1 00:00:06,718 --> 00:00:08,854 WE ARE CERTAINLY HAPPY TO BE 2 00:00:08,854 --> 00:00:11,089 HERE TODAY FOR OUR OCTOBER 3 00:00:11,089 --> 00:00:12,157 SESSION OF THE OHSRP EDUCATION 4 00:00:12,157 --> 00:00:14,192 SERIES WHICH FEATURES A 5 00:00:14,192 --> 00:00:15,727 PRESENTATION ENTITLED 6 00:00:15,727 --> 00:00:16,295 CONSIDERATIONS FOR INFORMED 7 00:00:16,295 --> 00:00:16,962 CONSENT IN CELL AND GENE THERAPY 8 00:00:16,962 --> 00:00:20,232 TRIALS. 9 00:00:20,232 --> 00:00:22,200 BEFORE I INTRODUCE OUR I'LL 10 00:00:22,200 --> 00:00:23,602 REMIND YOU THE PRESENTATION WILL 11 00:00:23,602 --> 00:00:27,139 BE ARCHIVED IN THE PAST EVENTS 12 00:00:27,139 --> 00:00:32,210 SECTION OF THE NIH VIVDEO SITE 13 00:00:32,210 --> 00:00:34,680 AND POSTED ON THE OHSRP WEBSITE 14 00:00:34,680 --> 00:00:37,583 APPROXIMATELY ONE TO TWO WEEKS 15 00:00:37,583 --> 00:00:39,851 AFTER THE SECTION IN THE 16 00:00:39,851 --> 00:00:41,420 PRESENTATION ARCHIVED SECTION OF 17 00:00:41,420 --> 00:00:42,487 THE OHSRP EDUCATION AND TRAINING 18 00:00:42,487 --> 00:00:43,455 WEB PAGE. 19 00:00:43,455 --> 00:00:45,223 DURING THE SESSION WE ENCOURAGE 20 00:00:45,223 --> 00:00:47,526 YOU TO SUBMIT QUESTIONS BY 21 00:00:47,526 --> 00:00:49,261 CLICKING ON THE BOX ENTITLED 22 00:00:49,261 --> 00:00:51,830 LIVE FEEDBACK LINK. 23 00:00:51,830 --> 00:00:54,800 OUR GUEST SPEAKER IS DR. DANIEL 24 00:00:54,800 --> 00:00:57,102 KAVANAGH ADVISER FOR GENE 25 00:00:57,102 --> 00:01:01,940 THERAPY AND VACCINES AND 26 00:01:01,940 --> 00:01:05,611 BIOLOGICS AS A LABORATORY LEAD 27 00:01:05,611 --> 00:01:08,213 AND WORKS WITH SPONSORS AND CROs 28 00:01:08,213 --> 00:01:10,048 AND INSTITUTIONS USING THE 29 00:01:10,048 --> 00:01:10,882 INSTITUTIONAL BIO SAFETY 30 00:01:10,882 --> 00:01:14,653 COMMITTEE OTHERWISE KNOWN AS AN 31 00:01:14,653 --> 00:01:16,622 IBC AND OTHER CLINICAL TRIAL 32 00:01:16,622 --> 00:01:19,324 SUPPORT SERVICES IN 16 33 00:01:19,324 --> 00:01:19,725 COUNTRIES. 34 00:01:19,725 --> 00:01:21,994 PRIOR HE WAS ASSISTANT PROFESSOR 35 00:01:21,994 --> 00:01:23,695 OF MEDICINE AT HARVARD MEDICAL 36 00:01:23,695 --> 00:01:26,298 SCHOOL AND VICE CHAIR OF THE 37 00:01:26,298 --> 00:01:27,232 BRIGHAM IBC. 38 00:01:27,232 --> 00:01:30,402 HE WAS ALSO A CO-CHAIR OF A 39 00:01:30,402 --> 00:01:33,905 PHASE 1 HUMAN GENE TRANSFER 40 00:01:33,905 --> 00:01:38,577 CLINICAL TRIAL AT NGH AND HOLDS 41 00:01:38,577 --> 00:01:41,079 A REGULATORY AFFAIRS SOCIETY 42 00:01:41,079 --> 00:01:41,847 CERTIFICATE AND SERVES ON THE 43 00:01:41,847 --> 00:01:43,782 TECHNICAL AND REVIEW COMMITTEE 44 00:01:43,782 --> 00:01:45,484 FOR THE ASSOCIATION FOR BIO 45 00:01:45,484 --> 00:01:47,319 SAFETY AND BIO SECURITY 46 00:01:47,319 --> 00:01:48,553 INTERNATIONAL AND THE BIO 47 00:01:48,553 --> 00:01:49,888 INDUSTRY COMMITTEE FOR THE 48 00:01:49,888 --> 00:01:51,657 AMERICAN SOCIETY OF GENE AND 49 00:01:51,657 --> 00:01:53,325 CELL THERAPY. 50 00:01:53,325 --> 00:01:59,264 DR. KAVANAGH, PLEASE GO AHEAD. 51 00:01:59,264 --> 00:02:02,134 >> THANK YOU. 52 00:02:02,134 --> 00:02:05,637 LET ME KNOW IF THE SLIDES APPEAR 53 00:02:05,637 --> 00:02:05,971 CORRECTLY. 54 00:02:05,971 --> 00:02:09,374 >> THEY LOOK GREAT. 55 00:02:09,374 --> 00:02:12,310 >> THANK YOU TO OHSRP FOR 56 00:02:12,310 --> 00:02:15,514 ARRANGING THE PRESENTATION. 57 00:02:15,514 --> 00:02:16,281 IT'S BASED ON A PREVIOUS 58 00:02:16,281 --> 00:02:20,218 PRESENTATION INTENDED FOR AN 59 00:02:20,218 --> 00:02:23,822 AUDIENCE WITH MIXED BACKGROUND 60 00:02:23,822 --> 00:02:25,223 IN MOLECULAR BIOLOGY OR GENE 61 00:02:25,223 --> 00:02:25,457 THERAPY. 62 00:02:25,457 --> 00:02:28,226 WE'LL TRY TO INTRODUCE SOME 63 00:02:28,226 --> 00:02:33,465 BASIC CONCEPTS AND ALSO ADDRESS 64 00:02:33,465 --> 00:02:35,000 SOME OF THE MORE COMPLEX ISSUES 65 00:02:35,000 --> 00:02:40,072 FACING RESEARCH IN THIS AREA AND 66 00:02:40,072 --> 00:02:48,980 INFORMED CONSENT. 67 00:02:48,980 --> 00:02:52,217 I'M AN EMPLOYEE OF WC 68 00:02:53,151 --> 00:02:53,518 G. 69 00:02:53,518 --> 00:02:55,287 FOR TODAY'S AGENDA WE'LL SPEND 70 00:02:55,287 --> 00:02:57,622 TIME DEFINING GENE THERAPY AND 71 00:02:57,622 --> 00:02:59,524 GENE TRANSFER RESEARCH. 72 00:02:59,524 --> 00:03:02,260 WE'LL LOOK AT SOME NIH HAD AND 73 00:03:02,260 --> 00:03:05,263 FDA GUIDANCE FOR INFORMED 74 00:03:05,263 --> 00:03:06,898 CONSENT IN THE SECTOR. 75 00:03:06,898 --> 00:03:08,934 CONSIDER BEST PRACTICES FOR IRBs 76 00:03:08,934 --> 00:03:12,804 AND FOR INSTITUTIONAL BIO SAFETY 77 00:03:12,804 --> 00:03:16,675 COMMITTEES TO WORK TOGETHER ON 78 00:03:16,675 --> 00:03:17,976 ICD REVIEW. 79 00:03:17,976 --> 00:03:20,145 WE'LL LOOK AT THE MAJOR 80 00:03:20,145 --> 00:03:21,780 CATEGORIES OF RISK WITH CELL 81 00:03:21,780 --> 00:03:23,982 EDITING AND THERAPY RESEARCH AND 82 00:03:23,982 --> 00:03:27,119 MOST IMPORTANT PART OF TODAY'S 83 00:03:27,119 --> 00:03:29,888 PRESENTATION IS SOME INFORMATION 84 00:03:29,888 --> 00:03:34,459 ABOUT PATIENT PERSPECTIVES ON 85 00:03:34,459 --> 00:03:36,595 THE CLINICAL TRIALS AND AT THE 86 00:03:36,595 --> 00:03:38,797 END I'LL BRING UP UNRESOLVED 87 00:03:38,797 --> 00:03:42,334 ISSUES OR CONTINUING CHALLENGES. 88 00:03:42,334 --> 00:03:45,737 I IMAGINE ALMOST EVERYBODY ON 89 00:03:45,737 --> 00:03:48,273 TODAY'S CALL IS AWARE OF GENERAL 90 00:03:48,273 --> 00:03:51,042 REQUIREMENTS FOR ICDs. 91 00:03:51,042 --> 00:03:54,179 THERE HAS TO BE A DESCRIPTION OF 92 00:03:54,179 --> 00:03:57,215 THE RESEARCH OF THE RISK AND 93 00:03:57,215 --> 00:03:57,482 BENEFITS. 94 00:03:57,482 --> 00:04:02,020 ALTERNATIVES TO PARTICIPATION, 95 00:04:02,020 --> 00:04:02,654 CONFIDENTIALITY, COMPENSATION 96 00:04:02,654 --> 00:04:04,322 AND WHO TO CONTACT. 97 00:04:04,322 --> 00:04:08,226 VERY IMPORTANTLY THE RESEARCH IS 98 00:04:08,226 --> 00:04:17,502 VOLUNTARY AND INFORMATION 99 00:04:17,502 --> 00:04:19,137 GATHERED THAT'S IDENTIFIABLE AND 100 00:04:19,137 --> 00:04:21,072 THAT'S ANYTHING REVIEWED AT 101 00:04:21,072 --> 00:04:21,406 INSTITUTIONS. 102 00:04:21,406 --> 00:04:24,476 WHEN IT COMES TO GENE TRANSFER 103 00:04:24,476 --> 00:04:25,877 RESEARCH, WHAT WE'RE TALKING 104 00:04:25,877 --> 00:04:28,280 ABOUT HERE ARE LESS ABOUT 105 00:04:28,280 --> 00:04:29,281 REQUIREMENTS, MORE ABOUT WHAT 106 00:04:29,281 --> 00:04:31,416 WE'RE CALLING CONSIDERATIONS OR 107 00:04:31,416 --> 00:04:32,450 BEST PRACTICES THAT MAY APPLY 108 00:04:32,450 --> 00:04:36,021 DIFFERENTLY TO DIFFERENT 109 00:04:36,021 --> 00:04:39,157 STUDIES. 110 00:04:39,157 --> 00:04:41,092 AS FAR AS I'M AWARE ANY SUCH 111 00:04:41,092 --> 00:04:42,894 STUDY SHOULD INCLUDE AN 112 00:04:42,894 --> 00:04:45,330 EXPLANATION THIS THAT THE 113 00:04:45,330 --> 00:04:48,633 PRODUCT CONTAINS GENETICALLY 114 00:04:48,633 --> 00:04:51,336 MODIFIED DNA OR RNA OR CAPABLE 115 00:04:51,336 --> 00:04:53,405 OF MODIFYING THE DNA AND RNA 116 00:04:53,405 --> 00:04:55,240 THROUGH SOME TYPE OF GENE 117 00:04:55,240 --> 00:04:55,473 EDITING. 118 00:04:55,473 --> 00:04:57,008 I CAN'T THINK OF EXCEPTIONS 119 00:04:57,008 --> 00:04:59,211 WHERE THAT WOULD NOT BE 120 00:04:59,211 --> 00:04:59,477 INCLUDED. 121 00:04:59,477 --> 00:05:00,145 WHERE IT'S APPROPRIATE TO THE 122 00:05:00,145 --> 00:05:03,582 RESEARCH UNDER REVIEW, THERE ARE 123 00:05:03,582 --> 00:05:07,986 OTHER CONSIDERATIONS THAT APPLY. 124 00:05:07,986 --> 00:05:12,023 RISK OF GENETIC MODIFICATIONS, 125 00:05:12,023 --> 00:05:15,527 REPRODUCTIVE RISKS, VECTOR 126 00:05:15,527 --> 00:05:15,760 EFFECTS. 127 00:05:15,760 --> 00:05:17,395 TRANS GENE EFFECTS. 128 00:05:17,395 --> 00:05:19,130 WE'LL LOOK AT THEM LATER IN THE 129 00:05:19,130 --> 00:05:20,799 PRESENTATION AND EACH HAS TO BE 130 00:05:20,799 --> 00:05:21,433 CONSIDERED IN THE CONTEXT OF A 131 00:05:21,433 --> 00:05:31,743 PARTICULAR STUDY. 132 00:05:36,648 --> 00:05:42,020 LET'S ARE -- REVIEW THE 133 00:05:42,020 --> 00:05:43,154 TECHNOLOGY. 134 00:05:43,154 --> 00:05:45,023 INFORMATION IS STORED IN DNA, 135 00:05:45,023 --> 00:05:46,124 TRANSCRIBED IN RNA AND 136 00:05:46,124 --> 00:05:47,626 TRANSLATED INTO PROTEINS AND 137 00:05:47,626 --> 00:05:49,895 PROTEINS ARE DOING THE HEAVY 138 00:05:49,895 --> 00:05:55,100 LIFTING FOR MACHINERY OF THE 139 00:05:55,100 --> 00:06:00,972 CELL. 140 00:06:00,972 --> 00:06:02,407 AND HUMAN GENE TRANSFER RESEARCH 141 00:06:02,407 --> 00:06:05,410 SAY DEFINITION CONTAINED IN THE 142 00:06:05,410 --> 00:06:09,214 NIH GUIDELINE FOR RESEARCH 143 00:06:09,214 --> 00:06:10,715 INVOLVING RECOMBINANT MOLECULES 144 00:06:10,715 --> 00:06:12,751 RELATED TO THE CONCEPT OF GENE 145 00:06:12,751 --> 00:06:13,852 THERAPY AND WE'LL GO BACK AND 146 00:06:13,852 --> 00:06:19,024 FORTH BETWEEN THE CONCEPTS IN 147 00:06:19,024 --> 00:06:19,724 TODAY'S PRESENTATION. 148 00:06:19,724 --> 00:06:22,594 IN GENERAL UNDER THE NIH 149 00:06:22,594 --> 00:06:24,029 GUIDELINES HUMAN GENE TRANSFER 150 00:06:24,029 --> 00:06:27,232 INVOLVES ADMINISTRATION TO A 151 00:06:27,232 --> 00:06:35,407 HUMAN SUBJECT AND RNA PRODUCTS 152 00:06:35,407 --> 00:06:40,211 OR OLICO NUCLEOTIDES THAT DON'T 153 00:06:40,211 --> 00:06:43,281 PRODUCE LASTING CHANGES IN THE 154 00:06:43,281 --> 00:06:45,951 CELL AND GUIDELINES NEEDS TO BE 155 00:06:45,951 --> 00:06:49,287 APPROVED BY AN INSTITUTIONAL BIO 156 00:06:49,287 --> 00:06:51,423 SAFETY COMMITTEE APPROVED BY THE 157 00:06:51,423 --> 00:06:52,757 NIH OR INSTITUTION AND WITHIN 158 00:06:52,757 --> 00:06:56,294 THIS CATEGORY THERE IS FDA 159 00:06:56,294 --> 00:06:58,430 MARKETING APPROVAL FOR A GROWING 160 00:06:58,430 --> 00:07:00,131 NUMBER OF PRODUCTS INCLUDING 161 00:07:00,131 --> 00:07:03,835 VECTORED GENE THERAPIES FOR 162 00:07:03,835 --> 00:07:05,270 INHERITED DISEASE, EX VIVO 163 00:07:05,270 --> 00:07:06,338 ENGINEERED CELLULAR THERAPIES 164 00:07:06,338 --> 00:07:10,909 FOR THE TREATMENT OF CANCER OR 165 00:07:10,909 --> 00:07:13,211 INHERITED DISEASES. 166 00:07:13,211 --> 00:07:23,722 WE SEE ONCOLYTIC VIRUSES AND 167 00:07:31,563 --> 00:07:38,269 mRNA GENE THERAPY. 168 00:07:38,269 --> 00:07:39,504 WE SEE PRODUCTS THAT ARE 169 00:07:39,504 --> 00:07:44,242 DELIVERING DNA OR RNA SUCH AS AN 170 00:07:44,242 --> 00:07:47,612 RNA VECTOR AND RNA PRODUCTS 171 00:07:47,612 --> 00:07:48,680 PRODUCE TYPICALLY TRANSIENT 172 00:07:48,680 --> 00:07:54,085 CHANGES IN THE GENETIC CONTENT 173 00:07:54,085 --> 00:07:54,786 OF THE CELL. 174 00:07:54,786 --> 00:08:00,725 AND SOME AS CLASSIFIED AS GENE 175 00:08:00,725 --> 00:08:02,260 THERAPY IF THEY'RE NOT 176 00:08:02,260 --> 00:08:07,599 CLASSIFIED AS VACCINES. 177 00:08:07,599 --> 00:08:10,235 WHEN DNA IS ADDED TO THE CELL, 178 00:08:10,235 --> 00:08:15,173 SOME OR BUT NOT ALL PRODUCTS 179 00:08:15,173 --> 00:08:18,009 MAKE PERMANENT CHANGES TO DNA IN 180 00:08:18,009 --> 00:08:18,676 THE CHROMOSOME. 181 00:08:18,676 --> 00:08:21,713 SOME OF THESE MAY BE DERIVED 182 00:08:21,713 --> 00:08:26,618 FROM RETROVIRUSES OR TRANSPOSONS 183 00:08:26,618 --> 00:08:28,353 THAT PROVIDE DNA INTEGRATED IN 184 00:08:28,353 --> 00:08:29,387 THE CHROMOSOME. 185 00:08:29,387 --> 00:08:31,856 THE CAPACITY FOR INTEGRATION 186 00:08:31,856 --> 00:08:34,659 INTRODUCES SAFETY CONSIDERATIONS 187 00:08:34,659 --> 00:08:36,027 NEED TO BE CONSIDERED AS PART OF 188 00:08:36,027 --> 00:08:40,331 THE RISK ASSESSMENT. 189 00:08:40,331 --> 00:08:44,235 THIS ENTIRE CATEGORY OF HUMAN 190 00:08:44,235 --> 00:08:45,203 GENE TRANSFER PRODUCTS INCLUDES 191 00:08:45,203 --> 00:08:47,172 A REALLY BROAD AND GROWING 192 00:08:47,172 --> 00:08:51,276 VARIETY OF MODALITIES. 193 00:08:51,276 --> 00:08:53,011 WE SEE CAR T CELLS AND OTHER 194 00:08:53,011 --> 00:08:57,749 GENETICALLY MODIFIED EFFECTERS. 195 00:08:57,749 --> 00:09:00,018 NON-REPLICATING VIRAL VECTORS, 196 00:09:00,018 --> 00:09:04,222 mRNA VACCINES AND GENE 197 00:09:04,222 --> 00:09:06,024 THERAPIES. 198 00:09:06,024 --> 00:09:09,227 OTHER PRODUCTS SUCH AS LIVE O 199 00:09:09,227 --> 00:09:14,999 ONOLYTIC VIRUSES AND GENETICALLY 200 00:09:14,999 --> 00:09:18,036 MODIFIED ANIMALS ARE ALL BEING 201 00:09:18,036 --> 00:09:19,537 USED IN CLINICAL TRIALS IN ONE 202 00:09:19,537 --> 00:09:20,472 WAY OR ANOTHER. 203 00:09:20,472 --> 00:09:22,607 WE WON'T ADDRESS ALL TODAY 204 00:09:22,607 --> 00:09:23,575 BECAUSE WE'RE FOCUSSING ON 205 00:09:23,575 --> 00:09:27,045 TRADITIONAL CONCEPTS OF GENE 206 00:09:27,045 --> 00:09:27,579 THERAPY AND GENE EDITING. 207 00:09:27,579 --> 00:09:29,714 WHEN IT COMES TO DELIVERY OF 208 00:09:29,714 --> 00:09:35,353 THESE PRODUCTS IN CLINICAL 209 00:09:35,353 --> 00:09:39,190 DOSING THERE'S TWO PRIMARY 210 00:09:39,190 --> 00:09:39,390 TYPES. 211 00:09:39,390 --> 00:09:45,296 IN VIVO GENE DELIVERY WITH THE 212 00:09:45,296 --> 00:09:51,436 DNA AND RNA IS INTRODUCED BY 213 00:09:51,436 --> 00:09:53,905 INJECTION OR INFUSION AND LEADS 214 00:09:53,905 --> 00:09:56,274 TO A GENETICALLY MODIFIED CELLS 215 00:09:56,274 --> 00:10:01,146 AND LIPID AND NANO PARTICLES MAY 216 00:10:01,146 --> 00:10:02,180 CONTAIN mRNA AS PART OF A 217 00:10:02,180 --> 00:10:05,416 VACCINE FOR GENE THERAPY OR FOR 218 00:10:05,416 --> 00:10:09,921 VACCINES OR GENE THERAPY. 219 00:10:09,921 --> 00:10:13,491 THERE ARE REPLICATING AND 220 00:10:13,491 --> 00:10:15,026 NON-REPLICATING VECTORS THAT 221 00:10:15,026 --> 00:10:17,228 ACCOMPLISH THAT IN VIVO. 222 00:10:17,228 --> 00:10:19,297 EX VIVO IS A SEPARATE FORM OF 223 00:10:19,297 --> 00:10:21,266 DELIVERY WHERE PRODUCTS ARE 224 00:10:21,266 --> 00:10:24,035 REMOVED FROM HUMAN DONOR, 225 00:10:24,035 --> 00:10:26,804 GENETICALLY MODIFIED IN THE LAB 226 00:10:26,804 --> 00:10:29,340 UNDER CONTROLLED CONDITIONS AND 227 00:10:29,340 --> 00:10:32,377 INFUSED INTO A SUBJECT IN THE 228 00:10:32,377 --> 00:10:42,020 CASE OF OTOLOGOUS SELLS AND HAVE 229 00:10:42,020 --> 00:10:44,088 DIFFERENT TYPES OF RISK THAT 230 00:10:44,088 --> 00:10:44,722 NEED TO BE EXPLAINED IN INFORMED 231 00:10:44,722 --> 00:10:48,226 CONSENT. 232 00:10:48,226 --> 00:10:49,661 SO WHEN THESE TRIALS COME TO AN 233 00:10:49,661 --> 00:10:51,296 INSTITUTION NEAR YOU, WHAT IS 234 00:10:51,296 --> 00:10:54,832 INVOLVED IN INSTITUTIONAL REVIEW 235 00:10:54,832 --> 00:10:57,101 OF INFORMED CONSENT FOR SUBJECTS 236 00:10:57,101 --> 00:11:05,009 CONSIDERING PARTICIPATION? 237 00:11:05,009 --> 00:11:09,180 INTERESTING HISTORY TO REVIEW IS 238 00:11:09,180 --> 00:11:10,014 THAT INVOLVED INSTITUTIONAL BIO 239 00:11:10,014 --> 00:11:15,153 SAFETY COMMITTEES AND IRBs. 240 00:11:15,153 --> 00:11:16,454 SO THE CHANGING ROLES OF THESE 241 00:11:16,454 --> 00:11:20,491 TWO ROLES HAS GONE THROUGH A 242 00:11:20,491 --> 00:11:22,594 NUMBER OF PHASES IN RECENT 243 00:11:22,594 --> 00:11:23,228 YEARS. 244 00:11:23,228 --> 00:11:26,798 PRIOR TO 2016, THE NIH REQUIRED 245 00:11:26,798 --> 00:11:30,635 UNDER THE NIH GUIDELINES 246 00:11:30,635 --> 00:11:31,803 INSTITUTIONAL BIO SAFETY 247 00:11:31,803 --> 00:11:34,472 COMMITTEES TO REVIEW THE 248 00:11:34,472 --> 00:11:39,544 DOCUMENTS AND NIH LISTED POINTS 249 00:11:39,544 --> 00:11:42,547 TO CONSIDER AND ADVISED BY THE 250 00:11:42,547 --> 00:11:44,449 COMMITTEE AT NIH AND THE NIH 251 00:11:44,449 --> 00:11:48,920 GUIDELINES INCLUDED AN APPENDIX 252 00:11:48,920 --> 00:11:52,290 X REQUIRING IBC REVIEW OF 253 00:11:52,290 --> 00:11:55,927 SUBJECT SAFETY ISSUES SUCH AS 254 00:11:55,927 --> 00:11:57,028 SERIOUS ADVERSE EVENTS. 255 00:11:57,028 --> 00:12:01,032 AFTER THE AMENDMENT TO 2016 AND 256 00:12:01,032 --> 00:12:07,472 UP TO 2019, THERE WAS CONTINUING 257 00:12:07,472 --> 00:12:08,339 REQUIREMENT FOR THE 258 00:12:08,339 --> 00:12:09,240 INSTITUTIONAL BIO SAFETY 259 00:12:09,240 --> 00:12:12,310 COMMITTEES TO REVIEW THE CONCEPT 260 00:12:12,310 --> 00:12:12,977 DOCUMENTS. 261 00:12:12,977 --> 00:12:17,148 THE ACTUAL POINTS TO CONSIDER 262 00:12:17,148 --> 00:12:20,652 WERE LESS SPECIFIC THE IBC WERE 263 00:12:20,652 --> 00:12:24,188 TO PERFORM A TYPE OF ASSESSMENT. 264 00:12:24,188 --> 00:12:27,392 DURING THIS PERIOD THERE WERE 265 00:12:27,392 --> 00:12:29,761 FEW PROTOCOLS REVIEWED BY THE 266 00:12:29,761 --> 00:12:29,927 RAC. 267 00:12:29,927 --> 00:12:32,230 AFTER THE MOST RECENT AMENDMENT 268 00:12:32,230 --> 00:12:37,302 TO THE GUIDELINES IN 2019, IBC 269 00:12:37,302 --> 00:12:37,969 REVIEW OF INFORMED CONSENT 270 00:12:37,969 --> 00:12:41,906 DOCUMENTS IS NO LONGER REQUIRED. 271 00:12:41,906 --> 00:12:44,142 THE PRIMARY RESPONSIBILITY FOR 272 00:12:44,142 --> 00:12:46,611 PARTICIPANT SAFETY AND CONSENT 273 00:12:46,611 --> 00:12:48,479 REVIEW IS PLACED ON THE 274 00:12:48,479 --> 00:12:50,214 SHOULDERS OF THE IRB. 275 00:12:50,214 --> 00:12:52,817 THE OLD APPENDIX M WAS DELETED 276 00:12:52,817 --> 00:12:55,053 AND THE RAC WAS REPURPOSED AND 277 00:12:55,053 --> 00:12:58,856 RENAMED SO THERE WAS NO LONGER A 278 00:12:58,856 --> 00:13:00,625 PRE-REVIEW STEP BEFORE IT LANDS 279 00:13:00,625 --> 00:13:03,094 ON THE DESK OF THE IRB WHO IS 280 00:13:03,094 --> 00:13:05,697 REQUIRED TO CONDUCT THESE 281 00:13:05,697 --> 00:13:06,864 REVIEWS OF THE INFORMED CONSENT 282 00:13:06,864 --> 00:13:14,672 AND OTHER ASPECTS OF ENROLLMENT. 283 00:13:14,672 --> 00:13:16,240 SO THERE'S NOW A DIVISION OF 284 00:13:16,240 --> 00:13:19,310 LABOR WHEN IT COMES TO MINIMAL 285 00:13:19,310 --> 00:13:19,977 REQUIREMENTS OF INFORMED CONSENT 286 00:13:19,977 --> 00:13:23,448 REVIEW DOCUMENTS. 287 00:13:23,448 --> 00:13:27,452 THE IRB IS THERE TO REVIEW 288 00:13:27,452 --> 00:13:28,686 CLINICAL TRIALS WITH OR WITHOUT 289 00:13:28,686 --> 00:13:29,821 GENE THERAPY FOCUSSING ON THE 290 00:13:29,821 --> 00:13:31,255 PROTECTION OF THE STUDY 291 00:13:31,255 --> 00:13:32,156 PARTICIPANTS LOOKING AT THE 292 00:13:32,156 --> 00:13:34,225 RISK, BENEFIT, CONSENT, 293 00:13:34,225 --> 00:13:36,027 COMPENSATION AND THE OTHER 294 00:13:36,027 --> 00:13:40,198 ISSUES WE DISCUSSED. 295 00:13:40,198 --> 00:13:47,405 THE IBC IS REQUIRED TO REVIEW 296 00:13:47,405 --> 00:13:49,006 THE TRIALS BUT THE FOCUS OF THE 297 00:13:49,006 --> 00:13:51,909 IBC IS NOT PROTECTING STUDY 298 00:13:51,909 --> 00:13:54,779 PARTICIPANTS AS A MINIMAL 299 00:13:54,779 --> 00:13:57,482 MANDATE BUT TO PROTECT STAFF, 300 00:13:57,482 --> 00:14:00,651 AND THE PUBLIC FOCUSSING ON 301 00:14:00,651 --> 00:14:03,688 DISINFECTING AND ACCIDENTAL 302 00:14:03,688 --> 00:14:06,691 EXPOSURES AND OCCUPATIONAL 303 00:14:06,691 --> 00:14:06,924 HEALTH. 304 00:14:06,924 --> 00:14:11,796 THOSE ARE ALL REQUIRED 305 00:14:11,796 --> 00:14:16,234 CONSIDERATIONS OF IS THE IBC A 306 00:14:16,234 --> 00:14:20,238 USEFUL DIVISION OF LABOR. 307 00:14:20,238 --> 00:14:24,642 HOWEVER, THESE COMMITTEES AND 308 00:14:24,642 --> 00:14:25,476 THE SERVICE OF THEIR 309 00:14:25,476 --> 00:14:28,246 INSTITUTIONS DON'T HAVE TO BE 310 00:14:28,246 --> 00:14:30,014 COMPLETELY SEPARATED IN THE 311 00:14:30,014 --> 00:14:30,948 WORKS THEY DO. 312 00:14:30,948 --> 00:14:34,519 IRBs MAY OR MAY NOT HAVE EXPERT 313 00:14:34,519 --> 00:14:36,087 MEMBERS FAMILIAR WITH ALL 314 00:14:36,087 --> 00:14:37,922 ASPECTS OF GENETIC ENGINEERING 315 00:14:37,922 --> 00:14:41,025 AND MOLECULAR BIOLOGY. 316 00:14:41,025 --> 00:14:44,695 ADVERSELY, IBC OFTEN HAVE 317 00:14:44,695 --> 00:14:47,131 MEMBERS WITH STRONG INTEREST IN 318 00:14:47,131 --> 00:14:48,800 HUMAN BIO PROTECTION AND ETHICS. 319 00:14:48,800 --> 00:14:50,835 WHEN ONE OF THESE PROTOCOLS 320 00:14:50,835 --> 00:14:53,571 COMES TO AN INSTITUTION THE 321 00:14:53,571 --> 00:14:56,174 INSTITUTIONS MAY REQUEST IBC 322 00:14:56,174 --> 00:14:58,576 REVIEW OF THE ICD AND 323 00:14:58,576 --> 00:15:00,278 PUBLIC-FACING DOCUMENTS. 324 00:15:00,278 --> 00:15:07,285 IRBs CAN REQUEST A CONSULT AND 325 00:15:07,285 --> 00:15:13,891 THEY CAN ATTEND IBC MEETINGS. 326 00:15:13,891 --> 00:15:17,695 WHAT WE DO IN MY DIVISION WE 327 00:15:17,695 --> 00:15:19,397 SOMETIMES HAVE JOURNAL CLUBS AND 328 00:15:19,397 --> 00:15:20,164 SEMINARS AND SHARE KNOWLEDGE ON 329 00:15:20,164 --> 00:15:30,708 NEW TECHNOLOGY AND PUBLICATIONS. 330 00:15:31,242 --> 00:15:32,543 ALONG WITH THE PREVIOUS 331 00:15:32,543 --> 00:15:33,744 REQUIREMENT OF INFORMED CONSENT 332 00:15:33,744 --> 00:15:35,279 REVIEW FROM THE NIH THERE WAS A 333 00:15:35,279 --> 00:15:38,683 LIST OF POINTS TO CONSIDER AND 334 00:15:38,683 --> 00:15:41,319 THESE ARE STILL USEFUL TODAY 335 00:15:41,319 --> 00:15:44,255 WHEN YOU'RE OPENING NEW ICD AND 336 00:15:44,255 --> 00:15:47,325 THINGS TO THINK ABOUT. 337 00:15:47,325 --> 00:15:49,560 IS THE INVESTIGATIONAL NATURE OF 338 00:15:49,560 --> 00:15:53,664 THE PRODUCT PROPERLY DESCRIBED. 339 00:15:53,664 --> 00:15:55,933 IS LONG-TERM FOLLOW-UP 340 00:15:55,933 --> 00:15:56,834 CONSIDERATION DESCRIBED. 341 00:15:56,834 --> 00:16:01,272 ARE THERE REPRODUCTIVE ISSUES. 342 00:16:01,272 --> 00:16:02,540 IS THERE REQUEST FOR AUTOPSY. 343 00:16:02,540 --> 00:16:04,075 WE SEE THAT SOMETIMES. 344 00:16:04,075 --> 00:16:06,077 DEPENDING ON WHICH WAY THE MEDIA 345 00:16:06,077 --> 00:16:10,348 IS GO THERE MAY BE INTEREST IN 346 00:16:10,348 --> 00:16:11,949 MEDIA OF THE PROJECT. 347 00:16:11,949 --> 00:16:13,184 THESE CAN SERVE AS GUIDE POSTS 348 00:16:13,184 --> 00:16:17,021 WHEN REVIEWING THE DUMES. 349 00:16:17,021 --> 00:16:19,390 -- DOCUMENTS. 350 00:16:19,390 --> 00:16:22,293 THE SECOND POINT WAS LONG-TERM 351 00:16:22,293 --> 00:16:22,560 FOLLOW-UP. 352 00:16:22,560 --> 00:16:25,162 FDA HAS ISSUED GUIDANCE FOR 353 00:16:25,162 --> 00:16:27,632 INDUSTRY AND GENE THERAPY. 354 00:16:27,632 --> 00:16:29,433 THE REQUIREMENT FOR INTEGRATION 355 00:16:29,433 --> 00:16:32,436 OF LONG-TERM FOLLOW-UP DEPENDS 356 00:16:32,436 --> 00:16:35,840 ON THE NATURE OF THE PRODUCT. 357 00:16:35,840 --> 00:16:38,476 AND SPECIFICALLY DEPENDENT ON 358 00:16:38,476 --> 00:16:40,011 EXPECTED POTENTIAL RISK OF 359 00:16:40,011 --> 00:16:41,879 DELAYED ADVERSE EVENTS 360 00:16:41,879 --> 00:16:44,248 ASSOCIATED WITH A PARTICULAR 361 00:16:44,248 --> 00:16:48,019 INVESTIGATIONAL PRODUCT. 362 00:16:48,019 --> 00:16:52,189 A 15 YEAR LTFU MAY BE 363 00:16:52,189 --> 00:16:53,791 RECOMMENDED DEPENDING ON RISK 364 00:16:53,791 --> 00:16:57,295 AND DELAYED ADVERSE VNTZ OF A 365 00:16:57,295 --> 00:16:59,997 PARTICULAR CONCERN AND MAY 366 00:16:59,997 --> 00:17:04,235 MODIFY THE CHROMOSOME SUCH AS 367 00:17:04,235 --> 00:17:06,537 GENETIC CONSTRUCTS KNOWN OR GENE 368 00:17:06,537 --> 00:17:08,873 EDITING MODALITIES. 369 00:17:08,873 --> 00:17:10,975 FOR THESE TYPE OF PRODUCT AS A 370 00:17:10,975 --> 00:17:13,711 PRIMARY CONCERN IS MALIGNANT 371 00:17:13,711 --> 00:17:16,147 TRANSFORMATION MEANING A CHANGE 372 00:17:16,147 --> 00:17:18,416 IN THE CHROMOSOME COULD LEAD TO 373 00:17:18,416 --> 00:17:25,590 ACTIVATION OF AN ONO GEEB GENE 374 00:17:25,590 --> 00:17:29,493 AND COULD TRANSFORM CELLS TO 375 00:17:29,493 --> 00:17:30,127 MALIGNANT TRANSFORMATION. 376 00:17:30,127 --> 00:17:32,496 THIS COULD APPEAR LONG AFTER 377 00:17:32,496 --> 00:17:33,731 DOSING AND CONTINUOUS MONITORING 378 00:17:33,731 --> 00:17:36,968 FOR THIS IS OFTEN RECOMMENDED. 379 00:17:36,968 --> 00:17:38,970 THERE ARE ALSO OTHER POTENTIAL 380 00:17:38,970 --> 00:17:41,305 DELAYED ADVERSE EVENTS THAT 381 00:17:41,305 --> 00:17:44,241 COULD EFFECT IMMUNOLOGY OR OTHER 382 00:17:44,241 --> 00:17:47,478 TOXICITIES THAT MAY APPEAR AND 383 00:17:47,478 --> 00:17:48,813 REQUIRE CONSIDERATION DEPENDING 384 00:17:48,813 --> 00:17:49,413 ON THE NATURE OF THE PRODUCT 385 00:17:49,413 --> 00:17:59,590 OVER TIME. 386 00:18:04,428 --> 00:18:06,764 IT MUST HAVE OBSERVATIONS AND 387 00:18:06,764 --> 00:18:08,299 TIME INTERVALS AND STUDY VISIT 388 00:18:08,299 --> 00:18:09,767 CONTACTS AND DETAILS AS TO WHAT 389 00:18:09,767 --> 00:18:15,706 THE CONTACTS WILL INVOLVE. 390 00:18:15,706 --> 00:18:17,174 IT NICE TO BE THOUGHT OF IN 391 00:18:17,174 --> 00:18:20,244 ADVANCE AND EXPLAINED AT THE 392 00:18:20,244 --> 00:18:26,751 TIME OF CONSENT. 393 00:18:26,751 --> 00:18:31,822 IN AGAIN YOU MUST REVISE 394 00:18:31,822 --> 00:18:34,925 INFORMED CONSENT DOCUMENTS NEW 395 00:18:34,925 --> 00:18:39,463 EVENTS WITH THE PRODUCT OR 396 00:18:39,463 --> 00:18:40,231 PROCEDURES THAT CREATES 397 00:18:40,231 --> 00:18:41,365 INTERESTING RESPONSIBILITIES 398 00:18:41,365 --> 00:18:44,268 OVER A 15-YEAR FOLLOW-UP PERIOD 399 00:18:44,268 --> 00:18:47,171 IN TERMS OF REVISING INFORMED 400 00:18:47,171 --> 00:18:48,239 CONSENT AND CONTAINING 401 00:18:48,239 --> 00:18:52,209 INFORMATION TO THE ENROLLED 402 00:18:52,209 --> 00:19:02,386 SUBJECTS. 403 00:19:04,288 --> 00:19:05,556 SO WHAT SHOULD WE CONSIDER IN 404 00:19:05,556 --> 00:19:07,024 LOOKING AT THE CATEGORIES OF 405 00:19:07,024 --> 00:19:08,659 GENE RESEARCH. 406 00:19:08,659 --> 00:19:13,230 I THINK OF HUMAN PRODUCTS BEING 407 00:19:13,230 --> 00:19:15,433 COMPRISED OF TWO COMPONENTS. 408 00:19:15,433 --> 00:19:20,037 ONE IS A TRANS GENE WHICH IS 409 00:19:20,037 --> 00:19:21,605 GENETICALLY ENGINEERED DNA OR 410 00:19:21,605 --> 00:19:24,008 RNA AND ENCODING SOME KIND OF 411 00:19:24,008 --> 00:19:24,542 THERAPEUTIC GENE PRODUCT 412 00:19:24,542 --> 00:19:26,477 PROTEIN. 413 00:19:26,477 --> 00:19:28,546 THE OTHER COMPONENT WOULD BE THE 414 00:19:28,546 --> 00:19:32,216 DELIVERY METHOD OR VEHICLE SUCH 415 00:19:32,216 --> 00:19:35,019 AS THE EX VIVO MANUFACTURER LIKE 416 00:19:35,019 --> 00:19:37,788 A CAR T CELL. 417 00:19:37,788 --> 00:19:41,792 COULD BE A VIRAL VECTOR OR NANO 418 00:19:41,792 --> 00:19:47,231 PARTICLE AND IN THINKING ABOUT 419 00:19:47,231 --> 00:19:56,073 CATEGORIES OF RISK THEY MAY 420 00:19:56,073 --> 00:19:57,608 APPLY TO THE TRANS GENES. 421 00:19:57,608 --> 00:19:58,275 THERE'S A VARIETY OF RISKS THAT 422 00:19:58,275 --> 00:20:04,215 COULD APPLY. 423 00:20:04,215 --> 00:20:06,016 ENCODED PROTEINS MAY INDUCE DOSE 424 00:20:06,016 --> 00:20:12,690 LIMITING TOXICITIES. 425 00:20:12,690 --> 00:20:15,226 WHEN YOU'RE EXPRESSING A 426 00:20:15,226 --> 00:20:16,127 CLOTTING FACTOR TO TREAT 427 00:20:16,127 --> 00:20:17,561 HEMOPHILIA THERE IS GOING TO BE 428 00:20:17,561 --> 00:20:21,932 A THERAPEUTIC WINDOW AND 429 00:20:21,932 --> 00:20:24,835 EXPRESSION BEYOND THAT POINT HAS 430 00:20:24,835 --> 00:20:26,737 POTENTIAL RISK TO LEAD TO ADE 431 00:20:26,737 --> 00:20:35,446 VERSE EVENTS SUCH AS THROMB 432 00:20:35,446 --> 00:20:35,746 THROMBOSIS-. 433 00:20:35,746 --> 00:20:36,347 THERE'S POTENTIAL FOR OTHER 434 00:20:36,347 --> 00:20:37,481 ISSUES SO THAT HAS TO BE 435 00:20:37,481 --> 00:20:37,782 CONSIDERED. 436 00:20:37,782 --> 00:20:39,917 WHEN THE ENCODED PROTEIN IS 437 00:20:39,917 --> 00:20:42,520 CAPABLE OF MODIFYING THE 438 00:20:42,520 --> 00:20:47,591 CHROMOSOME THEN THERE'S OBVIOUS 439 00:20:47,591 --> 00:20:58,068 RISKS TO THIS AND INHERITED 440 00:21:01,172 --> 00:21:07,211 DISEASES AN ESSENTIAL PROTEIN IS 441 00:21:07,211 --> 00:21:08,913 NOT EXPRESSED BECAUSE OF A 442 00:21:08,913 --> 00:21:09,780 GENETIC DEAL EFFECT. 443 00:21:09,780 --> 00:21:15,920 INTRODUCING THAT PROTEIN AS A 444 00:21:15,920 --> 00:21:20,825 NOVEL GENE PRODUCT POSES RISK AS 445 00:21:20,825 --> 00:21:24,662 IDENTIFYING IT TO NON-SELF 446 00:21:24,662 --> 00:21:26,297 LEADING TO IMMUNE REACTION THAT 447 00:21:26,297 --> 00:21:27,364 CAN INTERFERE WITH FUTURE 448 00:21:27,364 --> 00:21:37,074 TREATMENTS. 449 00:21:37,074 --> 00:21:45,683 I NOT BE AN IMPORTANT RISK. 450 00:21:45,683 --> 00:21:47,151 IT INVOLVES MOLECULAR ANALYSIS 451 00:21:47,151 --> 00:21:50,087 OF THE TRANS GENE AND DATA IN 452 00:21:50,087 --> 00:21:51,722 RELEVANT MODELS AND PRIOR 453 00:21:51,722 --> 00:21:54,024 EXPERIENCE WITH THE MOST SIMILAR 454 00:21:54,024 --> 00:22:00,231 PRODUCTS AVAILABLE. 455 00:22:00,231 --> 00:22:02,099 THE OTHER COMPONENT IS THE 456 00:22:02,099 --> 00:22:05,636 DELIVERY METHOD AND VECTOR AND 457 00:22:05,636 --> 00:22:08,839 THOSE MAY HAVE THEIR OWN RISK. 458 00:22:08,839 --> 00:22:12,276 IF THE VECTOR IS AN IMMUNE 459 00:22:12,276 --> 00:22:16,247 EFFECTER CELL IN VIVO THEY'RE 460 00:22:16,247 --> 00:22:20,251 ASSOCIATED WITH CYTOKINE RELEASE 461 00:22:20,251 --> 00:22:23,854 SYNDROME AND NEURO TOXICITY 462 00:22:23,854 --> 00:22:24,221 SYNDROME. 463 00:22:24,221 --> 00:22:26,757 OTHER WELL DESCRIBED POTENTIAL 464 00:22:26,757 --> 00:22:28,225 ADVERSE EVENTS THAT ARE OFTEN 465 00:22:28,225 --> 00:22:29,059 DESCRIBED AS KNOWN RISKS FOR 466 00:22:29,059 --> 00:22:33,397 THESE INTERVENTIONS. 467 00:22:33,397 --> 00:22:39,203 WHEN CELLS ARE MODIFIED EX VIVO 468 00:22:39,203 --> 00:22:41,038 THE CELLS COULD BE MALIGNANT OR 469 00:22:41,038 --> 00:22:43,741 SUBJECT TO TRANSFORMATION 470 00:22:43,741 --> 00:22:44,508 BECAUSE OF GROWTH IN VITRO AND 471 00:22:44,508 --> 00:22:48,012 THAT NEEDS TO BE CONSIDERED AS A 472 00:22:48,012 --> 00:22:49,947 POTENTIAL RISK. 473 00:22:49,947 --> 00:22:52,616 WHEN THE VEHICLE'S AN NANO 474 00:22:52,616 --> 00:22:54,585 PARTICLE DEPENDING ON CLINICAL 475 00:22:54,585 --> 00:22:57,821 EXPERIENCE WITH THAT CART 476 00:22:57,821 --> 00:23:00,157 PARTICLE THE COMPONENTS COULD BE 477 00:23:00,157 --> 00:23:02,726 TOXIC OR IMMUNOGENIC. 478 00:23:02,726 --> 00:23:05,696 THERE'S NEW METHODS OF 479 00:23:05,696 --> 00:23:06,330 DEVELOPING PARTICLES AND 480 00:23:06,330 --> 00:23:08,699 EXCITING NEW TECHNOLOGY BUT THEY 481 00:23:08,699 --> 00:23:09,199 HAVE TO BE EXAMINED FOR 482 00:23:09,199 --> 00:23:18,142 POTENTIAL RISKS. 483 00:23:18,142 --> 00:23:21,178 WHEN THE VICTORY CLASS CAN 484 00:23:21,178 --> 00:23:22,780 MODIFY THE CHROMOSOME THERE'S 485 00:23:22,780 --> 00:23:25,249 ADDITIONAL MUTAGENESIS AND WE 486 00:23:25,249 --> 00:23:26,750 DISCUSSED SOME OF THOSE ASPECTS 487 00:23:26,750 --> 00:23:36,894 ALREADY. 488 00:23:37,695 --> 00:23:39,997 ANOTHER KNOWN CATEGORY IS THE 489 00:23:39,997 --> 00:23:43,867 IMMUNE RESPONSE TO THE VECTOR. 490 00:23:43,867 --> 00:23:47,271 WE SEE GENE THERAPY FOR RARE 491 00:23:47,271 --> 00:23:49,139 INHERITED DISEASE USING THESE 492 00:23:49,139 --> 00:23:52,142 VECTORS WITH A LOT OF PROMISING 493 00:23:52,142 --> 00:23:55,079 ASPECTS BUT ALSO INDUCE IMMUNE 494 00:23:55,079 --> 00:23:55,612 RESPONSES. 495 00:23:55,612 --> 00:23:57,614 AFTER DOSING WHEN AN IMMUNE 496 00:23:57,614 --> 00:24:00,117 RESPONSE DEVELOPS TO THE VECTOR, 497 00:24:00,117 --> 00:24:02,419 THAT CAN INTERFERE WITH 498 00:24:02,419 --> 00:24:03,554 OTHERWISE DESIRABLE APPROACHES 499 00:24:03,554 --> 00:24:07,624 TO RESEARCH SUCH AS A DOSE 500 00:24:07,624 --> 00:24:09,193 ESCALATION STUDY WHERE REPEATED 501 00:24:09,193 --> 00:24:09,793 DOSING IN THIS CASE IS NOT 502 00:24:09,793 --> 00:24:18,002 POSSIBLE. 503 00:24:18,002 --> 00:24:21,071 THAT MAKES IT MORE DIFFICULT TO 504 00:24:21,071 --> 00:24:24,541 ANTICIPATE TOLERATED DOSES AND 505 00:24:24,541 --> 00:24:26,910 IN YOUR INFORMED CONSENT FORM 506 00:24:26,910 --> 00:24:32,249 YOU HAVE TO EXPLAIN WHAT THE 507 00:24:32,249 --> 00:24:35,652 LIMITATIONS ARE AND WHETHER IT'S 508 00:24:35,652 --> 00:24:36,353 INFORMATIVE AND UNDERSTANDABLE 509 00:24:36,353 --> 00:24:38,555 TO THE READING AUDIENCE. 510 00:24:38,555 --> 00:24:43,660 IMPORTANTLY, AFTER DOSING WITH A 511 00:24:43,660 --> 00:24:45,863 PARTICULAR SUBJECT WHO THAT 512 00:24:45,863 --> 00:24:48,032 IMMUNE RESPONSE IS EXPECTED TO 513 00:24:48,032 --> 00:24:49,800 BE REFRACTORY TO SUBSEQUENT 514 00:24:49,800 --> 00:24:56,273 DOSING WITH A SIMILAR PRODUCT. 515 00:24:56,273 --> 00:24:58,108 A LOT OF RESEARCH IS TRYING TO 516 00:24:58,108 --> 00:25:03,247 ADDRESS THESE ISSUES AND MAKE 517 00:25:03,247 --> 00:25:06,417 THEM LESS OF A PROBLEM BUT THE 518 00:25:06,417 --> 00:25:11,021 INABILITY TO REDOSE WITH THE 519 00:25:11,021 --> 00:25:15,726 ITEMS DUE TO IMMUNE RESPONSES. 520 00:25:15,726 --> 00:25:17,394 THERE'S BEEN NICE AND 521 00:25:17,394 --> 00:25:20,264 INFORMATIVE SEMINARS SPONSORED 522 00:25:20,264 --> 00:25:21,632 BY DIFFERENT AGENCIES ADDRESSING 523 00:25:21,632 --> 00:25:24,802 POTENTIAL ADVERSE EFFECTS. 524 00:25:24,802 --> 00:25:28,105 USUALLY ASSOCIATED WITH HIGH 525 00:25:28,105 --> 00:25:30,841 DOSES THAT ARE USED FOR CERTAIN 526 00:25:30,841 --> 00:25:32,042 INDICATIONS. 527 00:25:32,042 --> 00:25:40,250 AND THESE TOXICITIES INCLUDE 528 00:25:40,250 --> 00:25:43,087 HEPATOTOXICITIES AND THE DOSE 529 00:25:43,087 --> 00:25:45,789 AND RISKS HAVE TO BE CONSIDERED 530 00:25:45,789 --> 00:25:55,299 AND EXPLAINED CAREFULLY. 531 00:25:55,299 --> 00:25:59,203 SO THOSE NOW QUALIFY AS THE 532 00:25:59,203 --> 00:25:59,837 OLDER TECHNOLOGIES. 533 00:25:59,837 --> 00:26:02,172 WE NOW HAVE NEW CATEGORIES AND 534 00:26:02,172 --> 00:26:03,907 MODALITIES COMING ONLINE AND 535 00:26:03,907 --> 00:26:07,411 APPEARING IN THE CLINIC AND 536 00:26:07,411 --> 00:26:08,011 POSSIBLY BEING CONSIDERED FOR 537 00:26:08,011 --> 00:26:14,518 FDA APPROVAL. 538 00:26:14,518 --> 00:26:16,620 THESE ARE CRISPR AND RELATED 539 00:26:16,620 --> 00:26:18,288 GENE EDITING PROJECTS. 540 00:26:18,288 --> 00:26:21,158 AS A SIGN OF THE TIMES WE SAW AN 541 00:26:21,158 --> 00:26:22,126 ANNOUNCEMENT IN THE FEDERAL 542 00:26:22,126 --> 00:26:23,961 REGISTER ABOUT PROPOSED CHANGING 543 00:26:23,961 --> 00:26:34,338 TO THE NIH GUIDELINES. 544 00:26:35,172 --> 00:26:37,307 MOST ARE NOT RELATED TO 545 00:26:37,307 --> 00:26:40,944 COLLABORATES AND INFORMED 546 00:26:40,944 --> 00:26:44,081 CONSENT AND THERE'S A POPULATION 547 00:26:44,081 --> 00:26:47,117 TO CHANGE HUMAN GENE RESEARCH TO 548 00:26:47,117 --> 00:26:48,685 HAVE TECHNIQUES NOT USUALLY 549 00:26:48,685 --> 00:26:49,286 COVERED. 550 00:26:49,286 --> 00:26:52,222 THIS REFLECTS THE GROWING 551 00:26:52,222 --> 00:26:52,890 REALITY OF SEEING THESE IN THE 552 00:26:52,890 --> 00:27:00,063 CLINIC. 553 00:27:00,063 --> 00:27:03,033 GENE EDITING IS A CATEGORY OF 554 00:27:03,033 --> 00:27:05,969 INTERVENTION THAT REWRITES THE 555 00:27:05,969 --> 00:27:06,570 GENETIC CODE. 556 00:27:06,570 --> 00:27:09,072 MOST FAMOUSLY THAT MEANS CRISPR 557 00:27:09,072 --> 00:27:09,673 AND RELATED TECHNOLOGIES. 558 00:27:09,673 --> 00:27:13,977 THEY HAVE THE TO PRECISELY ADD 559 00:27:13,977 --> 00:27:16,747 AND DELETE GENETIC INFORMATION 560 00:27:16,747 --> 00:27:17,915 FROM THE CHROMOSOME. 561 00:27:17,915 --> 00:27:25,189 AS MENTIONED, CERTAIN APPROACHES 562 00:27:25,189 --> 00:27:27,491 DO NOT QUALIFY UNDER THE CURRENT 563 00:27:27,491 --> 00:27:28,592 NIH GUIDELINES BUT IF THE 564 00:27:28,592 --> 00:27:36,066 PROPOSED CHANGES ARE IMPLEMENT 565 00:27:36,066 --> 00:27:40,270 ED AND WHEN WE TALK ABOUT THE 566 00:27:40,270 --> 00:27:42,940 CONCEPT WE HAVE TO MENTION 567 00:27:42,940 --> 00:27:45,342 SOMATIC CELL EDITING MEANS 568 00:27:45,342 --> 00:27:46,577 MODIFYING CELLS FOR THERAPEUTIC 569 00:27:46,577 --> 00:27:50,080 PURPOSES IN A HUMAN SUBJECT NOT 570 00:27:50,080 --> 00:27:51,715 ENGAGING IN INTENTIONAL 571 00:27:51,715 --> 00:27:53,183 MODIFICATION OF GERM LINE CELLS 572 00:27:53,183 --> 00:27:57,087 THAT WOULD LEAD TO INTENTIONAL 573 00:27:57,087 --> 00:27:58,555 HERITABLE MODIFICATIONS PASSED 574 00:27:58,555 --> 00:28:00,624 ON TO HUMAN GENERATIONS. 575 00:28:00,624 --> 00:28:02,693 THAT'S NOT HAPPENING IN ANY 576 00:28:02,693 --> 00:28:03,594 CLINICAL TRIALS AND WE'RE NOT 577 00:28:03,594 --> 00:28:06,330 GOING TO TALK ABOUT IT HERE BUT 578 00:28:06,330 --> 00:28:06,897 IT'S THE FOCUS OF A LOT OF 579 00:28:06,897 --> 00:28:10,901 OPINION. 580 00:28:10,901 --> 00:28:16,340 SO WHEN WE LOOK AT THIS CATEGORY 581 00:28:16,340 --> 00:28:20,344 OF INTERVENTION, IT WOULD 582 00:28:20,344 --> 00:28:22,312 INCLUDE THE INTERVENTIONS THAT 583 00:28:22,312 --> 00:28:28,252 MODIFY THE DNA BASED ON PRIME 584 00:28:28,252 --> 00:28:29,519 EDITORS RISKS WOULD INCLUDE 585 00:28:29,519 --> 00:28:32,122 ERRORS THAT RESULT IN OFF-TARGET 586 00:28:32,122 --> 00:28:33,824 EDITING MEANING CHANGING THE 587 00:28:33,824 --> 00:28:35,125 GENETIC CODE IN A PLACE OUTSIDE 588 00:28:35,125 --> 00:28:39,730 OF WHERE YOU WANTED TO DO IT. 589 00:28:39,730 --> 00:28:41,598 UNWANTED DELETIONS AND POTENTIAL 590 00:28:41,598 --> 00:28:45,269 TRANS LOCATIONS OF CHROMOSOMAL 591 00:28:45,269 --> 00:28:45,435 DNA. 592 00:28:45,435 --> 00:28:47,104 WE CURRENTLY HAVE VERY GOOD 593 00:28:47,104 --> 00:28:52,709 METHODS FOR DETECTING ERRORS BUT 594 00:28:52,709 --> 00:28:55,445 THE LIMIT OF SENSITIVITY ARE 595 00:28:55,445 --> 00:28:57,214 SOMETIMES DIFFICULT TO DEFINE IN 596 00:28:57,214 --> 00:28:59,082 THE CONTEXT OF A CLINICAL TRIAL 597 00:28:59,082 --> 00:29:00,951 AND WHAT THE CLINICALLY 598 00:29:00,951 --> 00:29:04,254 ACCEPTABLE ERROR RATE IS 599 00:29:04,254 --> 00:29:06,923 DIFFICULT TO DEFINE. 600 00:29:06,923 --> 00:29:09,459 THERE'S UNDETERMINED AREA 601 00:29:09,459 --> 00:29:12,229 BETWEEN WHAT IS ACCEPTABLE AND 602 00:29:12,229 --> 00:29:17,968 DEFINITIVELY DETECTABLE. 603 00:29:17,968 --> 00:29:21,138 THE DIFFERENT TYPES OF APPROACH 604 00:29:21,138 --> 00:29:24,741 IN VIVO AND EX VIVO WHEN THE EX 605 00:29:24,741 --> 00:29:29,212 VIVO APPLICATION IS USED, CELLS 606 00:29:29,212 --> 00:29:34,451 ARE MODIFIED IN THE LABORATORY, 607 00:29:34,451 --> 00:29:37,654 PETRI DISH UNDER THE CONTROLLED 608 00:29:37,654 --> 00:29:39,356 CONDITIONS IT'S EASIER TO 609 00:29:39,356 --> 00:29:40,257 IDENTIFY ERRORS. 610 00:29:40,257 --> 00:29:45,128 THERE'S A POTENTIAL CONCERN 611 00:29:45,128 --> 00:29:51,635 THERE COULD BE EXPANSION OF 612 00:29:51,635 --> 00:29:53,437 CELLS WITH INAPPROPRIATE 613 00:29:53,437 --> 00:29:55,739 REPLICATION BECAUSE OF SOME ONYO 614 00:29:55,739 --> 00:29:56,273 GENIC EVENT. 615 00:29:56,273 --> 00:29:58,008 THAT HAS TO BE CONSIDERED AS A 616 00:29:58,008 --> 00:29:58,608 POTENTIAL RISK. 617 00:29:58,608 --> 00:30:04,247 GENE EDITING MAY ALSO BE 618 00:30:04,247 --> 00:30:06,116 PERFORMED IN VIVO WHERE THE 619 00:30:06,116 --> 00:30:10,187 MACHINERY IS INTRODUCED TO THE 620 00:30:10,187 --> 00:30:11,555 NANO PARTICLE. 621 00:30:11,555 --> 00:30:16,026 IT'S MORE DIFFICULT TO TRACK THE 622 00:30:16,026 --> 00:30:17,394 SPECIFIC ERRORS THAT MAY BE 623 00:30:17,394 --> 00:30:18,462 OCCURRING IN VIVO. 624 00:30:18,462 --> 00:30:24,101 SO THIS GREATER UNCERTAINTY IN 625 00:30:24,101 --> 00:30:29,206 THAT CASE AND THERE WON'T BE 626 00:30:29,206 --> 00:30:33,610 INTENTIONAL MODIFICATION AND THE 627 00:30:33,610 --> 00:30:35,145 POTENTIAL IN VIVO DELIVERY FOR 628 00:30:35,145 --> 00:30:36,146 GERM LINE MODIFICATION THROUGH A 629 00:30:36,146 --> 00:30:39,149 VARIETY OF TECHNIQUES, 630 00:30:39,149 --> 00:30:40,250 THEORETICAL APPROACHES NEEDS TO 631 00:30:40,250 --> 00:30:43,754 BE CONSIDERED. 632 00:30:43,754 --> 00:30:47,491 OF COURSE, PRECLINICAL DESIGN OF 633 00:30:47,491 --> 00:30:50,894 THESE CLINICAL TRIALS IS MEANT 634 00:30:50,894 --> 00:30:51,928 TO ADEQUATELY ADDRESS THESE 635 00:30:51,928 --> 00:30:53,330 POINTS BUT IT'S SOMETHING THAT 636 00:30:53,330 --> 00:30:54,898 THE IRB'S NEED TO TAKE INTO 637 00:30:54,898 --> 00:30:57,501 CONSIDERATION. 638 00:30:57,501 --> 00:31:00,303 IT SHOULD BE PART OF INFORMED 639 00:31:00,303 --> 00:31:06,209 CONSENT WHEN APPROPRIATE. 640 00:31:06,209 --> 00:31:08,278 IN DRAFT GUIDANCE FROM FDA, WE 641 00:31:08,278 --> 00:31:10,180 SEE PRIOR TO ENROLLING SUBJECTS 642 00:31:10,180 --> 00:31:14,084 SHOULD BE ASKED TO PROVIDE 643 00:31:14,084 --> 00:31:19,122 VOLUNTARY INFORMED CONSENT TO 644 00:31:19,122 --> 00:31:19,723 LONG-TERM FOLLOW-UP. 645 00:31:19,723 --> 00:31:23,026 SO IF THERE'S A DOSING PROTOCOL 646 00:31:23,026 --> 00:31:25,495 AND LONG-TERM FOLLOW-UP PROTOCOL 647 00:31:25,495 --> 00:31:26,863 AND CONSENT TO THE LONG-TERM 648 00:31:26,863 --> 00:31:30,100 FOLLOW-UP SHOULD PROCEED 649 00:31:30,100 --> 00:31:31,134 ENROLLMENT, THERE'S LOGISTICAL 650 00:31:31,134 --> 00:31:33,870 QUESTIONS TO CONSIDER ABOUT HOW 651 00:31:33,870 --> 00:31:35,071 YOU DO YOUR INFORMED CONSENT 652 00:31:35,071 --> 00:31:38,742 PROCESS TO COVER ALL YOUR BASES 653 00:31:38,742 --> 00:31:39,443 IN ADVANCE. 654 00:31:39,443 --> 00:31:41,211 THERE'S A LOT OF ACCEPTABLE 655 00:31:41,211 --> 00:31:42,078 APPROACHES BUT SOMETHING TO 656 00:31:42,078 --> 00:31:42,712 THINK ABOUT WHILE PLANNING YOUR 657 00:31:42,712 --> 00:31:53,023 INFORMED CONSENT. 658 00:31:55,292 --> 00:31:57,727 WE CAN SEE PATIENT PERSPECTIVES 659 00:31:57,727 --> 00:32:01,832 ARE REALLY IMPORTANT. 660 00:32:01,832 --> 00:32:07,337 THERE'S PATIENT ADVOCACY GROUPS 661 00:32:07,337 --> 00:32:09,139 AND PEOPLE ENROLLED PROVIDING 662 00:32:09,139 --> 00:32:10,507 INPUT AND IT'S A VALUABLE SOURCE 663 00:32:10,507 --> 00:32:11,408 OF INFORMATION. 664 00:32:11,408 --> 00:32:14,110 I'VE HAD THE PRIVILEGE OF 665 00:32:14,110 --> 00:32:16,179 SPEAKING TO PATIENT ADVOCATES 666 00:32:16,179 --> 00:32:18,081 AND CLINICAL TRIAL PARTICIPANTS 667 00:32:18,081 --> 00:32:19,783 AND ROUNDTABLES AND DIFFERENT 668 00:32:19,783 --> 00:32:23,286 CONFERENCES AND IT'S ALWAYS 669 00:32:23,286 --> 00:32:27,224 VALUABLE SOURCE OF END POINT. 670 00:32:27,224 --> 00:32:32,062 COLLATING SOME OF THE ADVICE 671 00:32:32,062 --> 00:32:40,270 FROM THE GROUPS WE HEAR INFORMED 672 00:32:40,270 --> 00:32:43,073 CONSENT THERAPY IS TOO LONG AND 673 00:32:43,073 --> 00:32:45,141 IT'S AN ONGOING ISSUE WHEN 674 00:32:45,141 --> 00:32:51,114 THERE'S A LONG BENEFITING AND 675 00:32:51,114 --> 00:32:57,287 HOW DO WE ADDRESS WHAT NEEDS TO 676 00:32:57,287 --> 00:33:01,091 BE ADDRESSED IN A MANAGEABLE 677 00:33:01,091 --> 00:33:01,291 SCOPE. 678 00:33:01,291 --> 00:33:03,059 THE SCIENCE OF GENE TRANSFER IS 679 00:33:03,059 --> 00:33:03,660 DIFFICULT TO UNDERSTAND AND 680 00:33:03,660 --> 00:33:08,265 DIFFICULT FOR ALL OF US TO KEEP 681 00:33:08,265 --> 00:33:10,700 UP WITH IT WHEN WE'RE 682 00:33:10,700 --> 00:33:13,103 PROFESSIONALS AND EXPLAINING IT 683 00:33:13,103 --> 00:33:17,073 TO A LAY AUDIENCE IS AN ART OF 684 00:33:17,073 --> 00:33:17,741 INTERPRETATION THAT REQUIRES A 685 00:33:17,741 --> 00:33:19,109 LOT OF ATTENTION AND IS A SOURCE 686 00:33:19,109 --> 00:33:29,586 OF CONCERN FOR PARTICIPANTS. 687 00:33:30,153 --> 00:33:36,259 WHEN IT COMES TO NON-EXPERTS 688 00:33:36,259 --> 00:33:38,295 THEY EXPRESS DIFFICULTY 689 00:33:38,295 --> 00:33:48,838 ASSESSING AND IN AN ERROR WHERE 690 00:33:56,313 --> 00:33:58,481 THERE'S AMOUNT OF DISTRUST IN 691 00:33:58,481 --> 00:34:00,650 MEDICINE AND IRBs CAN PLAY AN 692 00:34:00,650 --> 00:34:01,851 IMPORTANT ROLE IN MAINTAINING 693 00:34:01,851 --> 00:34:02,786 CONFIDENCE IN THE PROCESS AND 694 00:34:02,786 --> 00:34:12,629 LISTENING TO CONCERNS. 695 00:34:12,629 --> 00:34:14,297 ALONG THIS LINE I WAS INTERESTED 696 00:34:14,297 --> 00:34:17,000 TO READ THIS PARTICULAR PAPER 697 00:34:17,000 --> 00:34:17,634 CALLED IMPROVING PATIENT 698 00:34:17,634 --> 00:34:19,469 INFORMED CONSENT FOR HEMOPHILIA 699 00:34:19,469 --> 00:34:24,941 GENE THERAPY CASE FOR CHANGE BY 700 00:34:24,941 --> 00:34:26,943 PHYSICIAN PATIENT ADVOCATES AND 701 00:34:26,943 --> 00:34:28,478 IDENTIFYING POINTS OF CONCERN 702 00:34:28,478 --> 00:34:33,249 AND ALSO CONSTRUCTIVE ADVICE. 703 00:34:33,249 --> 00:34:36,086 SO IT'S WORTH LOOKING UP FOR 704 00:34:36,086 --> 00:34:46,396 THOSE INTERESTED. 705 00:34:47,397 --> 00:34:52,669 AND IDENTIFY INFORMATION OVER 706 00:34:52,669 --> 00:34:53,069 LOAD. 707 00:34:53,069 --> 00:34:55,505 IT'S A RISK WHEN SOMEONE LIKE 708 00:34:55,505 --> 00:34:56,740 MYSELF GETS INTERESTED IN 709 00:34:56,740 --> 00:35:00,977 READING ALL ASPECTS OF MOLECULAR 710 00:35:00,977 --> 00:35:01,845 INTERVENTION AND HAS MORE 711 00:35:01,845 --> 00:35:03,913 INFORMATION THAN IS USEFUL. 712 00:35:03,913 --> 00:35:06,249 WE NEED TO THINK ABOUT AVOIDING 713 00:35:06,249 --> 00:35:15,091 THAT PROBLEM. 714 00:35:15,091 --> 00:35:18,094 FOR GENE THERAPY THERE MAY BE 715 00:35:18,094 --> 00:35:19,329 MISCONCEPTION AND DIFFICULTY 716 00:35:19,329 --> 00:35:20,830 DRAWING THE LINE BETWEEN 717 00:35:20,830 --> 00:35:21,598 RESEARCH AND TREATMENT AND WITH 718 00:35:21,598 --> 00:35:26,102 THE BEST OF INTENTIONS IT'S AN 719 00:35:26,102 --> 00:35:31,274 ONGOING TENSION AND IDENTIFIED 720 00:35:31,274 --> 00:35:33,543 IN THE PAPER AS POTENTIAL POINT 721 00:35:33,543 --> 00:35:34,911 OF CONFUSION FOR SUBJECTS 722 00:35:34,911 --> 00:35:45,321 CONSIDERING ENROLLMENT. 723 00:35:47,323 --> 00:35:49,592 THERAPEUTIC OPTIMISM AND HYPE 724 00:35:49,592 --> 00:35:55,965 AND WE WANT INTERVENTIONS TO 725 00:35:55,965 --> 00:35:58,735 SUCCEED AND ARE WE PROVIDING 726 00:35:58,735 --> 00:35:59,302 REALISTIC ASSESSMENTS OF 727 00:35:59,302 --> 00:36:07,877 POTENTIAL BENEFITS AND RISKS. 728 00:36:07,877 --> 00:36:08,578 I QUOTED THIS PARTICULAR 729 00:36:08,578 --> 00:36:10,547 STATEMENT BECAUSE I LIKE THE 730 00:36:10,547 --> 00:36:11,781 WORDING. 731 00:36:11,781 --> 00:36:13,316 PATIENTS DESIRE FOR IMPROVEMENT 732 00:36:13,316 --> 00:36:16,019 AND HEALTH-RELATED QUALITY OF 733 00:36:16,019 --> 00:36:20,223 LIFE IN FEASIBLY DESPERATE 734 00:36:20,223 --> 00:36:21,324 MEDICALLY CIRCUMSTANCES CAN 735 00:36:21,324 --> 00:36:22,792 UNDERMINE THEIR DECISIONAL 736 00:36:22,792 --> 00:36:23,059 CAPACITY. 737 00:36:23,059 --> 00:36:30,100 IN OTHER WORDS, WHAT QUALITY OF 738 00:36:30,100 --> 00:36:37,874 LIFE IS SO BAD IS DECISION 739 00:36:37,874 --> 00:36:39,309 IMPAIRED AND HOW DO IRB'S 740 00:36:39,309 --> 00:36:45,315 ACCOUNT FOR THAT AS PART OF THE 741 00:36:45,315 --> 00:36:51,788 INFORMED CONSENT PROCESS. 742 00:36:51,788 --> 00:36:54,124 IT'S IN IMPORTANT QUESTION AND 743 00:36:54,124 --> 00:36:57,560 MORE VISUAL AIDS AS PART OF THE 744 00:36:57,560 --> 00:36:58,194 INFORMED CONSENT DOCUMENTATION. 745 00:36:58,194 --> 00:37:00,730 SOME TYPE OF FREQUENTLY ASKED 746 00:37:00,730 --> 00:37:01,664 QUESTION LIST FOR PATIENT 747 00:37:01,664 --> 00:37:04,501 QUESTIONS AND CONCERNS AND 748 00:37:04,501 --> 00:37:08,238 DEVELOPMENT OF STANDARDIZED 749 00:37:08,238 --> 00:37:08,805 LEXICONS FOR PREFERRED 750 00:37:08,805 --> 00:37:09,773 TERMINOLOGY THEY'RE PROBABLY 751 00:37:09,773 --> 00:37:10,840 DIFFERENT FOR DIFFERENT 752 00:37:10,840 --> 00:37:11,474 POPULATIONS BUT USEFUL FOR THE 753 00:37:11,474 --> 00:37:16,946 FIELD IN GENERAL. 754 00:37:16,946 --> 00:37:21,317 SO WHEN WE THINK ABOUT 755 00:37:21,317 --> 00:37:24,220 INFORMATION OVERLOAD, HOW DO YOU 756 00:37:24,220 --> 00:37:25,922 SEPARATE SIGNAL FROM NOISE. 757 00:37:25,922 --> 00:37:30,093 WHEN WE TALK ABOUT DETAILED 758 00:37:30,093 --> 00:37:32,262 SPECULATIVE RISK ASSESSMENT, 759 00:37:32,262 --> 00:37:33,163 TECHNICAL, MOLECULAR INFORMATION 760 00:37:33,163 --> 00:37:34,864 I DOVE INTO THE FIRST LEVEL OF 761 00:37:34,864 --> 00:37:40,103 THAT BUT THERE'S MANY MORE 762 00:37:40,103 --> 00:37:44,274 LAYERS YOU COULD GET INTO 763 00:37:44,274 --> 00:37:44,941 COMPREHENSIVE MEDICAL ANALYSIS 764 00:37:44,941 --> 00:37:48,077 OR ALL PARTS OF DUE DILIGENCE. 765 00:37:48,077 --> 00:37:53,850 THE IBC REGULATORS AND AUTHORS 766 00:37:53,850 --> 00:37:55,385 THIS SHOULD BE PART OF THEIR 767 00:37:55,385 --> 00:37:57,654 DISCUSSION DURING PREPARATION. 768 00:37:57,654 --> 00:37:58,421 WHEN IT COMES TO THE INFORMED 769 00:37:58,421 --> 00:38:00,857 CONSENT PROCESS WE NEED A FILTER 770 00:38:00,857 --> 00:38:03,593 TO AVOID THE INFORMATION 771 00:38:03,593 --> 00:38:04,260 OVERLOAD. 772 00:38:04,260 --> 00:38:05,895 THERE SHOULD BE A FOCUS ON PLAIN 773 00:38:05,895 --> 00:38:08,264 LANGUAGE AND INFORMATION THAT IS 774 00:38:08,264 --> 00:38:13,336 LIKELY TO AFFECT WILLINGNESS TO 775 00:38:13,336 --> 00:38:13,837 PARTICIPATE. 776 00:38:13,837 --> 00:38:14,804 WE CAN STILL HAVE TECHNICAL 777 00:38:14,804 --> 00:38:16,272 INFORMATION AVAILABLE FOR 778 00:38:16,272 --> 00:38:19,876 SUBJECTS WHO ASK AND SOME IN 779 00:38:19,876 --> 00:38:23,279 RARE DISEASE THE SUBJECTS ARE 780 00:38:23,279 --> 00:38:26,850 SOMETIMES EXPERTS THEMSELVES AND 781 00:38:26,850 --> 00:38:28,017 THAT'S WONDERFUL BUT THE PROCESS 782 00:38:28,017 --> 00:38:31,454 HAS TO ALLOW FOR SUBJECTS WHO 783 00:38:31,454 --> 00:38:36,092 ARE LESS WELL INFORMED AND NOT 784 00:38:36,092 --> 00:38:40,263 NECESSARILY IN A POSITION TO 785 00:38:40,263 --> 00:38:50,807 READ AND NEXT IS CONSIDERATION 786 00:39:01,584 --> 00:39:03,019 OF WHAT MANY OF US CONSIDER TO 787 00:39:03,019 --> 00:39:08,892 BE UNSOLVED PROBLEMS IN THIS 788 00:39:08,892 --> 00:39:12,095 AREA. 789 00:39:12,095 --> 00:39:15,598 SO THESE ARE ISSUES RELATED TO 790 00:39:15,598 --> 00:39:22,205 SHEDDING AND COMMUNITY RISK. 791 00:39:22,205 --> 00:39:23,539 FOR SOME THE MODIFIED OBJECTS 792 00:39:23,539 --> 00:39:26,209 ARE EXPECTED TO BE SHED FROM 793 00:39:26,209 --> 00:39:32,248 INJECTION SITES OR BODY FLUIDS. 794 00:39:32,248 --> 00:39:36,085 SO CURRENT FDA GUIDANCE 795 00:39:36,085 --> 00:39:41,958 CONSIDERING RISK OF TRANSMISSION 796 00:39:41,958 --> 00:39:44,761 TO OTHER PEOPLE AND NON 797 00:39:44,761 --> 00:39:49,966 PARTICIPANTS IS OFTEN EXTREMELY 798 00:39:49,966 --> 00:39:53,436 LOW PROBABILITY AND A TRADE-OFF 799 00:39:53,436 --> 00:39:54,904 AGAIN RISK AND INFLAMMATION. 800 00:39:54,904 --> 00:39:58,107 EXPOSURE TO INTIMATE CONTACT OF 801 00:39:58,107 --> 00:40:03,546 THE PUBLIC COULD IMPLY HARM TO 802 00:40:03,546 --> 00:40:13,756 THE GROUPS. 803 00:40:15,658 --> 00:40:18,094 WHEN ONE SIBLING RECEIVES A GENE 804 00:40:18,094 --> 00:40:22,365 THERAPY WITH AN AAV VECTOR AND 805 00:40:22,365 --> 00:40:24,334 MAY BE SHEDDING AND MAY POSSIBLY 806 00:40:24,334 --> 00:40:25,802 EXPOSE HOUSEHOLD MEMBERS TO THE 807 00:40:25,802 --> 00:40:28,705 SHED VECTOR, IS THERE A RISK IS 808 00:40:28,705 --> 00:40:33,743 THAT A SIBLING MAY BE EXPOSED 809 00:40:33,743 --> 00:40:35,478 AND THEN BE INELIGIBLE FOR 810 00:40:35,478 --> 00:40:42,652 TREATMENT IN THE FUTURE? 811 00:40:42,652 --> 00:40:46,756 THERE HAS TO BE A REALISTIC RISK 812 00:40:46,756 --> 00:40:51,728 ASSESSMENT AND ADVICE GIVEN TO 813 00:40:51,728 --> 00:40:52,261 SUBJECTS. 814 00:40:52,261 --> 00:40:58,735 THERE'S OTHER THEORETICAL RISK 815 00:40:58,735 --> 00:41:00,203 WITH EXPOSURE TO MATERIALS AND 816 00:41:00,203 --> 00:41:01,637 THEY SOMETIMES PROVIDE 817 00:41:01,637 --> 00:41:03,673 INSTRUCTIONS FOR PARTICIPANTS. 818 00:41:03,673 --> 00:41:04,741 THOSE ARE PARTICIPANT-FACING 819 00:41:04,741 --> 00:41:05,008 DOCUMENTS. 820 00:41:05,008 --> 00:41:11,748 THEY MAY BE REVIEWED BY THE IRB 821 00:41:11,748 --> 00:41:13,916 BUT ALSO LOOK LIKE HAZARD REVIEW 822 00:41:13,916 --> 00:41:15,351 DOCUMENTS SO MAY BE REVIEWED BY 823 00:41:15,351 --> 00:41:18,454 THE IBC. 824 00:41:18,454 --> 00:41:20,823 THE REVIEW MAY NOT BE MANDATED 825 00:41:20,823 --> 00:41:23,960 DEPENDING ON HOW YOU READ 826 00:41:23,960 --> 00:41:25,795 CERTAIN GUIDANCES BUT LIKELY 827 00:41:25,795 --> 00:41:26,662 THEY HAVE COMPLIMENTARY VIEW 828 00:41:26,662 --> 00:41:27,997 POINTS ON THE DOCUMENTS IN TERMS 829 00:41:27,997 --> 00:41:32,602 OF DUE DILIGENCE BOTH COMMITTEES 830 00:41:32,602 --> 00:41:38,207 MAY BE INVOLVED IN REVIEW. 831 00:41:38,207 --> 00:41:40,276 THE SECRETARY'S ADVISORY 832 00:41:40,276 --> 00:41:42,245 COMMITTEE ON HUMAN RESEARCH 833 00:41:42,245 --> 00:41:47,750 PROTECTION, SACHRP HAS ADVISE. 834 00:41:47,750 --> 00:41:49,919 THEY ADVISE IRBs MAY CONSIDER 835 00:41:49,919 --> 00:41:52,655 RISK TO NON SUBJECT AS 836 00:41:52,655 --> 00:41:53,856 THIRD-PARTY RISK. 837 00:41:53,856 --> 00:41:56,325 ALSO WHILE EMPHASIZING A NEED TO 838 00:41:56,325 --> 00:41:58,428 AVOID UNNECESSARY OR DUPLICATIVE 839 00:41:58,428 --> 00:42:00,096 REVIEWS OF SAFETY 840 00:42:00,096 --> 00:42:06,069 CONSIDERATIONS. 841 00:42:06,069 --> 00:42:07,537 THIS ADVISE HIGHLIGHTS 842 00:42:07,537 --> 00:42:08,171 PARTICULAR CONSIDERATIONS 843 00:42:08,171 --> 00:42:10,606 RELATED TO THE RISK SUCH AS THE 844 00:42:10,606 --> 00:42:13,309 PROBABILITY AND FORESEEABILITY 845 00:42:13,309 --> 00:42:16,045 AND MAGNITUDE OF A RISK. 846 00:42:16,045 --> 00:42:17,313 THOSE CATEGORIES ARE REALLY 847 00:42:17,313 --> 00:42:19,482 USING IN GENERAL WHEN WE TALK 848 00:42:19,482 --> 00:42:25,955 ABOUT ALL THESE RISK ASSESSMENTS 849 00:42:25,955 --> 00:42:27,123 BECAUSE EACH OF THESE FACTORS 850 00:42:27,123 --> 00:42:30,793 PLAYS A ROLE IN WHETHER OR NOT 851 00:42:30,793 --> 00:42:33,029 WE SHOULD SPEND TIME DURING THE 852 00:42:33,029 --> 00:42:33,830 CONSENT PROCESS IN ADDRESSING 853 00:42:33,830 --> 00:42:42,738 THE ISSUES. 854 00:42:42,738 --> 00:42:44,073 OTHER ISSUE THAT MAY BE 855 00:42:44,073 --> 00:42:48,111 CONSIDERED UNRESOLVED IS CONSENT 856 00:42:48,111 --> 00:42:52,248 AND LONG-TERM FOLLOW-UP. 857 00:42:52,248 --> 00:42:55,751 WHEN SUBJECTS ARE UNDER AGE 858 00:42:55,751 --> 00:42:58,654 CHILDREN MAY BE ENROLLED UP 859 00:42:58,654 --> 00:42:59,589 CLINICAL TRIALS WITH PLANNED 860 00:42:59,589 --> 00:42:59,856 FOLLOW-UP. 861 00:42:59,856 --> 00:43:04,527 IF A CHILD IS OLD ENOUGH TO 862 00:43:04,527 --> 00:43:08,931 UNDERSTAND THE PROCESS THEN 863 00:43:08,931 --> 00:43:10,032 ASSENT MAY BE REQUIRED BUT AT 864 00:43:10,032 --> 00:43:10,933 WHEN THEY'RE YOUNG IT WON'T 865 00:43:10,933 --> 00:43:16,339 HAPPEN AT THE TIME OF DOSING. 866 00:43:16,339 --> 00:43:18,474 HOWEVER THEY'RE ENROLLED IN A 867 00:43:18,474 --> 00:43:20,276 LONG-TERM FOLLOW-UP FOR 15 868 00:43:20,276 --> 00:43:20,476 YEARS. 869 00:43:20,476 --> 00:43:23,179 AT WHAT AGE ARE ASSENT AND 870 00:43:23,179 --> 00:43:25,648 REASCENT BE RECOMMENDED SHOULD 871 00:43:25,648 --> 00:43:27,683 IT BE WHEN A CHILD REACH A 872 00:43:27,683 --> 00:43:29,886 CERTAIN AGE OR PARTICIPATE IN 873 00:43:29,886 --> 00:43:32,522 THE LONG-TERM FOLLOW-UP OR FOR 874 00:43:32,522 --> 00:43:40,263 SOME TYPES OF INTERVENTIONS FOR 875 00:43:40,263 --> 00:43:40,530 REDOSING. 876 00:43:40,530 --> 00:43:42,565 OVER AN EXTENDED TIME PERIOD IS 877 00:43:42,565 --> 00:43:51,140 IT RECOMMENDED TO HAVE RE-ASSENT 878 00:43:51,140 --> 00:43:55,011 BE NEEDED AND HOW THEY SHOULD BE 879 00:43:55,011 --> 00:43:57,079 INFORMED OF NEW INFORMATION OVER 880 00:43:57,079 --> 00:44:01,517 LONG-TERM FOLLOW-UP AS BEING A 881 00:44:01,517 --> 00:44:08,257 REQUIREMENT OF THE PROTOCOL AND 882 00:44:08,257 --> 00:44:13,529 HOW ARE THEY EXPRESSED IN AN 883 00:44:13,529 --> 00:44:16,165 AGE-APPROPRIATE MANNER. 884 00:44:16,165 --> 00:44:21,604 WE DISCUSS THESE QUESTIONS FOR 885 00:44:21,604 --> 00:44:25,274 ADULT PARTICIPANTS WHEN HAVE YOU 886 00:44:25,274 --> 00:44:26,342 SUBJECT ARE CHILDREN, 887 00:44:26,342 --> 00:44:28,511 COMMUNICATION IS ADVISABLE OR 888 00:44:28,511 --> 00:44:34,684 REQUIRED BUT INTERPRETATION AND 889 00:44:34,684 --> 00:44:38,387 AGE APPROPRIATE LEVEL IS 890 00:44:38,387 --> 00:44:39,722 REQUIRED WITH SPECIAL EXPERTISE 891 00:44:39,722 --> 00:44:43,593 AND THERE'S A RIGHT TO WITHDRAW 892 00:44:43,593 --> 00:44:48,097 PRESUMABLY INCLUDE THE LONG-TERM 893 00:44:48,097 --> 00:44:49,165 FOLLOW-UP STUDIES CHILDREN GOING 894 00:44:49,165 --> 00:44:50,399 THROUGH DIFFERENT STAGES OF 895 00:44:50,399 --> 00:44:52,268 CHILDHOOD AND ADOLESCENTS ARE 896 00:44:52,268 --> 00:44:55,304 GOING TO HAVE DIFFERENT 897 00:44:55,304 --> 00:45:00,509 ATTITUDES TOWARDS COMPLIANCE AND 898 00:45:00,509 --> 00:45:02,278 PARTICIPATION AND MAINTENANCE OF 899 00:45:02,278 --> 00:45:03,212 ASSENT AND UNDERSTANDING OF 900 00:45:03,212 --> 00:45:07,216 THEIR RIGHTS AS AN ONGOING ISSUE 901 00:45:07,216 --> 00:45:08,818 THAT NEEDS TO BE CONSIDERED BY 902 00:45:08,818 --> 00:45:10,620 IRBs BY PARENTS AND GUARDIANS 903 00:45:10,620 --> 00:45:15,791 AND PARTICIPANTS THEMSELVES. 904 00:45:15,791 --> 00:45:21,264 ANOTHER ASPECT OF ASSENT IS 905 00:45:21,264 --> 00:45:23,699 ADULTS WITH VARYING COMPETENTS 906 00:45:23,699 --> 00:45:27,436 AND A NEW AREA OF GENE TRANSFER 907 00:45:27,436 --> 00:45:31,540 RESEARCH INVOLVES BEHAVIORAL 908 00:45:31,540 --> 00:45:33,142 INTERVENTIONS OR GENE THERAPY 909 00:45:33,142 --> 00:45:34,410 INTENDED TO ADDRESS BEHAVIORAL 910 00:45:34,410 --> 00:45:36,646 HEALTH AND WE'LL ALSO SEE ASSENT 911 00:45:36,646 --> 00:45:39,882 ISSUES BECOMING PROMINENT IN 912 00:45:39,882 --> 00:45:42,084 THOSE AREAS OF THOSE CLINICAL 913 00:45:42,084 --> 00:45:44,987 TRIALS MOVING FORWARD. 914 00:45:44,987 --> 00:45:47,456 IN SUMMARY FOR TODAY'S 915 00:45:47,456 --> 00:45:49,492 PRESENTATION, CELL AND GENE 916 00:45:49,492 --> 00:45:51,560 THERAPY CAN ENCOMPASS A WIDE 917 00:45:51,560 --> 00:45:53,195 RANGE OF INVESTIGATIONAL 918 00:45:53,195 --> 00:45:53,696 PRODUCT. 919 00:45:53,696 --> 00:45:56,299 EACH WITH SPECIFIC RISKS AND 920 00:45:56,299 --> 00:45:58,834 CONCERNS FOR HUMAN SUBJECT 921 00:45:58,834 --> 00:46:00,069 PROTECTION. 922 00:46:00,069 --> 00:46:01,237 VARIOUS THERAPIES INVOLVE CLASS 923 00:46:01,237 --> 00:46:07,176 RISK COMMON TO THE VECTOR OR 924 00:46:07,176 --> 00:46:07,710 MODALITY. 925 00:46:07,710 --> 00:46:13,916 EACH GENE THERAPY INVOLVE TRANS 926 00:46:13,916 --> 00:46:15,017 GENES THAT REQUIRES CAREFUL 927 00:46:15,017 --> 00:46:15,985 EVALUATION BASED ON KNOWN 928 00:46:15,985 --> 00:46:21,390 BIOLOGY OF THOSE INTERVENTIONS. 929 00:46:21,390 --> 00:46:23,793 PREPARING AN ICD TO ADDRESS ALL 930 00:46:23,793 --> 00:46:24,960 THE COMPLEX BIOLOGY IS 931 00:46:24,960 --> 00:46:25,928 CHALLENGING AND LIKELY TO 932 00:46:25,928 --> 00:46:27,296 REQUIRE SEVERAL INTERVENTIONS 933 00:46:27,296 --> 00:46:29,765 AND THE INPUT OF A LOT OF 934 00:46:29,765 --> 00:46:32,268 DIFFERENT EXPERT VOICES. 935 00:46:32,268 --> 00:46:34,904 USEFUL GUIDANCE HAS BEEN 936 00:46:34,904 --> 00:46:38,841 PUBLISHED BY THE FDA AND NIH BY 937 00:46:38,841 --> 00:46:39,475 PROFESSIONAL ORGANIZATIONS AND 938 00:46:39,475 --> 00:46:42,078 BY PATIENT ADVOCACY GROUPS. 939 00:46:42,078 --> 00:46:46,849 AND IRBs AND IBCs CAN WORK 940 00:46:46,849 --> 00:46:47,616 TOGETHER TO OPTIMIZE INFORMED 941 00:46:47,616 --> 00:46:52,254 CONSENT DOCUMENT REVIEWED. 942 00:46:52,254 --> 00:46:52,988 -- REVIEWS. 943 00:46:52,988 --> 00:47:04,200 SO I'VE SET ASIDE SOME TIME FOR 944 00:47:04,200 --> 00:47:05,434 QUESTIONS I MAY HAVE QUESTIONS 945 00:47:05,434 --> 00:47:07,903 COMING IN AND MAY BE AVAILABLE 946 00:47:07,903 --> 00:47:09,004 FOR FURTHER DISCUSSION IF 947 00:47:09,004 --> 00:47:09,438 ANYONE'S INTERESTED. 948 00:47:09,438 --> 00:47:09,640 THANK YOU VERY MUCH. 949 00:47:09,640 --> 00:47:11,943 ONE QUESTION THAT CAME UP 950 00:47:11,943 --> 00:47:15,279 RELATED TO A POINT YOU MADE 951 00:47:15,279 --> 00:47:18,149 OBVIOUSLY THIS IS INCREDIBLY 952 00:47:18,149 --> 00:47:19,350 COMPLEX TOPIC HARD FOR EVEN SOME 953 00:47:19,350 --> 00:47:22,520 OF US IN THE FIELD TO UNDERSTAND 954 00:47:22,520 --> 00:47:24,889 HAS THERE BEEN ANY DATA 955 00:47:24,889 --> 00:47:26,257 COLLECTED REGARDING THE REAL 956 00:47:26,257 --> 00:47:32,163 LEVEL OF COMPREHENSION OF 957 00:47:32,163 --> 00:47:33,564 POTENTIAL SUBJECTS? 958 00:47:33,564 --> 00:47:36,000 >> SO A GREAT QUESTION, I DO NOT 959 00:47:36,000 --> 00:47:42,373 HAVE DATA TOP OF MIND BUT IT'S 960 00:47:42,373 --> 00:47:45,109 SOMETHING THAT OBVIOUSLY SHOULD 961 00:47:45,109 --> 00:47:46,944 BE INVESTIGATED ON AN ONGOING 962 00:47:46,944 --> 00:47:48,879 BASIS AND SOMETHING THAT SHOULD 963 00:47:48,879 --> 00:47:55,820 BE DONE. 964 00:47:55,820 --> 00:47:57,722 I'VE SEEN SOME DATA AT 965 00:47:57,722 --> 00:48:00,624 CONFERENCES AND POSTERS BUT I 966 00:48:00,624 --> 00:48:04,462 CAN'T CITE THAT TODAY. 967 00:48:04,462 --> 00:48:05,763 >> YOU MENTIONED ASSENT AND SOME 968 00:48:05,763 --> 00:48:08,199 THERAPIES PROVIDED TO CHILDREN. 969 00:48:08,199 --> 00:48:09,600 HAVE THERE BEEN LONG-TERM 970 00:48:09,600 --> 00:48:10,468 FOLLOW-UP IN TERMS OF THEIR 971 00:48:10,468 --> 00:48:12,636 LEVEL OF UNDERSTANDING OVER 972 00:48:12,636 --> 00:48:12,870 TIME? 973 00:48:12,870 --> 00:48:15,439 OBVIOUS SOME ARE VERY YOUNG 974 00:48:15,439 --> 00:48:17,708 PROBABLY AT AN AGE WHEN ASSENT 975 00:48:17,708 --> 00:48:22,780 CAN BE OBTAINED AND IS THERE 976 00:48:22,780 --> 00:48:26,183 CONCERN OF THE FOLLOW-UP 977 00:48:26,183 --> 00:48:27,051 OBVIOUSLY NEEDED. 978 00:48:27,051 --> 00:48:29,487 >> I HEAR HOW TO DO THE 979 00:48:29,487 --> 00:48:31,055 FOLLOW-UP AND MAINTAIN THESE 980 00:48:31,055 --> 00:48:31,355 ISSUES. 981 00:48:31,355 --> 00:48:36,394 AS ALWAYS DATA WOULD BE 982 00:48:36,394 --> 00:48:39,063 WONDERFUL AND I DO NOT HAVE DATA 983 00:48:39,063 --> 00:48:42,033 OTHER THAN REMEMBERING SEEING 984 00:48:42,033 --> 00:48:43,768 POSTERS AT ASGCT BUT WORTH 985 00:48:43,768 --> 00:48:53,944 PURSUING. 986 00:48:55,112 --> 00:48:57,281 >> OBVIOUSLY THE DEVIL IS IN THE 987 00:48:57,281 --> 00:48:58,783 DETAILS AND THE FORMS ARE TOO 988 00:48:58,783 --> 00:48:59,183 LONG. 989 00:48:59,183 --> 00:48:59,817 THERE'S POTENTIAL RISKS INVOLVED 990 00:48:59,817 --> 00:49:02,620 HERE. 991 00:49:02,620 --> 00:49:07,058 ARE ANY TIPS IN TERMS OF RBIs 992 00:49:07,058 --> 00:49:08,826 YOU MENTIONED CONSIDERATIONS. 993 00:49:08,826 --> 00:49:09,827 IS THERE VARIABLE BETWEEN IRBs 994 00:49:09,827 --> 00:49:12,797 IN TERMS OF WHAT THEY THINK IS 995 00:49:12,797 --> 00:49:13,064 ESSENTIAL? 996 00:49:13,064 --> 00:49:15,299 TRYING TO OF COURSE WEIGH WHAT 997 00:49:15,299 --> 00:49:17,268 SUBJECTS NEED TO UNDERSTAND TO 998 00:49:17,268 --> 00:49:19,003 MAKE AN EDUCATED DECISION AS TO 999 00:49:19,003 --> 00:49:24,241 WHETHER THIS IS APPROPRIATE FOR 1000 00:49:24,241 --> 00:49:25,409 THEM OR NOT VERSUS THERE BEING 1001 00:49:25,409 --> 00:49:30,881 TOO MUCH OR NOT ENOUGH. 1002 00:49:30,881 --> 00:49:34,618 >> I'M SURE THERE IS FOR BETTER 1003 00:49:34,618 --> 00:49:36,954 OR WORSE AND SOME REVIEWS ARE 1004 00:49:36,954 --> 00:49:39,990 PERFORMED BY LOCAL INSTITUTIONAL 1005 00:49:39,990 --> 00:49:44,195 IRBs AND SOME BY CENTRAL IRBs 1006 00:49:44,195 --> 00:49:45,696 WHO HAVE DIFFERENT EXPERIENCES 1007 00:49:45,696 --> 00:49:51,869 WITH A BROAD RANGE OF THESE 1008 00:49:51,869 --> 00:49:54,872 PROTOCOLS. 1009 00:49:54,872 --> 00:49:58,642 A 1010 00:49:58,642 --> 00:49:59,777 AND INFORM WHAT THEY THINK IS 1011 00:49:59,777 --> 00:50:01,579 IMPORTANT AND COULD BE WHAT 1012 00:50:01,579 --> 00:50:06,517 THEY'VE BEEN READING RECENTLY 1013 00:50:06,517 --> 00:50:08,352 AND THAT'S WHY A GROUP 1014 00:50:08,352 --> 00:50:09,353 CONSIDERATION OF WHAT'S TRULY 1015 00:50:09,353 --> 00:50:14,458 GOING TO BE REALLY EFFECTING 1016 00:50:14,458 --> 00:50:16,861 SUBJECT'S DECISION TO 1017 00:50:16,861 --> 00:50:18,329 PARTICIPATE OR NOT IN AN 1018 00:50:18,329 --> 00:50:18,896 INFORMED WAY IS THE MOST 1019 00:50:18,896 --> 00:50:24,401 IMPORTANT QUESTION. 1020 00:50:24,401 --> 00:50:25,769 THERE'S NO SIMPLE SOLUTION 1021 00:50:25,769 --> 00:50:26,704 BECAUSE WE DON'T KNOW IN ADVANCE 1022 00:50:26,704 --> 00:50:27,938 WHAT'S GOING TO HAPPEN. 1023 00:50:27,938 --> 00:50:30,808 WE HAVE TO MAKE A BEST GUESS TO 1024 00:50:30,808 --> 00:50:40,885 WHAT IS GOING TO BE IMPORTANT. 1025 00:50:40,885 --> 00:50:45,089 >> YOU SPOKE OF EX VIVO MODIFIED 1026 00:50:45,089 --> 00:50:47,057 CELLS BECOMING MALIGNANT PRIOR 1027 00:50:47,057 --> 00:50:48,025 TO ADMINISTRATION. 1028 00:50:48,025 --> 00:50:49,627 HOW COULD THAT POSSIBLY BE 1029 00:50:49,627 --> 00:50:51,795 EVALUATED AHEAD OF TIME? 1030 00:50:51,795 --> 00:50:53,430 OBVIOUSLY IT CAN'T OR YOU 1031 00:50:53,430 --> 00:50:56,100 WOULDN'T HAVE MENTIONED IT 1032 00:50:56,100 --> 00:50:57,868 BUT -- 1033 00:50:57,868 --> 00:51:03,107 >> IT'S A RARE RISK BUT 1034 00:51:03,107 --> 00:51:07,378 SOMETHING DEPENDING ON THE 1035 00:51:07,378 --> 00:51:09,914 SOURCE OF THE CELLS. 1036 00:51:09,914 --> 00:51:13,984 CERTAIN WAYS OF ACQUIRING CELLS 1037 00:51:13,984 --> 00:51:17,221 FOR EX VIVO MODIFICATION CAN 1038 00:51:17,221 --> 00:51:19,657 BRING IN A MALIGNANT CELL A RARE 1039 00:51:19,657 --> 00:51:21,659 EVENT BUT FOR TUMORS SOMETIMES 1040 00:51:21,659 --> 00:51:22,826 IT MAY HAPPEN. 1041 00:51:22,826 --> 00:51:23,394 IT COULD BE CAUGHT IN MOST 1042 00:51:23,394 --> 00:51:33,504 CASES. 1043 00:51:35,406 --> 00:51:37,241 AND WHEN YOU CHANGE CHROMOSOME 1044 00:51:37,241 --> 00:51:38,909 THERE'S ALWAYS A RISK YOU'LL 1045 00:51:38,909 --> 00:51:41,011 ACTIVATE AN ONCOGENE AND IF 1046 00:51:41,011 --> 00:51:43,747 YOU'RE EXPANDING YOURSELVES EX 1047 00:51:43,747 --> 00:51:46,784 VIVO DURING THAT PROCESS THERE 1048 00:51:46,784 --> 00:51:47,418 COULD BE OVER GROWTH OF 1049 00:51:47,418 --> 00:51:53,891 TRANSFORMED CELLS. 1050 00:51:53,891 --> 00:51:56,227 THERE ARE PROTECTIVE MEASURES IN 1051 00:51:56,227 --> 00:51:57,995 PLACE DURING MANUFACTURING TO 1052 00:51:57,995 --> 00:52:00,798 AVOID THOSE AFFECTS AND IT'S NOT 1053 00:52:00,798 --> 00:52:03,067 BEEN A MAJOR CONCERN IN CLINICAL 1054 00:52:03,067 --> 00:52:07,705 TRIALS SO FAR BUT IT'S A 1055 00:52:07,705 --> 00:52:08,839 CONSIDERATION THAT COULD APPEAR 1056 00:52:08,839 --> 00:52:11,275 ESPECIALLY AS MORE AND MORE 1057 00:52:11,275 --> 00:52:12,042 TRIALS ARE EXECUTED USING THOSE 1058 00:52:12,042 --> 00:52:22,286 TECHNOLOGIES. 1059 00:52:24,388 --> 00:52:25,756 >> LET ME SEE IF OTHER QUESTIONS 1060 00:52:25,756 --> 00:52:26,790 HAVE COME IN? 1061 00:52:26,790 --> 00:52:28,726 I DON'T SEE ANY BUT IF WE HAVE 1062 00:52:28,726 --> 00:52:30,894 ANY THAT COME IN I WILL FORWARD 1063 00:52:30,894 --> 00:52:31,695 THOSE TO YOU. 1064 00:52:31,695 --> 00:52:33,897 I'M SURE PEOPLE -- THIS HAS BEEN 1065 00:52:33,897 --> 00:52:39,036 VERY THOUGHT PROVOKE. 1066 00:52:39,036 --> 00:52:41,505 THERE'S MORE TO THIS THAN SOME 1067 00:52:41,505 --> 00:52:42,539 OF US HAVE UNDERSTOOD IN TERMS 1068 00:52:42,539 --> 00:52:45,409 OF THE RISK AND HOW TO CONVEY 1069 00:52:45,409 --> 00:52:46,377 AND WHAT TO CONVEY. 1070 00:52:46,377 --> 00:52:47,278 LOTS TO THINK ABOUT. 1071 00:52:47,278 --> 00:52:50,314 THANK YOU FOR JOINING US TODAY. 1072 00:52:50,314 --> 00:52:50,948 THANK YOU VERY MUCH. 1073 00:52:50,948 --> 00:52:51,982 WE APPRECIATE IT. 1074 00:52:51,982 --> 00:52:53,417 AS A MENTIONED EARLIER THE LINK 1075 00:52:53,417 --> 00:52:55,052 TO THE VIDEOCAST IN THE SLIDES 1076 00:52:55,052 --> 00:52:58,188 WILL BE POSTED ON OUR WEBSITE 1077 00:52:58,188 --> 00:52:58,989