:03:44,808
 TRIAL AND THE AREA OF PAIN.

2668
02:03:44,808 --> 02:03:46,677
 WITH YOU SOME OTHER THINGS,

2669
02:03:46,677 --> 02:03:48,645
 WHAT WE'RE TRYING TO DO WITH

2670
02:03:48,645 --> 02:03:50,013
 RESEARCH IS APPROXIMATE TRUTH

2671
02:03:50,013 --> 02:03:51,715
 AND WE DON'T REALLY KNOW HOW

2672
02:03:51,715 --> 02:03:53,283
 TO GET THERE, AS YOU WERE

2673
02:03:53,283 --> 02:03:54,218
 SUGGESTING.

2674
02:03:54,218 --> 02:03:56,854
 I AM NOT SURE LOOKING AT A

2675
02:03:56,854 --> 02:03:58,121
 MULTITUDE OF DATA IS

2676
02:03:58,121 --> 02:04:00,657
 NECESSARILY GOING TO HELP US

2677
02:04:00,657 --> 02:04:01,425
 GET THERE.

2678
02:04:01,425 --> 02:04:02,860
 I THINK THERE ARE SOME

2679
02:04:02,860 --> 02:04:04,528
 PRINCIPLES WE IMPOSE ON WHAT

2680
02:04:04,528 --> 02:04:06,930
 WE DO TO BETTER UNDERSTAND IT.

2681
02:04:06,930 --> 02:04:10,567
 FOR EXAMPLE, THE 0 TO 10 SCALE

2682
02:04:10,567 --> 02:04:12,135
 IS AN ABSOLUTELY TERRIBLE

2683
02:04:12,135 --> 02:04:14,238
 SCALE WHEN IT COMES TO

2684
02:04:14,238 --> 02:04:16,840
 UNDERSTANDING WHETHER YOU HAVE

2685
02:04:16,840 --> 02:04:20,043
 A HEADACHE THAT SAY IS AT A

2686
02:04:20,043 --> 02:04:21,912
 FIVE, THEN TO SAY IT HAS GONE

2687
02:04:21,912 --> 02:04:23,313
 FROM FIVE TO SEVEN, I DON'T

2688
02:04:23,313 --> 02:04:25,616
 KNOW WHAT THAT MEANS.

2689
02:04:25,616 --> 02:04:29,786
 BUT ON THE OTHER HAND, ON A

2690
02:04:29,786 --> 02:04:31,889
 CLINICAL TRIAL AND WE GO FROM

2691
02:04:31,889 --> 02:04:37,194
 FIVE TO SEVEN, I CAN SAY THAT

2692
02:04:37,194 --> 02:04:40,364
 THERE WAS SOME BENEFIT. 

2693
02:04:40,364 --> 02:04:43,333
 AND IN A TRIAL SITUATION, IT

2694
02:04:43,333 --> 02:04:44,301
 COMMUNICATES WELL ACROSS

2695
02:04:44,301 --> 02:04:46,003
 CULTURE AND OTHER THINGS BUT I

2696
02:04:46,003 --> 02:04:47,971
 THINK WHAT WE'RE STUCK WITH IS

2697
02:04:47,971 --> 02:04:49,239
 REALLY UNDERSTANDING HOW TO

2698
02:04:49,239 --> 02:04:52,009
 BEST GET THE DATA OUT OF THAT

2699
02:04:52,009 --> 02:04:57,548
 PARTICULAR SCALE OR ANY SCALE,

2700
02:04:57,548 --> 02:04:59,182
 AND DIFFERENT PATIENTS ARE

2701
02:04:59,182 --> 02:05:06,456
 GOING TO RESPOND IN VERY

2702
02:05:06,456 --> 02:05:07,157
 DIFFERENT WAYS.

2703
02:05:07,157 --> 02:05:08,992
 AND WHAT WE NEED TO COME UP

2704
02:05:08,992 --> 02:05:11,662
 WITH, AND I COULDN'T AGREE

2705
02:05:11,662 --> 02:05:16,700
 WITH YOU MORE, A MECHANISM

2706
02:05:16,700 --> 02:05:18,001
 THAT IS SPECIFIC WITH THE

2707
02:05:18,001 --> 02:05:19,736
 QUESTION IS ASKS AND WHAT IS

2708
02:05:19,736 --> 02:05:22,940
 BEST TO LOOK AT THAT.

2709
02:05:22,940 --> 02:05:26,176
 USUALLY CLINICAL TRIAL MAKES

2710
02:05:26,176 --> 02:05:27,411
 SENSE, SECONDARY OUTCOMES

2711
02:05:27,411 --> 02:05:28,812
 MAKES SENSE, PERHAPS TRAINING

2712
02:05:28,812 --> 02:05:32,583
 PEOPLE IN THE USE OF THIS

2713
02:05:32,583 --> 02:05:37,888
 SCALE, ESPECIALLY IN THE

2714
02:05:37,888 --> 02:05:39,590
 OBVIOUS MODE WITH A PARENT

2715
02:05:39,590 --> 02:05:43,427
 LOOKING AT A CHILD OR AN OWNER

2716
02:05:43,427 --> 02:05:46,597
 LOOKING AT A DOG AND

2717
02:05:46,597 --> 02:05:47,864
 UNDERSTANDING THE CULTURE

2718
02:05:47,864 --> 02:05:49,333
 MIGHT BE VERY IMPORTANT IN

2719
02:05:49,333 --> 02:05:49,900
 DOING THAT.

2720
02:05:49,900 --> 02:05:53,503
 BUT AT THE END OF THE DAY, A

2721
02:05:53,503 --> 02:05:54,972
 MEASURE WORKS IF PEOPLE ARE

2722
02:05:54,972 --> 02:05:57,040
 CONSISTENT ABOUT USING IT.

2723
02:05:57,040 --> 02:06:01,578
 SO IF SOMEBODY STARTS AT 7 AND

2724
02:06:01,578 --> 02:06:12,155
 GOES DOWN OR STARTS AT A 5 AND

2725
02:06:16,727 --> 02:06:19,162
 GOES DOWN, THEN THAT IS A

2726
02:06:19,162 --> 02:06:20,998
 NUMBER IN THE TRIAL BUT I

2727
02:06:20,998 --> 02:06:23,433
 WOULD ARGUE THAT IT WILL BE

2728
02:06:23,433 --> 02:06:24,501
 VERY DIFFERENT DEPENDING ON

2729
02:06:24,501 --> 02:06:26,870
 THE QUESTION WE'RE ASKING AND

2730
02:06:26,870 --> 02:06:29,673
 WILL BE DIFFERENT IN DIFFERENT

2731
02:06:29,673 --> 02:06:30,073
 POPULATIONS.

2732
02:06:30,073 --> 02:06:31,508
 SO I THINK THERE WILL BE

2733
02:06:31,508 --> 02:06:34,478
 COMMON SENSE THAT GOES INTO

2734
02:06:34,478 --> 02:06:34,778
 THIS.

2735
02:06:34,778 --> 02:06:37,581
 ADDING DATA TO IT IS A REALLY

2736
02:06:37,581 --> 02:06:39,116
 GREAT IDEA BUT AT THE END OF

2737
02:06:39,116 --> 02:06:41,118
 THE DAY WHAT WE ARE STUCK WITH

2738
02:06:41,118 --> 02:06:43,720
 IS HOW TO ANSWER THE QUESTIONS

2739
02:06:43,720 --> 02:06:45,555
 IN TERMS OF BENEFITS SO I

2740
02:06:45,555 --> 02:06:46,256
 WOULD STOP THERE.

2741
02:06:46,256 --> 02:06:47,724
 THE QUESTION I WOULD HAVE WITH

2742
02:06:47,724 --> 02:06:50,127
 REGARD TO ALL OF THIS IS, YOU

2743
02:06:50,127 --> 02:06:52,729
 KNOW, WE HAVE BEEN STRUGGLING

2744
02:06:52,729 --> 02:06:55,699
 A LITTLE BIT TO THINK ABOUT

2745
02:06:55,699 --> 02:06:57,768
 HOW HUMANS AND ANIMAL RESULTS

2746
02:06:57,768 --> 02:07:06,243
 ARE DIFFERENT AND I WOULD ASK 

2747
02:07:06,243 --> 02:07:07,010
 MY ANIMAL COLLEAGUES, WHAT IS

2748
02:07:07,010 --> 02:07:08,311
 IMPORTANT FOR THE ANIMAL?

2749
02:07:08,311 --> 02:07:10,180
 AND WHEN YOU SAY A SHEEP IS IN

2750
02:07:10,180 --> 02:07:12,215
 PAIN OR A COW IS IN PAIN, I AM

2751
02:07:12,215 --> 02:07:16,086
 ALL IN FAVOR OF PREVENTING

2752
02:07:16,086 --> 02:07:16,386
 THAT.

2753
02:07:16,386 --> 02:07:18,055
 BUT HOW DO YOU DECIDE SORT OF

2754
02:07:18,055 --> 02:07:20,824
 WHAT IS ENOUGH FOR WHAT

2755
02:07:20,824 --> 02:07:21,825
 BENEFIT IS THERE?

2756
02:07:21,825 --> 02:07:24,127
 WE CAN COME UP WITH NUMBERS,

2757
02:07:24,127 --> 02:07:25,962
 LIKE WE CAN LOOK AT THE FORCE

2758
02:07:25,962 --> 02:07:28,999
 THEY PUT ON THEIR PAW AND SO

2759
02:07:28,999 --> 02:07:32,502
 ON BUT AT SOME POINT -- IN THE

2760
02:07:32,502 --> 02:07:35,972
 HUMAN I SAY HOW ARE YOU DOING

2761
02:07:35,972 --> 02:07:41,678
 BUT FOR THE ANIMAL I AM HAVING

2762
02:07:41,678 --> 02:07:45,749
 TROUBLE UNDERSTANDING AT WHAT

2763
02:07:45,749 --> 02:07:47,718
 POINT DO YOU CONSIDER THE PAIN

2764
02:07:47,718 --> 02:07:48,985
 IS GOOD ENOUGH AND I THINK IT

2765
02:07:48,985 --> 02:07:51,054
 COMES DOWN TO THAT.

2766
02:07:51,054 --> 02:07:53,824
 >> I JUST HEARD FROM JOHN
ON

2767
02:07:53,824 --> 02:07:55,659
 THE BBC THAT WE HAVE JUST A

2768
02:07:55,659 --> 02:07:57,527
 MINUTE LEFT SO ANY COMMENTS ON

2769
02:07:57,527 --> 02:08:00,297
 THAT, HOW DO WE DEFINE WHAT IS

2770
02:08:00,297 --> 02:08:02,466
 ACTUALLY IMPORTANT TO AN

2771
02:08:02,466 --> 02:08:03,934
 ANIMAL TO MOVE FORWARD TO

2772
02:08:03,934 --> 02:08:11,975
 FINDING AN IMPORTANT CHANGE IN

2773
02:08:11,975 --> 02:08:12,509
 AN OUTCOME MEASURE.

2774
02:08:12,509 --> 02:08:15,445
 >> SO I WOULD LIKE TO SAY

2775
02:08:15,445 --> 02:08:18,915
 SOMETHING, MY OPINION AND A

2776
02:08:18,915 --> 02:08:21,985
 BOLD PICKUP POINT IS THE

2777
02:08:21,985 --> 02:08:26,857
 PAINFUL STATE AND A NONPAINFUL

2778
02:08:26,857 --> 02:08:29,626
 STATE, SO WHAT I WOULD

2779
02:08:29,626 --> 02:08:30,460
 CONSIDER IN TREATMENT.

2780
02:08:30,460 --> 02:08:33,163
 >> THANKS FOR THAT STUDY
AND

2781
02:08:33,163 --> 02:08:35,065
 IF YOU HAD BEHAVIORALLISTS

2782
02:08:35,065 --> 02:08:37,801
 HERE, I THINK THEY WOULD

2783
02:08:37,801 --> 02:08:41,905
 PROBABLY COMMENT ON THE STUDY

2784
02:08:41,905 --> 02:08:43,507
 WITH ANIMALS WHERE THEY HAVE

2785
02:08:43,507 --> 02:08:45,242
 TO PAY A COST FOR BENEFIT AND

2786
02:08:45,242 --> 02:08:47,344
 YOU CAN LOOK HOW HARD THEY

2787
02:08:47,344 --> 02:08:49,412
 WORK TO GAIN THAT BENEFIT AS A

2788
02:08:49,412 --> 02:08:51,515
 MEASURE OF HOW IMPORTANT THAT

2789
02:08:51,515 --> 02:08:56,987
 BENEFIT IS, IF THAT MAKES

2790
02:08:56,987 --> 02:08:57,754
 SENSE.

2791
02:08:57,754 --> 02:08:59,389
 >> CONDITION BY
PREFERENCE?

2792
02:08:59,389 --> 02:09:02,325
 >>  YES, THOSE SORTS OF
ASSAYS

2793
02:09:02,325 --> 02:09:05,295
 THAT CAN LOOK AT HOW MOTIVATED

2794
02:09:05,295 --> 02:09:09,266
 AN ANIMAL IS TO REMOVE ITSELF

2795
02:09:09,266 --> 02:09:12,369
 FROM AN ADVERSE EFFECT OR

2796
02:09:12,369 --> 02:09:13,403
 POTENTIAL TREATMENT.

2797
02:09:13,403 --> 02:09:16,506
 I THINK THERE MAY BE WAYS OF

2798
02:09:16,506 --> 02:09:19,543
 GETTING TO THAT, LABORIOUS

2799
02:09:19,543 --> 02:09:21,211
 WAYS.

2800
02:09:21,211 --> 02:09:21,745
 [LAUGHTER]

2801
02:09:21,745 --> 02:09:23,146
 >> OKAY, WITH THAT, DO I
HAVE

2802
02:09:23,146 --> 02:09:25,115
 TIME FOR ONE MORE?

2803
02:09:25,115 --> 02:09:28,051
 OKAY, ONE LAST QUESTION.

2804
02:09:28,051 --> 02:09:31,922
 >>  THANK YOU ALL, I AM

2805
02:09:31,922 --> 02:09:34,191
 CURIOUS WHAT YOUR THOUGHTS

2806
02:09:34,191 --> 02:09:36,593
 WOULD BE THAT WE TAKE TO THE

2807
02:09:36,593 --> 02:09:39,029
 PET OWNER, WHAT ASK IT LOOK

2808
02:09:39,029 --> 02:09:40,997
 LIKE TO -- DOES IT LOOK LIKE

2809
02:09:40,997 --> 02:09:43,166
 TO ACTUALLY PUT IT IN THEIR

2810
02:09:43,166 --> 02:09:45,101
 HANDS FOR THE PRACTICE WE'RE

2811
02:09:45,101 --> 02:09:48,538
 TALKING ABOUT IN THE CLINICAL

2812
02:09:48,538 --> 02:09:49,806
 STUDY, MAKING IT USEFUL.

2813
02:09:49,806 --> 02:09:52,709
 AS FAR AS THE GAIT ANALYSIS IS

2814
02:09:52,709 --> 02:09:56,880
 GREAT IN RESEARCH BUT NOT

2815
02:09:56,880 --> 02:09:58,114
 PRACTICAL FOR VETERINARIANS TO

2816
02:09:58,114 --> 02:10:00,317
 HAVE THAT IN A PRACTICE.

2817
02:10:00,317 --> 02:10:03,353
 SO WHAT DOES IT LOOK LIKE TO

2818
02:10:03,353 --> 02:10:09,926
 MAKE IT MORE AVAILABLE AND PUT

2819
02:10:09,926 --> 02:10:10,460
 IT OUT THERE.

2820
02:10:10,460 --> 02:10:12,729
 >> THAT IS A LEAD-IN FOR
YOU,

2821
02:10:12,729 --> 02:10:13,897
 I GUESS.

2822
02:10:13,897 --> 02:10:16,366
 >> WELL, I DID MY TALK
LEADING

2823
02:10:16,366 --> 02:10:19,035
 TO WAYS TO TRY AND DO THAT AND

2824
02:10:19,035 --> 02:10:21,972
 IN MANY WAYS WE'RE SCARFING

2825
02:10:21,972 --> 02:10:23,039
 THE SURFACE OF THAT AT THE

2826
02:10:23,039 --> 02:10:23,740
 MOMENT.

2827
02:10:23,740 --> 02:10:31,081
 A LOT OF WORK PUT INTO PATIENT

2828
02:10:31,081 --> 02:10:32,349
 OUTCOMES IN MEDICINE AND

2829
02:10:32,349 --> 02:10:33,817
 LOOKING AT HOW EFFECTIVE THAT

2830
02:10:33,817 --> 02:10:37,020
 CAN BE BUT THERE ARE BARRIERS.

2831
02:10:37,020 --> 02:10:38,989
 YOU CAN PROVIDE GREAT TOOLS TO

2832
02:10:38,989 --> 02:10:40,056
 PATIENTS BUT THERE ARE THINGS

2833
02:10:40,056 --> 02:10:41,791
 THAT GET IN THE WAY SUCH AS

2834
02:10:41,791 --> 02:10:43,093
 LIFE AND HAVING A JOB.

2835
02:10:43,093 --> 02:10:47,697
 SO ONE OF THE BIGGEST FACTORS

2836
02:10:47,697 --> 02:10:51,835
 THAT INFLUENCES WHERE PATIENTS

2837
02:10:51,835 --> 02:10:55,338
 REPORT THEIR OUTCOMES. 

2838
02:10:55,338 --> 02:10:58,708
 IN THE UK, WHETHER YOU HAVE

2839
02:10:58,708 --> 02:11:00,210
 THE FORM OR NOT.

2840
02:11:00,210 --> 02:11:02,379
 SO WE HAVE A LOT TO THINK

2841
02:11:02,379 --> 02:11:03,880
 ABOUT HOW TO ROLL THESE TOOLS

2842
02:11:03,880 --> 02:11:07,284
 OUT TO THE OWNER BUT IF WE

2843
02:11:07,284 --> 02:11:10,020
 EVEN REACH A SMALL PERCENTAGE

2844
02:11:10,020 --> 02:11:11,955
 OF THEM, THAT WOULD BE GREAT

2845
02:11:11,955 --> 02:11:12,789
 PROGRESS BECAUSE FOR THE

2846
02:11:12,789 --> 02:11:15,091
 MOMENT THEY ARE LOCKED OUT.

2847
02:11:15,091 --> 02:11:15,892
 >>  GREAT, THANKS FOR
THOSE

2848
02:11:15,892 --> 02:11:16,259
 COMMENTS.

2849
02:11:16,259 --> 02:11:18,228
 I THINK WITH THAT WE WILL DRAW

2850
02:11:18,228 --> 02:11:19,629
 THE MORNING TO A CLOSE.

2851
02:11:19,629 --> 02:11:24,567
 WE WILL COME BACK HERE AT 12: 

2852
02:11:24,567 --> 02:11:27,771
 30:00 P.M. FOR THE NEXT

2853
02:11:27,771 --> 02:11:32,309
 SESSION, LUNCH IS JUST OUT THE

2854
02:11:32,309 --> 02:11:35,345
 DOOR BUT PLEASE, HELP ME JOIN

2855
02:11:35,345 --> 02:11:39,950
 ALL OF OUR SPEAKERS FROM THIS 

2856
02:11:39,950 --> 02:11:40,450
 MORNING.

2857
02:11:40,450 --> 02:11:42,810
 THANKS.

2858
02:11:42,810 --> 02:11:43,710
>> GOOD AFTERNOON.

2859
02:11:43,710 --> 02:11:45,679
WE'LL GET STARTED FOR OUR

2860
02:11:45,679 --> 02:11:46,580
AFTERNOON SESSION.

2861
02:11:46,580 --> 02:11:50,818
I'M CHERYL JOHNSON FROM THE

2862
02:11:50,818 --> 02:11:59,026
CENTER OF VETERINARY MEDICINE.

2863
02:11:59,026 --> 02:12:00,594
FIRST I'D LIKE TO INTRODUCE

2864
02:12:00,594 --> 02:12:00,961
DR. JOHN FARRAR.

2865
02:12:00,961 --> 02:12:01,929
HE IS A PROFESSOR OF

2866
02:12:01,929 --> 02:12:02,563
EPIDEMIOLOGY, NEUROLOGY GEE AND

2867
02:12:02,563 --> 02:12:06,400
ANESTHESIA AT THE UNIVERSITY OF

2868
02:12:06,400 --> 02:12:07,000
PENNSYLVANIA AND THE PRESIDENT

2869
02:12:07,000 --> 02:12:07,601
OF THE US ASSOCIATION FOR THE

2870
02:12:07,601 --> 02:12:08,535
STUDY OF PAIN.

2871
02:12:08,535 --> 02:12:09,136
HE'S BEEN INVOLVED IN CLINICAL

2872
02:12:09,136 --> 02:12:10,237
RESEARCH FOR 30 YEARS AND FOCUS

2873
02:12:10,237 --> 02:12:10,771
IS ON THE MEASUREMENT AND

2874
02:12:10,771 --> 02:12:13,740
MEANING OF PAIN AND RELATED

2875
02:12:13,740 --> 02:12:15,709
SYMPTOMS, STUDY DESIGN, CONDUCT,

2876
02:12:15,709 --> 02:12:17,578
ANALYSIS AND INTERPRETATION OF

2877
02:12:17,578 --> 02:12:24,084
STUDIES OF THE EFFICACY OF PAIN.

2878
02:12:24,084 --> 02:12:34,361
DR. JOHN FARRAR.

2879
02:12:50,244 --> 02:12:54,515
>> SO, GOOD AFTERNOON AND
IT'S

2880
02:12:54,515 --> 02:12:58,418
ALWAYS DANGEROUS TO SPEAK RIGHT

2881
02:12:58,418 --> 02:13:00,587
AFTER LUNCH.

2882
02:13:00,587 --> 02:13:01,388
POST-PRANNIAL SYMPTOMS BEING

2883
02:13:01,388 --> 02:13:02,990
WHAT THEY ARE BUT I WILL TRY AND

2884
02:13:02,990 --> 02:13:04,391
KEEP YOU INTERESTED IN WHAT I'M

2885
02:13:04,391 --> 02:13:06,326
GOING TO BE TALKING ABOUT.

2886
02:13:06,326 --> 02:13:08,095
MY ROLE HERE TODAY IS TO

2887
02:13:08,095 --> 02:13:09,696
INTRODUCE THE TOPIC THIS MORNING

2888
02:13:09,696 --> 02:13:11,398
AND TO TALK A LITTLE BIT ABOUT

2889
02:13:11,398 --> 02:13:13,700
HOW WE THINK ABOUT OUTCOMES AND

2890
02:13:13,700 --> 02:13:18,405
WHAT WE DO WITH THEM.

2891
02:13:18,405 --> 02:13:21,542
SO, THE FIRST THING -- THE FIRST

2892
02:13:21,542 --> 02:13:23,010
THING THAT I WANT TO REMIND

2893
02:13:23,010 --> 02:13:24,878
EVERYBODY IS THAT OBVIOUSLY,

2894
02:13:24,878 --> 02:13:26,079
CLINICAL TRIALS IS WHAT WE ARE

2895
02:13:26,079 --> 02:13:28,181
TRYING TO DEAL WITH HERE AND A

2896
02:13:28,181 --> 02:13:29,616
CLEAR STATEMENT OF WHAT THE

2897
02:13:29,616 --> 02:13:31,952
QUESTION IS WE'RE TRYING TO

2898
02:13:31,952 --> 02:13:33,086
ANSWER IS OBVIOUSLY THE BIGGEST

2899
02:13:33,086 --> 02:13:35,122
ISSUE IN TRYING TO DECIDE HOW WE

2900
02:13:35,122 --> 02:13:37,057
DO THE STUDY, WHAT WE STUDY,

2901
02:13:37,057 --> 02:13:39,126
WHAT POPULATION WE STUDY.

2902
02:13:39,126 --> 02:13:40,494
BUT THERE ARE OTHER FACTORS THAT

2903
02:13:40,494 --> 02:13:42,462
GO INTO THAT AND I JUST DON'T

2904
02:13:42,462 --> 02:13:44,031
WANT US TO FORGET THE FACT THAT

2905
02:13:44,031 --> 02:13:45,966
THE IT'S NOT ALL ABOUT OUTCOMES.

2906
02:13:45,966 --> 02:13:48,468
IT'S ABOUT HOW THE STUDY IS

2907
02:13:48,468 --> 02:13:50,137
CONDUCTED AND WHAT GOES ON WITH

2908
02:13:50,137 --> 02:13:50,537
THAT.

2909
02:13:50,537 --> 02:13:52,773
AND THAT PARALLEL RANDOMIZED

2910
02:13:52,773 --> 02:13:53,807
DESIGNS IS THE GOLD STANDARD BUT

2911
02:13:53,807 --> 02:13:56,143
THERE ARE NEW ADAPTIVE WAYS OF

2912
02:13:56,143 --> 02:13:57,177
DEALING WITH CLINICAL TRIALS AND

2913
02:13:57,177 --> 02:13:59,046
YOU'RE GOING TO HEAR MORE ABOUT

2914
02:13:59,046 --> 02:14:00,047
THAT TODAY AS WELL.

2915
02:14:00,047 --> 02:14:02,549
I'LL SPEAK ABOUT IT BRIEFLY.

2916
02:14:02,549 --> 02:14:05,852
TYPES OF TRIAL ENDPOINTS,

2917
02:14:05,852 --> 02:14:08,155
SINGLE, MULTIPLE ENDPOINTS,

2918
02:14:08,155 --> 02:14:09,089
COMPOSITE ENDPOINTS, AND I'M

2919
02:14:09,089 --> 02:14:10,457
GOING TO TALK BRIEFLY ABOUT THE

2920
02:14:10,457 --> 02:14:12,292
ROLE OF SURROGATE ENDPOINTS AND

2921
02:14:12,292 --> 02:14:13,961
THE ROLE OF BIOMARKERS, WHICH

2922
02:14:13,961 --> 02:14:16,163
ARE OBVIOUSLY A KEY AND

2923
02:14:16,163 --> 02:14:19,333
IMPORTANT THING TO THINK ABOUT

2924
02:14:19,333 --> 02:14:21,001
THE DEVELOPMENT OF NEW PRODUCTS.

2925
02:14:21,001 --> 02:14:23,236
HOW DO WE HANDLE MULTIPLE

2926
02:14:23,236 --> 02:14:23,503
ENDPOINTS?

2927
02:14:23,503 --> 02:14:24,371
LET'S START WITH THAT.

2928
02:14:24,371 --> 02:14:25,973
IF YOU HAVE GOT FIVE DIFFERENT

2929
02:14:25,973 --> 02:14:27,474
THINGS YOU WANT TO MEASURE, YOU

2930
02:14:27,474 --> 02:14:29,076
CAN MEASURE EACH OF THEM

2931
02:14:29,076 --> 02:14:30,677
SEPARATELY AND THEN YOU CAN

2932
02:14:30,677 --> 02:14:32,879
ANALYZE EACH OF THEM SEPARATELY.

2933
02:14:32,879 --> 02:14:34,448
IF YOU DO THAT KIND OF THING,

2934
02:14:34,448 --> 02:14:36,450
THEN YOU NEED TO CORRECT FOR THE

2935
02:14:36,450 --> 02:14:38,018
MULTIPLE COMPARISONS ISSUE,

2936
02:14:38,018 --> 02:14:40,220
WHICH IS THAT IF YOU STUDY

2937
02:14:40,220 --> 02:14:42,222
ENOUGH THINGS, ONE OF THEM WILL

2938
02:14:42,222 --> 02:14:44,858
TURN OUT TO BE STATISTICALLY

2939
02:14:44,858 --> 02:14:45,258
SIGNIFICANT.

2940
02:14:45,258 --> 02:14:46,326
THE ADAGE I LIKE IS IF YOU

2941
02:14:46,326 --> 02:14:48,962
TORTURE THE DATA ENOUGH, IT WILL

2942
02:14:48,962 --> 02:14:49,196
CONFESS.

2943
02:14:49,196 --> 02:14:50,631
AND YOU GOT TO BE CAREFUL

2944
02:14:50,631 --> 02:14:51,798
BECAUSE THIS IS SOMETHING THAT

2945
02:14:51,798 --> 02:14:55,035
HAPPENS ON A REGULAR BASIS, LESS

2946
02:14:55,035 --> 02:14:56,003
IN THE CURRENT ENVIRONMENT THAN

2947
02:14:56,003 --> 02:14:56,837
IT DID BEFORE.

2948
02:14:56,837 --> 02:14:58,138
AND THERE ARE A BUNCH OF

2949
02:14:58,138 --> 02:15:00,140
DIFFERENT WAYS TO HANDLE

2950
02:15:00,140 --> 02:15:01,174
MULTIPLE ENDPOINTS.

2951
02:15:01,174 --> 02:15:02,242
YOU'LL HEAR PERHAPS MORE ABOUT

2952
02:15:02,242 --> 02:15:03,844
THIS IN THE STATISTICS ISSUES,

2953
02:15:03,844 --> 02:15:06,046
BUT THE SEQUENTIAL REJECTION

2954
02:15:06,046 --> 02:15:06,913
PROCEDURE WHERE YOU LOOK FIRST

2955
02:15:06,913 --> 02:15:08,448
AT ONE AND THEN AT THE SECOND

2956
02:15:08,448 --> 02:15:09,950
AND THEN AT THE THIRD AS YOU GO

2957
02:15:09,950 --> 02:15:12,019
DOWN IN TERMS OF IMPORTANCE.

2958
02:15:12,019 --> 02:15:13,720
THERE ARE COMBINED ENDPOINTS AND

2959
02:15:13,720 --> 02:15:16,156
I WOULD REMIND YOU THAT A

2960
02:15:16,156 --> 02:15:17,557
QUESTIONNAIRE, A

2961
02:15:17,557 --> 02:15:19,259
PATIENT-REPORTED OUTCOME IS A

2962
02:15:19,259 --> 02:15:20,160
COMBINED ENDPOINT.

2963
02:15:20,160 --> 02:15:22,829
YOU'RE TAKING SIX QUESTIONS AND

2964
02:15:22,829 --> 02:15:23,930
YOU'RE DOING SOMETHING TO THEM.

2965
02:15:23,930 --> 02:15:25,932
YOU'RE ADDING THEM UP OR

2966
02:15:25,932 --> 02:15:27,567
MULTIPLYING THE RESULTS OR

2967
02:15:27,567 --> 02:15:29,136
DIVIDING THEM BY WHO KNOWS WHAT.

2968
02:15:29,136 --> 02:15:31,938
IF YOU WANT A REAL EXAMPLE OF

2969
02:15:31,938 --> 02:15:33,473
HOW COMPLICATED IT CAN GET, GO

2970
02:15:33,473 --> 02:15:36,643
LOOK AT THE SF36 AND HOW THOSE

2971
02:15:36,643 --> 02:15:39,780
QUESTIONS ARE ANALYZED.

2972
02:15:39,780 --> 02:15:43,183
.46 TIMES THAT AND .82 TIMES

2973
02:15:43,183 --> 02:15:46,486
THAT AND IF IT'S TUESDAY,.73

2974
02:15:46,486 --> 02:15:47,387
TIMES THAT ONE.

2975
02:15:47,387 --> 02:15:49,690
IT'S COMPLICATED I VE TO HAVE A

2976
02:15:49,690 --> 02:15:50,824
WAY TO DO IT.

2977
02:15:50,824 --> 02:15:52,292
THE QUESTION THAT COMES UP IS

2978
02:15:52,292 --> 02:15:54,294
WHO GETS TO DECIDE HOW THEY ARE

2979
02:15:54,294 --> 02:15:57,330
PUT TOGETHER AND WHAT'S

2980
02:15:57,330 --> 02:15:57,664
IMPORTANT?

2981
02:15:57,664 --> 02:15:58,765
THEN THERE ARE OTHER WAYS OF

2982
02:15:58,765 --> 02:15:59,666
THINKING ABOUT THINGS.

2983
02:15:59,666 --> 02:16:01,902
WE HEARD THIS MORNING ABOUT THE

2984
02:16:01,902 --> 02:16:05,672
GLOBAL MEASURES AS WELL AND I'M

2985
02:16:05,672 --> 02:16:07,808
A BIG FAN OF THE IDEA THAT YOU

2986
02:16:07,808 --> 02:16:09,376
CAN USE A GLOBAL BUT WHAT YOU

2987
02:16:09,376 --> 02:16:10,811
REALLY WANT TO DO AT LEAST IN

2988
02:16:10,811 --> 02:16:11,678
HUMANS, IS TO MAKE SURE THAT

2989
02:16:11,678 --> 02:16:12,979
THEY ARE THINKING ABOUT THE

2990
02:16:12,979 --> 02:16:14,314
THINGS THAT YOU WANT THEM TO

2991
02:16:14,314 --> 02:16:16,183
CONSIDER WHEN THEY ANSWER THAT

2992
02:16:16,183 --> 02:16:16,883
GLOBAL QUESTION.

2993
02:16:16,883 --> 02:16:18,885
AND THE GLOBAL QUESTION CAN BE

2994
02:16:18,885 --> 02:16:19,720
ABOUT GENERAL THINGS.

2995
02:16:19,720 --> 02:16:22,522
IT CAN ALSO BE ABOUT PAIN AND

2996
02:16:22,522 --> 02:16:23,490
FATIGUE AND SPECIFICS.

2997
02:16:23,490 --> 02:16:26,093
SO WE CAN DO THESE.

2998
02:16:26,093 --> 02:16:28,462
THE PRINCIPLES OF COMBINED ENDS

2999
02:16:28,462 --> 02:16:30,263
POINTS, OBVIOUSLY WHEN YOU

3000
02:16:30,263 --> 02:16:31,498
COMBINE ENDPOINTS, THEY

3001
02:16:31,498 --> 02:16:32,566
OBVIOUSLY HAVE TO HAVE A

3002
02:16:32,566 --> 02:16:34,101
CLINICAL RELEVANCE TO EACH

3003
02:16:34,101 --> 02:16:34,401
OTHER.

3004
02:16:34,401 --> 02:16:35,702
THEY NEED TO BE RELATED.

3005
02:16:35,702 --> 02:16:37,904
THEY NEED TO BE PROSPECTIVELY

3006
02:16:37,904 --> 02:16:38,305
IDENTIFIED.

3007
02:16:38,305 --> 02:16:39,940
YOU CAN'T IDENTIFY THEM LATER.

3008
02:16:39,940 --> 02:16:43,910
I MEAN, YOU CAN BUT THEN IT'S A

3009
02:16:43,910 --> 02:16:46,213
HYPOTHESIS GENERATING A

3010
02:16:46,213 --> 02:16:47,914
HYPOTHESIS PROVING STUDY.

3011
02:16:47,914 --> 02:16:49,316
SO THE PRECISION OF MEASUREMENT

3012
02:16:49,316 --> 02:16:51,218
AND VALUES F ONE OF THEM IS

3013
02:16:51,218 --> 02:16:52,719
HIGHLY VARIABLE AND THE OTHER

3014
02:16:52,719 --> 02:16:54,354
ONE IS VERY SPECIFIC, PROBABLY

3015
02:16:54,354 --> 02:16:55,856
DON'T WANT TO COMBINE THEM

3016
02:16:55,856 --> 02:16:57,324
BECAUSE YOU'RE GOING TO MITIGATE

3017
02:16:57,324 --> 02:17:00,327
THE ABILITY TO DETECT A

3018
02:17:00,327 --> 02:17:00,861
DIFFERENCE.

3019
02:17:00,861 --> 02:17:03,230
THERE SHOULD BE LITTLE

3020
02:17:03,230 --> 02:17:04,464
THERAPEUTIC INTERACTION BETWEEN

3021
02:17:04,464 --> 02:17:05,832
THEM, AND I'LL TALK A LITTLE BIT

3022
02:17:05,832 --> 02:17:07,167
MORE ABOUT SOME OF THAT.

3023
02:17:07,167 --> 02:17:08,869
BUT THE IDEA IS THAT IT

3024
02:17:08,869 --> 02:17:10,537
SHOULDN'T BE MEASURING FIVE

3025
02:17:10,537 --> 02:17:12,005
THINGS THAT ARE ALL THE SAME.

3026
02:17:12,005 --> 02:17:13,273
BECAUSE YOU'RE NOT NECESSARILY

3027
02:17:13,273 --> 02:17:14,875
GOING TO BENEFIT FROM THAT.

3028
02:17:14,875 --> 02:17:15,909
AND IT'S BEST IF THE MEASURES

3029
02:17:15,909 --> 02:17:17,878
ARE EQUALLY SENSITIVE OR

3030
02:17:17,878 --> 02:17:19,446
RESPONSIVE TO THE THERAPY.

3031
02:17:19,446 --> 02:17:21,014
I MEAN IF SOME ARE LESS

3032
02:17:21,014 --> 02:17:22,149
RESPONSIVE AND SOME ARE MORE,

3033
02:17:22,149 --> 02:17:24,151
THEN AGAIN YOU ADD VARIABILITY.

3034
02:17:24,151 --> 02:17:25,552
AND THEN THERE ARE CERTAIN

3035
02:17:25,552 --> 02:17:26,720
PROPERTIES THAT ARE LISTED HERE

3036
02:17:26,720 --> 02:17:28,522
I WON'T SPEND TIME TALKING

3037
02:17:28,522 --> 02:17:29,556
ABOUT, BUT THEY ARE THERE FOR

3038
02:17:29,556 --> 02:17:30,657
YOU TO LOOK AT.

3039
02:17:30,657 --> 02:17:31,758
ONE OF THE STRENGTHS THAT

3040
02:17:31,758 --> 02:17:33,727
GENERATES A SINGLE SCORE FOR THE

3041
02:17:33,727 --> 02:17:35,061
CONCEPT, SO YOU'RE INTERESTED IN

3042
02:17:35,061 --> 02:17:36,963
QUALITY OF LIFE, YOU COME UP

3043
02:17:36,963 --> 02:17:38,098
WITH FIVE OR SIX DIFFERENT

3044
02:17:38,098 --> 02:17:39,566
QUESTIONS AND COMBINE THEM INTO

3045
02:17:39,566 --> 02:17:43,870
A SCORE AND YOU GET A SINGLE

3046
02:17:43,870 --> 02:17:44,704
OUTCOME YOU CAN MEASURE.

3047
02:17:44,704 --> 02:17:46,473
YOU DON'T HAVE TO DEAL WITH THE

3048
02:17:46,473 --> 02:17:48,041
MULTIPLE OUTCOMES AND ISSUES

3049
02:17:48,041 --> 02:17:50,844
RELATED TO THE STATISTICS.

3050
02:17:50,844 --> 02:17:53,346
SO IT AVOIDS THE MULTIPLE

3051
02:17:53,346 --> 02:17:53,647
COMPARISONS.

3052
02:17:53,647 --> 02:17:55,549
THERE ARE MULTIPLE QUESTIONS

3053
02:17:55,549 --> 02:17:56,449
THAT MAYBE BETTER, THE

3054
02:17:56,449 --> 02:17:58,451
DEFINITION OF THE OUTCOME OF

3055
02:17:58,451 --> 02:17:58,819
INTEREST, RIGHT?

3056
02:17:58,819 --> 02:18:00,353
WE CAN'T NECESSARILY AGREE ON

3057
02:18:00,353 --> 02:18:02,222
WHAT QUALITY OF LIFE MEANS TO US

3058
02:18:02,222 --> 02:18:03,857
BUT WE HAVE A GENERAL CONCEPT OF

3059
02:18:03,857 --> 02:18:05,859
WHAT IT MEANS TO A POPULATION

3060
02:18:05,859 --> 02:18:08,962
AND BY COMBINING MEASURES, WE

3061
02:18:08,962 --> 02:18:10,730
CAN CREATE THAT LATENT CONSTRUCT

3062
02:18:10,730 --> 02:18:13,366
OF QUALITY OF LIFE.

3063
02:18:13,366 --> 02:18:15,001
ALLOW MULTIPLE WAYS TO ACHIEVE A

3064
02:18:15,001 --> 02:18:15,302
SCORE.

3065
02:18:15,302 --> 02:18:16,570
AND THIS IS A BIG ISSUE I'LL

3066
02:18:16,570 --> 02:18:18,772
TALK ABOUT IN A MINUTE WHEN WE

3067
02:18:18,772 --> 02:18:20,006
TALK ABOUT COMPOSITES.

3068
02:18:20,006 --> 02:18:22,142
IF YOU'RE TESTING SOMETHING THAT

3069
02:18:22,142 --> 02:18:23,877
COULD MANIFEST IN FOUR-FIVE

3070
02:18:23,877 --> 02:18:25,679
DIFFERENT WAY, YOU MAY GET A

3071
02:18:25,679 --> 02:18:27,981
BETTER ANSWER OR A MORE ROBUST

3072
02:18:27,981 --> 02:18:29,583
ANSWER IF YOU LOOK AT ALL OF

3073
02:18:29,583 --> 02:18:31,384
THOSE PARTICULAR OUTCOMES

3074
02:18:31,384 --> 02:18:31,818
TOGETHER.

3075
02:18:31,818 --> 02:18:33,787
BUT THE WEAKNESSES ARE OBVIOUSLY

3076
02:18:33,787 --> 02:18:34,921
THERE AS WELL.

3077
02:18:34,921 --> 02:18:36,590
DEPENDS ON THE STRENGTH AND

3078
02:18:36,590 --> 02:18:37,824
VALIDITY OF THE MEASURE.

3079
02:18:37,824 --> 02:18:39,993
IT DEPENDS ON THE RESEARCHER OR

3080
02:18:39,993 --> 02:18:41,795
WHO DESIGNED THE STUDY.

3081
02:18:41,795 --> 02:18:44,331
IF YOU ASK A QUALITY OF LIFE

3082
02:18:44,331 --> 02:18:45,899
MEASURE AND YOU ASK TWO ABOUT

3083
02:18:45,899 --> 02:18:50,670
PHYSICAL FUNCTION AND ONE ABOUT

3084
02:18:50,670 --> 02:18:53,106
EMOTIONAL, YOU'RE GETTING

3085
02:18:53,106 --> 02:18:54,407
PHYSICAL FUNCTION TWICE THE

3086
02:18:54,407 --> 02:18:55,809
WEIGHT COMPARED TO EMOTION.

3087
02:18:55,809 --> 02:18:57,711
UNLESS YOU DO SOME MANIPULATIONS

3088
02:18:57,711 --> 02:18:59,913
TO MAKE THAT WORK OUT.

3089
02:18:59,913 --> 02:19:02,649
YOU NEED A JUSTIFICATION TO SAY

3090
02:19:02,649 --> 02:19:03,683
WHAT MOST IMPORTANT FOR THE

3091
02:19:03,683 --> 02:19:04,751
PARTICIPANTS AND THE QUESTION

3092
02:19:04,751 --> 02:19:06,953
THAT WAS ASKED EARLIER TODAY IS,

3093
02:19:06,953 --> 02:19:08,488
WHAT ABOUT THE FACT THAT PEOPLE

3094
02:19:08,488 --> 02:19:10,023
HAVE DIFFERENT VIEWS OF THE

3095
02:19:10,023 --> 02:19:10,390
WORLD?

3096
02:19:10,390 --> 02:19:11,625
AND THINGS THAT ARE IMPORTANT TO

3097
02:19:11,625 --> 02:19:13,193
ONE PERSON MAY NOT BE IMPORTANT

3098
02:19:13,193 --> 02:19:14,160
TO ANOTHER.

3099
02:19:14,160 --> 02:19:16,229
HOW CAN WE INCORPORATE THAT?

3100
02:19:16,229 --> 02:19:18,398
IT'S NOT AN EASY QUESTION TO ASK

3101
02:19:18,398 --> 02:19:20,400
AND I'M HAVE TO TALK ABOUT IT

3102
02:19:20,400 --> 02:19:21,234
MORE IN THE DISCUSSION.

3103
02:19:21,234 --> 02:19:23,470
AND THEN THERE ARE CONCEPTS AND

3104
02:19:23,470 --> 02:19:24,104
LANGUAGE THAT NEED TO BE

3105
02:19:24,104 --> 02:19:24,404
APPROPRIATE.

3106
02:19:24,404 --> 02:19:25,705
AND OBVIOUSLY WHEN WE'RE USING

3107
02:19:25,705 --> 02:19:27,407
WORDS, WE HAVE TO THINK ABOUT

3108
02:19:27,407 --> 02:19:29,009
THOSE WORDS AS THEY APPLY TO

3109
02:19:29,009 --> 02:19:31,011
PEOPLE WHO EVEN SPEAK THE

3110
02:19:31,011 --> 02:19:31,678
LANGUAGE IN THE UNITED STATES,

3111
02:19:31,678 --> 02:19:32,679
FOR INSTANCE, PEOPLE COME FROM

3112
02:19:32,679 --> 02:19:34,814
MANY, MANY DIFFERENT CULTURES.

3113
02:19:34,814 --> 02:19:36,583
AND WE ALL SPEAK ENGLISH, AT

3114
02:19:36,583 --> 02:19:37,317
LEAST IN PART.

3115
02:19:37,317 --> 02:19:38,919
BUT OUR INTERPRETATION OF THOSE

3116
02:19:38,919 --> 02:19:39,986
WORDS MAY BE DIFFERENT.

3117
02:19:39,986 --> 02:19:41,821
SO IT'S NOT JUST THAT WE HAVE TO

3118
02:19:41,821 --> 02:19:43,123
TRANSLATE THEM IN A DIFFERENT

3119
02:19:43,123 --> 02:19:44,391
LANGUAGE, BUT WE HAVE TO THINK

3120
02:19:44,391 --> 02:19:46,626
ABOUT HOW THEY APPLY.

3121
02:19:46,626 --> 02:19:49,262
SO, SWITCHING, AND I UNDERLINED

3122
02:19:49,262 --> 02:19:49,629
COMPOSITE.

3123
02:19:49,629 --> 02:19:52,065
THERE IS NO STRICT DEFINITION OF

3124
02:19:52,065 --> 02:19:54,167
MULTIPLE OR COMBINED OR

3125
02:19:54,167 --> 02:19:54,501
COMPOSITE.

3126
02:19:54,501 --> 02:19:56,369
AND THESE WORDS GET USED A

3127
02:19:56,369 --> 02:19:57,637
LITTLE BIT INTERCHANGEABLY.

3128
02:19:57,637 --> 02:19:58,738
WHAT I'M TALKING ABOUT HERE

3129
02:19:58,738 --> 02:20:01,908
ABOUT A COMPOSITE IS, OUTCOMES

3130
02:20:01,908 --> 02:20:03,777
THAT ARE SIMILAR AND MEASURING

3131
02:20:03,777 --> 02:20:06,446
SIMILAR THINGS THAT YOU PUT

3132
02:20:06,446 --> 02:20:09,683
TOGETHER, NOT AN SF36 QUALITY OF

3133
02:20:09,683 --> 02:20:11,351
LIFE MEASURE, WHICH I TALKED

3134
02:20:11,351 --> 02:20:12,319
ABOUT BEFORE.

3135
02:20:12,319 --> 02:20:13,820
SO CHRONIC DISEASE MANIFESTS

3136
02:20:13,820 --> 02:20:16,823
THEMSELVES IN MANY WAYS.

3137
02:20:16,823 --> 02:20:19,259
WE HEARD ABOUT A VERY

3138
02:20:19,259 --> 02:20:20,727
DERMATOLOGIC DISEASE THAT CAN

3139
02:20:20,727 --> 02:20:22,228
OCCUR AS DIFFERENT KINDS OF

3140
02:20:22,228 --> 02:20:25,098
RASHES AND AFFECT THE BODY AS A

3141
02:20:25,098 --> 02:20:26,700
WHOLE AND CAUSE JOINTS TO HURT.

3142
02:20:26,700 --> 02:20:27,934
THERE ARE DIFFERENT WAYS TO

3143
02:20:27,934 --> 02:20:29,235
MANIFEST.

3144
02:20:29,235 --> 02:20:30,203
EXAMINING THE TREATMENT IN SUCH

3145
02:20:30,203 --> 02:20:32,038
CASES REQUIRES MEASURING

3146
02:20:32,038 --> 02:20:33,239
OUTCOMES RELATED TO ALL

3147
02:20:33,239 --> 02:20:35,141
APPROPRIATE DISEASE

3148
02:20:35,141 --> 02:20:35,508
MANIFESTATIONS.

3149
02:20:35,508 --> 02:20:36,676
IF YOU'RE INTERESTED IN HOW THE

3150
02:20:36,676 --> 02:20:38,878
DRUG THAT YOU'RE USING WORKS,

3151
02:20:38,878 --> 02:20:40,447
YOU OUGHT TO KNOW AND LOOK AT

3152
02:20:40,447 --> 02:20:43,883
ALL OF THOSE VARIOUS OUTCOMES AS

3153
02:20:43,883 --> 02:20:44,651
INDIVIDUAL OUTCOMES.

3154
02:20:44,651 --> 02:20:45,785
PROBABLY AS SECONDARY.

3155
02:20:45,785 --> 02:20:47,454
AND THEN SOME SORT OF COMBINED

3156
02:20:47,454 --> 02:20:49,556
OUTCOME TO GIVE YOU YOUR

3157
02:20:49,556 --> 02:20:49,789
PRIMARY.

3158
02:20:49,789 --> 02:20:51,958
AND THE EXAMINATION OF SINGLETON

3159
02:20:51,958 --> 02:20:54,928
OUTCOMES CAN BE MISLEADING OR

3160
02:20:54,928 --> 02:20:55,662
MISSING IMPORTANT CONCEPTS.

3161
02:20:55,662 --> 02:21:00,934
IF YOU'RE ONLY INTERESTED IN

3162
02:21:00,934 --> 02:21:02,769
RASH AND THE MANNEST STATION OF

3163
02:21:02,769 --> 02:21:04,170
LUPUS IN SOME OTHER FEATURE OF

3164
02:21:04,170 --> 02:21:05,772
THAT DISEASE, THEN YOU'RE GOING

3165
02:21:05,772 --> 02:21:09,676
TO MISS THE OUTCOME OF INTEREST.

3166
02:21:09,676 --> 02:21:11,277
COMPOSITE ENDPOINTS EXAMPLES.

3167
02:21:11,277 --> 02:21:12,846
CONSTRUCTED FROM TWO OR MORE

3168
02:21:12,846 --> 02:21:15,382
CLINICALLY RELEVANT SINGLETON OR

3169
02:21:15,382 --> 02:21:16,616
COMPONENT ENDPOINTS, MULTIPLE

3170
02:21:16,616 --> 02:21:18,485
MEASURES OF THE SAME PHENOMENON.

3171
02:21:18,485 --> 02:21:20,387
MEASURES OF SEQUENTIAL EVENTS

3172
02:21:20,387 --> 02:21:21,788
CAN BE USEFUL.

3173
02:21:21,788 --> 02:21:24,991
MEASURES OF DIFFERENTIAL

3174
02:21:24,991 --> 02:21:26,493
PHENOMENON THOUGHT TO BE OF THE

3175
02:21:26,493 --> 02:21:28,094
SAME MECHANISM.

3176
02:21:28,094 --> 02:21:29,429
SOME EXAMPLES ARE, IF YOU'RE

3177
02:21:29,429 --> 02:21:31,798
INTERESTED IN VASCULAR DECIDE

3178
02:21:31,798 --> 02:21:33,500
AND WHAT MIGHT LEAD TO VASCULAR

3179
02:21:33,500 --> 02:21:35,035
DISEASE, YOU'RE NOT JUST GOING

3180
02:21:35,035 --> 02:21:36,069
TO STUDY HEART.

3181
02:21:36,069 --> 02:21:37,203
YOU'RE GOING TO STUDY PROBABLY

3182
02:21:37,203 --> 02:21:38,471
HEART AND YOU WANT TO THE STUDY

3183
02:21:38,471 --> 02:21:39,406
BRAIN WITH REGARDS TO STROKE.

3184
02:21:39,406 --> 02:21:41,107
YOU WANT TO KNOW ABOUT HOW THE

3185
02:21:41,107 --> 02:21:43,343
KIDNEYS ARE FUNCTIONS.

3186
02:21:43,343 --> 02:21:43,510
ING.

3187
02:21:43,510 --> 02:21:44,310
BECAUSE VASCULAR DISEASE WILL

3188
02:21:44,310 --> 02:21:46,312
EFFECT ALL OF THOSE AND

3189
02:21:46,312 --> 02:21:47,714
DIFFERENT PATIENTS MAY MANIFEST

3190
02:21:47,714 --> 02:21:49,082
DIFFERENT OUTCOMES.

3191
02:21:49,082 --> 02:21:50,316
YOU WANT TO COMBINE THOSE.

3192
02:21:50,316 --> 02:21:52,419
YOU CAN COMBINE BY SAYING, ANY

3193
02:21:52,419 --> 02:21:55,488
ONE OF THESE, YES/NO.

3194
02:21:55,488 --> 02:21:56,990
OR YOU COULD SAY I'M INTERESTED

3195
02:21:56,990 --> 02:21:58,525
BECAUSE SOMETIMES PEOPLE HAVE

3196
02:21:58,525 --> 02:21:59,359
WORST VASCULAR DISEASE AND I'M

3197
02:21:59,359 --> 02:22:00,527
GOING TO ADD THEM UP.

3198
02:22:00,527 --> 02:22:04,097
I'M GOING TO GET 1, 2, 3,

3199
02:22:04,097 --> 02:22:06,599
CARDIAC STROKE, KIDNEY DISEASE.

3200
02:22:06,599 --> 02:22:09,536
OBVIOUSLY THE ISSUE OF

3201
02:22:09,536 --> 02:22:12,005
CARDIOVASCULAR DISEASE ITSELF,

3202
02:22:12,005 --> 02:22:15,608
ANGINA, MI, SUDDEN DEATH,

3203
02:22:15,608 --> 02:22:16,309
ALLERGIC RESPONSES AND

3204
02:22:16,309 --> 02:22:18,745
SNEEZING -- COUGHING OR ASTHMA

3205
02:22:18,745 --> 02:22:19,813
AND YOU MIGHT WANT TO LOOK AT

3206
02:22:19,813 --> 02:22:20,747
ALL OF THOSE.

3207
02:22:20,747 --> 02:22:23,583
THE STRENGTHS THAT CAN IMPROVE

3208
02:22:23,583 --> 02:22:25,452
RESOLVING ABILITY BECAUSE YOU'RE

3209
02:22:25,452 --> 02:22:28,321
MEASURING ALL THREE IN VASCULAR

3210
02:22:28,321 --> 02:22:29,622
DISEASE, YOU'RE GOING TO BE

3211
02:22:29,622 --> 02:22:31,424
BETTER AT DETECTING DIFFERENCES

3212
02:22:31,424 --> 02:22:34,160
IN CHANGE AND SO IT'S GOING TO

3213
02:22:34,160 --> 02:22:35,128
INCREASE THE EFFECT SIZE.

3214
02:22:35,128 --> 02:22:37,230
IT MAY IMPROVE THE EFFICIENCY,

3215
02:22:37,230 --> 02:22:39,332
MAY GIVE A MORE EFFICIENT TRIAL

3216
02:22:39,332 --> 02:22:41,434
WITH LESS PATIENTS, MORE

3217
02:22:41,434 --> 02:22:42,569
ACCURATELY ANSWER THE BIOLOGICAL

3218
02:22:42,569 --> 02:22:44,637
QUESTION BECAUSE IF THE QUESTION

3219
02:22:44,637 --> 02:22:47,040
IS ABOUT WHAT HAPPENS IN THE

3220
02:22:47,040 --> 02:22:48,007
VASCULATURE, THIS EN THAT IS

3221
02:22:48,007 --> 02:22:50,310
GOING TO EFFECT ALL THE ORGANS F

3222
02:22:50,310 --> 02:22:50,977
YOU'RE INTERESTED IN WHAT

3223
02:22:50,977 --> 02:22:56,983
HAPPENS TO MYOCARDIUM WHEN IT'S

3224
02:22:56,983 --> 02:22:57,484
MADE AKNOCKSIC, THAT'S A

3225
02:22:57,484 --> 02:22:58,751
DIFFERENT QUESTION AND YOU

3226
02:22:58,751 --> 02:23:00,153
WOULDN'T OBVIOUSLY WANT TO STUDY

3227
02:23:00,153 --> 02:23:05,291
STROKE AS PART OF THAT OR KIDNEY

3228
02:23:05,291 --> 02:23:05,692
DISEASE.

3229
02:23:05,692 --> 02:23:07,961
AND THEN IT MAY HELP PREVENT

3230
02:23:07,961 --> 02:23:08,561
ACCIDENTAL INCORRECT

3231
02:23:08,561 --> 02:23:10,830
INTERPRETATION OF SINGLETON

3232
02:23:10,830 --> 02:23:13,833
ENDPOINTS THAT OCCUR BY CHANCE.

3233
02:23:13,833 --> 02:23:15,168
OKAY, NOW THERE ARE PROBLEMS,

3234
02:23:15,168 --> 02:23:17,270
RIGHT?

3235
02:23:17,270 --> 02:23:18,271
COMPOSITE ENDPOINTS CAN BE

3236
02:23:18,271 --> 02:23:19,139
COMPLICATED TO CONSTRUCT.

3237
02:23:19,139 --> 02:23:20,473
YOU GOT TO BE ABLE TO

3238
02:23:20,473 --> 02:23:21,875
DEMONSTRATE THAT THEY ARE

3239
02:23:21,875 --> 02:23:23,543
ACTUALLY RELATED.

3240
02:23:23,543 --> 02:23:25,578
THEY CAN BE COMPLICATED TO

3241
02:23:25,578 --> 02:23:25,845
INTERPRET.

3242
02:23:25,845 --> 02:23:27,647
IF YOU LOOK AT VASCULAR DISEASE

3243
02:23:27,647 --> 02:23:29,115
FOR THE THREE ORGANS THEN HOW DO

3244
02:23:29,115 --> 02:23:31,050
YOU DEAL WITH THE FACT THAT THEY

3245
02:23:31,050 --> 02:23:31,784
ARE DIFFERENT?

3246
02:23:31,784 --> 02:23:33,186
OBVIOUSLY A SECONDARY WAY OF

3247
02:23:33,186 --> 02:23:34,687
LOOKING AT THAT WOULD BE TO LOOK

3248
02:23:34,687 --> 02:23:35,955
AT THEM SEPARATELY AND THAT

3249
02:23:35,955 --> 02:23:39,859
WOULD BE ONE WAY TO DO THAT.

3250
02:23:39,859 --> 02:23:42,362
ENDPOINTS THAT ARE TO BE

3251
02:23:42,362 --> 02:23:43,496
COMBINED MUST BE BALANCED IF

3252
02:23:43,496 --> 02:23:43,763
RELATED.

3253
02:23:43,763 --> 02:23:45,198
YOU GOT TO BE ABLE TO MEASURE

3254
02:23:45,198 --> 02:23:47,200
WHAT YOU'RE ACTUALLY LOOKING

3255
02:23:47,200 --> 02:23:47,500
FOR.

3256
02:23:47,500 --> 02:23:51,638
AND SO THEY MUST MAKE BIOLOGIC

3257
02:23:51,638 --> 02:23:52,172
SENSE.

3258
02:23:52,172 --> 02:23:53,706
THIS IS JUST HORSE SENSE, RIGHT?

3259
02:23:53,706 --> 02:23:56,743
YOU GOT TO HAVE SOME IDEA ABOUT

3260
02:23:56,743 --> 02:23:58,511
HOW THIS IS ALL RELATED.

3261
02:23:58,511 --> 02:24:01,414
SO LET'S CONSIDER TWO EXAMPLES

3262
02:24:01,414 --> 02:24:01,781
HERE.

3263
02:24:01,781 --> 02:24:04,317
ONE OF THEM, IN BOTH CASES WE'RE

3264
02:24:04,317 --> 02:24:07,187
INTERESTED IN FATAL AND

3265
02:24:07,187 --> 02:24:07,520
NON-FATAL MIs.

3266
02:24:07,520 --> 02:24:09,622
AND IF WE JUST LOOK AT TREATMENT

3267
02:24:09,622 --> 02:24:11,925
1 AND TREATMENT 2, IN THIS CASE,

3268
02:24:11,925 --> 02:24:13,593
TREATMENT 1, IF YOU ADD THEM

3269
02:24:13,593 --> 02:24:15,695
TOGETHER, THERE ARE MORE EVENTS

3270
02:24:15,695 --> 02:24:16,863
IN TREATMENT 1 THAN IN TREATMENT

3271
02:24:16,863 --> 02:24:18,231
2 SO OBVIOUSLY THAT WORKS

3272
02:24:18,231 --> 02:24:18,631
BETTER.

3273
02:24:18,631 --> 02:24:20,500
BUT ON THE OTHER HAND, THE

3274
02:24:20,500 --> 02:24:24,470
NON-FATAL MIs ARE MORE THAN

3275
02:24:24,470 --> 02:24:25,238
THE NON-FATAL MIs IN TREATMENT

3276
02:24:25,238 --> 02:24:25,438
ONE.

3277
02:24:25,438 --> 02:24:27,440
SO DEPENDS ON THE QUESTION

3278
02:24:27,440 --> 02:24:28,041
YOU'RE ASKING.

3279
02:24:28,041 --> 02:24:31,010
IF YOU WERE STUDYING JUST

3280
02:24:31,010 --> 02:24:32,445
NON-FATAL MIs, YOU PROBABLY

3281
02:24:32,445 --> 02:24:33,613
WOULD GET THE WRONG ANSWER HERE.

3282
02:24:33,613 --> 02:24:35,181
AND HERE IS AN EXAMPLE WHERE IF

3283
02:24:35,181 --> 02:24:36,449
YOU ADD THEM TOGETHER, THEY BOTH

3284
02:24:36,449 --> 02:24:38,718
HAVE EXACTLY THE SAME NUMBER OF

3285
02:24:38,718 --> 02:24:41,487
EVENTS BUT TREATMENT 2 HAS MORE

3286
02:24:41,487 --> 02:24:44,924
NON-FATAL THAN FATAL MIs SO IS

3287
02:24:44,924 --> 02:24:45,425
TREATMENT 2 BETTER THAN

3288
02:24:45,425 --> 02:24:46,726
TREATMENT 1?

3289
02:24:46,726 --> 02:24:48,828
ONE COULD ARGUE NON-FATAL IS

3290
02:24:48,828 --> 02:24:50,029
PROBABLY BETTER THAN FATAL.

3291
02:24:50,029 --> 02:24:52,098
BUT IT'S DIFFERENT THAN THE

3292
02:24:52,098 --> 02:24:53,533
OTHERS, RIGHT?

3293
02:24:53,533 --> 02:24:55,535
OKAY, SO, LET'S SWITCH NOW TO

3294
02:24:55,535 --> 02:24:57,537
THINKING ABOUT PRIMARY END

3295
02:24:57,537 --> 02:24:58,271
POINTS IN CLINICAL TRIALS AND

3296
02:24:58,271 --> 02:25:00,773
I'M A BIT OF A RADICAL ABOUT

3297
02:25:00,773 --> 02:25:01,040
THIS.

3298
02:25:01,040 --> 02:25:02,809
FROM MY PERSPECTIVE IN HUMAN

3299
02:25:02,809 --> 02:25:05,078
BEINGS, THERE ARE ONLY THREE

3300
02:25:05,078 --> 02:25:06,079
PRIMARY OUTCOMES.

3301
02:25:06,079 --> 02:25:06,980
ONLY.

3302
02:25:06,980 --> 02:25:08,214
ONE, YOU GOT TO BE BORN, GOT TO

3303
02:25:08,214 --> 02:25:10,283
JOIN THE PARTY TO PLAY.

3304
02:25:10,283 --> 02:25:12,118
SECOND, DEATH, WE ARE TRYING TO

3305
02:25:12,118 --> 02:25:14,887
PREVENT THAT MOSTLY.

3306
02:25:14,887 --> 02:25:17,290
AND EVERYTHING ELSE IS ALL OF

3307
02:25:17,290 --> 02:25:18,691
YOUR LIFE.

3308
02:25:18,691 --> 02:25:20,293
EVERYBODY AGREES, RIGHT?

3309
02:25:20,293 --> 02:25:20,493
YES.

3310
02:25:20,493 --> 02:25:22,428
WE'LL HEAR ABOUT THIS LATER.

3311
02:25:22,428 --> 02:25:23,997
BUT I WOULD ARGUE THAT THE ONLY

3312
02:25:23,997 --> 02:25:25,398
REASON WE TREAT EVERYTHING ELSE

3313
02:25:25,398 --> 02:25:27,233
IS TO MAKE PEOPLE'S LIVES

3314
02:25:27,233 --> 02:25:27,500
BETTER.

3315
02:25:27,500 --> 02:25:30,303
NOW THAT INCLUDES KEEPING THEIR

3316
02:25:30,303 --> 02:25:30,937
GLUCOSE UNDER CONTROL SO THEY

3317
02:25:30,937 --> 02:25:31,904
DON'T DEVELOP ALL THE SIDE

3318
02:25:31,904 --> 02:25:33,539
EFFECTS OF DIABETES.

3319
02:25:33,539 --> 02:25:36,509
IT MEANS MAKING SURE THAT THEIR

3320
02:25:36,509 --> 02:25:37,844
HEART INJECTION FRACTIONS ARE

3321
02:25:37,844 --> 02:25:38,811
IMPROVED SO THEY CAN DO THE

3322
02:25:38,811 --> 02:25:39,812
THINGS THEY WANT TO DO.

3323
02:25:39,812 --> 02:25:42,448
BUT HONESTLY THINKING, I THINK

3324
02:25:42,448 --> 02:25:43,716
THAT'S A REASONABLE WAY OF

3325
02:25:43,716 --> 02:25:45,318
APPROACHING IT.

3326
02:25:45,318 --> 02:25:47,687
AND IN ANIMALS, I WAS A LITTLE

3327
02:25:47,687 --> 02:25:48,221
BIT STUCK.

3328
02:25:48,221 --> 02:25:49,756
YOU GOT TO BE BORN TO BE PART OF

3329
02:25:49,756 --> 02:25:51,024
THE PARTY.

3330
02:25:51,024 --> 02:25:53,993
THERE IS DEATH WHICH WE ARE

3331
02:25:53,993 --> 02:25:55,261
TRYING TO PREVENT OR MAKE IT

3332
02:25:55,261 --> 02:25:55,962
HAPPEN LATER.

3333
02:25:55,962 --> 02:25:57,130
AND I WAS WASN'T SURE WHAT

3334
02:25:57,130 --> 02:25:58,665
QUALITY OF LIFE IN ANIMALS

3335
02:25:58,665 --> 02:26:00,033
CONSISTED OF SO I CALLED IT

3336
02:26:00,033 --> 02:26:02,435
REDUCED SUFFERING.

3337
02:26:02,435 --> 02:26:03,670
I'M WELCOME INPUT FROM ALL OF

3338
02:26:03,670 --> 02:26:03,836
YOU.

3339
02:26:03,836 --> 02:26:07,640
THE OTHER THING I ADDED HERE IS

3340
02:26:07,640 --> 02:26:07,940
PRODUCT.

3341
02:26:07,940 --> 02:26:13,613
SO MEAT OR EGGS OR MILK.

3342
02:26:13,613 --> 02:26:14,947
BECAUSE CLEARLY IN ANIMALS THOSE

3343
02:26:14,947 --> 02:26:16,049
ARE IMPORTANT ISSUES THAT NEED

3344
02:26:16,049 --> 02:26:17,717
TO BE CONSIDERED AS PRIMARY

3345
02:26:17,717 --> 02:26:17,984
OUTCOMES.

3346
02:26:17,984 --> 02:26:20,253
AND THE FDA DEFINES CLINICALLY

3347
02:26:20,253 --> 02:26:22,055
MEANINGFUL AS HOW THE ANIMALS

3348
02:26:22,055 --> 02:26:23,890
FEEL, FUNCTION OR SURVIVE.

3349
02:26:23,890 --> 02:26:26,759
AGAIN, I DON'T KNOW IF THAT IS

3350
02:26:26,759 --> 02:26:28,261
TRUE BUT I WOULD PUT THAT IN.

3351
02:26:28,261 --> 02:26:29,562
AND I WOULD ARGUE THAT ALL THE

3352
02:26:29,562 --> 02:26:31,431
REST OF THEM ARE SURROGATE

3353
02:26:31,431 --> 02:26:32,565
ANIMALS.

3354
02:26:32,565 --> 02:26:32,965
EVERYTHING ELSE.

3355
02:26:32,965 --> 02:26:34,667
SO WHEN YOU DEAL WITH A

3356
02:26:34,667 --> 02:26:35,568
SURROGATE, THERE ARE SOME ISSUES

3357
02:26:35,568 --> 02:26:41,574
YOU HAVE TO THINK ABOUT.

3358
02:26:41,574 --> 02:26:43,710
NOW SURROGATE OUTCOMES ARE AN

3359
02:26:43,710 --> 02:26:45,178
INDICATOR OR SIGN USED IN PLACE

3360
02:26:45,178 --> 02:26:46,379
OF ANOTHER TO TELL IF THE

3361
02:26:46,379 --> 02:26:48,481
TREATMENT IS WORKING.

3362
02:26:48,481 --> 02:26:50,717
SURROGATE ENDPOINTS MIGHT

3363
02:26:50,717 --> 02:26:51,317
INCLUDE SHRINKING OF THE TUMOR

3364
02:26:51,317 --> 02:26:55,455
OR LOWER BIOMARKER LEVELS, RIG 

3365
02:26:55,455 --> 02:26:55,855
RIGHT?

3366
02:26:55,855 --> 02:26:58,257
AND IT GOES ON TO SAY THAT THE

3367
02:26:58,257 --> 02:27:00,293
BENEFITS USED INSTEAD OF STRONG

3368
02:27:00,293 --> 02:27:01,494
INDICATORS SUCH AS LONGER

3369
02:27:01,494 --> 02:27:03,262
SURVIVAL OR IMPROVED QUALITY OF

3370
02:27:03,262 --> 02:27:04,397
LIFE, BECAUSE THE RESULTS OF THE

3371
02:27:04,397 --> 02:27:06,699
TRIAL MAY BE MEASURED SOONER.

3372
02:27:06,699 --> 02:27:09,202
AND THIS IS ABSOLUTELY TRUE.

3373
02:27:09,202 --> 02:27:11,671
THAT'S WHY WE USE MARKERS AND

3374
02:27:11,671 --> 02:27:13,005
BIOMARKERS AND SURROGATES TO TRY

3375
02:27:13,005 --> 02:27:13,940
TO GET A ANSWER SOONER.

3376
02:27:13,940 --> 02:27:17,143
THE RISK IS THAT THE SURROGATE

3377
02:27:17,143 --> 02:27:18,411
ENDPOINTS ARE NOT ALWAYS

3378
02:27:18,411 --> 02:27:20,146
INDICATORS OF THE OUTCOME.

3379
02:27:20,146 --> 02:27:21,314
THEY MUST BE IN THE CAUSAL

3380
02:27:21,314 --> 02:27:23,282
PATHWAY TO BE A SURROGATE, IN

3381
02:27:23,282 --> 02:27:24,884
THE PATHWAY, NOT JUST RELATED TO

3382
02:27:24,884 --> 02:27:25,885
THE PATHWAY.

3383
02:27:25,885 --> 02:27:28,521
AND THERE MUST BE AN UNDERLYING

3384
02:27:28,521 --> 02:27:30,723
SCIENTIFIC BASIS FOR THEM.

3385
02:27:30,723 --> 02:27:32,425
SO EVIDENCE TO INFER CAUSATION,

3386
02:27:32,425 --> 02:27:33,926
THERE IS A BUNCH OF

3387
02:27:33,926 --> 02:27:35,194
CONVERSATIONS ABOUT THIS OUTSIDE

3388
02:27:35,194 --> 02:27:36,596
OF THIS AREA.

3389
02:27:36,596 --> 02:27:39,732
EXPOSURE MUST PRECEDE THE

3390
02:27:39,732 --> 02:27:41,200
OUTCOME.

3391
02:27:41,200 --> 02:27:42,201
EXPOSURE MUST PRECEDE THE

3392
02:27:42,201 --> 02:27:42,902
OUTCOME.

3393
02:27:42,902 --> 02:27:44,237
YOU WOULD BE SURPRISED HOW MANY

3394
02:27:44,237 --> 02:27:45,571
ARTICLES THERE ARE WHERE THE

3395
02:27:45,571 --> 02:27:48,808
EXPOSURE CAME LATER.

3396
02:27:48,808 --> 02:27:50,510
A PERSON MOVED INTO AN AREA

3397
02:27:50,510 --> 02:27:51,911
WHERE THERE IS HIGH RADIATION

3398
02:27:51,911 --> 02:27:52,979
AND THEN TWO YEARS LATER

3399
02:27:52,979 --> 02:27:54,147
DEVELOPED A TUMOR.

3400
02:27:54,147 --> 02:27:55,615
FINE, BUT YOU FORGOT THAT THEY

3401
02:27:55,615 --> 02:27:58,518
WERE LIVING NEXT TO A

3402
02:27:58,518 --> 02:27:59,619
RADIOACTIVE DUMP BEFORE THEY

3403
02:27:59,619 --> 02:28:00,820
EVER GOT THERE.

3404
02:28:00,820 --> 02:28:04,223
SO DID THE HIGH-TENTION WIRES

3405
02:28:04,223 --> 02:28:05,191
CAUSE THE TUMOR?

3406
02:28:05,191 --> 02:28:06,993
I DOUBT IT.

3407
02:28:06,993 --> 02:28:08,194
STRENGTH OF ASSOCIATION

3408
02:28:08,194 --> 02:28:10,596
OBVIOUSLY NEEDS TO BE THERE.

3409
02:28:10,596 --> 02:28:11,230
PLAUSIBLE EXPLANATION FOR

3410
02:28:11,230 --> 02:28:12,398
CAUSATION HAS TO MAKE SENSE AND

3411
02:28:12,398 --> 02:28:13,633
THERE SHOULD BE, HOPEFULLY, SOME

3412
02:28:13,633 --> 02:28:15,501
SORT OF DOSE RESPONSE.

3413
02:28:15,501 --> 02:28:18,638
NOT ALL ASSOCIATIONS ARE CAUSAL.

3414
02:28:18,638 --> 02:28:20,440
IF YOU LEARN ONE THING IN

3415
02:28:20,440 --> 02:28:22,208
EPIDEMIOLOGY, EVER IN YOUR LIFE,

3416
02:28:22,208 --> 02:28:24,010
IT'S THAT ASSOCIATION DOES NOT

3417
02:28:24,010 --> 02:28:25,478
PROVE CAUSATION.

3418
02:28:25,478 --> 02:28:26,345
AND GOOD SURROGATES ARE

3419
02:28:26,345 --> 02:28:30,049
GENERALLY NOT MARKERS OF DISEASE

3420
02:28:30,049 --> 02:28:30,316
SEVERITY.

3421
02:28:30,316 --> 02:28:31,617
THAT'S A TOUGHER ONE AND WE CAN

3422
02:28:31,617 --> 02:28:32,718
TALK MORE ABOUT THAT.

3423
02:28:32,718 --> 02:28:35,221
SO HERE IS A DIAGRAM, THE

3424
02:28:35,221 --> 02:28:36,823
INTERVENTION SHOULD WORK ON THE

3425
02:28:36,823 --> 02:28:37,089
SURROGATE.

3426
02:28:37,089 --> 02:28:39,025
YOU'LL NOTICE THE ARROWS POINT

3427
02:28:39,025 --> 02:28:40,860
IN ONE DIRECTION TOWARDS THE

3428
02:28:40,860 --> 02:28:41,127
OUTCOME.

3429
02:28:41,127 --> 02:28:42,728
SO THE SURROGATE IS IN THE

3430
02:28:42,728 --> 02:28:44,363
CAUSAL PATHWAY.

3431
02:28:44,363 --> 02:28:48,401
EXAMPLES, PHYSIOLOGIC, PLOP,

3432
02:28:48,401 --> 02:28:51,337
OXYGENATION, HEMOGLOBIN A1C,

3433
02:28:51,337 --> 02:28:54,974
PATHOLOGY, TUMOR SIZE, HEALTH

3434
02:28:54,974 --> 02:28:56,142
SERVICES, SELVAGE, CHEMOTHERAPY,

3435
02:28:56,142 --> 02:28:58,578
A BUNCH OF WAYS TO THINK ABOUT

3436
02:28:58,578 --> 02:28:59,412
WHAT COULD BE SURROGATES.

3437
02:28:59,412 --> 02:29:01,547
WHY USE SURROGATE ENDPOINTS?

3438
02:29:01,547 --> 02:29:04,050
THEORETICALLY THEY SHORTEN THE

3439
02:29:04,050 --> 02:29:05,551
TIME HORIZON AND CAN INCREASE

3440
02:29:05,551 --> 02:29:07,320
THE POWER OF YOUR STUDY AND SAVE

3441
02:29:07,320 --> 02:29:07,520
MONEY.

3442
02:29:07,520 --> 02:29:09,589
SO AS AN EXAMPLE, YOU GOT A RISK

3443
02:29:09,589 --> 02:29:11,858
OF DEATH OF 10% AND THE RISK OF

3444
02:29:11,858 --> 02:29:15,161
THE PRIMARY OUTCOME THAT YOU

3445
02:29:15,161 --> 02:29:21,968
CHOOSE REDUCES THE DEATH BY 20%.

3446
02:29:21,968 --> 02:29:24,337
THEN LOOKING FOR A CHANGE IN 20%

3447
02:29:24,337 --> 02:29:26,606
OF YOUR POPULATION VERSUS 10% IS

3448
02:29:26,606 --> 02:29:30,142
GOING TO SAVE YOU IN TERMS OF

3449
02:29:30,142 --> 02:29:30,676
EFFICACY.

3450
02:29:30,676 --> 02:29:32,311
SO, IF THE ADVANTAGES OF THE

3451
02:29:32,311 --> 02:29:33,846
OUTCOME THAT YOU PICK IS A

3452
02:29:33,846 --> 02:29:36,015
CONTINUOUS VARIABLE AS OPPOSED

3453
02:29:36,015 --> 02:29:38,251
TO DICHOTOMOUS, DEATH IS

3454
02:29:38,251 --> 02:29:38,551
DICHOTOMOUS.

3455
02:29:38,551 --> 02:29:40,353
IN THIS CASE, IN THIS EXAMPLE,

3456
02:29:40,353 --> 02:29:41,687
THE MEAN IS 60 AND STANDARD

3457
02:29:41,687 --> 02:29:43,155
DEVIATION IS 20.

3458
02:29:43,155 --> 02:29:44,624
AND THE OBSERVATIONAL EVIDENCE

3459
02:29:44,624 --> 02:29:47,994
IS THAT A 10.INCREASE IN THE

3460
02:29:47,994 --> 02:29:50,696
MARKERS ASSOCIATED WITH 20%

3461
02:29:50,696 --> 02:29:53,566
INCREASE IN THE RISK OF DEATH,

3462
02:29:53,566 --> 02:29:55,501
OR ODDS RATIO 1.2.

3463
02:29:55,501 --> 02:29:56,569
WHEN WE LOOK AT THE RESULTS,

3464
02:29:56,569 --> 02:29:58,504
WHAT YOU CAN SEE IS THAT IF YOU

3465
02:29:58,504 --> 02:30:00,806
STUDY MORTALITY, AND THE

3466
02:30:00,806 --> 02:30:04,710
DIFFERENCES ARE FROM 10% TO 8%,

3467
02:30:04,710 --> 02:30:06,879
OR 10-4, THE NUMBERS YOU GET ARE

3468
02:30:06,879 --> 02:30:07,380
ABSOLUTELY HUGE.

3469
02:30:07,380 --> 02:30:09,181
IF YOU LOOK AT THE SURROGATE

3470
02:30:09,181 --> 02:30:10,850
MARKER, AND SAY WE'RE GOING TO

3471
02:30:10,850 --> 02:30:13,252
AFFECT THE SURROGATE DOWN BY

3472
02:30:13,252 --> 02:30:13,419
10%.

3473
02:30:13,419 --> 02:30:15,488
WHICH IS IT GOING TO EFFECT THAT

3474
02:30:15,488 --> 02:30:16,856
BY 20%.

3475
02:30:16,856 --> 02:30:19,492
THE NUMBERS NEEDED ARE 123 DOWN

3476
02:30:19,492 --> 02:30:22,228
TO 32 AND UP, DEPENDING ON WHICH

3477
02:30:22,228 --> 02:30:23,329
GROUP YOU PICK.

3478
02:30:23,329 --> 02:30:25,331
SO, THERE ARE WAYS TO LOOK AT

3479
02:30:25,331 --> 02:30:26,832
THIS THAT ARE OBVIOUSLY GOING TO

3480
02:30:26,832 --> 02:30:28,601
INCREASE YOUR ABILITY TO LOOK.

3481
02:30:28,601 --> 02:30:31,304
THE PROBLEM IS, YOU NEED TO BE

3482
02:30:31,304 --> 02:30:32,438
CLEAR THAT YOUR SURROGATE IS

3483
02:30:32,438 --> 02:30:33,372
RELATED TO THE OUTCOME.

3484
02:30:33,372 --> 02:30:36,442
AND THAT IS UP TO YOU TO DEFEND.

3485
02:30:36,442 --> 02:30:38,778
SO, THIS IS WHAT I WAS JUST

3486
02:30:38,778 --> 02:30:39,979
SAYING.

3487
02:30:39,979 --> 02:30:45,351
IN TERMS OF NUMBER 2, IF WE LOOK

3488
02:30:45,351 --> 02:30:48,321
HERE AT DEATH AND THE

3489
02:30:48,321 --> 02:30:48,955
COMPLEMENTARY -- OTHER MEASURE

3490
02:30:48,955 --> 02:30:50,957
YOU'RE GOING TO USE, OBVIOUSLY

3491
02:30:50,957 --> 02:30:53,759
THE NUMBER OF PEOPLE WHO DIE,

3492
02:30:53,759 --> 02:30:55,561
PART OF THEM ARE GOING TO HAVE

3493
02:30:55,561 --> 02:30:57,129
THIS VALLEY AND PART WILL NOT.

3494
02:30:57,129 --> 02:30:58,664
SO YOU WANT TO THINK ABOUT HOW

3495
02:30:58,664 --> 02:31:00,099
YOU'RE GOING IT DEAL WITH IT.

3496
02:31:00,099 --> 02:31:02,468
WHEN YOU DO THE MATH, YOU FIND

3497
02:31:02,468 --> 02:31:04,570
THAT THERE IS AN ODDS RATIO OF

3498
02:31:04,570 --> 02:31:05,371
ABOUT ONE.5.

3499
02:31:05,371 --> 02:31:07,173
IF YOU HAVE THE MARKER, VERSUS

3500
02:31:07,173 --> 02:31:08,808
IF YOU DON'T IN TERMS OF WHETHER

3501
02:31:08,808 --> 02:31:10,576
YOU'RE GOING TO DIE.

3502
02:31:10,576 --> 02:31:12,545
WHEN YOU CALCULATE THE SAMPLE

3503
02:31:12,545 --> 02:31:15,915
SIZES BASED ON JUST MORTALITY

3504
02:31:15,915 --> 02:31:18,017
AND THIS IS A STUDY WHERE YOU

3505
02:31:18,017 --> 02:31:20,252
HAVE TO STUDY PEOPLE A LONG TIME

3506
02:31:20,252 --> 02:31:22,622
TO SEE ANY DIFFERENCE AT ALL,

3507
02:31:22,622 --> 02:31:24,824
YOU NEED 56,000 PEOPLE TO STUDY

3508
02:31:24,824 --> 02:31:25,992
MORTALITY, WHEREAS IF YOU USE

3509
02:31:25,992 --> 02:31:30,563
THE SURROGATE, AND DROP THE

3510
02:31:30,563 --> 02:31:33,232
SURROGATE FROM .3 TO 1.5, THEN

3511
02:31:33,232 --> 02:31:36,969
YOU ONLY NEED 268 PATIENTS.

3512
02:31:36,969 --> 02:31:40,172
THE ASSUMPTION HERE IS THAT THIS

3513
02:31:40,172 --> 02:31:41,707
SURROGATE PREDICTS THE MORTALITY

3514
02:31:41,707 --> 02:31:42,775
IN SOME WAY.

3515
02:31:42,775 --> 02:31:44,210
IF YOU CAN'T PROVE THAT, THEN

3516
02:31:44,210 --> 02:31:46,412
THE SURROGATE IS NOT GOING TO BE

3517
02:31:46,412 --> 02:31:47,713
USEFUL TO YOU.

3518
02:31:47,713 --> 02:31:49,281
WHAT ARE THE RISKS OF SURROGATE?

3519
02:31:49,281 --> 02:31:50,916
THEY ARE NOT REALLY IN THE

3520
02:31:50,916 --> 02:31:52,218
CAUSAL PATHWAY AND IT'S

3521
02:31:52,218 --> 02:31:54,020
SOMETIMES REALLY HARD TO KNOW.

3522
02:31:54,020 --> 02:31:57,023
OTHER CAUSAL MECHANISMS EXIST.

3523
02:31:57,023 --> 02:31:58,624
EXPOSURE IS RELATED TO THE

3524
02:31:58,624 --> 02:31:59,425
OUTCOME IN OTHER WAYS AND YOU

3525
02:31:59,425 --> 02:32:01,427
HAVE TO HAVE A LEVEL OF

3526
02:32:01,427 --> 02:32:02,194
CONFIDENCE.

3527
02:32:02,194 --> 02:32:03,195
TO RUN THROUGH A YOU TOO, THIS

3528
02:32:03,195 --> 02:32:04,563
IS WHAT WE WERE TALKING ABOUT.

3529
02:32:04,563 --> 02:32:06,832
YOU NOTICE THE ARROWS GOING IN

3530
02:32:06,832 --> 02:32:09,702
ONE DIRECTION.

3531
02:32:09,702 --> 02:32:10,503
NOT THIS.

3532
02:32:10,503 --> 02:32:11,837
SURROGATES A CONFOUNDER HERE IF

3533
02:32:11,837 --> 02:32:12,838
YOU WANT TO BE SPECIFIC.

3534
02:32:12,838 --> 02:32:14,006
IT HAS AN INDEPENDENT

3535
02:32:14,006 --> 02:32:14,640
RELATIONSHIP WITH THE DISEASE

3536
02:32:14,640 --> 02:32:16,909
AND THE OUTCOME AND THE

3537
02:32:16,909 --> 02:32:17,843
MECHANISM FROM THE DISEASE TO

3538
02:32:17,843 --> 02:32:23,416
THE OUTCOME IS DIFFERENT.

3539
02:32:23,416 --> 02:32:25,017
THIS ONE IS WHERE IN FACT THE

3540
02:32:25,017 --> 02:32:26,585
SURROGATE IS THE IN THE PATHWAY

3541
02:32:26,585 --> 02:32:28,954
BUT IT'S ONLY A SMALL PART OF

3542
02:32:28,954 --> 02:32:29,655
THE OUTCOME.

3543
02:32:29,655 --> 02:32:30,756
THE LIKELIHOOD THAT THE

3544
02:32:30,756 --> 02:32:32,758
SURROGATE IS GOING TO HELP YOU

3545
02:32:32,758 --> 02:32:35,361
IS MINIMAL BECAUSE YOU'RE MOSTLY

3546
02:32:35,361 --> 02:32:37,697
NOT MEASURING THAT PARTICULAR

3547
02:32:37,697 --> 02:32:38,130
PATHWAY.

3548
02:32:38,130 --> 02:32:39,131
THE INTERVENTION COULD WORK

3549
02:32:39,131 --> 02:32:40,966
DIRECTLY ON THE OUTCOME AND SKIP

3550
02:32:40,966 --> 02:32:42,234
THE SURROGATE.

3551
02:32:42,234 --> 02:32:43,436
SO MEASURING THE SURROGATE IS

3552
02:32:43,436 --> 02:32:44,336
NOT GOING TO HELP YOU.

3553
02:32:44,336 --> 02:32:47,840
AND YOU CAN COME UP WITH A LOT

3554
02:32:47,840 --> 02:32:48,974
OF DIFFERENT EXAMPLES.

3555
02:32:48,974 --> 02:32:52,244
NOW LET'S TALK ABOUT UNINTENDED

3556
02:32:52,244 --> 02:32:53,345
CONSEQUENCES OF SURROGATES IS

3557
02:32:53,345 --> 02:32:53,546
ABOUT.

3558
02:32:53,546 --> 02:32:55,948
SO THERE IS ISSUES OF SUDDEN

3559
02:32:55,948 --> 02:32:59,351
DEATH, AND WE KNOW THAT IN

3560
02:32:59,351 --> 02:33:03,956
CARDIAC DISEASE THAT TREATING

3561
02:33:03,956 --> 02:33:05,057
IRREGULAR HEARTBEATS INCREASED

3562
02:33:05,057 --> 02:33:06,759
MORTALITY IN MOST CASES.

3563
02:33:06,759 --> 02:33:08,127
AND THAT'S JUST REPRESENTED

3564
02:33:08,127 --> 02:33:08,327
HERE.

3565
02:33:08,327 --> 02:33:10,162
SO WE HAVE TO BE VERY CAREFUL

3566
02:33:10,162 --> 02:33:12,932
ABOUT WHAT WE DO.

3567
02:33:12,932 --> 02:33:14,233
THIS IS ANOTHER EXAMPLE WHICH

3568
02:33:14,233 --> 02:33:15,768
I'M GOING TO GO QUICKLY THROUGH

3569
02:33:15,768 --> 02:33:16,969
SINCE I'M OVER TIME.

3570
02:33:16,969 --> 02:33:18,771
BUT THIS IS A GROWTH HORMONE

3571
02:33:18,771 --> 02:33:21,674
TREATMENT AND JUST TO MAKE THE

3572
02:33:21,674 --> 02:33:23,442
POINT HERE THAT IT TERPS OUT

3573
02:33:23,442 --> 02:33:24,677
THAT PEOPLE THOUGHT THIS IS HOW

3574
02:33:24,677 --> 02:33:26,479
GROWTH HORMONE WOULD EFFECT

3575
02:33:26,479 --> 02:33:28,114
STRENGTH AND IMMUNE FUNCTION TO

3576
02:33:28,114 --> 02:33:29,348
MAKE EVERYBODY BETTER.

3577
02:33:29,348 --> 02:33:31,884
THEY FORGOT THAT IT CAUSED FLUID

3578
02:33:31,884 --> 02:33:33,252
RETENTION, HYPOGLYCEMIA AND

3579
02:33:33,252 --> 02:33:35,254
INFECTIONS AND MADE PEOPLE

3580
02:33:35,254 --> 02:33:35,554
WORSE.

3581
02:33:35,554 --> 02:33:37,490
SO THE WHOLE POINT WAS THAT THE

3582
02:33:37,490 --> 02:33:38,691
SURROGATE THAT THEY CHOSE TO

3583
02:33:38,691 --> 02:33:41,727
LOOK AT WAS NOT REFLECTIVE OF

3584
02:33:41,727 --> 02:33:44,063
THE TOTALITY OF THE DISEASE THAT

3585
02:33:44,063 --> 02:33:46,532
WAS THERE.

3586
02:33:46,532 --> 02:33:47,433
SO, ARE SURROGATES ACCEPTABLE?

3587
02:33:47,433 --> 02:33:48,300
NOT REALLY.

3588
02:33:48,300 --> 02:33:50,102
IN PHASE III THEY CAN BE

3589
02:33:50,102 --> 02:33:51,704
ACCEPTABLE IN PHASE II AND THEY

3590
02:33:51,704 --> 02:33:54,406
CAN BE VERY USEFUL IN THE

3591
02:33:54,406 --> 02:33:55,207
INITIAL STUDIES OF OUTCOMES BUT

3592
02:33:55,207 --> 02:33:57,143
YOU HAVE TO DO SOME WORK TO

3593
02:33:57,143 --> 02:33:58,210
FIGURE OUT HOW THEY WORK.

3594
02:33:58,210 --> 02:33:59,512
I'M GOING TO END WITH THIS,

3595
02:33:59,512 --> 02:34:00,713
WHICH SOMEBODY ELSE IS GOING TO

3596
02:34:00,713 --> 02:34:02,448
TALK ABOUT, WHICH IS THAT THE

3597
02:34:02,448 --> 02:34:04,984
FDA HAS A GUIDANCE FOR INDUSTRY

3598
02:34:04,984 --> 02:34:07,720
NUMBER 268, THAT TALKS ABOUT THE

3599
02:34:07,720 --> 02:34:10,556
USE OF MEASURES AND ADAPTIVE

3600
02:34:10,556 --> 02:34:10,790
TRIALS.

3601
02:34:10,790 --> 02:34:11,957
AND WILL THERE ARE WAYS IN WHICH

3602
02:34:11,957 --> 02:34:14,093
WE CAN INCORPORATE SURROGATES

3603
02:34:14,093 --> 02:34:16,529
AND OTHER THINGS INTO ADAPTIVE

3604
02:34:16,529 --> 02:34:18,297
TRIALS THAT ARE USEFUL.

3605
02:34:18,297 --> 02:34:20,099
MEASURE SURROGATES BECAUSE YOU

3606
02:34:20,099 --> 02:34:21,567
CAN MEASURE THEM QUICKLY BUT

3607
02:34:21,567 --> 02:34:22,535
KEEP FOLLOWING PATIENTS AND LOOK

3608
02:34:22,535 --> 02:34:24,236
TO SEE IF THE RESPONSE HAPPENS

3609
02:34:24,236 --> 02:34:25,538
IN YOUR SURROGATE AS YOU'RE

3610
02:34:25,538 --> 02:34:28,674
MEASURING THE REST OF THE

3611
02:34:28,674 --> 02:34:29,041
PATIENTS EVENTS.

3612
02:34:29,041 --> 02:34:29,642
IF THE SURROGATE DOESN'T SHOW

3613
02:34:29,642 --> 02:34:31,644
YOU ANYTHING, YOU CAN STOP THE

3614
02:34:31,644 --> 02:34:31,844
TRIAL.

3615
02:34:31,844 --> 02:34:33,245
IF THE SURROGATE SUGGESTS THAT

3616
02:34:33,245 --> 02:34:34,647
THERE MIGHT BE AN OUTCOME OF

3617
02:34:34,647 --> 02:34:35,848
INTEREST, YOU MIGHT GO ON TO

3618
02:34:35,848 --> 02:34:38,217
MEASURE THE PRIMARY OUTCOME AND

3619
02:34:38,217 --> 02:34:39,451
CONTINUE THE TRIAL FOR ANOTHER

3620
02:34:39,451 --> 02:34:41,687
YEAR OR TWO IF THAT IS WHAT IT

3621
02:34:41,687 --> 02:34:43,222
WOULD TAKE.

3622
02:34:43,222 --> 02:34:45,090
AND I THINK THE MAIN FEATURE

3623
02:34:45,090 --> 02:34:48,060
HERE IS THAT ANY BIOMARKER THAT

3624
02:34:48,060 --> 02:34:50,529
IS USED MUST HAVE CLINICAL

3625
02:34:50,529 --> 02:34:52,498
SENSITIVITIES, SPECIFICITY,

3626
02:34:52,498 --> 02:34:54,333
POSITIVE AND NEGATIVE PREDICTIVE

3627
02:34:54,333 --> 02:34:55,100
VALUES TO BE USED TO DETERMINE

3628
02:34:55,100 --> 02:34:55,968
THE PATIENT POPULATION THAT YOU

3629
02:34:55,968 --> 02:34:57,937
WANT TO WORK WITH.

3630
02:34:57,937 --> 02:34:59,071
AND IT IS VERY IMPORTANT YOU

3631
02:34:59,071 --> 02:35:01,674
LOOK AT WHAT BIOMARKERS MEAN.

3632
02:35:01,674 --> 02:35:03,943
AND JUST A REAL QUICK COMMENT

3633
02:35:03,943 --> 02:35:04,710
ABOUT BIOMARKERS.

3634
02:35:04,710 --> 02:35:07,880
IT TURNED OUT THAT THEY LOOKED

3635
02:35:07,880 --> 02:35:11,851
AT STUDIES 1885,000 OF THEM, AND

3636
02:35:11,851 --> 02:35:13,052
BIOMARKERS MADE ALMOST NO

3637
02:35:13,052 --> 02:35:15,020
DIFFERENCE IN THOSE STUDIES.

3638
02:35:15,020 --> 02:35:15,688
WHY IS THAT?

3639
02:35:15,688 --> 02:35:18,390
GOT TO REMEMBER THAT HUMANS ARE

3640
02:35:18,390 --> 02:35:19,458
COMPLEX ANIMALS.

3641
02:35:19,458 --> 02:35:22,962
THERE ARE OVER 20,000

3642
02:35:22,962 --> 02:35:23,963
PROTEIN-CODED GENES AND THERE

3643
02:35:23,963 --> 02:35:26,899
ARE ALMOST 300,000 NON-REDUNDANT

3644
02:35:26,899 --> 02:35:27,967
PEPTIDES.

3645
02:35:27,967 --> 02:35:28,934
SO YOU PICK ONE AND YOU SAY,

3646
02:35:28,934 --> 02:35:31,370
THIS IS THE BEST THING SINCE

3647
02:35:31,370 --> 02:35:32,137
SLICED BREAD.

3648
02:35:32,137 --> 02:35:32,738
IT MIGHT BE.

3649
02:35:32,738 --> 02:35:34,440
BUT YOU GOT A LOT OF PROVING TO

3650
02:35:34,440 --> 02:35:36,141
BE ABLE TO USE AND FIGURE OUT

3651
02:35:36,141 --> 02:35:36,976
HOW THAT WORKS.

3652
02:35:36,976 --> 02:35:38,878
SO I'LL END WITH THIS,

3653
02:35:38,878 --> 02:35:40,145
COMPOSITES AND COMBINED

3654
02:35:40,145 --> 02:35:42,047
ENDPOINTS NEED TO BE CAREFULLY

3655
02:35:42,047 --> 02:35:42,648
DEFINED.

3656
02:35:42,648 --> 02:35:43,749
SURROGATE ENDPOINTS CAN

3657
02:35:43,749 --> 02:35:44,717
POTENTIALLY INCREASE THE

3658
02:35:44,717 --> 02:35:47,019
EFFICIENCY OF CLINICAL TRIALS.

3659
02:35:47,019 --> 02:35:48,120
THERE ARE SEVERAL KNOWN THREATS

3660
02:35:48,120 --> 02:35:50,356
THAT MUST BE ADDRESSED BEFORE

3661
02:35:50,356 --> 02:35:51,523
YOU IMPLEMENT THIS.

3662
02:35:51,523 --> 02:35:53,792
PHASE III TRIALS SHOULD BE

3663
02:35:53,792 --> 02:35:55,127
POWERED FOR THE PATIENT-CENTERED

3664
02:35:55,127 --> 02:35:58,497
OR ANIMAL-CENTERED ENDPOINT.

3665
02:35:58,497 --> 02:36:00,833
AND DECISION ANALYSIS CAN LINK

3666
02:36:00,833 --> 02:36:03,636
TRIAL EVIDENCE TO OBSERVED IN

3667
02:36:03,636 --> 02:36:03,836
DATA.

3668
02:36:03,836 --> 02:36:05,671
YOU CAN USE OBSERVATIONAL DATA

3669
02:36:05,671 --> 02:36:07,339
TO DECIDE ON WHAT THE OUTCOMES

3670
02:36:07,339 --> 02:36:08,707
ARE YOU SHOULD USE AND IMPROVE

3671
02:36:08,707 --> 02:36:10,542
THE WAY TO INTERPRET OUR

3672
02:36:10,542 --> 02:36:11,310
SURROGATE ENDPOINTS.

3673
02:36:11,310 --> 02:36:18,851
AND I'LL STOP THERE.

3674
02:36:18,851 --> 02:36:27,493
[ APPLAUSE ]

3675
02:36:27,493 --> 02:36:28,560
>> THANK YOU VERY MUCH DR.
JOHN

3676
02:36:28,560 --> 02:36:28,794
FARRAR.

3677
02:36:28,794 --> 02:36:31,563
NEXT I'D LIKE TO INTRODUCE MY

3678
02:36:31,563 --> 02:36:36,468
COLLEAGUE, DR. CLAIRE RUBERMAN.

3679
02:36:36,468 --> 02:36:37,336
A MATHEMATICAL STATISTICIAN IN

3680
02:36:37,336 --> 02:36:40,673
THE OFFICE OF NEW ANIMAL DRUG

3681
02:36:40,673 --> 02:36:41,674
EVALUATION FOR VETERINARY

3682
02:36:41,674 --> 02:36:43,208
MEDICINE IN FDA.

3683
02:36:43,208 --> 02:36:45,544
RECEIVED HER PH.D. FROM THE

3684
02:36:45,544 --> 02:36:47,746
JOHNS HOPKINS BLOOMBERG SCHOOL

3685
02:36:47,746 --> 02:36:50,916
OF PUBLIC HEALTH AND BA IN

3686
02:36:50,916 --> 02:36:52,284
MATHEMATICS.

3687
02:36:52,284 --> 02:36:53,686
DR. RUBERMAN.

3688
02:36:53,686 --> 02:37:01,961
[ APPLAUSE ]

3689
02:37:01,961 --> 02:37:06,165
>> GOOD AFTERNOON,
EVERYONE.

3690
02:37:06,165 --> 02:37:07,566
SO, TO START I'LL GIVE YOU A

3691
02:37:07,566 --> 02:37:10,803
LITTLE BIT OF A ROADMAP ABOUT MY

3692
02:37:10,803 --> 02:37:11,236
PRESENTATION TODAY.

3693
02:37:11,236 --> 02:37:13,405
THERE IS DEFINITELY A LOT OF

3694
02:37:13,405 --> 02:37:15,140
OVERLAP SO THANK YOU DR. JOHN

3695
02:37:15,140 --> 02:37:16,575
FARRAR FOR A LOT OF REALLY

3696
02:37:16,575 --> 02:37:17,910
IMPORTANT INTRODUCTIONS.

3697
02:37:17,910 --> 02:37:20,879
SO I'LL GIVE MORE BACKGROUND AND

3698
02:37:20,879 --> 02:37:22,281
THEN TALK ABOUT DIFFERENT TYPES

3699
02:37:22,281 --> 02:37:25,384
OF ENDPOINTS FROM A STATISTICAL

3700
02:37:25,384 --> 02:37:25,784
PERSPECTIVE.

3701
02:37:25,784 --> 02:37:28,654
BEFORE I GET INTO ENDPOINTS I

3702
02:37:28,654 --> 02:37:31,490
WANT TO NOTE THAT OUR

3703
02:37:31,490 --> 02:37:32,024
STATISTICAL CONSIDERATIONS

3704
02:37:32,024 --> 02:37:34,093
REALLY DEPEND ON THE TYPE OF

3705
02:37:34,093 --> 02:37:36,996
STUDY AND THE OBJECTIVE OF THE

3706
02:37:36,996 --> 02:37:37,296
STUDY.

3707
02:37:37,296 --> 02:37:38,998
SO I'LL DISTINGUISH BETWEEN

3708
02:37:38,998 --> 02:37:41,400
EXPLORATORY STUDIES WHERE OUR

3709
02:37:41,400 --> 02:37:43,469
GOAL IS TO GENERATE NEW

3710
02:37:43,469 --> 02:37:45,104
HYPOTHESES, TYPICALLY SMALLER,

3711
02:37:45,104 --> 02:37:48,107
MORE FLEXIBLE STUDIES WHERE WE

3712
02:37:48,107 --> 02:37:51,110
MAY EMPLOY STATISTICS AND FORMAL

3713
02:37:51,110 --> 02:37:53,879
MODELS, BUT WE DON'T NECESSARILY

3714
02:37:53,879 --> 02:37:56,382
PRE-DEFINE OUR PRIMARY ENDPOINTS

3715
02:37:56,382 --> 02:37:58,050
OR OUR METHODS.

3716
02:37:58,050 --> 02:38:00,419
IN CONTRAST, IN CONFIRMATORY

3717
02:38:00,419 --> 02:38:03,322
STUDIES, OUR GOAL IS TO TEST THE

3718
02:38:03,322 --> 02:38:04,623
VALIDITY OF AN ALREADY

3719
02:38:04,623 --> 02:38:06,091
ESTABLISHED HYPOTHESIS.

3720
02:38:06,091 --> 02:38:07,626
TYPICALLY THESE STUDIES ARE

3721
02:38:07,626 --> 02:38:08,727
DESIGNED WITH KNOWLEDGE ABOUT

3722
02:38:08,727 --> 02:38:12,331
PREVIOUS STUDIES OR OTHER

3723
02:38:12,331 --> 02:38:12,698
INFORMATION.

3724
02:38:12,698 --> 02:38:14,767
IN THESE CASES, IN A CONFIRM

3725
02:38:14,767 --> 02:38:17,736
TORE YOU STUDY, WE SUSPECT OUR

3726
02:38:17,736 --> 02:38:19,038
STATISTICAL METHODS AND MODELS

3727
02:38:19,038 --> 02:38:20,739
AS WELL AS A BASIS FOR THE STUDY

3728
02:38:20,739 --> 02:38:25,077
CONCLUSIONS ARE PRE-SPECIFIED.

3729
02:38:25,077 --> 02:38:27,646
SO, IN A CONFIRMATORY STUDY, WE

3730
02:38:27,646 --> 02:38:30,049
DEFINE OUR PRIMARY ENDPOINTS.

3731
02:38:30,049 --> 02:38:32,151
SO THE PRIMARY ENDPOINT OR IN

3732
02:38:32,151 --> 02:38:34,353
SOME CASES, THE FAMILY OF

3733
02:38:34,353 --> 02:38:35,854
PRIMARY ENDPOINTS ARE THE

3734
02:38:35,854 --> 02:38:37,256
ENDPOINTS UPON WHICH WE MAKE OUR

3735
02:38:37,256 --> 02:38:38,757
STUDY CONCLUSIONS.

3736
02:38:38,757 --> 02:38:40,659
SO THOSE CAN BE SINGLE, WHICH IS

3737
02:38:40,659 --> 02:38:42,694
PRETTY SELF EXPLANATORY.

3738
02:38:42,694 --> 02:38:43,796
AND WE HAVE A COUPLE OF

3739
02:38:43,796 --> 02:38:44,963
DIFFERENT OPTIONS AS WE HAVE

3740
02:38:44,963 --> 02:38:47,466
SEEN ABOUT MULTIPLE PRIMARY

3741
02:38:47,466 --> 02:38:47,800
ENDPOINTS.

3742
02:38:47,800 --> 02:38:50,269
ONE OPTION IS WE HAVE CO-PRIMARY

3743
02:38:50,269 --> 02:38:51,870
ENDPOINTS WHERE WE SAY THAT THE

3744
02:38:51,870 --> 02:38:53,338
SUCCESS OF THE STUDY DEPENDS ON

3745
02:38:53,338 --> 02:38:55,741
A POSITIVE OUTCOME IN ALL OF THE

3746
02:38:55,741 --> 02:38:56,041
END POINTS.

3747
02:38:56,041 --> 02:38:58,377
SO IN A PAIN STUDY, WE THINK

3748
02:38:58,377 --> 02:38:59,945
THAT IT'S CLINICALLY RELEVANT

3749
02:38:59,945 --> 02:39:03,015
THAT WE SHOW SUCCESS ACROSS ALL

3750
02:39:03,015 --> 02:39:03,916
THESE DIFFERENT FACETS OF PAIN.

3751
02:39:03,916 --> 02:39:06,485
IN CONTRAST, IN MULTIPLE PRIMARY

3752
02:39:06,485 --> 02:39:07,586
ENDPOINTS FOR THE PURPOSE OF

3753
02:39:07,586 --> 02:39:09,988
THIS TALK, I'M TALKING ABOUT

3754
02:39:09,988 --> 02:39:11,957
MULTIPLE ENDPOINTS WHERE IF WE

3755
02:39:11,957 --> 02:39:13,092
HAVE A TREATMENT EFFECT ON AT

3756
02:39:13,092 --> 02:39:14,860
LEAST ONE OF THESE ENDPOINTS,

3757
02:39:14,860 --> 02:39:16,595
THAT'S SUFFICIENT TO CONCLUDE

3758
02:39:16,595 --> 02:39:18,197
STUDY SUCCESS.

3759
02:39:18,197 --> 02:39:19,631
SO WE HAVE MANY DIFFERENT

3760
02:39:19,631 --> 02:39:20,999
AVENUES OR MULTIPLE AVENUES IN

3761
02:39:20,999 --> 02:39:22,701
WHICH TO SHOW SUCCESS.

3762
02:39:22,701 --> 02:39:25,304
AND THEN THE THIRD OPTION IS TO

3763
02:39:25,304 --> 02:39:26,905
DEFINE A COMPOSITE ENDPOINT

3764
02:39:26,905 --> 02:39:30,109
WHERE WE TAKE OUR MULTIPLE

3765
02:39:30,109 --> 02:39:31,743
ENDPOINTS AND WE COMBINE THEM

3766
02:39:31,743 --> 02:39:33,912
INTO SOME SINGLE VARIABLE AND

3767
02:39:33,912 --> 02:39:37,816
HAVE JUST ONE STATISTICAL

3768
02:39:37,816 --> 02:39:38,717
HYPOTHESIS.

3769
02:39:38,717 --> 02:39:40,619
SO BEFORE I GET INTO MORE

3770
02:39:40,619 --> 02:39:42,287
DETAILS, I WANT TO RECALL SOME

3771
02:39:42,287 --> 02:39:43,755
KEY STATISTICAL CONSIDERATIONS

3772
02:39:43,755 --> 02:39:45,724
IF WE ARE TALKING ABOUT JUST A

3773
02:39:45,724 --> 02:39:49,895
SINGLE HYPOTHESIS.

3774
02:39:49,895 --> 02:39:51,096
SO THE GENERAL FRAMEWORK THAT

3775
02:39:51,096 --> 02:39:52,998
WE'RE TALKING ABOUT WITH

3776
02:39:52,998 --> 02:39:55,033
HYPOTHESIS TESTING IS THAT WE

3777
02:39:55,033 --> 02:39:57,970
HAVE A NULL HYPOTHESIS ABOUT OUR

3778
02:39:57,970 --> 02:39:59,004
POPULATION.

3779
02:39:59,004 --> 02:40:01,874
OFTEN THIS IS SIMPLEST CASE NO

3780
02:40:01,874 --> 02:40:02,741
DIFFERENCE BETWEEN TWO GROUPS.

3781
02:40:02,741 --> 02:40:04,710
WE COLLECT DATA FROM A RANDOM

3782
02:40:04,710 --> 02:40:06,211
SAMPLE OF OBSERVATIONS THAT WE

3783
02:40:06,211 --> 02:40:09,014
HOPE IS REPRESENTATIVE OF OUR

3784
02:40:09,014 --> 02:40:09,982
POPULATION OF INTEREST.

3785
02:40:09,982 --> 02:40:15,220
WE CALCULATE SOME TEST

3786
02:40:15,220 --> 02:40:17,055
STATISTICS, THIS MAYBE SOMETHING

3787
02:40:17,055 --> 02:40:17,723
LIKE A MEAN OR DIFFERENCE IN

3788
02:40:17,723 --> 02:40:20,092
MEANSING AND COMPARE THE

3789
02:40:20,092 --> 02:40:21,527
OBSERVED RESULTS TO THE EXPECTED

3790
02:40:21,527 --> 02:40:22,794
RESULTS UNDER THE NULL

3791
02:40:22,794 --> 02:40:23,128
HYPOTHESIS.

3792
02:40:23,128 --> 02:40:25,030
SO WE LOOK AT THE DISTRIBUTION

3793
02:40:25,030 --> 02:40:27,733
OF THE TEST STATISTIC IF THE

3794
02:40:27,733 --> 02:40:28,634
NULL HYPOTHESIS WERE TRUE AND

3795
02:40:28,634 --> 02:40:31,436
THEN MAKE A DECISION EITHER TO

3796
02:40:31,436 --> 02:40:32,938
REJECT THE NULL AND ACCEPT THE

3797
02:40:32,938 --> 02:40:35,240
ALTERNATIVE, OR WE FAIL TO

3798
02:40:35,240 --> 02:40:36,909
REJECT THE NULL IF WE DON'T HAVE

3799
02:40:36,909 --> 02:40:37,543
SUFFICIENT EVIDENCE.

3800
02:40:37,543 --> 02:40:40,646
SO THERE ARE TWO WAYS IN WHICH

3801
02:40:40,646 --> 02:40:42,614
WE CAN MAKE A MISTAKE.

3802
02:40:42,614 --> 02:40:43,849
THIS TABLE WILL PROBABLY LOOK

3803
02:40:43,849 --> 02:40:46,285
FAMILIAR TO MANY FOLKS HERE.

3804
02:40:46,285 --> 02:40:48,120
BUT THIS IS A TWO BY TWO TABLE.

3805
02:40:48,120 --> 02:40:50,856
IN THE TOP LEFT, WE REJECT THE

3806
02:40:50,856 --> 02:40:52,491
NULL WHEN THE NULL HYPOTHESIS IS

3807
02:40:52,491 --> 02:40:53,358
ACTUALLY TRY.

3808
02:40:53,358 --> 02:40:56,962
SO THAT'S A TYPE I ERROR.

3809
02:40:56,962 --> 02:40:58,564
AND THE SIGNIFICANCE LEVEL,

3810
02:40:58,564 --> 02:41:00,265
ALPHA, IS THE THRESHOLD BELOW

3811
02:41:00,265 --> 02:41:02,067
WHICH THE TYPE I ERROR RATE

3812
02:41:02,067 --> 02:41:02,601
SHOULD BE CONTROLLED.

3813
02:41:02,601 --> 02:41:05,671
OFTEN WE SEE ALPHA STATUS .05.

3814
02:41:05,671 --> 02:41:07,573
AND THEN IN THE BOTTOM RIGHT, WE

3815
02:41:07,573 --> 02:41:12,711
HAVE THE ERROR WHERE WE FAIL TO

3816
02:41:12,711 --> 02:41:16,381
REJECT THE NULL HYPOTHESIS

3817
02:41:16,381 --> 02:41:17,549
BUT -- THE NULL, BUT THE NULL IS

3818
02:41:17,549 --> 02:41:19,785
ACTUALLY FALSE.

3819
02:41:19,785 --> 02:41:21,453
SOLE WE HAVE A FALSE NEGATIVE.

3820
02:41:21,453 --> 02:41:22,721
THE CONVERSE OF THAT IS THE

3821
02:41:22,721 --> 02:41:22,921
POWER.

3822
02:41:22,921 --> 02:41:25,524
SO THAT'S WHEN WE CORRECTLY

3823
02:41:25,524 --> 02:41:26,658
REJECT THE NULL.

3824
02:41:26,658 --> 02:41:30,596
SO POWER IS 1 MINUS THE TYPE II

3825
02:41:30,596 --> 02:41:31,530
ERROR.

3826
02:41:31,530 --> 02:41:34,499
SO WHAT HAPPENS WHEN WE MOVE TO

3827
02:41:34,499 --> 02:41:36,235
MULTIPLE TESTING?

3828
02:41:36,235 --> 02:41:38,103
SO INTUITIVELY IF WE HAVE

3829
02:41:38,103 --> 02:41:39,605
MULTIPLE HYPOTHESES THAT WE'RE

3830
02:41:39,605 --> 02:41:41,807
TESTING AND WE CAN CONCLUDE

3831
02:41:41,807 --> 02:41:43,709
STUDY SUCCESS, BASED OFF OF ANY

3832
02:41:43,709 --> 02:41:45,510
OF THESE HYPOTHESES, THEN WE

3833
02:41:45,510 --> 02:41:47,346
HAVE MORE CHANCES TO GET IT

3834
02:41:47,346 --> 02:41:47,646
WRONG.

3835
02:41:47,646 --> 02:41:50,816
SO THIS CONCEPT IS REFERRED TO

3836
02:41:50,816 --> 02:41:51,350
AS MULTIPLICITY.

3837
02:41:51,350 --> 02:41:54,052
THIS IS OUR HIGHER-THAN INTENDED

3838
02:41:54,052 --> 02:41:56,722
OVER ALL TYPE I ERROR RATE WHEN

3839
02:41:56,722 --> 02:41:57,923
CONDUCTING MULTIPLE TESTS

3840
02:41:57,923 --> 02:41:59,791
WITHOUT MAKING ANY STATISTICAL

3841
02:41:59,791 --> 02:42:00,092
ADJUSTMENTS.

3842
02:42:00,092 --> 02:42:01,326
AND THE FAMILY WISE ERROR RATE

3843
02:42:01,326 --> 02:42:03,262
IS THE PROBABILITY OF MAKING ONE

3844
02:42:03,262 --> 02:42:04,429
OR MORE TYPE I ERRORS.

3845
02:42:04,429 --> 02:42:08,300
SO THIS IS A SIMPLE EXAMPLE

3846
02:42:08,300 --> 02:42:10,135
SHOWING HOW THE FAMILY WISE

3847
02:42:10,135 --> 02:42:11,837
ERROR RATE CAN BE INFLATED AS WE

3848
02:42:11,837 --> 02:42:13,105
INCREASE THE NUMBER OF

3849
02:42:13,105 --> 02:42:13,372
ENDPOINTS.

3850
02:42:13,372 --> 02:42:15,307
HERE WE ARE STARTING WITH AN

3851
02:42:15,307 --> 02:42:18,210
ALPHA LEVEL OF .05 AND I'LL

3852
02:42:18,210 --> 02:42:19,645
ASSUME JUST IN THE SIMPLE

3853
02:42:19,645 --> 02:42:22,147
EXAMPLE WE HAVE UNCORRELATED

3854
02:42:22,147 --> 02:42:22,681
ENDPOINTS.

3855
02:42:22,681 --> 02:42:24,416
THE NUMBERS WILL CHANGE

3856
02:42:24,416 --> 02:42:25,450
DEPENDING ON THE CORRELATION.

3857
02:42:25,450 --> 02:42:27,319
WHEN YOU SEE THAT IF WE INCREASE

3858
02:42:27,319 --> 02:42:29,321
THE NUMBER OF ENDPOINTS, THE

3859
02:42:29,321 --> 02:42:30,922
FAMILY WISE ERROR RATE INCREASES

3860
02:42:30,922 --> 02:42:33,859
QUITE DRAMATICALLY.

3861
02:42:33,859 --> 02:42:35,694
SO WE HAVE A COUPLE OF OPTIONS

3862
02:42:35,694 --> 02:42:37,095
FOR HOW TO ADDRESS THIS.

3863
02:42:37,095 --> 02:42:40,432
ONE IS THAT WE DEFINE CO-PRIMARY

3864
02:42:40,432 --> 02:42:43,135
ENDPOINTS WHERE WE HAVE TO

3865
02:42:43,135 --> 02:42:45,971
ACHIEVE SIGNIFICANTS FOR EACH

3866
02:42:45,971 --> 02:42:47,205
INDIVIDUAL ENDPOINT.

3867
02:42:47,205 --> 02:42:48,740
OFTEN THE CHOICE AND DECISION TO

3868
02:42:48,740 --> 02:42:50,542
USE CO-PRIMARY ENDPOINTS CAN BE

3869
02:42:50,542 --> 02:42:52,744
DRIVEN BY CLINICAL FACTORS SO I

3870
02:42:52,744 --> 02:42:53,945
WON'T SPEND TOO MUCH TIME ON

3871
02:42:53,945 --> 02:42:54,146
THIS.

3872
02:42:54,146 --> 02:42:55,647
BUT I WANT TO NOTE THAT IF WE

3873
02:42:55,647 --> 02:42:57,649
HAVE CO-PRIMARY ENDPOINTS, WE NO

3874
02:42:57,649 --> 02:43:00,218
LONGER HAVE TO WORRY ABOUT

3875
02:43:00,218 --> 02:43:01,687
MULTIPLICITY BECAUSE WE ARE

3876
02:43:01,687 --> 02:43:02,754
REQUIRING STATISTICAL

3877
02:43:02,754 --> 02:43:05,190
SIGNIFICANCE FOR EACH ENDPOINT

3878
02:43:05,190 --> 02:43:05,857
INDIVIDUALLY.

3879
02:43:05,857 --> 02:43:06,458
HOWEVER, ON THE OTHER SIDE OF

3880
02:43:06,458 --> 02:43:09,261
THE EQUATION, THE POWER CAN BE

3881
02:43:09,261 --> 02:43:10,128
NEGATIVELY AFFECTED.

3882
02:43:10,128 --> 02:43:11,930
IT CAN BE HARDER TO CONCLUDE

3883
02:43:11,930 --> 02:43:14,399
THAT A STUDY SUCCESSFUL BECAUSE

3884
02:43:14,399 --> 02:43:18,236
WE HAVE TO OVERCOME MULTIPLE

3885
02:43:18,236 --> 02:43:18,470
HURDLES.

3886
02:43:18,470 --> 02:43:20,072
ANOTHER OPTION IS WE CAN GO BACK

3887
02:43:20,072 --> 02:43:22,874
TO THE FRAMEWORK OF MULTIPLE

3888
02:43:22,874 --> 02:43:24,676
PRIMARY ENDPOINTS WHERE YOU CAN

3889
02:43:24,676 --> 02:43:26,845
ACHIEVE STUDY SUCCESS WITH ANY

3890
02:43:26,845 --> 02:43:27,679
ONE INDIVIDUALLY.

3891
02:43:27,679 --> 02:43:29,247
BUT WE HAVE STATISTICAL

3892
02:43:29,247 --> 02:43:31,416
ADJUSTMENTS TO DEAL WITH THE

3893
02:43:31,416 --> 02:43:32,351
INFLATED TYPE I ERROR RATE.

3894
02:43:32,351 --> 02:43:34,152
AND I'LL SPEND SOME TIME TALKING

3895
02:43:34,152 --> 02:43:35,554
ABOUT SOME OPTIONS THAT WE HAVE.

3896
02:43:35,554 --> 02:43:37,155
AND THEN THE THIRD OPTION IS TO

3897
02:43:37,155 --> 02:43:38,757
CREATE A COMPOSITE ENDPOINT.

3898
02:43:38,757 --> 02:43:40,359
SO NOW WE HAVE TAKEN OUR

3899
02:43:40,359 --> 02:43:42,461
MULTIPLE ENDPOINTS AND BACK DOWN

3900
02:43:42,461 --> 02:43:44,796
TO ONE SINGLE ENDPOINT AND WE'RE

3901
02:43:44,796 --> 02:43:46,898
ONLY TESTING ONE HYPOTHESIS.

3902
02:43:46,898 --> 02:43:48,700
AND DR. JOHN FARRAR GAVE NICE

3903
02:43:48,700 --> 02:43:49,868
EXAMPLES OF THOSE AND I'LL TALK

3904
02:43:49,868 --> 02:43:53,205
A LITTLE BIT MORE ABOUT A COUPLE

3905
02:43:53,205 --> 02:43:56,274
OF ADDITIONAL STATISTICAL

3906
02:43:56,274 --> 02:43:56,641
CONSIDERATIONS.

3907
02:43:56,641 --> 02:43:58,877
SO THERE IS A NICE GUIDANCE FROM

3908
02:43:58,877 --> 02:44:02,314
INDUSTRY PUBLISHED BY OUR

3909
02:44:02,314 --> 02:44:04,116
COLLEAGUES AT CDER AND SEEBER.

3910
02:44:04,116 --> 02:44:06,551
AND THEY GIVE A NUMBER OF

3911
02:44:06,551 --> 02:44:08,120
DIFFERENT OPTIONS FOR

3912
02:44:08,120 --> 02:44:10,055
CONTROLLING THE FAMILY WISE

3913
02:44:10,055 --> 02:44:10,689
ERROR RATE.

3914
02:44:10,689 --> 02:44:12,257
I WON'T GO THROUGH ALL OF THE

3915
02:44:12,257 --> 02:44:14,626
OPTIONS BUT I WANT TO NOTE THAT

3916
02:44:14,626 --> 02:44:16,661
IN A CONFIRMATORY STUDY, IT'S

3917
02:44:16,661 --> 02:44:19,931
REALLY CRITICAL THAT IN ADDITION

3918
02:44:19,931 --> 02:44:21,700
TO PRE SPECIFYING OUR PRIMARY

3919
02:44:21,700 --> 02:44:23,435
ENDPOINTS AND THE OUR MODELS, IF

3920
02:44:23,435 --> 02:44:25,937
WE'RE GOING TO BE USING

3921
02:44:25,937 --> 02:44:27,839
STATISTICAL METHODS FOR

3922
02:44:27,839 --> 02:44:28,740
ADJUSTMENTS, THOSE METHODS

3923
02:44:28,740 --> 02:44:31,643
SHOULD ALSO BE PRE-SPECIFIED.

3924
02:44:31,643 --> 02:44:37,249
THE SIMPLEST METHOD WE CAN USE

3925
02:44:37,249 --> 02:44:39,251
IS THE BON FERONY METHOD.

3926
02:44:39,251 --> 02:44:42,154
WE DIVIDE OUR .05 BY THE NUMBER

3927
02:44:42,154 --> 02:44:43,822
OF CHOSEN ENDPOINTS, IN THE

3928
02:44:43,822 --> 02:44:46,224
SIMPLEST CASE.

3929
02:44:46,224 --> 02:44:49,528
SO WE HAVE 5 COPRIMARY

3930
02:44:49,528 --> 02:44:49,828
ENDPOINTS.

3931
02:44:49,828 --> 02:44:51,596
FOR EACH INDIVIDUAL ENDPOINT

3932
02:44:51,596 --> 02:44:53,131
WE'RE LOOKING AT WHETHER THE

3933
02:44:53,131 --> 02:44:54,633
P-VALUE IS LESS THAN .01.

3934
02:44:54,633 --> 02:44:56,968
WE CAN ALSO THINK ABOUT A

3935
02:44:56,968 --> 02:44:59,104
WEIGHTED BON FERONY WHERE WE UP

3936
02:44:59,104 --> 02:45:01,840
WEIGHT SOME OF THEM AND DOWN

3937
02:45:01,840 --> 02:45:02,474
WEIGHT OTHERS.

3938
02:45:02,474 --> 02:45:04,242
THIS IS A VERY SIMPLE METHOD.

3939
02:45:04,242 --> 02:45:05,844
IT DOESN'T REQUIRE ANY

3940
02:45:05,844 --> 02:45:07,179
ASSUMPTIONS ABOUT OUR DATA OR

3941
02:45:07,179 --> 02:45:09,247
HOW THE ENDPOINTS ARE

3942
02:45:09,247 --> 02:45:10,348
CORRELATED.

3943
02:45:10,348 --> 02:45:12,050
IT ONLY TAKES ONE STEP.

3944
02:45:12,050 --> 02:45:14,052
BUT THE DOWNSIDE IS THAT IT'S

3945
02:45:14,052 --> 02:45:14,953
VERY CONSERVATIVE.

3946
02:45:14,953 --> 02:45:16,922
SO WE SEE WE MAY HAVE OR OFTEN

3947
02:45:16,922 --> 02:45:19,558
HAVE A LOSS OF POWER USING THE

3948
02:45:19,558 --> 02:45:20,091
BON FERONY METHOD.

3949
02:45:20,091 --> 02:45:21,626
AND WE WANT TO BE CAREFUL

3950
02:45:21,626 --> 02:45:23,762
ESPECIALLY WITH A LOT OF

3951
02:45:23,762 --> 02:45:24,329
ENDPOINTS.

3952
02:45:24,329 --> 02:45:26,164
SO, I WON'T GO THROUGH THIS

3953
02:45:26,164 --> 02:45:27,566
SLIDE IN DETAIL BUT I WANT TO

3954
02:45:27,566 --> 02:45:28,900
NOTE THAT THERE ARE A NUMBER OF

3955
02:45:28,900 --> 02:45:31,536
DIFFERENT STATISTICAL METHODS.

3956
02:45:31,536 --> 02:45:32,938
SOME OF THEM MAKE ASSUMPTIONS

3957
02:45:32,938 --> 02:45:35,540
ABOUT HOW THE DATA IS

3958
02:45:35,540 --> 02:45:36,608
DISTRIBUTED OR WHETHER OR NOT

3959
02:45:36,608 --> 02:45:38,310
END POINTS ARE CORRELATED.

3960
02:45:38,310 --> 02:45:40,946
SOME OF THEM LOOK AT ALL

3961
02:45:40,946 --> 02:45:42,147
ENDPOINTS EQUALLY WHEREAS IN

3962
02:45:42,147 --> 02:45:46,384
OTHER CASES, YOU CAN TEST THE

3963
02:45:46,384 --> 02:45:48,887
ENDPOINTS IN A PRE-DEFINED ORDER

3964
02:45:48,887 --> 02:45:51,556
WHERE YOU START WITH THE MOST

3965
02:45:51,556 --> 02:45:52,491
CLINICALLY-RELEVANT ENDPOINTS.

3966
02:45:52,491 --> 02:45:54,493
SO THERE ARE A NUMBER OF

3967
02:45:54,493 --> 02:45:56,127
DIFFERENT OPTIONS AND IT'S

3968
02:45:56,127 --> 02:45:57,329
CRITICAL THAT THE STATISTICIAN

3969
02:45:57,329 --> 02:45:59,331
WORK WITH THE CLINICIAN TO

3970
02:45:59,331 --> 02:46:03,602
IDENTIFY WHAT METHOD MAY BE MOST

3971
02:46:03,602 --> 02:46:03,902
APPROPRIATE.

3972
02:46:03,902 --> 02:46:06,238
SO GOING BACK TO AN EXPLORATORY

3973
02:46:06,238 --> 02:46:11,409
STUDY, WE DON'T HAVE THE SAME

3974
02:46:11,409 --> 02:46:11,977
TYPE I ERROR CONCERN BECAUSE

3975
02:46:11,977 --> 02:46:13,845
WE'RE ASSUMING THAT AN

3976
02:46:13,845 --> 02:46:14,913
EXPLORATORY STUDY WILL BE

3977
02:46:14,913 --> 02:46:17,582
FOLLOWED UP WITH A CONFIRMATORY

3978
02:46:17,582 --> 02:46:17,916
STUDY.

3979
02:46:17,916 --> 02:46:19,117
HOWEVER, THERE IS STILL A RISK

3980
02:46:19,117 --> 02:46:21,753
THAT IF WE DO AN EXPLORATORY

3981
02:46:21,753 --> 02:46:25,790
STUDY, AND WE GET A REALLY LOW

3982
02:46:25,790 --> 02:46:27,158
P-VALUE, THAT WE OVERINTERPRET A

3983
02:46:27,158 --> 02:46:27,459
DIFFERENCE.

3984
02:46:27,459 --> 02:46:31,830
AND THIS IS REFERRED TO AS

3985
02:46:31,830 --> 02:46:33,331
SELECTIVE INFERENCE.

3986
02:46:33,331 --> 02:46:36,334
SO THIS IS A SLIDE, THIS PICTURE

3987
02:46:36,334 --> 02:46:38,770
FROM ERIC GIBSON OF NOVARTIS,

3988
02:46:38,770 --> 02:46:41,139
WHERE HE IS DEMONSTRATING THE

3989
02:46:41,139 --> 02:46:43,008
ISSUE WITH SELECTED INFERENCE

3990
02:46:43,008 --> 02:46:45,043
WHERE WE'RE DRAWING THE TARGET

3991
02:46:45,043 --> 02:46:48,480
AROUND THE ARROW.

3992
02:46:48,480 --> 02:46:54,419
AND THIS CAN LEAD TO PROBLEMS OF

3993
02:46:54,419 --> 02:46:56,454
LOW REPLIC ABILITY WHERE WE OVER

3994
02:46:56,454 --> 02:46:57,322
INTERPRET SOME DIFFERENCE AND

3995
02:46:57,322 --> 02:46:59,558
ARE UNABLE TO REPLICATE IT IN A

3996
02:46:59,558 --> 02:47:01,560
LATER STUDY.

3997
02:47:01,560 --> 02:47:04,763
AND THIS CAN BE QUANTIFIED WITH

3998
02:47:04,763 --> 02:47:05,397
THE FALSE DISCOVERY RATE, WHICH

3999
02:47:05,397 --> 02:47:09,234
IS THE EXPECTED PROPORTION OF

4000
02:47:09,234 --> 02:47:09,868
FALSE POSITIVE FINDINGS AMONG

4001
02:47:09,868 --> 02:47:10,669
ALL POSITIVE.

4002
02:47:10,669 --> 02:47:13,071
SO AMONG ALL REJECTED

4003
02:47:13,071 --> 02:47:13,371
HYPOTHESES.

4004
02:47:13,371 --> 02:47:15,740
AND THE FAMILY WISE ERROR RATE

4005
02:47:15,740 --> 02:47:17,242
WAS FIRST INTRODUCED IN THE

4006
02:47:17,242 --> 02:47:21,713
90s IN THE CONTEXT OF GENOME

4007
02:47:21,713 --> 02:47:22,581
WIDE STUDIES WHERE CONTROLLING

4008
02:47:22,581 --> 02:47:24,783
THE FAMILY WISE ERROR RATE WAS

4009
02:47:24,783 --> 02:47:25,584
FOUND TO BE TOO CONSERVATIVE

4010
02:47:25,584 --> 02:47:29,287
WHEN YOU HAVE A LARGE NUMBER OF

4011
02:47:29,287 --> 02:47:29,988
HYPOTHESES.

4012
02:47:29,988 --> 02:47:31,356
AND OFTEN YOU MIGHT -- THERE IS

4013
02:47:31,356 --> 02:47:32,891
A RISK YOU MIGHT MISS SOMETHING

4014
02:47:32,891 --> 02:47:36,061
IF YOU CONTROL THE FAMILY WISE

4015
02:47:36,061 --> 02:47:36,461
ERROR RATE.

4016
02:47:36,461 --> 02:47:39,364
SO A BIG GENOME-WIDE STUDY OR

4017
02:47:39,364 --> 02:47:40,899
EXPLORATORY STUDY WHERE YOU

4018
02:47:40,899 --> 02:47:45,937
DON'T WANT TO LOSE A ENDPOINT,

4019
02:47:45,937 --> 02:47:46,571
CONTROLLING THE FALSE DISCOVERY

4020
02:47:46,571 --> 02:47:50,675
RATE MIGHT BE A MORE APPROPRIATE

4021
02:47:50,675 --> 02:47:50,909
OPTION.

4022
02:47:50,909 --> 02:47:52,510
AND THIS SLIDE, THIS TABLE,

4023
02:47:52,510 --> 02:47:55,680
GIVES YOU SOME IN TUITION THAT

4024
02:47:55,680 --> 02:47:58,283
AS YOU INCREASE THE NUMBER OF

4025
02:47:58,283 --> 02:47:59,918
TESTS WHETHER BECAUSE OF AN

4026
02:47:59,918 --> 02:48:02,887
INCREASE IN ENDPOINTS OR PERHAPS

4027
02:48:02,887 --> 02:48:05,190
BECAUSE OF ADDITIONAL SUBGROUPS

4028
02:48:05,190 --> 02:48:08,293
OR DOSES, FOR ANY FIXED POWER

4029
02:48:08,293 --> 02:48:10,495
LEVEL, AS INCREASE THE NUMBER OF

4030
02:48:10,495 --> 02:48:11,396
TESTS, THE FALSE DISCOVERY RATE

4031
02:48:11,396 --> 02:48:14,599
WILL INCREASE QUITE

4032
02:48:14,599 --> 02:48:14,933
DRAMATICALLY.

4033
02:48:14,933 --> 02:48:16,601
AND I HAVE INCLUDED AT THE

4034
02:48:16,601 --> 02:48:18,570
BOTTOM A REALLY -- THE

4035
02:48:18,570 --> 02:48:19,804
RELATIONSHIP BETWEEN THE FALSE

4036
02:48:19,804 --> 02:48:21,906
DISCOVERY RATE AND THE FAMILY

4037
02:48:21,906 --> 02:48:24,109
WISE ERROR RATE.

4038
02:48:24,109 --> 02:48:25,410
AND SIMILAR TO HAVING A NUMBER

4039
02:48:25,410 --> 02:48:27,812
OF METHODS FOR CONTROLLING THE

4040
02:48:27,812 --> 02:48:30,015
FAMILY WISE ERROR RATE, WE ALSO

4041
02:48:30,015 --> 02:48:31,516
HAVE SOME STATISTICAL OPTIONS

4042
02:48:31,516 --> 02:48:33,818
FOR CONTROLLING THE FALSE

4043
02:48:33,818 --> 02:48:34,519
DISCOVERY RATE.

4044
02:48:34,519 --> 02:48:37,689
AND I'LL NOTE THAT THESE METHODS

4045
02:48:37,689 --> 02:48:39,524
ARE LESS CONSERVATIVE.

4046
02:48:39,524 --> 02:48:40,992
ANY METHOD THAT CONTROLS THE

4047
02:48:40,992 --> 02:48:43,928
FAMILY WISE ERROR RATE WILL ALSO

4048
02:48:43,928 --> 02:48:46,631
AUTOMATICALLY CONTROL THE FALSE

4049
02:48:46,631 --> 02:48:47,899
DISCOVERY RATE.

4050
02:48:47,899 --> 02:48:50,702
AND SO SOME OF THE METHODS ARE

4051
02:48:50,702 --> 02:48:53,004
THE BEN YAMENEY AND -- [

4052
02:48:53,004 --> 02:48:53,538
INAUDIBLE ]

4053
02:48:53,538 --> 02:48:53,772
METHOD.

4054
02:48:53,772 --> 02:48:55,507
AND THEN THERE HAS BEEN A LOT OF

4055
02:48:55,507 --> 02:48:58,943
LITERATURE AND WORK BY JOHN

4056
02:48:58,943 --> 02:49:00,712
STORY AND OTHERS TO INTRODUCE

4057
02:49:00,712 --> 02:49:03,581
ALTERNATIVE METHODS LIKE THE

4058
02:49:03,581 --> 02:49:04,449
POSITIVE FALSE DISCOVERY RATE.

4059
02:49:04,449 --> 02:49:07,719
THERE IS ADDITIONAL STATISTICAL

4060
02:49:07,719 --> 02:49:10,822
LITERATURE INTRODUCING THE OTHER

4061
02:49:10,822 --> 02:49:11,923
METHODS TO THIS.

4062
02:49:11,923 --> 02:49:13,692
SO SIMILAR TO THE FAMILY WISE

4063
02:49:13,692 --> 02:49:15,627
ERROR RATES, IT DEPENDS ON WHAT

4064
02:49:15,627 --> 02:49:18,029
DATA YOU HAVE AND YOUR

4065
02:49:18,029 --> 02:49:18,530
ASSUMPTIONS.

4066
02:49:18,530 --> 02:49:19,597
SO I'LL SWITCH GEARS A LITTLE

4067
02:49:19,597 --> 02:49:23,334
BIT AND TALK ABOUT COMPOSITE

4068
02:49:23,334 --> 02:49:24,836
ENDPOINTS FOR A FEW MINUTES.

4069
02:49:24,836 --> 02:49:28,907
SEWED AS MENTIONED BEFORE,

4070
02:49:28,907 --> 02:49:31,076
COMPOSITE ENDPOINTS IS WE DON'T

4071
02:49:31,076 --> 02:49:32,243
NEED TO CHOOSE A PRIMARY.

4072
02:49:32,243 --> 02:49:34,045
WE ALSO DON'T NEED TO ADJUST FOR

4073
02:49:34,045 --> 02:49:36,548
MULTIPLE TESTING.

4074
02:49:36,548 --> 02:49:38,850
HOWEVER, CLINICAL RELEVANCE AND

4075
02:49:38,850 --> 02:49:41,052
INTERPRETABILITY IS REALLY KEY

4076
02:49:41,052 --> 02:49:42,954
FOR NOT ONLY THE ENDPOINT AS A

4077
02:49:42,954 --> 02:49:46,024
WHOLE BUT ALSO THE INDIVIDUAL

4078
02:49:46,024 --> 02:49:46,324
COMPONENTS.

4079
02:49:46,324 --> 02:49:48,493
WE CAN THINK ABOUT WEIGHTING

4080
02:49:48,493 --> 02:49:49,561
WITH COM POSILATE ENDPOINTS IN A

4081
02:49:49,561 --> 02:49:52,564
NUMBER OF DIFFERENT WAYS --

4082
02:49:52,564 --> 02:49:53,965
COMPOSITE -- ONE IS IF WE ARE

4083
02:49:53,965 --> 02:49:55,867
COMBINING SCORES THAT ARE ON

4084
02:49:55,867 --> 02:49:58,236
MULTIPLE SCALES, SAY ONE SCALE

4085
02:49:58,236 --> 02:50:01,172
IS 0-3 AND THE OTHER IS 0-100.

4086
02:50:01,172 --> 02:50:04,109
IF YOU ADDED THE SCORES TOGETHER

4087
02:50:04,109 --> 02:50:06,878
THE ONE ON THE MUCH HIGHER SCALE

4088
02:50:06,878 --> 02:50:07,846
WOULD BE UP WEIGHTED.

4089
02:50:07,846 --> 02:50:11,116
SO WE WANT TO TAKE THAT INTO

4090
02:50:11,116 --> 02:50:12,884
ACCOUNT WHEN WE'RE CONSTRUCTING

4091
02:50:12,884 --> 02:50:15,353
OUR ENDPOINTS POTENTIALLY AT OUR

4092
02:50:15,353 --> 02:50:17,188
OWN WEIGHTS TO COUNTER ACT THAT.

4093
02:50:17,188 --> 02:50:18,890
WE CAN ALSO THINK ABOUT WEIGHTS

4094
02:50:18,890 --> 02:50:20,692
TO ACCOUNT FOR OUR

4095
02:50:20,692 --> 02:50:22,861
DIRECTIONALITY OF DIFFERENT

4096
02:50:22,861 --> 02:50:24,362
COMPONENTS AS WELL AS CLINICAL

4097
02:50:24,362 --> 02:50:26,364
IMPORTANCE AND SEVERITY.

4098
02:50:26,364 --> 02:50:28,566
AND AS A STATISTICIAN, I WANT TO

4099
02:50:28,566 --> 02:50:30,301
POINT OUT IF WE DO ANALYSIS ON

4100
02:50:30,301 --> 02:50:33,872
OUR COMPOSITE ENDPOINT, AND

4101
02:50:33,872 --> 02:50:36,074
STATISTICAL INFERENCE AND

4102
02:50:36,074 --> 02:50:37,909
CONCLUSIONS APPLY TO THAT

4103
02:50:37,909 --> 02:50:40,078
COMPOSITE ENDPOINT AS A WHOLE

4104
02:50:40,078 --> 02:50:41,312
AND WE CAN'T MAKE CONCLUSIONS

4105
02:50:41,312 --> 02:50:42,881
ABOUT THE INDIVIDUAL COMPONENTS.

4106
02:50:42,881 --> 02:50:44,082
SO THERE ARE OFTEN CASES WHERE

4107
02:50:44,082 --> 02:50:46,684
WE MIGHT WANT TO LOOK AT

4108
02:50:46,684 --> 02:50:48,319
SECONDARY ANALYSIS THAT LOOK AT

4109
02:50:48,319 --> 02:50:49,821
THE INDIVIDUAL COMPONENTS AFTER

4110
02:50:49,821 --> 02:50:53,758
WE MADE A CONCLUSION ABOUT THE

4111
02:50:53,758 --> 02:50:55,593
COMPOSITE AS A WHOLE.

4112
02:50:55,593 --> 02:50:57,328
SO I'LL CLOSE OUT WITH A COUPLE

4113
02:50:57,328 --> 02:50:59,397
OF ADDITIONAL THOUGHTS DEPENDING

4114
02:50:59,397 --> 02:51:01,933
ON THE TYPE.

4115
02:51:01,933 --> 02:51:04,602
COMPOSITE ENDPOINT -- SO WITH

4116
02:51:04,602 --> 02:51:05,303
CONTINUOUS DATA OFTEN OUR

4117
02:51:05,303 --> 02:51:06,805
ANALYSIS IS LOOKING AT A

4118
02:51:06,805 --> 02:51:08,573
DIFFERENCE IN GROUP MEANS WHICH

4119
02:51:08,573 --> 02:51:12,177
CAN BE INTERPRETED NICELY FOR AN

4120
02:51:12,177 --> 02:51:14,746
INDIVIDUAL AS WELL AS FOR A

4121
02:51:14,746 --> 02:51:14,946
GROUP.

4122
02:51:14,946 --> 02:51:17,215
I THINK DR. BROWN MADE A REALLY

4123
02:51:17,215 --> 02:51:18,716
IMPORTANT POINT IN HER TALK

4124
02:51:18,716 --> 02:51:20,752
EARLIER TODAY THEY WANT TO

4125
02:51:20,752 --> 02:51:22,320
REITERATE THAT IF WE HAVE

4126
02:51:22,320 --> 02:51:23,321
ORDINAL SCORES, THE SUM OR THE

4127
02:51:23,321 --> 02:51:26,124
MEAN OF THOSE SCORES IS NOT

4128
02:51:26,124 --> 02:51:26,457
INTERPRETABLE.

4129
02:51:26,457 --> 02:51:28,660
SO WE CAN'T ASSUME THAT

4130
02:51:28,660 --> 02:51:30,161
DISTANCES BETWEEN INTERVALS OR

4131
02:51:30,161 --> 02:51:31,963
CHANGES IN SCORES ARE EQUAL WHEN

4132
02:51:31,963 --> 02:51:35,333
WE'RE LOOKING AT TOGETHER.

4133
02:51:35,333 --> 02:51:37,602
AND THEN A DOWNSIDE WITH

4134
02:51:37,602 --> 02:51:38,937
CONTINUOUS COMPOSITE ENDPOINTS

4135
02:51:38,937 --> 02:51:42,740
AND DATA IN GENERAL IS THAT

4136
02:51:42,740 --> 02:51:43,308
EARLY WITHDRAWLS OFTEN MEAN

4137
02:51:43,308 --> 02:51:46,344
MISSING DATA THAT WE WANT TO

4138
02:51:46,344 --> 02:51:47,846
THINK ABOUT.

4139
02:51:47,846 --> 02:51:50,248
WE HAVE SEEN TODAY SOME NICE

4140
02:51:50,248 --> 02:51:52,650
EXAMPLES OF BINARY COMPOSITE END

4141
02:51:52,650 --> 02:51:54,452
POINTS DEFINING TREATMENTS,

4142
02:51:54,452 --> 02:51:55,520
SUCCESS OR FAILURE.

4143
02:51:55,520 --> 02:51:58,056
OR ANALYSIS ARE OFTEN LOOKING AT

4144
02:51:58,056 --> 02:51:59,958
DIFFERENCES IN PROPORTIONS AND I

4145
02:51:59,958 --> 02:52:02,861
WANT TO POINT OUT THAT WITH

4146
02:52:02,861 --> 02:52:04,863
BINARY DATA IN GENERAL, OUR

4147
02:52:04,863 --> 02:52:07,332
POWER IS PARTICULARLY SENSITIVE

4148
02:52:07,332 --> 02:52:10,635
TO VARIABILITY OF TREATMENT

4149
02:52:10,635 --> 02:52:12,437
EFFECTS BETWEEN SITES AND

4150
02:52:12,437 --> 02:52:13,972
BALANCES AND THE NUMBER OF

4151
02:52:13,972 --> 02:52:15,240
ANIMALS AT EACH SITE AS WELL AS

4152
02:52:15,240 --> 02:52:16,241
THE PLACEBO EFFECT.

4153
02:52:16,241 --> 02:52:17,742
THAT IS A CONSIDERATION IF WE

4154
02:52:17,742 --> 02:52:19,844
ARE TAKING CONTINUOUS DATA AND

4155
02:52:19,844 --> 02:52:24,716
TRANSFORMING IT INTO

4156
02:52:24,716 --> 02:52:25,183
SUCCESS/FAILURE.

4157
02:52:25,183 --> 02:52:28,186
THE POSITIVE BINARY COMPOSITE

4158
02:52:28,186 --> 02:52:30,455
ENDPOINTS OR DATA IN GENERAL, IS

4159
02:52:30,455 --> 02:52:32,257
THAT OFTEN WHEN WE PRE SPECIFIED

4160
02:52:32,257 --> 02:52:35,460
OUR OUTCOME WE CAN ACCOUNT FOR

4161
02:52:35,460 --> 02:52:36,661
EARLY WITHDRAWLS IN OUR

4162
02:52:36,661 --> 02:52:36,928
ANALYSIS.

4163
02:52:36,928 --> 02:52:38,363
SO THEY ARE NOT NECESSARILY

4164
02:52:38,363 --> 02:52:39,330
MISSING DATA.

4165
02:52:39,330 --> 02:52:40,665
THEY MAY BE ABLE TO BE INCLUDED

4166
02:52:40,665 --> 02:52:43,434
AS A TREATMENT FAILURE, FOR

4167
02:52:43,434 --> 02:52:43,735
EXAMPLE.

4168
02:52:43,735 --> 02:52:49,173
AND THEN FINALLY, THE THIRD KEY

4169
02:52:49,173 --> 02:52:51,175
POINT IS TIME TO EVENT DATA

4170
02:52:51,175 --> 02:52:53,211
WHERE STATISTICAL ANALYSIS IS

4171
02:52:53,211 --> 02:52:56,247
LOOKING AT SURVIVAL ANALYSIS

4172
02:52:56,247 --> 02:52:56,514
METHODS.

4173
02:52:56,514 --> 02:52:58,483
WE CAN ALSO LOOK AT THINGS LIKE

4174
02:52:58,483 --> 02:53:01,686
THE WIN RATIO IN WHICH CASE WE

4175
02:53:01,686 --> 02:53:04,889
CAN PRIORITIZE THE MOST

4176
02:53:04,889 --> 02:53:05,723
IMPORTANT ENDPOINTS.

4177
02:53:05,723 --> 02:53:08,493
THESE ARE REALLY NICE BECAUSE IF

4178
02:53:08,493 --> 02:53:10,828
WE HAVE A RARE OUTCOME, WE CAN

4179
02:53:10,828 --> 02:53:13,031
INCREASE THE NUMBER OF EXPECTED

4180
02:53:13,031 --> 02:53:14,933
EVENTS AND THEREFORE INCREASE

4181
02:53:14,933 --> 02:53:17,535
OUR POWER AND WE CAN ALSO LIKE

4182
02:53:17,535 --> 02:53:21,673
BINARY DATA, INCORPORATE EARLY

4183
02:53:21,673 --> 02:53:22,707
WITHDRAWLS.

4184
02:53:22,707 --> 02:53:24,242
SO, AGAIN, I JUST WANT TO

4185
02:53:24,242 --> 02:53:27,278
CONCLUDE BY SAYING THAT OUR --

4186
02:53:27,278 --> 02:53:29,280
AS SAID A LOT TODAY, WE WANT TO

4187
02:53:29,280 --> 02:53:30,648
BALANCE OUR STATISTICAL

4188
02:53:30,648 --> 02:53:33,685
CONSIDERATIONS WITH CLINICAL

4189
02:53:33,685 --> 02:53:34,052
CONSIDERATIONS.

4190
02:53:34,052 --> 02:53:36,854
WE LOOK - I MENTIONED P VALUES

4191
02:53:36,854 --> 02:53:38,523
AND SIGNIFICANCE BUT WE WANT TO

4192
02:53:38,523 --> 02:53:40,458
LOOK AT THE EFFECT SIZE AND

4193
02:53:40,458 --> 02:53:41,759
INTERPRETATION OF THE EFFECT

4194
02:53:41,759 --> 02:53:43,895
SIZE IN ADDITION TO THE P-VALUE.

4195
02:53:43,895 --> 02:53:46,431
IT'S REALLY IMPORTANT THAT WE IN

4196
02:53:46,431 --> 02:53:49,267
A CONFIRMATORY STUDY WE

4197
02:53:49,267 --> 02:53:50,868
PRE-SPECIFY OUR COMPOSITE

4198
02:53:50,868 --> 02:53:53,171
ENDPOINTS OR CO-PRIMARY

4199
02:53:53,171 --> 02:53:54,272
ENDPOINTS, AS WELL AS METHODS WE

4200
02:53:54,272 --> 02:53:56,441
MIGHT USE FOR OUR ADJUSTING FOR

4201
02:53:56,441 --> 02:53:57,709
MULTIPLE COMPARISONS.

4202
02:53:57,709 --> 02:54:01,346
AND WE ARE LES STRINGENT WITH

4203
02:54:01,346 --> 02:54:02,981
PRE-SPECIFICATION IN EXPLORATORY

4204
02:54:02,981 --> 02:54:04,582
STUDIES BUT WE WANT TO BE

4205
02:54:04,582 --> 02:54:05,750
CAREFUL WITH INTERPRETING

4206
02:54:05,750 --> 02:54:07,852
MULTIPLE STATISTICAL TESTS.

4207
02:54:07,852 --> 02:54:09,053
SO IT'S IMPORTANT TO THINK ABOUT

4208
02:54:09,053 --> 02:54:11,222
WHAT METHODS WE MIGHT WANT TO DO

4209
02:54:11,222 --> 02:54:13,291
TO COUNTER ACT THIS.

4210
02:54:13,291 --> 02:54:15,393
SO THANK YOU ALL FOR YOUR

4211
02:54:15,393 --> 02:54:15,893
ATTENTION.

4212
02:54:15,893 --> 02:54:26,104
[ APPLAUSE ]

4213
02:54:41,586 --> 02:54:44,188
>> GOOD AFTERNOON, I'M
EMILY

4214
02:54:44,188 --> 02:54:45,690
SUBMIT AT THE FDA CENTER FOR

4215
02:54:45,690 --> 02:54:46,357
VETERINARY MEDICINE.

4216
02:54:46,357 --> 02:54:50,795
OUR NEXT SPEAKER IS DR. HANS

4217
02:54:50,795 --> 02:54:54,766
COETZEE FROM KANSAS STATE

4218
02:54:54,766 --> 02:54:55,833
UNIVERSITY THE ASSOCIATE DEAN

4219
02:54:55,833 --> 02:54:57,168
FOR RESEARCH.

4220
02:54:57,168 --> 02:54:58,569
HE EARNED HIS BACHELOR OF

4221
02:54:58,569 --> 02:55:00,571
VETERINARY SCIENCE DEGREE FROM

4222
02:55:00,571 --> 02:55:04,375
SOUTH AFRICA AND ALSO WAS

4223
02:55:04,375 --> 02:55:06,844
AWARDED A SPECIAL CERTIFICATE IN

4224
02:55:06,844 --> 02:55:07,879
PRODUCTION FROM THE ROYAL

4225
02:55:07,879 --> 02:55:09,580
COLLEGE OF VETERINARY SURGEONS.

4226
02:55:09,580 --> 02:55:12,583
HE ALSO EARNED A DOCTORATE IN

4227
02:55:12,583 --> 02:55:14,385
VETERINARY MICROBIOLOGY AND

4228
02:55:14,385 --> 02:55:16,254
HOLDS DUAL BOARD CERTIFICATION,

4229
02:55:16,254 --> 02:55:18,990
THE AMERICAN COLLEGE OF

4230
02:55:18,990 --> 02:55:19,657
VETERINARY CLINICAL PHARMACOLOGY

4231
02:55:19,657 --> 02:55:20,892
AND THE AMERICAN COLLEGE OF

4232
02:55:20,892 --> 02:55:22,794
ANIMAL WELFARE AND A EUROPEAN

4233
02:55:22,794 --> 02:55:25,496
SPECIALIST IN ANIMAL WELFARE

4234
02:55:25,496 --> 02:55:25,897
SCIENCE.

4235
02:55:25,897 --> 02:55:27,799
I'D LIKE TO WELCOME HIM TO

4236
02:55:27,799 --> 02:55:30,501
DISCUSS EXAMPLES OF MULTIPLE AND

4237
02:55:30,501 --> 02:55:32,937
COMPOSITE ENDPOINTS.

4238
02:55:32,937 --> 02:55:36,240
[ APPLAUSE ]

4239
02:55:36,240 --> 02:55:37,041
>> THANK YOU VERY MUCH,

4240
02:55:37,041 --> 02:55:37,308
EVERYONE.

4241
02:55:37,308 --> 02:55:38,609
I APPRECIATE YOU HANGING IN

4242
02:55:38,609 --> 02:55:40,278
THERE FOR THE AFTERNOON SESSION.

4243
02:55:40,278 --> 02:55:42,046
THIS IS A PHOTOGRAPH OF THE LAB

4244
02:55:42,046 --> 02:55:46,084
FROM A FEW YEARS AGO AS

4245
02:55:46,084 --> 02:55:48,019
DR. DAVID ANDERSON WITH THE

4246
02:55:48,019 --> 02:55:49,554
CAMERA SHOOTING EXIT SPEED

4247
02:55:49,554 --> 02:55:51,522
DEVICE TO MEASURE HOW FAST THE

4248
02:55:51,522 --> 02:55:53,591
ANIMALS ARE LEAVING THE SHOOT.

4249
02:55:53,591 --> 02:55:57,628
AND THEN THERE IS ALSO THE

4250
02:55:57,628 --> 02:55:58,262
UBIQUITOUS FLYPAPER YOU REQUIRE

4251
02:55:58,262 --> 02:56:01,332
EVERY TIME YOU DO FOOD ANIMAL

4252
02:56:01,332 --> 02:56:03,434
RESEARCH TO GET THE FLIES OFF

4253
02:56:03,434 --> 02:56:04,135
THE COW.

4254
02:56:04,135 --> 02:56:06,737
IT'S PRETTY EVENTFUL OUT THERE

4255
02:56:06,737 --> 02:56:07,038
IN THE BARN.

4256
02:56:07,038 --> 02:56:08,439
SO GET READY TO SEE SOME COWS.

4257
02:56:08,439 --> 02:56:09,841
WE HAVE PLENTY OF COW EXAMPLES

4258
02:56:09,841 --> 02:56:11,843
COMING UP HERE.

4259
02:56:11,843 --> 02:56:13,511
JUST MY CURRENT DISCLOSURES.

4260
02:56:13,511 --> 02:56:15,713
I CONSULT FOR A NUMBER OF

4261
02:56:15,713 --> 02:56:16,581
DIFFERENT COMPANIES.

4262
02:56:16,581 --> 02:56:19,117
MOST OF THE WORK YOU'LL SEE

4263
02:56:19,117 --> 02:56:20,218
PRESENTED TODAY WAS FUNDED BY

4264
02:56:20,218 --> 02:56:23,588
THE USDA AND THEN I ALSO HAVE

4265
02:56:23,588 --> 02:56:26,257
RECEIVED ETHICAL OVERSIGHT FOR

4266
02:56:26,257 --> 02:56:27,758
ALL STUDIES WE WILL BE REPORTING

4267
02:56:27,758 --> 02:56:30,661
HERE THIS AFTERNOON.

4268
02:56:30,661 --> 02:56:31,462
SO MOST OF THE INFORMATION I

4269
02:56:31,462 --> 02:56:33,397
HAVE IN TERMS OF DEFINITIONS

4270
02:56:33,397 --> 02:56:35,199
COMES FROM THESE TWO SOURCES,

4271
02:56:35,199 --> 02:56:38,569
ONE ALREADY REFERENCED HERE BY

4272
02:56:38,569 --> 02:56:40,071
DR. RUBERMAN IN TERMS OF

4273
02:56:40,071 --> 02:56:41,305
DISCUSSING THE MULTIPLE

4274
02:56:41,305 --> 02:56:42,740
ENDPOINTS IN CLINICAL TRIALS

4275
02:56:42,740 --> 02:56:45,610
GUIDANCE FROM FDA AND THE OTHER

4276
02:56:45,610 --> 02:56:46,611
IS A PAREN THAT WAS PUBLISHED

4277
02:56:46,611 --> 02:56:48,679
SEVERAL YEARS AGO AND INCREDIBLE

4278
02:56:48,679 --> 02:56:50,281
USEFUL RESOURCE ON ANALYZING

4279
02:56:50,281 --> 02:56:51,616
MULTIPLE ENDPOINTS IN CLINICAL

4280
02:56:51,616 --> 02:56:52,450
TRIALS OF PAIN.

4281
02:56:52,450 --> 02:56:53,918
SO WE'LL TALK ABOUT THE

4282
02:56:53,918 --> 02:56:55,219
DEFINITIONS, THAT'S WHERE THEY

4283
02:56:55,219 --> 02:56:55,720
COME FROM.

4284
02:56:55,720 --> 02:56:59,490
I WANT TO VERY BRIEFLY COVER THE

4285
02:56:59,490 --> 02:56:59,790
DEFINITIONS.

4286
02:56:59,790 --> 02:57:01,192
I HAVE BEEN WELL SET UP BUT WHEN

4287
02:57:01,192 --> 02:57:03,294
I TALK ABOUT A PRIMARY ENDPOINT,

4288
02:57:03,294 --> 02:57:05,596
I'M TALKING ABOUT VARIABLES

4289
02:57:05,596 --> 02:57:07,231
CAPABLE OF PROVIDING THE MOST

4290
02:57:07,231 --> 02:57:09,200
CLINICALLY RELEVANT AND

4291
02:57:09,200 --> 02:57:11,736
CONVINCING EVIDENCE.

4292
02:57:11,736 --> 02:57:12,403
WHAT IS THAT?

4293
02:57:12,403 --> 02:57:13,704
THAT'S WHAT WE ARE TRYING TO

4294
02:57:13,704 --> 02:57:15,973
FIGURE OUT NOW FOR 15 YEARS.

4295
02:57:15,973 --> 02:57:18,543
I RECALL 15 YEARS AGO MICHELLE

4296
02:57:18,543 --> 02:57:20,845
INVITED ME TO THE FDA TO PRESENT

4297
02:57:20,845 --> 02:57:22,547
A STAFF COLLEGE ON PAIN

4298
02:57:22,547 --> 02:57:24,949
ASSESSMENT IN FOODANCE MALLS AND

4299
02:57:24,949 --> 02:57:26,317
WE ARE STILL WRESTLING ON WHAT

4300
02:57:26,317 --> 02:57:27,418
CONSTITUTES THAT CLINICALLY

4301
02:57:27,418 --> 02:57:30,788
RELEVANT AND CONVINCING EVIDENCE

4302
02:57:30,788 --> 02:57:33,691
FOR PROVING THIS.

4303
02:57:33,691 --> 02:57:35,159
MULTIPLE ENDPOINTS.

4304
02:57:35,159 --> 02:57:36,928
THESE ARE SIGNIFICANT RESULTS

4305
02:57:36,928 --> 02:57:37,795
TYPICALLY REQUIRED FOR SEVERAL

4306
02:57:37,795 --> 02:57:38,963
PRIMARY ENDPOINTS TO BE

4307
02:57:38,963 --> 02:57:41,098
CONSIDERED A TRIAL POSITIVE.

4308
02:57:41,098 --> 02:57:43,401
AND REQUIRING EACH OF THESE

4309
02:57:43,401 --> 02:57:44,435
ENDPOINTS TO BE SIGNIFICANT DOES

4310
02:57:44,435 --> 02:57:47,538
HAVE IMPACT IN TERMS OF THE

4311
02:57:47,538 --> 02:57:48,439
STATISTICAL POWER AS CLARED HAS

4312
02:57:48,439 --> 02:57:49,840
ALREADY TALKED ABOUT THIS

4313
02:57:49,840 --> 02:57:50,675
AFTERNOON.

4314
02:57:50,675 --> 02:57:52,543
-- CLAIRE -- IN TERMS OF

4315
02:57:52,543 --> 02:57:54,946
SECONDARY ENDPOINTS, THESE

4316
02:57:54,946 --> 02:57:56,447
PROVIDE BACKGROUND AND A GREATER

4317
02:57:56,447 --> 02:57:58,849
UNDERSTANDING OF PRIMARY

4318
02:57:58,849 --> 02:57:59,383
ENDPOINTS.

4319
02:57:59,383 --> 02:58:03,054
THEY SEPARATE COMPONENTS OF

4320
02:58:03,054 --> 02:58:04,488
COMPOSITE ENDPOINTS.

4321
02:58:04,488 --> 02:58:06,490
THEY ARE IMPORTANT GIVEN THE

4322
02:58:06,490 --> 02:58:08,125
TREATMENTS OBJECTIVES BUT FOR

4323
02:58:08,125 --> 02:58:09,961
WHICH THE STUDY MAY NOT HAVE

4324
02:58:09,961 --> 02:58:10,728
ADEQUATE POWER.

4325
02:58:10,728 --> 02:58:12,230
THEY CAN AID IN THE

4326
02:58:12,230 --> 02:58:13,631
UNDERSTANDING OF THE MECHANISM

4327
02:58:13,631 --> 02:58:14,932
OF ACTION OF THE TREATMENT.

4328
02:58:14,932 --> 02:58:18,035
THEY RELATE TO THE SECONDARY

4329
02:58:18,035 --> 02:58:19,136
HYPOTHESIS ANOTHER MAJOR

4330
02:58:19,136 --> 02:58:20,438
OBJECTIVE OF THE TREATMENT AND

4331
02:58:20,438 --> 02:58:23,541
ARE INTENDED TO BE USED FOR

4332
02:58:23,541 --> 02:58:27,678
EXPLORATORY NAN SIS.

4333
02:58:27,678 --> 02:58:27,979
 ANALYSIS.

4334
02:58:27,979 --> 02:58:29,947
AND THEN ALREADY DISCUSSED,

4335
02:58:29,947 --> 02:58:31,716
THERE ARE EXPLORATORY ENDPOINTS

4336
02:58:31,716 --> 02:58:32,483
AS WELL.

4337
02:58:32,483 --> 02:58:34,185
THESE SHOULD BE PRE-SPECIFIED,

4338
02:58:34,185 --> 02:58:38,356
OCCASIONALLY WE'LL DO SOME

4339
02:58:38,356 --> 02:58:40,391
POST-HOC ANALYSIS BUT PRE

4340
02:58:40,391 --> 02:58:41,959
SPECIFYING THE EXPLORATORY

4341
02:58:41,959 --> 02:58:43,894
ANALYSIS IS CRITICAL AND THESE

4342
02:58:43,894 --> 02:58:45,396
ARE NOT DIRECTLY RELATED TO THE

4343
02:58:45,396 --> 02:58:47,465
PRIMARY OBJECTIVE SO THEY ARE

4344
02:58:47,465 --> 02:58:48,933
HYPOTHESIS GENERATED.

4345
02:58:48,933 --> 02:58:51,168
AND THEN THE COMPOSITE

4346
02:58:51,168 --> 02:58:52,503
ENDPOINTS, MULTIPLE ENDPOINTS

4347
02:58:52,503 --> 02:58:54,372
COMBINED INTO A SINGLE VARIABLE

4348
02:58:54,372 --> 02:58:55,973
AND I'LL SHOW AN EXAMPLE AT THE

4349
02:58:55,973 --> 02:58:56,907
END OF THE PRESENTATION.

4350
02:58:56,907 --> 02:58:59,977
THIS IS USEFUL WHEN A DISEASE

4351
02:58:59,977 --> 02:59:02,179
HAS MANY CLINICALLY-IMPORTANT

4352
02:59:02,179 --> 02:59:03,481
MANIFESTATIONS AND THIS APPROACH

4353
02:59:03,481 --> 02:59:05,983
TYPICALLY INCREASES THE

4354
02:59:05,983 --> 02:59:07,018
STATISTICAL POWER AS HAS ALREADY

4355
02:59:07,018 --> 02:59:08,219
BEEN DISCUSSED.

4356
02:59:08,219 --> 02:59:09,620
HOPEFULLY THAT WILL SET US UP IN

4357
02:59:09,620 --> 02:59:10,721
TERMS OF BEING ON THE SAME PAGE

4358
02:59:10,721 --> 02:59:12,723
IN TERMS OF WHAT WE ARE TALKING

4359
02:59:12,723 --> 02:59:14,625
ABOUT WHEN WE TALK ABOUT THESE

4360
02:59:14,625 --> 02:59:17,995
DIFFERENT ENDPOINTS AND THEIR

4361
02:59:17,995 --> 02:59:18,296
APPLICATION.

4362
02:59:18,296 --> 02:59:20,498
SO WHY DO WE CARE ABOUT MULTIPLE

4363
02:59:20,498 --> 02:59:22,700
OR COMPOSITE ENDPOINTS IN PAIN

4364
02:59:22,700 --> 02:59:22,967
STUDIES?

4365
02:59:22,967 --> 02:59:25,503
IF THERE IS NOTHING ELSE YOU'RE

4366
02:59:25,503 --> 02:59:27,204
TAKING AWAY FROM THIS MEETING,

4367
02:59:27,204 --> 02:59:29,674
PAIN IS COMPLICATED.

4368
02:59:29,674 --> 02:59:31,108
WE VIOLENT YET FIGURED OUT THE

4369
02:59:31,108 --> 02:59:33,244
SINGLE ENDPOINT THAT WORKS

4370
02:59:33,244 --> 02:59:34,211
RELIABLY EVERY TIME.

4371
02:59:34,211 --> 02:59:35,713
WE TRY TO MEASURE PAIN IN THE

4372
02:59:35,713 --> 02:59:36,714
FOOD ANIMAL.

4373
02:59:36,714 --> 02:59:38,649
MOST OF THE TRIALS WE CONDUCT

4374
02:59:38,649 --> 02:59:41,385
HAVE MULTIPLE ENDPOINTS TO TRY

4375
02:59:41,385 --> 02:59:44,422
TO ASSESS PAIN AND ANALGESIC

4376
02:59:44,422 --> 02:59:46,223
DRUG EFFICACY.

4377
02:59:46,223 --> 02:59:48,326
WHEN WE HAVE MORE THAN ONE

4378
02:59:48,326 --> 02:59:49,627
ENDPOINT AND MORE THAN ONE

4379
02:59:49,627 --> 02:59:51,696
ENDPOINT IS ANALYZED IN A SINGLE

4380
02:59:51,696 --> 02:59:53,698
TRIAL, WE HAVE THIS INCREASED

4381
02:59:53,698 --> 02:59:56,901
LIKELIHOOD OF HAVING A FALSE

4382
02:59:56,901 --> 02:59:57,935
CONCLUSION ABOUT THE DRUG SO WE

4383
02:59:57,935 --> 03:00:00,838
HAVE TO MAKE THAT ADJUSTMENT FOR

4384
03:00:00,838 --> 03:00:01,872
THE MULTIPLICITY ISSUE.

4385
03:00:01,872 --> 03:00:03,040
AND SO THE GREATER THE NUMBER OF

4386
03:00:03,040 --> 03:00:04,575
THE STATISTICAL TESTS WE

4387
03:00:04,575 --> 03:00:06,143
PERFORM, THE HIGHER PROBABILITY

4388
03:00:06,143 --> 03:00:07,945
THAT ONE OR MORE OF THEM WILL

4389
03:00:07,945 --> 03:00:09,680
YIELD THE STATISTICALLY

4390
03:00:09,680 --> 03:00:10,815
SIGNIFICANT RESULTS BY CHANCE

4391
03:00:10,815 --> 03:00:11,015
ALONE.

4392
03:00:11,015 --> 03:00:13,451
SO I REALLY APPRECIATE THE FIRST

4393
03:00:13,451 --> 03:00:16,153
TWO SPEAKERS IN SETTING UP THIS

4394
03:00:16,153 --> 03:00:17,722
ASPECT OF THE PRESENTATION.

4395
03:00:17,722 --> 03:00:19,256
I WENT THROUGH THOSE PRETTY

4396
03:00:19,256 --> 03:00:20,758
QUICK BECAUSE THAT'S A RECAP OF

4397
03:00:20,758 --> 03:00:22,560
WHAT HAS ALREADY BEEN TALKED

4398
03:00:22,560 --> 03:00:24,095
ABOUT.

4399
03:00:24,095 --> 03:00:25,663
SO THE BIG DIFFERENCE IN FOOD

4400
03:00:25,663 --> 03:00:26,964
ANIMALS, OUR DOMAINS ARE

4401
03:00:26,964 --> 03:00:27,231
DIFFERENT.

4402
03:00:27,231 --> 03:00:30,267
A LOT HAS BEEN SAID TODAY AND

4403
03:00:30,267 --> 03:00:31,335
YESTERDAY ABOUT DOMAINS.

4404
03:00:31,335 --> 03:00:33,437
IN HUMAN MEDICINE, GENERALLY

4405
03:00:33,437 --> 03:00:34,939
ACCEPTED THAT THERE ARE SIX CORE

4406
03:00:34,939 --> 03:00:36,874
DOMAINS FOR ASSESSING CHRONIC

4407
03:00:36,874 --> 03:00:37,141
PAIN.

4408
03:00:37,141 --> 03:00:38,943
PAIN ITSELF, PHYSICAL

4409
03:00:38,943 --> 03:00:40,845
FUNCTIONING, EMOTIONAL

4410
03:00:40,845 --> 03:00:42,346
FUNCTIONING, PARTICIPANT RATINGS

4411
03:00:42,346 --> 03:00:44,348
OF GLOBAL IMPROVEMENT, SYMPTOMS

4412
03:00:44,348 --> 03:00:47,585
AND ADVERSE EFFECTS AND THEN

4413
03:00:47,585 --> 03:00:48,152
PARTICIPANT DISPOSITION.

4414
03:00:48,152 --> 03:00:51,288
BUT ON THE FOOD ANIMAL SIDE AS

4415
03:00:51,288 --> 03:00:52,656
MENTIONED YESTERDAY, WE TALK

4416
03:00:52,656 --> 03:00:54,191
ABOUT THESE THREE PRIMARY

4417
03:00:54,191 --> 03:00:55,559
DOMAINS WHICH ARE ALSO THE

4418
03:00:55,559 --> 03:00:57,194
DOMAINS WE ASSESS WHEN ASSESSING

4419
03:00:57,194 --> 03:00:58,562
ANIMAL WELFARE.

4420
03:00:58,562 --> 03:01:00,398
THOSE ARE BASIC HEALTH AND

4421
03:01:00,398 --> 03:01:03,067
FUNCTIONING, NATURAL LIVING AND

4422
03:01:03,067 --> 03:01:06,337
THE EFFECT OF STEPS.

4423
03:01:06,337 --> 03:01:09,073
EARLIER TODAY, IT WAS TALKED

4424
03:01:09,073 --> 03:01:11,409
ABOUT THE COMPOSITE SCALES AND

4425
03:01:11,409 --> 03:01:12,977
SEVERAL OF THOSE HAVE ALREADY

4426
03:01:12,977 --> 03:01:13,577
BEEN DESCRIBED.

4427
03:01:13,577 --> 03:01:16,447
AS TALKED ABOUT YESTERDAY, THE

4428
03:01:16,447 --> 03:01:18,783
PAIN SCALE AND FACIAL GRIMACE

4429
03:01:18,783 --> 03:01:19,884
SCALES ARE ALSO SCALES WE USE TO

4430
03:01:19,884 --> 03:01:21,786
TRY TO ASSESS THE BEHAVIORAL

4431
03:01:21,786 --> 03:01:24,088
OUTCOMES OF THOSE EFFECTIVE

4432
03:01:24,088 --> 03:01:24,321
STATES.

4433
03:01:24,321 --> 03:01:27,158
WE ALSO ASSESS NEUROENDOCRINE

4434
03:01:27,158 --> 03:01:28,492
OUTCOMES AND PHYSIOLOGICAL

4435
03:01:28,492 --> 03:01:28,893
OUTCOMES AS WELL.

4436
03:01:28,893 --> 03:01:32,096
WHEN WE TALK ABOUT FOOD ANIMALS,

4437
03:01:32,096 --> 03:01:35,232
PARTICULARLY IN ACUTE PAIN

4438
03:01:35,232 --> 03:01:36,901
SETTING AND THESE THREE PRIMARY

4439
03:01:36,901 --> 03:01:39,370
DOMAINS, HEALTH AND FUNCTIONING,

4440
03:01:39,370 --> 03:01:40,371
EFFECTIVE STATES AND THE NATURAL

4441
03:01:40,371 --> 03:01:40,604
LIVING.

4442
03:01:40,604 --> 03:01:41,972
SO IN TERMS OF HOW WE ASSESS

4443
03:01:41,972 --> 03:01:43,441
THOSE, THIS IS OUR FIRST EXAMPLE

4444
03:01:43,441 --> 03:01:45,543
OF A COM POSILATE SCALE THAT IS

4445
03:01:45,543 --> 03:01:47,611
QUITE COMMONLY USED NOW IN TERMS

4446
03:01:47,611 --> 03:01:49,947
OF TRYING TO ASSESS PAIN.

4447
03:01:49,947 --> 03:01:55,653
THIS IS THE COW PAIN SCALE

4448
03:01:55,653 --> 03:01:58,155
DESCRIBED FROM THE UNIVERSITY OF

4449
03:01:58,155 --> 03:02:00,524
IN COPENHAGEN.

4450
03:02:00,524 --> 03:02:01,559
SIX ENDPOINTS THAT THE COME OUT

4451
03:02:01,559 --> 03:02:02,259
OF THIS SCALE.

4452
03:02:02,259 --> 03:02:04,862
THE FIRST TWO OF THEM ARE

4453
03:02:04,862 --> 03:02:06,764
MEASURED ON A 0-1.

4454
03:02:06,764 --> 03:02:09,467
SO BINARY OUTCOME AND THEN THE

4455
03:02:09,467 --> 03:02:13,003
REMAINING FOUR OUTCOMES ARE

4456
03:02:13,003 --> 03:02:14,872
MEASURED ON A 3-POINT SCALE.

4457
03:02:14,872 --> 03:02:16,106
SO WHEN YOU ADD UP THOSE

4458
03:02:16,106 --> 03:02:18,442
TOGETHER, YOU END UP WITH A

4459
03:02:18,442 --> 03:02:20,044
COMPOSITE SCORE OUT OF 10.

4460
03:02:20,044 --> 03:02:21,245
THAT'S ONE OF THE SCALES THAT

4461
03:02:21,245 --> 03:02:24,048
FOLKS TRIED TO USE TO ASSESS

4462
03:02:24,048 --> 03:02:25,282
ANALGESIC DRUG EFFICACY.

4463
03:02:25,282 --> 03:02:26,550
THIS IS THE FIRST POINT OF

4464
03:02:26,550 --> 03:02:28,052
CHALLENGE FOR US FROM THE FOOD

4465
03:02:28,052 --> 03:02:29,553
ANIMAL SIDE IS WE HAVE REALLY

4466
03:02:29,553 --> 03:02:32,556
STRUGGLED TO REPRODUCE THESE IN

4467
03:02:32,556 --> 03:02:32,990
DIFFERENT SETTINGS.

4468
03:02:32,990 --> 03:02:35,292
SOMETIMES WE SAID, MAYBE IT'S A

4469
03:02:35,292 --> 03:02:36,994
SPECIFIC THING, MAYBE IT'S JUST

4470
03:02:36,994 --> 03:02:38,362
THE WAY WE RAISE CATTLE IN THE

4471
03:02:38,362 --> 03:02:39,230
UNITED STATES VERSUS EUROPE.

4472
03:02:39,230 --> 03:02:41,665
WE HAVE REALLY STRUGGLED TO GET

4473
03:02:41,665 --> 03:02:43,868
THESE ENDPOINTS AND SCALES TO BE

4474
03:02:43,868 --> 03:02:45,069
REPRODUCED RELIABLY EVERY TIME

4475
03:02:45,069 --> 03:02:46,670
WE TRY TO USE THEM.

4476
03:02:46,670 --> 03:02:48,105
WE ARE DOING MORE WORK IN THAT

4477
03:02:48,105 --> 03:02:51,275
AREA BECAUSE THERE IS MORE WORK

4478
03:02:51,275 --> 03:02:51,642
WARRANTED.

4479
03:02:51,642 --> 03:02:53,878
MY COLLEAGUE WHO IS HERE, FIRST

4480
03:02:53,878 --> 03:02:55,779
DESCRIBED THIS FACIAL GRIMACE

4481
03:02:55,779 --> 03:02:56,780
SCALE IN PIG LETS AND THIS IS

4482
03:02:56,780 --> 03:02:58,616
ANOTHER INCREDIBLY USEFUL SCALE

4483
03:02:58,616 --> 03:03:00,384
IN TERMS OF TRYING TO ASSESS

4484
03:03:00,384 --> 03:03:03,888
PAIN USING A BEHAVIOR SCALE IN

4485
03:03:03,888 --> 03:03:04,088
PIGS.

4486
03:03:04,088 --> 03:03:05,389
THE CHALLENGE WITH THIS IS

4487
03:03:05,389 --> 03:03:08,092
HAVING ALL THE TESTERS, WE

4488
03:03:08,092 --> 03:03:10,528
STRUGGLE TO RECRUIT STUDENTS IN

4489
03:03:10,528 --> 03:03:11,428
THE NYE LAB BECAUSE NO ONE LIKES

4490
03:03:11,428 --> 03:03:13,731
WATCHING THE VIDEOS WHEN LOOKING

4491
03:03:13,731 --> 03:03:14,598
AT DIFFERENT ENDPOINTS.

4492
03:03:14,598 --> 03:03:16,901
THESE SCALES ARE VERY, VERY TIME

4493
03:03:16,901 --> 03:03:19,803
CONSUMING TO ANALYZE AND I WAS

4494
03:03:19,803 --> 03:03:21,572
ENCOURAGED BY THE DISCUSSION

4495
03:03:21,572 --> 03:03:22,840
ABOUT MACHINE LEARNING YESTERDAY

4496
03:03:22,840 --> 03:03:25,075
THAT THERE MAY BE SOME MACHINE

4497
03:03:25,075 --> 03:03:26,477
LEARNING OPPORTUNITIES FOR US TO

4498
03:03:26,477 --> 03:03:28,512
BE ABLE TO AUTOMATE THESE

4499
03:03:28,512 --> 03:03:29,580
SCALES.

4500
03:03:29,580 --> 03:03:30,848
BUT ABI'S WORK IS OUT STANDING

4501
03:03:30,848 --> 03:03:33,117
IN MOVING THE SCALE FORWARD IN

4502
03:03:33,117 --> 03:03:34,218
TERMS OF UNDERSTANDING HOW WE

4503
03:03:34,218 --> 03:03:36,287
MIGHT BE ABLE TO MEASURE PAIN IN

4504
03:03:36,287 --> 03:03:38,589
PIG LETS BUT IT SURE WOULD BE

4505
03:03:38,589 --> 03:03:39,924
GREAT IF WE COULD AUTOMATE THAT.

4506
03:03:39,924 --> 03:03:41,125
THEN IN TERMS OF SOME OF THE

4507
03:03:41,125 --> 03:03:42,760
OTHER SCALES THAT ARE OUT THERE.

4508
03:03:42,760 --> 03:03:45,029
THE SCALE THAT IS USED MOST

4509
03:03:45,029 --> 03:03:46,697
COMMONLY BY -- THE ONE WE PUT IN

4510
03:03:46,697 --> 03:03:49,233
THE HANDS OF FARMERS AND SAID,

4511
03:03:49,233 --> 03:03:52,937
USE THIS SCALE, IS WHAT IS KNOWN

4512
03:03:52,937 --> 03:03:53,938
AS THE [ INAUDIBLE ]

4513
03:03:53,938 --> 03:03:54,171
SYSTEM.

4514
03:03:54,171 --> 03:03:55,172
THIS WAS DESCRIBED IN THE

4515
03:03:55,172 --> 03:03:57,608
JOURNAL OF THEORY GENEALOGY.

4516
03:03:57,608 --> 03:04:00,210
IT HAS NOTHING TO DO WITH ANIMAL

4517
03:04:00,210 --> 03:04:01,211
WELFARE BUT WAS DESCRIBED

4518
03:04:01,211 --> 03:04:02,813
SEVERAL YEARS AGO AND WIDELY

4519
03:04:02,813 --> 03:04:04,949
ADOPTED BY THE DAIRY INDUSTRY

4520
03:04:04,949 --> 03:04:07,117
AND A 5-POINT SCALE FOCUSING ON

4521
03:04:07,117 --> 03:04:09,420
THE BACK OF THE ANIMAL AND WHAT

4522
03:04:09,420 --> 03:04:10,821
ITS FEET ARE DOING.

4523
03:04:10,821 --> 03:04:12,423
IF THEIR BACK ARCHES, THE FIRST

4524
03:04:12,423 --> 03:04:14,792
SIGN OF TROUBLE IN TERMS OF

4525
03:04:14,792 --> 03:04:15,059
LAMENESS.

4526
03:04:15,059 --> 03:04:16,727
IF THE BACK ARCHES AND THE

4527
03:04:16,727 --> 03:04:18,929
ANIMAL STARTS TO WALK WITH A

4528
03:04:18,929 --> 03:04:20,631
SHORT STRIDE, WE SEE PROGRESSION

4529
03:04:20,631 --> 03:04:21,865
IN LAMENESS AND THEN WHEN WE SEE

4530
03:04:21,865 --> 03:04:23,734
THE ANIMAL FAVORING THE LIMB AND

4531
03:04:23,734 --> 03:04:25,469
SCORES 4-5, THAT'S WHEN WE RUN

4532
03:04:25,469 --> 03:04:27,538
INTO ISSUES AND 5 IS WHERE THE

4533
03:04:27,538 --> 03:04:29,139
ANIMAL IS NON-WEIGHT BEARING.

4534
03:04:29,139 --> 03:04:30,741
THIS IS A SCALE THAT HAS BEEN

4535
03:04:30,741 --> 03:04:32,743
EASIEST FOR IMPLEMENT ON FARMS

4536
03:04:32,743 --> 03:04:33,978
BECAUSE IT'S VERY

4537
03:04:33,978 --> 03:04:34,345
STRAIGHTFORWARD.

4538
03:04:34,345 --> 03:04:37,648
WE BASICALLY LOOK AT THE BACK,

4539
03:04:37,648 --> 03:04:38,282
LOOKING AT THE STRIDE LENGTH AND

4540
03:04:38,282 --> 03:04:39,516
THE FEET AND WE'RE DONE.

4541
03:04:39,516 --> 03:04:41,251
SO, THAT'S BEEN REPRODUCED

4542
03:04:41,251 --> 03:04:42,853
SEVERAL TIMES IN DIFFERENT

4543
03:04:42,853 --> 03:04:44,455
STUDIES AND HAS BEEN USED SOME

4544
03:04:44,455 --> 03:04:46,657
IN ANALGESIC STUDIES AS I WILL

4545
03:04:46,657 --> 03:04:47,358
SHOW IN A MOMENT.

4546
03:04:47,358 --> 03:04:48,859
THIS THE IS A SCALE THAT

4547
03:04:48,859 --> 03:04:51,228
DR. LUNA TALKED ABOUT.

4548
03:04:51,228 --> 03:04:53,764
THIS WAS THE ONE DEVELOPED AND

4549
03:04:53,764 --> 03:04:57,668
LOOKING AT LOCOMOTION BEHAVIORS,

4550
03:04:57,668 --> 03:04:59,703
ACTIVITY, APPETITE,

4551
03:04:59,703 --> 03:05:01,772
MISCELLANEOUS ACTIVITIES AND

4552
03:05:01,772 --> 03:05:03,974
GIVING COMPOSITE SCORE OUT OF 10

4553
03:05:03,974 --> 03:05:06,143
WHEN YOU ADD THE CATEGORIES

4554
03:05:06,143 --> 03:05:06,410
TOGETHER.

4555
03:05:06,410 --> 03:05:09,880
THESE SCORES ARE SIMILAR.

4556
03:05:09,880 --> 03:05:12,383
THIS IS THE UCPS IS ON THE LEFT

4557
03:05:12,383 --> 03:05:15,252
AND CPS IS ON THE RIGHT AND THE

4558
03:05:15,252 --> 03:05:17,187
BEHAVIORS ARE SUMMARIZED IN THE

4559
03:05:17,187 --> 03:05:18,122
COLUMN TO YOUR RIGHT.

4560
03:05:18,122 --> 03:05:20,491
AND YOU'LL NOTICE THAT MOST OF

4561
03:05:20,491 --> 03:05:22,526
THE FOCUS IN BOTH SCORING

4562
03:05:22,526 --> 03:05:24,395
SYSTEMS ARE BASED ON THE

4563
03:05:24,395 --> 03:05:25,262
ATTENTION AND INTERACTION THAT

4564
03:05:25,262 --> 03:05:28,465
THE ANIMAL HAS WITH ITS

4565
03:05:28,465 --> 03:05:29,299
ENVIRONMENT BACK POSITION IS

4566
03:05:29,299 --> 03:05:30,434
IMPORTANT AND THESE TWO SCORES

4567
03:05:30,434 --> 03:05:30,934
AS WELL.

4568
03:05:30,934 --> 03:05:35,205
THE HEAD POSITION IS ALSO

4569
03:05:35,205 --> 03:05:36,040
EXAMINED IN THE TWO SCORING

4570
03:05:36,040 --> 03:05:37,708
SYSTEMS AND MOVEMENT WITH OR

4571
03:05:37,708 --> 03:05:39,710
WITHOUT STIMULATION IS REALLY

4572
03:05:39,710 --> 03:05:41,845
THE FOURTH AREA THAT IS

4573
03:05:41,845 --> 03:05:42,146
SUMMARIZED.

4574
03:05:42,146 --> 03:05:43,714
SOME OF THE BEHAVIORS THAT ARE

4575
03:05:43,714 --> 03:05:45,349
NOT CONSERVED ACROSS THE TWO

4576
03:05:45,349 --> 03:05:47,651
SCORING SYSTEMS, BUT ALL OF THIS

4577
03:05:47,651 --> 03:05:48,919
DISTILLS DOWN TO THE MAIN

4578
03:05:48,919 --> 03:05:49,253
ENDPOINTS.

4579
03:05:49,253 --> 03:05:50,821
WHAT IS THE ANIMAL DOING?

4580
03:05:50,821 --> 03:05:52,523
HOW IS IT BEHAVING IN ITS

4581
03:05:52,523 --> 03:05:52,823
ENVIRONMENT?

4582
03:05:52,823 --> 03:05:55,626
DOES IT MOVE WITHOUT

4583
03:05:55,626 --> 03:05:56,126
STIMULATION?

4584
03:05:56,126 --> 03:05:57,227
WHAT'S THE HEAD POSITION?

4585
03:05:57,227 --> 03:06:00,064
THOSE ARE THE AREAS WE FOCUS ON.

4586
03:06:00,064 --> 03:06:02,066
THE ONE WE USED QUITE COMMONLY

4587
03:06:02,066 --> 03:06:05,369
IN MY LAB HAS BEEN BASICALLY

4588
03:06:05,369 --> 03:06:06,937
DOING A VAS SCORE.

4589
03:06:06,937 --> 03:06:11,842
SO THERE ARE TWO CALFS.

4590
03:06:11,842 --> 03:06:12,710
PEN A AND PEN B.

4591
03:06:12,710 --> 03:06:14,878
AND THE ONCE YOU CAN ACCLAMATE

4592
03:06:14,878 --> 03:06:15,913
TO THE SEA SICKNESS OF THE

4593
03:06:15,913 --> 03:06:17,481
CAMERA MOVING UP AND DOWN, YOU

4594
03:06:17,481 --> 03:06:19,083
MIGHT BE ABLE TO HAVE A LOOK AT

4595
03:06:19,083 --> 03:06:22,453
THOSE TWO PENS OF CALFS AND

4596
03:06:22,453 --> 03:06:24,221
FAIRLY QUICKLY PERHAPS PROVIDE

4597
03:06:24,221 --> 03:06:25,422
AN ASSESSMENT FOR ME.

4598
03:06:25,422 --> 03:06:27,257
THE INTERACTIVE PART HERE.

4599
03:06:27,257 --> 03:06:30,094
WHO BELIEVES THAT PEN A RECEIVED

4600
03:06:30,094 --> 03:06:32,229
AN ANALGESIC DRUG BEFORE THEY

4601
03:06:32,229 --> 03:06:34,031
WERE CASTRATED?

4602
03:06:34,031 --> 03:06:34,932
SHOW OF HANDS.

4603
03:06:34,932 --> 03:06:37,534
NON RESPONDERS?

4604
03:06:37,534 --> 03:06:39,436
PEN B.

4605
03:06:39,436 --> 03:06:40,437
ANY TAKERS FOR PEN B?

4606
03:06:40,437 --> 03:06:41,739
NOT VERY MANY TAKERS.

4607
03:06:41,739 --> 03:06:42,773
ONE FOR PEN B.

4608
03:06:42,773 --> 03:06:44,441
THE DIFFERENCE WITH PEN B, A LOT

4609
03:06:44,441 --> 03:06:46,210
OF THOSE ANIMALS ARE NOT COMING

4610
03:06:46,210 --> 03:06:48,145
UP TO THE GATE TO SEE WHAT THE

4611
03:06:48,145 --> 03:06:49,379
PERSON WITH THE CAMERA IS DOING.

4612
03:06:49,379 --> 03:06:51,749
WE SEE A LOT OF ARCHED BACKS IN

4613
03:06:51,749 --> 03:06:52,316
PEN B.

4614
03:06:52,316 --> 03:06:53,751
PEN B IS THE GROUP THAT DIDN'T

4615
03:06:53,751 --> 03:06:55,586
GET ANY ANALGESIA.

4616
03:06:55,586 --> 03:06:57,988
THOSE ANIMALS ARE NOT SUPER

4617
03:06:57,988 --> 03:06:58,288
INTERACTIVE.

4618
03:06:58,288 --> 03:06:59,923
PEN A ALTHOUGH THERE ARE A FEW

4619
03:06:59,923 --> 03:07:02,559
ANIMALS STANDING WITH ABNORMAL

4620
03:07:02,559 --> 03:07:03,994
GATE, MAJORITY OF COMING UP AND

4621
03:07:03,994 --> 03:07:05,095
REALLY INTERESTED IN THE PERSON

4622
03:07:05,095 --> 03:07:06,396
TAKING THE VIDEO.

4623
03:07:06,396 --> 03:07:08,198
AND SO WE WERE ABLE TO SCALE

4624
03:07:08,198 --> 03:07:12,402
THIS ON A 0-10 LINE AND THAT

4625
03:07:12,402 --> 03:07:14,705
GIVES US A CONTINUOUS SCALE

4626
03:07:14,705 --> 03:07:18,776
OUTCOME THAT WE CAN THEN ANALYZE

4627
03:07:18,776 --> 03:07:20,677
USING A MIXED MODEL.

4628
03:07:20,677 --> 03:07:21,812
THESE ARE SOME OF THE BEHAVIORAL

4629
03:07:21,812 --> 03:07:23,213
ENDPOINTS WE MEASURED AND SOME

4630
03:07:23,213 --> 03:07:25,349
OF THOSE LEND THEMSELVES TO

4631
03:07:25,349 --> 03:07:28,118
BEING EITHER PART OF MULTIPLE

4632
03:07:28,118 --> 03:07:29,219
ENDPOINTS ANALYSIS OR THEY CAN

4633
03:07:29,219 --> 03:07:33,257
BE PART OF A COMPOSITE ANALYSIS

4634
03:07:33,257 --> 03:07:33,657
THEMSELVES.

4635
03:07:33,657 --> 03:07:35,826
IN TERMS OF THE ENDPOINTS, WE

4636
03:07:35,826 --> 03:07:39,496
COMMONLY MEASURE, THIS IS JUST A

4637
03:07:39,496 --> 03:07:40,597
SNAPSHOT OF SOME OF THE

4638
03:07:40,597 --> 03:07:42,132
ENDPOINTS THAT WE FOCUS ON WHEN

4639
03:07:42,132 --> 03:07:45,736
WE TRY TO ASSESS PAIN IN COWS.

4640
03:07:45,736 --> 03:07:47,604
SO ON THE TOP LEFT CORNER, THAT

4641
03:07:47,604 --> 03:07:48,806
IS INFRARED.

4642
03:07:48,806 --> 03:07:50,207
IF YOU LOOK AT THAT CALF AND

4643
03:07:50,207 --> 03:07:51,542
WATCH THE VIDEO FOR A LITTLE

4644
03:07:51,542 --> 03:07:53,544
BIT, YOU'LL SEE THAT THERE IS A

4645
03:07:53,544 --> 03:07:55,846
POINT WHERE THE COLOR CHANGES

4646
03:07:55,846 --> 03:07:57,080
FROM BRIGHT RED COLORS

4647
03:07:57,080 --> 03:07:58,382
INDICATING VERY GOOD PROFUSION

4648
03:07:58,382 --> 03:08:00,584
OF THE SKIN TO GREENS AND

4649
03:08:00,584 --> 03:08:01,318
YELLOWS, WHICH JUST HAPPENED IN

4650
03:08:01,318 --> 03:08:02,119
THAT VIDEO.

4651
03:08:02,119 --> 03:08:05,022
AND THAT'S THE POINT OF SURGICAL

4652
03:08:05,022 --> 03:08:05,322
CASTRATION.

4653
03:08:05,322 --> 03:08:07,891
WHAT WE ARE MEASURING THERE IS

4654
03:08:07,891 --> 03:08:11,128
EPINEPHRINE RELEASE CAUSING

4655
03:08:11,128 --> 03:08:12,329
PHASEO CONSTRUCTION RESULTS THE

4656
03:08:12,329 --> 03:08:14,064
BLOOD FLOW MOVING AWAY FROM THE

4657
03:08:14,064 --> 03:08:16,934
SKIN, CAUSING THE SKIN TO COOL.

4658
03:08:16,934 --> 03:08:18,669
WE CAN CAPTURE THAT AND MODEL

4659
03:08:18,669 --> 03:08:20,904
THOSE DATA USING SOME RESEARCH

4660
03:08:20,904 --> 03:08:21,171
SOFTWARE.

4661
03:08:21,171 --> 03:08:23,273
AND SO THE IRT IS PROVEN TO BE

4662
03:08:23,273 --> 03:08:25,475
QUITE A USEFUL TOOL IN SOME OF

4663
03:08:25,475 --> 03:08:27,177
THESE MULTIPLE ENDPOINT STUDIES.

4664
03:08:27,177 --> 03:08:31,248
AND WE HAVE MECHANICAL

4665
03:08:31,248 --> 03:08:32,082
THRESHOLD, ALL RIGHT RATE,

4666
03:08:32,082 --> 03:08:34,151
SUBSTANCE P ANALYSIS,

4667
03:08:34,151 --> 03:08:36,386
ACCELEROMETERS, DATA ANALYSIS

4668
03:08:36,386 --> 03:08:38,255
FOR THE PRESSURE MAP WE'LL TALK

4669
03:08:38,255 --> 03:08:38,455
ABOUT.

4670
03:08:38,455 --> 03:08:39,389
MEASURING SPEED AT WHICH THEY

4671
03:08:39,389 --> 03:08:41,158
LEAVE THE SHOOT WITH BARREL

4672
03:08:41,158 --> 03:08:41,491
RACING TIMERS.

4673
03:08:41,491 --> 03:08:44,528
SO YOU HAVE TO BE IN KANSAS FOR

4674
03:08:44,528 --> 03:08:44,928
THAT.

4675
03:08:44,928 --> 03:08:46,697
THIS IS TWO BARREL RACING TIMERS

4676
03:08:46,697 --> 03:08:48,098
SET UP TO MEASURE THE SPEED THE

4677
03:08:48,098 --> 03:08:50,801
ANIMAL IS LEAVING THE SHOOT.

4678
03:08:50,801 --> 03:08:51,368
WE MEASURE CORTISOL AND DONE

4679
03:08:51,368 --> 03:08:54,671
WORK WITH EEGs AS WELL.

4680
03:08:54,671 --> 03:08:56,673
LOTS OF ENDPOINTS WE MEASURE IN

4681
03:08:56,673 --> 03:08:59,576
FOOD ANIMALS SO THAT IS WHAT OUR

4682
03:08:59,576 --> 03:09:02,946
BOARD LOOKS LIKE.

4683
03:09:02,946 --> 03:09:05,983
WE THESE HAVE ALL HELPED US TO

4684
03:09:05,983 --> 03:09:06,917
GENERATE HYPOTHESES.

4685
03:09:06,917 --> 03:09:08,719
SO THE COLOR-CODING HERE IN A

4686
03:09:08,719 --> 03:09:11,588
SCALE OF THINGS THAT REALLY

4687
03:09:11,588 --> 03:09:13,156
HAVEN'T SERVED US WELL IN TERMS

4688
03:09:13,156 --> 03:09:16,159
OF MULTIPLE ENDPOINT STUDIES,

4689
03:09:16,159 --> 03:09:17,494
AND THEN THINGS THAT ARE USEFUL

4690
03:09:17,494 --> 03:09:18,962
AND THINGS THAT ARE PROVEN

4691
03:09:18,962 --> 03:09:22,633
USEFUL AS PRIMARY ENDPOINTS,

4692
03:09:22,633 --> 03:09:23,367
THERMOGRAPHY AND PRESSURE MAT

4693
03:09:23,367 --> 03:09:23,734
ANALYSIS.

4694
03:09:23,734 --> 03:09:25,102
THERE ARE LOTS OF WORK TO BE

4695
03:09:25,102 --> 03:09:25,836
DONE IN THIS SPACE STILL IN

4696
03:09:25,836 --> 03:09:28,272
TERMS OF TRYING TO REFINE THE

4697
03:09:28,272 --> 03:09:29,706
MEASUREMENT OF THESE ENDPOINTS.

4698
03:09:29,706 --> 03:09:32,109
IT HAS ELECTRODERMAL ACTIVITIES

4699
03:09:32,109 --> 03:09:33,710
NOT BEING USEFUL.

4700
03:09:33,710 --> 03:09:35,045
EXIT SPEED HASN'T EITHER AND

4701
03:09:35,045 --> 03:09:36,613
GROWTH AND PERFORMANCE IS NOT

4702
03:09:36,613 --> 03:09:37,214
USEFUL EITHER.

4703
03:09:37,214 --> 03:09:39,683
SO IN TERMS OF HOW WE DETERMINE

4704
03:09:39,683 --> 03:09:41,051
THE OPTIMAL PRIMARY ENDPOINT,

4705
03:09:41,051 --> 03:09:44,588
THIS WAS MENTIONED YESTERDAY IN

4706
03:09:44,588 --> 03:09:47,691
A PRESENTATION.

4707
03:09:47,691 --> 03:09:51,094
THIS IS WORK DONE THAT USED ROC

4708
03:09:51,094 --> 03:09:52,829
CURVES TO OPTIMIZE THE ENDPOINTS

4709
03:09:52,829 --> 03:09:54,598
WE COULD MEASURE IN TERMS OF

4710
03:09:54,598 --> 03:09:56,500
ASSESSING PRIMARY ENDPOINTS.

4711
03:09:56,500 --> 03:09:58,702
FOR CASTRATION, DEHORNING AND

4712
03:09:58,702 --> 03:10:01,705
MAINTENANCE, PLASMA CORTISOL

4713
03:10:01,705 --> 03:10:02,606
STILL CAME OUT ON TOP.

4714
03:10:02,606 --> 03:10:05,375
WE ROLE OUR ICE ON CORTISOL

4715
03:10:05,375 --> 03:10:06,109
BECAUSE IT'S NOT REALLY PAIN

4716
03:10:06,109 --> 03:10:08,178
SPECIFIC, IT IS VERY, VERY

4717
03:10:08,178 --> 03:10:09,313
SUSCEPTIBLE TO THE EFFECTS OF

4718
03:10:09,313 --> 03:10:10,514
ANALGESIC DRUG AND GIVES US

4719
03:10:10,514 --> 03:10:13,083
PRETTY GOOD SENSITIVITY AND

4720
03:10:13,083 --> 03:10:14,084
SPECIFICITY ACROSS DIFFERENT

4721
03:10:14,084 --> 03:10:16,119
STUDIES THAT WE ASSESSED.

4722
03:10:16,119 --> 03:10:19,289
FOR ABDOMINAL STUDY, IRT PROVED

4723
03:10:19,289 --> 03:10:25,195
TO HAVE THE HIGHEST AUC UNDER

4724
03:10:25,195 --> 03:10:26,196
THE RAW CARVE AT .73.

4725
03:10:26,196 --> 03:10:28,398
WE STILL HAVE SOME WORK TO DO IN

4726
03:10:28,398 --> 03:10:30,834
TERMS OF REFINING ENDPOINTS.

4727
03:10:30,834 --> 03:10:32,436
CORTISOL IS STILL THE MOST

4728
03:10:32,436 --> 03:10:34,438
WIDELY REPORTED ENDPOINT IN FOOD

4729
03:10:34,438 --> 03:10:40,010
ANIMAL MEDICINE IN TERMS OF

4730
03:10:40,010 --> 03:10:40,844
MEASURING PAIN.

4731
03:10:40,844 --> 03:10:42,346
TO SWITCH TO THE BEST EXAMPLE OF

4732
03:10:42,346 --> 03:10:47,351
A MULTIPLE ENDPOINT SCENARIO WAS

4733
03:10:47,351 --> 03:10:48,118
THE APPROVAL OF BANT MEAN

4734
03:10:48,118 --> 03:10:49,219
TRANSDERMAL.

4735
03:10:49,219 --> 03:10:52,723
OR TRANSDERMAL FORMULATION FOR

4736
03:10:52,723 --> 03:10:53,423
SYSTEMIC ABSORPTION THROUGH THE

4737
03:10:53,423 --> 03:10:54,057
SKIN.

4738
03:10:54,057 --> 03:10:57,227
SO THIS IS GUIDANCE 123 FROM FDA

4739
03:10:57,227 --> 03:10:59,663
IN WHICH SECTION 6 ON LABELING

4740
03:10:59,663 --> 03:11:01,431
SPECIFIES THE USE OF VALIDATED

4741
03:11:01,431 --> 03:11:03,133
METHODS OF PAIN ASSESSMENT IN

4742
03:11:03,133 --> 03:11:05,168
THE TARGET SPECIES THAT ARE

4743
03:11:05,168 --> 03:11:06,903
ENCOURAGED AND RECOMMENDED FOR

4744
03:11:06,903 --> 03:11:09,172
THE ASSESSMENT OF PAIN.

4745
03:11:09,172 --> 03:11:11,108
SO PRIOR TO 2017, WE STRUGGLED

4746
03:11:11,108 --> 03:11:13,076
TO COME UP WITH THESE VALIDATED

4747
03:11:13,076 --> 03:11:15,879
METHODS OF PAIN ASSESSMENT.

4748
03:11:15,879 --> 03:11:17,848
BUT THEN THERE WAS THIS APPROVAL

4749
03:11:17,848 --> 03:11:19,483
AND I'LL WALK YOU THROUGH THAT

4750
03:11:19,483 --> 03:11:20,751
THAT GAVE US SOME GUIDANCE IN

4751
03:11:20,751 --> 03:11:23,954
TERMS OF HOW WE MIGHT USE

4752
03:11:23,954 --> 03:11:25,956
MULTIPLE ENDPOINTS IN PAIN

4753
03:11:25,956 --> 03:11:27,257
STUDIES IN FOOD ANIMALS.

4754
03:11:27,257 --> 03:11:29,059
SO THAT'S THE FOI AND THAT'S

4755
03:11:29,059 --> 03:11:30,160
WHAT THE DRUG LOOKS LIKE.

4756
03:11:30,160 --> 03:11:31,962
IT'S A PINK LIQUID APPLIED

4757
03:11:31,962 --> 03:11:33,463
TOPICALLY TO THE BACK AND THEN

4758
03:11:33,463 --> 03:11:34,865
ABSORBED THROUGH THE SKIN OF THE

4759
03:11:34,865 --> 03:11:37,601
ANIMAL AND THIS DRUG IS LABELED

4760
03:11:37,601 --> 03:11:40,003
FOR THE ALLEVIATION OF PAIN

4761
03:11:40,003 --> 03:11:41,605
ASSOCIATED WITH FOOT ROT IN

4762
03:11:41,605 --> 03:11:42,472
CATTLE.

4763
03:11:42,472 --> 03:11:45,208
SO THIS IS A GCP STUDY.

4764
03:11:45,208 --> 03:11:46,777
TWO DIFFERENT SITES AT WHICH THE

4765
03:11:46,777 --> 03:11:48,178
STUDY WAS CONDUCTED.

4766
03:11:48,178 --> 03:11:50,080
15 ANIMALS IN EACH TREATMENT

4767
03:11:50,080 --> 03:11:51,148
GROUP.

4768
03:11:51,148 --> 03:11:52,215
30 ANIMALS AT EACH SITE.

4769
03:11:52,215 --> 03:11:55,185
AND BASICALLY THE OVERALL DESIGN

4770
03:11:55,185 --> 03:11:58,021
OF THE STUDY IS THAT THERE WAS A

4771
03:11:58,021 --> 03:11:59,489
LAMENESS INDUCTION THAT OCCURRED

4772
03:11:59,489 --> 03:12:01,191
AT ABOUT 48 HOURS BEFORE

4773
03:12:01,191 --> 03:12:03,994
TREATMENT WAS EXPECTED TO OCCUR.

4774
03:12:03,994 --> 03:12:08,365
LAMENESS WAS INDUCED WITH THE

4775
03:12:08,365 --> 03:12:08,632
INJECTION.

4776
03:12:08,632 --> 03:12:10,333
AT APPROXIMATELY 48 HOURS AFTER

4777
03:12:10,333 --> 03:12:12,135
THE INJECTION, THOSE ANIMALS MET

4778
03:12:12,135 --> 03:12:18,008
THE ENTRY CRITERIA IF THEY HAD

4779
03:12:18,008 --> 03:12:19,009
LAMENESS SCORE AT 3.

4780
03:12:19,009 --> 03:12:22,412
A LESION SCORE OF 2-3 AND A

4781
03:12:22,412 --> 03:12:23,847
SWELLING SCORE OF 2-3.

4782
03:12:23,847 --> 03:12:25,615
AND AT THAT POINT IN TIME, THE

4783
03:12:25,615 --> 03:12:27,651
ANIMALS THAT MET THOSE INCLUSION

4784
03:12:27,651 --> 03:12:29,453
CRITERIA WERE RANDOMIZED TO

4785
03:12:29,453 --> 03:12:35,358
TREATMENT AND THEY RECEIVED

4786
03:12:35,358 --> 03:12:36,827
EITHER THIS OR A DYE.

4787
03:12:36,827 --> 03:12:38,228
AT SIX HOURS AFTER TREATMENT,

4788
03:12:38,228 --> 03:12:39,629
THE OUTCOME MEASURES WERE TAKEN

4789
03:12:39,629 --> 03:12:41,031
AT THAT POINT IN TIME.

4790
03:12:41,031 --> 03:12:43,433
SO TWO PHASES TO THIS STUDY.

4791
03:12:43,433 --> 03:12:45,202
THE INITIAL INDUCTION PHASE

4792
03:12:45,202 --> 03:12:47,771
WHERE THE ANIMALS WERE EXPOSED

4793
03:12:47,771 --> 03:12:49,473
TO THE BACTERIUM AND BECAME

4794
03:12:49,473 --> 03:12:49,673
LAME.

4795
03:12:49,673 --> 03:12:52,042
ONCE THEY MET THE ENTRY CRITERIA

4796
03:12:52,042 --> 03:12:53,343
FOR LAMENESS, THEY WERE

4797
03:12:53,343 --> 03:12:54,144
RANDOMIZED INTO TREATMENT GROUPS

4798
03:12:54,144 --> 03:12:56,847
AND THE OUTCOME MEASURES WERE

4799
03:12:56,847 --> 03:12:58,582
TAKEN AT SIX HOURS AFTER.

4800
03:12:58,582 --> 03:12:59,816
SO THE LAMENESS SCORING SYSTEM

4801
03:12:59,816 --> 03:13:01,651
IS WHAT I DESCRIBED PREVIOUSLY.

4802
03:13:01,651 --> 03:13:02,953
IT LOOKS SPECIFICALLY AT THE

4803
03:13:02,953 --> 03:13:04,488
ANIMALS WALKING OR STANDING WITH

4804
03:13:04,488 --> 03:13:07,958
A STRAIGHT BACK OR ARCHED BACK

4805
03:13:07,958 --> 03:13:09,860
AND THEN AT THE HEAD, NOT WEIGHT

4806
03:13:09,860 --> 03:13:11,761
BEARING OR FAVORING A LIMB.

4807
03:13:11,761 --> 03:13:15,265
SO THE SAME 5-POINT SCALE.

4808
03:13:15,265 --> 03:13:16,900
THE OTHER ENDPOINT THAT WAS

4809
03:13:16,900 --> 03:13:20,337
MEASURED HERE WAS THE DATA

4810
03:13:20,337 --> 03:13:21,705
ANALYSIS THAT WAS PERFORMED WITH

4811
03:13:21,705 --> 03:13:23,173
THE PRESSURE MAT.

4812
03:13:23,173 --> 03:13:25,575
LAMENESS WAS SCORED PRIOR TO

4813
03:13:25,575 --> 03:13:26,977
INDUCTION AND THEN A DAY AFTER

4814
03:13:26,977 --> 03:13:27,878
PRIOR TO ENROLLMENT.

4815
03:13:27,878 --> 03:13:30,046
SO APPROXIMATELY 48 HOURS AFTER

4816
03:13:30,046 --> 03:13:30,313
INDUCTION.

4817
03:13:30,313 --> 03:13:32,182
AND THEN THE ANIMALS WERE

4818
03:13:32,182 --> 03:13:33,583
TREATED AND LAMENESS WAS SCORED

4819
03:13:33,583 --> 03:13:35,685
AGAIN AT 6 HOURS AFTER

4820
03:13:35,685 --> 03:13:35,986
TREATMENT.

4821
03:13:35,986 --> 03:13:38,688
AND SO THIS REALTIME DATA

4822
03:13:38,688 --> 03:13:40,190
ANALYSIS SYSTEM WAS USED TO

4823
03:13:40,190 --> 03:13:43,426
EVALUATE THE MAXIMUM FORCE

4824
03:13:43,426 --> 03:13:44,027
APPLIED TO THE LAME FLOOR AND

4825
03:13:44,027 --> 03:13:45,495
THEN THE CONTACT AREA AT THE

4826
03:13:45,495 --> 03:13:47,397
TIME OF THE MAXIMUM FORCE

4827
03:13:47,397 --> 03:13:47,631
APPLIED.

4828
03:13:47,631 --> 03:13:48,732
THIS IS AN EXAMPLE HERE.

4829
03:13:48,732 --> 03:13:50,867
NOT FROM THIS STUDY BUT THIS IS

4830
03:13:50,867 --> 03:13:52,402
ANIMAL CROSSING OVER THE

4831
03:13:52,402 --> 03:13:55,005
PRESSURE MAT SHOWING THE FOOT

4832
03:13:55,005 --> 03:13:57,674
FALLS USED TO ASSESS THE MAXIMUM

4833
03:13:57,674 --> 03:14:00,076
TOTAL FORCE IN THE CONTACT AREA.

4834
03:14:00,076 --> 03:14:02,812
SO THE TREATMENT SUCCESS

4835
03:14:02,812 --> 03:14:04,047
CRITERIA STATISTICALLY

4836
03:14:04,047 --> 03:14:05,382
SIGNIFICANT DIFFERENCE OF

4837
03:14:05,382 --> 03:14:06,983
TREATMENT SUCCESS BETWEEN

4838
03:14:06,983 --> 03:14:09,686
TREATED AND CONTROLLED GROUPS

4839
03:14:09,686 --> 03:14:10,987
WAS ASSESSED SIX HOURS AFTER

4840
03:14:10,987 --> 03:14:12,756
TREATMENT AND THE TWO OUTCOMES

4841
03:14:12,756 --> 03:14:14,291
THAT WERE REQUIRED WAS

4842
03:14:14,291 --> 03:14:16,026
IMPROVEMENT IN THE LAMENESS

4843
03:14:16,026 --> 03:14:17,827
SCORE AND THEN IMPROVEMENT IN

4844
03:14:17,827 --> 03:14:20,197
TOTAL FORCE AND CONTACT AREA.

4845
03:14:20,197 --> 03:14:22,098
SO THEY USED BOTH THE VISUAL

4846
03:14:22,098 --> 03:14:23,700
SCORING SYSTEM OF LAMENESS AND

4847
03:14:23,700 --> 03:14:25,902
THE PRESSURE MAT SCORES TO TRY

4848
03:14:25,902 --> 03:14:28,038
TO ASSESS WHETHER THERE WAS AN

4849
03:14:28,038 --> 03:14:30,006
EFFECT OF TREATMENT IN THIS --

4850
03:14:30,006 --> 03:14:30,907
IN THESE ANIMALS.

4851
03:14:30,907 --> 03:14:34,344
THESE ARE THE OUTCOME FROM THE

4852
03:14:34,344 --> 03:14:34,511
FOI.

4853
03:14:34,511 --> 03:14:37,113
LAMENESS SCORE IMPROVEMENT 15-15

4854
03:14:37,113 --> 03:14:39,449
ANIMALS IMPROVED WITH THE

4855
03:14:39,449 --> 03:14:40,817
TRANSDERMAL AT SIX HOURS AFTER

4856
03:14:40,817 --> 03:14:41,318
TREATMENT.

4857
03:14:41,318 --> 03:14:43,920
ONLY ONE-15 ANIMALS IMPROVED IN

4858
03:14:43,920 --> 03:14:45,722
THE CONTROL GROUP FOR LAMENESS

4859
03:14:45,722 --> 03:14:45,922
SCORE.

4860
03:14:45,922 --> 03:14:47,224
AND THEN IN TERMS OF THE TWO

4861
03:14:47,224 --> 03:14:48,225
OUTCOMES MEASURED ON THE

4862
03:14:48,225 --> 03:14:50,527
PRESSURE MAT THE MAXIMUM FORCE

4863
03:14:50,527 --> 03:14:52,529
AND THE CONTACT AREA AT SITE 1

4864
03:14:52,529 --> 03:14:56,099
SHOWED STATISTICALLY SIGNIFICANT

4865
03:14:56,099 --> 03:14:57,834
DIFFERENCE AFTER TREATMENT FOR

4866
03:14:57,834 --> 03:14:59,903
BOTH FORCE AND CONTACT AREA.

4867
03:14:59,903 --> 03:15:01,471
AND SIMILAR OUTCOMES WERE

4868
03:15:01,471 --> 03:15:05,208
MEASURED IN THE CONTROL GROUP AT

4869
03:15:05,208 --> 03:15:06,009
THE SECOND SITE.

4870
03:15:06,009 --> 03:15:07,944
SO STATISTICALLY SIGNIFICANT

4871
03:15:07,944 --> 03:15:09,112
IMPROVEMENTS SEEN IN THESE

4872
03:15:09,112 --> 03:15:10,847
ANIMALS, BOTH IN THE LAMENESS

4873
03:15:10,847 --> 03:15:11,982
SCORE AND ALSO IN THE PRESSURE

4874
03:15:11,982 --> 03:15:13,483
MAT OUTCOMES.

4875
03:15:13,483 --> 03:15:14,718
SO ACROSSIC EXAMPLE OF A

4876
03:15:14,718 --> 03:15:17,087
MULTIPLE ENDPOINT STUDY.

4877
03:15:17,087 --> 03:15:18,421
-- A CLASSIC EXAMPLE.

4878
03:15:18,421 --> 03:15:20,423
SO EFFECTIVE PAIN CONTROL WAS

4879
03:15:20,423 --> 03:15:22,459
DEMONSTRATED AT SIX HOURS AFTER

4880
03:15:22,459 --> 03:15:22,859
TREATMENT.

4881
03:15:22,859 --> 03:15:24,060
THE PAIN ASSESSMENT OCCURRED

4882
03:15:24,060 --> 03:15:26,463
WITH MULTIPLE ENDPOINTS WHICH

4883
03:15:26,463 --> 03:15:27,430
WAS BOTH LAMENESS SCORE AND

4884
03:15:27,430 --> 03:15:29,032
CONTACT AREA AND FORCE.

4885
03:15:29,032 --> 03:15:31,601
AND THIS WAS REPLICATED AT TWO

4886
03:15:31,601 --> 03:15:33,570
LOCATIONS SHOWING THAT THIS

4887
03:15:33,570 --> 03:15:35,005
EXPERIMENTAL MODEL WAS AN

4888
03:15:35,005 --> 03:15:36,840
EFFECTIVE MODEL IN INDUCING

4889
03:15:36,840 --> 03:15:38,074
LAMENESS AND DEMONSTRATING THAT

4890
03:15:38,074 --> 03:15:39,976
THE USE OF THESE MULTIPLE

4891
03:15:39,976 --> 03:15:42,145
ENDPOINTS WAS USEFUL IN TERMS OF

4892
03:15:42,145 --> 03:15:44,614
ASSESSING ANALGESIC EFFECTS IN

4893
03:15:44,614 --> 03:15:45,048
FOOT ROT.

4894
03:15:45,048 --> 03:15:48,551
SO TO FINISH UP, JUST SOME WORK

4895
03:15:48,551 --> 03:15:50,453
IN PROGRESS.

4896
03:15:50,453 --> 03:15:51,554
MY GRADUATE STUDENT TRIED TO

4897
03:15:51,554 --> 03:15:53,790
DEVELOP A COMPOSITE ENDPOINT

4898
03:15:53,790 --> 03:15:55,892
SCALE FOR THESE PHYSIOLOGICAL

4899
03:15:55,892 --> 03:15:58,595
OUTCOMES BY NORMALIZING THE DATA

4900
03:15:58,595 --> 03:15:59,729
USING NORMALIZATION EQUATION.

4901
03:15:59,729 --> 03:16:02,465
SO HE WAS TRYING TO GET DATA ON

4902
03:16:02,465 --> 03:16:07,370
TO A 0-10 SCALE WITH X BEING THE

4903
03:16:07,370 --> 03:16:09,372
INDIVIDUAL VALUE EACH ANIMAL.

4904
03:16:09,372 --> 03:16:11,474
THE X MAX BEING THE MAXIMUM

4905
03:16:11,474 --> 03:16:13,877
RESPONSE AND THE X MIN BEING THE

4906
03:16:13,877 --> 03:16:17,080
MINIMUM RESPONSE WE OBSERVED.

4907
03:16:17,080 --> 03:16:18,581
ENDPOINTS WERE CORTISOL,

4908
03:16:18,581 --> 03:16:21,518
MECHANICAL THRESHOLD, OCULAR

4909
03:16:21,518 --> 03:16:22,886
THERMOGRAPHY, THE DIFFERENCE IN

4910
03:16:22,886 --> 03:16:25,422
TEMP BETWEEN A HORN AND THE EYE

4911
03:16:25,422 --> 03:16:28,858
AND HEART RATE AND WE HAD 185

4912
03:16:28,858 --> 03:16:33,663
CALFS AND THEY WERE RANDOMIZED

4913
03:16:33,663 --> 03:16:38,001
INTO GROUPS AND THERE WAS ALSO A

4914
03:16:38,001 --> 03:16:38,835
SHAM GROUP THAT WAS NOT EXPOSED

4915
03:16:38,835 --> 03:16:40,603
TO THE DE-HORNING PROCEDURE.

4916
03:16:40,603 --> 03:16:42,539
ALL THE DRUGS WERE ADMINISTERED

4917
03:16:42,539 --> 03:16:44,808
IN TWO MILLIGRAMS PER KILO GRAM.

4918
03:16:44,808 --> 03:16:47,143
SO WHEN WE ANALYZED THESE DATA

4919
03:16:47,143 --> 03:16:48,912
USING CONVENTIONAL STATISTICS,

4920
03:16:48,912 --> 03:16:50,113
WE DIDN'T SEE ANYTHING THAT WAS

4921
03:16:50,113 --> 03:16:51,147
SUPER EXCITING.

4922
03:16:51,147 --> 03:16:53,616
SO THE GREEN AND THE RED ARE

4923
03:16:53,616 --> 03:16:54,918
SIGNIFICANTLY DIFFERENT AND THE

4924
03:16:54,918 --> 03:16:56,820
YELLOW WERE NOT SIGNIFICANTLY

4925
03:16:56,820 --> 03:16:57,921
DIFFERENT FROM THE OTHER GROUPS.

4926
03:16:57,921 --> 03:17:00,123
AND SO, FOR THE SAME CHANGE IN

4927
03:17:00,123 --> 03:17:02,425
HEART RATE, WE SAW A SIGNIFICANT

4928
03:17:02,425 --> 03:17:05,729
DIFFERENCE BETWEEN THE ANIMALS

4929
03:17:05,729 --> 03:17:07,530
THAT RECEIVED -- AND SHAM GROUP

4930
03:17:07,530 --> 03:17:08,164
COMPARED WITH THE OTHER GROUPS

4931
03:17:08,164 --> 03:17:09,099
IN THE STUDY.

4932
03:17:09,099 --> 03:17:12,369
WE DIDN'T SEE ANYTHING

4933
03:17:12,369 --> 03:17:13,603
SIGNIFICANT EXCEPT THIS GROUP

4934
03:17:13,603 --> 03:17:17,440
FOR THE SAME CHANGE IN OCULAR

4935
03:17:17,440 --> 03:17:18,007
DEMORNING TEMPERATURE.

4936
03:17:18,007 --> 03:17:19,342
MECHANICAL THRESHOLD NO

4937
03:17:19,342 --> 03:17:20,777
DIFFERENCE BETWEEN THE TREATMENT

4938
03:17:20,777 --> 03:17:21,010
GROUPS.

4939
03:17:21,010 --> 03:17:22,612
THERE WAS ONLY A DIFFERENCE

4940
03:17:22,612 --> 03:17:24,981
BETWEEN TREATMENT AND SHAM AND

4941
03:17:24,981 --> 03:17:26,483
THEN AVERAGE DAY-TO-DAY NO

4942
03:17:26,483 --> 03:17:27,884
DIFFERENCE ACROSS-THE-BOARD.

4943
03:17:27,884 --> 03:17:29,586
WHEN MAT DID HIS ADJUSTMENTS OF

4944
03:17:29,586 --> 03:17:31,988
THE DATA, HE DID OBSERVE THERE

4945
03:17:31,988 --> 03:17:33,957
WAS SEPARATION THAT OCCURRED

4946
03:17:33,957 --> 03:17:35,558
BETWEEN THE DIFFERENT GROUPS.

4947
03:17:35,558 --> 03:17:37,560
THE PLACEBO AND THE GROUP THAT

4948
03:17:37,560 --> 03:17:40,196
RECEIVED THE -- HAD THE HIGHEST

4949
03:17:40,196 --> 03:17:41,765
PAIN STRESS INDEX WHEN HE DID

4950
03:17:41,765 --> 03:17:43,333
THE NORMALIZATION PROCEDURE AND

4951
03:17:43,333 --> 03:17:44,868
THAT WAS SIGNIFICANTLY DIFFERENT

4952
03:17:44,868 --> 03:17:48,004
AT 4 AND 8 HOURS COMPARED WITH

4953
03:17:48,004 --> 03:17:50,140
THE OTHER GROUPS.

4954
03:17:50,140 --> 03:17:52,275
AND THEN OF COURSE THE SHAM

4955
03:17:52,275 --> 03:17:52,776
GROUP WAS SIGNIFICANTLY

4956
03:17:52,776 --> 03:17:53,977
DIFFERENT FROM ALL OF THEM

4957
03:17:53,977 --> 03:17:54,978
THROUGHOUT THE STUDY.

4958
03:17:54,978 --> 03:17:57,180
BUT THAT DIFFERENCE WAS LAST

4959
03:17:57,180 --> 03:17:58,214
AFTER 24 HOURS.

4960
03:17:58,214 --> 03:17:59,883
SO THE TAKE HOME MESSAGE IS

4961
03:17:59,883 --> 03:18:01,184
THERE ARE SOME OPPORTUNITIES FOR

4962
03:18:01,184 --> 03:18:04,587
US TO PERHAPS REFINE THESE

4963
03:18:04,587 --> 03:18:05,922
COMPOSITE SCORES IN THE FUTURE

4964
03:18:05,922 --> 03:18:07,390
IN A WAY THAT MAKES SENSE FOR US

4965
03:18:07,390 --> 03:18:09,592
TO BE ABLE TO ANALYZE THESE

4966
03:18:09,592 --> 03:18:10,326
PHYSIOLOGICAL ENDPOINTS.

4967
03:18:10,326 --> 03:18:11,895
SO APPRECIATE YOUR TIME AND

4968
03:18:11,895 --> 03:18:12,762
ATTENTION TODAY.

4969
03:18:12,762 --> 03:18:14,697
THE CONCLUSIONS THAT WE STILL

4970
03:18:14,697 --> 03:18:17,000
NEED THESE ANALGESIC DRUGS IN

4971
03:18:17,000 --> 03:18:18,601
FOOD ANIMALS BECOMING CRITICALLY

4972
03:18:18,601 --> 03:18:20,703
IMPORTANT FOR US IN TERMS OF

4973
03:18:20,703 --> 03:18:22,005
MEETING SOME OF THE CONSUMER

4974
03:18:22,005 --> 03:18:23,473
CONCERNS ABOUT HOW CATTLE ARE

4975
03:18:23,473 --> 03:18:25,408
BEING RAISED AND PIGS.

4976
03:18:25,408 --> 03:18:26,342
CONSIDERABLE PROGRESS IS BEING

4977
03:18:26,342 --> 03:18:28,411
MADE IN VALIDATING THESE METHODS

4978
03:18:28,411 --> 03:18:29,479
AND WE STILL HAVE OPPORTUNITIES

4979
03:18:29,479 --> 03:18:30,413
TO THE REFINE THEM AND

4980
03:18:30,413 --> 03:18:32,115
PARTICULARLY IN TERMS OF

4981
03:18:32,115 --> 03:18:32,415
VALIDATION.

4982
03:18:32,415 --> 03:18:33,416
SO THAT'S ALL I HAVE.

4983
03:18:33,416 --> 03:18:35,018
I ACKNOWLEDGE MY FUNDING

4984
03:18:35,018 --> 03:18:36,119
AGENCIES TODAY AND THANK YOU FOR

4985
03:18:36,119 --> 03:18:37,520
YOUR TIME AND ATTENTION.

4986
03:18:37,520 --> 03:18:40,056
APPRECIATE IT.

4987
03:18:40,056 --> 03:18:50,266
[ APPLAUSE ]

4988
03:18:51,568 --> 03:18:52,335
>> THANK YOU.

4989
03:18:52,335 --> 03:18:53,803
I REMEMBER 15 YEARS AGO WHEN YOU

4990
03:18:53,803 --> 03:18:55,638
CAME AND TALKED TO FDA.

4991
03:18:55,638 --> 03:18:57,240
I'M SURPRISED IT HAS ALREADY

4992
03:18:57,240 --> 03:18:58,308
BEEN 15 YEARS.

4993
03:18:58,308 --> 03:18:59,642
BUT THANK YOU FOR SHOWING US ALL

4994
03:18:59,642 --> 03:19:10,119
THE PROGRESS YOU HAVE MADE.

4995
03:19:15,191 --> 03:19:16,659
OUR NEXT SPEAKER IS ANOTHER

4996
03:19:16,659 --> 03:19:18,361
COLLEAGUE FROM FDA CENTER FOR

4997
03:19:18,361 --> 03:19:20,663
VETERINARY MEDICINE, DR. QIAO

4998
03:19:20,663 --> 03:19:21,331
ZHANG.

4999
03:19:21,331 --> 03:19:23,233
AND DR. QIAO ZHANG IS A

5000
03:19:23,233 --> 03:19:24,534
BIOSTATISTICIAN IN THE OFFICE OF

5001
03:19:24,534 --> 03:19:26,769
NEW ANIMAL DRUG EVALUATION.

5002
03:19:26,769 --> 03:19:28,938
SHE RECEIVED HER PH.D. IN

5003
03:19:28,938 --> 03:19:30,240
STATISTICS AT STONY BROOK

5004
03:19:30,240 --> 03:19:32,041
UNIVERSITY IN LONG ISLAND,

5005
03:19:32,041 --> 03:19:32,308
NEW YORK.

5006
03:19:32,308 --> 03:19:33,643
AND I'D LIKE TO WELCOME HER TO

5007
03:19:33,643 --> 03:19:35,845
TALK ABOUT ADAPTIVE AND OTHER

5008
03:19:35,845 --> 03:19:37,213
INNOVATIVE PAIN MEASUREMENT

5009
03:19:37,213 --> 03:19:38,615
STUDY DESIGNS.

5010
03:19:38,615 --> 03:19:47,790
[ APPLAUSE ]

5011
03:19:47,790 --> 03:19:48,725
>> GOOD AFTERNOON,
EVERYONE.

5012
03:19:48,725 --> 03:19:51,394
THANK YOU FOR STAYING FOR THE

5013
03:19:51,394 --> 03:19:51,961
LAST TALK.

5014
03:19:51,961 --> 03:19:54,831
IT WON'T BE LONG, I PROMISE.

5015
03:19:54,831 --> 03:19:57,867
SO I'M GOING TO TALK ABOUT

5016
03:19:57,867 --> 03:20:00,637
ADAPTIVE AND NORMATIVE PAIN

5017
03:20:00,637 --> 03:20:02,171
MEASUREMENTS STUDY DESIGNS.

5018
03:20:02,171 --> 03:20:05,742
SO I WILL START WITH

5019
03:20:05,742 --> 03:20:06,876
INTRODUCTION ABOUT THE

5020
03:20:06,876 --> 03:20:08,444
DEFINITIONS FOR THE ADAPTIVE

5021
03:20:08,444 --> 03:20:10,780
DESIGN AND ENRICHMENT DESIGN

5022
03:20:10,780 --> 03:20:12,482
ACCORDING TO THE GUIDANCE 268.

5023
03:20:12,482 --> 03:20:15,385
AND THEN I WILL TALK ABOUT TWO

5024
03:20:15,385 --> 03:20:18,254
EXAMPLES IN ADAPTIVE DESIGN AND

5025
03:20:18,254 --> 03:20:19,689
ONE EXAMPLE IN ENRICHMENT

5026
03:20:19,689 --> 03:20:19,923
DESIGN.

5027
03:20:19,923 --> 03:20:22,191
AND FINALLY I WILL WRAP UP WITH

5028
03:20:22,191 --> 03:20:24,961
SOME TAKE-HOME MESSAGES.

5029
03:20:24,961 --> 03:20:28,531
SO THE GUIDANCE, GFI268 PROVIDES

5030
03:20:28,531 --> 03:20:30,633
SOME RECOMMENDATIONS AND

5031
03:20:30,633 --> 03:20:31,701
CONSIDERATIONS FOR DIFFERENT

5032
03:20:31,701 --> 03:20:33,269
TYPES OF ENORMATIVE DESIGNS.

5033
03:20:33,269 --> 03:20:35,805
SO ACCORDING TO THE GUIDANCE,

5034
03:20:35,805 --> 03:20:37,807
THE ADAPTIVE DESIGN REFERS TO

5035
03:20:37,807 --> 03:20:39,809
THE CLINICAL EFFECTIVENESS STUDY

5036
03:20:39,809 --> 03:20:42,211
DESIGN THAT ALLOWS FOR

5037
03:20:42,211 --> 03:20:44,247
PROSPECTIVELY PLANNED

5038
03:20:44,247 --> 03:20:44,581
MODIFICATIONS.

5039
03:20:44,581 --> 03:20:48,284
AND THE MODIFICATIONS MAY IMPACT

5040
03:20:48,284 --> 03:20:50,753
THE SAMPLE SIZE OR THE DURATION

5041
03:20:50,753 --> 03:20:52,388
OF THE STUDY.

5042
03:20:52,388 --> 03:20:54,424
THE ENDPOINT AND OTHER STUDY

5043
03:20:54,424 --> 03:20:55,124
FEATURES AS WELL.

5044
03:20:55,124 --> 03:20:58,328
THE ENRICHMENT DESIGN REFERS TO

5045
03:20:58,328 --> 03:20:59,996
PROSPECTIVE USE OF ANY

5046
03:20:59,996 --> 03:21:01,998
CHARACTERISTIC TO SELECT A STUDY

5047
03:21:01,998 --> 03:21:02,832
POPULATION.

5048
03:21:02,832 --> 03:21:04,834
AND IT IS MORE LIKELY TO DETECT

5049
03:21:04,834 --> 03:21:07,236
THE DRUG EFFECT IN THAT SELECTED

5050
03:21:07,236 --> 03:21:09,405
POPULATION THAN THE UNSELECTED

5051
03:21:09,405 --> 03:21:09,706
POPULATION.

5052
03:21:09,706 --> 03:21:12,275
FOR EXAMPLE, THE HIGH PLACEBO

5053
03:21:12,275 --> 03:21:13,776
EFFECT IS ALWAYS A CONCERN IN

5054
03:21:13,776 --> 03:21:16,412
THE PAIN MEASUREMENT STUDIES AND

5055
03:21:16,412 --> 03:21:18,748
WE WOULD LIKE TO SELECT THOSE

5056
03:21:18,748 --> 03:21:21,284
PATIENTS NOT RESPONDING TO THE

5057
03:21:21,284 --> 03:21:25,655
PLACEBO AND EXPECT TO DETECT A

5058
03:21:25,655 --> 03:21:27,023
HIGHER -- IN THIS POPULATION.

5059
03:21:27,023 --> 03:21:29,258
I'LL TALK MORE ABOUT THIS

5060
03:21:29,258 --> 03:21:31,628
EXAMPLE WHEN I INTRODUCE THE

5061
03:21:31,628 --> 03:21:33,129
PLACEBO DESIGN.

5062
03:21:33,129 --> 03:21:35,832
SO I THINK THE COMMON KEYWORD

5063
03:21:35,832 --> 03:21:38,368
FOR THESE TWO DESIGNS ARE

5064
03:21:38,368 --> 03:21:39,268
PROSPECTIVE.

5065
03:21:39,268 --> 03:21:41,971
SO THAT MEANS ALL THE ADAPTATION

5066
03:21:41,971 --> 03:21:44,807
OR ENRICHMENT FEATURES NEED TOUR

5067
03:21:44,807 --> 03:21:46,643
PRE SPECIFIED IN THE PROTOCOL

5068
03:21:46,643 --> 03:21:48,411
AND THIS IS ALSO POINTED OUT IN

5069
03:21:48,411 --> 03:21:49,912
THE GUIDANCE.

5070
03:21:49,912 --> 03:21:52,682
SO IN THE PROTOCOL, I NEED TO

5071
03:21:52,682 --> 03:21:55,251
SPECIFY THE NUMBER AND TIMING OF

5072
03:21:55,251 --> 03:21:56,986
THE INTERIM ANALYSIS.

5073
03:21:56,986 --> 03:21:59,322
THE STATISTICAL ANALYSIS METHODS

5074
03:21:59,322 --> 03:22:02,692
AND THE ADAPTATION CRITERIA AND

5075
03:22:02,692 --> 03:22:05,361
ALGORITHM GOVERNING FOR

5076
03:22:05,361 --> 03:22:08,364
ADAPTATION DECISIONS.

5077
03:22:08,364 --> 03:22:10,900
SO AS DR. RUBERMAN INTRODUCED,

5078
03:22:10,900 --> 03:22:14,504
THE EXPLORATORY STUDY AND THE

5079
03:22:14,504 --> 03:22:16,773
CONFORM TERRI STUDY MAY HAVE

5080
03:22:16,773 --> 03:22:17,373
DIFFERENT PURPOSE.

5081
03:22:17,373 --> 03:22:20,410
SO THEREFORE THEY MAY REQUIRE

5082
03:22:20,410 --> 03:22:24,247
DIFFERENT STATISTICAL JUDGMENTS.

5083
03:22:24,247 --> 03:22:26,616
SO THE GUIDANCE 268 PROVIDES

5084
03:22:26,616 --> 03:22:29,185
GENERAL RECOMMENDATIONS FOR THE

5085
03:22:29,185 --> 03:22:34,023
CONFIRMATORY STUDIES.

5086
03:22:34,023 --> 03:22:36,092
SO -- THE TALK I'M GOING TO GIVE

5087
03:22:36,092 --> 03:22:38,327
TODAY ALSO FOCUS ON CONFIRMATORY

5088
03:22:38,327 --> 03:22:39,128
STUDIES ONLY.

5089
03:22:39,128 --> 03:22:40,730
BUT ALL THE METHODS WE DISCUSS

5090
03:22:40,730 --> 03:22:42,432
TODAY AND IN THE GUIDANCE ARE

5091
03:22:42,432 --> 03:22:45,768
ALSO APPLICABLE TO THE

5092
03:22:45,768 --> 03:22:47,637
EXPLORATORY STUDIES JUST WITH

5093
03:22:47,637 --> 03:22:50,540
FEWER RESTRICTIONS ON THE

5094
03:22:50,540 --> 03:22:53,843
ADJUSTMENTS FOR MULTIPLICITY.

5095
03:22:53,843 --> 03:22:56,446
HERE IS DIAGRAM TO SHOW YOU A

5096
03:22:56,446 --> 03:22:59,449
STANDARD ADAPTIVE DESIGN.

5097
03:22:59,449 --> 03:23:01,651
SO ALL THE KEY DESIGN FEATURES

5098
03:23:01,651 --> 03:23:03,619
NEEDS TO BE PRE SPECIFIED

5099
03:23:03,619 --> 03:23:06,089
CHOOSING THE HYPOTHESIS, THE

5100
03:23:06,089 --> 03:23:09,559
POWER, THE SAMPLE SIZE, TIMING

5101
03:23:09,559 --> 03:23:11,994
AND RULES FOR THE INTERIM

5102
03:23:11,994 --> 03:23:13,062
ANALYSIS, IA.

5103
03:23:13,062 --> 03:23:16,399
AND THEN AFTER THE STUDY IS

5104
03:23:16,399 --> 03:23:18,201
INITIATED AND ALL THE PATIENTS

5105
03:23:18,201 --> 03:23:21,037
ARE ENROLLING, THE INTERIM

5106
03:23:21,037 --> 03:23:23,740
ANALYSIS WILL BE CONDUCTED AT A

5107
03:23:23,740 --> 03:23:24,674
PLANNED TIME POINT AND BASED ON

5108
03:23:24,674 --> 03:23:27,443
THE INTERIM ANALYSIS RESULTS, WE

5109
03:23:27,443 --> 03:23:30,546
MAY MAKE ADAPTATIONS ON SAMPLE

5110
03:23:30,546 --> 03:23:32,982
SIZE OR TO STOP THE STUDY EARLY

5111
03:23:32,982 --> 03:23:34,517
FOR FEW UTILITY OR STOP THE

5112
03:23:34,517 --> 03:23:38,321
STUDY EARLY FOR EFFECTIVENESS OR

5113
03:23:38,321 --> 03:23:40,656
SOME OTHER ADAPTATIONS BY

5114
03:23:40,656 --> 03:23:40,890
DESIGN.

5115
03:23:40,890 --> 03:23:43,559
AND IF THE STUDY IS NOT STOPPED

5116
03:23:43,559 --> 03:23:45,361
FOR ANY REASON, IT WILL JUST

5117
03:23:45,361 --> 03:23:47,964
CONTINUE TO THE END AS PLANNED

5118
03:23:47,964 --> 03:23:49,966
AND A FINAL ANALYSIS WILL BE

5119
03:23:49,966 --> 03:23:51,901
CONDUCTED AND DRAW CONCLUSIONS.

5120
03:23:51,901 --> 03:23:54,303
TO ILLUSTRATE THE IDEA, I WILL

5121
03:23:54,303 --> 03:23:57,106
SHOW ONE INTERIM ANALYSIS HERE

5122
03:23:57,106 --> 03:23:58,107
BEING PRACTICED.

5123
03:23:58,107 --> 03:23:59,976
YOU MAY CONDUCT MORE THAN ONE

5124
03:23:59,976 --> 03:24:01,878
INTERIM ANALYSIS BUT MULTIPLE

5125
03:24:01,878 --> 03:24:03,446
INTERIM ANALYSIS MAY GIVE RISE

5126
03:24:03,446 --> 03:24:07,884
TO THE CONCERN OF THE STUDY

5127
03:24:07,884 --> 03:24:11,521
INTEGRITY DUE TO THE OPERATIONAL

5128
03:24:11,521 --> 03:24:12,889
BIAS.

5129
03:24:12,889 --> 03:24:14,991
SO -- MAY BE APPLIED

5130
03:24:14,991 --> 03:24:15,491
ACCORDINGLY.

5131
03:24:15,491 --> 03:24:16,492
THIS IS JUST SOMETHING YOU MAY

5132
03:24:16,492 --> 03:24:19,796
NEED TO KEEP IN MIND WHEN

5133
03:24:19,796 --> 03:24:22,398
DESIGNING ADAPTIVE DESIGN STUDY.

5134
03:24:22,398 --> 03:24:24,400
AND ALL THESE ADAPTATIONS MAY

5135
03:24:24,400 --> 03:24:26,302
APPLY TO ANY STUDY WITH

5136
03:24:26,302 --> 03:24:29,405
DIFFERENT TYPES OF ENDPOINTS.

5137
03:24:29,405 --> 03:24:31,607
IN TERMS OF THE PAIN MEASUREMENT

5138
03:24:31,607 --> 03:24:35,111
STUDIES, I CONSIDER THE

5139
03:24:35,111 --> 03:24:36,813
ADAPTATION IN SAMPLE SIZE AND

5140
03:24:36,813 --> 03:24:38,114
ADAPTATION TO STOP THE STUDY

5141
03:24:38,114 --> 03:24:39,615
EARLY FOR FEW UTILITY MAY BE

5142
03:24:39,615 --> 03:24:42,552
MORE FEASIBLE AND MORE

5143
03:24:42,552 --> 03:24:43,619
BENEFICIAL THAN THE OTHER TYPES

5144
03:24:43,619 --> 03:24:46,289
OF ADAPTATIONS.

5145
03:24:46,289 --> 03:24:49,525
SO NOW I'M GOING TO INTRODUCE

5146
03:24:49,525 --> 03:24:50,893
THE FIRST EXAMPLE.

5147
03:24:50,893 --> 03:24:52,962
THE SAMPLE CISORY ESTIMATION.

5148
03:24:52,962 --> 03:24:55,898
IT GIVES US A CHANCE TO MODIFY

5149
03:24:55,898 --> 03:24:58,734
AND EMPHASIZE DURING THE

5150
03:24:58,734 --> 03:25:07,743
UNDERGOING STUDY.

5151
03:25:07,743 --> 03:25:10,680
WE CALL IT BLINDED VERSUS

5152
03:25:10,680 --> 03:25:10,947
UNBIDDED.

5153
03:25:10,947 --> 03:25:14,483
IN THE BLINDED SSR, FOR EXAMPLE,

5154
03:25:14,483 --> 03:25:17,320
IN ONCOLOGY STUDY, THE NUMBER OF

5155
03:25:17,320 --> 03:25:19,255
EVENTS IS THE KEY FACTOR TO

5156
03:25:19,255 --> 03:25:21,057
DETERMINE THE POWER.

5157
03:25:21,057 --> 03:25:23,259
SO, WE WOULD LIKE TO MONITOR THE

5158
03:25:23,259 --> 03:25:25,528
EVENT RATE DURING THIS STUDY AND

5159
03:25:25,528 --> 03:25:27,363
IF THE EVENT RATE IS SMALLER

5160
03:25:27,363 --> 03:25:29,365
THAN EXPECTED, WE MAY WANT TO

5161
03:25:29,365 --> 03:25:31,467
INCREASE TOTAL SAMPLE SIZE TO

5162
03:25:31,467 --> 03:25:33,836
ACHIEVE THE TARGET NUMBER OF

5163
03:25:33,836 --> 03:25:34,070
EVENTS.

5164
03:25:34,070 --> 03:25:36,372
SO THAT'S A BLINDED DESIGN.

5165
03:25:36,372 --> 03:25:38,941
I THINK IN THE PAIN MEASUREMENT

5166
03:25:38,941 --> 03:25:42,178
STUDIES, IT'S LESS COMMONLY

5167
03:25:42,178 --> 03:25:42,378
USED.

5168
03:25:42,378 --> 03:25:45,047
BUT ONE ADVANTAGE OF BLINDED SSR

5169
03:25:45,047 --> 03:25:46,549
IS THAT IT IS GENERALLY BELIEVED

5170
03:25:46,549 --> 03:25:48,684
TO HAVE LIMITED OR NO IMPACT ON

5171
03:25:48,684 --> 03:25:51,087
THE FAMILY WISE ERROR RATE,

5172
03:25:51,087 --> 03:25:53,055
WHICH YOU MAY RECALL IS THE

5173
03:25:53,055 --> 03:25:56,559
PROBABILITY OF MAKING ONE FALSE

5174
03:25:56,559 --> 03:25:58,794
POSITIVE DECISION AMONG ALL THE

5175
03:25:58,794 --> 03:26:00,062
HYPOTHESIS TESTED.

5176
03:26:00,062 --> 03:26:04,367
SO ON THE OTHER HAND, THE

5177
03:26:04,367 --> 03:26:05,835
UNBLINDED SAMPLE SIZE ESTIMATION

5178
03:26:05,835 --> 03:26:07,270
ALLOWS TO ESTIMATE DURING THE

5179
03:26:07,270 --> 03:26:10,273
STUDY, HOWEVER THAT WOULD

5180
03:26:10,273 --> 03:26:10,973
INFLATE THE FAMILY WISE ERROR

5181
03:26:10,973 --> 03:26:16,679
RATE BECAUSE YOU DO USE THIS

5182
03:26:16,679 --> 03:26:16,979
REPEATEDLY.

5183
03:26:16,979 --> 03:26:18,748
SO APPROPRIATE METHOD SHOULD BE

5184
03:26:18,748 --> 03:26:28,291
APPLIED TO CONTROL THAT ERROR.

5185
03:26:28,291 --> 03:26:29,892
HERE IS ONE EXAMPLE.

5186
03:26:29,892 --> 03:26:30,826
THE CONDITION POWER.

5187
03:26:30,826 --> 03:26:33,029
THIS IS THE PROBABILITY THAT THE

5188
03:26:33,029 --> 03:26:36,098
FINAL STUDY RESULT WILL BE

5189
03:26:36,098 --> 03:26:36,732
STATISTICALLY SIGNIFICANT GIVEN

5190
03:26:36,732 --> 03:26:39,268
THE DATA OBSERVED SO FAR.

5191
03:26:39,268 --> 03:26:42,838
FOR EXAMPLE, IF WE WOULD LIKE TO

5192
03:26:42,838 --> 03:26:44,206
COMPARE THE TREATMENT ARM AND

5193
03:26:44,206 --> 03:26:48,711
CONTROL ARM, COMPARED TO SUCCESS

5194
03:26:48,711 --> 03:26:50,780
RATE BETWEEN TWO GROUPS, THE

5195
03:26:50,780 --> 03:26:54,517
INTERIM ANALYSIS WE OBSERVED 30%

5196
03:26:54,517 --> 03:26:57,086
THAT WE MAY ASK WHAT IS THE

5197
03:26:57,086 --> 03:26:59,021
PROBABILITY OF STATISTICAL

5198
03:26:59,021 --> 03:27:01,524
SIGNIFICANCE BY THE END OF THE

5199
03:27:01,524 --> 03:27:01,724
STUDY?

5200
03:27:01,724 --> 03:27:04,193
SO THAT MEANS WE ARE USING WHAT

5201
03:27:04,193 --> 03:27:05,728
WE HAVE OBSERVED SO FAR TO

5202
03:27:05,728 --> 03:27:06,829
PREDICT A RESULT BY THE END OF

5203
03:27:06,829 --> 03:27:08,097
THE STUDY.

5204
03:27:08,097 --> 03:27:10,900
GIVEN THE ASSUMPTION THAT THIS

5205
03:27:10,900 --> 03:27:11,834
WILL HOLD TRUE FOR THE REST OF

5206
03:27:11,834 --> 03:27:14,337
THE STUDY.

5207
03:27:14,337 --> 03:27:15,438
SO, THERE ARE SEVERAL

5208
03:27:15,438 --> 03:27:17,139
STATISTICAL METHODS THAT WE CAN

5209
03:27:17,139 --> 03:27:20,810
USE TO DO THE CALCULATION.

5210
03:27:20,810 --> 03:27:24,647
WE APPLY ONE OF THEM AND ACHIEVE

5211
03:27:24,647 --> 03:27:25,614
A RESULT OF 65%.

5212
03:27:25,614 --> 03:27:26,816
SO WHAT DOES THAT MEAN?

5213
03:27:26,816 --> 03:27:28,084
HOW ARE WE GOING TO MAKE

5214
03:27:28,084 --> 03:27:31,020
DECISIONS BASED ON THE

5215
03:27:31,020 --> 03:27:31,420
OBSERVATION?

5216
03:27:31,420 --> 03:27:34,623
THE BOTTOM GIVES YOU A SERIES OF

5217
03:27:34,623 --> 03:27:36,525
DECISION RULES THAT YOU MAY

5218
03:27:36,525 --> 03:27:38,427
APPLY IN THE STUDY.

5219
03:27:38,427 --> 03:27:40,563
BEFORE THE INTERIM ANALYSIS IS

5220
03:27:40,563 --> 03:27:44,033
CONDUCTED, WE WOULD LIKE TO

5221
03:27:44,033 --> 03:27:47,470
PRE-SELECT A MINIMUM CONDITIONAL

5222
03:27:47,470 --> 03:27:50,639
POWER AND TARGET CONDITIONAL

5223
03:27:50,639 --> 03:27:50,906
POWER.

5224
03:27:50,906 --> 03:27:53,642
THE CP MINIMUM IS A THRESHOLD

5225
03:27:53,642 --> 03:27:55,611
SUCH THAT IF THE OBSERVED

5226
03:27:55,611 --> 03:27:56,679
CONDITIONAL POWER IS SMALLER

5227
03:27:56,679 --> 03:27:59,415
THAN THIS NUMBER, WE CONSIDER

5228
03:27:59,415 --> 03:28:01,584
THE STUDY TO BE NOT PROMISING

5229
03:28:01,584 --> 03:28:03,419
AND HAS SMALL CHANCE TO SUCCEED.

5230
03:28:03,419 --> 03:28:05,621
SO IN THIS CASE, WE PROBABLY

5231
03:28:05,621 --> 03:28:09,925
WILL STOP THE STUDY FOR

5232
03:28:09,925 --> 03:28:10,292
FUTILITIY.

5233
03:28:10,292 --> 03:28:12,328
BUT IF IT IS OBSERVED BETWEEN

5234
03:28:12,328 --> 03:28:13,763
THE TWO NUMBERS, WE MAY CONSIDER

5235
03:28:13,763 --> 03:28:16,499
THE STUDY IS PROMISING BUT MAYBE

5236
03:28:16,499 --> 03:28:17,199
UNDER POWERED.

5237
03:28:17,199 --> 03:28:19,201
SO IN THIS CASE, WE MAY INCREASE

5238
03:28:19,201 --> 03:28:22,238
THE SAMPLE SIZE TO ACHIEVE THE

5239
03:28:22,238 --> 03:28:22,738
TARGET POWER.

5240
03:28:22,738 --> 03:28:25,508
AND LAST, IF THE OBSERVED

5241
03:28:25,508 --> 03:28:27,810
CONDITIONAL POWER IS LARGER THAN

5242
03:28:27,810 --> 03:28:28,978
YOUR TARGET POWER, THEN THE

5243
03:28:28,978 --> 03:28:31,113
STUDY SHOULD CONTINUE TO

5244
03:28:31,113 --> 03:28:34,316
ORIGINAL SAMPLE SIZE WITHOUT ANY

5245
03:28:34,316 --> 03:28:36,986
MODIFICATIONS.

5246
03:28:36,986 --> 03:28:40,489
SO, I THINK SSR IS QUITE

5247
03:28:40,489 --> 03:28:40,890
SELF-EXPLANATORY.

5248
03:28:40,890 --> 03:28:44,593
IT CAN HELP AVOIDING THE UNDER

5249
03:28:44,593 --> 03:28:45,995
POWERING ISSUE, LIKE IF YOU

5250
03:28:45,995 --> 03:28:47,730
OBSERVE LIKE A HIGHER PLACEBO

5251
03:28:47,730 --> 03:28:53,269
EFFECT IN A STUDY AND MAYBE

5252
03:28:53,269 --> 03:28:54,537
OVERESTIMATE AN EFFECT AND IN

5253
03:28:54,537 --> 03:28:55,838
THIS CASE YOU MAY HAVE A CHANCE

5254
03:28:55,838 --> 03:28:57,640
TO SAVE THE STUDY BY INCREASING

5255
03:28:57,640 --> 03:28:59,141
THE SAMPLE SIZE.

5256
03:28:59,141 --> 03:29:01,944
BUT ALSO, WE NEED TO CONSIDER

5257
03:29:01,944 --> 03:29:04,113
THE CONTROL OF ERRORS AND

5258
03:29:04,113 --> 03:29:04,747
BIASES.

5259
03:29:04,747 --> 03:29:06,549
THE FIRST ONE IS THE FAMILY WISE

5260
03:29:06,549 --> 03:29:09,018
ERROR RATE BECAUSE YOU DO

5261
03:29:09,018 --> 03:29:15,291
CONDUCT TESTING DURING THIS

5262
03:29:15,291 --> 03:29:15,524
PROCESS.

5263
03:29:15,524 --> 03:29:17,126
ALSO OVERPOWERING THE STUDY.

5264
03:29:17,126 --> 03:29:18,727
THAT MEANS YOU SELECT A SAMPLE

5265
03:29:18,727 --> 03:29:23,165
SIZE THAT CAN POWER A TEST OR

5266
03:29:23,165 --> 03:29:25,234
DETECT -- SO SMALL IT IS NO

5267
03:29:25,234 --> 03:29:26,469
LONGER CLINICALLY RELEVANT.

5268
03:29:26,469 --> 03:29:29,438
I THINK YOU MAY ADJUST THIS

5269
03:29:29,438 --> 03:29:33,142
ISSUE BY PRE SPECIFYING A

5270
03:29:33,142 --> 03:29:33,742
CLINICALLY-MEANINGFUL EFFECT

5271
03:29:33,742 --> 03:29:38,347
INSTEAD OF JUST COMPARING THE

5272
03:29:38,347 --> 03:29:41,550
RESULT TO ZERO BY DEFAULT.

5273
03:29:41,550 --> 03:29:45,121
ALSO ADAPTATIONS MAY BRING BIAS

5274
03:29:45,121 --> 03:29:51,093
INTO THE STUDY AND SO IN THIS

5275
03:29:51,093 --> 03:29:52,461
CASE, SOME STRAT GEWILL NEED TO

5276
03:29:52,461 --> 03:29:55,231
BE APPLIED TO MAINTAIN THE STUDY

5277
03:29:55,231 --> 03:29:56,499
INTEGRITY AND VALIDITY.

5278
03:29:56,499 --> 03:29:58,868
FOR EXAMPLE, YOU MAY WANT TO

5279
03:29:58,868 --> 03:30:01,470
CONSULT A THIRD STATISTICIAN TO

5280
03:30:01,470 --> 03:30:03,072
ASSESS THE ADAPTATION AND ALSO

5281
03:30:03,072 --> 03:30:05,875
YOU WILL LIKE TO MINIMIZE THE

5282
03:30:05,875 --> 03:30:08,010
BIAS AND MAINTAIN MASKING WHEN

5283
03:30:08,010 --> 03:30:12,281
YOU COMMUNICATE THE ADAPTATION

5284
03:30:12,281 --> 03:30:12,581
RESULTS.

5285
03:30:12,581 --> 03:30:15,551
AND ALSO TIMING IS VERY

5286
03:30:15,551 --> 03:30:15,818
IMPORTANT.

5287
03:30:15,818 --> 03:30:17,553
IF YOU CONDUCT THE ADAPTATION

5288
03:30:17,553 --> 03:30:21,190
TOO EARLY, YOU MAY BE MISGUIDED

5289
03:30:21,190 --> 03:30:23,726
BY THE UNRELIABLE ESTIMATES DUE

5290
03:30:23,726 --> 03:30:27,163
TO THE HIGHLY-VARIABLE SAMPLES.

5291
03:30:27,163 --> 03:30:29,265
AND IF YOU CONDUCT ADAPTATION

5292
03:30:29,265 --> 03:30:32,468
TOO LATE, THEN THERE IS A VERY

5293
03:30:32,468 --> 03:30:34,570
LIMITED WINDOW TO ADAPT A STUDY.

5294
03:30:34,570 --> 03:30:36,772
SO I THINK SSR WILL BE MORE

5295
03:30:36,772 --> 03:30:39,475
BENEFICIAL TO A STUDY WITH

5296
03:30:39,475 --> 03:30:42,178
RELATIVELY LONG ENROLLMENT

5297
03:30:42,178 --> 03:30:43,979
PROCESS, BUT SHORT OBSERVATION

5298
03:30:43,979 --> 03:30:44,213
WINDOW.

5299
03:30:44,213 --> 03:30:48,083
FOR EXAMPLE IF YOU HAVE A STUDY

5300
03:30:48,083 --> 03:30:50,319
PROBABLY WE NEED ABOUT AT LEAST

5301
03:30:50,319 --> 03:30:52,188
A YEAR TO FINISH ENROLLMENT BUT

5302
03:30:52,188 --> 03:30:53,889
YOUR ENDPOINT OBSERVATION WILL

5303
03:30:53,889 --> 03:30:57,993
BE LIKE ON DAY 30, PROBABLY IT

5304
03:30:57,993 --> 03:31:01,664
MAY BE WORTH TO TAKE A LOOK AT

5305
03:31:01,664 --> 03:31:02,398
THE STUDY AND THE RESULTS AND

5306
03:31:02,398 --> 03:31:09,672
SEE IF YOU NEED TO JUSTIFY THE

5307
03:31:09,672 --> 03:31:11,440
SAMPLE SIZE.

5308
03:31:11,440 --> 03:31:13,008
ALSO LAST CRASH IS STATISTICAL

5309
03:31:13,008 --> 03:31:14,243
METHODS.

5310
03:31:14,243 --> 03:31:15,778
ALTHOUGH THERE ARE SOME EXISTING

5311
03:31:15,778 --> 03:31:18,314
STATISTICAL METHODS TO CONDUCT

5312
03:31:18,314 --> 03:31:20,216
SSR, BUT THOSE METHODS MAY NOT

5313
03:31:20,216 --> 03:31:22,851
BE DIRECTLY APPLICABLE TO THE

5314
03:31:22,851 --> 03:31:24,920
ANIMAL STUDIES -- SORRY, ANIMAL

5315
03:31:24,920 --> 03:31:26,755
CLINICAL TRIALS, WHICH WE HAVE

5316
03:31:26,755 --> 03:31:28,624
DIFFERENT STUDY DESIGN STANDARDS

5317
03:31:28,624 --> 03:31:31,060
HUMAN CLINICAL TRIALS.

5318
03:31:31,060 --> 03:31:33,829
SO DESIGNING STUDY WITH SSR, ALL

5319
03:31:33,829 --> 03:31:35,130
THESE CONCERNS SHOULD BE TAKEN

5320
03:31:35,130 --> 03:31:38,734
INTO CONSIDERATION.

5321
03:31:38,734 --> 03:31:40,536
THE NEXT EXAMPLE WE TALK ABOUT

5322
03:31:40,536 --> 03:31:43,439
IS THE GROUP SEQUENTIAL DESIGN.

5323
03:31:43,439 --> 03:31:45,441
THIS DESIGN GIVES YOU A CHANCE

5324
03:31:45,441 --> 03:31:51,547
TO PROSPECTIVELY COMPARE THE

5325
03:31:51,547 --> 03:31:52,248
RESULTS AND WITH THE OPPORTUNITY

5326
03:31:52,248 --> 03:31:54,650
TO STOP THE STUDY EARLY FOR

5327
03:31:54,650 --> 03:31:55,251
EFFECTIVENESS.

5328
03:31:55,251 --> 03:31:58,854
AGAIN, YOU WILL NEED TO PRE

5329
03:31:58,854 --> 03:32:01,457
SPECIFY THE TIMING TO THE KEY

5330
03:32:01,457 --> 03:32:04,460
STUDY FACTORS AT A PLANNED

5331
03:32:04,460 --> 03:32:04,660
STAGE.

5332
03:32:04,660 --> 03:32:08,364
AND AFTER THE STUDY IS

5333
03:32:08,364 --> 03:32:10,065
INITIATED, YOU WILL LIKE BY THE

5334
03:32:10,065 --> 03:32:12,201
TIME OF THE FIRST INTERIM

5335
03:32:12,201 --> 03:32:13,869
ANALYSIS, YOU CONDUCT HYPOTHESIS

5336
03:32:13,869 --> 03:32:15,871
TESTING AND COMPARE THE P-VALUE

5337
03:32:15,871 --> 03:32:18,474
OBTAINED FROM THE TESTING TO A

5338
03:32:18,474 --> 03:32:20,876
PRE SPECIFIED ALPHA LEVEL,

5339
03:32:20,876 --> 03:32:21,944
CALLED ALPHA 1 HERE.

5340
03:32:21,944 --> 03:32:23,579
IF THE P-VALUE IS SMALLER THAN

5341
03:32:23,579 --> 03:32:27,283
THE ALPHA LEVEL, THAT MEANS THE

5342
03:32:27,283 --> 03:32:29,018
EFFECT YOU OBSERVED SO FAR IS

5343
03:32:29,018 --> 03:32:30,152
QUITE PROMISING AND YOU MAY STOP

5344
03:32:30,152 --> 03:32:32,788
THE STUDY FOR EARLY FOR

5345
03:32:32,788 --> 03:32:33,122
EFFECTIVENESS.

5346
03:32:33,122 --> 03:32:35,891
BUT IF IT'S LARGER THAN ALPHA 1,

5347
03:32:35,891 --> 03:32:37,893
YOU WILL NEED TO CONTINUE THE

5348
03:32:37,893 --> 03:32:40,529
STUDY UNTIL THE NEXT INTERIM

5349
03:32:40,529 --> 03:32:40,796
ANALYSIS.

5350
03:32:40,796 --> 03:32:43,399
AND THIS WHOLE PROCESS CAN BE

5351
03:32:43,399 --> 03:32:45,668
REPEATED UNTIL EITHER THE STUDY

5352
03:32:45,668 --> 03:32:48,771
IS STOPPED FOR EFFECTIVENESS

5353
03:32:48,771 --> 03:32:50,539
EARLY OR YOU CONTINUE TO THE END

5354
03:32:50,539 --> 03:32:50,873
AS PLANNED.

5355
03:32:50,873 --> 03:32:52,675
AND THEN A FINAL ANALYSIS SHOULD

5356
03:32:52,675 --> 03:32:55,311
BE CONDUCTED.

5357
03:32:55,311 --> 03:32:57,046
I WOULD LIKE TO DRAW ATTENTION

5358
03:32:57,046 --> 03:33:00,082
TO THE ALPHA LEVELS HERE.

5359
03:33:00,082 --> 03:33:03,052
ALPHA 1 AND ALPHA F.

5360
03:33:03,052 --> 03:33:05,154
ALL ARE SELECTED SUCH THAT THE

5361
03:33:05,154 --> 03:33:09,658
FAMILY WISE ERROR RATE IS

5362
03:33:09,658 --> 03:33:09,958
CONTROLLED.

5363
03:33:09,958 --> 03:33:12,261
SO, USUALLY THEY ARE MUCH

5364
03:33:12,261 --> 03:33:14,630
SMALLER THAN ALPHA LEVEL OF .05.

5365
03:33:14,630 --> 03:33:18,067
I GIVE YOU EXAMPLE IN THE NEXT

5366
03:33:18,067 --> 03:33:18,834
SLIDE.

5367
03:33:18,834 --> 03:33:21,603
SO THE GROUP SEQUENTIAL DESIGN

5368
03:33:21,603 --> 03:33:22,838
PROVIDES A CHANCE TO STOP THE

5369
03:33:22,838 --> 03:33:23,605
STUDY EARLY.

5370
03:33:23,605 --> 03:33:27,209
SO IT GENERALLY WILL REDUCE

5371
03:33:27,209 --> 03:33:28,243
EXPECTED SAMPLE SIZE AND THE

5372
03:33:28,243 --> 03:33:31,046
DURATION OF THE CLINICAL TRIALS.

5373
03:33:31,046 --> 03:33:33,482
BUT IN TERMS OF THE CONCERNS,

5374
03:33:33,482 --> 03:33:35,751
THE FIRST IS THE FAMILY WISE

5375
03:33:35,751 --> 03:33:36,585
ERROR RATE.

5376
03:33:36,585 --> 03:33:38,187
YOU'RE CONDUCTING MULTIPLE

5377
03:33:38,187 --> 03:33:39,855
TESTING, SO OF COURSE THE FAMILY

5378
03:33:39,855 --> 03:33:41,256
WISE ERROR RATE WILL BE

5379
03:33:41,256 --> 03:33:41,523
INFLATED.

5380
03:33:41,523 --> 03:33:43,359
IN THIS CASE, YOU WOULD NEED TO

5381
03:33:43,359 --> 03:33:44,560
ADJUST THE ALPHA LEVEL YOU WOULD

5382
03:33:44,560 --> 03:33:46,762
LIKE TO USE FOR EACH TEST.

5383
03:33:46,762 --> 03:33:50,199
HERE AT THE TABLE, IT SHOWS YOU

5384
03:33:50,199 --> 03:33:52,034
THE RELATIONSHIP BETWEEN THE

5385
03:33:52,034 --> 03:33:53,335
ALPHA LEVEL AND THE NUMBER OF

5386
03:33:53,335 --> 03:33:54,737
TESTING YOU WOULD LIKE TO

5387
03:33:54,737 --> 03:33:54,970
CONDUCT.

5388
03:33:54,970 --> 03:33:57,439
FOR EXAMPLE, IF YOU LIKE TO

5389
03:33:57,439 --> 03:33:59,208
CONDUCT TWO INTERIM ANALYSIS AND

5390
03:33:59,208 --> 03:34:01,410
ONE FINAL ANALYSIS, AND WOULD

5391
03:34:01,410 --> 03:34:03,412
LIKE TO USE THE SAME ALPHA LEVEL

5392
03:34:03,412 --> 03:34:05,047
FOR EACH TEST, THEN YOU NEED TO

5393
03:34:05,047 --> 03:34:08,517
COMPARE THE P-VALUE TO .022 FOR

5394
03:34:08,517 --> 03:34:09,551
EACH TEST.

5395
03:34:09,551 --> 03:34:13,021
AND AS THE NUMBER OF TESTS

5396
03:34:13,021 --> 03:34:14,623
INCREASES, THE ALPHA LEVEL FOR

5397
03:34:14,623 --> 03:34:18,494
EACH TEST WILL DECREASE

5398
03:34:18,494 --> 03:34:18,794
ACCORDINGLY.

5399
03:34:18,794 --> 03:34:20,863
SO THIS ALPHA LEVEL SHOULD BE

5400
03:34:20,863 --> 03:34:23,098
PRE SPECIFIED AS THEY NOT ONLY

5401
03:34:23,098 --> 03:34:25,067
JUST IMPACT THE FAMILY WISE

5402
03:34:25,067 --> 03:34:26,635
ERROR RATE, IT DEFINITELY IMPACT

5403
03:34:26,635 --> 03:34:27,336
YOUR POWER.

5404
03:34:27,336 --> 03:34:31,340
SO WE NEED THIS CRITERIA TO

5405
03:34:31,340 --> 03:34:32,641
CONDUCT THE POWER CALCULATION

5406
03:34:32,641 --> 03:34:35,144
FOR YOUR STUDY.

5407
03:34:35,144 --> 03:34:37,746
THE TIMING OF THE GROUP

5408
03:34:37,746 --> 03:34:39,348
SEQUENTIAL DESIGN IS IMPORTANT.

5409
03:34:39,348 --> 03:34:41,250
YOU WOULD LIKE TO TIME THIS SUCH

5410
03:34:41,250 --> 03:34:44,219
THAT IF THE TEST IS SIGNIFICANT,

5411
03:34:44,219 --> 03:34:45,554
STATISTICAL SIGNIFICANT.

5412
03:34:45,554 --> 03:34:47,456
YOU STILL HAVE SUFFICIENT SAMPLE

5413
03:34:47,456 --> 03:34:49,291
SIZE TO GENERALIZE YOUR RESULTS

5414
03:34:49,291 --> 03:34:52,094
TO THE TARGET POPULATION.

5415
03:34:52,094 --> 03:34:54,229
ALSO YOU WOULD LIKE TO HAVE

5416
03:34:54,229 --> 03:34:56,732
SUFFICIENT SAMPLE SIZE TO

5417
03:34:56,732 --> 03:34:58,434
ACHIEVE INDEPENDENT EVIDENCE AND

5418
03:34:58,434 --> 03:35:00,235
ALSO PROVIDE RELIABLE ASSESSMENT

5419
03:35:00,235 --> 03:35:03,105
OF SAFETY VARIABLES.

5420
03:35:03,105 --> 03:35:06,241
SO, THE STATISTICAL SIGNIFICANCE

5421
03:35:06,241 --> 03:35:09,244
HERE IS UNNECESSARY BUT NOT

5422
03:35:09,244 --> 03:35:09,545
SUFFICIENT.

5423
03:35:09,545 --> 03:35:12,147
THE CLINICAL RELEVANCE PLAYS A

5424
03:35:12,147 --> 03:35:13,182
VERY IMPORTANT ROLE TO DECIDE

5425
03:35:13,182 --> 03:35:16,051
WHETHER THE STUDY SHOULD BE

5426
03:35:16,051 --> 03:35:21,657
STOPPED FOR EFFECTIVENESS.

5427
03:35:21,657 --> 03:35:23,792
NOW LET'S SWITCH GEARS TO THE

5428
03:35:23,792 --> 03:35:24,827
ENRICHMENT DESIGN.

5429
03:35:24,827 --> 03:35:29,031
SO THE PLACEBO LEAD IN DESIGN IS

5430
03:35:29,031 --> 03:35:30,866
QUITE SELF-EXPLANATORY BY ITS

5431
03:35:30,866 --> 03:35:31,166
NAME.

5432
03:35:31,166 --> 03:35:34,203
SO ALL THE ELIGIBLE PATIENTS

5433
03:35:34,203 --> 03:35:35,938
WILL RECEIVE PLACEBO AND THEY

5434
03:35:35,938 --> 03:35:39,041
WILL BE OBSERVED FOR SOME

5435
03:35:39,041 --> 03:35:39,274
PERIOD.

5436
03:35:39,274 --> 03:35:43,445
WE CALL THIS PLACEBO-LEAD IN

5437
03:35:43,445 --> 03:35:43,779
PERIOD.

5438
03:35:43,779 --> 03:35:45,547
BY THE END OF THE PERIOD, EACH

5439
03:35:45,547 --> 03:35:48,450
PATIENT WILL BE CATEGORIZED AS

5440
03:35:48,450 --> 03:35:51,053
EITHER THE PLACEBO RESPONDER OR

5441
03:35:51,053 --> 03:35:52,454
NON RESPONDER BASED ON

5442
03:35:52,454 --> 03:35:55,057
CLINICALLY RELEVANT CRITERIA.

5443
03:35:55,057 --> 03:35:57,860
AND ONLY NON RESPONDERS WILL BE

5444
03:35:57,860 --> 03:36:00,462
OFFICIALLY ENROLLED INTO THE

5445
03:36:00,462 --> 03:36:02,297
STUDY AND WILL BE RANDOMIZED TO

5446
03:36:02,297 --> 03:36:03,966
EITHER THE TREATMENT ARM OR THE

5447
03:36:03,966 --> 03:36:05,968
PLACEBO ARM.

5448
03:36:05,968 --> 03:36:08,871
AND IN A STANDARD DESIGN TO

5449
03:36:08,871 --> 03:36:12,574
RESPONDERS WILL NOT BE FOLLOWED

5450
03:36:12,574 --> 03:36:12,808
ANYMORE.

5451
03:36:12,808 --> 03:36:14,810
SO THE EXPECTATION OF USING THIS

5452
03:36:14,810 --> 03:36:19,915
METHOD IS TO MITIGATE A PLACEBO

5453
03:36:19,915 --> 03:36:20,148
EFFECT.

5454
03:36:20,148 --> 03:36:22,885
HOWEVER, THIS BENEFIT IS QUITE

5455
03:36:22,885 --> 03:36:24,219
DEBATABLE.

5456
03:36:24,219 --> 03:36:25,988
ACCORDING TO A META-ANALYSIS

5457
03:36:25,988 --> 03:36:31,393
BASED ON 101 DEPRESSION STUDIES,

5458
03:36:31,393 --> 03:36:36,098
THIS PLACEBO EFFECT WAS NOT

5459
03:36:36,098 --> 03:36:37,399
DECREASED AS EXPECTED.

5460
03:36:37,399 --> 03:36:41,203
SO IT COULD BE DUE TO THE

5461
03:36:41,203 --> 03:36:45,140
LEAD-IN PERIOD WAS TOO SHORT.

5462
03:36:45,140 --> 03:36:47,009
I REMEMBER IT WAS SEVEN DAYS AND

5463
03:36:47,009 --> 03:36:49,011
SOME RESPONDERS MAY NOT HAVE

5464
03:36:49,011 --> 03:36:51,914
SUFFICIENT TIME TO SHOW THEIR

5465
03:36:51,914 --> 03:36:52,981
RESPONSE.

5466
03:36:52,981 --> 03:36:56,184
ALSO, IT COULD BE DUE TO THE

5467
03:36:56,184 --> 03:36:58,654
PATIENTS AND THE INVESTIGATORS

5468
03:36:58,654 --> 03:37:01,089
WERE NOT WELL HAVOCKED TO THE

5469
03:37:01,089 --> 03:37:02,925
STUDY FUTURE.

5470
03:37:02,925 --> 03:37:04,493
SO THERE WERE SEVERAL UPDATED

5471
03:37:04,493 --> 03:37:06,795
VERSIONS OF THIS PLACEBO LEAD-IN

5472
03:37:06,795 --> 03:37:07,596
DESIGN.

5473
03:37:07,596 --> 03:37:09,598
FOR EXAMPLE, MOST OF THE

5474
03:37:09,598 --> 03:37:10,632
PATIENTS AND THE INVESTIGATORS

5475
03:37:10,632 --> 03:37:13,802
ARE MASKED TO THE DURATION OF

5476
03:37:13,802 --> 03:37:17,639
THE LEAD-IN PERIOD SO THEY WILL

5477
03:37:17,639 --> 03:37:19,007
HAVE EXPECTED EXPECTATIONS ABOUT

5478
03:37:19,007 --> 03:37:20,342
THE RESPONSE.

5479
03:37:20,342 --> 03:37:24,079
AND ALSO, IN SOME STUDIES, THE

5480
03:37:24,079 --> 03:37:25,213
PLACEBO RESPONDERS WILL STAY IN

5481
03:37:25,213 --> 03:37:27,916
THE STUDY TO MAINTAIN MASKING.

5482
03:37:27,916 --> 03:37:29,418
SO SOME STRATEGIES MAY BE USED

5483
03:37:29,418 --> 03:37:32,588
TO IMPROVE THE DESIGN.

5484
03:37:32,588 --> 03:37:34,489
ONE ADVANTAGE OF USING THE

5485
03:37:34,489 --> 03:37:36,458
PLACEBO LEAD-IN DESIGN IS THAT

5486
03:37:36,458 --> 03:37:38,360
THE ENRICHMENT WAS CONDUCTED

5487
03:37:38,360 --> 03:37:40,629
BEFORE THE RANDOMIZATION AND

5488
03:37:40,629 --> 03:37:46,168
THIS WILL NOT REQUIRE A FORMAL

5489
03:37:46,168 --> 03:37:46,568
ALPHA ADJUSTMENT.

5490
03:37:46,568 --> 03:37:50,872
BUT I THINK THE MAIN CONCERN FOR

5491
03:37:50,872 --> 03:37:53,141
THIS METHOD IS THAT IT MAY NOT

5492
03:37:53,141 --> 03:37:55,611
BE GENERALIZABLE TO TARGET

5493
03:37:55,611 --> 03:37:55,911
POPULATION.

5494
03:37:55,911 --> 03:38:00,315
FOR EXAMPLE, IF THE RESULT WE

5495
03:38:00,315 --> 03:38:02,651
OBTAINED BASED ON THE PLACEBO

5496
03:38:02,651 --> 03:38:05,454
NON-RESPONDERS, MAY NOT BE THE

5497
03:38:05,454 --> 03:38:06,655
SAME AS THE RESPONDERS.

5498
03:38:06,655 --> 03:38:08,023
SO THEREFORE THE RESULTS MAY NOT

5499
03:38:08,023 --> 03:38:11,259
BE GENERALIZABLE TO THE WHOLE

5500
03:38:11,259 --> 03:38:11,727
POPULATION.

5501
03:38:11,727 --> 03:38:13,629
SO THEREFORE WE MAY NEED TO HAVE

5502
03:38:13,629 --> 03:38:16,031
LABELING IMPLICATIONS OR HAVE A

5503
03:38:16,031 --> 03:38:18,634
NARROWER INDICATION TO REFLECT A

5504
03:38:18,634 --> 03:38:23,372
SUB POPULATION STUDY.

5505
03:38:23,372 --> 03:38:26,475
TO WRAP IT UP, I THINK THE

5506
03:38:26,475 --> 03:38:28,877
KEYWORD FOR THIS TOPIC IS

5507
03:38:28,877 --> 03:38:29,177
PROSPECTIVE.

5508
03:38:29,177 --> 03:38:32,381
SO IF YOU WOULD LIKE TO USE ANY

5509
03:38:32,381 --> 03:38:35,050
ADAPTATION OR ENRICHMENT IN YOUR

5510
03:38:35,050 --> 03:38:37,719
STUDY, YOU WILL NEED TO

5511
03:38:37,719 --> 03:38:40,355
PROSPECTIVELY SPECIFY ALL THE

5512
03:38:40,355 --> 03:38:45,327
KEY FEATURES OR ADAPTATION RULES

5513
03:38:45,327 --> 03:38:46,094
AT A PLANNED STAGE.

5514
03:38:46,094 --> 03:38:49,531
ALSO THE STATISTICAL HYPOTHESIS

5515
03:38:49,531 --> 03:38:50,799
TESTING METHODS SHOULD BE

5516
03:38:50,799 --> 03:38:52,501
APPLIED TO PUBLICLY CONTROLLED

5517
03:38:52,501 --> 03:38:53,468
FAMILY WISE ERROR RATE.

5518
03:38:53,468 --> 03:38:57,272
ALSO WE MAY NEED TO PAY EXTRA

5519
03:38:57,272 --> 03:38:58,407
ATTENTION TO THE

5520
03:38:58,407 --> 03:39:01,109
GENERALIZABILITY OF THE

5521
03:39:01,109 --> 03:39:05,347
EFFECTIVENESS DATA -- RESULTS.

5522
03:39:05,347 --> 03:39:08,350
SO IF YOU PLAN TO PLAN A STUDY

5523
03:39:08,350 --> 03:39:10,552
WITH ANY ADAPTATIONS OR

5524
03:39:10,552 --> 03:39:12,487
ENRICHMENT, I HIGHLY ENCOURAGE

5525
03:39:12,487 --> 03:39:16,892
THE EARLY INVOLVEMENT OF A

5526
03:39:16,892 --> 03:39:17,993
STATISTICIAN BECAUSE IT WOULD

5527
03:39:17,993 --> 03:39:19,828
FACILITATE A WHOLE PROCESS AND

5528
03:39:19,828 --> 03:39:23,765
MAKING THE COMMUNIQUESES MORE

5529
03:39:23,765 --> 03:39:24,232
EFFICIENT.

5530
03:39:24,232 --> 03:39:26,601
AND HERE ARE THE REFERENCES I

5531
03:39:26,601 --> 03:39:26,902
USED.

5532
03:39:26,902 --> 03:39:28,370
AND THANK YOU FOR YOUR

5533
03:39:28,370 --> 03:39:29,705
ATTENTION.

5534
03:39:29,705 --> 03:39:39,915
[ APPLAUSE ]

5535
03:39:44,486 --> 03:39:45,320
>> THANK YOU VERY MUCH TO
ALL OF

5536
03:39:45,320 --> 03:39:46,421
OUR SPEAKERS.

5537
03:39:46,421 --> 03:39:50,025
I'D LIKE TO INVITE OUR SPEAKERS

5538
03:39:50,025 --> 03:40:00,502
UP FOR THE PANEL DISCUSSION.

5539
03:40:44,446 --> 03:40:45,680
>> WHAT MIGHT BE SOME

5540
03:40:45,680 --> 03:40:46,248
CONSIDERATIONS FOR ADAPTIVE

5541
03:40:46,248 --> 03:40:49,117
SELECTION OF A PRIMARY ENDPOINT

5542
03:40:49,117 --> 03:40:59,694
AMONG MULTIPLE CANDIDATE POINTS.

5543
03:40:59,694 --> 03:41:04,666
>> THAT'S A HARD QUESTION.

5544
03:41:04,666 --> 03:41:08,036
REALLY.

5545
03:41:08,036 --> 03:41:12,707
SO THERE IS SUCH A DESIGN AS

5546
03:41:12,707 --> 03:41:14,543
ADAPTIVE ENDPOINT SELECTION

5547
03:41:14,543 --> 03:41:15,010
DESIGN.

5548
03:41:15,010 --> 03:41:18,313
IN THIS DESIGN IT BASICALLY

5549
03:41:18,313 --> 03:41:20,549
IS -- WE'LL START WITH MULTIPLE

5550
03:41:20,549 --> 03:41:24,619
ENDPOINTS AND THEN AFTER THE

5551
03:41:24,619 --> 03:41:25,821
FIRST STAGE THEN SOME

5552
03:41:25,821 --> 03:41:26,855
ADAPTATIONS WILL BE APPLIED AND

5553
03:41:26,855 --> 03:41:29,724
YOU WILL CHOOSE THE FINAL

5554
03:41:29,724 --> 03:41:32,360
ENDPOINT BASED ON THIS DESIGN.

5555
03:41:32,360 --> 03:41:33,929
I THINK ALONG WITH THE OTHER --

5556
03:41:33,929 --> 03:41:36,798
LIKE ALL THE OTHER ADAPTATIONS,

5557
03:41:36,798 --> 03:41:39,134
AGAIN ALL THE RULES, ADAPTATION

5558
03:41:39,134 --> 03:41:41,937
RULES AND STUDY DESIGN AND

5559
03:41:41,937 --> 03:41:43,672
STATISTICAL METHODS, SHOULD BE

5560
03:41:43,672 --> 03:41:44,472
PRE SPECIFIED.

5561
03:41:44,472 --> 03:41:47,676
BUT ALONG WITH THAT, THE AAT

5562
03:41:47,676 --> 03:41:49,044
THAT POINTIVE SELECTION IN

5563
03:41:49,044 --> 03:41:53,248
ENDPOINTS ACTUALLY WILL INFLATE

5564
03:41:53,248 --> 03:41:54,850
THE FAMILY WISE ERROR RATE DUE

5565
03:41:54,850 --> 03:41:55,917
TO TWO REASONS.

5566
03:41:55,917 --> 03:41:57,485
ONE IS THE MULTIPLE TESTING,

5567
03:41:57,485 --> 03:41:59,988
BECAUSE YOU HAVE MULTIPLE

5568
03:41:59,988 --> 03:42:01,823
ENDPOINTS AND ANOTHER ONE IS THE

5569
03:42:01,823 --> 03:42:02,858
SELECTION PROCESS.

5570
03:42:02,858 --> 03:42:06,294
SO THAT BASICALLY WILL REQUIRE

5571
03:42:06,294 --> 03:42:07,529
EVEN MORE RIGOROUS CONTROL OF

5572
03:42:07,529 --> 03:42:09,531
THE FAMILY WISE ERROR RATE.

5573
03:42:09,531 --> 03:42:11,967
AND SOMETIMES THE MULTIPLE

5574
03:42:11,967 --> 03:42:14,936
TESTING STRATEGIES ARE SO

5575
03:42:14,936 --> 03:42:17,239
COMPLICATED AND IT MAKES IT SO

5576
03:42:17,239 --> 03:42:19,808
VERY HARD TO COMMUNICATE WITH

5577
03:42:19,808 --> 03:42:20,742
THE CONDITIONS ABOUT THE PROCESS

5578
03:42:20,742 --> 03:42:22,544
AND THE RESULTS AND SOMETIMES

5579
03:42:22,544 --> 03:42:24,045
THESE MAY BE EVEN DIFFICULT TO

5580
03:42:24,045 --> 03:42:27,449
COMMUNICATE WITH THE

5581
03:42:27,449 --> 03:42:28,183
STATISTICAL -- AS WELL.

5582
03:42:28,183 --> 03:42:30,252
SO IF THIS IS THE METHOD YOU

5583
03:42:30,252 --> 03:42:34,456
WOULD LIKE TO USE IN YOUR STUDY,

5584
03:42:34,456 --> 03:42:37,959
A MORE EXTENSIVE DISCUSSIONS AND

5585
03:42:37,959 --> 03:42:39,728
COMPUTATIONS WILL BE REQUIRED TO

5586
03:42:39,728 --> 03:42:41,563
PLAN THE STUDY.

5587
03:42:41,563 --> 03:42:43,965
>> SO IF I COULD JUST SAY
ONE

5588
03:42:43,965 --> 03:42:44,232
THING.

5589
03:42:44,232 --> 03:42:45,533
BOTH OF YOU COMMENTED ON THE

5590
03:42:45,533 --> 03:42:47,269
DIFFERENCE BETWEEN THE

5591
03:42:47,269 --> 03:42:49,237
EXPLORATORY AND CONFIRMED

5592
03:42:49,237 --> 03:42:49,471
TRIALS.

5593
03:42:49,471 --> 03:42:53,041
AND I THINK IN AN EXPLORATORY

5594
03:42:53,041 --> 03:42:54,476
SETTING, ADAPTIVE CHOICE OF

5595
03:42:54,476 --> 03:42:56,244
OUTCOMES CAN BE A USEFUL TOOL,

5596
03:42:56,244 --> 03:42:58,747
MEANING YOU START OUT WITH

5597
03:42:58,747 --> 03:43:00,248
THREE-FOUR, AS I SUGGESTED

5598
03:43:00,248 --> 03:43:01,583
BRIEFLY AT THE END OF MY TALK.

5599
03:43:01,583 --> 03:43:03,551
YOU MIGHT USE A BIOMARKER AND

5600
03:43:03,551 --> 03:43:07,856
YOU'RE LOOKING TO SEE WHEN YOU

5601
03:43:07,856 --> 03:43:08,623
ADMINISTER YOUR TREATMENT

5602
03:43:08,623 --> 03:43:09,491
WHETHER THE BIOMARKER RESPONDS

5603
03:43:09,491 --> 03:43:12,360
IN THE WAY YOU EXPECT IT TO

5604
03:43:12,360 --> 03:43:12,594
RESPOND.

5605
03:43:12,594 --> 03:43:14,963
AND YOU'RE THEN MEASURING OTHER

5606
03:43:14,963 --> 03:43:16,364
FUNCTIONAL OUTCOMES AND OTHER

5607
03:43:16,364 --> 03:43:17,565
OUTCOMES AS YOU MOVE FORWARD.

5608
03:43:17,565 --> 03:43:19,668
IF YOU FIND THAT THE BIOMARKER

5609
03:43:19,668 --> 03:43:21,937
THAT YOU ARE CONVINCED IS

5610
03:43:21,937 --> 03:43:23,371
ACTUALLY SHOULD RESPOND TO THE

5611
03:43:23,371 --> 03:43:25,674
TREATMENT THAT YOU'RE GIVING,

5612
03:43:25,674 --> 03:43:28,510
YOU'RE GETTING A THYROID

5613
03:43:28,510 --> 03:43:30,078
MEDICINE AND THE TSH CAN CHANGE,

5614
03:43:30,078 --> 03:43:30,779
FOR INSTANCE.

5615
03:43:30,779 --> 03:43:32,914
I'M USING A RIDICULOUS EXAMPLE.

5616
03:43:32,914 --> 03:43:34,616
BUT THE POINT IS, IF YOU FIND

5617
03:43:34,616 --> 03:43:36,017
YOUR BIOMARKER DOESN'T, THAT

5618
03:43:36,017 --> 03:43:37,152
MEANS THAT MAYBE THE TREATMENT

5619
03:43:37,152 --> 03:43:38,486
ISN'T GETTING TO WHERE IT NEEDS

5620
03:43:38,486 --> 03:43:39,821
TO BE.

5621
03:43:39,821 --> 03:43:41,122
IT ISN'T BEING ABSORBED.

5622
03:43:41,122 --> 03:43:42,090
SOMETHING IS GOING ON WITH IT

5623
03:43:42,090 --> 03:43:44,626
AND THEN YOU CAN ABANDON THE

5624
03:43:44,626 --> 03:43:46,194
CONTINUED MONITORING OF THE

5625
03:43:46,194 --> 03:43:48,563
TRIAL BECAUSE IT'S NOT CAUSING

5626
03:43:48,563 --> 03:43:51,099
THE EFFECT THAT YOU THINK.

5627
03:43:51,099 --> 03:43:51,933
THAT'S PROBABLY NOT APPLICABLE

5628
03:43:51,933 --> 03:43:54,402
TO A CONFIRMATORY TRIAL BUT YOU

5629
03:43:54,402 --> 03:43:56,705
PROBABLY WANT, IF YOU HAVE A

5630
03:43:56,705 --> 03:43:57,605
BIOMARKER, TO ASSESS WHETHER THE

5631
03:43:57,605 --> 03:44:00,508
TREATMENT IS ACTUALLY DOING WHAT

5632
03:44:00,508 --> 03:44:01,943
YOU THINK IN THE ANIMAL OR THE

5633
03:44:01,943 --> 03:44:02,277
HUMAN.

5634
03:44:02,277 --> 03:44:03,912
IT'S PROBABLY A REASONABLE THING

5635
03:44:03,912 --> 03:44:06,514
TO INCLUDE IN CONFIRMATORY

5636
03:44:06,514 --> 03:44:09,584
TRIALS JUST TO BE SURE THAT THE

5637
03:44:09,584 --> 03:44:10,418
LOTS ARE REASONABLE.

5638
03:44:10,418 --> 03:44:12,787
THAT THE DRUG DIDN'T GET LEFT IN

5639
03:44:12,787 --> 03:44:14,823
THE SUN AND BAKED TO DEATH.

5640
03:44:14,823 --> 03:44:18,193
SO YOU CAN MAKE SURE THAT YOU'RE

5641
03:44:18,193 --> 03:44:19,294
DOING WHAT YOU THINK.

5642
03:44:19,294 --> 03:44:20,395
>> ONE OF THE DISCUSSIONS
WE

5643
03:44:20,395 --> 03:44:23,732
HAVE ON THE FOOD ANIMAL SIDE

5644
03:44:23,732 --> 03:44:25,300
ALWAYS IS HOW LONG THE

5645
03:44:25,300 --> 03:44:26,201
CLIMATIZATION PERIOD SHOULD BE

5646
03:44:26,201 --> 03:44:27,802
AND WHETHER THE CLIMATIZATION

5647
03:44:27,802 --> 03:44:29,604
PERIOD IS BEING SUFFICIENT AND

5648
03:44:29,604 --> 03:44:30,805
EFFECTIVE TO BE ABLE TO GIVE US

5649
03:44:30,805 --> 03:44:32,307
MEANINGFUL DATA WHEN WE PULL THE

5650
03:44:32,307 --> 03:44:33,775
TRIGGER ON THE STUDY ITSELF.

5651
03:44:33,775 --> 03:44:36,011
SO I THINK MEASURING SOME OF OUR

5652
03:44:36,011 --> 03:44:37,746
PROSPECTIVE ENDPOINTS IN THESE

5653
03:44:37,746 --> 03:44:40,115
ANIMALS ON ARRIVAL AND THEN

5654
03:44:40,115 --> 03:44:41,216
RE-MEASURING THEM CLOSER TO THE

5655
03:44:41,216 --> 03:44:43,818
START OF THE STUDY TO SEE

5656
03:44:43,818 --> 03:44:45,987
WHETHER THEIR POPULATIONS WITHIN

5657
03:44:45,987 --> 03:44:48,890
OUR POPULATION THAT HAVEN'T

5658
03:44:48,890 --> 03:44:50,258
ACCLIMATED WELL TO OUR FACILITY,

5659
03:44:50,258 --> 03:44:52,093
THAT COULD MAKE OUR TRIALS MORE

5660
03:44:52,093 --> 03:44:54,729
POWERFUL BY BEING ABLE TO HAVE

5661
03:44:54,729 --> 03:44:56,398
THAT ASSESSMENT TOOL IN TERMS OF

5662
03:44:56,398 --> 03:44:58,099
MAKING BETTER DECISIONS WITH THE

5663
03:44:58,099 --> 03:45:00,068
STUDY POPULATION.

5664
03:45:00,068 --> 03:45:01,503
>> JUST IN HUMANS, WHAT
THAT

5665
03:45:01,503 --> 03:45:03,471
MEANS IS WE MEASURE PAIN FOR

5666
03:45:03,471 --> 03:45:04,873
SEVEN DAYS BEFORE YOU ENROLL

5667
03:45:04,873 --> 03:45:06,408
THEM IN THE TRIAL.

5668
03:45:06,408 --> 03:45:08,443
WE ARE LOOKING TO SEE THAT

5669
03:45:08,443 --> 03:45:09,778
PATIENTS ARE ABLE TO DO WHAT WE

5670
03:45:09,778 --> 03:45:12,113
ARE ASKING OF THEM.

5671
03:45:12,113 --> 03:45:14,816
AND THERE IS A RUN-IN PROCEDURAL

5672
03:45:14,816 --> 03:45:15,984
RUN-IN THAT IS VERY, VERY

5673
03:45:15,984 --> 03:45:17,118
EFFECTIVE IN MAKING SURE THAT

5674
03:45:17,118 --> 03:45:18,753
YOU GET PATIENTS WHO CAN

5675
03:45:18,753 --> 03:45:20,121
ACTUALLY DO WHAT YOU'RE THINKING

5676
03:45:20,121 --> 03:45:20,321
ABOUT.

5677
03:45:20,321 --> 03:45:21,556
BECAUSE WHEN YOU ENROLL PEOPLE

5678
03:45:21,556 --> 03:45:23,892
IN TRIALS, THEY TEND TO GET

5679
03:45:23,892 --> 03:45:25,393
BETTER IN PAIN STUDIES IN

5680
03:45:25,393 --> 03:45:26,327
PARTICULAR, AND WE CAN TALK

5681
03:45:26,327 --> 03:45:28,563
ABOUT THE PLACEBO RUN-IN.

5682
03:45:28,563 --> 03:45:31,366
I HAVE TO SAY, I DISAGREE WITH

5683
03:45:31,366 --> 03:45:33,334
THAT PROCESS.

5684
03:45:33,334 --> 03:45:34,702
BUT THE ISSUE IS THE SAME HERE.

5685
03:45:34,702 --> 03:45:37,072
WE WANT TO CLIMATIZE PEOPLE TO

5686
03:45:37,072 --> 03:45:38,740
THE PROCEDURES THAT WE'RE DOING

5687
03:45:38,740 --> 03:45:40,542
AND MAKE SURE THEY ARE WILLING

5688
03:45:40,542 --> 03:45:43,578
TO DO THEM BEFORE YOU RANDOMIZE

5689
03:45:43,578 --> 03:45:44,312
THEM.

5690
03:45:44,312 --> 03:45:50,552
SO IT'S THE SAME KIND OF THING.

5691
03:45:50,552 --> 03:45:51,019
>> THANK YOU.

5692
03:45:51,019 --> 03:45:52,220
THANK YOU VERY MUCH FOR THE

5693
03:45:52,220 --> 03:45:52,554
PRESENTATIONS.

5694
03:45:52,554 --> 03:45:54,889
I HAD JUST A COUPLE OF QUESTIONS

5695
03:45:54,889 --> 03:45:57,425
IF YOU DON'T MIND, STATISTICALLY

5696
03:45:57,425 --> 03:45:58,359
RELATED.

5697
03:45:58,359 --> 03:46:02,230
SO IN PAIN STUDIES, WHAT'S THE

5698
03:46:02,230 --> 03:46:03,731
FAVORED WAY, BEST WAY -- I'D

5699
03:46:03,731 --> 03:46:05,033
LIKE YOUR THOUGHTS ON HOW TO

5700
03:46:05,033 --> 03:46:06,634
HANDLE MISSING DATA.

5701
03:46:06,634 --> 03:46:09,204
SHOULD WE BE LOOKING AT LAST

5702
03:46:09,204 --> 03:46:10,839
OBSERVATION CARRIED FORWARD,

5703
03:46:10,839 --> 03:46:13,308
USING A MEAN OF THE REST OF THE

5704
03:46:13,308 --> 03:46:14,943
SUBJECTS IN THAT GROUP AT THAT

5705
03:46:14,943 --> 03:46:15,610
TIME POINT?

5706
03:46:15,610 --> 03:46:20,615
MANY STATISTICAL PACKAGES WANT A

5707
03:46:20,615 --> 03:46:23,518
COMPLETE DATASET.

5708
03:46:23,518 --> 03:46:25,854
>> THAT'S A GREAT
QUESTION.

5709
03:46:25,854 --> 03:46:31,126
I THINK PROBABLY THE ANSWER

5710
03:46:31,126 --> 03:46:31,693
DIFFERS A LITTLE BIT BETWEEN

5711
03:46:31,693 --> 03:46:33,995
ACADEMIC AND REGULATORY SETTING.

5712
03:46:33,995 --> 03:46:36,064
I THINK OFTEN IN A REGULATORY

5713
03:46:36,064 --> 03:46:39,534
SETTING, WE AREN'T USING AS MANY

5714
03:46:39,534 --> 03:46:40,301
IMPLEMENTATION METHODS.

5715
03:46:40,301 --> 03:46:43,238
SO WE MAY BE LOOKING AT -- IF WE

5716
03:46:43,238 --> 03:46:47,308
HAVE THE BINARY END POINT,

5717
03:46:47,308 --> 03:46:49,744
LOOKING AT THE DEFINED TREATMENT

5718
03:46:49,744 --> 03:46:52,046
FAILURES POTENTIALLY FOR ANIMALS

5719
03:46:52,046 --> 03:46:53,748
WHO ARE WITHDRAWN EARLY AND

5720
03:46:53,748 --> 03:46:55,717
LOOKING TO MINIMIZE MISSING

5721
03:46:55,717 --> 03:46:55,917
DATA.

5722
03:46:55,917 --> 03:46:58,319
BUT IT CERTAINLY -- I THINK IT'S

5723
03:46:58,319 --> 03:47:00,755
HARDER TO IMPROSECUTE THE

5724
03:47:00,755 --> 03:47:03,992
STUDIES WE'RE LOOKING AT.

5725
03:47:03,992 --> 03:47:05,260
>> I THINK AT LEAST IN
HUMAN

5726
03:47:05,260 --> 03:47:07,762
STUDIES, THERE IS A DIFFERENCE

5727
03:47:07,762 --> 03:47:10,365
BETWEEN DIFFERENT KINDS OF

5728
03:47:10,365 --> 03:47:11,466
MISSING DATA.

5729
03:47:11,466 --> 03:47:12,634
IF YOU MISS A COUPLE OF POINTS

5730
03:47:12,634 --> 03:47:15,336
IN MEASURING THE DATA OR YOU

5731
03:47:15,336 --> 03:47:17,539
LOSE SOME DATA, BY THE END YOU

5732
03:47:17,539 --> 03:47:19,741
HAVE FOLLOW-UP DATA.

5733
03:47:19,741 --> 03:47:21,042
THAT'S A SITUATION WHERE

5734
03:47:21,042 --> 03:47:22,544
IMPLEMENTATION IS VERY OFTEN

5735
03:47:22,544 --> 03:47:24,946
USED TO GET A SENSE OF WHAT

5736
03:47:24,946 --> 03:47:26,114
WOULD HAVE HAPPENED IN BETWEEN.

5737
03:47:26,114 --> 03:47:27,282
YOU DON'T REALLY HAVE TO DO

5738
03:47:27,282 --> 03:47:27,482
THAT.

5739
03:47:27,482 --> 03:47:28,850
YOU CAN JUST USE THE DATA THAT

5740
03:47:28,850 --> 03:47:31,719
IS AVAILABLE IN THOSE

5741
03:47:31,719 --> 03:47:32,053
CIRCUMSTANCES.

5742
03:47:32,053 --> 03:47:33,388
IT'S WHY PATIENTS DROP OUT OR

5743
03:47:33,388 --> 03:47:34,355
YOU STOP COLLECTING DATA.

5744
03:47:34,355 --> 03:47:36,157
THERE IS A STRONG ARGUMENT FOR

5745
03:47:36,157 --> 03:47:37,759
NOT HAVING THEM DROP OUT FROM

5746
03:47:37,759 --> 03:47:39,093
THE COLLECTION OF THE DATA BUT

5747
03:47:39,093 --> 03:47:41,162
JUST DROP OUT FROM USING THE

5748
03:47:41,162 --> 03:47:41,963
DRUG.

5749
03:47:41,963 --> 03:47:44,065
AND YOU CAN INFER THINGS ABOUT

5750
03:47:44,065 --> 03:47:45,533
THE PATIENTS RELATED TO THAT.

5751
03:47:45,533 --> 03:47:48,770
THERE IS A NATIONAL ACADEMY OF

5752
03:47:48,770 --> 03:47:50,905
SCIENCE PIECE THAT TALKS ABOUT

5753
03:47:50,905 --> 03:47:52,373
THAT IN SPECIFIC AND BASICALLY

5754
03:47:52,373 --> 03:47:53,641
MIXED MODELING IS WHAT IS DONE

5755
03:47:53,641 --> 03:47:55,443
TO TRY TO USE ALL THE DATA THAT

5756
03:47:55,443 --> 03:47:58,646
IS AVAILABLE TO YOU.

5757
03:47:58,646 --> 03:48:01,182
IN TERMS OF DRAWING GRAPHS AND

5758
03:48:01,182 --> 03:48:02,050
OTHER THINGS, YOU HAVE TO DO

5759
03:48:02,050 --> 03:48:03,952
SOMETHING AND IT CAN GET VERY

5760
03:48:03,952 --> 03:48:04,786
COMPLICATED THERE.

5761
03:48:04,786 --> 03:48:05,820
BUT THERE ARE SOME VERY

5762
03:48:05,820 --> 03:48:06,921
STRAIGHTFORWARD WAYS OF TRYING

5763
03:48:06,921 --> 03:48:07,789
TO HANDLE IT.

5764
03:48:07,789 --> 03:48:09,891
THE BOTTOM LINE IS, IF YOU HAVE

5765
03:48:09,891 --> 03:48:12,260
GOT 20% MISSING DATA, YOU'RE

5766
03:48:12,260 --> 03:48:12,961
PROBABLY OKAY.

5767
03:48:12,961 --> 03:48:16,331
IF YOU HAVE GOT 40% OR SOMETHING

5768
03:48:16,331 --> 03:48:17,632
HIGHER, THEN YOU'RE DONE.

5769
03:48:17,632 --> 03:48:18,800
AND THE LAST COMMENT IS THAT IF

5770
03:48:18,800 --> 03:48:21,169
YOU DO A RESPONDER ANALYSIS, AND

5771
03:48:21,169 --> 03:48:22,737
WE TALKED A LOT THIS MORNING

5772
03:48:22,737 --> 03:48:24,639
ABOUT THAT, THEN MISSING --

5773
03:48:24,639 --> 03:48:26,774
PEOPLE WHO DROP OUT ARE NON

5774
03:48:26,774 --> 03:48:28,776
RESPONDERS BY DEFINITION.

5775
03:48:28,776 --> 03:48:30,845
SO THERE ISN'T ANY MISSING DATA

5776
03:48:30,845 --> 03:48:31,980
IN THAT SENSE.

5777
03:48:31,980 --> 03:48:34,415
AND SO, THE NICE THING ABOUT A

5778
03:48:34,415 --> 03:48:36,050
RESPONDER ANALYSIS IS THAT IT

5779
03:48:36,050 --> 03:48:37,352
DOESN'T EXPLAIN WHY THEY DROPPED

5780
03:48:37,352 --> 03:48:39,053
OUT AND SIDE EFFECTS AND LACK OF

5781
03:48:39,053 --> 03:48:39,320
EFFICACY.

5782
03:48:39,320 --> 03:48:40,455
BUT IT DOES ACCOUNT FOR THE FACT

5783
03:48:40,455 --> 03:48:43,157
THAT THEY ARE NOT THERE ANYMORE.

5784
03:48:43,157 --> 03:48:43,524
>> THANK YOU.

5785
03:48:43,524 --> 03:48:44,459
I HAVE ONE MORE QUESTION.

5786
03:48:44,459 --> 03:48:46,060
SO YOU MENTIONED RESPONDER

5787
03:48:46,060 --> 03:48:46,394
ANALYSIS.

5788
03:48:46,394 --> 03:48:47,895
WE TALKED ABOUT SUCCESS FAILURE.

5789
03:48:47,895 --> 03:48:50,231
AND AS WE SEE MORE OF THESE

5790
03:48:50,231 --> 03:48:52,000
RESULTS COMING OUT IN STUDIES,

5791
03:48:52,000 --> 03:48:54,902
WE CAN SEE THE DELTA VARIES

5792
03:48:54,902 --> 03:48:56,271
QUITE A BIT.

5793
03:48:56,271 --> 03:48:58,239
SUCCESS FAILURE DELTAS AND

5794
03:48:58,239 --> 03:49:00,842
OBVIOUSLY INCREASED SAMPLE SIZE.

5795
03:49:00,842 --> 03:49:02,243
YOU CAN GET THAT P-VALUE WHERE

5796
03:49:02,243 --> 03:49:05,213
YOU WANT IT, BUT ANY THOUGHTS ON

5797
03:49:05,213 --> 03:49:09,517
WHAT IS AN APPROPRIATE DELTA

5798
03:49:09,517 --> 03:49:11,719
BETWEEN SUCCESS IN THE TREATMENT

5799
03:49:11,719 --> 03:49:14,922
AND PLACEBO GROUP?

5800
03:49:14,922 --> 03:49:16,824
HOW SEPARATED DO THEY NEED TO

5801
03:49:16,824 --> 03:49:16,991
BE?

5802
03:49:16,991 --> 03:49:19,494
IS THERE A DEGREE OF SEPARATION

5803
03:49:19,494 --> 03:49:21,095
THAT GIVES YOU BETTER FEELING

5804
03:49:21,095 --> 03:49:24,132
COLLECTIVELY ABOUT THE

5805
03:49:24,132 --> 03:49:24,499
THERAPEUTIC?

5806
03:49:24,499 --> 03:49:27,035
>> SO, I WANT TO BE VERY
CLEAR

5807
03:49:27,035 --> 03:49:28,703
ABOUT SOMETHING THAT JEN WATERS

5808
03:49:28,703 --> 03:49:30,605
SAID, WHICH IS THAT THE

5809
03:49:30,605 --> 03:49:31,306
CLINICALLY-IMPORTANT DIFFERENCE

5810
03:49:31,306 --> 03:49:33,675
OR THE MINIMALLY-IMPORTANT

5811
03:49:33,675 --> 03:49:35,310
DIFFERENCE, WHATEVER, IS

5812
03:49:35,310 --> 03:49:36,110
APPLICABLE TO THE INDIVIDUAL.

5813
03:49:36,110 --> 03:49:38,212
IT'S NOT APPLICABLE TO THE

5814
03:49:38,212 --> 03:49:38,413
STUDY.

5815
03:49:38,413 --> 03:49:40,315
AND SO WHAT WE'RE DOING IS

5816
03:49:40,315 --> 03:49:41,683
CONVERTING INDIVIDUALS FROM A

5817
03:49:41,683 --> 03:49:44,619
NUMBER TO A RESPONDER OR NON

5818
03:49:44,619 --> 03:49:44,886
RESPONDER.

5819
03:49:44,886 --> 03:49:46,220
YOU THEN CALCULATE THE

5820
03:49:46,220 --> 03:49:47,955
PROPORTION OF PEOPLE WHO RESPOND

5821
03:49:47,955 --> 03:49:49,524
OR DON'T RESPOND.

5822
03:49:49,524 --> 03:49:53,328
THE DIFFERENCE BETWEEN THE

5823
03:49:53,328 --> 03:49:54,762
GROUPS IS NOT AN IDENTIFIABLE --

5824
03:49:54,762 --> 03:49:56,931
THERE ISN'T A WAY OF DETERMINING

5825
03:49:56,931 --> 03:49:58,599
WHAT THAT IS ABSENT

5826
03:49:58,599 --> 03:50:00,735
UNDERSTANDING THE DISEASE.

5827
03:50:00,735 --> 03:50:03,171
IF I TREAT HEADACHE AND I HAVE A

5828
03:50:03,171 --> 03:50:04,906
5% DIFFERENCE IN RESPONSE

5829
03:50:04,906 --> 03:50:05,807
BETWEEN TWO DRUGS, I WOULD SAY

5830
03:50:05,807 --> 03:50:07,542
THAT IS PROBABLY NOT

5831
03:50:07,542 --> 03:50:08,076
SIGNIFICANT.

5832
03:50:08,076 --> 03:50:10,845
IF I AM TREATING SEXIST OR

5833
03:50:10,845 --> 03:50:14,015
CARDIAC FAILURE AND I HAVE A 5%

5834
03:50:14,015 --> 03:50:16,317
CHANGE IN MORTALITY, I'D SAY

5835
03:50:16,317 --> 03:50:18,052
THAT'S PRETTY GOOD DIFFERENCE.

5836
03:50:18,052 --> 03:50:19,721
SO IT REALLY IS DEPENDENT ON

5837
03:50:19,721 --> 03:50:21,322
WHAT YOU'RE LOOKING AT.

5838
03:50:21,322 --> 03:50:22,223
AND I DON'T KNOW HOW TO

5839
03:50:22,223 --> 03:50:23,891
INTERPRET THAT WITH ANIMALS BUT

5840
03:50:23,891 --> 03:50:25,426
I THINK THE POINT IS, IT'S GOING

5841
03:50:25,426 --> 03:50:27,395
TO VARY TREMENDOUSLY.

5842
03:50:27,395 --> 03:50:28,896
THE PROBLEM THAT WE ARE PLAYING

5843
03:50:28,896 --> 03:50:30,765
WITH HERE AND WE WERE TALKING AT

5844
03:50:30,765 --> 03:50:32,367
LUNCH, IF YOU HAVE A DRUG THAT

5845
03:50:32,367 --> 03:50:33,735
CURES PAIN, JUST YOU TAKE ONE

5846
03:50:33,735 --> 03:50:35,937
PILL AND YOU'RE DONE, NO MORE

5847
03:50:35,937 --> 03:50:38,840
PAIN, ALL OF THIS IS MOOT.

5848
03:50:38,840 --> 03:50:40,141
YOU JUST GIVE PEOPLE THE THING

5849
03:50:40,141 --> 03:50:41,109
AND SEE WHAT HAPPENS.

5850
03:50:41,109 --> 03:50:42,343
THE TROUBLE IS, WE'RE NOT DOING

5851
03:50:42,343 --> 03:50:42,543
THAT.

5852
03:50:42,543 --> 03:50:45,179
WE ARE LOOKING AT CHANGES IN 10

5853
03:50:45,179 --> 03:50:46,447
OR 10 OR 30%.

5854
03:50:46,447 --> 03:50:48,116
AND WHEN WE GET INTO THAT LEVEL,

5855
03:50:48,116 --> 03:50:50,284
IT'S VERY HARD TO KNOW WHAT IS

5856
03:50:50,284 --> 03:50:54,322
GOING TO BE RELEVANT.

5857
03:50:54,322 --> 03:50:55,823
>> THANK YOU.

5858
03:50:55,823 --> 03:50:57,759
>> HI, KANSAS STATE.

5859
03:50:57,759 --> 03:51:02,597
THIS RESPONDER-NON-RESPONDER AND

5860
03:51:02,597 --> 03:51:05,566
EFFECT SIZE ISSUE IS KIND OF

5861
03:51:05,566 --> 03:51:08,035
A -- I'M INTERESTED TO HEAR HOW

5862
03:51:08,035 --> 03:51:10,872
HOW YOU PULL THESE THINGS APART.

5863
03:51:10,872 --> 03:51:13,775
THE LAST SPEAKER MENTIONED

5864
03:51:13,775 --> 03:51:16,210
PARSING THE PLACEBO GROUP INTO

5865
03:51:16,210 --> 03:51:17,545
RESPONDERS AND NON RESPONDERS,

5866
03:51:17,545 --> 03:51:19,313
WHICH I THOUGHT WAS REALLY AN

5867
03:51:19,313 --> 03:51:21,182
INTERESTING POINT.

5868
03:51:21,182 --> 03:51:22,950
BUT THE QUESTION IS, WHEN YOU

5869
03:51:22,950 --> 03:51:25,052
LOOK AT THE RESPONSE TO A DRUG

5870
03:51:25,052 --> 03:51:29,290
AND YOU HAVE THE UNIMODAL SHIFT,

5871
03:51:29,290 --> 03:51:31,893
YOU CAN INTERPRET.

5872
03:51:31,893 --> 03:51:33,728
WHAT HAPPENS WHEN YOU HAVE TWO

5873
03:51:33,728 --> 03:51:33,928
MODES?

5874
03:51:33,928 --> 03:51:36,497
YOU HAVE A RESPONDING GROUP THAT

5875
03:51:36,497 --> 03:51:39,801
IS QUITE SHIFTED FROM THE

5876
03:51:39,801 --> 03:51:41,068
NON-RESPONDING GROUP.

5877
03:51:41,068 --> 03:51:43,638
DO ANY OF OUR DESIGNS ACCOUNT

5878
03:51:43,638 --> 03:51:45,072
FOR THAT KIND OF CONDITION WHERE

5879
03:51:45,072 --> 03:51:50,578
THERE IS A CLEAR

5880
03:51:50,578 --> 03:51:53,247
RESPONDER/NON-RESPOND RENNER

5881
03:51:53,247 --> 03:51:53,448
GROUP?

5882
03:51:53,448 --> 03:51:56,884
>> LET ME TRY TO
UNDERSTAND YOUR

5883
03:51:56,884 --> 03:51:57,785
QUESTION.

5884
03:51:57,785 --> 03:51:59,887
SO YOU MEAN, THE TREATMENT GROUP

5885
03:51:59,887 --> 03:52:02,557
AND PLACEBO GROUP, THEY HAVE

5886
03:52:02,557 --> 03:52:06,394
DIFFERENT TYPES OF DISTRIBUTION?

5887
03:52:06,394 --> 03:52:06,661
SORRY.

5888
03:52:06,661 --> 03:52:10,131
CAN YOU REPEAT THAT PART?

5889
03:52:10,131 --> 03:52:12,733
>> YES, SORRY IF IT'S
UNCLEAR.

5890
03:52:12,733 --> 03:52:15,837
WHEN YOU GIVE THE DRUG AND YOU

5891
03:52:15,837 --> 03:52:17,472
HAVE PATIENTS THAT RESPOND TO

5892
03:52:17,472 --> 03:52:20,274
THE DRUG AND PATIENTS THAT DON'T

5893
03:52:20,274 --> 03:52:21,542
RESPOND TO THE DRUG -- SO

5894
03:52:21,542 --> 03:52:24,278
INSTEAD OF HAVING TA SKEWED

5895
03:52:24,278 --> 03:52:26,280
UNIMODAL DISTRIBUTION, YOU HAVE

5896
03:52:26,280 --> 03:52:27,982
A BI-MODAL DISTRIBUTION OF

5897
03:52:27,982 --> 03:52:29,917
RESPONDERS AND NON RESPONDERS.

5898
03:52:29,917 --> 03:52:32,420
THAT IS WHAT I'M ASKING ABOUT.

5899
03:52:32,420 --> 03:52:34,388
BECAUSE MOST OF OUR STATISTICAL

5900
03:52:34,388 --> 03:52:40,394
ANALYSIS, I MEAN, WE USE THE

5901
03:52:40,394 --> 03:52:42,897
UNIMODAL DISTRIBUTION.

5902
03:52:42,897 --> 03:52:46,434
>> SO I CAN START THERE.

5903
03:52:46,434 --> 03:52:49,003
THERE ARE SOME VERY KEY FEATURES

5904
03:52:49,003 --> 03:52:51,606
TO THE STUDY OF PAIN THAT I

5905
03:52:51,606 --> 03:52:52,773
THINK ARE IMPORTANT.

5906
03:52:52,773 --> 03:52:56,978
IN A GRAPH THAT JENNIFER WAS

5907
03:52:56,978 --> 03:53:00,181
NICE ENOUGH TO SHOW, WHICH WAS

5908
03:53:00,181 --> 03:53:03,985
SHOWING THE RESULTS IN MULTIPLE

5909
03:53:03,985 --> 03:53:06,954
DIFFERENT DISEASES, CRON LOW

5910
03:53:06,954 --> 03:53:08,489
BACK PAIN, ET CETERA, THERE WAS

5911
03:53:08,489 --> 03:53:09,624
A VERY TIGHT RELATIONSHIP

5912
03:53:09,624 --> 03:53:13,394
BETWEEN THE CHANGE IN PAIN AND

5913
03:53:13,394 --> 03:53:16,330
THE LEVEL ON THE GLOBAL SCALE.

5914
03:53:16,330 --> 03:53:17,765
WHAT ALSO WE TESTED IN THAT

5915
03:53:17,765 --> 03:53:19,433
STUDY WAS WHETHER IT MADE A

5916
03:53:19,433 --> 03:53:20,868
DIFFERENCE WHETHER YOU GOT THE

5917
03:53:20,868 --> 03:53:21,536
PLACEBO OR NOT.

5918
03:53:21,536 --> 03:53:23,004
AND IT TURNED OUT THAT THE

5919
03:53:23,004 --> 03:53:24,605
PEOPLE WHO RESPONDED IN THE

5920
03:53:24,605 --> 03:53:26,874
PLACEBO GROUP HAD EXACTLY THE

5921
03:53:26,874 --> 03:53:28,509
SAME CURVE, WHICH WAS REALLY

5922
03:53:28,509 --> 03:53:29,877
IMPORTANT BECAUSE IT MEANT THAT

5923
03:53:29,877 --> 03:53:31,712
WE WEREN'T DIFFERENTIATING

5924
03:53:31,712 --> 03:53:33,114
BETWEEN PEOPLE IN THE TREATMENT

5925
03:53:33,114 --> 03:53:35,182
AND PLACEBO GROUP BY DESIGNATING

5926
03:53:35,182 --> 03:53:37,685
PEOPLE AS RESPONDERS.

5927
03:53:37,685 --> 03:53:38,786
YOUR POINT, AND I'M NOT SURE

5928
03:53:38,786 --> 03:53:40,388
THIS IS YOUR QUESTION BUT I'M

5929
03:53:40,388 --> 03:53:43,691
GOING TO ANSWER THE QUESTION I

5930
03:53:43,691 --> 03:53:44,492
WANT TO ANSWER.

5931
03:53:44,492 --> 03:53:46,193
NO MATTER WHAT WE USE, THERE IS

5932
03:53:46,193 --> 03:53:47,595
A CERTAIN PERCENTAGE OF PEOPLE

5933
03:53:47,595 --> 03:53:50,231
THAT DON'T RESPOND, EVEN WITH

5934
03:53:50,231 --> 03:53:51,232
THE VERY BEST THERAPY.

5935
03:53:51,232 --> 03:53:52,600
THERE IS A GROUP THAT DON'T

5936
03:53:52,600 --> 03:53:53,401
RESPOND.

5937
03:53:53,401 --> 03:53:54,802
IT IS INHERENT TO WHAT WE WANT

5938
03:53:54,802 --> 03:53:57,705
TO DO IN MEDICINE, AS WE BEGIN

5939
03:53:57,705 --> 03:53:58,806
TO PERSONALIZE IT TO TRY AND

5940
03:53:58,806 --> 03:54:01,108
UNDERSTAND WHAT THAT GROUP IS

5941
03:54:01,108 --> 03:54:01,442
BEFORE.

5942
03:54:01,442 --> 03:54:03,878
AND SO BEING ABLE TO DETECT A

5943
03:54:03,878 --> 03:54:05,279
GROUP OF PEOPLE IN THE TREATMENT

5944
03:54:05,279 --> 03:54:08,716
GROUP WHO DON'T RESPOND IS A KEY

5945
03:54:08,716 --> 03:54:10,184
FEATURE OF TRYING TO TREAT

5946
03:54:10,184 --> 03:54:12,253
PEOPLE MORE APPROPRIATELY AND

5947
03:54:12,253 --> 03:54:12,853
PREVENTING THEIR PAIN.

5948
03:54:12,853 --> 03:54:15,356
IN A STUDY WE ARE CONDUCTING OR

5949
03:54:15,356 --> 03:54:16,490
FINISHING UP AT THE UNIVERSITY

5950
03:54:16,490 --> 03:54:17,792
OF PENNSYLVANIA, WE ARE LOOKING

5951
03:54:17,792 --> 03:54:19,727
AT PATIENTS AFTER THE THIRD

5952
03:54:19,727 --> 03:54:23,331
MOLAR EXTRACTION WHO GET

5953
03:54:23,331 --> 03:54:23,598
IBUPROFEN.

5954
03:54:23,598 --> 03:54:25,633
80% OF THEM RESPOND BUT 20%

5955
03:54:25,633 --> 03:54:25,866
DON'T.

5956
03:54:25,866 --> 03:54:27,234
AND IT TURNS OUT THAT THERE ARE

5957
03:54:27,234 --> 03:54:28,736
SOME DIFFERENCES IN BLOOD

5958
03:54:28,736 --> 03:54:30,771
MEASURES AND BIOMARKERS THAT

5959
03:54:30,771 --> 03:54:33,741
MIGHT HELP US TO IDENTIFY THIS.

5960
03:54:33,741 --> 03:54:35,242
THIS IS NOT FINAL BY ANY MEANS

5961
03:54:35,242 --> 03:54:37,979
BUT IT TURNS OUT THAT LEUCOCYTE

5962
03:54:37,979 --> 03:54:39,280
ACTIVATION, WHICH IS AN

5963
03:54:39,280 --> 03:54:41,849
INDICATION OF INFLAMMATORY

5964
03:54:41,849 --> 03:54:43,150
PROCESS, IS -- AND PEOPLE WHO

5965
03:54:43,150 --> 03:54:45,786
HAVE A LIKE OOCYTE THAT IS VERY

5966
03:54:45,786 --> 03:54:48,656
ACTIVATED, THEY RESPOND BETTER

5967
03:54:48,656 --> 03:54:50,891
TO THE ANTI-INFLAMMATORY.

5968
03:54:50,891 --> 03:54:51,859
AND THE ONES WHO DON'T HAVE A

5969
03:54:51,859 --> 03:54:54,428
LOT OF LEUCOCYTE ACTIVATION

5970
03:54:54,428 --> 03:54:55,663
DON'T RESPOND AS WELL.

5971
03:54:55,663 --> 03:54:57,098
THAT SORT OF MAKES SENSE.

5972
03:54:57,098 --> 03:54:58,566
I'M NOT SAYING IT'S TRUE.

5973
03:54:58,566 --> 03:54:59,634
I'M JUST SAYING IT MAKES SENSE

5974
03:54:59,634 --> 03:55:00,868
FROM THE PERSPECTIVE THAT IF YOU

5975
03:55:00,868 --> 03:55:05,973
HAVE GOT A LOT OF

5976
03:55:05,973 --> 03:55:06,807
INFLAMMATION -- WOULD WORK.

5977
03:55:06,807 --> 03:55:08,442
AND THIS IS A KEY QUESTION.

5978
03:55:08,442 --> 03:55:10,444
THAT'S WHY I THINK THE RESPONDER

5979
03:55:10,444 --> 03:55:11,345
ANALYSIS APPROACH IS SO

5980
03:55:11,345 --> 03:55:11,779
IMPORTANT.

5981
03:55:11,779 --> 03:55:14,582
LOOKING FOR THAT BIMODALITY,

5982
03:55:14,582 --> 03:55:16,050
LOOKING FOR THE GROUPS THAT

5983
03:55:16,050 --> 03:55:18,653
DON'T RESPOND, IDENTIFYING

5984
03:55:18,653 --> 03:55:20,554
GENOTYPES OF THOSE PEOPLE,

5985
03:55:20,554 --> 03:55:24,191
HOPEFULLY IN ADVANCE, WOULD BE

5986
03:55:24,191 --> 03:55:26,260
JUST A BOOM TO OUR TREATMENT OF

5987
03:55:26,260 --> 03:55:28,829
ALL DISEASES, FRANKLY.

5988
03:55:28,829 --> 03:55:30,731
>> AND JUST TO THINK
ABOUT, IF

5989
03:55:30,731 --> 03:55:32,366
YOU TALK ABOUT STATISTICAL

5990
03:55:32,366 --> 03:55:38,472
METHOD, JUST LIKE THE PLACEBO

5991
03:55:38,472 --> 03:55:39,740
DESIGN -- TREATMENT WITHDRAWAL

5992
03:55:39,740 --> 03:55:40,174
DESIGN.

5993
03:55:40,174 --> 03:55:42,276
IT'S LIKE THE OPPOSITE, EVERYONE

5994
03:55:42,276 --> 03:55:44,679
IS RECEIVING THE TREATMENT AND

5995
03:55:44,679 --> 03:55:46,981
THE RESPONDERS ARE NON

5996
03:55:46,981 --> 03:55:49,083
RESPONDERS WILL BE SEPARATED

5997
03:55:49,083 --> 03:55:50,551
AFTER THE LEAD-IN PERIOD AND

5998
03:55:50,551 --> 03:55:52,286
THEN ONLY THE RESPONDERS WILL BE

5999
03:55:52,286 --> 03:55:53,421
CONTINUED THROUGH THE STUDY AND

6000
03:55:53,421 --> 03:55:56,824
SOME OF THEM WILL BE

6001
03:55:56,824 --> 03:55:58,659
RERANDOMIZED TO THE PLACEBO

6002
03:55:58,659 --> 03:56:00,361
GROUP AND THEN THE ANALYSIS WILL

6003
03:56:00,361 --> 03:56:01,862
BE BASED ON THESE PATIENTS ONLY.

6004
03:56:01,862 --> 03:56:03,764
I THINK THE SAME ISSUE AS THE

6005
03:56:03,764 --> 03:56:05,266
PLACEBO LEAD-IN DESIGN.

6006
03:56:05,266 --> 03:56:06,634
HOW ARE YOU GOING TO INTERPRET

6007
03:56:06,634 --> 03:56:08,836
THE RESULTS AND HOW ARE YOU

6008
03:56:08,836 --> 03:56:12,006
GOING TO GENERALIZE THE RESULTS?

6009
03:56:12,006 --> 03:56:19,914
IT WILL BE SOMETHING TO CONSI 

6010
03:56:19,914 --> 03:56:20,181
CONSIDER.

6011
03:56:20,181 --> 03:56:21,015
>> THANK YOU.

6012
03:56:21,015 --> 03:56:28,155
DO WE KNOW ABOUT IMPORTANCE OF

6013
03:56:28,155 --> 03:56:32,460
PLACEBO EFFECT IN PAIN AND

6014
03:56:32,460 --> 03:56:34,395
CLINICAL TRIAL?

6015
03:56:34,395 --> 03:56:38,699
IF WE CHOOSE RATHER A COMPOSITE

6016
03:56:38,699 --> 03:56:44,038
CRITERIA RATHER THAN -- CRITE 

6017
03:56:44,038 --> 03:56:44,305
CRITERIA.

6018
03:56:44,305 --> 03:56:47,241
FOR THE SAME CLINICAL TRIAL, IF

6019
03:56:47,241 --> 03:56:50,811
YOU SELECT A COMPOSITE ENDPOINT

6020
03:56:50,811 --> 03:56:53,647
RATHER THAN A MULTIPLE ENDPOINT,

6021
03:56:53,647 --> 03:56:58,886
WHAT IS THE PLACEBO EFFECT

6022
03:56:58,886 --> 03:56:59,186
IMPORTANCE?

6023
03:56:59,186 --> 03:57:01,756
DO WE SEE SOME DIFFERENCE OR

6024
03:57:01,756 --> 03:57:01,922
NOT?

6025
03:57:01,922 --> 03:57:04,091
BEYOND THE FACT THAT AS IT HAS

6026
03:57:04,091 --> 03:57:05,626
BEEN EXPLAINED REGARDING

6027
03:57:05,626 --> 03:57:07,428
STATISTICAL APPROACH, THERE IS

6028
03:57:07,428 --> 03:57:09,630
PRO AND CONS FOR THE COMPOSITE

6029
03:57:09,630 --> 03:57:11,198
OR MULTIPLE.

6030
03:57:11,198 --> 03:57:12,767
BUT REGARDING SPECIFICALLY THE

6031
03:57:12,767 --> 03:57:14,502
PLACEBO EFFECT, WHAT DO WE KNOW

6032
03:57:14,502 --> 03:57:16,771
ABOUT THIS?

6033
03:57:16,771 --> 03:57:19,073
>> I THINK THIS IS AN
IMPORTANT

6034
03:57:19,073 --> 03:57:21,375
QUESTION THAT HAS NOT BEEN

6035
03:57:21,375 --> 03:57:23,677
COMPLETELY ANSWERED YET.

6036
03:57:23,677 --> 03:57:25,246
BUT, FOR EXAMPLE, IF YOU WERE TO

6037
03:57:25,246 --> 03:57:29,683
LOOK AT PHYSICAL FUNCTION VERSUS

6038
03:57:29,683 --> 03:57:31,418
REPORT OF PAIN AND DO SOME SORT

6039
03:57:31,418 --> 03:57:33,521
OF COMPOSITE WHERE YOU LOOK AT

6040
03:57:33,521 --> 03:57:35,256
PAIN PLUS PHYSICAL FUNCTION, THE

6041
03:57:35,256 --> 03:57:37,158
ISSUE THERE IS THAT IT MAY BE

6042
03:57:37,158 --> 03:57:39,160
THAT PEOPLE SAY, OH, YES, I'M

6043
03:57:39,160 --> 03:57:40,027
FEELING BETTER.

6044
03:57:40,027 --> 03:57:41,562
BUT THEY DON'T HAVE ANY CHANGE

6045
03:57:41,562 --> 03:57:44,698
IN THEIR WALKING ABILITY.

6046
03:57:44,698 --> 03:57:46,700
BECAUSE THE PAIN IS STILL THERE

6047
03:57:46,700 --> 03:57:48,068
AND THEY ARE STILL LAME BY IT.

6048
03:57:48,068 --> 03:57:50,471
SO THERE IS THE POSSIBILITY THAT

6049
03:57:50,471 --> 03:57:52,673
IF YOU PICK MORE FUNCTIONAL

6050
03:57:52,673 --> 03:57:53,774
MEASURES OR OTHER THINGS, YOU

6051
03:57:53,774 --> 03:57:57,511
MIGHT HAVE A SMALLER DEGREE OF A

6052
03:57:57,511 --> 03:57:58,379
PLACEBO EFFECT.

6053
03:57:58,379 --> 03:58:00,281
NOW, THE REASON THAT THAT IS

6054
03:58:00,281 --> 03:58:01,515
CONTROVERSIAL IS BECAUSE WHEN

6055
03:58:01,515 --> 03:58:03,384
PEOPLE THINK THEY DON'T HAVE

6056
03:58:03,384 --> 03:58:05,686
MORE PAIN, THEY TURN ON THEIR

6057
03:58:05,686 --> 03:58:06,587
ENDOGENOUS SYSTEMS AND THEY

6058
03:58:06,587 --> 03:58:08,789
DON'T HAVE MORE PAIN AND SO

6059
03:58:08,789 --> 03:58:10,324
THEIR PHYSICAL FUNCTION ACTUALLY

6060
03:58:10,324 --> 03:58:11,025
GETS BETTER.

6061
03:58:11,025 --> 03:58:12,893
IT IS NOT A DONE DEAL BY ANY

6062
03:58:12,893 --> 03:58:14,695
MEANS, BUT LOOKING AT THE

6063
03:58:14,695 --> 03:58:16,463
DIFFERENT OUTCOMES, I THINK IS

6064
03:58:16,463 --> 03:58:18,399
AN IMPORTANT ONE.

6065
03:58:18,399 --> 03:58:19,700
I'LL TAKE THE OPPORTUNITY TO SAY

6066
03:58:19,700 --> 03:58:22,503
ONE THING ABOUT THE PLACEBO

6067
03:58:22,503 --> 03:58:22,970
RUN-IN TRIAL.

6068
03:58:22,970 --> 03:58:25,973
I HAVE TO SAY THAT I ACTUALLY

6069
03:58:25,973 --> 03:58:27,575
DISAGREE WITH THE CONCEPT OF A

6070
03:58:27,575 --> 03:58:29,677
PLACEBO RUN-IN TRIAL.

6071
03:58:29,677 --> 03:58:31,312
PRIMARILY BECAUSE IT'S NOT A

6072
03:58:31,312 --> 03:58:33,180
PLACEBO RUN-IN TRIAL.

6073
03:58:33,180 --> 03:58:36,150
IT'S A PLACEBO-TREATED GROUP RUN

6074
03:58:36,150 --> 03:58:36,617
OF-IN TRIAL.

6075
03:58:36,617 --> 03:58:38,485
WHAT HAPPENS IN ANY GROUP THAT

6076
03:58:38,485 --> 03:58:39,687
YOU TREAT THERE IS NATURAL

6077
03:58:39,687 --> 03:58:40,888
HISTORY OF DISEASE.

6078
03:58:40,888 --> 03:58:41,989
SOME PEOPLE GET BETTER.

6079
03:58:41,989 --> 03:58:44,158
THERE IS REGRESSION TO THE MEAN.

6080
03:58:44,158 --> 03:58:45,392
PEOPLE WHO START AT A HIGH LEVEL

6081
03:58:45,392 --> 03:58:47,027
ARE GOING TO GO TO A LOW-LEVEL.

6082
03:58:47,027 --> 03:58:49,530
AND THEN THERE IS THE MIND/BODY

6083
03:58:49,530 --> 03:58:50,097
PLACEBO EFFECT.

6084
03:58:50,097 --> 03:58:52,166
THE TROUBLE WITH RUN-IN TRIAL IS

6085
03:58:52,166 --> 03:58:53,767
THAT YOU'RE EXCLUDING PEOPLE WHO

6086
03:58:53,767 --> 03:58:56,003
HAVE NATURAL VARIATION IN THEIR

6087
03:58:56,003 --> 03:58:56,704
DISEASE.

6088
03:58:56,704 --> 03:58:58,005
THOSE ARE EXACTLY THE ONES YOU

6089
03:58:58,005 --> 03:58:59,340
WANT IN YOUR TRIAL.

6090
03:58:59,340 --> 03:59:00,174
BECAUSE THEY HAVE NATURAL

6091
03:59:00,174 --> 03:59:02,610
VARIATION AND YOU WANT TO SEE IF

6092
03:59:02,610 --> 03:59:04,111
THAT CHANGE GETS BETTER OR

6093
03:59:04,111 --> 03:59:04,612
WORSE.

6094
03:59:04,612 --> 03:59:09,216
THE 101 TRIALS FOR DEPRESSION,

6095
03:59:09,216 --> 03:59:11,619
THEY FOUND THAT THE PLACEBO

6096
03:59:11,619 --> 03:59:13,420
RUN-IN DID NOT EFFECT THE

6097
03:59:13,420 --> 03:59:14,121
OUTCOMES.

6098
03:59:14,121 --> 03:59:16,390
AND THE SAME HAS BEEN FOUND IN

6099
03:59:16,390 --> 03:59:17,458
SEVERAL PAIN TRIALS AS WELL.

6100
03:59:17,458 --> 03:59:21,061
AND SO THE CONCEPT OF EXCLUDING

6101
03:59:21,061 --> 03:59:22,730
PEOPLE WHO RESPOND TO PLACEBO IS

6102
03:59:22,730 --> 03:59:25,065
JUST NOT A GOOD ONE.

6103
03:59:25,065 --> 03:59:26,867
HOWEVER, WE WERE TALKING ABOUT

6104
03:59:26,867 --> 03:59:28,035
THIS BEFORE.

6105
03:59:28,035 --> 03:59:29,570
PHENOTYPING YOUR PATIENTS, YOUR

6106
03:59:29,570 --> 03:59:31,538
ANIMALS, BEFORE YOU PUT THEM IN

6107
03:59:31,538 --> 03:59:34,341
YOUR TRIAL, WE KNOW THAT IN MICE

6108
03:59:34,341 --> 03:59:39,446
THERE IS THE WIMP SPECIES AND --

6109
03:59:39,446 --> 03:59:40,014
THE WIMP GROUP AND THE STOIC

6110
03:59:40,014 --> 03:59:40,247
GROUP.

6111
03:59:40,247 --> 03:59:42,049
IT TURNS OUT BLACK 6, THE ONE

6112
03:59:42,049 --> 03:59:43,651
MOST COMMONLY USED IS RIGHT IN

6113
03:59:43,651 --> 03:59:45,052
THE MIDDLE, WHICH IS LUCKY.

6114
03:59:45,052 --> 03:59:46,420
WE KNOW IN HUMANS, IT'S THE

6115
03:59:46,420 --> 03:59:46,620
SAME.

6116
03:59:46,620 --> 03:59:49,456
THERE ARE PEOPLE WHO RESPOND

6117
03:59:49,456 --> 03:59:51,325
REALLY WELL WITH PAIN.

6118
03:59:51,325 --> 03:59:53,260
THERE ARE THOSE WHO DON'T

6119
03:59:53,260 --> 03:59:54,361
RESPOND WELL TO PAIN.

6120
03:59:54,361 --> 03:59:56,864
AND WE NEED TO HAVE A PHENOTYPE

6121
03:59:56,864 --> 03:59:59,233
BEFORE WE START OUR TRIAL.

6122
03:59:59,233 --> 04:00:00,868
IN ANIMALS YOU WERE TALKING

6123
04:00:00,868 --> 04:00:03,170
ABOUT BEING ANXIOUS AFTER

6124
04:00:03,170 --> 04:00:04,772
TRAVELING HUNDREDS OF MILES AND

6125
04:00:04,772 --> 04:00:06,640
THEN TESTING THEM ALL OF A

6126
04:00:06,640 --> 04:00:06,874
SUDDEN.

6127
04:00:06,874 --> 04:00:08,375
IT'S LIKELY IN COWS AND SHEEP

6128
04:00:08,375 --> 04:00:10,611
AND ALL THE REST, THAT THEY ARE

6129
04:00:10,611 --> 04:00:12,079
GOING TO BE STOIC ANIMALS AND

6130
04:00:12,079 --> 04:00:12,346
NON-STOIC.

6131
04:00:12,346 --> 04:00:14,882
YOU MIGHT WANT TO DO SOME SORT

6132
04:00:14,882 --> 04:00:15,816
OF EXPERIMENTAL TEST,

6133
04:00:15,816 --> 04:00:16,650
EXPERIMENTAL PAIN, JUST A LITTLE

6134
04:00:16,650 --> 04:00:19,086
BIT OF HEAT OR SOMETHING, TO SEE

6135
04:00:19,086 --> 04:00:21,555
WHO RESPONDS TO THE PAIN BEFORE

6136
04:00:21,555 --> 04:00:23,257
YOU GO ENROLLING THEM UNTIL A

6137
04:00:23,257 --> 04:00:23,457
TRIAL.

6138
04:00:23,457 --> 04:00:25,659
SO THE PHENOTYPING OF PEOPLE

6139
04:00:25,659 --> 04:00:28,062
BEFORE YOU ENROLL THEM, I THINK

6140
04:00:28,062 --> 04:00:29,630
IS A VITAL ISSUE.

6141
04:00:29,630 --> 04:00:31,565
BUT I THINK THAT THE PLACEBO

6142
04:00:31,565 --> 04:00:32,967
RUN-IN IS PROBABLY NOT THE RIGHT

6143
04:00:32,967 --> 04:00:34,802
WAY TO DO THAT.

6144
04:00:34,802 --> 04:00:39,273
DID THAT ANSWER YOUR QUESTION?

6145
04:00:39,273 --> 04:00:41,875
>> I HAVE A QUESTION FOR
THE

6146
04:00:41,875 --> 04:00:42,176
PANEL.

6147
04:00:42,176 --> 04:00:43,277
WHAT ARE THE STAT ACTIVITY CALL

6148
04:00:43,277 --> 04:00:47,181
AND CLINICAL CONSIDERATIONS --

6149
04:00:47,181 --> 04:00:48,482
STATISTICAL -- ASSESSING A

6150
04:00:48,482 --> 04:00:52,419
SINGLE ENDPOINT AT MULTIPLE

6151
04:00:52,419 --> 04:00:57,691
POINTS VERSUS MULTIPLE ENDPOINTS

6152
04:00:57,691 --> 04:00:59,460
AT A SINGLE TIME POINT?

6153
04:00:59,460 --> 04:01:01,662
>> GOING BACK TO YOUR
POINT

6154
04:01:01,662 --> 04:01:03,263
ABOUT PAIN WAXING AND WANNING

6155
04:01:03,263 --> 04:01:05,566
AND POTENTIALLY NOT KNOWING WHEN

6156
04:01:05,566 --> 04:01:08,769
A DRUG IS GOING TO TAKE INTO

6157
04:01:08,769 --> 04:01:10,404
EFFECT, HAVING A SINGLE ENDPOINT

6158
04:01:10,404 --> 04:01:12,539
THAT YOU ASSESS AT MULTIPLE

6159
04:01:12,539 --> 04:01:15,409
TIMES IS A REALLY GREAT WAY TO

6160
04:01:15,409 --> 04:01:16,577
THINK ABOUT THIS.

6161
04:01:16,577 --> 04:01:19,413
A NICE POINT ALSO IF WE HAVE ONE

6162
04:01:19,413 --> 04:01:21,682
ENDPOINT WE LOOK AT AT MULTIPLE

6163
04:01:21,682 --> 04:01:24,084
TIME POINTS IS THAT WE CAN

6164
04:01:24,084 --> 04:01:26,086
ANALYZE POTENTIALLY IN A SINGLE

6165
04:01:26,086 --> 04:01:29,089
MODEL AND GAIN SOME POWER FROM

6166
04:01:29,089 --> 04:01:29,857
ONE ANALYSIS.

6167
04:01:29,857 --> 04:01:32,593
SO USING SOME INFORMATION FROM

6168
04:01:32,593 --> 04:01:33,894
THE OTHER TIME POINTS.

6169
04:01:33,894 --> 04:01:35,496
THE DOWNSIDE, THOUGH, IF WE HAVE

6170
04:01:35,496 --> 04:01:39,600
A MODEL WITH A TREATMENT EFFECT

6171
04:01:39,600 --> 04:01:41,802
AS WELL AS LOOKING AT THE

6172
04:01:41,802 --> 04:01:44,338
TREATMENT BY TIME INTERACTION,

6173
04:01:44,338 --> 04:01:45,806
IT CAN SOMETIMES BE DIFFICULT TO

6174
04:01:45,806 --> 04:01:48,776
MAKE CONCLUSIONS IF YOU SEE, FOR

6175
04:01:48,776 --> 04:01:51,078
EXAMPLE, THAT THERE IS A

6176
04:01:51,078 --> 04:01:52,012
SIGNIFICANT TREATMENT EFFECT AT

6177
04:01:52,012 --> 04:01:53,814
ONE TIME POINT AND THEN THE DRUG

6178
04:01:53,814 --> 04:01:55,015
DOESN'T WORK AT ANOTHER.

6179
04:01:55,015 --> 04:01:57,718
IT'S HARDER TO KNOW WHAT TO DO.

6180
04:01:57,718 --> 04:02:00,087
AND THEN I THINK POINTS ABOUT

6181
04:02:00,087 --> 04:02:02,523
WHETHER OR NOT TO HAVE MULTIPLE

6182
04:02:02,523 --> 04:02:04,825
ENDPOINTS AT A SINGLE TIME

6183
04:02:04,825 --> 04:02:06,693
POINT -- IF YOU'RE MORE

6184
04:02:06,693 --> 04:02:07,828
CONFIDENT ABOUT THAT BEING A

6185
04:02:07,828 --> 04:02:10,898
GOOD CHOICE OF TIME POINTS, BUT

6186
04:02:10,898 --> 04:02:13,600
PERHAPS THERE ARE MULTIPLE

6187
04:02:13,600 --> 04:02:14,768
DIFFERENT ASPECTS OF PAIN THAT

6188
04:02:14,768 --> 04:02:16,437
YOU WANT TO ANALYZE.

6189
04:02:16,437 --> 04:02:18,539
>> I THINK FOR US, IT
BECOMES A

6190
04:02:18,539 --> 04:02:21,508
QUESTION OF WHETHER YOU'RE

6191
04:02:21,508 --> 04:02:22,142
STUDYING INTEROR

6192
04:02:22,142 --> 04:02:23,310
INTRAINDIVIDUALS VARIATION,

6193
04:02:23,310 --> 04:02:25,679
BECAUSE WE ONLY HAVE SO MUCH

6194
04:02:25,679 --> 04:02:27,915
TIME AND SO MANY ANIMALS AND SO

6195
04:02:27,915 --> 04:02:29,183
MUCH HELP.

6196
04:02:29,183 --> 04:02:30,617
AND WHEN YOU START RUNNING

6197
04:02:30,617 --> 04:02:32,719
ANIMALS THROUGH THE SHOOT

6198
04:02:32,719 --> 04:02:33,720
REPEATEDLY, YOU'RE LIMITING THE

6199
04:02:33,720 --> 04:02:36,323
NUMBER OF ANIMALS YOU HAVE ON

6200
04:02:36,323 --> 04:02:37,591
TRIAL.

6201
04:02:37,591 --> 04:02:39,259
SO IT BECOMES AN

6202
04:02:39,259 --> 04:02:40,260
INTRA-INDIVIDUAL VARIABILITY

6203
04:02:40,260 --> 04:02:41,895
STUDY AND THEN YOU RUN INTO THE

6204
04:02:41,895 --> 04:02:42,996
RISK OF HABITATION.

6205
04:02:42,996 --> 04:02:44,832
THE ANIMALS GET USED TO THAT

6206
04:02:44,832 --> 04:02:46,500
FACILITY AND THAT IMPACTS THE

6207
04:02:46,500 --> 04:02:47,134
ENDPOINTS AS WELL BECAUSE THEY

6208
04:02:47,134 --> 04:02:48,268
HAVE SEEN IT ALL BEFORE.

6209
04:02:48,268 --> 04:02:49,736
IF YOU BRING IN A LARGE NUMBER

6210
04:02:49,736 --> 04:02:51,205
OF ANIMALS BUT YOU ONLY RUN THEM

6211
04:02:51,205 --> 04:02:53,140
THROUGH A COUPLE OF TIMES, YOU

6212
04:02:53,140 --> 04:02:54,741
GET MORE INTEREST-INDIVIDUAL

6213
04:02:54,741 --> 04:02:57,377
VARIATION ASSESSED BUT YOU'RE

6214
04:02:57,377 --> 04:03:00,147
THEN RUNNING INTO THIS ISSUE OF

6215
04:03:00,147 --> 04:03:01,882
THOSE ANIMALS AREN'T HABITUATING

6216
04:03:01,882 --> 04:03:03,917
EITHER SO THEY ARE BASICALLY --

6217
04:03:03,917 --> 04:03:05,586
IT COULD BE A POSITIVE OR A

6218
04:03:05,586 --> 04:03:06,520
NEGATIVE THING.

6219
04:03:06,520 --> 04:03:08,755
>> AND IF I COULD JUST
MAKE ONE

6220
04:03:08,755 --> 04:03:09,356
QUICK COMMENT.

6221
04:03:09,356 --> 04:03:11,225
WE MENTIONED ABOUT THE FACT THAT

6222
04:03:11,225 --> 04:03:12,826
PAIN, AT LEAST, VARIES OVER

6223
04:03:12,826 --> 04:03:13,527
TIME.

6224
04:03:13,527 --> 04:03:15,229
AND IF YOU IMAGINE THAT THE PAIN

6225
04:03:15,229 --> 04:03:16,930
IS VARYING IN YOUR TREATMENT

6226
04:03:16,930 --> 04:03:18,932
GROUP AND YOUR PLACEBO GROUP BUT

6227
04:03:18,932 --> 04:03:20,968
IT'S VARYING AT A SLIGHTLY

6228
04:03:20,968 --> 04:03:22,169
DIFFERENT FREQUENCY, THERE WILL

6229
04:03:22,169 --> 04:03:23,604
BE SOMETIMES WHEN THEY COME

6230
04:03:23,604 --> 04:03:24,605
CLOSER TOGETHER AND SOMETIMES

6231
04:03:24,605 --> 04:03:27,508
WHEN THE LINES BECOME FURTHER

6232
04:03:27,508 --> 04:03:27,741
APART.

6233
04:03:27,741 --> 04:03:31,512
AND SO I THINK JIM CAMPBELL'S

6234
04:03:31,512 --> 04:03:32,179
DISCUSSION THIS MORNING, WHICH

6235
04:03:32,179 --> 04:03:33,947
WAS TO LOOK AT ALL OF THE DATA

6236
04:03:33,947 --> 04:03:39,319
OVER TIME, IS MUCH STRONGER

6237
04:03:39,319 --> 04:03:40,220
INDICATION OF THE -- WHAT'S

6238
04:03:40,220 --> 04:03:41,688
GOING ON WITH THE GROUPS AND

6239
04:03:41,688 --> 04:03:43,157
WITH THE PATIENTS INDIVIDUALLY.

6240
04:03:43,157 --> 04:03:46,126
AND SO, I'M VERY MUCH IN FAVOR

6241
04:03:46,126 --> 04:03:47,528
OF MEASURING PAIN THROUGHOUT THE

6242
04:03:47,528 --> 04:03:49,029
STUDY AND IN FACT, THERE IS SOME

6243
04:03:49,029 --> 04:03:50,531
STUDIES THAT ARE 12 WEEKS LONG

6244
04:03:50,531 --> 04:03:53,033
AND THEY MEASURE EVERY DAY.

6245
04:03:53,033 --> 04:03:54,501
I DON'T KNOW HOW THEY DO THAT.

6246
04:03:54,501 --> 04:03:56,170
BUT THE POINT IS, YOU JUST GET A

6247
04:03:56,170 --> 04:03:58,672
LOT OF DATA TO BE ABLE TO LOOK

6248
04:03:58,672 --> 04:04:00,774
AT IT AND IT GIVES YOU MORE

6249
04:04:00,774 --> 04:04:02,643
POWER TO DIFFERENTIATE BETWEEN

6250
04:04:02,643 --> 04:04:02,876
GROUPS.

6251
04:04:02,876 --> 04:04:05,112
I THINK THAT WILL BE MY CHOICE.

6252
04:04:05,112 --> 04:04:07,047
MULTIPLE MEASURES ALWAYS A GOOD

6253
04:04:07,047 --> 04:04:08,549
IDEA RIGHT AT THE BEGINNING.

6254
04:04:08,549 --> 04:04:09,550
GET EVERYTHING RIGHT AT THE

6255
04:04:09,550 --> 04:04:16,290
BEGINNING AND AT THE END.

6256
04:04:16,290 --> 04:04:19,826
>> ONE MORE QUESTION.

6257
04:04:19,826 --> 04:04:20,661
>> THANK YOU.

6258
04:04:20,661 --> 04:04:22,196
I WAS WONDERING IF WE ARE

6259
04:04:22,196 --> 04:04:23,864
LOOKING AT THE BINARY OUTCOME

6260
04:04:23,864 --> 04:04:27,034
MEASUREMENT OF SUCCESS VERSUS

6261
04:04:27,034 --> 04:04:30,170
FAILURE, WE SEE THAT NOW

6262
04:04:30,170 --> 04:04:32,272
SOMETIMES USED IN STUDIES BUT

6263
04:04:32,272 --> 04:04:35,108
I'M WONDERING -- BECAUSE

6264
04:04:35,108 --> 04:04:36,710
SOMETIMES EVEN DO NOT PROVIDE

6265
04:04:36,710 --> 04:04:40,547
THE INITIAL DATA ANYMORE.

6266
04:04:40,547 --> 04:04:42,316
FOR EXAMPLE, [ INAUDIBLE ]

6267
04:04:42,316 --> 04:04:43,684
WONDERING IF THIS -- I REALLY

6268
04:04:43,684 --> 04:04:44,685
DON'T LIKE THIS.

6269
04:04:44,685 --> 04:04:46,186
BUT I WAS WONDERING WHAT YOUR

6270
04:04:46,186 --> 04:04:50,557
OPINION IS ABOUT THIS.

6271
04:04:50,557 --> 04:04:52,593
>> CAN YOU REPEAT THE
PART?

6272
04:04:52,593 --> 04:04:54,428
SO YOU'RE WONDERING ABOUT BINARY

6273
04:04:54,428 --> 04:04:56,129
ENDPOINTS IF THE THEY DON'T

6274
04:04:56,129 --> 04:04:58,198
PROVIDE WHAT?

6275
04:04:58,198 --> 04:04:59,399
>> THE ORIGINAL DATA.

6276
04:04:59,399 --> 04:05:05,839
SO THEY GO FROM CONTINUOUS DATA,

6277
04:05:05,839 --> 04:05:07,808
FOR EXAMPLE, SUCCESS AND FAILURE

6278
04:05:07,808 --> 04:05:10,477
AND IMPROVEMENT AND -- I WAS

6279
04:05:10,477 --> 04:05:12,412
WONDERING WHAT YOUR OPINION IS

6280
04:05:12,412 --> 04:05:12,913
ABOUT THAT?

6281
04:05:12,913 --> 04:05:14,448
NOT GIVING THE ORIGINAL

6282
04:05:14,448 --> 04:05:16,383
CONTINUOUS DATA ANYMORE BUT ONLY

6283
04:05:16,383 --> 04:05:19,386
PROVIDING THE SUCCESS RATE.

6284
04:05:19,386 --> 04:05:20,787
>> THAT'S A GREAT
QUESTION.

6285
04:05:20,787 --> 04:05:22,789
I THINK THAT THERE IS OFTENTIMES

6286
04:05:22,789 --> 04:05:24,925
WHERE IT CAN BE HELPFUL TO LOOK

6287
04:05:24,925 --> 04:05:27,494
AT THE ORIGINAL DATA AS PERHAPS

6288
04:05:27,494 --> 04:05:29,329
SOMETHING AS A SECONDARY OUTCOME

6289
04:05:29,329 --> 04:05:30,998
THAT YOU DON'T NECESSARILY HAVE

6290
04:05:30,998 --> 04:05:34,201
A FORMAL ANALYSIS BUT YOU HAVE

6291
04:05:34,201 --> 04:05:35,269
SOME STATISTICS.

6292
04:05:35,269 --> 04:05:37,104
I THINK IT CAN GIVE A LOT OF IN

6293
04:05:37,104 --> 04:05:39,706
TUITION AS TO HOW THE OUTCOME

6294
04:05:39,706 --> 04:05:43,277
WAS CONSTRUCTED.

6295
04:05:43,277 --> 04:05:43,977
>> FELLOWS THAT WORK WITH
ME

6296
04:05:43,977 --> 04:05:45,812
KNOW THAT THE ANSWER TO ANY

6297
04:05:45,812 --> 04:05:46,713
QUESTION ABOUT SHOULD I DO THIS

6298
04:05:46,713 --> 04:05:51,618
OR SHOULD I DO THAT IS, BOTH.

6299
04:05:51,618 --> 04:05:53,620
AND SO I THINK YOU HAVE THE

6300
04:05:53,620 --> 04:05:53,854
DATA.

6301
04:05:53,854 --> 04:05:57,924
YOU SHOULD LOOK AT IT BOTH WAYS.

6302
04:05:57,924 --> 04:05:59,226
OR IN MANY DIFFERENT WAYS, TO

6303
04:05:59,226 --> 04:06:00,060
TRY TO UNDERSTAND IT.

6304
04:06:00,060 --> 04:06:02,195
THE TROUBLE IS, YOU HAVE TO PICK

6305
04:06:02,195 --> 04:06:03,597
ONE AS THE PRIMARY.

6306
04:06:03,597 --> 04:06:05,299
AND AS DR. CAMPBELL SUGGESTED,

6307
04:06:05,299 --> 04:06:07,267
SOMETIMES WE GET THE WRONG ONE.

6308
04:06:07,267 --> 04:06:08,802
AND EVERYTHING ELSE IS POSITIVE

6309
04:06:08,802 --> 04:06:11,104
BUT YOU JUST CAN'T DEAL WITH IT.

6310
04:06:11,104 --> 04:06:12,739
THE LAST THING I WOULD SAY IS

6311
04:06:12,739 --> 04:06:14,374
THAT THE ISSUE ABOUT

6312
04:06:14,374 --> 04:06:16,610
DICHOTOMIZING DATA GOING FROM A

6313
04:06:16,610 --> 04:06:19,579
CONTINUOUS TO A DIE COT MISSCALE

6314
04:06:19,579 --> 04:06:21,181
IS YOU OBVIOUSLY LOSE POWER IN

6315
04:06:21,181 --> 04:06:24,518
THE PROCESS -- DICHOTOMOUS

6316
04:06:24,518 --> 04:06:25,185
SCALE -- IF YOU MEASURE THAT

6317
04:06:25,185 --> 04:06:28,522
OVER TIME AND WE ARE ABOUT TO

6318
04:06:28,522 --> 04:06:29,923
PUBLISH A PAPER ON THIS, IF YOU

6319
04:06:29,923 --> 04:06:31,358
MEASURE THAT OVER TIME YOU

6320
04:06:31,358 --> 04:06:33,226
REGRAIN ALMOST ALL THE POWER OF

6321
04:06:33,226 --> 04:06:34,494
LOOKING AT 50% OVER A LONG

6322
04:06:34,494 --> 04:06:34,995
PERIOD OF TIME.

6323
04:06:34,995 --> 04:06:36,697
THERE ARE WAYS TO THINK ABOUT

6324
04:06:36,697 --> 04:06:38,432
TAKING DATA AND MANIPULATING IT

6325
04:06:38,432 --> 04:06:40,233
IN A WAY SO THAT YOU DON'T LOSE

6326
04:06:40,233 --> 04:06:41,735
A TREMENDOUS AMOUNT OF POWER BUT

6327
04:06:41,735 --> 04:06:43,203
YOU STILL ARE ABLE TO LOOK AT

6328
04:06:43,203 --> 04:06:44,471
THE DIFFERENT OUTCOMES.

6329
04:06:44,471 --> 04:06:47,607
I THINK THE OUTCOMES PROVIDE YOU

6330
04:06:47,607 --> 04:06:48,942
DIFFERENT INFORMATION AND THEY

6331
04:06:48,942 --> 04:06:49,776
ARE BOTH IMPORTANT.

6332
04:06:49,776 --> 04:06:51,111
>> I THINK THE CHALLENGE
HERE IS

6333
04:06:51,111 --> 04:06:52,612
WE OFTEN GET A DISCONNECT

6334
04:06:52,612 --> 04:06:53,613
BETWEEN THE CLINICAL AND

6335
04:06:53,613 --> 04:06:54,514
RESEARCH SETTING AS WELL.

6336
04:06:54,514 --> 04:06:56,917
FROM A FOOD ANIMAL SIDE, OUR

6337
04:06:56,917 --> 04:06:58,585
PRODUCER WILL SAY THE COW GOT

6338
04:06:58,585 --> 04:06:59,619
BETTER OR SHE DIDN'T.

6339
04:06:59,619 --> 04:07:02,255
THERE IS NO IN BETWEEN

6340
04:07:02,255 --> 04:07:02,823
CONTINUOUS SCALE.

6341
04:07:02,823 --> 04:07:05,592
BUT FROM A RESEARCH SIDE, THE

6342
04:07:05,592 --> 04:07:06,326
CONTINUOUS SCALE WORKS BEST.

6343
04:07:06,326 --> 04:07:07,861
BUT AT THE END OF THE DAY, OUR

6344
04:07:07,861 --> 04:07:11,198
CLIENTS ARE LOOKING AT IT FROM A

6345
04:07:11,198 --> 04:07:12,366
DICHOTOMOUS, YES THEY GOT

6346
04:07:12,366 --> 04:07:13,500
BETTER, NO THEY DIDN'T.

6347
04:07:13,500 --> 04:07:14,801
IT'S TRANSLATING IT INTO A

6348
04:07:14,801 --> 04:07:16,069
LANGUAGE THEY UNDERSTAND AND

6349
04:07:16,069 --> 04:07:17,671
THAT ANIMAL LOOKS BETTER BECAUSE

6350
04:07:17,671 --> 04:07:19,306
IT GOT AN ANALGESIC.

6351
04:07:19,306 --> 04:07:20,340
THAT IS EVENTUALLY WHERE WE WILL

6352
04:07:20,340 --> 04:07:22,609
BE IN TERMS OF HOW THESE DRUGS

6353
04:07:22,609 --> 04:07:23,343
ARE USED.

6354
04:07:23,343 --> 04:07:25,612
>> AND THAT'S A KEY ISSUE.

6355
04:07:25,612 --> 04:07:26,613
CLINICAL DECISION-MAKING IS

6356
04:07:26,613 --> 04:07:27,114
DICHOTOMOUS.

6357
04:07:27,114 --> 04:07:28,415
I'M GOING TO GIVE THEM A DRUG.

6358
04:07:28,415 --> 04:07:29,015
I'M NOT.

6359
04:07:29,015 --> 04:07:30,550
THEY ARE GOING TO GET BETTER,

6360
04:07:30,550 --> 04:07:31,118
THEY ARE NOT.

6361
04:07:31,118 --> 04:07:32,819
SO YOU HAVE TO CONVERT WHATEVER

6362
04:07:32,819 --> 04:07:35,222
YOU DO INTO DICHOTOMOUS TO BE

6363
04:07:35,222 --> 04:07:39,493
USEFUL CLINICALLY.

6364
04:07:39,493 --> 04:07:40,227
>> THANK YOU.

6365
04:07:40,227 --> 04:07:42,629
>> I'D LIKE TO THANK OUR
PANEL

6366
04:07:42,629 --> 04:07:44,131
VERY MUCH --

6367
04:07:44,131 --> 04:07:45,065
>> JUST ONE QUESTION.

6368
04:07:45,065 --> 04:07:46,032
I THINK EVERYTHING THAT ALL OF

6369
04:07:46,032 --> 04:07:47,434
YOU HAVE SAID HERE IS VERY

6370
04:07:47,434 --> 04:07:47,701
VALUABLE.

6371
04:07:47,701 --> 04:07:51,605
MY NAME IS DEBRA AND I WORK WITH

6372
04:07:51,605 --> 04:07:53,640
BIOTREES ED (?) AND PHENOTYPING

6373
04:07:53,640 --> 04:07:55,742
IN ADVANCE OF STUDIES I THINK IS

6374
04:07:55,742 --> 04:07:56,943
REALLY WHERE IT'S AT.

6375
04:07:56,943 --> 04:07:59,045
AND I ALSO BELIEVE THAT YOU,

6376
04:07:59,045 --> 04:08:01,548
DR. JOHN FARRAR MENTIONED OUR

6377
04:08:01,548 --> 04:08:04,117
MOVE TOWARDS PRECISION MEDICINE.

6378
04:08:04,117 --> 04:08:06,319
AND IN LISTENING TO THAT, AND I

6379
04:08:06,319 --> 04:08:09,022
THINK JUST LACKING STATISTICAL

6380
04:08:09,022 --> 04:08:11,458
KNOWLEDGE LIKE SOME OF OUR TOWN

6381
04:08:11,458 --> 04:08:13,627
MEMBERS WHO ARE OBVIOUSLY VERY

6382
04:08:13,627 --> 04:08:15,862
TALENTED, WHAT I'M CURIOUS ABOUT

6383
04:08:15,862 --> 04:08:17,531
IS, IF WE PHENOTYPE AT THE

6384
04:08:17,531 --> 04:08:21,268
BEGINNING OF A STUDY AND THEN WE

6385
04:08:21,268 --> 04:08:23,837
LOOK AT THOSE DIFFERENT GROUPS,

6386
04:08:23,837 --> 04:08:27,174
IS IT BEST TO LOOK AT THE

6387
04:08:27,174 --> 04:08:29,910
STATISTICAL ANALYSIS AS

6388
04:08:29,910 --> 04:08:32,646
SUBGROUPS OR TO THEN TAKE THOSE

6389
04:08:32,646 --> 04:08:37,517
PHENOTYPES AND THEN STRAT FINEM

6390
04:08:37,517 --> 04:08:39,052
INTO YOUR RANDOMIZATION?

6391
04:08:39,052 --> 04:08:40,854
-- STRATIFY -- I'M NOT QUITE

6392
04:08:40,854 --> 04:08:42,622
SURE HOW THAT WOULD WORK OUT

6393
04:08:42,622 --> 04:08:43,623
STATISTICALLY BUT I KNOW IT'S

6394
04:08:43,623 --> 04:08:52,999
KEY TO PAIN AND HOW PAIN WORKS.

6395
04:08:52,999 --> 04:08:54,534
>> I'M NOT BASHFUL.

6396
04:08:54,534 --> 04:08:58,505
IF YOU HAVE THE MONEY TO RUN ALL

6397
04:08:58,505 --> 04:09:00,040
OF THE GROUPS BUT TO POWER IT

6398
04:09:00,040 --> 04:09:01,942
FOR THE PHENOTYPE THAT YOU THINK

6399
04:09:01,942 --> 04:09:04,010
IS VALID, THEN MORE POWER TO

6400
04:09:04,010 --> 04:09:04,177
YOU.

6401
04:09:04,177 --> 04:09:04,811
DO IT ALL.

6402
04:09:04,811 --> 04:09:06,980
THE TROUBLE IS, THAT WE DON'T

6403
04:09:06,980 --> 04:09:08,381
GENERALLY HAVE THAT.

6404
04:09:08,381 --> 04:09:10,550
SO PHENOTYPING THE IDEA, IS TO

6405
04:09:10,550 --> 04:09:11,651
STUDY ONLY THE ONES THAT YOU

6406
04:09:11,651 --> 04:09:13,653
THINK ARE GOING TO RESPOND AND

6407
04:09:13,653 --> 04:09:14,754
NOT STUDY THE OTHERS.

6408
04:09:14,754 --> 04:09:17,090
IF YOU ARE IN FACT STUDYING A

6409
04:09:17,090 --> 04:09:18,725
POPULATION AND TRYING TO

6410
04:09:18,725 --> 04:09:21,061
UNDERSTAND WITHIN THAT

6411
04:09:21,061 --> 04:09:23,129
POPULATION AND TO RETRO FIT

6412
04:09:23,129 --> 04:09:24,965
PHENOTYPES, THEN YOU END UP WITH

6413
04:09:24,965 --> 04:09:26,967
SUBGROUP ANALYSIS AND SUBGROUP

6414
04:09:26,967 --> 04:09:27,968
ANALYSIS HAVE ALL THE PROBLEMS

6415
04:09:27,968 --> 04:09:29,236
THAT GO WITH THAT.

6416
04:09:29,236 --> 04:09:30,570
MULTIPLE COMPARISONS AND OTHER

6417
04:09:30,570 --> 04:09:31,805
KINDS OF ISSUES.

6418
04:09:31,805 --> 04:09:34,908
BUT IT IS FROM AN EXPLORATORY

6419
04:09:34,908 --> 04:09:35,275
PERSPECTIVE.

6420
04:09:35,275 --> 04:09:36,409
EVERY TIME I TALK TO A GROUP

6421
04:09:36,409 --> 04:09:38,545
THAT IS TRYING TO DO A STUDY, I

6422
04:09:38,545 --> 04:09:40,180
SAY LOOK TO THE ONES WHO DON'T

6423
04:09:40,180 --> 04:09:40,480
RESPOND.

6424
04:09:40,480 --> 04:09:42,649
GO FIND THE ONES WHERE SOMETHING

6425
04:09:42,649 --> 04:09:44,017
ISN'T WORKING AND LET'S TRY TO

6426
04:09:44,017 --> 04:09:45,519
FIGURE OUT WHAT THAT IS AND

6427
04:09:45,519 --> 04:09:47,087
TRIED TO FIGURE OUT HOW TO MAKE

6428
04:09:47,087 --> 04:09:48,121
IT BETTER FOR THEM.

6429
04:09:48,121 --> 04:09:50,590
AND THEN FIGURE OUT HOW CAN I

6430
04:09:50,590 --> 04:09:52,492
IDENTIFY THE ONES AND HOW IT

6431
04:09:52,492 --> 04:09:52,692
WORKS?

6432
04:09:52,692 --> 04:09:55,595
STOW LOOKING AT IT, STRATIFY IT

6433
04:09:55,595 --> 04:09:58,732
AND SUBGROUPS ARE BOTH VALID.

6434
04:09:58,732 --> 04:10:00,300
I TOLD YOU, BOTH.

6435
04:10:00,300 --> 04:10:02,302
THEY ARE BOTH VALID WAYS OF

6436
04:10:02,302 --> 04:10:03,603
LOOKING AT IT.

6437
04:10:03,603 --> 04:10:05,572
THE PRIMARY OUT AND HAS TO BE

6438
04:10:05,572 --> 04:10:06,806
FOCUSED ON THE STUDY GROUP

6439
04:10:06,806 --> 04:10:08,542
YOU'RE LOOKING AT.

6440
04:10:08,542 --> 04:10:10,443
>> AND I JUST DID,
LISTENING TO

6441
04:10:10,443 --> 04:10:11,811
EACH OF YOU SPEAK AS WELL, I

6442
04:10:11,811 --> 04:10:13,179
THINK THAT ONE KEY FINDING, AND

6443
04:10:13,179 --> 04:10:16,950
I BELIEVE WHAT YOU SAID AS WELL,

6444
04:10:16,950 --> 04:10:18,518
THE EXEXSPORE TORY DESIGN IS A

6445
04:10:18,518 --> 04:10:18,919
GOOD ROUTE.

6446
04:10:18,919 --> 04:10:20,287
AND LOSE AND LOSE EARLY.

6447
04:10:20,287 --> 04:10:23,156
LOSE WELL AND LOSE EARLY.

6448
04:10:23,156 --> 04:10:26,893
BECAUSE THEN YOU CAN DEFINE WHAT

6449
04:10:26,893 --> 04:10:30,697
YOUR PARAMETERS ARE TO WIN.

6450
04:10:30,697 --> 04:10:33,166
PAIN IS COMPLEX.

6451
04:10:33,166 --> 04:10:33,700
>> THANK YOU VERY MUCH.

6452
04:10:33,700 --> 04:10:40,774
AND THANK YOU TO OUR PANEL.

6453
04:10:40,774 --> 04:10:50,984
[ APPLAUSE ]

6454
04:10:58,825 --> 04:11:00,327
>> ALL RIGHT, WHAT GREAT

6455
04:11:00,327 --> 04:11:00,660
DISCUSSION.

6456
04:11:00,660 --> 04:11:02,429
I'M JUST GOING TO TAKE A COUPLE

6457
04:11:02,429 --> 04:11:04,397
OF MINUTES HERE TO WRAP THINGS

6458
04:11:04,397 --> 04:11:04,898
UP.

6459
04:11:04,898 --> 04:11:06,299
WE WILL COME BACK TO FUTURE

6460
04:11:06,299 --> 04:11:09,502
PLANNING IN A SECOND.

6461
04:11:09,502 --> 04:11:11,304
FIRSTLY I WANT TO THANK ALL OF

6462
04:11:11,304 --> 04:11:13,607
YOU, ALL OF THE ATTENDEES, THE

6463
04:11:13,607 --> 04:11:14,708
ENGAGEMENT YOU HAVE ALL SHOWN,

6464
04:11:14,708 --> 04:11:16,042
THE DISCUSSION I KNOW HAS BEEN

6465
04:11:16,042 --> 04:11:16,610
GOING ON.

6466
04:11:16,610 --> 04:11:18,912
I HAVE BEEN LISTENING AND THERE

6467
04:11:18,912 --> 04:11:20,213
IS GREAT DISCUSSION OUT THERE

6468
04:11:20,213 --> 04:11:22,582
AND ALSO, THANK ALL OF THE

6469
04:11:22,582 --> 04:11:25,819
SPEAKERS FOR SHARING THEIR

6470
04:11:25,819 --> 04:11:27,454
KNOWLEDGE AND ENGAGING IN THE

6471
04:11:27,454 --> 04:11:27,754
DISCUSSION.

6472
04:11:27,754 --> 04:11:31,491
SO THANK YOU, EVERYONE.

6473
04:11:31,491 --> 04:11:33,927
AND THEN THIS SLIDE IS PRETTY

6474
04:11:33,927 --> 04:11:34,494
IMPORTANT.

6475
04:11:34,494 --> 04:11:35,629
WE COULD NOT COME TOGETHER OR

6476
04:11:35,629 --> 04:11:38,398
HAVE THIS MEETING WITHOUT OUR

6477
04:11:38,398 --> 04:11:39,532
SPONSORS.

6478
04:11:39,532 --> 04:11:41,067
SO SINCERE THANKS TO THE MAY DAY

6479
04:11:41,067 --> 04:11:43,269
FUND FOR REALLY SHORING UP THE

6480
04:11:43,269 --> 04:11:45,338
MAJORITY OF THE SPONSORSHIP WE

6481
04:11:45,338 --> 04:11:48,408
NEEDED TO PUT THIS EVENT ON.

6482
04:11:48,408 --> 04:11:51,645
AND I'D ALSO DUE THANKS TO THE

6483
04:11:51,645 --> 04:11:53,947
NIH, PARTICULARLY MARIE GILL,

6484
04:11:53,947 --> 04:11:55,248
MIKE LA SHIN SKI, FOR THEIR

6485
04:11:55,248 --> 04:11:57,117
SUPPORT, BOTH WITHIN THE NIH

6486
04:11:57,117 --> 04:12:01,054
BEING ADVOCATES FOR THE CORE

6487
04:12:01,054 --> 04:12:02,322
MEETING AND THEN ALSO TO

6488
04:12:02,322 --> 04:12:04,724
EVERYONE ELSE, ALL THE OTHER

6489
04:12:04,724 --> 04:12:08,028
STAFF BEHIND-THE-SCENES WHO

6490
04:12:08,028 --> 04:12:08,328
WORK.

6491
04:12:08,328 --> 04:12:08,928
THANK YOU.

6492
04:12:08,928 --> 04:12:10,230
THOSE WHO WORK AT THE NIH TO

6493
04:12:10,230 --> 04:12:11,564
HELP MAKE THIS HAPPEN.

6494
04:12:11,564 --> 04:12:12,932
[ APPLAUSE ]

6495
04:12:12,932 --> 04:12:14,100
AND THEN ALSO THANKS TO THE

6496
04:12:14,100 --> 04:12:16,236
MORRIS ANIMAL FOUNDATION AND THE

6497
04:12:16,236 --> 04:12:17,837
COMPARATIVE PAIN RESEARCH AND

6498
04:12:17,837 --> 04:12:18,805
EDUCATION CENTER FOR THE THE

6499
04:12:18,805 --> 04:12:19,439
ADDITIONAL SUPPORT.

6500
04:12:19,439 --> 04:12:29,949
I WANT TO ACKNOWLEDGE -- DON'T

6501
04:12:31,851 --> 04:12:32,719
WORRY.

6502
04:12:32,719 --> 04:12:35,321
I WANT TO ACKNOWLEDGE THE

6503
04:12:35,321 --> 04:12:36,222
ORGANIZING COMMITTEE.

6504
04:12:36,222 --> 04:12:37,991
YOU'LL FIND THE LIST OF EVERYONE

6505
04:12:37,991 --> 04:12:40,326
WHO IS IT ON THE ORGANIZING

6506
04:12:40,326 --> 04:12:42,729
COMMITTEE IN THE PROCEEDINGS.

6507
04:12:42,729 --> 04:12:45,231
AND ALSO THANK DANE JOHNSON,

6508
04:12:45,231 --> 04:12:46,433
JOHN COLE AND THE REST OF THE

6509
04:12:46,433 --> 04:12:49,569
TEAM AT THE NORTH CAROLINA STATE

6510
04:12:49,569 --> 04:12:50,336
UNIVERSITY CONTINUING EDUCATION

6511
04:12:50,336 --> 04:12:52,238
UNIT WHO HAVE HELPED DO ALL THE

6512
04:12:52,238 --> 04:12:54,307
ORGANIZATION AND BRING THIS

6513
04:12:54,307 --> 04:12:54,574
TOGETHER.

6514
04:12:54,574 --> 04:12:56,409
JUST A COUPLE OF OTHER THINGS.

6515
04:12:56,409 --> 04:12:57,610
A NUMBER OF PEOPLE ASKED ABOUT

6516
04:12:57,610 --> 04:12:59,345
WHETHER THE SLIDES WILL BE

6517
04:12:59,345 --> 04:12:59,612
AVAILABLE.

6518
04:12:59,612 --> 04:13:02,048
THEY WILL BE AVAILABLE IN PDF

6519
04:13:02,048 --> 04:13:05,652
FORMAT AND ALL ATTENDEES WILL BE

6520
04:13:05,652 --> 04:13:07,053
COMMUNICATED WITH BY DANE,

6521
04:13:07,053 --> 04:13:08,054
INDICATING WHERE YOU'LL BE ABLE

6522
04:13:08,054 --> 04:13:10,557
TO PICK UP THOSE PDFs OF THE

6523
04:13:10,557 --> 04:13:10,790
SLIDES.

6524
04:13:10,790 --> 04:13:12,726
AND DON'T FORGET THE

6525
04:13:12,726 --> 04:13:13,860
PROCEEDINGS, YOU SHOULD HAVE HAD

6526
04:13:13,860 --> 04:13:16,863
A LINK SENT TO YOU FOR THE

6527
04:13:16,863 --> 04:13:18,431
PROCEEDINGS.

6528
04:13:18,431 --> 04:13:20,233
WHAT HAS BEEN DISCUSSED IN THIS

6529
04:13:20,233 --> 04:13:21,534
MEETING WILL BE WRITTEN UP, A

6530
04:13:21,534 --> 04:13:22,569
COMBINATION OF THE COMMITTEE,

6531
04:13:22,569 --> 04:13:24,437
THE SPEAKERS GETTH TOGETHER TO

6532
04:13:24,437 --> 04:13:26,606
WRITE IT UP, WHETHER ONE

6533
04:13:26,606 --> 04:13:28,541
DOCUMENT OR A COUPLE, BUT WE ARE

6534
04:13:28,541 --> 04:13:30,143
ALL ONBOARD ABOUT DOING THAT,

6535
04:13:30,143 --> 04:13:31,444
AREN'T WE?

6536
04:13:31,444 --> 04:13:31,711
YES?

6537
04:13:31,711 --> 04:13:35,081
WE WILL START NEXT WEEK.

6538
04:13:35,081 --> 04:13:37,150
IT'S A LOT OF WORK.

6539
04:13:37,150 --> 04:13:38,318
IT'S A VERY IMPORTANT THING TO

6540
04:13:38,318 --> 04:13:38,752
BE DOING.

6541
04:13:38,752 --> 04:13:42,722
AND SO WITH THAT, THEN, IT JUST

6542
04:13:42,722 --> 04:13:45,258
REMAINS FOR ME TO SAY, I THINK

6543
04:13:45,258 --> 04:13:46,292
MICHELLE WHO WAS INVOLVED IN THE

6544
04:13:46,292 --> 04:13:48,061
INITIAL PLANNING OF THIS

6545
04:13:48,061 --> 04:13:48,795
MEETING, WOULD HAVE BEEN PROUD

6546
04:13:48,795 --> 04:13:49,796
OF THIS MEETING.

6547
04:13:49,796 --> 04:13:51,931
AND WHEREVER YOU ARE, MICHELLE,

6548
04:13:51,931 --> 04:13:53,299
THANK YOU FOR EVERYTHING THAT

6549
04:13:53,299 --> 04:13:55,835
YOU HAVE DONE IN THE PAST TO

6550
04:13:55,835 --> 04:13:58,404
MAKE THESE MEETINGS A SUCCESS,

6551
04:13:58,404 --> 04:13:59,239
INCLUDING THIS ONE.

6552
04:13:59,239 --> 04:14:05,278
AND WITH THAT -- I KNOW WE ARE

6553
04:14:05,278 --> 04:14:07,847
PAST 2:30 HERE AND PEOPLE MAY

6554
04:14:07,847 --> 04:14:08,548
HAVE TO LEAVE.

6555
04:14:08,548 --> 04:14:10,350
I WANT TO HAVE AN OPEN

6556
04:14:10,350 --> 04:14:13,086
DISCUSSION, IF ANYONE HAS ANY

6557
04:14:13,086 --> 04:14:13,686
THOUGHTS THEY'D LIKE TO SHARE

6558
04:14:13,686 --> 04:14:16,856
ABOUT THEMES FOR FUTURE

6559
04:14:16,856 --> 04:14:17,123
MEETINGS?

6560
04:14:17,123 --> 04:14:18,458
THE CORE MEETING ORIGINALLY WAS

6561
04:14:18,458 --> 04:14:20,393
SET UP TO DISCUSS THE

6562
04:14:20,393 --> 04:14:24,264
MEASUREMENT OF PAIN IN ANIMALS

6563
04:14:24,264 --> 04:14:28,168
WITH THE JEWELLISM OF IMPROVING

6564
04:14:28,168 --> 04:14:29,936
HUMAN HEALTH THROUGH PROVING OUR

6565
04:14:29,936 --> 04:14:31,504
ABILITY TO USE AND UNDERSTAND

6566
04:14:31,504 --> 04:14:34,140
ANIMAL MODELS AND ALSO IMPROVING

6567
04:14:34,140 --> 04:14:35,675
VETERINARY SPECIES HEALTH BY

6568
04:14:35,675 --> 04:14:38,044
IMPROVING OUR ABILITY TO MEASURE

6569
04:14:38,044 --> 04:14:39,479
AND THEREFORE TREAT PAIN.

6570
04:14:39,479 --> 04:14:41,848
SO THAT'S THE OVERARCHING THEME.

6571
04:14:41,848 --> 04:14:45,151
IF YOU HAVE OTHER IDEAS, PLEASE

6572
04:14:45,151 --> 04:14:45,585
SHARE THOSE.

6573
04:14:45,585 --> 04:14:47,654
AND YOU DON'T HAVE TO DO IT NOW,

6574
04:14:47,654 --> 04:14:49,789
BUT IF YOU HAVE COMMENTS YOU'D

6575
04:14:49,789 --> 04:14:52,826
LIKE TO SHARE WITH EVERYONE NOW

6576
04:14:52,826 --> 04:14:54,828
ABOUT THE POTENTIAL CONTENT,

6577
04:14:54,828 --> 04:14:56,329
THEMES OF FUTURE MEETINGS,

6578
04:14:56,329 --> 04:14:57,497
PLEASE DO.

6579
04:14:57,497 --> 04:14:59,799
OTHERWISE JUST REACH OUT TO

6580
04:14:59,799 --> 04:15:01,000
ANYONE ON THE ORGANIZING

6581
04:15:01,000 --> 04:15:01,267
COMMITTEE.

6582
04:15:01,267 --> 04:15:11,211
IT LOOKS LIKE WE HAVE --

6583
04:15:11,211 --> 04:15:14,013
>> I'LL MENTION A COUPLE
OF

6584
04:15:14,013 --> 04:15:14,247
THINGS.

6585
04:15:14,247 --> 04:15:14,681
CORNELL UNIVERSITY.

6586
04:15:14,681 --> 04:15:17,684
I'M NOT A PAIN EXPERT BUT I

6587
04:15:17,684 --> 04:15:18,885
FOCUS ON ARTIFICIAL

6588
04:15:18,885 --> 04:15:19,219
INTELLIGENCE.

6589
04:15:19,219 --> 04:15:23,089
I WANT TO MAKE A COUPLE OF

6590
04:15:23,089 --> 04:15:26,693
POINTS, OBSERVATIONS AND TO

6591
04:15:26,693 --> 04:15:29,829
SHARE FOR POTENTIAL THOUGHTS.

6592
04:15:29,829 --> 04:15:31,397
THE FIRST THOUGHT I HAD WAS JUST

6593
04:15:31,397 --> 04:15:34,033
THE WHOLE ISSUE OF METROLOGIY

6594
04:15:34,033 --> 04:15:36,603
AND HOW WE MEASURE THINGS.

6595
04:15:36,603 --> 04:15:39,806
AND I THINK THAT THERE CERTAINLY

6596
04:15:39,806 --> 04:15:41,608
IS SPACE WHERE THERE ARE

6597
04:15:41,608 --> 04:15:43,943
CHALLENGES IN SORT OF MEASURING

6598
04:15:43,943 --> 04:15:44,277
SOMETHING.

6599
04:15:44,277 --> 04:15:47,413
BUT THEN THERE ARE OTHER AREAS

6600
04:15:47,413 --> 04:15:50,083
WHERE YOU CAN REALLY MEASURE

6601
04:15:50,083 --> 04:15:51,718
SOMETHING VERY WELL AND

6602
04:15:51,718 --> 04:15:52,785
ACCURATELY AND PRECISELY.

6603
04:15:52,785 --> 04:15:53,887
THOSE ARE THE KINDS OF THINGS

6604
04:15:53,887 --> 04:15:56,022
THAT YOU HAVE A LOT OF CONTROL

6605
04:15:56,022 --> 04:15:56,389
OVER.

6606
04:15:56,389 --> 04:15:58,391
SO I HEAR THERE WAS SOME TALKS

6607
04:15:58,391 --> 04:16:01,895
ABOUT SENSORS TO MEASURE CERTAIN

6608
04:16:01,895 --> 04:16:02,161
THINGS.

6609
04:16:02,161 --> 04:16:04,130
NOW THESE THINGS WE CAN CONTROL

6610
04:16:04,130 --> 04:16:05,531
VERY WELL AND MEASURE.

6611
04:16:05,531 --> 04:16:07,100
WE CAN STANDARDIZE THESE THINGS.

6612
04:16:07,100 --> 04:16:08,935
WE CAN CALIBRATE THEM.

6613
04:16:08,935 --> 04:16:10,303
WE CAN PERFORM QUALITY ASSURANCE

6614
04:16:10,303 --> 04:16:12,639
ON THESE THINGS.

6615
04:16:12,639 --> 04:16:14,507
AND THIS IS CRITICAL FOR US TO

6616
04:16:14,507 --> 04:16:17,410
BE ABLE TO ENSURE THAT WE HAVE

6617
04:16:17,410 --> 04:16:18,912
APPLES-TO-APPLES COMPARISONS

6618
04:16:18,912 --> 04:16:22,048
WHEN WE DO -- WHEN WE REPORT OUR

6619
04:16:22,048 --> 04:16:22,248
DATA.

6620
04:16:22,248 --> 04:16:24,017
THAT WAS MY FIRST OBSERVATION

6621
04:16:24,017 --> 04:16:26,319
WAS TO WHAT EXTENT WE MIGHT BE

6622
04:16:26,319 --> 04:16:30,023
ABLE TO STANDARDIZE A LOT OF OUR

6623
04:16:30,023 --> 04:16:31,524
QUANTITATIVE DATA?

6624
04:16:31,524 --> 04:16:33,893
THE SECOND ONE IS KIND OF LINKED

6625
04:16:33,893 --> 04:16:36,629
TO THE WHOLE ARTIFICIAL

6626
04:16:36,629 --> 04:16:37,797
INTELLIGENCE QUESTION.

6627
04:16:37,797 --> 04:16:40,733
IN THAT PARTICULARLY WITH

6628
04:16:40,733 --> 04:16:41,601
MEDICINE, WE HAVE SERIOUS

6629
04:16:41,601 --> 04:16:43,670
CHALLENGES WITH DATA

6630
04:16:43,670 --> 04:16:46,639
HARMONIZATION AND DATA

6631
04:16:46,639 --> 04:16:46,906
STANDARDS.

6632
04:16:46,906 --> 04:16:49,375
IF YOU ARE SICK, YOU GO TO A

6633
04:16:49,375 --> 04:16:49,642
HOSPITAL.

6634
04:16:49,642 --> 04:16:51,844
YOU DEMANDED TO HAVE YOUR CT

6635
04:16:51,844 --> 04:16:52,045
SCANS.

6636
04:16:52,045 --> 04:16:54,213
YOU CAN GET THEM ON A DISK AND

6637
04:16:54,213 --> 04:16:56,215
IT HAS VERY SPECIFIC FORMAT THAT

6638
04:16:56,215 --> 04:16:58,017
IS RECOGNIZED INTERNATIONALLY.

6639
04:16:58,017 --> 04:16:59,319
THERE ARE STANDARDS FOR THESE

6640
04:16:59,319 --> 04:16:59,819
THINGS.

6641
04:16:59,819 --> 04:17:01,454
THERE IS INTEROPERABILITY FOR US

6642
04:17:01,454 --> 04:17:03,823
TO BE ABLE TO ACCESS THAT DATA

6643
04:17:03,823 --> 04:17:07,126
AND UNDERSTAND WHAT THE PIXELS

6644
04:17:07,126 --> 04:17:09,329
MEAN AND IN A RICH DEGREE OF

6645
04:17:09,329 --> 04:17:10,830
METADATA THAT HAS BEEN CURATED

6646
04:17:10,830 --> 04:17:13,733
BY A SERIES OF EXPERTS.

6647
04:17:13,733 --> 04:17:16,436
AGAIN, THEY MAKE THE DATA

6648
04:17:16,436 --> 04:17:18,604
TRANSPARENCY, EASY FOR US TO

6649
04:17:18,604 --> 04:17:19,572
UNDERSTAND WHAT THAT DATA IS.

6650
04:17:19,572 --> 04:17:22,408
I THINK THAT THAT IS A REALLY

6651
04:17:22,408 --> 04:17:24,243
CRITICAL CHALLENGE FOR FOLKS IN

6652
04:17:24,243 --> 04:17:26,045
VETERINARY MEDICINE WHERE WE

6653
04:17:26,045 --> 04:17:27,914
HAVE VERY DIFFERENT SYSTEMS.

6654
04:17:27,914 --> 04:17:29,315
THEY HAVE DIFFERENT FORMATS OF

6655
04:17:29,315 --> 04:17:32,051
THE DATA AND SOME OF THEM DON'T

6656
04:17:32,051 --> 04:17:34,220
HAVE ANY METADATA AT ALL.

6657
04:17:34,220 --> 04:17:37,190
SO FOR EVEN -- EVEN IF WE ARE

6658
04:17:37,190 --> 04:17:40,159
THINKING ABOUT AI AS BEING A

6659
04:17:40,159 --> 04:17:41,961
PANACEA TO SOLVE ALL OF OUR

6660
04:17:41,961 --> 04:17:44,630
PROBLEMS, I HAVE NEWS FOR YOU.

6661
04:17:44,630 --> 04:17:46,432
THAT IS IF WE DON'T HAVE DATA

6662
04:17:46,432 --> 04:17:47,734
STANDARDS, THERE IS NO WAY FOR

6663
04:17:47,734 --> 04:17:53,539
US TO BE ABLE TO REALLY BUILD

6664
04:17:53,539 --> 04:17:53,940
MULTIEL-PLATFORM,

6665
04:17:53,940 --> 04:17:54,607
MULTI-INSTITUTIONAL DATASETS FOR

6666
04:17:54,607 --> 04:17:57,977
US TO REALLY LEARN FROM THE

6667
04:17:57,977 --> 04:17:58,177
DATA.

6668
04:17:58,177 --> 04:17:59,746
THAT WAS AN IMPORTANT THINGS.

6669
04:17:59,746 --> 04:18:03,383
AND THEN THE FINAL POINT WAS

6670
04:18:03,383 --> 04:18:06,052
SORTAVE -- SOMETHING MY PH.D.

6671
04:18:06,052 --> 04:18:07,020
ADVISER WOULD SAY TO ME.

6672
04:18:07,020 --> 04:18:10,123
THAT WAS RELATED TO THE GENERAL

6673
04:18:10,123 --> 04:18:11,924
IDEA THAT IF YOUR TOOLS AREN'T

6674
04:18:11,924 --> 04:18:14,093
WORKING, FIND A BETTER TOOL.

6675
04:18:14,093 --> 04:18:15,361
BUT THE WORST THING YOU WANT TO

6676
04:18:15,361 --> 04:18:17,630
DO IS BUILD MORE RULES FOR THE

6677
04:18:17,630 --> 04:18:19,399
TOOLS THAT ARE NOT WORKING.

6678
04:18:19,399 --> 04:18:20,666
IN OTHER WORDS, IF WE'RE FINDING

6679
04:18:20,666 --> 04:18:23,669
THAT WE HAVE THESE DEVICES THAT

6680
04:18:23,669 --> 04:18:26,339
REQUIRE SO MUCH ENERGY AND

6681
04:18:26,339 --> 04:18:27,940
EFFORT TO BE ABLE TO EXTRACT

6682
04:18:27,940 --> 04:18:29,275
USEFUL INFORMATION FROM, THEN WE

6683
04:18:29,275 --> 04:18:30,643
REALLY HAVE TO ASK OURSELVES, IS

6684
04:18:30,643 --> 04:18:32,045
THIS THE RIGHT THING WE'RE

6685
04:18:32,045 --> 04:18:32,378
DOING?

6686
04:18:32,378 --> 04:18:33,846
AND ARE THERE BETTER

6687
04:18:33,846 --> 04:18:34,747
TECHNOLOGIES OR TECHNIQUES WE

6688
04:18:34,747 --> 04:18:37,016
CAN USE TO HELP QUANTIFY AND

6689
04:18:37,016 --> 04:18:38,584
CREATE THE KINDS OF LATITUDE

6690
04:18:38,584 --> 04:18:40,186
THAT WE NEED IN OUR DATASETS TO

6691
04:18:40,186 --> 04:18:43,156
CREATE THE POWER WE ARE LOOKING

6692
04:18:43,156 --> 04:18:44,390
FOR IN OUR STUDIES.

6693
04:18:44,390 --> 04:18:47,927
SO THOSE ARE THE THREE THINGS I

6694
04:18:47,927 --> 04:18:50,063
THOUGHT TO SHARE WITH THIS

6695
04:18:50,063 --> 04:18:50,263
GROUP.

6696
04:18:50,263 --> 04:18:51,330
>> THANK YOU.

6697
04:18:51,330 --> 04:18:53,032
TWO GREAT IDEAS AND ONE WARNING.

6698
04:18:53,032 --> 04:18:55,101
WE WILL BUST OUR BUBBLE IF WE

6699
04:18:55,101 --> 04:19:00,139
DON'T FIGURE OUT DATA

6700
04:19:00,139 --> 04:19:01,674
COMPATIBILITY.

6701
04:19:01,674 --> 04:19:05,511
THANK YOU.

6702
04:19:05,511 --> 04:19:07,346
>> SO, I'LL MAKE MINE
QUICK.

6703
04:19:07,346 --> 04:19:08,748
I THINK SOMETHING THAT COULD

6704
04:19:08,748 --> 04:19:10,550
REALLY ADD TO THE CONVERSATION

6705
04:19:10,550 --> 04:19:12,552
IS A DISCUSSION OF THE

6706
04:19:12,552 --> 04:19:13,152
NEUROGENETICS OF PAIN.

6707
04:19:13,152 --> 04:19:15,455
FOR INSTANCE, WE KNOW OF MANY

6708
04:19:15,455 --> 04:19:19,559
MEN DEALING IN MONOGENETIC

6709
04:19:19,559 --> 04:19:20,860
TRAITS, CONTROLLED ION CHANNELS.

6710
04:19:20,860 --> 04:19:22,628
THERE IS NATURAL VARIATION AMONG

6711
04:19:22,628 --> 04:19:26,265
HUMAN BEINGS AND AMONG NON-HUMAN

6712
04:19:26,265 --> 04:19:27,800
MALLS AND I THINK TALKING ABOUT

6713
04:19:27,800 --> 04:19:31,471
THIS GENETIC DIMENSION OF

6714
04:19:31,471 --> 04:19:33,673
WELFARE COULD BE A REALLY

6715
04:19:33,673 --> 04:19:36,075
INTERESTING ANGLE AND IF YOU'RE

6716
04:19:36,075 --> 04:19:37,210
INTERESTED, I COULD MAYBE EVEN

6717
04:19:37,210 --> 04:19:38,978
HELP PUT TOGETHER A PANEL OF

6718
04:19:38,978 --> 04:19:40,713
SCIENTISTS IF YOU WANTED TO DO

6719
04:19:40,713 --> 04:19:42,982
LIKE A SPECIAL SESSION ON THIS.

6720
04:19:42,982 --> 04:19:44,851
SO THANKS FOR ORGANIZING THIS.

6721
04:19:44,851 --> 04:19:46,619
THIS WAS WONDERFUL AND I REALLY

6722
04:19:46,619 --> 04:19:46,919
ENJOYED IT.

6723
04:19:46,919 --> 04:19:50,590
>> THANK YOU FOR THOSE
THOUGHTS.

6724
04:19:50,590 --> 04:19:52,425
>> HI, LATARSHA CRAWFORD

6725
04:19:52,425 --> 04:19:54,961
UNIVERSITY OF WISCONSIN, SCHOOL

6726
04:19:54,961 --> 04:19:55,461
OF VETERINARY MEDICINE.

6727
04:19:55,461 --> 04:19:56,062
THANK YOU VERY MUCH.

6728
04:19:56,062 --> 04:19:58,264
I ENJOYED THIS REALLY SINCE DAY

6729
04:19:58,264 --> 04:19:59,298
ONE SEVERAL YEARS AGO.

6730
04:19:59,298 --> 04:20:00,666
ONE THING I DID WANT TO JUST

6731
04:20:00,666 --> 04:20:01,934
KIND OF COMMENT ON THAT I THINK

6732
04:20:01,934 --> 04:20:04,570
COULD BE REALLY INFORMATIVE FOR

6733
04:20:04,570 --> 04:20:06,672
THIS GROUP OF FOLKS IS PERHAPS A

6734
04:20:06,672 --> 04:20:08,474
BETTER UNDERSTANDING OR A MORE

6735
04:20:08,474 --> 04:20:09,809
CLEAR DISCUSSION OF SOME OF THE

6736
04:20:09,809 --> 04:20:11,077
PERIPHERAL MECHANISMS OF PAIN.

6737
04:20:11,077 --> 04:20:15,314
SO THERE IS A LOT OF TALK ABOUT

6738
04:20:15,314 --> 04:20:16,916
CENTRAL SENSITIZATION AND HOW

6739
04:20:16,916 --> 04:20:18,251
INTERESTING AND COMPLEX THAT IS.

6740
04:20:18,251 --> 04:20:20,353
BUT I THINK THAT JUST BECAUSE

6741
04:20:20,353 --> 04:20:23,122
PAIN IS CHRONIC OR MULTI-FOCAL

6742
04:20:23,122 --> 04:20:25,224
OR JUST BECAUSE THERE ARE AREAS

6743
04:20:25,224 --> 04:20:27,426
OF SECONDARY HYPERALGESIA OR

6744
04:20:27,426 --> 04:20:29,462
THAT SORT OF THING, DOESN'T MEAN

6745
04:20:29,462 --> 04:20:32,231
IT'S SOLELY CENTRAL IN TERMS OF

6746
04:20:32,231 --> 04:20:33,332
THE LONG TERM EFFECTS THAT ARE

6747
04:20:33,332 --> 04:20:34,867
HAPPENING OR THE WAYS IN WHICH

6748
04:20:34,867 --> 04:20:37,136
THE SENSORY SYSTEM IS CHANGING.

6749
04:20:37,136 --> 04:20:39,338
AND I THINK THAT MAYBE SOME

6750
04:20:39,338 --> 04:20:40,940
FURTHER DISCUSSION ABOUT

6751
04:20:40,940 --> 04:20:42,608
PERIPHERAL MECHANISMS AND

6752
04:20:42,608 --> 04:20:44,243
PLASTICITY THAT LIES WITHIN THE

6753
04:20:44,243 --> 04:20:46,345
PERIPHERY IS ALSO PROBABLY WORTH

6754
04:20:46,345 --> 04:20:47,146
OUR UNDERSTANDING AND PERHAPS

6755
04:20:47,146 --> 04:20:48,948
DIVING A LITTLE BIT DEEPER INTO

6756
04:20:48,948 --> 04:20:49,115
IT.

6757
04:20:49,115 --> 04:20:51,017
AND I'M HAPPY TO BE A PART OF

6758
04:20:51,017 --> 04:20:52,785
THAT DISCUSSION.

6759
04:20:52,785 --> 04:20:55,755
>> LOVELY, THANK YOU.

6760
04:20:55,755 --> 04:20:57,723
I'M WRITING ALL OF THESE DOWN.

6761
04:20:57,723 --> 04:20:59,258
THIS IS GREAT AND SAVING US A

6762
04:20:59,258 --> 04:21:00,660
LOT OF HOMEWORK.

6763
04:21:00,660 --> 04:21:02,762
>> HI, ABI, KANSAS STATE

6764
04:21:02,762 --> 04:21:03,062
UNIVERSITY.

6765
04:21:03,062 --> 04:21:06,832
SO I'M A LARGE ANIMAL PAIN

6766
04:21:06,832 --> 04:21:07,133
RESEARCHER.

6767
04:21:07,133 --> 04:21:08,868
AND I HEARD A LOT THE LAST

6768
04:21:08,868 --> 04:21:10,570
COUPLE OF DAYS ABOUT US TALKING

6769
04:21:10,570 --> 04:21:12,038
ABOUT SELF REPORT BEING THE GOLD

6770
04:21:12,038 --> 04:21:13,072
STANDARD AND I CERTAINLY FEEL

6771
04:21:13,072 --> 04:21:15,041
THAT WAY WHEN I'M DEALING WITH

6772
04:21:15,041 --> 04:21:16,842
MY PIGS T WOULD BE FANTASTIC IF

6773
04:21:16,842 --> 04:21:18,244
THEY COULD JUST TELL ME THAT

6774
04:21:18,244 --> 04:21:20,813
THEY ARE IN PAIN.

6775
04:21:20,813 --> 04:21:22,048
BUT SOMETHING THAT STRUCK ME IN

6776
04:21:22,048 --> 04:21:23,583
JUST SITTING AND HEARING THE

6777
04:21:23,583 --> 04:21:26,319
HUMAN HEALTH PERSPECTIVE IS THAT

6778
04:21:26,319 --> 04:21:29,855
I AM NOT WORRIED THAT MY PIGS

6779
04:21:29,855 --> 04:21:31,958
ARE GOING TO BE MOTIVATED TO

6780
04:21:31,958 --> 04:21:33,559
SHOW THAT THEY ARE IN MORE PAIN

6781
04:21:33,559 --> 04:21:37,230
WHEN THEY ARE NOT NECESSARILY IN

6782
04:21:37,230 --> 04:21:37,530
PAIN.

6783
04:21:37,530 --> 04:21:39,932
MY SIGNIFICANT OTHER IS A FAMILY

6784
04:21:39,932 --> 04:21:41,634
MEDICINE PHYSICIAN IN RURAL

6785
04:21:41,634 --> 04:21:42,635
KANSAS AND SOMETHING HE DEALS

6786
04:21:42,635 --> 04:21:44,837
WITH A LOT IS PEOPLE

6787
04:21:44,837 --> 04:21:46,772
SELF-REPORTING HIGH AMOUNTS OF

6788
04:21:46,772 --> 04:21:50,443
PAIN TO GAIN ACCESS TO CERTAIN

6789
04:21:50,443 --> 04:21:51,143
DRUGS.

6790
04:21:51,143 --> 04:21:53,279
AND HE SEES PEOPLE THAT ARE ON

6791
04:21:53,279 --> 04:21:55,448
SUCH HIGH DOSES OF OPIOIDS THAT

6792
04:21:55,448 --> 04:21:58,050
HONESTLY WOULD TAKE A

6793
04:21:58,050 --> 04:21:58,351
RHINOCEROS.

6794
04:21:58,351 --> 04:22:01,387
AND I THINK THERE IS JUST THIS

6795
04:22:01,387 --> 04:22:03,556
CONCERN NOW THAT PERHAPS SELF

6796
04:22:03,556 --> 04:22:06,092
REPORT IN HUMAN MEDICINE IS NOT

6797
04:22:06,092 --> 04:22:07,159
NECESSARILY THE GOLD STANDARD

6798
04:22:07,159 --> 04:22:09,862
BECAUSE PEOPLE ARE MOTIVATED IN

6799
04:22:09,862 --> 04:22:14,400
CERTAIN CASES TO SUFFER HIGHER

6800
04:22:14,400 --> 04:22:15,268
LEVELS OF PAIN TO GAIN ACCESS TO

6801
04:22:15,268 --> 04:22:15,968
CERTAIN DRUGS.

6802
04:22:15,968 --> 04:22:17,436
THAT MIGHT BE A NICE PIECE TO

6803
04:22:17,436 --> 04:22:18,771
THIS DISCUSSION OF HOW WE KIND

6804
04:22:18,771 --> 04:22:20,439
OF DEAL WITH THIS SORT OF OPIOID

6805
04:22:20,439 --> 04:22:22,475
CRISIS WE ARE SEEING IN PEOPLE

6806
04:22:22,475 --> 04:22:26,379
SAYING THAT THEY ARE IN CERTAIN

6807
04:22:26,379 --> 04:22:29,248
LEVELS OF PAIN TO BE MOTIVATED

6808
04:22:29,248 --> 04:22:30,016
FOR OTHER REASONS.

6809
04:22:30,016 --> 04:22:33,753
SO THAT WAS JUST MY TWO CENTS.

6810
04:22:33,753 --> 04:22:34,053
>> GREAT.

6811
04:22:34,053 --> 04:22:35,721
THANK YOU VERY MUCH FITS IN THE

6812
04:22:35,721 --> 04:22:39,458
WITH THE WHOLE HEAL INITIATIVE.

6813
04:22:39,458 --> 04:22:40,459
>> SORRY TO STAND UP IN
THE WAY

6814
04:22:40,459 --> 04:22:41,961
OF OTHERS.

6815
04:22:41,961 --> 04:22:43,195
I DIDN'T REALIZE.

6816
04:22:43,195 --> 04:22:44,864
A COUPLE OF THOUGHTS.

6817
04:22:44,864 --> 04:22:48,067
IN TERMS OF DATA

6818
04:22:48,067 --> 04:22:48,968
STANDARDIZATION, FOR ANYBODY

6819
04:22:48,968 --> 04:22:51,937
THAT HAS SUBMITTED DATA TO THE

6820
04:22:51,937 --> 04:22:53,372
FDA, YOU UNDERSTAND THAT THERE

6821
04:22:53,372 --> 04:22:55,608
ARE REQUIREMENTS AS TO WHAT

6822
04:22:55,608 --> 04:22:56,976
FORMAT THAT DATA SHOULD TAKE.

6823
04:22:56,976 --> 04:22:58,644
I DON'T HONESTLY KNOW IF THE

6824
04:22:58,644 --> 04:23:02,081
ANIMAL DATA IS AS RESTRICT AS

6825
04:23:02,081 --> 04:23:02,448
HUMAN.

6826
04:23:02,448 --> 04:23:06,752
BUT HAVING JUST WORKED WITH THE

6827
04:23:06,752 --> 04:23:09,221
DART SYSTEM AND 40 OR 45

6828
04:23:09,221 --> 04:23:09,955
DIFFERENT STUDIES.

6829
04:23:09,955 --> 04:23:11,757
THERE IS A STANDARD APPROACH TO

6830
04:23:11,757 --> 04:23:13,559
RECORDING OF THAT DATA.

6831
04:23:13,559 --> 04:23:18,364
AND MAYBE THERE ISN'T A NEED TO

6832
04:23:18,364 --> 04:23:19,699
RE-CREATE THE WHEEL.

6833
04:23:19,699 --> 04:23:25,838
IT'S AN STDM FORMAT, C DISK

6834
04:23:25,838 --> 04:23:26,972
PROCESS.

6835
04:23:26,972 --> 04:23:28,207
SOMEWHAT CUMBERSOME BUT IT

6836
04:23:28,207 --> 04:23:28,407
WORKS.

6837
04:23:28,407 --> 04:23:30,676
AND SO MAYBE IF THAT WERE

6838
04:23:30,676 --> 04:23:32,678
ADOPTED IN AT LEAST LARGER

6839
04:23:32,678 --> 04:23:35,481
MEDICAL CENTERS THAT DO

6840
04:23:35,481 --> 04:23:36,582
RESEARCH, DATA COULD BE IN A

6841
04:23:36,582 --> 04:23:38,818
MORE STANDARDIZED FORMAT.

6842
04:23:38,818 --> 04:23:42,088
OBVIOUSLY, IN HEALTH CARE WE

6843
04:23:42,088 --> 04:23:44,056
HAVE OUR STANDARDIZED FORMAT.

6844
04:23:44,056 --> 04:23:46,792
DATA IS BEING TRANSITIONED INTO

6845
04:23:46,792 --> 04:23:49,528
OMAL AND THE A BUNCH OF OTHER

6846
04:23:49,528 --> 04:23:50,062
INITIALS I DON'T CLAIM TO

6847
04:23:50,062 --> 04:23:50,363
UNDERSTAND.

6848
04:23:50,363 --> 04:23:53,366
AND THAT KIND OF SYSTEM CAN ALSO

6849
04:23:53,366 --> 04:23:55,368
WORK AND AI CAN HELP IN THE

6850
04:23:55,368 --> 04:24:00,005
TRANSITION OF DATA TO THAT

6851
04:24:00,005 --> 04:24:03,075
PERSPECTIVE.

6852
04:24:03,075 --> 04:24:06,212
WITH REGARDS TO THE LAST

6853
04:24:06,212 --> 04:24:07,680
SPEAKER, AS SOMEBODY WAS TAKING

6854
04:24:07,680 --> 04:24:09,515
CARE OF PATIENTS FOR A VERY LONG

6855
04:24:09,515 --> 04:24:10,983
TIME, PAIN IS SELF REPORTED AND

6856
04:24:10,983 --> 04:24:13,786
WILL ALWAYS BE SELF REPORTED.

6857
04:24:13,786 --> 04:24:16,088
AND THERE JUST ISN'T ANY WAY

6858
04:24:16,088 --> 04:24:16,355
AROUND IT.

6859
04:24:16,355 --> 04:24:19,291
THE POINT MADE ABOUT

6860
04:24:19,291 --> 04:24:20,893
COMPLAINING, THAT IS CLEARLY AN

6861
04:24:20,893 --> 04:24:22,695
ISSUE IN CLINICAL CARE.

6862
04:24:22,695 --> 04:24:24,296
IN RESEARCH, I THINK THAT THAT

6863
04:24:24,296 --> 04:24:25,798
IS LESS OF A PROBLEM AS LONG AS

6864
04:24:25,798 --> 04:24:27,867
WE ARE CAREFUL ABOUT WHO WE

6865
04:24:27,867 --> 04:24:30,069
ENROLL IN TRIALS.

6866
04:24:30,069 --> 04:24:31,370
WITH REGARDS TO THE THIRD THING

6867
04:24:31,370 --> 04:24:33,472
THAT WAS MENTIONED, WHICH IS

6868
04:24:33,472 --> 04:24:38,711
MONITORS OR WAYS OF

6869
04:24:38,711 --> 04:24:39,378
UNDERSTANDING.

6870
04:24:39,378 --> 04:24:40,880
IN SMALL ANIMAL STUDIES, THEY

6871
04:24:40,880 --> 04:24:44,917
HAVE STARTED TO USE VIDEO

6872
04:24:44,917 --> 04:24:47,286
RECORDING OF MOTION AS A WAY OF

6873
04:24:47,286 --> 04:24:47,620
UNDERSTANDING.

6874
04:24:47,620 --> 04:24:49,088
AND THERE IS NO REASON WHY THAT

6875
04:24:49,088 --> 04:24:52,391
CAN'T BE ADOPTED TO COWS IN A

6876
04:24:52,391 --> 04:24:54,593
CORAL OR SHEEP IN A FIELD OR

6877
04:24:54,593 --> 04:24:55,394
OTHER THINGS.

6878
04:24:55,394 --> 04:24:58,497
SO UNDERSTANDING HOW TO EMPLOY

6879
04:24:58,497 --> 04:25:00,499
SOME OF THE TECHNOLOGY THAT IS

6880
04:25:00,499 --> 04:25:01,801
RAPIDLY BEING DEVELOPED, AND

6881
04:25:01,801 --> 04:25:04,136
THEN ANALYZED EITHER THROUGH AI

6882
04:25:04,136 --> 04:25:07,006
OR OTHER MECHANISMS TO NOT HAVE

6883
04:25:07,006 --> 04:25:08,541
TO PUT THINGS ON TO ANIMALS TO

6884
04:25:08,541 --> 04:25:11,210
SEE HOW THEY ARE MOVING, BUT

6885
04:25:11,210 --> 04:25:12,578
JUST OBSERVE THEM.

6886
04:25:12,578 --> 04:25:15,281
THE LAST THING IS, I AGREE WITH

6887
04:25:15,281 --> 04:25:16,482
YOU THAT WE PROBABLY KNOW IF

6888
04:25:16,482 --> 04:25:18,584
YOUR PIGS ARE IN PAIN, BUT IN

6889
04:25:18,584 --> 04:25:21,353
SMALL ANIMAL STUDIES, WE KNOW

6890
04:25:21,353 --> 04:25:22,888
THAT IF YOU PUT -- INJECT

6891
04:25:22,888 --> 04:25:24,490
SOMETHING INTO A MALE MOUSE AND

6892
04:25:24,490 --> 04:25:26,225
PUT IT IN WITH OTHER MALE MICE,

6893
04:25:26,225 --> 04:25:29,728
IT WILL NOT RESPOND WITH PAIN

6894
04:25:29,728 --> 04:25:31,030
BEHAVIOR AS STRONGLY.

6895
04:25:31,030 --> 04:25:32,531
BECAUSE THEY ARE AFRAID THE

6896
04:25:32,531 --> 04:25:34,834
OTHER MICE WILL COME BEAT IT UP.

6897
04:25:34,834 --> 04:25:36,535
WHEREAS IF YOU PUT THEM IN WITH

6898
04:25:36,535 --> 04:25:39,138
THE FEMALES, THEY ARE JUST

6899
04:25:39,138 --> 04:25:40,539
LICKING THEIR PAW UNTIL THEY

6900
04:25:40,539 --> 04:25:41,474
CAN'T STOP.

6901
04:25:41,474 --> 04:25:43,309
SO I WOULD ARGUE THAT IN FACT IN

6902
04:25:43,309 --> 04:25:46,111
LOOKING AT PIGS AND LOOKING AT

6903
04:25:46,111 --> 04:25:47,546
GOATS AND LOOKING AT ANIMALS,

6904
04:25:47,546 --> 04:25:49,882
MIXING THEM UP -- I A LOT OF

6905
04:25:49,882 --> 04:25:51,383
THESE ARE CASTRATED, BUT THE

6906
04:25:51,383 --> 04:25:52,551
BOTTOM LINE IS THAT I THINK

6907
04:25:52,551 --> 04:25:54,653
THERE MAY BE WELL BE DIFFERENCES

6908
04:25:54,653 --> 04:25:57,356
IN THE WAY ANIMALS RESPOND BASED

6909
04:25:57,356 --> 04:25:58,157
ON THEIR ENVIRONMENT.

6910
04:25:58,157 --> 04:25:59,725
SO WE KNOW THAT THE PLACEBO

6911
04:25:59,725 --> 04:26:00,960
EFFECT OCCURS IN PIGS AND

6912
04:26:00,960 --> 04:26:03,963
ANIMALS AND HORSES AND

6913
04:26:03,963 --> 04:26:05,097
EVERYWHERE.

6914
04:26:05,097 --> 04:26:08,300
SO, IT'S NOT THE SAME BUT IT IS

6915
04:26:08,300 --> 04:26:08,801
ALSO AN ISSUE.

6916
04:26:08,801 --> 04:26:11,670
IN TERMS OF WHAT MIGHT BE DONE

6917
04:26:11,670 --> 04:26:13,239
HERE, I THINK THAT MAYBE

6918
04:26:13,239 --> 04:26:15,174
COMBINING WHAT WE KNOW FROM

6919
04:26:15,174 --> 04:26:17,376
SMALL ANIMAL INTO LARGE ANIMAL,

6920
04:26:17,376 --> 04:26:19,178
AND WE TALKED ABOUT THIS BEFORE,

6921
04:26:19,178 --> 04:26:21,480
MIGHT BE AN INTERESTING WAY OF

6922
04:26:21,480 --> 04:26:23,349
SORT OF BRINGING TOGETHER GROUPS

6923
04:26:23,349 --> 04:26:25,150
THAT COULD LEARN FROM EACH

6924
04:26:25,150 --> 04:26:25,918
OTHER.

6925
04:26:25,918 --> 04:26:28,754
I LOVED THE PICTURES OF LAMBS

6926
04:26:28,754 --> 04:26:32,992
AND SHEEP THAT WERE IN PAIN.

6927
04:26:32,992 --> 04:26:34,393
JEFF MOGUL, 15 YEARS AGO, CAME

6928
04:26:34,393 --> 04:26:38,664
UP WITH A MOUSE SCALE -- I

6929
04:26:38,664 --> 04:26:39,565
HONESTLY CAN'T TELL THE

6930
04:26:39,565 --> 04:26:39,999
DIFFERENCE.

6931
04:26:39,999 --> 04:26:42,001
BUT I THINK THAT THAT COULD BE

6932
04:26:42,001 --> 04:26:42,368
EXPANDED.

6933
04:26:42,368 --> 04:26:45,070
AGAIN, AI AND OBSERVATIONAL FACE

6934
04:26:45,070 --> 04:26:46,805
RECOGNITION AND ALL OF THIS

6935
04:26:46,805 --> 04:26:47,373
STUFF.

6936
04:26:47,373 --> 04:26:48,274
SO, TWO THINGS.

6937
04:26:48,274 --> 04:26:50,075
ONE IS SMALL AND LARGE ANIMAL

6938
04:26:50,075 --> 04:26:51,176
TOGETHER AND THE OTHER ONE IS

6939
04:26:51,176 --> 04:26:52,945
THE TECHNOLOGY THAT WAS

6940
04:26:52,945 --> 04:26:54,780
SUGGESTED FOR ADVANCEMENT OF

6941
04:26:54,780 --> 04:26:56,982
WAYS TO MEASURE INTERACTIONS

6942
04:26:56,982 --> 04:26:59,652
BETWEEN ANIMALS OR RESPONSES TO

6943
04:26:59,652 --> 04:27:01,787
PAINFUL STIMULI MIGHT BE USEFUL.

6944
04:27:01,787 --> 04:27:02,087
>> GREAT.

6945
04:27:02,087 --> 04:27:03,122
THANK YOU FOR THOSE COMMENTS.

6946
04:27:03,122 --> 04:27:03,856
AND YOU'RE RIGHT.

6947
04:27:03,856 --> 04:27:06,959
THE FDA HAS FIGURED OUT HOW DATA

6948
04:27:06,959 --> 04:27:08,627
SHOULD BE PACKAGED UP AND IN

6949
04:27:08,627 --> 04:27:15,568
ORDER TO MAKE IT WORK AND BE

6950
04:27:15,568 --> 04:27:17,069
VERIFIABLE AND THE NIH HAS AN

6951
04:27:17,069 --> 04:27:18,404
ONGOING INITIATIVE TO MAKE DATA,

6952
04:27:18,404 --> 04:27:28,948
GOT TO GET THIS RIDE, FINDABLE,

6953
04:27:29,214 --> 04:27:30,783
SEARCHABLE.

6954
04:27:30,783 --> 04:27:31,116
>> RELIABLE.

6955
04:27:31,116 --> 04:27:35,054
>> BUT THAT'S A VERY
IMPORTANT

6956
04:27:35,054 --> 04:27:36,589
PART OF SHARING DATA.

6957
04:27:36,589 --> 04:27:38,857
WE NEED TO MAKE SURE IT'S IN A

6958
04:27:38,857 --> 04:27:40,893
FORMAT THAT EVERYONE CAN USE AND

6959
04:27:40,893 --> 04:27:41,660
IN THE RIGHT PLACE.

6960
04:27:41,660 --> 04:27:43,529
YOUR COMMENTS ARE WELL TAKEN.

6961
04:27:43,529 --> 04:27:45,264
AI WILL NOT MOVE FORWARD UNLESS

6962
04:27:45,264 --> 04:27:46,966
THE DATA REPOSITORIES ARE THERE

6963
04:27:46,966 --> 04:27:48,267
IN A WAY THAT CAN BE READ.

6964
04:27:48,267 --> 04:27:50,803
I THINK THAT WILL BE A GREAT

6965
04:27:50,803 --> 04:27:52,171
THEME TO BRING PEOPLE TOGETHER

6966
04:27:52,171 --> 04:27:53,505
AND TALK ABOUT COLLABORATION,

6967
04:27:53,505 --> 04:27:55,507
HOW DO WE COLLABORATE TO CREATE

6968
04:27:55,507 --> 04:28:00,145
THOSE APPROPRIATE DATASETS.

6969
04:28:00,145 --> 04:28:00,412
THANK YOU.

6970
04:28:00,412 --> 04:28:01,981
>> I GREATLY ENJOYED THE
PAST

6971
04:28:01,981 --> 04:28:03,449
FEW DAYS, THANK YOU.

6972
04:28:03,449 --> 04:28:06,585
I WOULD BE REMISS AND NOT

6973
04:28:06,585 --> 04:28:11,090
PLUGGING MAYBE AN ANALYSIS OF

6974
04:28:11,090 --> 04:28:12,891
MOLECULAR BASIS FOR PAIN,

6975
04:28:12,891 --> 04:28:14,293
MOLECULAR ALTERATIONS THAT

6976
04:28:14,293 --> 04:28:14,827
OCCUR.

6977
04:28:14,827 --> 04:28:16,295
THERE HAS BEEN SO MUCH WORK

6978
04:28:16,295 --> 04:28:20,799
USING RNA SEQUENCING AND IN SITU

6979
04:28:20,799 --> 04:28:23,602
HYBRIDIZATION LOOKING AT EVENTS,

6980
04:28:23,602 --> 04:28:26,405
CERTAINLY IN THE PERIPHERY AND

6981
04:28:26,405 --> 04:28:27,873
CENTRALLY.

6982
04:28:27,873 --> 04:28:30,009
I THINK WE COULD DO THAT.

6983
04:28:30,009 --> 04:28:31,477
AND JOHN, I REALLY LIKE THE IDEA

6984
04:28:31,477 --> 04:28:33,979
OF LOOKING AT ETHOLOGICAL KIND

6985
04:28:33,979 --> 04:28:36,815
OF EXPERIMENTAL DESIGNS, ANIMAL

6986
04:28:36,815 --> 04:28:37,149
INTERACTIONS.

6987
04:28:37,149 --> 04:28:38,217
YOU COULD PICK THINGS OUT.

6988
04:28:38,217 --> 04:28:40,386
THERE ARE SOME REALLY GREAT

6989
04:28:40,386 --> 04:28:44,723
STUDIES THAT HAVE BEEN DONE ON

6990
04:28:44,723 --> 04:28:45,524
MICE.

6991
04:28:45,524 --> 04:28:46,925
>> THAT WHOLE SOCIAL
THING,

6992
04:28:46,925 --> 04:28:49,194
THAT'S A GREAT IDEA.

6993
04:28:49,194 --> 04:28:51,697
I MEAN, IT'S UNDERSTANDING THE

6994
04:28:51,697 --> 04:28:53,599
EFFECTS OF PAIN BEHAVIORS ON

6995
04:28:53,599 --> 04:28:57,036
SOCIAL INTERACTIONS AND ON

6996
04:28:57,036 --> 04:28:59,138
SOCIAL INTERACTIONS IS A AREA OF

6997
04:28:59,138 --> 04:28:59,838
MEASUREMENT THAT I DON'T THINK

6998
04:28:59,838 --> 04:29:04,076
HAS BEEN EXPLORED VERY MUCH.

6999
04:29:04,076 --> 04:29:05,711
>> I'M VERYING TROUBLE
SEEING

7000
04:29:05,711 --> 04:29:07,913
AGAINST THE LIGHTS.

7001
04:29:07,913 --> 04:29:08,814
>> JAMES HARRIS.

7002
04:29:08,814 --> 04:29:10,716
FIRST TIME ATTENDING THIS

7003
04:29:10,716 --> 04:29:10,983
WORKSHOP.

7004
04:29:10,983 --> 04:29:11,817
THANK YOU VERY MUCH FOR PUTTING

7005
04:29:11,817 --> 04:29:12,418
THIS TOGETHER.

7006
04:29:12,418 --> 04:29:14,820
I APPRECIATED THE DUALITY OF THE

7007
04:29:14,820 --> 04:29:17,022
HUMAN WORK GOING TOWARDS HUMAN

7008
04:29:17,022 --> 04:29:18,490
AND HUMAN GOING TOWARDS ANIMAL.

7009
04:29:18,490 --> 04:29:22,695
WE HEARD A LOT ABOUT PAIN

7010
04:29:22,695 --> 04:29:24,296
ASSESSMENT COMING FROM THE HUMAN

7011
04:29:24,296 --> 04:29:24,997
WORLD.

7012
04:29:24,997 --> 04:29:26,699
THERE IS MORE A CLASSIFICATION,

7013
04:29:26,699 --> 04:29:31,003
LIKE WHAT IS THE PAIN GENERATOR?

7014
04:29:31,003 --> 04:29:32,504
WHICH DR. CRAWFORD POINTED OUT

7015
04:29:32,504 --> 04:29:32,805
PERIPHERAL.

7016
04:29:32,805 --> 04:29:35,007
FOR HUMAN WORK, THERE IS A LOT

7017
04:29:35,007 --> 04:29:36,508
OF DEVELOPMENT TO UNDERSTANDING

7018
04:29:36,508 --> 04:29:38,911
WHAT TYPE OF PAIN YOU'RE

7019
04:29:38,911 --> 04:29:43,015
TREATING WHETHER NEUROPATHIC, OR

7020
04:29:43,015 --> 04:29:43,382
NEUROSUSCEPTIVE.

7021
04:29:43,382 --> 04:29:45,584
AND THAT IS NEEDED FOR

7022
04:29:45,584 --> 04:29:46,318
REIMBURSEMENT, WHICH IS PRETTY

7023
04:29:46,318 --> 04:29:49,188
MUCH THE REASON THAT ALL

7024
04:29:49,188 --> 04:29:51,990
COMPANIES ARE DOING DEVELOPMENT.

7025
04:29:51,990 --> 04:29:53,992
SO, I APPRECIATE ALL OF THESE

7026
04:29:53,992 --> 04:29:55,828
PRODUCTION ANIMALS AND LIVESTOCK

7027
04:29:55,828 --> 04:29:56,995
STUDIES THAT I THINK COULD ALSO

7028
04:29:56,995 --> 04:29:59,098
BE HELPFUL TOL UNDERSTAND

7029
04:29:59,098 --> 04:30:00,332
CLASSIFICATION AND WE HAVE A

7030
04:30:00,332 --> 04:30:02,801
WIDE RANGE OF SMALL ANIMAL

7031
04:30:02,801 --> 04:30:03,035
MODELS.

7032
04:30:03,035 --> 04:30:05,003
APPRECIATE THE NIH FOR THE

7033
04:30:05,003 --> 04:30:06,805
FUNDING, BUT I THINK A MORE

7034
04:30:06,805 --> 04:30:08,474
DEVELOPED DISCUSSION ABOUT PAIN,

7035
04:30:08,474 --> 04:30:09,608
DIFFERENT PAIN GENERATORS AND

7036
04:30:09,608 --> 04:30:11,276
SOURCES AND CLASSIFICATION

7037
04:30:11,276 --> 04:30:12,711
BETWEEN HUMAN AND ANIMAL WORK

7038
04:30:12,711 --> 04:30:14,413
COULD BE REALLY HELPFUL.

7039
04:30:14,413 --> 04:30:16,849
>> SO YOU THINK THAT
SPEAKS TO

7040
04:30:16,849 --> 04:30:17,750
PAIN PHENOTYPING?

7041
04:30:17,750 --> 04:30:19,651
LIKE REALLY UNDERSTANDING THE

7042
04:30:19,651 --> 04:30:24,823
PHENOTYPE AND THE ENDOTYPE.

7043
04:30:24,823 --> 04:30:27,126
THERE ARE COMMENTS ABOUT

7044
04:30:27,126 --> 04:30:29,394
PHENOTYPING IN ORDER TO

7045
04:30:29,394 --> 04:30:30,596
UNDERSTAND WHAT SUBJECTS WE'RE

7046
04:30:30,596 --> 04:30:32,197
BRINGING INTO STUDIES.

7047
04:30:32,197 --> 04:30:33,599
I'M THINKING YOUR CONCEPT ABOUT

7048
04:30:33,599 --> 04:30:35,134
WHAT IS DRIVING THE PAIN SPEAKS

7049
04:30:35,134 --> 04:30:36,935
TO THE ENDOTYPE.

7050
04:30:36,935 --> 04:30:40,305
WHAT EXACTLY IS GOING ON ON A

7051
04:30:40,305 --> 04:30:41,306
MOLECULAR AND CELLULAR BASIS.

7052
04:30:41,306 --> 04:30:42,841
>> I THINK THE WHOLE PAIN
FIELD

7053
04:30:42,841 --> 04:30:45,577
IS STILL WORKING ON ENDOTYPE

7054
04:30:45,577 --> 04:30:46,779
VERSUS PHENOTYPE AS FAR AS WE DO

7055
04:30:46,779 --> 04:30:50,783
ALL OF OUR MEDICINE MOSTLY ON

7056
04:30:50,783 --> 04:30:51,483
SYMPTOMS ANYWAY BUT HOW DO WE

7057
04:30:51,483 --> 04:30:52,818
TRANSITION FROM WHAT WE SEE NOW

7058
04:30:52,818 --> 04:30:54,353
TO A DEEPER UNDERSTANDING SO

7059
04:30:54,353 --> 04:30:58,457
THAT WE CAN DO THIS

7060
04:30:58,457 --> 04:31:00,659
PERSONALIZATION OF PAIN

7061
04:31:00,659 --> 04:31:01,226
TREATMENT?

7062
04:31:01,226 --> 04:31:01,593
>> THANK YOU.

7063
04:31:01,593 --> 04:31:02,728
>> THIS HAS BEEN A GREAT
DEAL OF

7064
04:31:02,728 --> 04:31:03,128
FUN.

7065
04:31:03,128 --> 04:31:04,196
I REALLY ENJOYED THIS.

7066
04:31:04,196 --> 04:31:06,165
JUST ONE COMMENT AND THEN MAYBE

7067
04:31:06,165 --> 04:31:09,668
AN IDEA FOR THE FUTURE.

7068
04:31:09,668 --> 04:31:11,637
AT FDA, I DON'T WORK FOR CDM BUT

7069
04:31:11,637 --> 04:31:14,273
I DO REVIEW NON-CLINICAL ANIMAL

7070
04:31:14,273 --> 04:31:15,073
DATA FOR HUMAN DRUGS.

7071
04:31:15,073 --> 04:31:17,209
I WILL SAY THAT SEND F THAT'S

7072
04:31:17,209 --> 04:31:20,879
WHAT YOU'RE REFERRING TO, IN A

7073
04:31:20,879 --> 04:31:23,182
STANDARDIZED FORMAT, RIGHT NOW I

7074
04:31:23,182 --> 04:31:26,518
WORK FOR THE CENTER FOR BY

7075
04:31:26,518 --> 04:31:27,052
LOGICS.

7076
04:31:27,052 --> 04:31:27,653
THE STANDARDIZED FORMAT IS

7077
04:31:27,653 --> 04:31:30,756
REQUIRED FOR ALL TOXICOLOGY DATA

7078
04:31:30,756 --> 04:31:32,558
FOR SMALL MOLECULES AS WELL AS

7079
04:31:32,558 --> 04:31:33,692
LARGE COMING INTO FDA.

7080
04:31:33,692 --> 04:31:35,060
THAT IS SOMETHING THAT IS MOVING

7081
04:31:35,060 --> 04:31:35,260
ALONG.

7082
04:31:35,260 --> 04:31:36,728
IT'S NOT REQUIRED FOR DISCOVERY

7083
04:31:36,728 --> 04:31:38,564
BUT CERTAINLY FOR SAFETY.

7084
04:31:38,564 --> 04:31:40,465
AND I WAS JUST THINKING, ONE OF

7085
04:31:40,465 --> 04:31:41,366
THE THINGS THAT SURPRISED ME

7086
04:31:41,366 --> 04:31:43,068
WHEN I CAME FROM CLINICAL

7087
04:31:43,068 --> 04:31:45,470
STARTING TO WORK IN REGULATORY,

7088
04:31:45,470 --> 04:31:48,273
THAT IS, I THINK A NICE ADD IS

7089
04:31:48,273 --> 04:31:51,643
THAT THE FDA WILL SOLICIT

7090
04:31:51,643 --> 04:31:53,178
PATIENT PERSPECTIVES WHEN IT AND

7091
04:31:53,178 --> 04:31:55,714
TO THE APPROVAL OF A NEW

7092
04:31:55,714 --> 04:31:55,948
PRODUCT.

7093
04:31:55,948 --> 04:31:57,015
SO WHEN I WAS LISTENING TO ONE

7094
04:31:57,015 --> 04:32:00,085
OF THE FORMER TALKS ABOUT WHAT'S

7095
04:32:00,085 --> 04:32:01,186
CONSIDERED GOOD?

7096
04:32:01,186 --> 04:32:03,088
LIKE WHAT'S CONSIDERED A

7097
04:32:03,088 --> 04:32:03,355
RESPONSE?

7098
04:32:03,355 --> 04:32:04,790
I THINK IT WOULD BE INTERESTING

7099
04:32:04,790 --> 04:32:06,124
TO HEAR PERSPECTIVES FROM

7100
04:32:06,124 --> 04:32:08,060
PRODUCERS AND OWNERS AND

7101
04:32:08,060 --> 04:32:09,161
STAKEHOLDERS IN ANIMAL

7102
04:32:09,161 --> 04:32:11,363
INDUSTRIES AS TO WHAT IS THE

7103
04:32:11,363 --> 04:32:13,465
BENCHMARK OF I'M GOING TO APPLY

7104
04:32:13,465 --> 04:32:15,367
THIS OR NOT AND IS THAT

7105
04:32:15,367 --> 04:32:18,203
DIFFERENT FROM THE ACADEMIC

7106
04:32:18,203 --> 04:32:18,871
CLINICIAN, THE RESEARCH

7107
04:32:18,871 --> 04:32:20,572
SCIENTIST AND HOW THOSE TWO

7108
04:32:20,572 --> 04:32:21,473
PERSPECTIVES WOULD HAVE TO COME

7109
04:32:21,473 --> 04:32:25,077
TOGETHER TO HAVE A SUCCESSFUL

7110
04:32:25,077 --> 04:32:28,780
OUTCOME.

7111
04:32:28,780 --> 04:32:30,816
>> SO, SPEAKING OF
STAKEHOLDERS

7112
04:32:30,816 --> 04:32:32,184
TO FIND OUT WHAT WOULD BE

7113
04:32:32,184 --> 04:32:33,385
MEANINGFUL IN THEIR EYES IN

7114
04:32:33,385 --> 04:32:34,553
TERMS OF THE TYPE OF RESPONSE

7115
04:32:34,553 --> 04:32:35,687
THEY WANT TO SEE?

7116
04:32:35,687 --> 04:32:36,588
>> BECAUSE AT THE END OF
THE

7117
04:32:36,588 --> 04:32:37,856
DAY, YOU COULD HAVE ALL THESE

7118
04:32:37,856 --> 04:32:40,158
PAPERS AND LIKE HIGH-IMPACT

7119
04:32:40,158 --> 04:32:42,060
JOURNALS BUT IF IT DOESN'T

7120
04:32:42,060 --> 04:32:43,061
IMFACT BOOTS ON THE GROUNDWORK

7121
04:32:43,061 --> 04:32:45,197
THAT IS ACTUALLY HAPPENING IN

7122
04:32:45,197 --> 04:32:48,800
WHATEVER SETTING, PRODUCTION

7123
04:32:48,800 --> 04:32:49,768
SETTING, CLINICAL PRACTICE, I

7124
04:32:49,768 --> 04:32:53,572
THINK THE GAIN IS LESS.

7125
04:32:53,572 --> 04:32:56,708
>> THANK YOU.

7126
04:32:56,708 --> 04:33:01,179
GREAT COMMENTS.

7127
04:33:01,179 --> 04:33:02,481
>> VERONICA SMITH, MEDICAL

7128
04:33:02,481 --> 04:33:03,949
ETHICS, AUSTRALIA.

7129
04:33:03,949 --> 04:33:06,885
THANK YOU FOR THE LAST TWO DAYS.

7130
04:33:06,885 --> 04:33:10,055
IT MADE OUR FLIGHT WORTH IT.

7131
04:33:10,055 --> 04:33:13,492
JUST A COUPLE OF -- JUST A

7132
04:33:13,492 --> 04:33:14,693
COMMENT AS SOMEONE WHO HAS BEEN

7133
04:33:14,693 --> 04:33:17,596
WORKING WITH ANIMALS FOR OVER 20

7134
04:33:17,596 --> 04:33:20,699
YEARS AND IS A FARMER AS WELL

7135
04:33:20,699 --> 04:33:24,102
FOR THE LAST 10.

7136
04:33:24,102 --> 04:33:28,006
IT IS FRUSTRATING TO HEAR

7137
04:33:28,006 --> 04:33:32,711
EVERYONE SAY SO MUCH ABOUT THE

7138
04:33:32,711 --> 04:33:33,845
ANIMALS AREN'T TELLING YOU.

7139
04:33:33,845 --> 04:33:35,914
YOU CAN'T TALK TO THEM.

7140
04:33:35,914 --> 04:33:40,118
THE ANIMALS REALLY ARE.

7141
04:33:40,118 --> 04:33:42,287
AND YOU ALL KNOW.

7142
04:33:42,287 --> 04:33:44,323
THEY ARE TALKING TO YOU EVERY

7143
04:33:44,323 --> 04:33:45,590
MINUTE AND TELLING YOU WHETHER

7144
04:33:45,590 --> 04:33:47,592
THEY ARE IN PAIN OR WHETHER THEY

7145
04:33:47,592 --> 04:33:49,494
ARE HAPPY.

7146
04:33:49,494 --> 04:33:51,196
AND THERE IS A WORD I LIKE TO

7147
04:33:51,196 --> 04:33:53,598
USE WHICH IS, WELL-BEING, RATHER

7148
04:33:53,598 --> 04:33:55,467
THAN WELFARE.

7149
04:33:55,467 --> 04:33:58,804
AND THAT'S ABOUT ANIMAL'S

7150
04:33:58,804 --> 04:34:02,841
QUALITY OF LIFE.

7151
04:34:02,841 --> 04:34:04,609
SO, I SORT OF WANT EVERYONE TO

7152
04:34:04,609 --> 04:34:05,844
STOP SAYING THAT THEIR ANIMALS

7153
04:34:05,844 --> 04:34:07,012
AREN'T TALKING TO THEM.

7154
04:34:07,012 --> 04:34:10,515
BECAUSE YOU KNOW THAT THEY ARE.

7155
04:34:10,515 --> 04:34:13,352
BUT, ALSO THAT LEADS TO FOR

7156
04:34:13,352 --> 04:34:14,119
FUTURE PLANNING.

7157
04:34:14,119 --> 04:34:16,321
MAYBE WE NEED TO BE DOING MORE

7158
04:34:16,321 --> 04:34:19,591
WORK IN WHAT IS NORMAL.

7159
04:34:19,591 --> 04:34:22,694
SO BEHAVIOR IN ANIMAL THAT IS IN

7160
04:34:22,694 --> 04:34:26,498
A HAPPY STATE, AND THEN THIS

7161
04:34:26,498 --> 04:34:27,733
WILL FREAK THE CVM PEOPLE OUT.

7162
04:34:27,733 --> 04:34:30,302
IS MAYBE RATHER THAN LOOKING AT

7163
04:34:30,302 --> 04:34:31,837
THEIR RESPONSE COMPARED TO A

7164
04:34:31,837 --> 04:34:33,405
PLACEBO, LOOK AT THEIR RESPONSE

7165
04:34:33,405 --> 04:34:36,808
COMPARED TO WHAT THAT

7166
04:34:36,808 --> 04:34:38,477
STANDARDIZED NORMAL SHOULD BE.

7167
04:34:38,477 --> 04:34:41,513
BUT THAT'S GOING TO ALSO HELP

7168
04:34:41,513 --> 04:34:43,215
OUR AI FRIENDS BECAUSE WE'LL

7169
04:34:43,215 --> 04:34:45,417
HAVE THAT BANK OF INFORMATION

7170
04:34:45,417 --> 04:34:47,419
ABOUT WHAT WE CONSIDER TO BE

7171
04:34:47,419 --> 04:34:48,153
NORMAL BEHAVIOR.

7172
04:34:48,153 --> 04:34:52,624
YES, WE'LL HAVE TO MEET AND

7173
04:34:52,624 --> 04:34:55,560
STUDY WITH DIFFERENT SEXUAL

7174
04:34:55,560 --> 04:34:56,962
SPECIES INTERACTIONS AND

7175
04:34:56,962 --> 04:35:01,033
ENVIRONMENTAL INTERACTIONS

7176
04:35:01,033 --> 04:35:02,601
AND -- ALL SORTS OF -- AND AGE

7177
04:35:02,601 --> 04:35:03,668
GROUP INTERACTIONS AS WELL.

7178
04:35:03,668 --> 04:35:05,637
SO THERE IS A LOT TO DO BUT

7179
04:35:05,637 --> 04:35:06,538
MAYBE THAT'S SOMETHING WE NEED

7180
04:35:06,538 --> 04:35:08,740
TO FOCUS ON.

7181
04:35:08,740 --> 04:35:09,574
>> GREAT COMMENTS.

7182
04:35:09,574 --> 04:35:14,713
THANK YOU.

7183
04:35:14,713 --> 04:35:17,949
>> MARK WISE, NICE TO MEET
YOU.

7184
04:35:17,949 --> 04:35:21,319
REALLY ENJOYED THE MEETING AND

7185
04:35:21,319 --> 04:35:22,754
THESE COMMENTS.

7186
04:35:22,754 --> 04:35:26,725
WHAT I HEARD WAS, YESTERDAY WE

7187
04:35:26,725 --> 04:35:31,596
HEARD THE C SONG VERSUS THE LOAD

7188
04:35:31,596 --> 04:35:31,863
MEASURES.

7189
04:35:31,863 --> 04:35:33,932
AND WHAT IT SOUNDS LIKE THINGS

7190
04:35:33,932 --> 04:35:36,468
THAT WE'RE STRUGGLING WITH IS

7191
04:35:36,468 --> 04:35:37,602
THE METROLOGIY COMPONENT THAT

7192
04:35:37,602 --> 04:35:41,273
WAS BROUGHT UP EARLIER.

7193
04:35:41,273 --> 04:35:43,141
AND AND WE DON'T KNOW WHAT ARE

7194
04:35:43,141 --> 04:35:45,343
THE MOST SENSITIVE MEASURES AND

7195
04:35:45,343 --> 04:35:47,746
WE'RE DANCING AROUND THE

7196
04:35:47,746 --> 04:35:48,613
SENSITIVE MEASURES AND THEN

7197
04:35:48,613 --> 04:35:50,916
SCALING THESE MEASURES OR

7198
04:35:50,916 --> 04:35:52,617
NORMALIZING THESE MEASURES.

7199
04:35:52,617 --> 04:35:56,388
AND TODAY THE TALK ABOUT

7200
04:35:56,388 --> 04:35:58,790
MULTIDIMENSIONAL MEASURES AND

7201
04:35:58,790 --> 04:36:01,460
INTEGRATING OR PARSING THOSE.

7202
04:36:01,460 --> 04:36:03,161
SO I DON'T REALLY KNOW THE

7203
04:36:03,161 --> 04:36:06,064
ANSWER BUT I THINK THAT SOMEHOW

7204
04:36:06,064 --> 04:36:08,066
WE HAVE TO MAYBE THROUGH A

7205
04:36:08,066 --> 04:36:09,367
META-ANALYSIS OR SOME KIND OF

7206
04:36:09,367 --> 04:36:11,269
STATISTICAL ANALYSIS, DETERMINE

7207
04:36:11,269 --> 04:36:15,207
WHICH OF OUR TESTING IS THE MOST

7208
04:36:15,207 --> 04:36:18,710
SENSITIVE FOR US SO WE'RE NOT

7209
04:36:18,710 --> 04:36:21,079
MEASURING FIVE DIFFERENT, 10

7210
04:36:21,079 --> 04:36:23,682
DIFFERENT, 20 DIFFERENT WAYS.

7211
04:36:23,682 --> 04:36:25,684
OR EVEN MEASURING THE SAME THING

7212
04:36:25,684 --> 04:36:29,855
IN SLIGHTLY DIFFERENT FACETS OF

7213
04:36:29,855 --> 04:36:30,122
THE PRIMP.

7214
04:36:30,122 --> 04:36:33,692
SO MAYBE SOME KIND OF PULLING

7215
04:36:33,692 --> 04:36:36,261
TOGETHER THAT SO THAT WE COULD

7216
04:36:36,261 --> 04:36:39,464
HAVE A MORE UNIFIED MEASURE

7217
04:36:39,464 --> 04:36:40,632
RATHER THAN ALL OF THESE

7218
04:36:40,632 --> 04:36:44,102
DIFFERENT -- AND IT MAY BE

7219
04:36:44,102 --> 04:36:46,204
HELPFUL TO MOVE TO HEAR FROM THE

7220
04:36:46,204 --> 04:36:48,940
HUMAN SIDE OF THINGS, BECAUSE

7221
04:36:48,940 --> 04:36:50,742
THE ISSUE, ESPECIALLY THE

7222
04:36:50,742 --> 04:36:52,711
REGULATORY ISSUE THAT I HEAR IS,

7223
04:36:52,711 --> 04:36:55,981
WE START OFF WITH VERY NARROW

7224
04:36:55,981 --> 04:36:58,183
POPULATIONS THAT WE'RE TESTING

7225
04:36:58,183 --> 04:37:00,385
WITHIN AND WE CAN GENERALIZE AN

7226
04:37:00,385 --> 04:37:02,487
EFFECT SIZE BUT AS WE MOVE INTO

7227
04:37:02,487 --> 04:37:07,025
BROADER AND MORE DIVERSE

7228
04:37:07,025 --> 04:37:08,894
POPULATIONS, THE EFFECT SIZES

7229
04:37:08,894 --> 04:37:12,364
CHANGE OR WE HAVE RESPONDER AND

7230
04:37:12,364 --> 04:37:12,898
NON-RESPONDER POPULATIONS.

7231
04:37:12,898 --> 04:37:14,499
AND UNTIL WE GET TO THAT, THAT

7232
04:37:14,499 --> 04:37:19,204
WE CAN PHENOTYPE AND DO IT RIGHT

7233
04:37:19,204 --> 04:37:22,707
AND THEN SCALING FOR THE

7234
04:37:22,707 --> 04:37:24,876
APPROPRIATE PHENOTYPE,

7235
04:37:24,876 --> 04:37:27,045
EVERYTHING IS JUST FUZZ.

7236
04:37:27,045 --> 04:37:28,413
IT'S A HAZE.

7237
04:37:28,413 --> 04:37:31,917
SO I DON'T KNOW HOW DO YOU IT.

7238
04:37:31,917 --> 04:37:34,186
BUT SOMEHOW IT NEEDS TO GET

7239
04:37:34,186 --> 04:37:35,220
INTEGRATED BECAUSE THE

7240
04:37:35,220 --> 04:37:37,889
REGULATORY COMPONENT IS GOING TO

7241
04:37:37,889 --> 04:37:41,493
BE TOUGH TO OVERCOME BECAUSE AS

7242
04:37:41,493 --> 04:37:43,195
WE ENCOMPASS LARGER AND MORE

7243
04:37:43,195 --> 04:37:44,729
DIVERSE POPULATIONS AND THE

7244
04:37:44,729 --> 04:37:47,399
EFFECT SIZES IMPACTED, THEN HOW

7245
04:37:47,399 --> 04:37:52,437
DO WE REACH REGULATORY ENDPOI 

7246
04:37:52,437 --> 04:37:52,704
ENDPOINTS?

7247
04:37:52,704 --> 04:37:54,706
THAT WAS VERY POORLY WORDED.

7248
04:37:54,706 --> 04:37:55,507
>> NOT AT ALL.

7249
04:37:55,507 --> 04:37:57,108
GREAT COMMENTS.

7250
04:37:57,108 --> 04:37:58,310
AND I THINK FROM ALL OF THE

7251
04:37:58,310 --> 04:37:59,711
COMMENTS AND EVERYTHING WE HEARD

7252
04:37:59,711 --> 04:38:01,413
IT'S CLEAR WE ARE MOVING IN THE

7253
04:38:01,413 --> 04:38:02,614
RIGHT DIRECTION.

7254
04:38:02,614 --> 04:38:04,015
IT'S ALL POSITIVE BECAUSE WE ARE

7255
04:38:04,015 --> 04:38:05,116
HAVING DISCUSSIONS AND COMING

7256
04:38:05,116 --> 04:38:08,720
TOGETHER TO MEET LIKE THIS AND

7257
04:38:08,720 --> 04:38:10,522
TO DISCUSS THESE DIFFICULTIES

7258
04:38:10,522 --> 04:38:11,523
AND HURDLES AND THESE

7259
04:38:11,523 --> 04:38:11,856
OPPORTUNITIES.

7260
04:38:11,856 --> 04:38:13,592
SO THANK YOU TO EVERYONE.

7261
04:38:13,592 --> 04:38:15,093
SAFE JOURNEY HOME.

7262
04:38:15,093 --> 04:38:17,929
AND SEE YOU NEXT TIME.

7263
04:38:17,929 --> 04:38:19,931
I DON'T KNOW WHEN THAT WILL BE.

7264
04:38:19,931 --> 04:38:30,141
[ APPLAUSE ]