1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:45,560 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:45,560 --> 00:00:47,640 TODAY WE'RE GOING TO TALK 12 00:00:47,640 --> 00:00:49,760 ABOUT THE QUESTION OF WHETHER OR 13 00:00:49,760 --> 00:00:51,920 NOT THERE SHOULD BE LIMITS ON 14 00:00:51,920 --> 00:00:54,320 THE RISKS OF RESEARCH WITH 15 00:00:54,320 --> 00:00:55,240 COMPETENT ADULTS. 16 00:00:55,240 --> 00:00:58,280 SO, OUTSIDE OF THE RESEARCH 17 00:00:58,280 --> 00:00:59,400 SETTING WE LET COMPETENT ADULTS 18 00:00:59,400 --> 00:01:02,120 DO LOTS OF RISKY EVEN CRAZY 19 00:01:02,120 --> 00:01:02,360 THINGS. 20 00:01:02,360 --> 00:01:05,200 THEY GET TO CLIMB MOUNTAINS. 21 00:01:05,200 --> 00:01:10,440 THEY GET TO CLIMB MOUNTAINS TO 22 00:01:10,440 --> 00:01:11,680 RESCUE STRANDED MOUNTAIN 23 00:01:11,680 --> 00:01:11,960 CLIMBERS. 24 00:01:11,960 --> 00:01:16,200 AS MY COLLEAGUES POINT OUT SOME 25 00:01:16,200 --> 00:01:17,000 CRAZY PEOPLE RIDE MOTORCYCLES, 26 00:01:17,000 --> 00:01:19,520 THEY RIDE THEM IN CHARITY 27 00:01:19,520 --> 00:01:21,080 RALLIES, SO WE ALLOW PEOPLE 28 00:01:21,080 --> 00:01:22,400 OUTSIDE RESEARCH TO DO RISKY 29 00:01:22,400 --> 00:01:22,760 THINGS. 30 00:01:22,760 --> 00:01:28,760 NOW TURN TO THE RESEARCH 31 00:01:28,760 --> 00:01:29,200 SETTINGS. 32 00:01:29,200 --> 00:01:31,040 RESEARCH THAT POSES HIDE RISK IS 33 00:01:31,040 --> 00:01:32,800 CONSIDERED WIDELY ACCEPTABLE 34 00:01:32,800 --> 00:01:35,760 WHEN IT OFFERS PARTICIPANTS 35 00:01:35,760 --> 00:01:36,280 COMPENSATING POTENTIAL FOR 36 00:01:36,280 --> 00:01:36,920 CLINICAL BENEFITS. 37 00:01:36,920 --> 00:01:40,800 ONE OF THE EXEMPLARS OF THIS 38 00:01:40,800 --> 00:01:42,520 RESEARCH ON METHODS TO TREAT 39 00:01:42,520 --> 00:01:46,120 CANCER THAT INVOLVES BONE MARROW 40 00:01:46,120 --> 00:01:48,920 TRANSPLANTATION, CAN INVOLVE A 41 00:01:48,920 --> 00:01:51,000 SIGNIFICANT RISK OF MORBIDITY, 42 00:01:51,000 --> 00:01:53,160 EVEN MORTALITY, AND TYPICALLY 43 00:01:53,160 --> 00:01:54,160 THAT RESEARCH IS REGARDED AS 44 00:01:54,160 --> 00:01:56,800 ACCEPTABLE AS LONG AS THE 45 00:01:56,800 --> 00:01:58,280 PARTICIPANTS HAVE A COMPENSATING 46 00:01:58,280 --> 00:02:00,320 POTENTIAL FOR CLINICAL BENEFIT. 47 00:02:00,320 --> 00:02:01,640 THAT RAISES THE ETHICAL QUESTION 48 00:02:01,640 --> 00:02:04,120 FOR TODAY OF WHAT ABOUT RESEARCH 49 00:02:04,120 --> 00:02:07,800 THAT DOES NOT OFFER THE 50 00:02:07,800 --> 00:02:09,640 PARTICIPANTS THEMSELVES A 51 00:02:09,640 --> 00:02:11,240 COMPENSATING POTENTIAL FOR 52 00:02:11,240 --> 00:02:11,720 CLINICAL BENEFIT. 53 00:02:11,720 --> 00:02:13,800 SO, GUIDELINES IN THE U.S. AND 54 00:02:13,800 --> 00:02:15,400 AROUND THE WORLD HAVE VERY 55 00:02:15,400 --> 00:02:18,920 STRICT LIMITS ON THE RISKS TO 56 00:02:18,920 --> 00:02:19,920 WHICH RESEARCHERS CAN EXPOSE 57 00:02:19,920 --> 00:02:22,240 INDIVIDUALS WHO CAN'T GIVE 58 00:02:22,240 --> 00:02:24,200 INFORMED CONSENT, THE PARADIGM 59 00:02:24,200 --> 00:02:25,640 EXAMPLE HERE IS CHILDREN. 60 00:02:25,640 --> 00:02:28,400 THAT RAISES THE QUESTION FOR 61 00:02:28,400 --> 00:02:30,400 TODAY ABOUT COMPETENT ADULTS. 62 00:02:30,400 --> 00:02:32,600 TO WHAT EXTENT SHOULD WE ALLOW 63 00:02:32,600 --> 00:02:34,600 COMPETENT ADULTS TO AGREE TO DO 64 00:02:34,600 --> 00:02:37,000 SO TO FACE HIGH RISKS OF 65 00:02:37,000 --> 00:02:38,640 RESEARCH IN THE CONTEXT OF 66 00:02:38,640 --> 00:02:40,560 STUDIES THAT WON'T BENEFIT THEM 67 00:02:40,560 --> 00:02:42,600 BUT OFFER THE POTENTIAL TO LEARN 68 00:02:42,600 --> 00:02:45,000 THINGS THAT MIGHT HELP PEOPLE IN 69 00:02:45,000 --> 00:02:45,800 THE FUTURE. 70 00:02:45,800 --> 00:02:47,000 REGULATIONS INCLUDING U.S. 71 00:02:47,000 --> 00:02:49,400 REGULATIONS HAVE NO UPPER LIMITS 72 00:02:49,400 --> 00:02:50,320 ON RESEARCH WITH COMPETENT 73 00:02:50,320 --> 00:02:51,240 ADULTS. 74 00:02:51,240 --> 00:02:53,200 AT LEAST IN PRINCIPLE, ACCORDING 75 00:02:53,200 --> 00:02:54,960 TO THE REGULATIONS, YOU COULD 76 00:02:54,960 --> 00:02:57,080 HAVE ANY LEVEL OF RISKS, AS LONG 77 00:02:57,080 --> 00:02:58,400 AS THEY ARE MINIMIZED, AS LONG 78 00:02:58,400 --> 00:03:01,640 AS IT'S SOCIALLY VALUABLE, IT 79 00:03:01,640 --> 00:03:02,440 GETS APPROVED AND INDIVIDUALS 80 00:03:02,440 --> 00:03:03,400 CONSENT. 81 00:03:03,400 --> 00:03:05,800 AT THE SAME TIME IRBs, THE 82 00:03:05,800 --> 00:03:06,960 COMMITTEES THAT REVIEW AND 83 00:03:06,960 --> 00:03:09,200 APPROVE RESEARCH STUDIES, TEND 84 00:03:09,200 --> 00:03:11,280 TO BE VERY SKEPTICAL OF HIGH 85 00:03:11,280 --> 00:03:13,000 RISK RESEARCH AND OFTEN REGARD 86 00:03:13,000 --> 00:03:15,400 HIGHER RISK RESEARCH EVEN IN 87 00:03:15,400 --> 00:03:17,600 COMPETENT ADULTS AS ETHICALLY 88 00:03:17,600 --> 00:03:18,200 PROBLEMATIC. 89 00:03:18,200 --> 00:03:22,840 SO THAT RAISES OUR QUESTION FOR 90 00:03:22,840 --> 00:03:23,840 TODAY, A STRAIGHTFORWARD ONE, 91 00:03:23,840 --> 00:03:24,640 NOT NECESSARILY A SIMPLE ONE, 92 00:03:24,640 --> 00:03:27,360 WHICH IS WHO IS RIGHT IN THIS 93 00:03:27,360 --> 00:03:27,560 CASE? 94 00:03:27,560 --> 00:03:29,360 ARE THE REGULATIONS TOO 95 00:03:29,360 --> 00:03:29,680 PERMISSIVE? 96 00:03:29,680 --> 00:03:32,280 SHOULD WE HAVE UPPER LIMITS ON 97 00:03:32,280 --> 00:03:34,000 RESEARCH WITH COMPETENT ADULTS? 98 00:03:34,000 --> 00:03:35,360 OR ARE REVIEW COMMITTEES BEING 99 00:03:35,360 --> 00:03:37,760 TOO CAUTIOUS? 100 00:03:37,760 --> 00:03:40,200 ARE THEY BLOCKING APPROPRIATE 101 00:03:40,200 --> 00:03:41,520 AND ETHICALLY ACCEPTABLE 102 00:03:41,520 --> 00:03:41,800 RESEARCH? 103 00:03:41,800 --> 00:03:43,920 SO TO DISCUSS THESE QUESTIONS WE 104 00:03:43,920 --> 00:03:46,400 HAVE TWO PRESENTERS. 105 00:03:46,400 --> 00:03:48,200 FIRST PAUL KIMMEL, SENIOR 106 00:03:48,200 --> 00:03:49,600 ADVISER TO DIRECTOR OF THE 107 00:03:49,600 --> 00:03:51,200 NATIONAL INSTITUTES OF DIABETES 108 00:03:51,200 --> 00:03:53,600 AND DIGESTIVE AND KIDNEY 109 00:03:53,600 --> 00:03:57,000 DISORDERS, NIDDK, AT THE NIH. 110 00:03:57,000 --> 00:03:58,320 PAUL WILL PRESENT A CASE FOR US. 111 00:03:58,320 --> 00:03:59,600 TO HELP US THINK THROUGH THE 112 00:03:59,600 --> 00:04:01,520 ETHICS OF THIS CASE WE'RE 113 00:04:01,520 --> 00:04:03,400 FORTUNATE TODAY TO HAVE ALEX 114 00:04:03,400 --> 00:04:07,600 CAPRON, WHO IS AT THE UNIVERSITY 115 00:04:07,600 --> 00:04:11,800 OF SOUTHERN CALIFORNIA, A 116 00:04:11,800 --> 00:04:13,200 UNIVERSITY PROFESSOR, ALSO THE 117 00:04:13,200 --> 00:04:15,680 HEALTH CARE LAW POLICY AND 118 00:04:15,680 --> 00:04:16,080 ETHICS. 119 00:04:16,080 --> 00:04:17,920 AND MORE IMPORTANTLY FOR TODAY'S 120 00:04:17,920 --> 00:04:20,080 SESSION ALEX IS WIDELY REGARDED 121 00:04:20,080 --> 00:04:25,880 AS ONE OF THE MOST IMPORTANT 122 00:04:25,880 --> 00:04:26,520 COMMENTATORS ON RESEARCH ETHICS 123 00:04:26,520 --> 00:04:27,800 OVER 30 YEARS IN THE U.S. AND 124 00:04:27,800 --> 00:04:30,000 AROUND THE WORLD. 125 00:04:30,000 --> 00:04:31,800 SO WE'RE LUCKY TO HAVE HIM HELP 126 00:04:31,800 --> 00:04:32,960 US THINK THROUGH THE QUESTIONS 127 00:04:32,960 --> 00:04:33,480 TODAY. 128 00:04:33,480 --> 00:04:36,800 TO START US OFF, PAUL. 129 00:04:36,800 --> 00:04:38,320 >> THANK YOU, DAVE. 130 00:04:38,320 --> 00:04:41,560 I'M THRILLED TO BE HERE WITH YOU 131 00:04:41,560 --> 00:04:42,760 AND THE AUDIENCE. 132 00:04:42,760 --> 00:04:46,440 AND I'M GOING TO SLIGHTLY 133 00:04:46,440 --> 00:04:51,000 REFRAIN DAVE'S QUESTION TO THINK 134 00:04:51,000 --> 00:04:52,600 ABOUT ALTRUISTIC PARTICIPANTS IN 135 00:04:52,600 --> 00:04:53,600 CLINICAL RESEARCH WHERE THERE 136 00:04:53,600 --> 00:04:55,320 MIGHT BE SOME RISKS AND TO GIVE 137 00:04:55,320 --> 00:04:58,440 YOU A FRAMEWORK I'M GOING TO 138 00:04:58,440 --> 00:05:07,400 TELL YOU ABOUT THE KPMP PROGRAM, 139 00:05:07,400 --> 00:05:09,400 WITHIN I NIDDK, KIDNEY PRECISION 140 00:05:09,400 --> 00:05:10,240 MEDICINE PROJECT. 141 00:05:10,240 --> 00:05:11,320 NO CONFLICTS OF INTEREST. 142 00:05:11,320 --> 00:05:16,920 WE'RE GOING TO TALK ABOUT THIS 143 00:05:16,920 --> 00:05:17,800 KIDNEY PROJECT, DESCRIBE THE 144 00:05:17,800 --> 00:05:18,640 SCIENTIFIC POTENTIAL VALUE OF 145 00:05:18,640 --> 00:05:20,800 LOOKING AT KIDNEY TISSUE FROM 146 00:05:20,800 --> 00:05:23,720 HEALTHY INDIVIDUALS WHEN WE'RE 147 00:05:23,720 --> 00:05:25,440 TRYING TO DISCERN MECHANISMS OF 148 00:05:25,440 --> 00:05:27,520 DISEASE IN PATIENTS WITH KIDNEY 149 00:05:27,520 --> 00:05:29,280 DISEASE, AND WE'LL DISCUSS IN 150 00:05:29,280 --> 00:05:32,680 GREAT DETAIL THE POSSIBILITY OF 151 00:05:32,680 --> 00:05:33,640 OBTAINING TISSUE FROM ALTRUISTIC 152 00:05:33,640 --> 00:05:39,400 VOLUME VOLUNTEERS WITHOUT 153 00:05:39,400 --> 00:05:43,880 KIDNEY DISEASE THREE RESEARCH 154 00:05:43,880 --> 00:05:44,160 BIOPSIES. 155 00:05:44,160 --> 00:05:45,160 ACUTE KIDNEY -- 156 00:05:45,160 --> 00:05:45,960 >> WE CAN'T SEE YOUR SLIDES. 157 00:05:45,960 --> 00:05:48,600 I DON'T KNOW IF YOU BROUGHT THEM 158 00:05:48,600 --> 00:05:50,960 UP YET. 159 00:05:50,960 --> 00:05:51,880 >> I HAVE. 160 00:05:51,880 --> 00:05:54,320 THIS IS THE THIRD SLIDE. 161 00:05:54,320 --> 00:05:55,520 WE NEED SOME HELP. 162 00:05:55,520 --> 00:05:57,240 >> THEY ARE OPEN ON YOUR DESK 163 00:05:57,240 --> 00:06:02,440 TYPE, DID YOU SHARE SCREEN? 164 00:06:02,440 --> 00:06:10,000 >> I TRY THAT AGAIN. 165 00:06:10,000 --> 00:06:12,040 >> THERE YOU GO. 166 00:06:12,040 --> 00:06:15,400 CLICK SLIDE SHOW, WE'LL BE GOOD. 167 00:06:15,400 --> 00:06:17,920 >> CAN YOU SEE IT NOW? 168 00:06:17,920 --> 00:06:18,320 >> LOOKS GREAT. 169 00:06:18,320 --> 00:06:19,080 >> YOU KNOW, THERE'S NOTHING 170 00:06:19,080 --> 00:06:23,000 LIKE A PRESENTATION WITHOUT A 171 00:06:23,000 --> 00:06:24,080 TECHNICAL GLITCH. 172 00:06:24,080 --> 00:06:26,400 SO, TO GIVE A CONTEXT FOR THE 173 00:06:26,400 --> 00:06:28,280 KINDS OF PATIENTS WE'RE TRYING 174 00:06:28,280 --> 00:06:30,240 TO ULTIMATELY HELP WITH THE 175 00:06:30,240 --> 00:06:33,240 RESEARCH, KIDNEY DISEASE CAN BE 176 00:06:33,240 --> 00:06:34,520 SOMEWHAT CATEGORIZED INTO ACUTE 177 00:06:34,520 --> 00:06:39,360 KIDNEY INJURY AND CHRONIC KIDNEY 178 00:06:39,360 --> 00:06:42,400 DISEASE, AND THEY IMPOSE A 179 00:06:42,400 --> 00:06:43,080 SIGNIFICANT HEALTH BURDEN 180 00:06:43,080 --> 00:06:43,920 GLOBALLY. 181 00:06:43,920 --> 00:06:46,400 JUST IN THE UNITED STATES, THE 182 00:06:46,400 --> 00:06:49,920 ESTIMATE IS BETWEEN 1 IN 7 OR 8 183 00:06:49,920 --> 00:06:51,800 AMERICANS HAVE CHRONIC KIDNEY 184 00:06:51,800 --> 00:06:54,400 DISEASE, AND AKI IS A COMMON 185 00:06:54,400 --> 00:06:57,680 COMPLICATION OF PATIENTS IN THE 186 00:06:57,680 --> 00:06:58,800 HOSPITAL, AFFECTED 187 00:06:58,800 --> 00:06:59,360 DISPROPORTIONATELY ELDERLY 188 00:06:59,360 --> 00:07:00,000 PEOPLE, MEN AND AFRICAN 189 00:07:00,000 --> 00:07:04,760 AMERICANS IN THE UNITED STATES. 190 00:07:04,760 --> 00:07:06,400 AND ACUTE KIDNEY INJURY AND 191 00:07:06,400 --> 00:07:08,280 CHRONIC KIDNEY DISEASE ARE OFTEN 192 00:07:08,280 --> 00:07:11,480 DIAGNOSED BY RENAL BIOPSY WITHIN 193 00:07:11,480 --> 00:07:13,080 THE CLINICAL SITUATION. 194 00:07:13,080 --> 00:07:16,360 THERE ARE SELECT BUT WELL 195 00:07:16,360 --> 00:07:18,400 ESTABLISHED KIDNEY DISEASES, 196 00:07:18,400 --> 00:07:28,760 SUCH AS NEPHROTIC SYNDROME OR 197 00:07:28,760 --> 00:07:33,400 ACUTE GLOMERAL NEPHRITIS, THE 198 00:07:33,400 --> 00:07:36,680 DIAGNOSIS IS UNRAVELED BY USING 199 00:07:36,680 --> 00:07:39,560 A KIDNEY BIOPSY, HAVING A 200 00:07:39,560 --> 00:07:40,320 PATHOLOGIST DETERMINE THE 201 00:07:40,320 --> 00:07:41,800 DISEASE BY LOOKING AT TISSUE 202 00:07:41,800 --> 00:07:44,960 UNDER THE MICROSCOPE. 203 00:07:44,960 --> 00:07:47,840 TECHNIQUE WAS DEVELOPED IN THE 204 00:07:47,840 --> 00:07:50,640 19 50s IN EXPERIMENTS ON 205 00:07:50,640 --> 00:07:53,360 VOLUNTEERS WITH KIDNEY DISEASE, 206 00:07:53,360 --> 00:07:57,040 REFINED OVER DECADES WITH A WELL 207 00:07:57,040 --> 00:07:59,480 UNDERSTOOD RISK/BENEFIT RATIO. 208 00:07:59,480 --> 00:08:01,440 BUT ALTHOUGH ACUTE KIDNEY INJURY 209 00:08:01,440 --> 00:08:03,560 AND CHRONIC KIDNEY DISEASE ARE 210 00:08:03,560 --> 00:08:05,200 OFTEN DIAGNOSED BY RENAL BIOPSY, 211 00:08:05,200 --> 00:08:06,840 IN MANY CASES PATIENTS WITH 212 00:08:06,840 --> 00:08:09,240 KIDNEY DISEASE WHO ARE CARED FOR 213 00:08:09,240 --> 00:08:12,560 BY NEPHROLOGISTS NEVER HAVE 214 00:08:12,560 --> 00:08:14,200 BIOPSIES. 215 00:08:14,200 --> 00:08:15,960 PRECISELY BECAUSE THE CLINICAL 216 00:08:15,960 --> 00:08:18,360 CONSEQUENCES ARE SUPPOSEDLY WELL 217 00:08:18,360 --> 00:08:18,960 APPRECIATED. 218 00:08:18,960 --> 00:08:20,400 AND TWO EXAMPLES ARE PATIENTS 219 00:08:20,400 --> 00:08:22,480 WHO HAVE KIDNEY DISEASE BECAUSE 220 00:08:22,480 --> 00:08:24,160 OF HYPERTENSION OR HIGH BLOOD 221 00:08:24,160 --> 00:08:27,840 PRESSURE, A VERY COMMON FORM OF 222 00:08:27,840 --> 00:08:30,120 CHRONIC KIDNEY DISEASE, AND A 223 00:08:30,120 --> 00:08:35,120 VERY COMMON CLINICAL SYNDROME, 224 00:08:35,120 --> 00:08:37,440 HOSPITALIZED PATIENTS WITH AKI, 225 00:08:37,440 --> 00:08:40,000 ACUTE TUBULAR NECROSIS, ATN, 226 00:08:40,000 --> 00:08:41,200 WHICH IS A DEVASTATING 227 00:08:41,200 --> 00:08:46,960 COMPLICATION IN ILL PATIENTS IN 228 00:08:46,960 --> 00:08:52,600 THE HOSPITAL. IT IS PREDICATED 229 00:08:52,600 --> 00:08:54,360 ON UNDERSTANDING NEW DISEASES IN 230 00:08:54,360 --> 00:08:55,680 THE KIDNEY DISEASE POPULATION, 231 00:08:55,680 --> 00:08:57,360 AND THAT'S BECAUSE THERE ARE 232 00:08:57,360 --> 00:08:59,200 REALLY VERY FEW EFFECTIVE 233 00:08:59,200 --> 00:09:01,000 THERAPIES FOR PATIENTS WITH 234 00:09:01,000 --> 00:09:05,240 CHRONIC KIDNEY DISEASE, WE USE A 235 00:09:05,240 --> 00:09:07,600 SPECIFIC KIND OF 236 00:09:07,600 --> 00:09:08,360 ANTI-HYPERTENSIVE ANGIO TENSIVE 237 00:09:08,360 --> 00:09:17,640 CONVERTING ENZYME INHIBITORS OR 238 00:09:17,640 --> 00:09:18,800 RECEPTOR BLOCKERS, IN A WELL 239 00:09:18,800 --> 00:09:19,960 CONTROLLED RANGE FOR PATIENTS 240 00:09:19,960 --> 00:09:20,760 WITH CHRONIC KIDNEY DISEASE, AND 241 00:09:20,760 --> 00:09:22,440 THERE'S A NEW SET OF DRUGS THAT 242 00:09:22,440 --> 00:09:27,560 HAVE BEEN PRIMARILY USED IN 243 00:09:27,560 --> 00:09:28,040 DIABETIC PATIENTS, SGLT2 244 00:09:28,040 --> 00:09:29,000 INHIBITORS THAT HAVE SHOWN GREAT 245 00:09:29,000 --> 00:09:30,840 PROMISE FOR PATIENTS WITH AND 246 00:09:30,840 --> 00:09:33,280 WITHOUT DIABETES WHO HAVE KIDNEY 247 00:09:33,280 --> 00:09:33,600 DISEASE. 248 00:09:33,600 --> 00:09:35,680 THERE ARE REALLY NO CURRENT 249 00:09:35,680 --> 00:09:37,160 CLINICALLY EFFECTIVE TREATMENTS 250 00:09:37,160 --> 00:09:39,040 FOR PATIENTS WITH AKI. 251 00:09:39,040 --> 00:09:42,920 AND AS A RESULT, AKI CAN OFTEN 252 00:09:42,920 --> 00:09:45,360 LEAD TO CKD AND HAVE DIVERSITY 253 00:09:45,360 --> 00:09:48,320 STATING CONSEQUENCES IN LOW AND 254 00:09:48,320 --> 00:09:49,320 HIGH-INCOME COUNTRIES. 255 00:09:49,320 --> 00:09:52,000 TO ADDRESS THESE ISSUES OF 256 00:09:52,000 --> 00:09:53,040 UNDERSTANDING PATHOGENESIS AND 257 00:09:53,040 --> 00:09:55,440 TREATMENT OF PATIENTS WITH 258 00:09:55,440 --> 00:09:57,360 KIDNEY DISEASE, THE NIDDK 259 00:09:57,360 --> 00:10:00,400 STARTED THE KIDNEY PRECISION 260 00:10:00,400 --> 00:10:02,400 MEDICINE PROJECT IN 2017. 261 00:10:02,400 --> 00:10:03,760 AND IT'S FUNCTIONING UNDER A 262 00:10:03,760 --> 00:10:04,320 COOPERATIVE AGREEMENT WHICH 263 00:10:04,320 --> 00:10:06,400 MEANS THE NIH IS WORKING 264 00:10:06,400 --> 00:10:08,600 TOGETHER WITH THE INVESTIGATORS. 265 00:10:08,600 --> 00:10:12,440 THE GOAL OF THE KPMP IS TO 266 00:10:12,440 --> 00:10:16,600 IDENTIFY THOSE PATHWAYS THAT MAY 267 00:10:16,600 --> 00:10:18,800 WORK TO CAUSE WORSE DISEASE IN 268 00:10:18,800 --> 00:10:22,120 PATIENTS WHO HAVE CHRONIC KIDNEY 269 00:10:22,120 --> 00:10:24,080 DISEASE OR HAVE ACUTE KIDNEY 270 00:10:24,080 --> 00:10:24,400 INJURY. 271 00:10:24,400 --> 00:10:26,880 ALSO TO IDENTIFY POTENTIAL 272 00:10:26,880 --> 00:10:28,400 PROTECTIVE PATHWAYS THAT MIGHT 273 00:10:28,400 --> 00:10:31,400 BE USED AS TARGETS FOR DRUG 274 00:10:31,400 --> 00:10:31,920 THERAPIES. 275 00:10:31,920 --> 00:10:35,080 WHEN WE STARTED THE KPMP IN 2016 276 00:10:35,080 --> 00:10:37,080 BEFORE WE FUNDED THE SITES WE 277 00:10:37,080 --> 00:10:39,360 INVOLVED PATIENT REPRESENTATIVES 278 00:10:39,360 --> 00:10:41,960 AND THE FDA BECAUSE WE WERE 279 00:10:41,960 --> 00:10:44,000 CONCERNED ABOUT THE ETHICS AND 280 00:10:44,000 --> 00:10:45,360 SAFETY OF DOING KIDNEY BIOPSIES 281 00:10:45,360 --> 00:10:48,400 IN PATIENTS WHO WE DIDN'T 282 00:10:48,400 --> 00:10:51,240 USUALLY DO KIDNEY BIOPSIES IN, 283 00:10:51,240 --> 00:10:54,000 AND WE WERE CONCERNED GETTING 284 00:10:54,000 --> 00:10:55,840 COMMUNITY INPUT, SO THAT WE WERE 285 00:10:55,840 --> 00:10:57,280 ASSURED THAT THE RESEARCH WAS 286 00:10:57,280 --> 00:11:00,760 DONE IN AN ETHICAL MANNER. 287 00:11:00,760 --> 00:11:03,000 AND PATIENTS WERE INVOLVED IN 288 00:11:03,000 --> 00:11:05,120 THE CALL FOR RESEARCH AND THEY 289 00:11:05,120 --> 00:11:08,320 WERE INVOLVED IN THE STUDY AS IT 290 00:11:08,320 --> 00:11:10,680 WAS DESIGNED BY THE STEERING 291 00:11:10,680 --> 00:11:11,920 COMMITTEE, AND PATIENTS ARE 292 00:11:11,920 --> 00:11:13,600 INVOLVED IN ALL ASPECTS OF THE 293 00:11:13,600 --> 00:11:15,400 STUDY ON AN ONGOING BASIS, SO 294 00:11:15,400 --> 00:11:18,400 WE'RE VERY PROUD OF OUR PATIENT 295 00:11:18,400 --> 00:11:19,760 ENGAGEMENT WORK IN KPMP. 296 00:11:19,760 --> 00:11:21,360 WHY DO WE NEED TO DO KIDNEY 297 00:11:21,360 --> 00:11:23,200 BIOPSIES IN PATIENTS WHERE WE 298 00:11:23,200 --> 00:11:24,600 WOULD NEVER DO KIDNEY BIOPSIES 299 00:11:24,600 --> 00:11:26,200 IN THE CLINICAL SITUATION? 300 00:11:26,200 --> 00:11:28,720 IN ORDER TO DEVELOP NEW 301 00:11:28,720 --> 00:11:31,040 THERAPIES, WE HAVE TO UNDERSTAND 302 00:11:31,040 --> 00:11:34,320 THE PATHWAYS AT A MOLECULAR 303 00:11:34,320 --> 00:11:36,040 LEVEL OF KIDNEY DISEASE WE 304 00:11:36,040 --> 00:11:36,920 CURRENTLY DON'T UNDERSTAND, AND 305 00:11:36,920 --> 00:11:40,400 THE BEST WAY TO DO THAT IS TO 306 00:11:40,400 --> 00:11:44,440 OBTAIN KIDNEY TISSUE AND TO 307 00:11:44,440 --> 00:11:45,080 EVALUATE BIOCHEMISTRY AND OTHER 308 00:11:45,080 --> 00:11:46,400 ASPECTS OF THE TISSUE. 309 00:11:46,400 --> 00:11:51,200 AND SO TO ADDRESS OUR GAPS IN 310 00:11:51,200 --> 00:11:51,720 UNDERSTANDING PATHWAYS AND 311 00:11:51,720 --> 00:11:57,600 POTENTIAL TARGETS AVAILABLE KPMP 312 00:11:57,600 --> 00:11:59,480 IS DOING BIOPSIES AND STUDYING 313 00:11:59,480 --> 00:12:01,120 TISSUES FROM PATIENTS WITH 314 00:12:01,120 --> 00:12:02,000 COMMON KIDNEY DISEASES. 315 00:12:02,000 --> 00:12:05,480 SO, THE KPMP IS SET UP WITH SIX 316 00:12:05,480 --> 00:12:06,560 RECRUITMENT SITES, WHERE 317 00:12:06,560 --> 00:12:07,840 PHYSICIANS OBTAIN TISSUE FROM 318 00:12:07,840 --> 00:12:09,560 PATIENTS IN WHOM BIOPSIES ARE 319 00:12:09,560 --> 00:12:10,800 NOT CLINICALLY INDICATED, AND 320 00:12:10,800 --> 00:12:13,640 SPECIFICALLY THIS IS DONE IN THE 321 00:12:13,640 --> 00:12:15,440 COMMON KIDNEY DISEASES 322 00:12:15,440 --> 00:12:16,560 HYPERTENSIVE KIDNEY DISEASE AND 323 00:12:16,560 --> 00:12:18,400 KIDNEY DISEASE IN THOSE WITH 324 00:12:18,400 --> 00:12:21,200 DIABETES AS WELL AS AKI PATIENTS 325 00:12:21,200 --> 00:12:24,120 WITH THIS DISEASE ATN. 326 00:12:24,120 --> 00:12:32,200 THE BIOPSIES UNDERGO OMICS 327 00:12:32,200 --> 00:12:32,720 ANALYSIS, TRANSCRIPTOMICS, 328 00:12:32,720 --> 00:12:33,360 PROTEOMICS, METABOLOMICS ACROSS 329 00:12:33,360 --> 00:12:35,720 THE COUNTRY AND ONE OF THE 330 00:12:35,720 --> 00:12:38,120 IMPORTANT ASPECTS TO MAKE THESE 331 00:12:38,120 --> 00:12:39,600 PROCEDURES AS ETHICAL AND SAFE 332 00:12:39,600 --> 00:12:42,360 AS POSSIBLE AND IN ORDER TO 333 00:12:42,360 --> 00:12:43,680 PREVENT PATIENTS FROM UNDERGOING 334 00:12:43,680 --> 00:12:45,960 ANY COSTS, WE'VE WORKED OUT A 335 00:12:45,960 --> 00:12:50,840 WAY SO WE CAN COVER TREATMENTS 336 00:12:50,840 --> 00:12:52,760 IF NECESSARY BY INSURANCE, WHICH 337 00:12:52,760 --> 00:12:55,880 IS AN INNOVATION AT NIH. 338 00:12:55,880 --> 00:12:57,160 THE KPMP WAS FUNDED IN 2017. 339 00:12:57,160 --> 00:12:59,360 WE STARTED TO DO BIOPSIES IN 340 00:12:59,360 --> 00:13:04,080 2019 BECAUSE IT TOOK A LONG TIME 341 00:13:04,080 --> 00:13:06,000 TO OPERATIONALIZE THIS 342 00:13:06,000 --> 00:13:06,400 CONSORTIUM. 343 00:13:06,400 --> 00:13:08,560 WE WERE UNFORTUNATELY RIGHT 344 00:13:08,560 --> 00:13:11,440 AFTER STARTING THE KPMP SLOWED 345 00:13:11,440 --> 00:13:14,200 BY THE COVID PANDEMIC, BUT WE 346 00:13:14,200 --> 00:13:16,040 HAVE A LITTLE MORE THAN 32 347 00:13:16,040 --> 00:13:18,800 BIOPSIES FROM AKI PATIENTS, 348 00:13:18,800 --> 00:13:19,960 ALMOST 100 BIOPSIES FROM CKD 349 00:13:19,960 --> 00:13:24,000 PATIENTS NOW OVER THE LAST 2 1/2 350 00:13:24,000 --> 00:13:25,080 YEARS. 351 00:13:25,080 --> 00:13:26,360 WE'VE HAD NO DEATHS WITHIN KPMP. 352 00:13:26,360 --> 00:13:28,160 I WILL TELL YOU ABOUT THE RISKS 353 00:13:28,160 --> 00:13:29,720 OF RENAL BIOPSY. 354 00:13:29,720 --> 00:13:31,480 IT'S STILL EARLY DAYS BUT WE'RE 355 00:13:31,480 --> 00:13:34,120 VERY PLEASED THAT WE HAVE HAD 356 00:13:34,120 --> 00:13:36,680 MINIMAL HARMS, TO ANYBODY. 357 00:13:36,680 --> 00:13:37,680 THE COMPLICATIONS WITHIN THE 358 00:13:37,680 --> 00:13:40,520 KPMP ARE CONSISTENT WITH THE 359 00:13:40,520 --> 00:13:41,520 GENERAL CLINICAL EXPERIENCE. 360 00:13:41,520 --> 00:13:42,400 THEY INCLUDE BLEEDING AT THE 361 00:13:42,400 --> 00:13:47,160 BIOPSY SITE, FROM THE KIDNEY, 362 00:13:47,160 --> 00:13:48,600 LOSS OF BLOOD RESULTING IN 363 00:13:48,600 --> 00:13:50,800 CHANGES IN LABORATORY TESTS OF 364 00:13:50,800 --> 00:13:52,440 HEMOGLOBIN, AND HEMATOMAS AROUND 365 00:13:52,440 --> 00:13:53,960 THE KIDNEY. 366 00:13:53,960 --> 00:13:56,680 AND WE HAVE A VERY EXTENSIVE 367 00:13:56,680 --> 00:13:58,880 DATA SAFETY AND MONITORING BOARD 368 00:13:58,880 --> 00:13:59,760 WITH PATIENT REPRESENTATIVE 369 00:13:59,760 --> 00:14:03,560 WHICH HAS HELPED US EVALUATE OUR 370 00:14:03,560 --> 00:14:04,080 WORK. 371 00:14:04,080 --> 00:14:05,400 THE BIOPSIES HAVE BEEN VERY 372 00:14:05,400 --> 00:14:06,400 INTERESTING IN THESE PATIENTS 373 00:14:06,400 --> 00:14:08,080 WHO WOULD NOT USUALLY CLINICALLY 374 00:14:08,080 --> 00:14:09,480 GET A BIOPSY. 375 00:14:09,480 --> 00:14:12,080 AND MANY HAVE SHOWN US UNUSUAL 376 00:14:12,080 --> 00:14:13,200 FEATURES THAT WERE UNSUSPECTED 377 00:14:13,200 --> 00:14:13,840 IN THIS GROUP. 378 00:14:13,840 --> 00:14:16,720 SO, SOME OF THE BIOPSIES HAVE 379 00:14:16,720 --> 00:14:19,000 ASPECTS OF ACUTE KIDNEY INJURY 380 00:14:19,000 --> 00:14:20,760 AND CHRONIC KIDNEY DISEASE, 381 00:14:20,760 --> 00:14:23,360 SIMULTANEOUSLY, WHEN THAT WAS 382 00:14:23,360 --> 00:14:23,800 RELATIVELY UNEXPECTED. 383 00:14:23,800 --> 00:14:26,600 AND IN SUBSTANTIAL AMOUNT OF 384 00:14:26,600 --> 00:14:29,280 CASES UP TO 1/5 THE BIOPSIES 385 00:14:29,280 --> 00:14:31,680 YELLEDDED INFORMATION THAT HAS 386 00:14:31,680 --> 00:14:34,000 BEEN UNSUSPECTED AND THAT HAVE 387 00:14:34,000 --> 00:14:37,440 ACTUALLY CHANGED MEDICAL 388 00:14:37,440 --> 00:14:39,200 MANAGEMENT OF PATIENTS. 389 00:14:39,200 --> 00:14:41,560 COLLECTING KIDNEY TISSUE FROM 390 00:14:41,560 --> 00:14:42,560 PATIENTS WITHOUT KIDNEY DISEASE 391 00:14:42,560 --> 00:14:45,040 COULD HELP US IDENTIFY SPECIFIC 392 00:14:45,040 --> 00:14:45,720 CHANGES IN MOLECULAR PATHWAYS 393 00:14:45,720 --> 00:14:47,400 THAT ARE ASSOCIATED WITH 394 00:14:47,400 --> 00:14:48,760 DISEASES LIKE HYPERTENSIVE 395 00:14:48,760 --> 00:14:50,160 KIDNEY DISEASE OR DIABETIC 396 00:14:50,160 --> 00:14:51,440 KIDNEY DISEASE. 397 00:14:51,440 --> 00:14:54,000 BUT IN ORDER TO EVALUATE WHETHER 398 00:14:54,000 --> 00:14:57,360 THERE ARE CHANGES PRESENT, WE 399 00:14:57,360 --> 00:15:00,000 NEED TO HAVE REFERENCE TISSUE TO 400 00:15:00,000 --> 00:15:01,920 PUT IT INTO PERSPECTIVE, TO SEE 401 00:15:01,920 --> 00:15:05,640 WHAT'S NORMAL, AND WHAT'S NOT, 402 00:15:05,640 --> 00:15:07,560 IN THESE NEW STUDIES. 403 00:15:07,560 --> 00:15:09,480 IT'S REALLY NOT POSSIBLE TO 404 00:15:09,480 --> 00:15:11,000 ESTIMATE THE CHANCES THAT 405 00:15:11,000 --> 00:15:12,760 STUDYING HEALTHY KIDNEY TISSUE 406 00:15:12,760 --> 00:15:14,400 WILL LEAD TO VALUABLE INSIGHTS 407 00:15:14,400 --> 00:15:17,920 THAT WILL HELP TO IMPROVE THE 408 00:15:17,920 --> 00:15:19,080 TREATMENT FOR PATIENTS BECAUSE 409 00:15:19,080 --> 00:15:21,240 WE DON'T HAVE NEW TREATMENTS 410 00:15:21,240 --> 00:15:24,200 THAT WE'RE GOING TO USE IN THE 411 00:15:24,200 --> 00:15:26,400 PATIENTS WHO ARE VOLUNTEERING TO 412 00:15:26,400 --> 00:15:31,240 GIVE A KIDNEY BIOPSY AND GIVE UP 413 00:15:31,240 --> 00:15:33,520 TISSUE WITHIN THE KPMP. 414 00:15:33,520 --> 00:15:36,280 AND WE ALSO EXPECT THAT THE 415 00:15:36,280 --> 00:15:39,440 CLINICAL BENEFITS, IF WE MOVE TO 416 00:15:39,440 --> 00:15:41,120 PATIENTS WITH NORMAL KIDNEY 417 00:15:41,120 --> 00:15:44,120 FUNCTION, WHO ARE TOTALLY 418 00:15:44,120 --> 00:15:45,440 PARTICIPATING ON AN ALTRUISTIC 419 00:15:45,440 --> 00:15:46,760 BASIS WOULD NOT BE AVAILABLE. 420 00:15:46,760 --> 00:15:47,960 THERE WOULD BE NO CLINICAL 421 00:15:47,960 --> 00:15:49,560 BENEFIT TO HAVING A KIDNEY 422 00:15:49,560 --> 00:15:52,960 BIOPSY IN A PATIENT WITHOUT 423 00:15:52,960 --> 00:15:53,800 KIDNEY DISEASE. 424 00:15:53,800 --> 00:15:58,440 WE HAVE BEEN ABLE TO USE SOME 425 00:15:58,440 --> 00:16:00,800 REFERENCE TISSUE FROM KIDNEY 426 00:16:00,800 --> 00:16:02,880 DONORS, SO THESE INDIVIDUALS DO 427 00:16:02,880 --> 00:16:04,600 NOT HAVE KIDNEY DISEASE, AND 428 00:16:04,600 --> 00:16:06,440 THEY ALSO DO NOT REQUIRE A 429 00:16:06,440 --> 00:16:08,400 BIOPSY, THEY ARE DONATING A 430 00:16:08,400 --> 00:16:10,440 HEALTHY KIDNEY TO A PATIENT WHO 431 00:16:10,440 --> 00:16:12,400 NEEDS IT, KIDNEY TO TREAT END 432 00:16:12,400 --> 00:16:14,960 STAGE RENAL DISEASE BUT THESE 433 00:16:14,960 --> 00:16:16,720 KIDNEYS ARE NOT COMPARABLE TO 434 00:16:16,720 --> 00:16:18,240 BIOPSIES IN KPMP BECAUSE 435 00:16:18,240 --> 00:16:19,760 BASICALLY PATIENTS ARE 436 00:16:19,760 --> 00:16:21,000 UNDERGOING GENERAL ANESTHESIA TO 437 00:16:21,000 --> 00:16:23,880 REMOVE THE KIDNEY. 438 00:16:23,880 --> 00:16:26,400 SO, WE WOULDN'T BE COMPARING 439 00:16:26,400 --> 00:16:30,400 REFERENCE HEALTHY TISSUE TO THE 440 00:16:30,400 --> 00:16:30,800 KPMP STUDIES. 441 00:16:30,800 --> 00:16:33,480 SO, WHAT WE HAVE BEEN INTERESTED 442 00:16:33,480 --> 00:16:36,160 IN KPMP IS TO OBTAIN KIDNEY 443 00:16:36,160 --> 00:16:38,400 TISSUE FROM HEALTHY PEOPLE WHO 444 00:16:38,400 --> 00:16:39,480 ARE NOT UNDERGOING GENERAL 445 00:16:39,480 --> 00:16:41,560 ANESTHESIA, WE WOULD LIKE TO 446 00:16:41,560 --> 00:16:43,600 ENGAGE ALTRUISTIC VOLUNTEERS WHO 447 00:16:43,600 --> 00:16:46,320 WOULD SAY THEY WOULD UNDERGO 448 00:16:46,320 --> 00:16:47,480 KIDNEY BIOPSY WHEN THEIR 449 00:16:47,480 --> 00:16:49,000 COMPLETELY HEALTHY AND HAVE NO 450 00:16:49,000 --> 00:16:51,320 CHANCE OF CHANGING ANY CLINICAL 451 00:16:51,320 --> 00:16:54,200 SITUATION FOR THEM, AND THE 452 00:16:54,200 --> 00:16:55,320 PROPOSAL WAS TO START BY 453 00:16:55,320 --> 00:16:57,800 ENROLLING A VERY SMALL GROUP OF 454 00:16:57,800 --> 00:17:00,400 HEALTHY VOLUNTEERS AND HAVING 455 00:17:00,400 --> 00:17:03,560 THEM GO AFTER GIVING INFORMED 456 00:17:03,560 --> 00:17:05,200 CONSENT, A KIDNEY BIOPSY FOR 457 00:17:05,200 --> 00:17:06,400 RESEARCH PURPOSES USING THE SAME 458 00:17:06,400 --> 00:17:08,200 KIND OF TECHNIQUES THAT WE'RE 459 00:17:08,200 --> 00:17:12,840 USING IN CLINICAL PRACTICE AND 460 00:17:12,840 --> 00:17:13,600 IN KPMP. 461 00:17:13,600 --> 00:17:15,560 THE PROBLEM IS THAT IT'S UNCLEAR 462 00:17:15,560 --> 00:17:18,880 WHAT THE RISKS OF KIDNEY BIOPSY 463 00:17:18,880 --> 00:17:21,000 IN PATIENTS WHO UNDERGO A BIOPSY 464 00:17:21,000 --> 00:17:22,600 FOR RESEARCH PURPOSES WOULD BE. 465 00:17:22,600 --> 00:17:25,800 WE HAVE SOME GOOD DATA FOR 466 00:17:25,800 --> 00:17:27,560 PATIENTS WHO UNDERGO CLINICAL 467 00:17:27,560 --> 00:17:29,800 BIOPSY FOR CLINICAL REASONS, AND 468 00:17:29,800 --> 00:17:32,680 IN FACT KIDNEY BIOPSY IN HEALTHY 469 00:17:32,680 --> 00:17:34,960 PATIENTS, PEOPLE, MAY BE 470 00:17:34,960 --> 00:17:36,480 ACTUALLY LESS RISKY BUT WE DON'T 471 00:17:36,480 --> 00:17:38,200 KNOW ABOUT THAT BECAUSE WE 472 00:17:38,200 --> 00:17:41,800 HAVEN'T DONE THOSE STUDIES. 473 00:17:41,800 --> 00:17:44,240 THE RISKS FOR A CLINICAL KIDNEY 474 00:17:44,240 --> 00:17:46,000 BIOPSY IN PATIENTS WHO HAVE 475 00:17:46,000 --> 00:17:48,760 CHRONIC KIDNEY DISEASE OR ACUTE 476 00:17:48,760 --> 00:17:50,440 KIDNEY INJURY IS NOT COMPLETELY 477 00:17:50,440 --> 00:17:52,800 CLEAR BECAUSE THE RISK IS SO LOW 478 00:17:52,800 --> 00:17:55,400 YOU NEED TO HAVE LARGE SERIES OF 479 00:17:55,400 --> 00:17:58,120 UP TO 1,000 TO PERHAPS 10,000 480 00:17:58,120 --> 00:18:01,760 PATIENTS, BUT IT LOOKS LIKE THE 481 00:18:01,760 --> 00:18:02,640 GENERAL RISKS IN MOST STUDIES 482 00:18:02,640 --> 00:18:04,960 HAVE BEEN ONE TO THREE DEATHS IN 483 00:18:04,960 --> 00:18:08,040 1,000 PATIENTS, AND IN SOME 484 00:18:08,040 --> 00:18:11,840 OTHER STUDIES WHICH ARE, YOU 485 00:18:11,840 --> 00:18:13,240 KNOW, PRESUMABLY IN DIFFERENT 486 00:18:13,240 --> 00:18:15,480 POPULATIONS MUCH SMALLER, UP TO 487 00:18:15,480 --> 00:18:16,920 ONE IN SEVEN TO EIGHT THOUSAND 488 00:18:16,920 --> 00:18:21,520 PEOPLE, A VERY LOW RISK IN TERMS 489 00:18:21,520 --> 00:18:22,480 OF PERCENTAGES. 490 00:18:22,480 --> 00:18:25,200 THE MOST COMMON INTERVENTIONS 491 00:18:25,200 --> 00:18:26,400 ARE TO STOP BLEEDING, THAT 492 00:18:26,400 --> 00:18:29,080 HAPPENS ABOUT 3 TIMES IN 1,000 493 00:18:29,080 --> 00:18:37,560 PATIENTS, IN 1,000 PROCEDURES. 494 00:18:37,560 --> 00:18:39,680 MANY PATIENTS DEVELOP 495 00:18:39,680 --> 00:18:43,480 PERINEPHRIC HEMATOMA, NOT A 496 00:18:43,480 --> 00:18:44,000 CLINICALLY INCONSEQUENTIAL 497 00:18:44,000 --> 00:18:44,680 COMPLICATION. 498 00:18:44,680 --> 00:18:46,600 MORE PEOPLE TALK ABOUT PAIN AND 499 00:18:46,600 --> 00:18:48,240 SO UP TO 5% PATIENTS HAVE PAIN 500 00:18:48,240 --> 00:18:50,080 IN THE RENAL OF THE KIDNEY 501 00:18:50,080 --> 00:18:59,760 BIOPSY IN THE FLANK AND BACK, 5% 502 00:18:59,760 --> 00:19:02,160 HAVE BLOOD IN URINE FOR A 503 00:19:02,160 --> 00:19:04,240 LIMITED PERIOD OF TIME, 1 TO 2% 504 00:19:04,240 --> 00:19:07,320 WILL NEED A BLOOD TRANSUSING. 505 00:19:07,320 --> 00:19:10,360 THE KIDNEY BIOPSY DONE FOR 506 00:19:10,360 --> 00:19:16,240 CLINICAL INDICATIONS IS NOT RISK 507 00:19:16,240 --> 00:19:16,600 FREE. 508 00:19:16,600 --> 00:19:17,280 WE DEBATED, AS RESEARCHERS, 509 00:19:17,280 --> 00:19:19,400 WHETHER IT WOULD BE ETHICAL TO 510 00:19:19,400 --> 00:19:21,520 ASK HEALTHY ADULTS TO FACE THESE 511 00:19:21,520 --> 00:19:23,160 RISKS FOR RESEARCH PURPOSES. 512 00:19:23,160 --> 00:19:25,200 WE HAVE HAD THE PLEASURE OF 513 00:19:25,200 --> 00:19:27,000 VIGOROUS INVOLVEMENT OF 514 00:19:27,000 --> 00:19:27,600 COMMUNITY ENGAGEMENT WORKING 515 00:19:27,600 --> 00:19:30,280 GROUP PATIENTS, PATIENTS WHO HAD 516 00:19:30,280 --> 00:19:31,600 KIDNEY BIOPSIES, IN OUR WORK, 517 00:19:31,600 --> 00:19:33,360 AND WE'RE TRYING TO ENGAGE THE 518 00:19:33,360 --> 00:19:36,000 PARTICIPANTS WHO HAD KIDNEY 519 00:19:36,000 --> 00:19:37,600 BIOPSIES UNDER THE AEGIS OF THE 520 00:19:37,600 --> 00:19:41,720 KPMP GETTING FEEDBACK AND IN 521 00:19:41,720 --> 00:19:43,520 MOST CASES OUR PATIENT ADVISORS 522 00:19:43,520 --> 00:19:44,800 ARE ENTHUSIASTIC ABOUT ASKING 523 00:19:44,800 --> 00:19:48,360 FOR AN ALTRUISTIC VOLUNTEER TO 524 00:19:48,360 --> 00:19:49,800 PARTICIPATE BUT WE WERE 525 00:19:49,800 --> 00:19:52,560 CONCERNED ABOUT THE ETHICS OF 526 00:19:52,560 --> 00:19:56,800 THIS APPROACH AND WE INITIATED A 527 00:19:56,800 --> 00:19:57,920 BIOETHICS CONSULTATION WITH THE 528 00:19:57,920 --> 00:20:01,000 BIOETHICS TEAM AT NIH. 529 00:20:01,000 --> 00:20:04,200 AND AS DAVE HAS PUT IT, THE 530 00:20:04,200 --> 00:20:06,840 QUESTIONS THAT COME UP FROM THIS 531 00:20:06,840 --> 00:20:07,840 APPROACH TO RESEARCH IS, WHAT 532 00:20:07,840 --> 00:20:10,480 ARE THE ETHICAL LIMITS ON 533 00:20:10,480 --> 00:20:12,400 RESEARCH RISKS IN COMPETENT 534 00:20:12,400 --> 00:20:15,200 ADULTS AND HOW SHOULD THEY BE 535 00:20:15,200 --> 00:20:16,000 APPROACHED? 536 00:20:16,000 --> 00:20:18,280 HOW ARE THESE LIMITS DETERMINED? 537 00:20:18,280 --> 00:20:21,520 IS WHAT WE'RE PROPOSING IN KPMP 538 00:20:21,520 --> 00:20:22,960 CONSISTENT WITH REASONABLE RISKS 539 00:20:22,960 --> 00:20:24,800 TO TAKE TO ADVANCE A RESEARCH 540 00:20:24,800 --> 00:20:26,320 AGENDA WHICH COULD END UP 541 00:20:26,320 --> 00:20:28,200 HELPING MANY, MANY PATIENTS WITH 542 00:20:28,200 --> 00:20:31,320 KIDNEY DISEASE, NOT ONLY IN THE 543 00:20:31,320 --> 00:20:33,480 UNITED STATES BUT WORLDWIDE? 544 00:20:33,480 --> 00:20:36,320 IS IT MORE PROBLEMATIC TO EXPOSE 545 00:20:36,320 --> 00:20:36,960 HEALTHY INDIVIDUALS TO RESEARCH 546 00:20:36,960 --> 00:20:39,480 RISKS THAN PATIENTS WHO HAVE 547 00:20:39,480 --> 00:20:40,400 KIDNEY DISEASE? 548 00:20:40,400 --> 00:20:44,200 AND WOULD OUR STUDY BE ETHICALLY 549 00:20:44,200 --> 00:20:46,160 IMPROVED IF THE PATIENTS WERE 550 00:20:46,160 --> 00:20:47,680 PAID AN HONORARIUM FOR A BIOPSY? 551 00:20:47,680 --> 00:20:50,280 RIGHT NOW WE COVER COSTS OF 552 00:20:50,280 --> 00:20:52,880 BIOPSIES AND COMPLICATIONS WITH 553 00:20:52,880 --> 00:20:53,640 THE KPMP. 554 00:20:53,640 --> 00:21:00,200 SO, I'M VERY EAGER TO HEAR THE 555 00:21:00,200 --> 00:21:02,000 DISCUSSION FROM PROFESSOR CAPRON 556 00:21:02,000 --> 00:21:03,400 AND VERY INTERESTED TO HEAR WHAT 557 00:21:03,400 --> 00:21:05,200 OUR DISCUSSION IN THE LARGER 558 00:21:05,200 --> 00:21:06,880 AUDIENCE WILL TELL US ABOUT THIS 559 00:21:06,880 --> 00:21:08,520 APPROACH. 560 00:21:08,520 --> 00:21:09,320 THANK YOU VERY MUCH. 561 00:21:09,320 --> 00:21:09,960 >> THANK YOU, PAUL. 562 00:21:09,960 --> 00:21:12,840 IT'S A PLEASURE TO BE WITH YOU 563 00:21:12,840 --> 00:21:14,480 ALL TODAY. 564 00:21:14,480 --> 00:21:17,520 AND I HOPE WE CAN PROVOKE SOME 565 00:21:17,520 --> 00:21:20,960 QUESTIONS AND DISCUSSION ABOUT 566 00:21:20,960 --> 00:21:22,760 THE ALTRUISTIC PARTICIPATION IN 567 00:21:22,760 --> 00:21:26,440 GREATER THAN MINIMAL RISK 568 00:21:26,440 --> 00:21:27,360 RESEARCH USING THIS EXAMPLE. 569 00:21:27,360 --> 00:21:29,600 THE QUESTION I WAS ASSIGNED, 570 00:21:29,600 --> 00:21:32,160 SHOULD THERE BE LIMITS ON THE 571 00:21:32,160 --> 00:21:34,240 RISKS OF RESEARCH WITH COMPETENT 572 00:21:34,240 --> 00:21:34,680 ADULTS? 573 00:21:34,680 --> 00:21:37,640 I HAVE NO CONFLICTS TO REPORT. 574 00:21:37,640 --> 00:21:39,960 THE LEARNING OBJECTIVES I THINK 575 00:21:39,960 --> 00:21:45,040 HAVE BEEN DISTRIBUTED ALREADY. 576 00:21:45,040 --> 00:21:50,240 SO, IN MY REMARKS I REALIZE I 577 00:21:50,240 --> 00:21:51,560 MIGHT EXACERBATE PRESIDENT 578 00:21:51,560 --> 00:21:52,520 TRUMAN AFTER A FRUSTRATING 579 00:21:52,520 --> 00:21:54,840 MEETING WITH THE CHAIR OF HIS 580 00:21:54,840 --> 00:21:57,640 COUNCIL OF ECONOMIC ADVISORS HE 581 00:21:57,640 --> 00:22:01,680 EXCLAIMED, GIVE ME A ONE-ARMED 582 00:22:01,680 --> 00:22:06,000 ECONOMISTS, ALL MY ECONOMISTS 583 00:22:06,000 --> 00:22:09,120 SAY ONE HAND, BUT THEN, ON THE 584 00:22:09,120 --> 00:22:09,640 OTHER. 585 00:22:09,640 --> 00:22:13,360 I WILL TRY TO SITUATION WAIT THE 586 00:22:13,360 --> 00:22:17,640 ONE HAND AND THE OTHER WHICH I 587 00:22:17,640 --> 00:22:20,040 WILL DESCRIBE HISTORICALLY, AND 588 00:22:20,040 --> 00:22:24,120 SO THE FIRST THOUGHT HERE IS 589 00:22:24,120 --> 00:22:26,200 THAT WE HAVE TO REALIZE THE 590 00:22:26,200 --> 00:22:28,560 RULES WE LIVE WITH ARISE OUT OF 591 00:22:28,560 --> 00:22:30,760 A HISTORY OF ABUSES, AND THE 592 00:22:30,760 --> 00:22:32,120 FIRST SET OF ABUSES WHICH 593 00:22:32,120 --> 00:22:34,640 COVERED A LENGTHY PERIOD OF TIME 594 00:22:34,640 --> 00:22:36,120 LIE IN NOT HAVING CONSENT. 595 00:22:36,120 --> 00:22:38,280 AND THEY MIGHT LEAD TO THE 596 00:22:38,280 --> 00:22:42,320 CONCLUSION ON THE ONE HAND THAT 597 00:22:42,320 --> 00:22:43,600 WITH CONSENT THE RESEARCH THAT 598 00:22:43,600 --> 00:22:47,320 PAUL HAS DESCRIBED WOULD BE 599 00:22:47,320 --> 00:22:47,920 PERMISSIBLE. 600 00:22:47,920 --> 00:22:51,280 BUT AS WE LOOK THROUGH WHAT HAS 601 00:22:51,280 --> 00:22:52,040 HAPPENED, HISTORICALLY, WE CAN 602 00:22:52,040 --> 00:22:54,280 SEE I THINK THAT CONSENT IS NOT 603 00:22:54,280 --> 00:22:54,760 ENOUGH. 604 00:22:54,760 --> 00:22:56,000 AND THIS WOULD LEAD TO THE 605 00:22:56,000 --> 00:22:59,560 CONCLUSION THAT THE RESEARCH IS 606 00:22:59,560 --> 00:23:01,360 NOT PERMISSIBLE. 607 00:23:01,360 --> 00:23:03,440 I WILL ELABORATE ON THIS BY 608 00:23:03,440 --> 00:23:06,360 TALKING ABOUT RESEARCH BEGINNING 609 00:23:06,360 --> 00:23:08,000 WITH THOSE MOST INVOLVED. 610 00:23:08,000 --> 00:23:10,720 THE WORRY ABOUT SUBJECTS NOT 611 00:23:10,720 --> 00:23:12,600 HAVING FULL UNDERSTANDING AND 612 00:23:12,600 --> 00:23:14,640 THE ROLE THAT THE INTERESTS OF 613 00:23:14,640 --> 00:23:19,040 SOCIETY PLAY IN REACHING A 614 00:23:19,040 --> 00:23:19,280 JUDGMENT. 615 00:23:19,280 --> 00:23:20,880 I'LL THEN ADDRESS PROBLEMS 616 00:23:20,880 --> 00:23:24,800 FACING ETHICS CONSULTANTS AT 617 00:23:24,800 --> 00:23:28,880 NIH, OR AN IRB, LOOKING AT THE 618 00:23:28,880 --> 00:23:32,120 PROBLEM OF BENEFIT, NOT BEING 619 00:23:32,120 --> 00:23:34,600 ESTIMATABLE, AND LOOKING AT THE 620 00:23:34,600 --> 00:23:37,040 WAYS THAT RESEARCH RISKS COULD 621 00:23:37,040 --> 00:23:40,600 BE MINIMIZED BY USING OTHER 622 00:23:40,600 --> 00:23:41,560 SOURCES OF TISSUE. 623 00:23:41,560 --> 00:23:44,640 FINALLY, I WILL RESPOND TO THE 624 00:23:44,640 --> 00:23:47,040 QUESTIONS THAT WERE POSED BY DR. 625 00:23:47,040 --> 00:23:49,440 KIMMEL AND HIS COLLEAGUES. 626 00:23:49,440 --> 00:23:52,480 SO, I'M GOING TO ASSUME THAT AT 627 00:23:52,480 --> 00:23:57,600 LEAST AT A HIGH LEVEL THE PEOPLE 628 00:23:57,600 --> 00:23:58,840 JOINING THIS WEBINAR ARE 629 00:23:58,840 --> 00:24:04,280 FAMILIAR ARE THE FIRST STAGE OF 630 00:24:04,280 --> 00:24:06,800 HISTORY OF RESEARCH ETHICS. 631 00:24:06,800 --> 00:24:11,600 AND THE WHOLE THOUGHT HERE IS 632 00:24:11,600 --> 00:24:13,680 THAT SOME PHYSICIANS HAVE ALWAYS 633 00:24:13,680 --> 00:24:16,800 SOUGHT ANSWERS TO QUESTIONS 634 00:24:16,800 --> 00:24:18,800 ABOUT DISEASE, AND THAT STARTING 635 00:24:18,800 --> 00:24:21,640 ABOUT 150 YEARS AGO LEADING 636 00:24:21,640 --> 00:24:22,720 ACADEMIC PHYSICIANS STARTED 637 00:24:22,720 --> 00:24:24,800 USING THE SCIENTIFIC METHOD TO 638 00:24:24,800 --> 00:24:29,560 GET ANSWERS TO THAT PUZZLEMENT 639 00:24:29,560 --> 00:24:32,920 RATHER THAN SIMPLY LOOKING AT 640 00:24:32,920 --> 00:24:34,880 THEIR PATIENTS, MAKING GUESSES 641 00:24:34,880 --> 00:24:37,320 FOR CONSULTING ORACLES. 642 00:24:37,320 --> 00:24:40,160 AND IN PARTICULAR, THE LEADING 643 00:24:40,160 --> 00:24:42,840 ACADEMIC PHYSICIANS WERE THEN IN 644 00:24:42,840 --> 00:24:44,760 GERMANY AND THEY INVESTIGATED 645 00:24:44,760 --> 00:24:46,000 THE NATURE, CAUSE, AND 646 00:24:46,000 --> 00:24:48,200 TRANSMISSION OF SERIOUS DISEASES 647 00:24:48,200 --> 00:24:49,640 SUCH AS SYPHILIS AND GONORRHEA, 648 00:24:49,640 --> 00:24:53,440 AND THEY DID THIS BY 649 00:24:53,440 --> 00:24:55,640 INTENTIONALLY INFECTING 650 00:24:55,640 --> 00:24:56,600 INSTITUTIONALIZED PERSONS, AND 651 00:24:56,600 --> 00:24:57,640 POOR PATIENTS AT THE TIME MOST 652 00:24:57,640 --> 00:25:02,760 PATIENTS WHO WERE TREATED IN 653 00:25:02,760 --> 00:25:05,920 HOSPITALS WERE THOSE OF LOWER 654 00:25:05,920 --> 00:25:07,760 SOCIOECONOMIC STATUS, AND PEOPLE 655 00:25:07,760 --> 00:25:09,440 OF HIGHER STATUS USUALLY 656 00:25:09,440 --> 00:25:14,560 RECEIVED THEIR MEDICAL CARE AT 657 00:25:14,560 --> 00:25:15,120 HOME. 658 00:25:15,120 --> 00:25:18,040 WHEN THE EXPERIMENTS BECAME 659 00:25:18,040 --> 00:25:20,440 PUBLIC AROUND THE TURN OF THE 660 00:25:20,440 --> 00:25:23,840 20th CENTURY, THE PUBLIC AND 661 00:25:23,840 --> 00:25:25,960 PROFESSIONAL OUTCRY IN PRUSSIA 662 00:25:25,960 --> 00:25:29,720 LET THE GOVERNMENT TO PUT IN 663 00:25:29,720 --> 00:25:32,120 PLACE A LAW UNDER WHICH RESEARCH 664 00:25:32,120 --> 00:25:34,120 WAS PERMISSIBLE ONLY WITH 665 00:25:34,120 --> 00:25:36,640 CONSENT OF THOSE INVOLVED, AND 666 00:25:36,640 --> 00:25:39,800 THAT WOULD ALWAYS EXCLUDE 667 00:25:39,800 --> 00:25:40,960 CHILDREN OR INCOMPETENT 668 00:25:40,960 --> 00:25:44,240 PATIENTS, OR THOSE WHO WERE 669 00:25:44,240 --> 00:25:44,880 INSTITUTIONALIZED. 670 00:25:44,880 --> 00:25:45,720 SO, ONE COULD SAY, WELL, THAT 671 00:25:45,720 --> 00:25:47,040 WOULD BE THE END OF THE STORY, 672 00:25:47,040 --> 00:25:49,760 AS LONG AS CONSENT IS OBTAINED 673 00:25:49,760 --> 00:25:52,200 FROM A COMPETENT PERSON, THEN 674 00:25:52,200 --> 00:25:54,240 THE RESEARCH IS OKAY. 675 00:25:54,240 --> 00:25:55,520 BUT THAT'S DECIDEDLY NOT THE END 676 00:25:55,520 --> 00:26:00,040 OF THE STORY, AS YOU KNOW. 677 00:26:00,040 --> 00:26:04,520 AND INDEED, IN GERMANY ITSELF 678 00:26:04,520 --> 00:26:09,960 WHERE PRUSSIAN LAW BECAME PART 679 00:26:09,960 --> 00:26:12,800 OF THE GERMAN LAW PRIOR TO THE 680 00:26:12,800 --> 00:26:15,640 1930s IN CONCENTRATION CAMPS 681 00:26:15,640 --> 00:26:19,240 NAZI PHYSICIANS CARRIED OUT 682 00:26:19,240 --> 00:26:20,360 DEADLY RESEARCH AND 683 00:26:20,360 --> 00:26:21,360 INTERESTINGLY PROBABLY FAILED TO 684 00:26:21,360 --> 00:26:23,120 LEARN AS MUCH FROM THE RESEARCH 685 00:26:23,120 --> 00:26:25,840 AS THEY COULD BECAUSE OF THE WAY 686 00:26:25,840 --> 00:26:27,440 THEY TREATED THE SUBJECTS, NONE 687 00:26:27,440 --> 00:26:32,080 OF WHOM WERE OF COURSE GIVING 688 00:26:32,080 --> 00:26:32,320 CONSENT. 689 00:26:32,320 --> 00:26:36,720 BUT THE PROBLEMS WEREN'T LIMITED 690 00:26:36,720 --> 00:26:37,560 TO THAT TOTALITARIAN REGIME. 691 00:26:37,560 --> 00:26:44,240 IN THE UNITED STATES BEGINNING 692 00:26:44,240 --> 00:26:46,840 EARLIER IN 1932 RESEARCHERS FROM 693 00:26:46,840 --> 00:26:48,720 THE PUBLIC HEALTH SERVICE 694 00:26:48,720 --> 00:26:50,160 CARRIED OUT AN OBSERVATIONAL 695 00:26:50,160 --> 00:26:54,760 STUDY OF THE NATURAL COURSE OF 696 00:26:54,760 --> 00:26:59,480 SYPHILIS IN SEVERAL HUNDRED 697 00:26:59,480 --> 00:27:00,840 AFRICAN AMERICAN FARMERS IN 698 00:27:00,840 --> 00:27:02,320 TUSKEGEE, ALABAMA. 699 00:27:02,320 --> 00:27:07,880 AND THAT STUDY WENT ON, ALWAYS 700 00:27:07,880 --> 00:27:09,160 DISGUISING FROM THE 701 00:27:09,160 --> 00:27:10,720 PARTICIPANTS, WHAT WAS THE 702 00:27:10,720 --> 00:27:12,800 NATURE OF THE STUDY AND 703 00:27:12,800 --> 00:27:15,880 WITHHOLDING FROM THEM THE 704 00:27:15,880 --> 00:27:19,160 BENEFITS OF PENICILLIN ONCE THAT 705 00:27:19,160 --> 00:27:21,640 HAD BEEN DISCOVERED, AND USED 706 00:27:21,640 --> 00:27:25,640 EFFECTIVELY AS TREATMENT FOR 707 00:27:25,640 --> 00:27:26,400 SYPHILIS. 708 00:27:26,400 --> 00:27:27,880 AFTER THE WAR, THE UNITED STATES 709 00:27:27,880 --> 00:27:33,320 GOVERNMENT CARRIED OUT FOR MANY 710 00:27:33,320 --> 00:27:36,640 YEARS, AGAIN WITHOUT CONSENT OR 711 00:27:36,640 --> 00:27:37,960 INFORMATION, OR IN POPULATIONS 712 00:27:37,960 --> 00:27:45,240 SUCH AS CHILDREN IN ORPHANAGES 713 00:27:45,240 --> 00:27:48,080 AND PRISONERS, IN FACILITIES OF 714 00:27:48,080 --> 00:27:50,760 THE STATE AND FEDERAL 715 00:27:50,760 --> 00:27:52,440 GOVERNMENT, THAT INVOLVED 716 00:27:52,440 --> 00:27:54,720 IRRADIATING OR GIVING FOOD OR 717 00:27:54,720 --> 00:28:00,880 OTHER SUBSTANCE THAT CONTAINED 718 00:28:00,880 --> 00:28:01,200 ISOTOPES. 719 00:28:01,200 --> 00:28:06,720 AND THE EXPERIMENTS CARRIED OUT 720 00:28:06,720 --> 00:28:08,800 BY CHESTER SOUTHAM FROM MEMORIAL 721 00:28:08,800 --> 00:28:09,680 SLOAN-KETTERING IN NEW YORK AT 722 00:28:09,680 --> 00:28:15,720 THE JEWISH CHRONIC DISEASE 723 00:28:15,720 --> 00:28:16,240 HOSPITAL, AMONG ELDERLY 724 00:28:16,240 --> 00:28:18,240 DEBILITATED PATIENTS, ANY NUMBER 725 00:28:18,240 --> 00:28:20,920 OF WHOM HAD ACTUALLY SURVIVED 726 00:28:20,920 --> 00:28:25,280 THE HOLOCAUST, AND THEN WERE 727 00:28:25,280 --> 00:28:28,240 EXPOSED TO INJECTIONS OF LIVE 728 00:28:28,240 --> 00:28:31,080 CULTURED CANCER CELLS TO SEE 729 00:28:31,080 --> 00:28:32,880 WHETHER THEY REJECTED THEM, THAT 730 00:28:32,880 --> 00:28:34,040 TOOK PLACE IN 1963. 731 00:28:34,040 --> 00:28:36,240 AND THERE WERE MANY OTHER CASES 732 00:28:36,240 --> 00:28:39,080 OF THIS SORT, THE LIST GOES ON 733 00:28:39,080 --> 00:28:39,800 AND ON. 734 00:28:39,800 --> 00:28:42,800 AND SO, ALL OF THIS OCCURRED 735 00:28:42,800 --> 00:28:45,640 DESPITE THE FACT THAT IN 1947 736 00:28:45,640 --> 00:28:48,800 THE U.S. MILITARY TRIBUNAL THAT 737 00:28:48,800 --> 00:28:52,360 WAS PASSING JUDGMENT ON THE NAZI 738 00:28:52,360 --> 00:28:55,720 PHYSICIANS AND IN THEIR JUDGMENT 739 00:28:55,720 --> 00:28:58,440 EXPLAINED WHAT WOULD AMOUNT TO 740 00:28:58,440 --> 00:29:00,720 ETHICAL RESEARCH AND THAT BECAME 741 00:29:00,720 --> 00:29:04,160 KNOWN AS THE TEN POINTS, BECAME 742 00:29:04,160 --> 00:29:06,760 KNOWN AS THE NIRENBERG CODE, THE 743 00:29:06,760 --> 00:29:08,480 FIRST POINT BEGINS THE VOLUNTARY 744 00:29:08,480 --> 00:29:10,640 CONSENT OF THE HUMAN SUBJECT IS 745 00:29:10,640 --> 00:29:13,320 ABSOLUTELY ESSENTIAL. 746 00:29:13,320 --> 00:29:16,640 AND THAT WAS REPEATEDLY IGNORED 747 00:29:16,640 --> 00:29:21,440 BY PROMINENT RESEARCHERS 748 00:29:21,440 --> 00:29:23,200 INCLUDING THOSE WORKING FOR THE 749 00:29:23,200 --> 00:29:23,640 GOVERNMENT. 750 00:29:23,640 --> 00:29:26,040 WHY DID THIS HAPPEN? 751 00:29:26,040 --> 00:29:28,760 THE CONVENTIONAL EXPLANATION FOR 752 00:29:28,760 --> 00:29:33,800 SUCH ABUSES IS THAT THE SINGLE 753 00:29:33,800 --> 00:29:37,040 MINDED PURSUIT OF SCIENTIFIC 754 00:29:37,040 --> 00:29:39,880 OBJECTIVES DISTORTS THE VISION, 755 00:29:39,880 --> 00:29:40,840 UNDERSTANDING, PERCEPTION, 756 00:29:40,840 --> 00:29:41,640 ATTITUDE OF PHYSICIAN 757 00:29:41,640 --> 00:29:42,440 INVESTIGATORS DURING THIS 758 00:29:42,440 --> 00:29:43,920 PERIOD. 759 00:29:43,920 --> 00:29:45,680 SO THEY WERE LOOKING AT THIS 760 00:29:45,680 --> 00:29:48,840 SCENE BUT THEY WERE ACTUALLY 761 00:29:48,840 --> 00:29:52,280 SEEING SOMETHING DIFFERENT, THAT 762 00:29:52,280 --> 00:29:55,400 THEY WERE NOT TREATING THE HUMAN 763 00:29:55,400 --> 00:29:56,840 INDIVIDUALS WHO WERE THEIR 764 00:29:56,840 --> 00:29:58,760 SUBJECTS IN RESEARCH, AS HUMAN 765 00:29:58,760 --> 00:29:59,840 BEINGS, BUT TREATING THEM AS 766 00:29:59,840 --> 00:30:02,320 THOUGH THEY WERE GUINEA PIGS, OF 767 00:30:02,320 --> 00:30:05,240 COURSE THE WORST ABUSES WERE 768 00:30:05,240 --> 00:30:08,720 WITH THE NAZI CONCENTRATION CAMP 769 00:30:08,720 --> 00:30:11,800 DOCTORS FOR WHOM DISPENSING WITH 770 00:30:11,800 --> 00:30:15,960 LIVES OF THESE PATIENTS, THESE 771 00:30:15,960 --> 00:30:17,240 PERSONS RATHER, WAS THOUGHT OF 772 00:30:17,240 --> 00:30:21,400 AS NOTHING, JUST LIKE TREATING A 773 00:30:21,400 --> 00:30:22,880 LAB ANIMAL WHO IS EUTHANIZED 774 00:30:22,880 --> 00:30:25,720 AFTER THE RESEARCH. 775 00:30:25,720 --> 00:30:28,040 NOW, THAT'S OBVIOUSLY -- THIS IS 776 00:30:28,040 --> 00:30:32,520 A CARICATURE, MORE OR LESS THE 777 00:30:32,520 --> 00:30:36,280 EXPLANATION, HOW DID THIS 778 00:30:36,280 --> 00:30:38,320 HAPPEN, HOW DID CONSCIENTIOUS 779 00:30:38,320 --> 00:30:40,320 PHYSICIAN FALL INTO THIS. 780 00:30:40,320 --> 00:30:42,320 IT'S REALLY THAT THEY DISTANCED 781 00:30:42,320 --> 00:30:42,840 THEMSELVES FROM PEOPLE 782 00:30:42,840 --> 00:30:45,400 PARTICIPATING IN THE RESEARCH IN 783 00:30:45,400 --> 00:30:47,200 ORDER TO REACH THE SCIENTIFIC 784 00:30:47,200 --> 00:30:52,160 GOALS THAT THEY WERE DRIVEN TO 785 00:30:52,160 --> 00:30:53,040 REACH. 786 00:30:53,040 --> 00:30:56,440 SO, ONE CAN SAY THAT IF THE 787 00:30:56,440 --> 00:30:57,640 PROBLEM IS SIMPLY THAT 788 00:30:57,640 --> 00:30:59,160 PHYSICIANS WERE DISREGARDING THE 789 00:30:59,160 --> 00:31:00,720 RIGHTS OF THE INDIVIDUALS, 790 00:31:00,720 --> 00:31:05,600 WHETHER THEY WERE PATIENTS OR 791 00:31:05,600 --> 00:31:07,240 HEALTHY INDIVIDUALS, TO EXERCISE 792 00:31:07,240 --> 00:31:10,000 THE CHOICE ABOUT WHETHER TO 793 00:31:10,000 --> 00:31:11,040 PARTICIPATE IN RESEARCH, THEN 794 00:31:11,040 --> 00:31:17,360 WHAT WOULD BE NEEDED WOULD BE 795 00:31:17,360 --> 00:31:18,800 MAKING INFORMED CONSENT, A 796 00:31:18,800 --> 00:31:21,560 GUARANTEE, MAKING SURE IT'S 797 00:31:21,560 --> 00:31:22,760 ALWAYS OBTAINED, WHETHER THE 798 00:31:22,760 --> 00:31:25,440 STANDARD IS A REFERENCE TO THE 799 00:31:25,440 --> 00:31:29,600 NUREMBERG CODE OR THE 800 00:31:29,600 --> 00:31:32,640 DECLARATION OF HELSINKI WHICH 801 00:31:32,640 --> 00:31:34,640 THE WORLD MEDICAL ASSOCIATION 802 00:31:34,640 --> 00:31:36,000 FIRST ADOPTED IN 1964. 803 00:31:36,000 --> 00:31:37,240 THERE WERE STILL OBJECTIONS THAT 804 00:31:37,240 --> 00:31:42,760 THAT WASN'T GOING TO WORK. 805 00:31:42,760 --> 00:31:43,880 FOR EXAMPLE, HENRY BEECHER, 806 00:31:43,880 --> 00:31:45,640 HARVARD ANESTHESIOLOGIST WHO 807 00:31:45,640 --> 00:31:47,920 SHOCKED THE MEDICAL WORLD IN 808 00:31:47,920 --> 00:31:49,840 1966, WITH HIS NEW ENGLAND 809 00:31:49,840 --> 00:31:52,360 JOURNAL ARTICLE ABOUT ETHICS AND 810 00:31:52,360 --> 00:31:59,960 CLINICAL RESEARCH, IN WHICH HE 811 00:31:59,960 --> 00:32:00,760 DISCLOSED A BROAD PROBLEM, HE 812 00:32:00,760 --> 00:32:03,480 SAW IT AS GOOD PEOPLE, GOOD 813 00:32:03,480 --> 00:32:04,440 PHYSICIANS, WHO SIMPLY HAD 814 00:32:04,440 --> 00:32:08,600 WANDERED AWAY FROM THE PATH OF 815 00:32:08,600 --> 00:32:09,560 ETHICS, AND WERE PERFORMING 816 00:32:09,560 --> 00:32:11,560 RESEARCH THAT WAS OFTEN RISKY 817 00:32:11,560 --> 00:32:13,600 BUT WAS DONE WITHOUT THE 818 00:32:13,600 --> 00:32:17,600 KNOWLEDGE OR CONSENT OF THE 819 00:32:17,600 --> 00:32:18,800 PEOPLE INVOLVED. 820 00:32:18,800 --> 00:32:21,040 AND HE OFTEN SAID THAT INDEED, 821 00:32:21,040 --> 00:32:24,840 HE THOUGHT THE PROBLEM WAS THAT 822 00:32:24,840 --> 00:32:25,720 PHYSICIANS CAN ALWAYS OBTAIN 823 00:32:25,720 --> 00:32:27,440 CONSENT FROM THE PEOPLE THEY ARE 824 00:32:27,440 --> 00:32:28,960 DEALING WITH, PARTICULARLY 825 00:32:28,960 --> 00:32:30,640 PATIENTS BUT NOT ONLY THEM, BY 826 00:32:30,640 --> 00:32:32,920 THE WAY THEY PRESENT THINGS AND 827 00:32:32,920 --> 00:32:41,320 BY THE AUTHORITY THEY BRING TO 828 00:32:41,320 --> 00:32:42,840 THAT PHYSICIAN-PATIENT OR 829 00:32:42,840 --> 00:32:45,640 PHYSICIAN-SUBJECT ENCOUNTER. 830 00:32:45,640 --> 00:32:49,640 BUT IT WAS DEEPER THAN HENRY 831 00:32:49,640 --> 00:32:51,640 BEECHERREST CONCERNS ABOUT 832 00:32:51,640 --> 00:32:51,880 CONSENT. 833 00:32:51,880 --> 00:32:55,320 A WELL-KNOWN MORAL PHILOSOPHER, 834 00:32:55,320 --> 00:32:58,400 REFUGEE FROM GERMANY HAD HANS 835 00:32:58,400 --> 00:33:08,640 JONAS POSED THREE CHALLENGES IN 836 00:33:08,640 --> 00:33:09,440 A 1968 CONTRIBUTION, THE 837 00:33:09,440 --> 00:33:13,640 AMERICAN ACADEMY OF ARTS AND 838 00:33:13,640 --> 00:33:13,840 LETTERS. 839 00:33:13,840 --> 00:33:16,720 HE POSED THREE CHALLENGES. 840 00:33:16,720 --> 00:33:20,840 FIRST, THE INTEREST OF SOCIETY 841 00:33:20,840 --> 00:33:24,440 IN PROGRESS, WHICH IS VERY MUCH 842 00:33:24,440 --> 00:33:28,480 APPARENT IN THE SUPPORT FOR 843 00:33:28,480 --> 00:33:31,840 PHYSICIAN-SCIENTISTS TRYING TO 844 00:33:31,840 --> 00:33:32,960 CONQUER DISEASE, THAT INTEREST 845 00:33:32,960 --> 00:33:34,000 IS OPTIONAL. 846 00:33:34,000 --> 00:33:40,720 IT IS NOT A MORAL IMPERATIVE. 847 00:33:40,720 --> 00:33:42,600 IN HIS VIEW, WE DO NOT WRONG -- 848 00:33:42,600 --> 00:33:47,600 DO NOT DO A WRONG TO OUR 849 00:33:47,600 --> 00:33:52,280 PROGENY, IF WE HAVEN'T WE 850 00:33:52,280 --> 00:33:54,440 HAVEN'T YET CURED A DISEASE. 851 00:33:54,440 --> 00:33:55,640 OBVIOUSLY IF WE'RE ATTEMPTING 852 00:33:55,640 --> 00:33:57,240 AND ARE NEGLIGENT AND DON'T DO A 853 00:33:57,240 --> 00:34:00,840 GOOD JOB THAT CAN BE CRITICIZED, 854 00:34:00,840 --> 00:34:02,720 BUT THE CHOICE TO FAVOR 855 00:34:02,720 --> 00:34:04,440 PROGRESS, BENEFIT FOR FUTURE 856 00:34:04,440 --> 00:34:08,440 PEOPLE, OVER THE WELFARE OF 857 00:34:08,440 --> 00:34:10,040 EXISTING PEOPLE, AND 858 00:34:10,040 --> 00:34:11,760 PARTICULARLY IF THAT WELFARE 859 00:34:11,760 --> 00:34:14,560 WERE ACHIEVED WITHOUT THE FULL 860 00:34:14,560 --> 00:34:17,680 CONSENT AND PARTICIPATION OF 861 00:34:17,680 --> 00:34:22,120 THOSE CURRENT PEOPLE, IS NOT A 862 00:34:22,120 --> 00:34:23,280 WRONG. 863 00:34:23,280 --> 00:34:27,440 SECONDLY, HE SAID THAT IN 864 00:34:27,440 --> 00:34:28,720 CALLING FOR VOLUNTEERS FOR 865 00:34:28,720 --> 00:34:32,440 RESEARCH, EVEN UNDER THE MOST 866 00:34:32,440 --> 00:34:36,600 METICULOUS RULES, AMOUNTS TO A 867 00:34:36,600 --> 00:34:38,120 SORT OF CONSCRIPTION OF PEOPLE 868 00:34:38,120 --> 00:34:40,440 TO BE IN RESEARCH BECAUSE, 869 00:34:40,440 --> 00:34:42,840 AGAIN, OF THE ROLE OF SCIENCE 870 00:34:42,840 --> 00:34:45,360 AND RESEARCH IN SOCIETY THAT CAN 871 00:34:45,360 --> 00:34:49,440 CREATE A SENSE THAT THIS IS 872 00:34:49,440 --> 00:34:50,320 SOMETHING LIKE WARTIME SERVICE, 873 00:34:50,320 --> 00:34:53,560 THIS WOULD BE SOMETHING THAT 874 00:34:53,560 --> 00:34:57,760 WOULD BE IN SOME SENSE FELT TO 875 00:34:57,760 --> 00:34:59,880 BE OBLIGATORY BY SOME PEOPLE. 876 00:34:59,880 --> 00:35:03,240 HE SAID, SINCE SOME FORM OF 877 00:35:03,240 --> 00:35:05,680 SOLICITATION IS ALWAYS NECESSARY 878 00:35:05,680 --> 00:35:09,280 TO GET PEOPLE TO ENROLL, CONSENT 879 00:35:09,280 --> 00:35:13,640 CANNOT BE THE FULL ANSWER TO THE 880 00:35:13,640 --> 00:35:13,840 PROBLEM. 881 00:35:13,840 --> 00:35:17,000 AND FINALLY, HE SUGGESTED THAT 882 00:35:17,000 --> 00:35:18,560 THE PERSON'S CARRYING OUT 883 00:35:18,560 --> 00:35:20,680 MEDICAL RESEARCH SHOULD BE THE 884 00:35:20,680 --> 00:35:24,840 FIRST SUBJECTS, ALWAYS, BECAUSE 885 00:35:24,840 --> 00:35:26,320 OF THEIR FULL AUTONOMOUS 886 00:35:26,320 --> 00:35:28,440 IDENTIFICATION WITH THE PURPOSE 887 00:35:28,440 --> 00:35:30,320 OF THAT RESEARCH, AND HE WENT ON 888 00:35:30,320 --> 00:35:33,320 TO SAY THAT THEY HAVE THE 889 00:35:33,320 --> 00:35:35,360 STRONGEST MOTIVATION, THE 890 00:35:35,360 --> 00:35:36,480 FULLEST UNDERSTANDING, THE 891 00:35:36,480 --> 00:35:40,840 FREEST DECISION, AND THE 892 00:35:40,840 --> 00:35:45,560 GREATEST INTEGRATION WITH THEIR 893 00:35:45,560 --> 00:35:48,680 OWN PERSONAL TOTAL CHOSEN 894 00:35:48,680 --> 00:35:49,040 PURSUIT. 895 00:35:49,040 --> 00:35:51,400 AND SO THAT IDENTIFICATION WAS 896 00:35:51,400 --> 00:35:53,240 THE REASON THAT HE SAID THAT 897 00:35:53,240 --> 00:35:56,480 THIS WOULD BE A WAY TO ENSURE 898 00:35:56,480 --> 00:36:00,880 THE DIGNITY OF THE SUBJECT AS A 899 00:36:00,880 --> 00:36:03,040 RESEARCH PARTICIPANT. 900 00:36:03,040 --> 00:36:05,840 NOW, HE RECOGNIZED THAT THIS WAS 901 00:36:05,840 --> 00:36:09,000 NOT A PRACTICAL SOLUTION, THAT 902 00:36:09,000 --> 00:36:10,840 THERE WOULD NOT BE ENOUGH 903 00:36:10,840 --> 00:36:12,600 SCIENTISTS TO SERVE AS THE LARGE 904 00:36:12,600 --> 00:36:17,600 NUMBER OF SUBJECTS THAT ARE 905 00:36:17,600 --> 00:36:20,040 NEEDED FOR ALL FORMS OF 906 00:36:20,040 --> 00:36:20,480 BIOMEDICAL RESEARCH. 907 00:36:20,480 --> 00:36:23,120 BUT THAT WENT BACK TO HIS FIRST 908 00:36:23,120 --> 00:36:27,560 POINT, THAT IF THAT SLOWED THE 909 00:36:27,560 --> 00:36:28,160 PROCESS OF ADVANCING RESEARCH, 910 00:36:28,160 --> 00:36:32,840 IT WOULD BE FELT TO BE A GREAT 911 00:36:32,840 --> 00:36:35,560 TRAGEDY BY INDIVIDUALS WHO ARE 912 00:36:35,560 --> 00:36:37,280 WAITING FOR AND WANTING TO HAVE 913 00:36:37,280 --> 00:36:39,840 A TREATMENT FOR THEIR DISEASE, 914 00:36:39,840 --> 00:36:44,120 BUT IT WOULD NOT BE, IN HIS 915 00:36:44,120 --> 00:36:45,800 VIEW, A MORAL FAILING FOR 916 00:36:45,800 --> 00:36:48,960 SOCIETY TO MOVE IN THAT 917 00:36:48,960 --> 00:36:51,240 DIRECTION. 918 00:36:51,240 --> 00:36:53,120 SO, AROUND THIS TIME, STAGE 1 919 00:36:53,120 --> 00:36:55,280 BECOMES STAGE 2. 920 00:36:55,280 --> 00:36:58,600 AFTER THE PRESS REVEALED THE 921 00:36:58,600 --> 00:37:01,680 TUSKEGEE STUDY, THE 40-YEAR-LONG 922 00:37:01,680 --> 00:37:04,160 STUDY IN 1972, IN THE NATIONAL 923 00:37:04,160 --> 00:37:07,400 RESEARCH ACT CONGRESS INCLUDED A 924 00:37:07,400 --> 00:37:11,960 PROVISION THAT ESTABLISHED THE 925 00:37:11,960 --> 00:37:12,880 NATIONAL PERMISSION FOR 926 00:37:12,880 --> 00:37:15,480 PROTECTION OF HUMAN SUBJECTS OF 927 00:37:15,480 --> 00:37:17,760 BIOMEDICAL AND BEHAVIORAL 928 00:37:17,760 --> 00:37:19,040 RESEARCH, FOR YEARS, BETWEEN 929 00:37:19,040 --> 00:37:21,640 1974 AND 1978, EXAMINED A WIDE 930 00:37:21,640 --> 00:37:26,440 RANGE OF SPECIFIC TYPES OF 931 00:37:26,440 --> 00:37:29,640 RESEARCH, FETAL, WITH PRISONERS, 932 00:37:29,640 --> 00:37:32,600 WITH THE MENTALLY DISABLED, 933 00:37:32,600 --> 00:37:33,160 CHILDREN, SO FORTH. 934 00:37:33,160 --> 00:37:35,240 AND THE ISSUED WHAT IS KNOWN AS 935 00:37:35,240 --> 00:37:37,120 THE BELMONT REPORT, NAMED AFTER 936 00:37:37,120 --> 00:37:39,160 THE CONFERENCE CENTER, THE 937 00:37:39,160 --> 00:37:43,280 BELMONT CENTER, WHERE THE REPORT 938 00:37:43,280 --> 00:37:46,440 WAS FINALIZED IN 1978. 939 00:37:46,440 --> 00:37:48,640 AND THAT REPORT IDENTIFIES IN 940 00:37:48,640 --> 00:37:51,480 OUR MORAL TRADITIONS THREE 941 00:37:51,480 --> 00:37:53,200 ETHICAL PRINCIPLES THAT ARE SAID 942 00:37:53,200 --> 00:37:55,800 TO BE APPROPRIATE TO GUIDE THE 943 00:37:55,800 --> 00:37:59,560 ETHICS OF RESEARCH AND 944 00:37:59,560 --> 00:38:00,680 SUBSEQUENTLY HAVE BEEN 945 00:38:00,680 --> 00:38:04,080 ELABORATED FURTHER AS THE 946 00:38:04,080 --> 00:38:05,640 ETHICAL PRINCIPLES UNDERLYING 947 00:38:05,640 --> 00:38:17,760 MEDICAL PRACTICE, AND THEY ARE 948 00:38:17,760 --> 00:38:19,440 BENEFICENCE, RESPECT FOR 949 00:38:19,440 --> 00:38:22,080 PERSONS, AND PROTECTION OF THE 950 00:38:22,080 --> 00:38:29,120 SUBJECTS OF RESEARCH WHO CANNOT 951 00:38:29,120 --> 00:38:31,440 GIVE CONSENT CHILDREN AND THE 952 00:38:31,440 --> 00:38:38,320 LIKE, AND THE PRINCIPLE OF 953 00:38:38,320 --> 00:38:40,080 JUSTICE, REQUIRING ALL 954 00:38:40,080 --> 00:38:41,120 INSTITUTIONS RECEIVING FEDERAL 955 00:38:41,120 --> 00:38:43,920 FUNDING FOR RESEARCH WITH HUMAN 956 00:38:43,920 --> 00:38:45,000 SUBJECTS ESTABLISH AN 957 00:38:45,000 --> 00:38:47,200 INSTITUTIONAL REVIEW BOARD TO 958 00:38:47,200 --> 00:38:48,920 ENSURE THAT RISKS ARE MINIMIZED, 959 00:38:48,920 --> 00:38:51,120 THAT THE RATIO OF EXPECTED 960 00:38:51,120 --> 00:38:53,640 BENEFIT TO POSSIBLE HARM IS 961 00:38:53,640 --> 00:38:56,920 APPROPRIATE, THAT THERE'S FAIR 962 00:38:56,920 --> 00:38:59,640 SELECTION OF SUBJECTS, AND THAT 963 00:38:59,640 --> 00:39:00,840 INFORMED CONSENT, VOLUNTARY 964 00:39:00,840 --> 00:39:03,680 INFORMED CONSENT BE OBTAINED. 965 00:39:03,680 --> 00:39:06,440 SO, THE PROCESS OF THE 966 00:39:06,440 --> 00:39:08,760 COMMISSION'S WORK WAS TO PROVIDE 967 00:39:08,760 --> 00:39:10,360 THE BACKGROUND FOR THE 968 00:39:10,360 --> 00:39:13,680 REGULATIONS WHICH WERE THEN 969 00:39:13,680 --> 00:39:20,040 ADOPTED FOR THE FIRST TIME IN 970 00:39:20,040 --> 00:39:24,120 1981, TO GUIDE RESEARCH THAT IS 971 00:39:24,120 --> 00:39:24,840 FEDERALLY SUPPORTED. 972 00:39:24,840 --> 00:39:28,440 SO, WITH THE CREATION OF IRBs, 973 00:39:28,440 --> 00:39:31,000 THE CONCERNS ABOUT CONSENT MIGHT 974 00:39:31,000 --> 00:39:34,160 APPEAR TO HAVE BEEN QUIETED. 975 00:39:34,160 --> 00:39:38,240 IRBs CAN, AFTER ALL, REVISE 976 00:39:38,240 --> 00:39:44,520 CONSENT FORMS TO AVOID HENRY 977 00:39:44,520 --> 00:39:47,640 BEECHER'S WORRY PATIENTS WITH 978 00:39:47,640 --> 00:39:50,000 PRESENT IN A WAYS TO PERSUADE 979 00:39:50,000 --> 00:39:50,880 PATIENTS AND VOLUNTEERS, 980 00:39:50,880 --> 00:39:52,560 MATERIALS USED MUST BE APPROVED 981 00:39:52,560 --> 00:39:58,440 BY THE IRB TO AVOID SOLICITATION 982 00:39:58,440 --> 00:40:04,600 BECOMING CONSCRIPTION, AS JONAS 983 00:40:04,600 --> 00:40:06,840 HAD OBJECTED. 984 00:40:06,840 --> 00:40:08,360 FURTHER CONCERNING ABOUT CAPTIVE 985 00:40:08,360 --> 00:40:11,600 MEMBERS OF SOCIETY, NOT JUST 986 00:40:11,600 --> 00:40:12,440 INSTITUTIONS BUT LESSER 987 00:40:12,440 --> 00:40:14,120 SELF-DETERMINATION BECAUSE OF 988 00:40:14,120 --> 00:40:18,400 SOCIOECONOMIC STATUS OR THEIR 989 00:40:18,400 --> 00:40:22,400 POSITION IN SOCIETY, CAN BE 990 00:40:22,400 --> 00:40:24,640 ACHIEVED, OVERCOMING CONCERNS 991 00:40:24,640 --> 00:40:27,280 ABOUT THAT, BY THE IRB 992 00:40:27,280 --> 00:40:28,600 IMPLEMENTING PRINCIPLES OF 993 00:40:28,600 --> 00:40:28,840 JUSTICE. 994 00:40:28,840 --> 00:40:33,560 SO WE GO INTO STAGE 2, THINKING, 995 00:40:33,560 --> 00:40:36,560 WELL, PERHAPS PROBLEMS WITH 996 00:40:36,560 --> 00:40:38,760 CONSENT HAVE BEEN SOLVED, BUT 997 00:40:38,760 --> 00:40:40,840 IRBs DON'T EXIST JUST TO 998 00:40:40,840 --> 00:40:42,240 REVIEW AND REVISE CONSENT FORMS 999 00:40:42,240 --> 00:40:45,640 AS MUCH TIME AS MANY OF THEM 1000 00:40:45,640 --> 00:40:46,960 SPEND IN THAT PROCESS. 1001 00:40:46,960 --> 00:40:51,880 BEFORE GETTING TO THAT QUESTION, 1002 00:40:51,880 --> 00:40:56,920 THE QUESTION OF AUTONOMY, THEY 1003 00:40:56,920 --> 00:40:59,320 MUST ADDRESS BENEFICE, RISK 1004 00:40:59,320 --> 00:40:59,840 MINIMIZATION, APPROPRIATE 1005 00:40:59,840 --> 00:41:04,840 RELATIONSHIP OF BENEFIT TO RISK. 1006 00:41:04,840 --> 00:41:07,720 IRBs ALSO HAVE INSTITUTIONAL 1007 00:41:07,720 --> 00:41:09,560 OR COLLECTIVE CONCERNS ABOUT 1008 00:41:09,560 --> 00:41:12,920 PUBLIC PERCEPTIONS OF RESEARCH, 1009 00:41:12,920 --> 00:41:14,240 WHICH CAN DETERMINE THE 1010 00:41:14,240 --> 00:41:15,920 ACCEPTABILITY OF HIGH RISK OF 1011 00:41:15,920 --> 00:41:19,360 HARM IN A PARTICULAR RESEARCH 1012 00:41:19,360 --> 00:41:19,680 STUDY. 1013 00:41:19,680 --> 00:41:21,960 NOW, TO ILLUSTRATE THAT CONSIDER 1014 00:41:21,960 --> 00:41:28,560 THE U.S. SPACE PROGRAM IN THE 1015 00:41:28,560 --> 00:41:31,600 POST-SPUTNIK ERA, 1950s TO 1016 00:41:31,600 --> 00:41:32,720 EARLY 196 0s WHEN THERE WAS A 1017 00:41:32,720 --> 00:41:37,440 RACE TO THE MOON BETWEEN THE U. 1018 00:41:37,440 --> 00:41:39,720 S. AND THE USSR. 1019 00:41:39,720 --> 00:41:42,520 IT WOULD HAVE BEEN MUCH EASIER 1020 00:41:42,520 --> 00:41:44,720 AND CHEAPER IF THE INITIAL 1021 00:41:44,720 --> 00:41:46,880 MISSION TO THE MOON HAD BEEN ONE 1022 00:41:46,880 --> 00:41:47,800 WAY ONLY. 1023 00:41:47,800 --> 00:41:49,440 AND THAT MISSION COULD STILL 1024 00:41:49,440 --> 00:41:53,720 HAVE PRODUCED A GREAT DEAL OF 1025 00:41:53,720 --> 00:41:55,640 USEFUL RESEARCH RESULTS WHICH 1026 00:41:55,640 --> 00:41:57,640 THE ASTRONAUTS WOULD HAVE BEEN 1027 00:41:57,640 --> 00:42:02,640 ABLE TO TRANSMIT BACK TO EARTH 1028 00:42:02,640 --> 00:42:04,200 BEFORE THEIR WATER AND OXYGEN 1029 00:42:04,200 --> 00:42:09,360 EXPIRED AND THEY DIED ON THE 1030 00:42:09,360 --> 00:42:09,560 MOON. 1031 00:42:09,560 --> 00:42:12,640 MOREOVER, THERE WOULD HAVE BEEN 1032 00:42:12,640 --> 00:42:14,320 NO DEARTH OF WILLING ASTRONAUTS, 1033 00:42:14,320 --> 00:42:16,760 THE FAME AND GLORY FOR THE 1034 00:42:16,760 --> 00:42:18,920 BRAVERY INVOLVED ON BEING THE 1035 00:42:18,920 --> 00:42:20,840 FIRST PERSON ON THE MOON, EVEN 1036 00:42:20,840 --> 00:42:22,520 IF THAT PERSON WASN'T GOING TO 1037 00:42:22,520 --> 00:42:29,440 COME HOME FOR THE TICKER TAPE 1038 00:42:29,440 --> 00:42:31,640 PARADE WOULD HAVE MEANT LIKE 1039 00:42:31,640 --> 00:42:36,320 VOLUNTEERS IN WARTIME FOR 1040 00:42:36,320 --> 00:42:37,080 SUICIDE MISSIONS WHO GAIN 1041 00:42:37,080 --> 00:42:41,440 IMMORTALITY, THEY GO DOWN IN 1042 00:42:41,440 --> 00:42:44,280 HISTORY BOOKS, THEY ARE 1043 00:42:44,280 --> 00:42:45,680 REMEMBERED IN CELEBRATIONS AND 1044 00:42:45,680 --> 00:42:48,680 CHILDREN LOOK UP TO THEM, ALL 1045 00:42:48,680 --> 00:42:51,480 THAT WOULD HAVE PROVIDED PLENTY 1046 00:42:51,480 --> 00:42:54,520 OF WILLING VOLUNTEERS WHO WOULD 1047 00:42:54,520 --> 00:42:56,440 HAVE UNDERSTOOD VERY WELL THE 1048 00:42:56,440 --> 00:42:57,640 RISK INVOLVED. 1049 00:42:57,640 --> 00:43:00,960 BUT THE IDEA WAS REJECTED OUT OF 1050 00:43:00,960 --> 00:43:01,160 HAND. 1051 00:43:01,160 --> 00:43:06,880 IT WAS RECOGNIZED THAT THERE WAS 1052 00:43:06,880 --> 00:43:09,640 AN INSTITUTIONAL INTEREST IN 1053 00:43:09,640 --> 00:43:13,440 HAVING THE EFFORT TO RETURN 1054 00:43:13,440 --> 00:43:15,240 PEOPLE, BE SUCCESSFUL, AND WHAT 1055 00:43:15,240 --> 00:43:19,040 HAD BEEN THE REACTION EVEN TO 1056 00:43:19,040 --> 00:43:22,160 SENDING DOGS INTO SPACE WHO DIED 1057 00:43:22,160 --> 00:43:24,440 IN THE PROCESS INDICATED THAT 1058 00:43:24,440 --> 00:43:26,160 THE LOSS, THE INTENTIONAL LOSS 1059 00:43:26,160 --> 00:43:29,840 OF HUMAN LIFE IN THIS WAY WOULD 1060 00:43:29,840 --> 00:43:32,360 HAVE BEEN UNACCEPTABLE. 1061 00:43:32,360 --> 00:43:34,640 SO THEN WITH THE IRB AND WITH 1062 00:43:34,640 --> 00:43:36,200 THE RECOGNITION THAT CONSENT 1063 00:43:36,200 --> 00:43:37,680 ISN'T EVERYTHING, WE MOVE TO 1064 00:43:37,680 --> 00:43:41,920 WHAT ONE MIGHT CALL STAGE 3. 1065 00:43:41,920 --> 00:43:48,000 REMEMBERING THAT STAGE 2 HAD 1066 00:43:48,000 --> 00:43:49,640 ACTUALLY RESULTED IN RESEARCH 1067 00:43:49,640 --> 00:43:50,880 SUBJECTS BEING MORE PROTECTED, 1068 00:43:50,880 --> 00:43:52,480 THE NATIONAL COMMISSION WAS FOR 1069 00:43:52,480 --> 00:43:54,400 THE PROTECTION OF HUMAN SUBJECTS 1070 00:43:54,400 --> 00:43:59,440 AND THE OFFICE THAT WAS SET UP, 1071 00:43:59,440 --> 00:44:04,560 THE PREDECESSOR OF CURRENT 1072 00:44:04,560 --> 00:44:06,560 OFFICE WAS FOR PROTECT OF 1073 00:44:06,560 --> 00:44:07,960 RESEARCH SUBJECTS, BUT THE AIDS 1074 00:44:07,960 --> 00:44:11,520 CRISIS CHANGED THAT. 1075 00:44:11,520 --> 00:44:17,600 AND THE OBJECTIVES OF THE 1076 00:44:17,600 --> 00:44:21,200 EDUCATORS, ACT UP AND OTHER AIDS 1077 00:44:21,200 --> 00:44:23,440 ACTIVISTS WAS TO GIVE PATIENTS 1078 00:44:23,440 --> 00:44:24,760 CONTROL OVER RESEARCH. 1079 00:44:24,760 --> 00:44:28,160 PARTIALLY, THIS MEANT LESS 1080 00:44:28,160 --> 00:44:30,240 PATERNALISM AND MORE WILLINGNESS 1081 00:44:30,240 --> 00:44:33,480 TO ALLOW RISK, AND THE FEDERAL 1082 00:44:33,480 --> 00:44:36,160 OFFICIALS AT NIH AND AT THE FDA 1083 00:44:36,160 --> 00:44:37,640 WERE EVENTUALLY BROUGHT AROUND 1084 00:44:37,640 --> 00:44:40,480 TO EXACTLY THAT VIEW FROM 1085 00:44:40,480 --> 00:44:44,400 MEETING WITH AND DISCUSSING AND 1086 00:44:44,400 --> 00:44:47,880 COMING TO UNDERSTAND THESE 1087 00:44:47,880 --> 00:44:49,840 PATIENTS, AND THEIR DESIRE TO 1088 00:44:49,840 --> 00:44:51,800 PARTICIPATE MORE IN RESEARCH 1089 00:44:51,800 --> 00:44:54,120 EVEN IF IT WAS HIGH RISK. 1090 00:44:54,120 --> 00:44:56,920 THE MAIN TAKEAWAY, HOWEVER, FOR 1091 00:44:56,920 --> 00:45:02,160 REGULATORS I THINK WAS TO ENSURE 1092 00:45:02,160 --> 00:45:04,600 GREATER INCLUSION IN RESEARCH, 1093 00:45:04,600 --> 00:45:09,080 AND SO PEOPLE WITH -- LESS 1094 00:45:09,080 --> 00:45:11,000 LIKELY TO EXCLUDE PEOPLE FOR 1095 00:45:11,000 --> 00:45:12,200 COMORBIDITIES AND SO FORTH, 1096 00:45:12,200 --> 00:45:15,040 ALLOW MORE CHOICE ON THE PART OF 1097 00:45:15,040 --> 00:45:16,280 THE RESEARCH SUBJECTS, AS TO 1098 00:45:16,280 --> 00:45:19,080 THEIR WILLINGNESS TO TAKE RISKS. 1099 00:45:19,080 --> 00:45:21,920 WHERE DO WE STAND NOW? 1100 00:45:21,920 --> 00:45:24,960 WE'RE IN STAGE 3, AND AS TO 1101 00:45:24,960 --> 00:45:27,640 PATIENT SUBJECTS, I THINK THE 1102 00:45:27,640 --> 00:45:30,440 CONSENSUS NOT FROM A CHANGE IN 1103 00:45:30,440 --> 00:45:33,600 REGULATIONS BUT FROM THE WAY 1104 00:45:33,600 --> 00:45:35,680 THEY ARE APPLIED IS THEY SHOULD 1105 00:45:35,680 --> 00:45:37,000 BE DECISION MAKERS WHETHER TO 1106 00:45:37,000 --> 00:45:40,800 TRADE RISKS OF ILLNESS WITH THE 1107 00:45:40,800 --> 00:45:42,440 LIMITATIONS OF CURRENT 1108 00:45:42,440 --> 00:45:44,720 TREATMENTS FOR RISK OF STILL 1109 00:45:44,720 --> 00:45:45,640 EXPERIMENTAL INTERVENTIONS. 1110 00:45:45,640 --> 00:45:48,640 AND THE USUAL VIEW ABOUT THIS IS 1111 00:45:48,640 --> 00:45:51,200 THAT THAT CHOICE, THEIR ROLE IS 1112 00:45:51,200 --> 00:45:53,640 AS DECISION MAKERS COMES AT THE 1113 00:45:53,640 --> 00:45:55,440 POINT WHERE THOSE INTERVENTIONS 1114 00:45:55,440 --> 00:45:58,920 THAT ARE BEING TESTED ARE ONES 1115 00:45:58,920 --> 00:46:00,800 THAT A RESEARCHER AND THE IRBs 1116 00:46:00,800 --> 00:46:03,760 HAVE ALREADY DECIDED MEET THE 1117 00:46:03,760 --> 00:46:05,640 REQUIREMENTS, WELL DESIGNED, 1118 00:46:05,640 --> 00:46:08,400 RISKS HAVE BEEN MINIMIZED, AND 1119 00:46:08,400 --> 00:46:10,640 THAT OVERALL THE BENEFITS, NOT 1120 00:46:10,640 --> 00:46:13,040 NECESSARILY TO THE PARTICIPANTS 1121 00:46:13,040 --> 00:46:17,240 IN THE RESEARCH, BUT TO THE 1122 00:46:17,240 --> 00:46:18,640 ENTERPRISE, THE EVENTUAL 1123 00:46:18,640 --> 00:46:20,120 DEVELOPMENT OF THE KNOWLEDGE, 1124 00:46:20,120 --> 00:46:21,640 DISCOVERY OF A TREATMENT, 1125 00:46:21,640 --> 00:46:24,560 UNDERSTANDING OF DISEASE, THESE 1126 00:46:24,560 --> 00:46:27,360 BENEFITS OUTWEIGH THOSE RISKS. 1127 00:46:27,360 --> 00:46:30,440 BUT TODAY THAT VIEW GOES EVEN 1128 00:46:30,440 --> 00:46:33,000 FURTHER, THE ARGUMENT ABOUT 1129 00:46:33,000 --> 00:46:36,720 PATIENTS AS DECISION MAKERS IS 1130 00:46:36,720 --> 00:46:38,760 EMBODIED IN THE RIGHT TO TRY 1131 00:46:38,760 --> 00:46:42,120 LAWS AROUND THE COUNTRY UNDER 1132 00:46:42,120 --> 00:46:44,760 WHICH WITH THE COOPERATION OF 1133 00:46:44,760 --> 00:46:48,600 PRODUCER OF THE EXPERIMENTAL 1134 00:46:48,600 --> 00:46:49,840 INTERVENTION, USUALLY A 1135 00:46:49,840 --> 00:46:51,120 PHARMACEUTICAL COMPANY, PATIENTS 1136 00:46:51,120 --> 00:46:55,120 ARE ABLE TO SEEK EXPERIMENTAL 1137 00:46:55,120 --> 00:46:55,640 INTERVENTION OUTSIDE OF 1138 00:46:55,640 --> 00:46:56,400 PROTOCOL. 1139 00:46:56,400 --> 00:46:59,240 IN OTHER WORDS, NOT SIMPLY WITH 1140 00:46:59,240 --> 00:47:04,440 THOSE LIMITATIONS THAT APPLY TO 1141 00:47:04,440 --> 00:47:06,640 AN APPROVED PHASE 3 TRIAL. 1142 00:47:06,640 --> 00:47:08,480 ON THE ONE HAND, THEREFORE, WE 1143 00:47:08,480 --> 00:47:10,680 COULD SAY THAT COMPETENT ADULTS 1144 00:47:10,680 --> 00:47:13,520 SHOULD HAVE FREEDOM TO CONSENT, 1145 00:47:13,520 --> 00:47:16,280 EVEN TO SOMETHING THAT'S HIGH 1146 00:47:16,280 --> 00:47:16,920 RISK. 1147 00:47:16,920 --> 00:47:20,320 BUT, WE'RE STILL IN STAGE 2 AS 1148 00:47:20,320 --> 00:47:21,640 TO NORMAL VOLUNTEERS. 1149 00:47:21,640 --> 00:47:23,960 A CENTRAL PURPOSE OF THE ENTIRE 1150 00:47:23,960 --> 00:47:25,600 APPARATUS OF PRIOR REVIEW OF 1151 00:47:25,600 --> 00:47:28,040 RESEARCH IS TO LIMIT THE FREEDOM 1152 00:47:28,040 --> 00:47:30,960 OF RESEARCHERS TO SEEK OUT 1153 00:47:30,960 --> 00:47:33,160 PEOPLE WHO WILL TAKE BIG RISKS 1154 00:47:33,160 --> 00:47:36,760 AND/OR RISKS THAT ARE NOT 1155 00:47:36,760 --> 00:47:38,760 JUSTIFIED BY ADEQUATE BENEFIT. 1156 00:47:38,760 --> 00:47:41,040 ON THE OTHER HAND, IRBs CAN 1157 00:47:41,040 --> 00:47:45,400 AND SHOULD PROTECT EVEN 1158 00:47:45,400 --> 00:47:46,600 COMPETENT ADULTS FROM ACCEPTING 1159 00:47:46,600 --> 00:47:49,240 UNDUE RISKS, SO WE HAVE ON THE 1160 00:47:49,240 --> 00:47:51,440 ONE HAND FREEDOM TO CONSENT, 1161 00:47:51,440 --> 00:47:53,600 EVEN WHEN THERE'S RISKS, ON THE 1162 00:47:53,600 --> 00:47:57,240 OTHER I THINK THE SYSTEM SAYS WE 1163 00:47:57,240 --> 00:48:00,240 DON'T HAVE CONSENT AS THE FULLY 1164 00:48:00,240 --> 00:48:01,640 SUFFICIENT CASE IS FOR GOING 1165 00:48:01,640 --> 00:48:02,120 AHEAD. 1166 00:48:02,120 --> 00:48:05,000 LET ME TAKE A QUICK RUN AND 1167 00:48:05,000 --> 00:48:09,120 CONCLUSION AT THE QUESTIONS DR. 1168 00:48:09,120 --> 00:48:09,880 KIMMEL'S PRESENTATION ENDED 1169 00:48:09,880 --> 00:48:11,560 WITH. 1170 00:48:11,560 --> 00:48:13,520 FIRST, ARE THERE ETHICAL LIMITS 1171 00:48:13,520 --> 00:48:16,040 ON RESEARCH RISKS IN COMPETENT 1172 00:48:16,040 --> 00:48:16,240 ADULTS? 1173 00:48:16,240 --> 00:48:20,320 I SAY YES. 1174 00:48:20,320 --> 00:48:21,720 ESPECIALLY FOR NORMAL 1175 00:48:21,720 --> 00:48:22,040 VOLUNTEERS. 1176 00:48:22,040 --> 00:48:23,840 I MYSELF MIGHT ARGUE THAT HAS 1177 00:48:23,840 --> 00:48:24,840 THINGS BACKWARDS. 1178 00:48:24,840 --> 00:48:27,440 WE SHOULD BE MORE CONCERNED 1179 00:48:27,440 --> 00:48:29,600 ABOUT RISKS FOR PATIENTS BECAUSE 1180 00:48:29,600 --> 00:48:31,640 OF DIFFICULTIES OF THEIR 1181 00:48:31,640 --> 00:48:32,960 CONSENT, BUT THE CONVENTIONAL 1182 00:48:32,960 --> 00:48:35,840 VIEW IS WE SHOULD BE MORE 1183 00:48:35,840 --> 00:48:37,320 CONCERNED ABOUT NORMAL 1184 00:48:37,320 --> 00:48:37,640 VOLUNTEERS. 1185 00:48:37,640 --> 00:48:40,240 IF SO, DR. KIMMEL ASKED HOW ARE 1186 00:48:40,240 --> 00:48:41,560 THESE LIMITS DETERMINED? 1187 00:48:41,560 --> 00:48:44,480 THEY ARE DETERMINED BY IRBs, 1188 00:48:44,480 --> 00:48:45,560 RELYING ON MEMBERS' KNOWLEDGE, 1189 00:48:45,560 --> 00:48:48,240 WHAT IS KNOWN ABOUT RISKS, AND 1190 00:48:48,240 --> 00:48:49,640 OTHER RESEARCH, AT THEIR OWN AND 1191 00:48:49,640 --> 00:48:51,720 OTHER INSTITUTIONS. 1192 00:48:51,720 --> 00:48:53,600 THERE'S NO UNIFORM STANDARD. 1193 00:48:53,600 --> 00:48:55,640 EMPIRICAL STUDIES THAT HAVE BEEN 1194 00:48:55,640 --> 00:48:57,840 DONE SHOW DIFFERENT STANDARDS 1195 00:48:57,840 --> 00:48:59,480 BEING APPLIED. 1196 00:48:59,480 --> 00:49:01,800 IS THE PRESENT STUDY CONSISTENT 1197 00:49:01,800 --> 00:49:03,400 WITH WHATEVER LIMITS THERE ARE? 1198 00:49:03,400 --> 00:49:06,080 I THINK THERE'S NO WAY FOR ME TO 1199 00:49:06,080 --> 00:49:08,040 ANSWER AS TO WHAT THE CLINICAL 1200 00:49:08,040 --> 00:49:12,440 CENTER IRB HAS DONE IN THE ABOUT 1201 00:49:12,440 --> 00:49:17,280 NORMAL VOLUNTEERS IN RESEARCH 1202 00:49:17,280 --> 00:49:18,400 WITH COMPARABLE RISKS. 1203 00:49:18,400 --> 00:49:26,120 IS IT MORE PROBLEMATIC TO EXPOSE 1204 00:49:26,120 --> 00:49:27,240 HEALTHY INDIVIDUALS TO RESEARCH 1205 00:49:27,240 --> 00:49:29,040 RISKS YES, ESPECIALLY IN THIS 1206 00:49:29,040 --> 00:49:36,360 INSTANCE, IS THE OBVIOUS ANSWER. 1207 00:49:36,360 --> 00:49:39,240 FIRST BY THE RESEARCHEST 1208 00:49:39,240 --> 00:49:42,400 DESCRIPTION, NOT HAVING A KNOWN 1209 00:49:42,400 --> 00:49:48,040 BENEFIT DEFEATS THE RISK/BENEFIT 1210 00:49:48,040 --> 00:49:48,760 COMPARISON. 1211 00:49:48,760 --> 00:49:52,440 IF YOU THINK OF DIVISION YOU 1212 00:49:52,440 --> 00:50:01,320 HAVE ZERO AS THE BOTTOM PART OF 1213 00:50:01,320 --> 00:50:03,240 THE FRACTION. 1214 00:50:03,240 --> 00:50:04,840 WILL IT BE BENEFICIAL TO COMPARE 1215 00:50:04,840 --> 00:50:11,240 WITH NORMAL TISSUE? 1216 00:50:11,240 --> 00:50:13,760 WE DON'T KNOW. 1217 00:50:13,760 --> 00:50:18,800 DOES GENERAL ANESTHESIA AFFECT 1218 00:50:18,800 --> 00:50:22,560 WHEN MAKING COMPARISONS WITH 1219 00:50:22,560 --> 00:50:22,920 DISEASED TISSUE? 1220 00:50:22,920 --> 00:50:25,000 DEPARTMENT SEEM TO ME THERE'S AN 1221 00:50:25,000 --> 00:50:25,440 ANSWER. 1222 00:50:25,440 --> 00:50:27,200 DR. KIMMEL MAY SAY THERE IS BUT 1223 00:50:27,200 --> 00:50:31,560 THE FIRST POINT IS AN UNKNOWN. 1224 00:50:31,560 --> 00:50:34,560 AND IT SEEMS TO ME THAT THE 1225 00:50:34,560 --> 00:50:35,840 OTHER REASON WHY IT'S 1226 00:50:35,840 --> 00:50:37,280 PROBLEMATIC IS THAT RISK WOULD 1227 00:50:37,280 --> 00:50:45,640 BE MINIMIZED BY USING OTHER 1228 00:50:45,640 --> 00:50:49,160 SOURCES. 1229 00:50:49,160 --> 00:50:50,840 THE PRINCE NON-MALEFICENCE 1230 00:50:50,840 --> 00:50:51,560 INVOLVES AVOIDING RISK, HEALTHY 1231 00:50:51,560 --> 00:50:54,120 PERSONS SHOULD NOT BE SUBJECT TO 1232 00:50:54,120 --> 00:50:55,640 KIDNEY BIOPSY SOLELY FOR 1233 00:50:55,640 --> 00:50:56,760 RESEARCH BEFORE DETERMINING 1234 00:50:56,760 --> 00:50:58,520 STUDIES CANNOT BE DONE WITH 1235 00:50:58,520 --> 00:51:01,600 TISSUE OBTAINED FROM LIVING OR 1236 00:51:01,600 --> 00:51:04,120 DECEASED KIDNEY DONORS. 1237 00:51:04,120 --> 00:51:09,880 DECEASED KIDNEY DONORS WHOSE 1238 00:51:09,880 --> 00:51:13,040 KIDNEYS ARE PERFECT USABLE FOR 1239 00:51:13,040 --> 00:51:14,120 TRANSPLANTATION HAVE NOT 1240 00:51:14,120 --> 00:51:15,280 UNDERGONE GENERAL ANESTHESIA IN 1241 00:51:15,280 --> 00:51:17,000 REMOVAL OF THOSE KIDNEYS. 1242 00:51:17,000 --> 00:51:20,040 CARE WILL BE NEEDED TO AVOID 1243 00:51:20,040 --> 00:51:24,080 THERAPEUTIC MISCONCEPTION BY 1244 00:51:24,080 --> 00:51:30,640 KIDNEY DONORS, LIVING KIDNEY 1245 00:51:30,640 --> 00:51:33,560 DONORS AND YOU NEED TO INFORM 1246 00:51:33,560 --> 00:51:36,040 RECIPIENT SHOULD BE THERE 1247 00:51:36,040 --> 00:51:37,200 CONCERNED TAKING A BIOPSY WOULD 1248 00:51:37,200 --> 00:51:40,480 CHANGE THE UTILITY BUT BIOPSIES 1249 00:51:40,480 --> 00:51:42,960 ARE ALREADY DONE IN TRANSPLANT 1250 00:51:42,960 --> 00:51:43,440 SETTINGS. 1251 00:51:43,440 --> 00:51:46,360 AND FINALLY, WOULD THE STUDY BE 1252 00:51:46,360 --> 00:51:55,480 ETHICALLY BETTER OR WORSE IF THE 1253 00:51:55,480 --> 00:52:01,560 PARTICIPANTS WERE PAID, E G1 -- 1254 00:52:01,560 --> 00:52:04,280 E G, $1,000, THE ARGUMENTS IN 1255 00:52:04,280 --> 00:52:08,840 FAVOR OF PAYMENT INCLUDE PAYMENT 1256 00:52:08,840 --> 00:52:10,440 IS PERMITTED, NOT INHERENTLY 1257 00:52:10,440 --> 00:52:13,520 UNETHICAL, IF ALL OTHER ETHICAL 1258 00:52:13,520 --> 00:52:19,040 PRINCIPLES ARE SATISFIED, PARTS 1259 00:52:19,040 --> 00:52:19,640 PARTICIPATION IS PERMISSIBLE, 1260 00:52:19,640 --> 00:52:23,720 THAT IS THE IRB AND 1261 00:52:23,720 --> 00:52:25,000 INVESTIGATORS HAVE GONE THROUGH 1262 00:52:25,000 --> 00:52:27,880 THE PROCESS THEY NEED TO, AND SO 1263 00:52:27,880 --> 00:52:30,840 IF THERE IS AN INCENTIVE TO 1264 00:52:30,840 --> 00:52:33,640 PARTICIPATE BY GIVING MONEY, 1265 00:52:33,640 --> 00:52:36,040 THERE'S NOTHING WRONG WITH 1266 00:52:36,040 --> 00:52:36,360 PARTICIPATION. 1267 00:52:36,360 --> 00:52:40,240 BUT THE ARGUMENTS AGAINST 1268 00:52:40,240 --> 00:52:42,400 PAYMENT INCLUDE RISKY 1269 00:52:42,400 --> 00:52:43,560 EXPERIMENT, IT IS DISINGENUOUS 1270 00:52:43,560 --> 00:52:45,640 TO THINK PARTICIPANTS SHOULD BE 1271 00:52:45,640 --> 00:52:49,160 PAID SIMPLY FOR TIME AND 1272 00:52:49,160 --> 00:52:51,160 INCONVENIENCE, LIKE $1,000. 1273 00:52:51,160 --> 00:52:57,000 YOU'RE HAVING TO GO INTO THE 1274 00:52:57,000 --> 00:52:59,520 HOSPITAL, THE CLINICAL SETTING, 1275 00:52:59,520 --> 00:53:03,000 AND THERE'S A LIKELIHOOD 1276 00:53:03,000 --> 00:53:05,560 APPARENTLY SOME SUBSTANTIAL 1277 00:53:05,560 --> 00:53:09,640 LIKELIHOOD OF BLEEDING, INTERNAL 1278 00:53:09,640 --> 00:53:12,320 BLEEDING, ALSO INTO THE KIDNEY, 1279 00:53:12,320 --> 00:53:15,560 CAUSING INTO THE URINE, PAIN AND 1280 00:53:15,560 --> 00:53:17,760 DISCOMFORT AND SO FORTH. 1281 00:53:17,760 --> 00:53:21,400 SO $1,000 WOULD BE FINE FOR THAT 1282 00:53:21,400 --> 00:53:27,160 BUT WHAT MAKES THIS UNUSUAL IS 1283 00:53:27,160 --> 00:53:30,360 THE THREE-TENTHS OF A PERCENT 1284 00:53:30,360 --> 00:53:33,600 LIKELIHOOD OF DEATH BASED ON THE 1285 00:53:33,600 --> 00:53:36,080 EXISTING KNOWLEDGE. 1286 00:53:36,080 --> 00:53:37,640 OBVIOUSLY, EXISTING KNOWLEDGE 1287 00:53:37,640 --> 00:53:38,640 FROM A DIFFERENT SUBJECT BASE, 1288 00:53:38,640 --> 00:53:43,080 THAT IS TO SAY THE PEOPLE WHO 1289 00:53:43,080 --> 00:53:43,600 ARE UNDERGOING RESEARCH 1290 00:53:43,600 --> 00:53:45,640 BIOPSIES, AS PART OF THE STUDY 1291 00:53:45,640 --> 00:53:47,160 WHO HAVE KIDNEY DISEASE, ARE NOT 1292 00:53:47,160 --> 00:53:48,720 THE SAME AS THE NORMAL 1293 00:53:48,720 --> 00:53:50,440 VOLUNTEERS, BUT WE DON'T HAVE 1294 00:53:50,440 --> 00:53:52,960 DATA ON THAT AND IN THESE 1295 00:53:52,960 --> 00:53:53,640 CIRCUMSTANCES YOU PROBABLY TURN 1296 00:53:53,640 --> 00:53:56,240 TO THE DATA THAT YOU DO HAVE, 1297 00:53:56,240 --> 00:54:00,040 AND THAT'S WHAT DR. KIMMEL HAS 1298 00:54:00,040 --> 00:54:01,640 INCLUDED IN HIS PRESENTATION. 1299 00:54:01,640 --> 00:54:04,640 AND THE QUESTION THAT HE ASKS. 1300 00:54:04,640 --> 00:54:08,400 BUT, IT IS ALSO TRUE THAT 1301 00:54:08,400 --> 00:54:09,240 SETTING THOSE FINANCIAL REWARDS 1302 00:54:09,240 --> 00:54:11,440 WILL OFFSET A RISK AND THE 1303 00:54:11,440 --> 00:54:12,640 FINANCIAL REWARDS ARE VERY 1304 00:54:12,640 --> 00:54:17,640 LIKELY GIVEN THOSE RISKS TO BE 1305 00:54:17,640 --> 00:54:19,640 THOUGHT TO BE JUSTIFIED ABOVE 1306 00:54:19,640 --> 00:54:23,840 $1,000, WOULD CREATE AN UNDUE 1307 00:54:23,840 --> 00:54:26,640 INDUCEMENT THAT WOULD UNDERMINE 1308 00:54:26,640 --> 00:54:28,800 VOLUNTARINESS AND WOULD INDUCE 1309 00:54:28,800 --> 00:54:31,640 MORE POOR AND VULNERABLE 1310 00:54:31,640 --> 00:54:32,960 INDIVIDUALS TO ENROLL, THE EXACT 1311 00:54:32,960 --> 00:54:36,760 OPPOSITE OF THE CAUTION THAT 1312 00:54:36,760 --> 00:54:39,360 JONAS SUGGESTED ABOUT BEGINNING 1313 00:54:39,360 --> 00:54:42,240 WITH THE RESEARCHERS THEMSELVES. 1314 00:54:42,240 --> 00:54:45,400 SO, I THANK YOU AND I LOOK 1315 00:54:45,400 --> 00:54:53,600 FORWARD TO THE DISCUSSION. 1316 00:54:53,600 --> 00:54:56,120 >> THANK YOU, ALEX. 1317 00:54:56,120 --> 00:54:58,320 SOME PEOPLE HAVE SUGGESTED THAT 1318 00:54:58,320 --> 00:55:01,640 THE WAY IRBs SHOULD EVALUATE 1319 00:55:01,640 --> 00:55:05,080 PROPOSALS LIKE PAUL'S IS TO LOOK 1320 00:55:05,080 --> 00:55:07,040 AT ACTIVITIES AND CONTEXT 1321 00:55:07,040 --> 00:55:09,280 OUTSIDE OF RESEARCH, WHERE WE 1322 00:55:09,280 --> 00:55:11,280 LET PEOPLE FACE RISKS IN THE 1323 00:55:11,280 --> 00:55:12,760 CONTEXT OF ACTIVITIES THAT ARE 1324 00:55:12,760 --> 00:55:15,840 DESIGNED TO BENEFIT OTHERS. 1325 00:55:15,840 --> 00:55:17,600 SO, KIDNEY DONATION, LIVING 1326 00:55:17,600 --> 00:55:19,040 KIDNEY DONATION IS AN OBVIOUS 1327 00:55:19,040 --> 00:55:20,520 EXAMPLE. 1328 00:55:20,520 --> 00:55:24,040 OTHER PEOPLE HAVE TALKED ABOUT 1329 00:55:24,040 --> 00:55:25,360 THE RISKS OF RESCUING STRANDED 1330 00:55:25,360 --> 00:55:27,840 HIKERS, OTHER PEOPLE TALKED 1331 00:55:27,840 --> 00:55:30,240 ABOUT THE RISKS OF BEING AN EMT 1332 00:55:30,240 --> 00:55:32,040 OR BEING A FIREMAN, I WAS 1333 00:55:32,040 --> 00:55:35,880 WONDERING IF YOU HAD THOUGHTS ON 1334 00:55:35,880 --> 00:55:38,680 THAT APPROACH, WHEN IRBs, 1335 00:55:38,680 --> 00:55:39,880 THESE KINDS OF PROPOSALS, WOULD 1336 00:55:39,880 --> 00:55:41,440 THAT BE A GOOD STANDARD TO KEEP 1337 00:55:41,440 --> 00:55:42,600 IN MIND? 1338 00:55:42,600 --> 00:55:45,640 >> WELL, IF IT WERE, THE FACT 1339 00:55:45,640 --> 00:55:47,840 THAT WE KNOW KIDNEY DONATION HAS 1340 00:55:47,840 --> 00:55:50,640 A RISK THAT IS A TENTH OF THE 1341 00:55:50,640 --> 00:55:52,120 RISK THAT PAUL IS HYPOTHESIZING 1342 00:55:52,120 --> 00:55:53,920 HERE, THE ONLY ONE THAT THEY 1343 00:55:53,920 --> 00:55:57,440 HAVE TO GO ON, WOULD INDICATE 1344 00:55:57,440 --> 00:56:00,400 THAT IT DOESN'T SUPPORT THIS ON 1345 00:56:00,400 --> 00:56:06,680 THE RISK LEVEL ALONE. 1346 00:56:06,680 --> 00:56:09,640 MOREOVER, THAT VOLUNTARY CHOICE 1347 00:56:09,640 --> 00:56:13,040 THERE IS WITHIN THE CONTEXT OF 1348 00:56:13,040 --> 00:56:15,640 PROVIDING A WELL-KNOWN, 1349 00:56:15,640 --> 00:56:16,480 WELL-ESTABLISHED BENEFIT. 1350 00:56:16,480 --> 00:56:19,600 SO I THINK -- I WANT TO BE 1351 00:56:19,600 --> 00:56:20,040 UNDERSTOOD. 1352 00:56:20,040 --> 00:56:24,080 I ACTUALLY HAVE MUCH MORE 1353 00:56:24,080 --> 00:56:25,040 RESPECT FOR INDIVIDUALLY 1354 00:56:25,040 --> 00:56:26,080 INFORMED CONSENT, WHAT I'VE 1355 00:56:26,080 --> 00:56:28,400 TRIED TO EXPLAIN HERE IS WHAT I 1356 00:56:28,400 --> 00:56:29,800 THINK THE REGULATIONS, THE 1357 00:56:29,800 --> 00:56:31,960 SYSTEM OF REGULATIONS WE HAVE 1358 00:56:31,960 --> 00:56:35,640 NOW, WHICH IN EFFECT 1359 00:56:35,640 --> 00:56:36,720 SUBSTITUTED -- SUBSTITUTES A 1360 00:56:36,720 --> 00:56:39,360 COMMITTEE'S PATERNALISM FOR THE 1361 00:56:39,360 --> 00:56:40,440 OLD PATERNALISM OF PHYSICIANS 1362 00:56:40,440 --> 00:56:45,160 WHO USED TO MAKE THESE CHOICES, 1363 00:56:45,160 --> 00:56:48,440 AND THE DOCTORS THAT HENNY 1364 00:56:48,440 --> 00:56:49,120 BEECHER WERE COMPLAINING ABOUT 1365 00:56:49,120 --> 00:56:50,400 WERE DOING THAT THINKING I KNOW 1366 00:56:50,400 --> 00:56:52,040 WHAT IS BEST. 1367 00:56:52,040 --> 00:56:53,840 WE NOW HAVE SOMETHING ELSE, THE 1368 00:56:53,840 --> 00:56:58,240 WHOLE RATIONALE OF HAVING THAT 1369 00:56:58,240 --> 00:57:00,400 SYSTEM OF PRIOR REVIEW IS TO 1370 00:57:00,400 --> 00:57:03,680 LIMIT SOMETHING WHICH IS JUST AN 1371 00:57:03,680 --> 00:57:05,320 AGREEMENT BETWEEN THE INDIVIDUAL 1372 00:57:05,320 --> 00:57:08,880 SUBJECT AND THE RESEARCHER. 1373 00:57:08,880 --> 00:57:10,920 AS FOR EMPLOYMENT SITUATIONS AND 1374 00:57:10,920 --> 00:57:16,200 WAR, WHERE WE, YOU KNOW, WE 1375 00:57:16,200 --> 00:57:21,640 COLLECTIVELY DO CONSTRICT, 1376 00:57:21,640 --> 00:57:23,440 CONSCRIPT, EXCUSE ME, PEOPLE TO 1377 00:57:23,440 --> 00:57:27,920 GO INTO WAR RISKS ARE HIGH, FAR 1378 00:57:27,920 --> 00:57:31,080 ABOVE THREE IN A THOUSAND, SO 1379 00:57:31,080 --> 00:57:39,440 THAT ANALOGY GOES TOO FAR, IN MY 1380 00:57:39,440 --> 00:57:40,600 VIEW. 1381 00:57:40,600 --> 00:57:44,440 >> I WANT TO THANK PAUL AND ALEX 1382 00:57:44,440 --> 00:57:45,600 FOR A VERY INTERESTING AND 1383 00:57:45,600 --> 00:57:47,000 LIVELY SESSION. 1384 00:57:47,000 --> 00:57:48,360 AND THANK EVERYBODY FOR ETHICS 1385 00:57:48,360 --> 00:57:51,120 GRAND ROUNDS FOR THIS ACADEMIC 1386 00:57:51,120 --> 00:57:51,320 YEAR. 1387 00:57:51,320 --> 00:57:53,440 AND HOPEFULLY WE'LL SEE PEOPLE 1388 00:57:53,440 --> 00:57:55,040 BACK HERE AGAIN THE FIRST 1389 00:57:55,040 --> 00:57:57,240 WEDNESDAY IN OCTOBER, AT NOON, 1390 00:57:57,240 --> 00:57:58,240 FOR ANOTHER SESSION. 1391 00:57:58,240 --> 00:57:59,400 SO THANKS, YOU GUYS. 1392 00:57:59,400 --> 00:58:00,720 REALLY APPRECIATE IT. 1393 00:58:00,720 --> 00:58:02,760 LOOK FORWARD TO SEEING EVERYBODY 1394 00:58:02,760 --> 00:58:02,960 AGAIN. 1395 00:58:02,960 --> 00:00:00,000 BYE-BYE.