1 00:00:12,045 --> 00:00:13,413 Glad to be back here 2 00:00:13,413 --> 00:00:16,950 again to talk about this topic. 3 00:00:17,551 --> 00:00:19,953 Oops. 4 00:00:19,953 --> 00:00:20,554 All right. 5 00:00:20,554 --> 00:00:23,557 So you've seen this. So 6 00:00:23,924 --> 00:00:26,927 you know what it says. 7 00:00:27,160 --> 00:00:29,429 Let's start in 1966. 8 00:00:29,429 --> 00:00:32,799 How many people here have is very great. 9 00:00:33,700 --> 00:00:36,603 Have heard of this article. 10 00:00:36,603 --> 00:00:38,945 So you may recall, if you've read it, the 11 00:00:38,945 --> 00:00:39,573 following, 12 00:00:40,440 --> 00:00:43,677 almost half, not quite half, maybe a little over a third 13 00:00:44,845 --> 00:00:46,880 of examples involved, at least some people 14 00:00:46,880 --> 00:00:49,883 who probably had difficulty giving consent. 15 00:00:50,183 --> 00:00:52,419 For instance, 16 00:00:52,419 --> 00:00:55,289 they had some choice language 17 00:00:55,289 --> 00:00:58,258 back then that we would like to use. 18 00:00:58,258 --> 00:01:01,473 Those folks given hepatitis B drug biopsies taken, which 19 00:01:01,473 --> 00:01:02,162 challenges? 20 00:01:02,162 --> 00:01:05,132 Same drug. 21 00:01:07,501 --> 00:01:08,969 Another study 22 00:01:08,969 --> 00:01:13,607 in which they induced confusion and many people it's not clear 23 00:01:13,607 --> 00:01:15,442 how if they were able 24 00:01:15,442 --> 00:01:18,478 during the studies to say, look, I don't want to do this anymore. 25 00:01:20,480 --> 00:01:21,481 Experiments on 26 00:01:21,481 --> 00:01:24,518 unconscious patients was common without consent. 27 00:01:25,452 --> 00:01:29,122 Study of, impending coma and sick people. 28 00:01:29,122 --> 00:01:33,093 Very sick people with, failing a liver. So. 29 00:01:33,794 --> 00:01:35,954 And there were quite invasive procedures, 30 00:01:35,954 --> 00:01:36,797 as you can see. 31 00:01:37,531 --> 00:01:41,709 And you may recall, Doctor Beecher went through a 32 00:01:41,709 --> 00:01:42,135 comb 33 00:01:42,135 --> 00:01:45,272 through the literature, and he he found these studies. 34 00:01:45,939 --> 00:01:47,376 And then there, of course, several 35 00:01:47,376 --> 00:01:49,109 examples involving children and infants. 36 00:01:50,110 --> 00:01:55,415 So this has always been one of the central 37 00:01:56,450 --> 00:02:00,053 issues that led to what we now, 38 00:02:02,189 --> 00:02:04,057 accept as research 39 00:02:04,057 --> 00:02:07,060 regulations, laws that regulate, 40 00:02:07,661 --> 00:02:11,231 the ethical principles of, human subject research. 41 00:02:12,232 --> 00:02:15,582 But ironically, it's also been the topic 42 00:02:15,582 --> 00:02:16,503 that's had 43 00:02:16,803 --> 00:02:18,639 just had the most kind of evolution, 44 00:02:18,639 --> 00:02:19,506 because there is 45 00:02:19,506 --> 00:02:21,809 some issues that were never really 46 00:02:21,809 --> 00:02:24,044 fully resolved in the beginning. 47 00:02:24,678 --> 00:02:27,986 So let me just go through some of the history very 48 00:02:27,986 --> 00:02:28,582 quickly. 49 00:02:29,182 --> 00:02:32,235 This is national Commission is the, Belmont 50 00:02:32,235 --> 00:02:33,086 Commission. 51 00:02:33,086 --> 00:02:35,822 You know, that's another term that people 52 00:02:35,822 --> 00:02:36,156 use. 53 00:02:36,156 --> 00:02:40,160 They published many, books or monograph 54 00:02:40,827 --> 00:02:43,663 regarding very different topics. 55 00:02:43,663 --> 00:02:47,543 And it's interesting all of them became the 56 00:02:47,543 --> 00:02:48,535 foundation 57 00:02:48,535 --> 00:02:51,538 for the regulation that we have now. 58 00:02:52,105 --> 00:02:54,608 So if you read those and you read the regulations, 59 00:02:54,608 --> 00:02:57,444 you'll see that except for one where this 60 00:02:57,444 --> 00:03:00,280 this some other graph research involving 61 00:03:00,280 --> 00:03:03,421 those institutionalized as mentally infirm 62 00:03:03,421 --> 00:03:06,486 really that question that remained open. 63 00:03:07,954 --> 00:03:10,957 So it was again debated in 1982. 64 00:03:10,957 --> 00:03:14,094 In the broader context of how do you make health care 65 00:03:14,094 --> 00:03:17,097 and research decisions in, 66 00:03:19,399 --> 00:03:20,267 among people 67 00:03:20,267 --> 00:03:23,270 who have trouble giving their own consent? 68 00:03:23,770 --> 00:03:27,174 And then 1998 was a very active year 69 00:03:27,174 --> 00:03:30,587 because there had been some, scandals, 70 00:03:30,587 --> 00:03:31,845 controversies 71 00:03:31,845 --> 00:03:33,792 that occurred, in several studies, 72 00:03:33,792 --> 00:03:35,282 both East and West Coast. 73 00:03:35,849 --> 00:03:38,718 And this was around the time that I was actually 74 00:03:38,718 --> 00:03:41,721 getting into, doing work in this area. 75 00:03:42,222 --> 00:03:46,059 So that 1998 was, kind of a watershed 76 00:03:46,059 --> 00:03:48,415 in terms of these, publications or, 77 00:03:48,415 --> 00:03:49,963 official publications. 78 00:03:50,230 --> 00:03:52,182 There was one by the Maryland Attorney 79 00:03:52,182 --> 00:03:53,467 General's Working Group. 80 00:03:54,301 --> 00:03:56,636 The really famous one was the End back 81 00:03:56,636 --> 00:03:58,873 report, National Bioethics Advisory 82 00:03:58,873 --> 00:03:59,639 Commission, 83 00:04:00,740 --> 00:04:03,743 in 1998. 84 00:04:04,044 --> 00:04:06,246 New York Department of Health 85 00:04:06,246 --> 00:04:09,662 also had a working group and issued a report, a year 86 00:04:09,662 --> 00:04:10,450 after that. 87 00:04:11,885 --> 00:04:12,953 And this 88 00:04:12,953 --> 00:04:16,123 sort of percolated along with different, 89 00:04:16,123 --> 00:04:18,492 a lot of debates and studies and so forth that we, 90 00:04:18,492 --> 00:04:21,995 I sort of helped contribute to during the intervening years. 91 00:04:23,063 --> 00:04:25,599 And in 2009, 92 00:04:25,599 --> 00:04:28,602 there were some recommendations made by, 93 00:04:29,035 --> 00:04:30,998 what's called SAC Corp Secretary's 94 00:04:30,998 --> 00:04:32,672 Advisory committee and human 95 00:04:32,672 --> 00:04:37,611 research protections, meaning advising the DHHS 96 00:04:37,811 --> 00:04:40,814 secretary. 97 00:04:41,648 --> 00:04:43,650 And in 2015, 98 00:04:43,650 --> 00:04:47,053 we had another this is during, President Obama. 99 00:04:47,053 --> 00:04:50,056 Sears. 100 00:04:51,391 --> 00:04:54,394 And there was a, 101 00:04:59,799 --> 00:05:02,202 Nprm maybe I'm just having a little it's 102 00:05:02,202 --> 00:05:05,205 a know this for public. 103 00:05:06,940 --> 00:05:07,574 What is that? 104 00:05:07,574 --> 00:05:10,152 I mean, you know, I worked for the government 105 00:05:10,152 --> 00:05:11,011 proposed rule. 106 00:05:11,311 --> 00:05:11,912 There you go. 107 00:05:11,912 --> 00:05:13,787 I knew Hollywood now because she's a 108 00:05:13,787 --> 00:05:15,715 she knows all these technical terms. 109 00:05:16,149 --> 00:05:19,152 So the common rule 110 00:05:19,386 --> 00:05:23,790 had been in place for decades, and it it received a, 111 00:05:25,125 --> 00:05:26,159 revision. 112 00:05:26,159 --> 00:05:28,398 And one of the things that, addressed 113 00:05:28,398 --> 00:05:29,729 was this, this topic. 114 00:05:29,729 --> 00:05:32,966 And I'll tell you the change that took place. 115 00:05:32,966 --> 00:05:35,235 Okay. 116 00:05:35,235 --> 00:05:37,571 So throughout all this, 117 00:05:37,571 --> 00:05:42,709 I would say the most significant insight or agreement 118 00:05:43,310 --> 00:05:46,538 that the field among researchers, 119 00:05:46,538 --> 00:05:47,614 regulators 120 00:05:47,614 --> 00:05:50,617 and ethicists is this, 121 00:05:51,785 --> 00:05:55,120 agreement, which is that if you're going to involve those 122 00:05:55,120 --> 00:05:55,589 lacking 123 00:05:55,589 --> 00:05:58,099 or at risk for lacking a decision 124 00:05:58,099 --> 00:05:59,392 making capacity. 125 00:06:01,661 --> 00:06:05,699 You need to specifically justify what it is that you're doing 126 00:06:06,333 --> 00:06:09,302 by meeting these conditions. 127 00:06:10,170 --> 00:06:13,373 That research can't be done without this population. 128 00:06:13,373 --> 00:06:17,003 If you can more convenient more you do it with other 129 00:06:17,003 --> 00:06:17,911 populations, 130 00:06:17,911 --> 00:06:20,880 even if less conveniently. 131 00:06:21,681 --> 00:06:23,583 You have no, because there's no intrinsic 132 00:06:23,583 --> 00:06:25,810 justification for having to use that 133 00:06:25,810 --> 00:06:26,553 population. 134 00:06:27,420 --> 00:06:29,556 And that's related to this. 135 00:06:29,556 --> 00:06:33,927 Second point, research must be focused on the disorder 136 00:06:33,927 --> 00:06:36,795 causing the incapacity, which kind of makes sense, 137 00:06:36,795 --> 00:06:37,197 right? 138 00:06:37,197 --> 00:06:40,200 If you're going to involve them and if that population 139 00:06:40,533 --> 00:06:42,765 will benefit in some broad sense, 140 00:06:42,765 --> 00:06:45,538 because some research can benefit people 141 00:06:45,538 --> 00:06:47,816 in our current generation, but also people 142 00:06:47,816 --> 00:06:49,876 who have this disorder in the future. 143 00:06:50,677 --> 00:06:54,183 Now, I want to emphasize the third point, 144 00:06:54,183 --> 00:06:54,781 though 145 00:06:55,615 --> 00:06:59,486 rarely, it is okay to involve persons 146 00:06:59,486 --> 00:07:02,489 with decisional difficulties 147 00:07:03,189 --> 00:07:05,492 for other reasons, for other disorders. 148 00:07:06,660 --> 00:07:08,895 And these will be situations 149 00:07:08,895 --> 00:07:13,177 where if you exclude them based on the first two bullet 150 00:07:13,177 --> 00:07:13,800 points, 151 00:07:14,634 --> 00:07:17,637 it could actually amount to a kind of discrimination. 152 00:07:18,938 --> 00:07:21,976 This implies that there are some types of 153 00:07:21,976 --> 00:07:22,642 research 154 00:07:23,043 --> 00:07:26,646 that has more or less potential for benefit. 155 00:07:27,714 --> 00:07:29,516 And we all recognize that. 156 00:07:29,516 --> 00:07:32,719 So for example, if they're if they're testing 157 00:07:32,719 --> 00:07:35,722 a very promising, 158 00:07:36,122 --> 00:07:37,924 let's say a monoclonal antibody 159 00:07:37,924 --> 00:07:42,195 for treatment of melanoma and a person with 160 00:07:43,430 --> 00:07:45,332 developmental disability 161 00:07:45,332 --> 00:07:49,921 such that they may not be able to give consent or even be at 162 00:07:49,921 --> 00:07:50,303 risk 163 00:07:50,503 --> 00:07:53,506 for giving consent, has the same, 164 00:07:54,441 --> 00:07:57,344 the cancer to exclude them 165 00:07:57,344 --> 00:07:59,263 merely based on distinct disability 166 00:07:59,263 --> 00:08:01,348 in that case could be discrimination. 167 00:08:01,715 --> 00:08:04,517 So this thinking becoming 168 00:08:04,517 --> 00:08:07,620 more prominent in research ethics 169 00:08:07,620 --> 00:08:10,282 is actually a sign of tremendous progress 170 00:08:10,282 --> 00:08:11,191 in this area. 171 00:08:11,758 --> 00:08:14,227 Because we now realize that the first 172 00:08:14,227 --> 00:08:17,263 two bullet points here is widely accepted. 173 00:08:17,897 --> 00:08:18,965 And we're trying. 174 00:08:18,965 --> 00:08:23,937 And as any policy should, we should be sensitive 175 00:08:23,937 --> 00:08:26,940 to developments of the context 176 00:08:27,841 --> 00:08:31,244 so that are their unintended consequences. 177 00:08:31,945 --> 00:08:34,739 And this third point, I want to emphasize 178 00:08:34,739 --> 00:08:36,716 that along those lines okay. 179 00:08:37,384 --> 00:08:40,253 So I'm going to talk about this is making 180 00:08:40,253 --> 00:08:42,422 capacity impairment as a topic 181 00:08:44,090 --> 00:08:45,892 talk. 182 00:08:45,892 --> 00:08:48,895 And then to talk about, 183 00:08:49,295 --> 00:08:52,465 this, you know, notion 184 00:08:52,465 --> 00:08:54,757 that in theory, studies involving 185 00:08:54,757 --> 00:08:57,604 people who can't consent is permissible. 186 00:08:58,104 --> 00:08:58,872 Okay. 187 00:08:58,872 --> 00:09:00,840 Now the question is how do you do it? 188 00:09:00,840 --> 00:09:02,642 Who should give consent? 189 00:09:02,642 --> 00:09:04,511 And should there be limits to risk? 190 00:09:04,511 --> 00:09:06,813 Those are the two fundamental questions. 191 00:09:06,813 --> 00:09:10,638 When you raise the when you say I should be okay, 192 00:09:10,638 --> 00:09:10,950 but 193 00:09:11,284 --> 00:09:13,831 so but has to at least two major bullet 194 00:09:13,831 --> 00:09:14,354 points. 195 00:09:16,389 --> 00:09:17,390 I'm going to actually 196 00:09:17,390 --> 00:09:20,627 give you some, evidence that we've gathered. 197 00:09:20,627 --> 00:09:23,050 When I was before I came to NIH at 198 00:09:23,050 --> 00:09:23,763 Michigan, 199 00:09:23,763 --> 00:09:26,232 we did a lot of studies on this topic. 200 00:09:26,232 --> 00:09:29,803 And that, I think, really informs how 201 00:09:30,637 --> 00:09:35,508 we might make policy and also how do we incorporate 202 00:09:35,809 --> 00:09:38,540 the moral perspectives of the public 203 00:09:38,540 --> 00:09:41,347 into these kinds of decision making. 204 00:09:43,616 --> 00:09:44,150 And then I'll 205 00:09:44,150 --> 00:09:46,755 close with some additional protections of 206 00:09:46,755 --> 00:09:47,454 safeguards 207 00:09:47,454 --> 00:09:49,450 that I or these and investigators 208 00:09:49,450 --> 00:09:51,991 might consider, depending on the context. 209 00:09:52,959 --> 00:09:53,793 All right. 210 00:09:53,793 --> 00:09:56,896 So what is decision making capacity and impairment. 211 00:09:58,898 --> 00:10:02,368 So I want to make a distinction between adjudicated. 212 00:10:02,936 --> 00:10:05,672 In other words having gone to court 213 00:10:05,672 --> 00:10:07,650 decision about whether the person 214 00:10:07,650 --> 00:10:08,908 has capacity or not. 215 00:10:09,375 --> 00:10:12,323 We often use the terms capacity and competence 216 00:10:12,323 --> 00:10:13,413 interchangeably. 217 00:10:14,481 --> 00:10:17,851 Its meaning is basically do they have the ability 218 00:10:17,851 --> 00:10:20,854 sufficient to make a decision? 219 00:10:21,754 --> 00:10:24,257 In this case, when I say adjudicated. 220 00:10:24,257 --> 00:10:27,127 It's, it's the judge who makes that decision. 221 00:10:27,127 --> 00:10:29,529 So it has a special legal force. 222 00:10:29,529 --> 00:10:34,000 Notice that I don't distinguish between capacity incompetence 223 00:10:34,000 --> 00:10:36,946 as somehow lying between clinical and 224 00:10:36,946 --> 00:10:37,504 legal. 225 00:10:38,505 --> 00:10:41,327 I just want to warn you that there are many people out 226 00:10:41,327 --> 00:10:41,641 there 227 00:10:41,641 --> 00:10:42,509 who will tell you that's 228 00:10:42,509 --> 00:10:44,952 how the world is, and that's how you're supposed 229 00:10:44,952 --> 00:10:45,512 to use it. 230 00:10:45,812 --> 00:10:48,715 It just that, just outright not true. 231 00:10:48,715 --> 00:10:51,561 So I we can talk about that if you want, 232 00:10:51,561 --> 00:10:54,621 but, don't get misled by that distinction. 233 00:10:55,955 --> 00:10:58,232 When we just ordinarily talk about the 234 00:10:58,232 --> 00:10:58,591 terms 235 00:10:58,591 --> 00:11:01,262 in clinical practice or in a research setting, it 236 00:11:01,262 --> 00:11:01,861 just means 237 00:11:01,861 --> 00:11:05,671 a clinician's approximation of what the courts might or 238 00:11:05,671 --> 00:11:06,432 would say. 239 00:11:07,066 --> 00:11:09,302 And usually this carries the day. Why? 240 00:11:09,302 --> 00:11:12,122 Because there are special legal provisions 241 00:11:12,122 --> 00:11:14,807 that give certain persons the authority 242 00:11:14,807 --> 00:11:16,469 to make those decisions unless it's 243 00:11:16,469 --> 00:11:18,511 challenged, in which case it goes to court 244 00:11:20,046 --> 00:11:23,650 the abilities or the functional components. 245 00:11:23,650 --> 00:11:27,554 If you have sufficient amount of it of the right kind, 246 00:11:28,021 --> 00:11:31,658 then you would be deemed competent 247 00:11:31,658 --> 00:11:35,395 or have sufficient, capacity to make your own decisions. 248 00:11:36,229 --> 00:11:38,410 Now the abilities come in degrees 249 00:11:38,410 --> 00:11:39,732 and that we they go 250 00:11:39,732 --> 00:11:41,909 by the name of things like understanding, 251 00:11:41,909 --> 00:11:43,236 appreciating, reasoning, 252 00:11:43,236 --> 00:11:46,406 and communicating at stable choice. 253 00:11:46,406 --> 00:11:49,342 These are psychometric concepts. 254 00:11:49,342 --> 00:11:51,344 You know, I mean, you can have 255 00:11:51,344 --> 00:11:52,679 well-trained people 256 00:11:52,679 --> 00:11:56,049 who can operationalize these so that you can actually 257 00:11:56,049 --> 00:11:59,052 develop tools to, measure them. 258 00:11:59,319 --> 00:12:01,983 Of course, the caveat is because as you'll 259 00:12:01,983 --> 00:12:04,457 see, the concept is decision specific. 260 00:12:04,457 --> 00:12:08,528 You have to actually modify them for each context, 261 00:12:08,828 --> 00:12:12,198 which kind of puts some pressure on. 262 00:12:12,198 --> 00:12:15,570 What does it mean to have a validated instrument 263 00:12:15,570 --> 00:12:16,202 as such? 264 00:12:16,202 --> 00:12:18,571 Because you have to customize it to each situation. 265 00:12:20,440 --> 00:12:20,907 However, 266 00:12:20,907 --> 00:12:23,732 now the second component to this last 267 00:12:23,732 --> 00:12:24,877 bullet is yes, 268 00:12:24,877 --> 00:12:27,305 there are degrees that we can measure, 269 00:12:27,305 --> 00:12:29,349 but the concept is dichotomous. 270 00:12:30,316 --> 00:12:34,354 Decisions in life are dichotomous. 271 00:12:34,354 --> 00:12:35,822 It's yes or no. 272 00:12:35,822 --> 00:12:38,925 You know, so you you can decide 273 00:12:38,925 --> 00:12:41,928 to bring back the astronauts back 274 00:12:42,362 --> 00:12:46,213 using their vehicle or you're not sure how safe for 275 00:12:46,213 --> 00:12:46,666 this. 276 00:12:46,666 --> 00:12:48,334 So you have to make another decision. 277 00:12:48,334 --> 00:12:50,967 You can't just sort of do it or not 278 00:12:50,967 --> 00:12:52,772 do it at the same time. 279 00:12:53,072 --> 00:12:53,673 Same thing. 280 00:12:53,673 --> 00:12:55,800 So you have to you have to sort of use 281 00:12:55,800 --> 00:12:56,976 all that information 282 00:12:56,976 --> 00:12:59,979 and reduce it to yes, no. 283 00:13:01,814 --> 00:13:04,083 It's decision making capacity is part 284 00:13:04,083 --> 00:13:05,848 of the doctrine of informed consent, 285 00:13:05,848 --> 00:13:07,220 which has to be components, 286 00:13:08,354 --> 00:13:11,357 the ability or the capacity to make the decision. 287 00:13:12,091 --> 00:13:15,038 Having receive proper information, relevant 288 00:13:15,038 --> 00:13:15,928 information, 289 00:13:16,829 --> 00:13:19,465 and to be able to make the decision without, 290 00:13:20,733 --> 00:13:23,102 duress, coercion, 291 00:13:23,102 --> 00:13:26,072 undue influence. 292 00:13:27,640 --> 00:13:28,307 The modern 293 00:13:28,307 --> 00:13:31,605 functional model of decision making capacity has several 294 00:13:31,605 --> 00:13:32,311 components. 295 00:13:32,578 --> 00:13:35,048 One is the presumption of capacity. 296 00:13:35,048 --> 00:13:39,583 We usually say adults have the right to presume to be 297 00:13:39,583 --> 00:13:40,353 capable, 298 00:13:40,353 --> 00:13:43,592 unless you have a reason to suspend 299 00:13:43,592 --> 00:13:45,258 that presumption. 300 00:13:45,525 --> 00:13:48,281 It doesn't mean suspension, doesn't mean you say they're not 301 00:13:48,281 --> 00:13:48,695 capable. 302 00:13:48,961 --> 00:13:52,665 It just means you have no reason to investigate whether or not 303 00:13:52,665 --> 00:13:55,963 we need to make a decision about whether this person has capacity 304 00:13:55,963 --> 00:13:56,369 or not, 305 00:13:57,503 --> 00:13:59,288 but the presumption is they do, unless 306 00:13:59,288 --> 00:14:01,074 you have good reason to challenge it. 307 00:14:03,142 --> 00:14:04,744 You. We no longer use 308 00:14:04,744 --> 00:14:07,914 terms like senile, unsound mind. 309 00:14:07,914 --> 00:14:11,050 So if you go back to the laws and writings 310 00:14:11,250 --> 00:14:15,354 back in the early 20th century, we will also people. 311 00:14:15,555 --> 00:14:18,791 Doctors often use terms like this to say, 312 00:14:19,225 --> 00:14:19,792 you know, 313 00:14:19,792 --> 00:14:21,806 that person can't make their own decision 314 00:14:21,806 --> 00:14:23,329 because their mind is unsound, 315 00:14:23,329 --> 00:14:23,896 that that's it. 316 00:14:27,433 --> 00:14:28,534 Actual abilities 317 00:14:28,534 --> 00:14:31,537 relevant to the decision must be assessed. 318 00:14:32,405 --> 00:14:35,141 And the threshold. How? 319 00:14:35,141 --> 00:14:37,643 You know, there are many ways in which you can do this. 320 00:14:37,643 --> 00:14:38,745 Assessments. 321 00:14:38,745 --> 00:14:41,547 You can do it in such a way that. 322 00:14:41,547 --> 00:14:42,715 Let me give you an example. 323 00:14:42,715 --> 00:14:44,684 If a person, 324 00:14:44,684 --> 00:14:47,553 even with a mild dementia is in a hospital 325 00:14:47,553 --> 00:14:49,986 because they have an infection and the 326 00:14:49,986 --> 00:14:52,291 and somebody comes in and says, Mr. 327 00:14:52,291 --> 00:14:54,784 Jones, we're going to draw some blood 328 00:14:54,784 --> 00:14:55,862 for labs, okay. 329 00:14:55,862 --> 00:14:58,598 And he just puts his arm out. 330 00:14:58,598 --> 00:15:01,601 Now, are you going to use a full, 331 00:15:01,901 --> 00:15:04,337 complicated assessment to make sure he's giving 332 00:15:04,337 --> 00:15:04,804 consent? 333 00:15:04,804 --> 00:15:05,838 Probably not. 334 00:15:05,838 --> 00:15:08,430 Because in that context, mere assent 335 00:15:08,430 --> 00:15:11,310 might be something that is appropriate. 336 00:15:11,644 --> 00:15:13,638 On the other hand, if the same person is 337 00:15:13,638 --> 00:15:15,782 asked to participate in the clinical trial 338 00:15:16,482 --> 00:15:20,153 of neurosurgical implant of gene therapy, 339 00:15:21,087 --> 00:15:23,950 you know, and and if he says, well, doc, 340 00:15:23,950 --> 00:15:25,024 you know best, 341 00:15:25,391 --> 00:15:27,201 I'm willing to try whatever you want 342 00:15:27,201 --> 00:15:28,961 and articulates that that clearly. 343 00:15:29,495 --> 00:15:32,161 I would think that we would hold that person to a much higher 344 00:15:32,161 --> 00:15:32,598 standard. 345 00:15:33,266 --> 00:15:33,633 Okay. 346 00:15:35,168 --> 00:15:35,701 And as I 347 00:15:35,701 --> 00:15:38,704 said, it's tasked with decision specific. 348 00:15:38,905 --> 00:15:40,909 I want to spend a couple of minutes 349 00:15:40,909 --> 00:15:42,742 on this slide because you will, 350 00:15:43,276 --> 00:15:46,412 depending on where you're listening to me 351 00:15:46,712 --> 00:15:50,090 at this moment, you will be more or less 352 00:15:50,090 --> 00:15:50,850 familiar 353 00:15:50,850 --> 00:15:54,450 with this convention, this UN convention, 354 00:15:54,450 --> 00:15:55,855 very important. 355 00:15:56,589 --> 00:16:01,360 2008 was a convention that outlined 356 00:16:02,395 --> 00:16:05,398 the human rights based 357 00:16:06,599 --> 00:16:08,267 I guess, rights of persons 358 00:16:08,267 --> 00:16:11,437 with disabilities, very important. 359 00:16:11,437 --> 00:16:14,440 There was a problem with it in that. 360 00:16:16,676 --> 00:16:18,811 There was an article 361 00:16:18,811 --> 00:16:21,480 among the, in the convention 362 00:16:21,480 --> 00:16:24,584 that basically strongly implied 363 00:16:24,851 --> 00:16:28,855 that regardless of your abilities, 364 00:16:30,256 --> 00:16:33,693 what we what I just laid out as your decisional capacity 365 00:16:33,693 --> 00:16:36,269 and the abilities functional abilities 366 00:16:36,269 --> 00:16:37,897 you have legal capacity 367 00:16:38,764 --> 00:16:41,767 regardless of your functional status. 368 00:16:42,335 --> 00:16:44,085 And so it was directly challenging 369 00:16:44,085 --> 00:16:45,938 the concept of functional capacity. 370 00:16:47,406 --> 00:16:49,108 Consequently, it also said 371 00:16:49,108 --> 00:16:52,144 we need to get rid of all surrogate decision 372 00:16:52,144 --> 00:16:55,314 making regimes. 373 00:16:55,314 --> 00:17:00,686 Now I'm not going to go into the complicated political 374 00:17:00,686 --> 00:17:04,503 and other history of why this, came to be in the 375 00:17:04,503 --> 00:17:05,458 convention. 376 00:17:06,592 --> 00:17:09,695 There was a general comment explaining it in this sense 377 00:17:09,695 --> 00:17:12,698 that I just talked to you about, 378 00:17:15,067 --> 00:17:17,303 let's just say even countries 379 00:17:17,303 --> 00:17:20,940 that have ratified this accepted this convention 380 00:17:21,874 --> 00:17:24,944 almost always insert a 381 00:17:25,678 --> 00:17:28,614 what in America would call signing statements. 382 00:17:28,614 --> 00:17:30,950 You know, we think this is important. 383 00:17:30,950 --> 00:17:33,386 Wonderful convention we agreed to. 384 00:17:33,386 --> 00:17:37,790 However, insofar as article 12 is concerned, as it implies 385 00:17:37,790 --> 00:17:41,613 such and such, we reserve the right to xyzzy 386 00:17:41,613 --> 00:17:42,395 because. 387 00:17:42,728 --> 00:17:46,666 So this is a very important topic. 388 00:17:46,999 --> 00:17:50,002 But I'm going to put it aside 389 00:17:51,003 --> 00:17:53,072 because we are using the concept 390 00:17:53,072 --> 00:17:55,904 that the convention, at least the general comment 391 00:17:55,904 --> 00:17:56,309 number 392 00:17:56,309 --> 00:17:58,880 one of the convention says we can't, 393 00:17:58,880 --> 00:18:01,380 we shouldn't be using, but we are. 394 00:18:01,714 --> 00:18:04,650 And virtually every jurisdiction that I know 395 00:18:04,650 --> 00:18:05,051 does. 396 00:18:05,384 --> 00:18:05,751 Okay. 397 00:18:07,019 --> 00:18:07,587 So some 398 00:18:07,587 --> 00:18:10,723 disorders elevate the risk for incapacity, 399 00:18:11,390 --> 00:18:14,363 usually a most obvious ones that are ones that affect your 400 00:18:14,363 --> 00:18:14,927 cognition. 401 00:18:14,927 --> 00:18:15,361 Right. 402 00:18:15,361 --> 00:18:18,661 Neurodegenerative disorders Alzheimer's from the temporal 403 00:18:18,661 --> 00:18:19,298 dementias. 404 00:18:22,468 --> 00:18:25,571 Neurodevelopmental disorders. So, 405 00:18:26,672 --> 00:18:29,875 you know, learning disabilities, intellectual disabilities, 406 00:18:30,242 --> 00:18:33,012 related disorders, injuries 407 00:18:33,012 --> 00:18:36,114 and injuries like strokes, traumatic brain 408 00:18:36,114 --> 00:18:38,551 injury, people who suffer trauma 409 00:18:38,551 --> 00:18:43,589 from car accidents, war, for instance, or infections, 410 00:18:44,323 --> 00:18:46,869 and people who come into the hospital 411 00:18:46,869 --> 00:18:49,829 with acute situations that have temporary, 412 00:18:51,297 --> 00:18:52,598 loss of cognitive. 413 00:18:52,598 --> 00:18:56,235 So cognitive function, what we call acute 414 00:18:56,235 --> 00:18:59,338 confusion or states or delirium, 415 00:18:59,338 --> 00:19:02,141 psychotic disorders including I consider 416 00:19:02,141 --> 00:19:05,177 manic states a bipolar disorder 417 00:19:05,177 --> 00:19:09,482 as falling under psychotic, situations, 418 00:19:10,549 --> 00:19:13,819 mood disorders when severe eating disorders 419 00:19:13,819 --> 00:19:17,323 when severe gets affect decision making capacity. 420 00:19:17,656 --> 00:19:19,458 There are other areas of controversy. 421 00:19:19,458 --> 00:19:22,361 For instance, people who have, 422 00:19:22,361 --> 00:19:26,032 personality disorders who are under specific duress 423 00:19:26,665 --> 00:19:31,270 or distress and are decompensated in perhaps 424 00:19:32,371 --> 00:19:34,927 even though they don't have one of these 425 00:19:34,927 --> 00:19:35,374 major, 426 00:19:35,374 --> 00:19:38,377 severe like, psychotic disorders. 427 00:19:39,578 --> 00:19:41,313 Okay. 428 00:19:41,313 --> 00:19:43,371 The thing to take away from this slide 429 00:19:43,371 --> 00:19:44,183 is that notice 430 00:19:44,183 --> 00:19:46,670 that I'm saying these are risk factors 431 00:19:46,670 --> 00:19:47,586 not defining, 432 00:19:49,488 --> 00:19:52,324 not definitions of incapacity. 433 00:19:52,324 --> 00:19:55,327 All right. 434 00:19:56,362 --> 00:19:59,365 It's actually very common. 435 00:19:59,565 --> 00:20:02,101 In clinical work. 436 00:20:02,101 --> 00:20:04,537 So in general, hospital inpatients, 437 00:20:04,537 --> 00:20:07,565 if you do a survey going from room to room 438 00:20:07,565 --> 00:20:09,008 people, researchers 439 00:20:09,008 --> 00:20:13,345 find about 30 to 40% can't give their own consent. 440 00:20:13,846 --> 00:20:16,849 It's actually probably higher because a lot of these studies 441 00:20:16,849 --> 00:20:19,119 are based on interviews of people 442 00:20:19,119 --> 00:20:21,320 who are able to be interviewed. 443 00:20:21,520 --> 00:20:25,825 So if you count all those people who can't even do interviews, 444 00:20:25,825 --> 00:20:27,226 it'll be a little higher. 445 00:20:27,226 --> 00:20:30,629 So nursing homes, much higher, psychiatric 446 00:20:30,629 --> 00:20:32,896 inpatients, it really has to do with the 447 00:20:32,896 --> 00:20:33,632 kind of unit 448 00:20:33,632 --> 00:20:37,903 that you're, running, whether it's a you know, a 449 00:20:37,903 --> 00:20:39,238 Beverly Hills, 450 00:20:41,440 --> 00:20:41,941 you know, 451 00:20:41,941 --> 00:20:45,978 privately funded or whatever you may not have. 452 00:20:46,178 --> 00:20:49,181 They have a different severity of illness, 453 00:20:49,915 --> 00:20:52,947 distressing, but different type of illness 454 00:20:52,947 --> 00:20:53,452 versus 455 00:20:53,819 --> 00:20:58,724 a state run hospital where you hospitalized 456 00:20:58,724 --> 00:21:00,944 people who have no other resources 457 00:21:00,944 --> 00:21:01,727 or who are, 458 00:21:02,194 --> 00:21:04,549 putting themselves or others in danger, for 459 00:21:04,549 --> 00:21:05,097 instance. 460 00:21:05,097 --> 00:21:07,833 It will vary. 461 00:21:07,833 --> 00:21:09,741 If you just look at people with chronic 462 00:21:09,741 --> 00:21:11,403 psychoses, it varies quite a bit. 463 00:21:11,403 --> 00:21:13,925 But notice that it's only about half at 464 00:21:13,925 --> 00:21:14,507 maximum. 465 00:21:14,974 --> 00:21:17,632 So I think people should be aware 466 00:21:17,632 --> 00:21:20,613 that chronic psychoses by themselves 467 00:21:20,613 --> 00:21:25,384 don't create the kind of, severe automatically create 468 00:21:25,384 --> 00:21:28,387 severe decisional ability except under certain, 469 00:21:30,089 --> 00:21:31,123 a subset, I should say. 470 00:21:31,123 --> 00:21:33,526 I'll explain that in a bit. 471 00:21:33,526 --> 00:21:34,660 Mild to might. 472 00:21:34,660 --> 00:21:38,831 A moderate depression really doesn't affect capacity 473 00:21:39,932 --> 00:21:44,470 given the type of assessments that we now standardly do, 474 00:21:45,638 --> 00:21:48,641 because we generally 475 00:21:48,641 --> 00:21:51,644 these assessments aren't, 476 00:21:52,778 --> 00:21:55,881 as so demanding that we would, you know, 477 00:21:57,082 --> 00:22:02,221 that you might think because we, we kind of build in the balance 478 00:22:02,421 --> 00:22:05,491 that we live in a society that values autonomy. 479 00:22:05,491 --> 00:22:07,929 And it's really wrong if you're overly 480 00:22:07,929 --> 00:22:10,496 sensitive and finding people incapable. 481 00:22:11,163 --> 00:22:12,631 Okay. 482 00:22:12,631 --> 00:22:14,867 However, if you're very depressed, 483 00:22:14,867 --> 00:22:18,003 a certain minority will have, 484 00:22:18,003 --> 00:22:20,673 incapacity. 485 00:22:20,673 --> 00:22:23,309 Let me just talk about two disorders. 486 00:22:23,309 --> 00:22:27,213 Because they have their major, they're very common. 487 00:22:27,213 --> 00:22:30,249 Both. And there's been a lot of research. 488 00:22:30,549 --> 00:22:33,052 So this issue comes up a lot in research 489 00:22:33,052 --> 00:22:33,552 ethics. 490 00:22:34,053 --> 00:22:37,056 So Alzheimer's disease. 491 00:22:37,456 --> 00:22:39,091 About 40% of patients 492 00:22:39,091 --> 00:22:42,061 with even what used to be called mild cognitive impairment 493 00:22:42,661 --> 00:22:45,690 where, you know, technically they might fall on 494 00:22:45,690 --> 00:22:46,398 the border 495 00:22:46,398 --> 00:22:49,802 within normal range of certain cognitive tests, 496 00:22:51,470 --> 00:22:55,706 are found to lack capacity to give consent to a like a drug 497 00:22:55,706 --> 00:22:56,208 asked. 498 00:22:58,344 --> 00:23:00,512 In our study about, 499 00:23:00,512 --> 00:23:04,016 you know, two thirds to three quarters of patients 500 00:23:04,250 --> 00:23:07,354 with many mental scores, the minimal is a cognitive test 501 00:23:07,354 --> 00:23:07,686 here. 502 00:23:07,686 --> 00:23:09,321 The 3030 is perfect. 503 00:23:09,321 --> 00:23:12,358 Zero is, 504 00:23:12,358 --> 00:23:15,261 22, 23 is sort of on the border. 505 00:23:15,261 --> 00:23:18,264 You would say a person has moderate dementia. 506 00:23:20,466 --> 00:23:22,735 But you had moderate dementia 507 00:23:22,735 --> 00:23:25,471 and most would lack it 508 00:23:25,471 --> 00:23:28,507 ability to consent to a clinical trial. 509 00:23:28,507 --> 00:23:31,510 On the other hand, in a study that I was, 510 00:23:32,645 --> 00:23:36,215 I was part of, we're doing a 511 00:23:37,249 --> 00:23:39,887 part of it in the sense of doing the ethics and the 512 00:23:39,887 --> 00:23:40,352 capacity 513 00:23:40,352 --> 00:23:42,412 assessment of the clinical trial, 514 00:23:42,412 --> 00:23:44,223 which was called Kati study. 515 00:23:45,858 --> 00:23:47,710 When you look at the distribution of 516 00:23:47,710 --> 00:23:48,327 performance 517 00:23:48,327 --> 00:23:50,535 and the understanding score on a tool 518 00:23:50,535 --> 00:23:51,430 that was used, 519 00:23:52,231 --> 00:23:56,869 you can see the vast majority are above the cutoff 520 00:23:56,869 --> 00:24:00,252 that at least the experts who did the came 521 00:24:00,252 --> 00:24:02,508 up with this cutoff thought 522 00:24:03,609 --> 00:24:04,943 was a good cutoff 523 00:24:04,943 --> 00:24:07,146 to decide whether the person could or did 524 00:24:07,146 --> 00:24:09,348 or did not understand sufficient amount. 525 00:24:10,549 --> 00:24:12,384 And same for the appreciation, 526 00:24:12,384 --> 00:24:15,421 although, you see, it's a little bit less 527 00:24:15,421 --> 00:24:15,721 that. 528 00:24:15,721 --> 00:24:18,691 Just to give you an idea, to give you a contrast. 529 00:24:19,958 --> 00:24:20,893 All right. 530 00:24:20,893 --> 00:24:23,249 Now, if studies with people lacking 531 00:24:23,249 --> 00:24:24,730 or at risk of lacking 532 00:24:24,730 --> 00:24:27,733 DMC are permissible, who gives consent? 533 00:24:28,367 --> 00:24:28,834 Right. 534 00:24:28,834 --> 00:24:31,302 If you can't give consent, how are they going to 535 00:24:31,302 --> 00:24:31,971 participate? 536 00:24:32,237 --> 00:24:35,240 Somebody has to give permission, right? 537 00:24:37,576 --> 00:24:40,579 Now federal regulations allow in theory 538 00:24:40,980 --> 00:24:44,356 and pre 2018 a common rule said the 539 00:24:44,356 --> 00:24:45,417 following. 540 00:24:45,784 --> 00:24:48,287 You will often hear the term lawyer 541 00:24:48,287 --> 00:24:50,789 legally authorized representative. 542 00:24:51,290 --> 00:24:54,660 So this is a specific regulatory term 543 00:24:55,694 --> 00:24:57,696 where they're referring 544 00:24:57,696 --> 00:25:00,866 to people who would be authorized 545 00:25:00,866 --> 00:25:03,208 within these regulations that give consent 546 00:25:03,208 --> 00:25:05,270 for somebody else to be in research. 547 00:25:07,539 --> 00:25:08,741 How do they define it? 548 00:25:08,741 --> 00:25:11,643 They defined it as people who are authorized 549 00:25:11,643 --> 00:25:15,981 under applicable law, meaning nonfederal law. 550 00:25:16,281 --> 00:25:18,751 Specific or actually even law outside 551 00:25:18,751 --> 00:25:20,953 the research ethics regulations. 552 00:25:20,953 --> 00:25:22,421 If there were such a thing 553 00:25:22,421 --> 00:25:25,691 under the federal laws, I as far as I know, there isn't. 554 00:25:25,958 --> 00:25:28,235 However, there are state and local laws 555 00:25:28,235 --> 00:25:29,461 that may be relevant 556 00:25:30,195 --> 00:25:32,753 to consent on behalf of prospective subject to the 557 00:25:32,753 --> 00:25:33,265 subjects. 558 00:25:33,265 --> 00:25:36,268 Participate in the procedures involved in research. 559 00:25:37,169 --> 00:25:40,955 Okay, so what, you might ask, what does applicable law look 560 00:25:40,955 --> 00:25:41,340 like? 561 00:25:42,875 --> 00:25:45,077 And they are local state laws. 562 00:25:45,077 --> 00:25:48,614 And before the 2018, even now, 563 00:25:48,614 --> 00:25:51,177 very few states have actually addressed 564 00:25:51,177 --> 00:25:52,951 this and their state laws. 565 00:25:52,951 --> 00:25:56,288 It's not really high on the agenda of legislators 566 00:25:56,288 --> 00:25:58,891 because it's a very niche topic. 567 00:25:58,891 --> 00:26:01,527 So California, new Jersey, Virginia 568 00:26:02,694 --> 00:26:04,263 have had 569 00:26:04,263 --> 00:26:06,632 enactment of what I call modern laws. 570 00:26:06,632 --> 00:26:09,039 And you can if you can, just when you hear 571 00:26:09,039 --> 00:26:11,103 modern, you can just assume whoever 572 00:26:11,103 --> 00:26:13,420 wrote this understood that there were 573 00:26:13,420 --> 00:26:15,674 federal research ethics laws, okay. 574 00:26:15,674 --> 00:26:18,777 So they wrote with that 575 00:26:18,777 --> 00:26:21,180 in their knowledge base, 576 00:26:21,180 --> 00:26:24,183 whereas most other laws that could be invoked 577 00:26:25,284 --> 00:26:27,986 generally were written 578 00:26:27,986 --> 00:26:31,390 earlier for independent of considerations 579 00:26:31,390 --> 00:26:34,393 of research ethics. 580 00:26:35,360 --> 00:26:38,363 The revised common Rule, which 581 00:26:39,765 --> 00:26:42,167 really sort of, 582 00:26:42,167 --> 00:26:45,537 for most situations help resolve this uncertainty, 583 00:26:45,938 --> 00:26:49,115 because the question was, if you don't live in new Jersey, 584 00:26:49,115 --> 00:26:49,608 Virginia 585 00:26:49,608 --> 00:26:51,975 or California or some of these southern, 586 00:26:51,975 --> 00:26:52,744 places where 587 00:26:53,011 --> 00:26:54,904 either the attorney general has issued 588 00:26:54,904 --> 00:26:56,548 a statement or things like this. 589 00:26:58,550 --> 00:26:59,952 Who's LR? 590 00:26:59,952 --> 00:27:00,953 Right. 591 00:27:00,953 --> 00:27:03,956 So that was always a debatable question. 592 00:27:05,357 --> 00:27:10,562 Until, in 2018, the post 2018 593 00:27:10,829 --> 00:27:13,572 comment revise common rule says this 594 00:27:13,572 --> 00:27:15,934 if there is no applicable law, 595 00:27:17,002 --> 00:27:18,203 then it 596 00:27:18,203 --> 00:27:22,140 means an individual recognized by institutional policy. 597 00:27:22,140 --> 00:27:26,411 So it actually gives authority to academic 598 00:27:26,411 --> 00:27:29,515 institutions, research institutions, 599 00:27:29,515 --> 00:27:33,673 and other settings within which the person, is 600 00:27:33,673 --> 00:27:34,486 involved 601 00:27:34,486 --> 00:27:37,489 in research. 602 00:27:40,526 --> 00:27:40,959 All right. 603 00:27:40,959 --> 00:27:45,164 So putting aside that special institutional, 604 00:27:47,533 --> 00:27:48,500 not putting aside 605 00:27:48,500 --> 00:27:51,503 what's the right word, even if, sorry, 606 00:27:52,104 --> 00:27:55,363 the institutions have policies, they have to sort of appeal to 607 00:27:55,363 --> 00:27:55,941 something. 608 00:27:55,941 --> 00:27:56,575 Right. 609 00:27:56,575 --> 00:27:59,239 So I'm just going to go through different 610 00:27:59,239 --> 00:28:01,513 types of layer possibilities okay. 611 00:28:01,980 --> 00:28:04,269 So one is obviously legal guardians, 612 00:28:04,269 --> 00:28:05,350 legal guardians. 613 00:28:06,184 --> 00:28:09,187 Are people appointed by judges. 614 00:28:10,322 --> 00:28:13,859 So there's real legal clarity 615 00:28:13,859 --> 00:28:16,199 as to why they have the authority 616 00:28:16,199 --> 00:28:17,262 and who it is. 617 00:28:17,529 --> 00:28:21,600 But sometimes these are people who are total strangers to 618 00:28:22,801 --> 00:28:27,039 the person, the, the, who, who has lost capacity. 619 00:28:27,472 --> 00:28:31,109 So there's no necessarily link that you would hope to have 620 00:28:31,343 --> 00:28:33,711 if you think you want them to represent 621 00:28:33,711 --> 00:28:35,047 that person's wishes. 622 00:28:35,581 --> 00:28:37,623 Second type is health care proxies 623 00:28:37,623 --> 00:28:38,283 or durable 624 00:28:38,283 --> 00:28:42,087 power of attorneys, where the subject's own choice 625 00:28:43,455 --> 00:28:46,592 picks out who should serve 626 00:28:46,592 --> 00:28:49,628 to play that role. 627 00:28:49,628 --> 00:28:52,831 But usually that's for, clinical decisions. 628 00:28:53,832 --> 00:28:56,835 And it's extrapolated to research questions. 629 00:28:57,169 --> 00:28:59,104 De facto family. 630 00:28:59,104 --> 00:29:03,008 This is the most common because, as you'll see, 631 00:29:03,842 --> 00:29:06,297 very few people actually make research 632 00:29:06,297 --> 00:29:06,878 proxies. 633 00:29:06,878 --> 00:29:07,846 It's a nice idea. 634 00:29:07,846 --> 00:29:10,716 Research proxy is a great idea. 635 00:29:10,716 --> 00:29:13,719 Everybody figured out, you know, if I get incapacitated 636 00:29:14,019 --> 00:29:16,120 and I could be eligible for research, 637 00:29:16,120 --> 00:29:17,823 I would like this to be done. 638 00:29:19,291 --> 00:29:21,193 Virtually no one fills that out 639 00:29:21,193 --> 00:29:23,859 unless they're asked to after diagnosis 640 00:29:23,859 --> 00:29:25,364 in a special setting. 641 00:29:25,697 --> 00:29:28,634 So but there is a 642 00:29:28,634 --> 00:29:31,703 this possibility of a concurrent proxy directive, 643 00:29:31,703 --> 00:29:32,204 meaning 644 00:29:32,671 --> 00:29:35,478 if you're diagnosed with an illness 645 00:29:35,478 --> 00:29:36,842 like Alzheimer's 646 00:29:37,943 --> 00:29:40,779 but still able to make other types 647 00:29:40,779 --> 00:29:41,947 of decisions, 648 00:29:41,947 --> 00:29:44,491 one of those decisions could be to appoint 649 00:29:44,491 --> 00:29:45,884 somebody or, you know, 650 00:29:46,318 --> 00:29:48,000 that person might be fully capable 651 00:29:48,000 --> 00:29:49,187 of thinking, following. 652 00:29:50,289 --> 00:29:51,423 I can see that. 653 00:29:51,423 --> 00:29:53,568 I can, you know, I'll be overwhelmed 654 00:29:53,568 --> 00:29:55,594 by all that research information. 655 00:29:55,594 --> 00:29:58,597 Maybe I can't get my own consent, but 656 00:29:59,131 --> 00:30:01,700 my wife always helps me with these decisions. 657 00:30:01,700 --> 00:30:04,703 I trust her, so I'm going to. 658 00:30:04,703 --> 00:30:06,204 You can consult her. 659 00:30:06,204 --> 00:30:07,272 Something like that. 660 00:30:07,272 --> 00:30:10,275 Okay. 661 00:30:11,043 --> 00:30:14,446 This is a list that saccade the secretary's advisory 662 00:30:14,446 --> 00:30:17,582 committee, proposed, which I think is a good one. 663 00:30:18,517 --> 00:30:20,824 So obviously you go with the state law 664 00:30:20,824 --> 00:30:22,888 because that's what the law says. 665 00:30:23,655 --> 00:30:26,792 Dpos for, for health care, they're you extrapolate 666 00:30:26,792 --> 00:30:29,795 to the research context, 667 00:30:29,995 --> 00:30:34,633 hoping that the ethical cover that the, 668 00:30:35,934 --> 00:30:38,270 this provides for health care decisions 669 00:30:38,270 --> 00:30:42,340 also kind of extends to research. 670 00:30:43,308 --> 00:30:45,554 Not unreasonable, given that, you know, that 671 00:30:45,554 --> 00:30:45,911 person 672 00:30:45,911 --> 00:30:48,544 is supposed to represent your values and views or your 673 00:30:48,544 --> 00:30:49,081 interests. 674 00:30:50,282 --> 00:30:50,816 The legal 675 00:30:50,816 --> 00:30:54,052 guardian notice that it's third not in the top. 676 00:30:55,053 --> 00:30:57,389 And then the rest of it is, 677 00:30:57,389 --> 00:31:00,459 hierarchy for de facto family members, 678 00:31:00,826 --> 00:31:02,888 although eight is a if you don't have 679 00:31:02,888 --> 00:31:05,230 family members, there's special, writing. 680 00:31:05,230 --> 00:31:07,463 So this is very similar to what we have 681 00:31:07,463 --> 00:31:09,468 in the clinical center at the NIH. 682 00:31:09,768 --> 00:31:13,858 And I suspect this would be this is virtually identical 683 00:31:13,858 --> 00:31:14,973 across states. 684 00:31:15,273 --> 00:31:18,243 So virtually every state has a de facto 685 00:31:18,243 --> 00:31:20,421 family surrogate law for clinical 686 00:31:20,421 --> 00:31:21,213 situations. 687 00:31:21,480 --> 00:31:24,483 And most of them recapitulate 688 00:31:24,850 --> 00:31:27,853 an order very similar to this. 689 00:31:28,987 --> 00:31:31,923 This is just to tell you, you should go read it, 690 00:31:31,923 --> 00:31:34,893 because this is a horrifying, 691 00:31:35,894 --> 00:31:39,331 exposé of how guardianship laws can be, 692 00:31:40,499 --> 00:31:42,033 exploited. 693 00:31:42,033 --> 00:31:45,303 And, I just mentioned this is because, you know, 694 00:31:45,303 --> 00:31:49,167 it's important to realize how these things actually work, 695 00:31:49,167 --> 00:31:49,641 right? 696 00:31:49,641 --> 00:31:53,496 Guardianship laws, presumably, are supposed to protect people, 697 00:31:53,496 --> 00:31:53,745 but 698 00:31:55,280 --> 00:31:56,548 if you read this, you 699 00:31:56,548 --> 00:32:00,452 will value the importance of actually understanding 700 00:32:00,452 --> 00:32:02,795 how to play out and how to monitor it 701 00:32:02,795 --> 00:32:04,189 and keep people safe. 702 00:32:04,623 --> 00:32:09,694 So it's written by Rachel Aviv, who I arguably has written 703 00:32:09,694 --> 00:32:12,016 in some of the most seminal New Yorker 704 00:32:12,016 --> 00:32:14,032 article, said that has affected, 705 00:32:15,233 --> 00:32:16,735 health care policy in many ways. 706 00:32:16,735 --> 00:32:17,936 Actually. 707 00:32:17,936 --> 00:32:21,139 Okay, so what proportion of adults 708 00:32:21,139 --> 00:32:24,218 prepare the advanced directive I'm not going to go into this is 709 00:32:24,218 --> 00:32:24,609 a meta. 710 00:32:24,609 --> 00:32:26,611 This is a systematic review. 711 00:32:26,611 --> 00:32:29,581 And basically the bottom line is about a third. 712 00:32:30,182 --> 00:32:32,647 It doesn't matter how chronic your illness is or whether 713 00:32:32,647 --> 00:32:33,351 you're healthy. 714 00:32:34,619 --> 00:32:37,622 It's not something that people do. 715 00:32:37,622 --> 00:32:41,020 So again, you're going to have to fall 716 00:32:41,020 --> 00:32:42,093 back toward 717 00:32:42,093 --> 00:32:44,200 in most situations, this act of family 718 00:32:44,200 --> 00:32:45,697 surrogate decision making. 719 00:32:46,164 --> 00:32:49,167 Okay, I'm going to speed up a little bit. 720 00:32:51,436 --> 00:32:53,371 Just to recap this. 721 00:32:53,371 --> 00:32:54,639 So it appears that the fact 722 00:32:54,639 --> 00:32:56,757 that surrogates will have to be lawyers, 723 00:32:56,757 --> 00:32:58,610 this usually means family members. 724 00:32:58,610 --> 00:33:00,212 But is this acceptable? 725 00:33:00,212 --> 00:33:03,114 So we did a lot of research on this question 726 00:33:03,114 --> 00:33:05,517 and combining it with the risk benefit limits. 727 00:33:05,517 --> 00:33:08,520 So let me just go through some of our data. 728 00:33:08,520 --> 00:33:10,549 It's the most common approach about IRBs 729 00:33:10,549 --> 00:33:12,224 probably is something like this. 730 00:33:12,958 --> 00:33:15,961 Does it have prospect for direct benefit. 731 00:33:16,561 --> 00:33:17,495 Right. 732 00:33:17,495 --> 00:33:19,949 If there's no prospect of direct benefit, 733 00:33:19,949 --> 00:33:21,266 how much risk minimal 734 00:33:21,633 --> 00:33:23,614 so-called minor increase or a minimal risk 735 00:33:23,614 --> 00:33:25,170 and greater than minor increase? 736 00:33:25,537 --> 00:33:26,605 This should be familiar. 737 00:33:26,605 --> 00:33:29,608 If you have or will have 738 00:33:30,041 --> 00:33:32,244 some overview of the pediatric research 739 00:33:32,244 --> 00:33:32,978 regulations. 740 00:33:32,978 --> 00:33:35,313 This doesn't apply to adults actually. 741 00:33:35,313 --> 00:33:35,814 But this. 742 00:33:35,814 --> 00:33:37,661 With that, people have kind of imported 743 00:33:37,661 --> 00:33:39,651 this from the pediatric into how to think 744 00:33:39,651 --> 00:33:41,870 about this incapacitated person's 745 00:33:41,870 --> 00:33:43,955 participation in the research. 746 00:33:44,990 --> 00:33:48,159 Now. So how does the public view family 747 00:33:48,159 --> 00:33:50,962 surrogate and research and what level of risk is 748 00:33:50,962 --> 00:33:51,663 acceptable? 749 00:33:51,930 --> 00:33:52,898 We did a survey. 750 00:33:52,898 --> 00:33:55,039 This is a nationally representative 751 00:33:55,039 --> 00:33:57,669 sample of U.S public who are 50 and older. 752 00:33:58,637 --> 00:34:01,406 And we found that if you ask the question 753 00:34:01,406 --> 00:34:03,317 if patients can't make their own decisions 754 00:34:03,317 --> 00:34:04,409 about being in a study, 755 00:34:05,143 --> 00:34:08,460 and then you see the scenarios and the four columns, should 756 00:34:08,460 --> 00:34:09,247 their society 757 00:34:09,247 --> 00:34:11,481 allow their families to make that decision 758 00:34:11,481 --> 00:34:12,918 in their place, yes or no? 759 00:34:14,452 --> 00:34:17,822 So I'm only giving you the yes, definitely a probably yes. 760 00:34:18,423 --> 00:34:20,792 And it's interesting. 761 00:34:20,792 --> 00:34:22,928 Majorities say yes. 762 00:34:22,928 --> 00:34:27,622 So lumbar puncture, just a physiological study drug 763 00:34:27,622 --> 00:34:28,266 asked. 764 00:34:28,600 --> 00:34:31,149 I think we use something for Alzheimer's 765 00:34:31,149 --> 00:34:33,571 that was kind of similar to something 766 00:34:33,571 --> 00:34:35,576 as risky as taking Motrin and said 767 00:34:35,576 --> 00:34:37,876 aspirin, you know, something like that 768 00:34:38,777 --> 00:34:41,363 vaccine our city is there was an attempt 769 00:34:41,363 --> 00:34:42,914 to try to develop that, 770 00:34:44,215 --> 00:34:47,218 antibodies to your own, 771 00:34:49,187 --> 00:34:52,624 pathologic materials in the brain so that 772 00:34:54,392 --> 00:34:58,563 that is no longer a, the avenue that's pursued. 773 00:34:58,563 --> 00:35:01,213 But in case you were wondering why I have the word vaccine 774 00:35:01,213 --> 00:35:01,533 there, 775 00:35:01,766 --> 00:35:03,635 and then gene therapy. 776 00:35:03,635 --> 00:35:06,605 Okay, so this was a national sample. 777 00:35:06,605 --> 00:35:09,607 Just your typical cross-sectional. 778 00:35:09,975 --> 00:35:11,242 Not very. 779 00:35:11,242 --> 00:35:14,234 You know, we're not asking them, you know, to think about it. 780 00:35:14,234 --> 00:35:14,479 And. 781 00:35:14,479 --> 00:35:17,148 And what about this? We don't do any of that. 782 00:35:17,148 --> 00:35:20,485 However, we have done a study like that. 783 00:35:20,485 --> 00:35:23,488 This is what I call my wedding banquet research 784 00:35:23,488 --> 00:35:26,257 because we have it in hotel. 785 00:35:26,257 --> 00:35:31,296 What wedding back banquet rooms essentially with, you know, 6 to 786 00:35:31,296 --> 00:35:35,255 8, nine people, you know, room full of 60 people, maybe five, 787 00:35:35,255 --> 00:35:36,034 six tables. 788 00:35:36,568 --> 00:35:39,895 And we spent all day having experts talking on either 789 00:35:39,895 --> 00:35:40,271 side. 790 00:35:40,271 --> 00:35:41,172 I yeah. 791 00:35:44,576 --> 00:35:46,978 Both sides. 792 00:35:46,978 --> 00:35:49,746 And, you know, they kind of travel together in 793 00:35:49,746 --> 00:35:50,348 the room. 794 00:35:50,649 --> 00:35:53,652 So this is under the rubric of, 795 00:35:53,852 --> 00:35:57,689 democratic deliberative methods of doing research. 796 00:35:57,689 --> 00:35:59,724 It originates from political science. 797 00:35:59,724 --> 00:36:02,727 I did a lot of this when I was in back in Michigan. 798 00:36:03,161 --> 00:36:06,381 And it's interesting when you actually have people 799 00:36:06,381 --> 00:36:06,831 debate 800 00:36:06,831 --> 00:36:09,387 this here, people talk about that at the 801 00:36:09,387 --> 00:36:09,834 table. 802 00:36:11,669 --> 00:36:14,739 As people become more familiar, because most people don't know 803 00:36:14,739 --> 00:36:17,342 that there is a oversight and regulation of research 804 00:36:17,342 --> 00:36:18,843 by either of these, for instance. 805 00:36:18,843 --> 00:36:21,038 And there are all these regulatory 806 00:36:21,038 --> 00:36:21,813 components. 807 00:36:21,813 --> 00:36:24,449 And you hear both things, the history 808 00:36:24,449 --> 00:36:27,452 of the regulations and the need for this research. 809 00:36:27,685 --> 00:36:30,539 This is what you find is that you'll see in every 810 00:36:30,539 --> 00:36:30,889 case, 811 00:36:30,889 --> 00:36:33,741 the pre-post, there's a shift to greater 812 00:36:33,741 --> 00:36:34,526 acceptance 813 00:36:35,593 --> 00:36:37,796 of family surrogate 814 00:36:37,796 --> 00:36:40,799 consent for those types of research. 815 00:36:42,000 --> 00:36:43,668 So I'm not going to go through each number. 816 00:36:43,668 --> 00:36:46,671 Just notice the trend. 817 00:36:48,540 --> 00:36:49,507 And comments 818 00:36:49,507 --> 00:36:52,911 during deliberations were, really fascinating. 819 00:36:53,845 --> 00:36:55,947 One thing I would say is that, you know, 820 00:36:55,947 --> 00:36:58,049 these research ethics topics, we think, 821 00:36:58,049 --> 00:37:00,549 oh, you know, we need experts to really, 822 00:37:00,549 --> 00:37:02,487 you know, get their intuitions 823 00:37:02,487 --> 00:37:03,455 and so forth. 824 00:37:03,455 --> 00:37:06,424 Honestly, now that these questions 825 00:37:06,424 --> 00:37:09,227 most people can readily understand 826 00:37:09,227 --> 00:37:14,532 with dialog, and if people are quick 827 00:37:14,532 --> 00:37:17,822 to see the dilemma, potential solutions 828 00:37:17,822 --> 00:37:19,003 and so forth. 829 00:37:19,471 --> 00:37:21,106 And that's one of the most impressive 830 00:37:21,106 --> 00:37:23,086 things about when you engage the public 831 00:37:23,086 --> 00:37:24,609 in this kind of the research. 832 00:37:25,043 --> 00:37:27,205 So for example, comments during that 833 00:37:27,205 --> 00:37:29,247 deliberation, participant assess. 834 00:37:29,247 --> 00:37:32,550 But if the answer is no, you can't let families do this, 835 00:37:32,984 --> 00:37:34,709 that surrogates can't give consent, then 836 00:37:34,709 --> 00:37:36,521 there's no hope for ever getting anywhere 837 00:37:37,155 --> 00:37:38,695 because they've seen all the data, 838 00:37:38,695 --> 00:37:40,325 what likely needs are and so forth. 839 00:37:40,592 --> 00:37:41,793 So the answer has to be no. 840 00:37:41,793 --> 00:37:45,130 In my mind, yes, meaning they have to be allowed 841 00:37:45,130 --> 00:37:46,901 participant versus vote by voting 842 00:37:46,901 --> 00:37:48,833 no against surrogate in Parliament. 843 00:37:48,833 --> 00:37:50,755 What you're essentially doing is voting 844 00:37:50,755 --> 00:37:52,036 no to every other family. 845 00:37:52,504 --> 00:37:55,647 You're putting yourself in a position of impacting every 846 00:37:55,647 --> 00:37:56,040 family 847 00:37:56,040 --> 00:37:57,775 who has an Alzheimer's patient. 848 00:37:57,775 --> 00:37:59,630 I thought that's that's a particularly 849 00:37:59,630 --> 00:38:00,411 interesting way 850 00:38:00,411 --> 00:38:03,414 to articulate what a policy does. 851 00:38:04,149 --> 00:38:06,410 This is he's saying, look, it's a policy, 852 00:38:06,410 --> 00:38:08,286 and policy works this way, right? 853 00:38:09,120 --> 00:38:10,121 It's not just about me. 854 00:38:11,389 --> 00:38:13,324 However, they all 855 00:38:13,324 --> 00:38:15,960 repeatedly came back to, comments like this. 856 00:38:15,960 --> 00:38:17,962 So it seems as though we almost have no choice 857 00:38:17,962 --> 00:38:20,031 but to have some form of surrogate dissent. 858 00:38:20,031 --> 00:38:22,667 But the challenge is, how do we make it work? 859 00:38:22,667 --> 00:38:24,969 How do we build protections for the, 860 00:38:24,969 --> 00:38:26,839 you know, people with Alzheimer's 861 00:38:26,839 --> 00:38:27,972 and their families? 862 00:38:28,173 --> 00:38:30,141 And one of the interesting things was that 863 00:38:30,141 --> 00:38:33,144 when we asked people, 864 00:38:33,912 --> 00:38:35,413 should there be leeway, 865 00:38:35,413 --> 00:38:37,318 you know, a person says to you, yeah, 866 00:38:37,318 --> 00:38:39,017 I want to be in research or not. 867 00:38:40,251 --> 00:38:43,615 After you say that to them, if you later became 868 00:38:43,615 --> 00:38:44,689 incapacitated, 869 00:38:45,056 --> 00:38:48,126 how much leeway do you think your family members should have 870 00:38:48,927 --> 00:38:53,298 in going with what you said now, or maybe even going against it 871 00:38:53,932 --> 00:38:57,035 based on what they know then versus now? 872 00:38:57,302 --> 00:38:59,465 And you can see the vast majority think 873 00:38:59,465 --> 00:39:01,573 there should be at least some leeway. 874 00:39:02,040 --> 00:39:04,070 So I think most people understand 875 00:39:04,070 --> 00:39:05,977 the complexity and the limited 876 00:39:06,244 --> 00:39:09,265 complexity of the situation, the limitation of current 877 00:39:09,265 --> 00:39:09,881 knowledge. 878 00:39:09,881 --> 00:39:13,051 When you try to pin down the future of 879 00:39:13,451 --> 00:39:16,020 I want this, I don't want that. So, 880 00:39:17,288 --> 00:39:18,723 I think we often 881 00:39:18,723 --> 00:39:21,726 underestimate the wisdom of, 882 00:39:22,193 --> 00:39:25,196 you know, the public and a lot of these issues. 883 00:39:25,697 --> 00:39:28,166 Okay, I'm just going to run down the list 884 00:39:28,166 --> 00:39:32,704 of other potential protections depending on the situation. 885 00:39:32,971 --> 00:39:36,832 And I just want you to I'm going to contrast two situations very 886 00:39:36,832 --> 00:39:37,375 quickly. 887 00:39:37,609 --> 00:39:39,244 Mr. A has Alzheimer's. 888 00:39:39,244 --> 00:39:40,879 He can't give consent, 889 00:39:40,879 --> 00:39:44,299 but he's a retired professor, financially stable lot of 890 00:39:44,299 --> 00:39:44,983 resources. 891 00:39:44,983 --> 00:39:47,285 Family are support involved. 892 00:39:47,285 --> 00:39:49,610 He enrolls in a novel intervention 893 00:39:49,610 --> 00:39:51,456 only minor adverse events. 894 00:39:52,323 --> 00:39:53,791 Effects seen. 895 00:39:53,791 --> 00:39:56,361 And it has a goal of slowing down the disease. 896 00:39:56,361 --> 00:39:58,529 He really wants to be in the study. 897 00:39:58,529 --> 00:39:59,998 He has an altruistic motive. 898 00:39:59,998 --> 00:40:02,183 He and his desire for benefit, felt 899 00:40:02,183 --> 00:40:03,868 to be a worthwhile gamble. 900 00:40:04,535 --> 00:40:07,005 Now, to me, 901 00:40:07,005 --> 00:40:09,371 this person obviously is vulnerable, 902 00:40:09,371 --> 00:40:11,342 but the kind of vulnerability 903 00:40:11,342 --> 00:40:14,579 experience is very different from the following person. 904 00:40:15,913 --> 00:40:17,849 This person does have members. 905 00:40:17,849 --> 00:40:19,765 This person is did not have consent 906 00:40:19,765 --> 00:40:21,352 because he's quite impaired. 907 00:40:22,153 --> 00:40:24,956 This person meets the threshold 908 00:40:24,956 --> 00:40:28,660 for capacity, so in theory can consent for him or herself. 909 00:40:28,660 --> 00:40:31,138 However is single, estranged from family, 910 00:40:31,138 --> 00:40:31,863 unemployed, 911 00:40:31,863 --> 00:40:36,434 isolated in a minority group or city of a compound 912 00:40:36,434 --> 00:40:39,032 that's already marketed as being studied 913 00:40:39,032 --> 00:40:40,071 a meeting drug. 914 00:40:40,638 --> 00:40:43,641 And it's not a new paradigm, 915 00:40:44,375 --> 00:40:45,873 you know, it's you could even say 916 00:40:45,873 --> 00:40:47,779 there are strong marketing considerations 917 00:40:47,779 --> 00:40:49,347 this study like this. 918 00:40:49,347 --> 00:40:52,040 And he himself may not have a strong incentive 919 00:40:52,040 --> 00:40:52,684 to enroll. 920 00:40:52,684 --> 00:40:55,217 I think I would say that this person is, 921 00:40:55,217 --> 00:40:57,055 is more much more vulnerable 922 00:40:57,055 --> 00:40:59,862 than the previous person, even though this person has 923 00:40:59,862 --> 00:41:00,391 capacity. 924 00:41:00,692 --> 00:41:02,789 And I think this is really important 925 00:41:02,789 --> 00:41:04,595 to remember other protections. 926 00:41:05,129 --> 00:41:06,956 So you have to think about, depending 927 00:41:06,956 --> 00:41:08,733 on the context or things like this, 928 00:41:10,234 --> 00:41:12,103 how rigorous, how well 929 00:41:12,103 --> 00:41:15,106 defined, how much, who is for what the capacity assessment. 930 00:41:16,174 --> 00:41:18,059 Is there any way we can sort of work 931 00:41:18,059 --> 00:41:19,577 with the presumed abilities? 932 00:41:19,577 --> 00:41:23,281 Because that's a gradation to show. 933 00:41:23,281 --> 00:41:27,354 We have subject advocates, study partners, consent or city 934 00:41:27,354 --> 00:41:27,986 monitors 935 00:41:27,986 --> 00:41:31,640 independent of the researchers assessment of appropriate 936 00:41:31,640 --> 00:41:32,423 surrogates. 937 00:41:32,790 --> 00:41:37,362 You know, sometimes surrogates may also be 95 years old, right. 938 00:41:37,862 --> 00:41:41,966 And it's not the age that it makes you vulnerable 939 00:41:42,934 --> 00:41:45,742 or incapacitated, but that puts you at an 940 00:41:45,742 --> 00:41:46,838 increased risk. 941 00:41:46,838 --> 00:41:49,841 So there may be a need to assess that and other. 942 00:41:51,042 --> 00:41:52,977 So it should be tailored to context.