1 00:00:12,579 --> 00:00:13,580 What I'm going to talk to you about 2 00:00:13,580 --> 00:00:16,683 today is the ethical inclusion of children in research. 3 00:00:16,683 --> 00:00:20,429 And the goal of this talk is really to show you how we've 4 00:00:20,429 --> 00:00:20,954 shifted 5 00:00:21,221 --> 00:00:23,920 over time to recognizing the importance 6 00:00:23,920 --> 00:00:24,958 of responsible 7 00:00:24,958 --> 00:00:26,772 inclusion of children, instead of 8 00:00:26,772 --> 00:00:28,695 just focusing on their protection. 9 00:00:28,996 --> 00:00:31,591 Recognizing that if you just focus on 10 00:00:31,591 --> 00:00:32,432 protection, 11 00:00:32,432 --> 00:00:35,146 then you miss out on many potential 12 00:00:35,146 --> 00:00:37,704 benefits for children as a group 13 00:00:37,704 --> 00:00:40,774 and actually expose them to risks in clinical care. 14 00:00:43,810 --> 00:00:46,179 So the big motivation 15 00:00:46,179 --> 00:00:49,182 behind pediatric research, which I think a lot of people 16 00:00:49,383 --> 00:00:51,941 who haven't spent a lot of time thinking about pediatric 17 00:00:51,941 --> 00:00:52,352 research 18 00:00:52,352 --> 00:00:54,846 don't realize is that there's a great need 19 00:00:54,846 --> 00:00:56,390 to find the interventions 20 00:00:56,390 --> 00:00:57,975 and doses that work for children, 21 00:00:57,975 --> 00:00:59,993 given that they're not just small adults. 22 00:01:00,427 --> 00:01:05,565 This study was done to show even there are these enormous 23 00:01:05,565 --> 00:01:07,427 differences between adults and children 24 00:01:07,427 --> 00:01:09,002 with respect to heat perception. 25 00:01:09,536 --> 00:01:12,205 And this is because of things like the surface 26 00:01:12,205 --> 00:01:15,242 area to body mass ratio and the metabolic rate. 27 00:01:15,242 --> 00:01:17,553 And in different kids or even that there 28 00:01:17,553 --> 00:01:19,980 is lower in they're closer to the ground. 29 00:01:20,247 --> 00:01:23,025 So all of these things, in many cases, 30 00:01:23,025 --> 00:01:23,684 not all, 31 00:01:24,251 --> 00:01:26,853 suggest that there's a need to do specific research 32 00:01:26,853 --> 00:01:29,191 on children for different interventions 33 00:01:29,191 --> 00:01:30,390 and conditions. And 34 00:01:31,358 --> 00:01:32,159 this quote, I think, 35 00:01:32,159 --> 00:01:34,146 really sums it up nicely that the vast 36 00:01:34,146 --> 00:01:36,029 majority of drugs were not designed 37 00:01:36,029 --> 00:01:39,032 or developed for pediatric or infant populations. 38 00:01:40,701 --> 00:01:43,097 So what I'd like to do today is first talk about this 39 00:01:43,097 --> 00:01:43,503 question 40 00:01:43,503 --> 00:01:46,338 of when to enroll children in research 41 00:01:46,338 --> 00:01:47,307 with respect 42 00:01:47,307 --> 00:01:51,078 to other types of research, particularly research in adults. 43 00:01:51,445 --> 00:01:54,181 Then we'll talk about risks and benefits, 44 00:01:54,181 --> 00:01:56,116 and turn to decision making, 45 00:01:56,116 --> 00:01:59,119 focusing on consent and decent. 46 00:02:00,287 --> 00:02:02,637 So first, when we enroll children in 47 00:02:02,637 --> 00:02:03,290 research, 48 00:02:03,690 --> 00:02:06,560 the first question is who is a child? 49 00:02:06,560 --> 00:02:08,806 And legally and culturally, that actually 50 00:02:08,806 --> 00:02:10,998 varies quite a bit from place to place. 51 00:02:11,698 --> 00:02:13,718 The typical definition is that children 52 00:02:13,718 --> 00:02:15,168 or people who are too young 53 00:02:15,168 --> 00:02:17,229 to give their own consent legally, 54 00:02:17,229 --> 00:02:18,805 and in the United States, 55 00:02:18,805 --> 00:02:21,358 this actually even within the United States, this 56 00:02:21,358 --> 00:02:21,775 varies. 57 00:02:21,775 --> 00:02:23,443 So there are two states where, 58 00:02:24,511 --> 00:02:25,612 you don't 59 00:02:25,612 --> 00:02:28,156 have the ability to give general counsel 60 00:02:28,156 --> 00:02:28,982 your 19 year 61 00:02:28,982 --> 00:02:32,019 A minor until you're 19. 62 00:02:32,019 --> 00:02:34,321 And then around the world, this varies as well. 63 00:02:34,321 --> 00:02:37,391 There is at least one country for youth to be 21. 64 00:02:39,526 --> 00:02:41,461 And we'll talk more about consent. 65 00:02:41,461 --> 00:02:43,369 But part of the problem that arises 66 00:02:43,369 --> 00:02:44,731 is that because children 67 00:02:44,731 --> 00:02:47,167 can't give their own consent, at least legally 68 00:02:47,167 --> 00:02:49,032 and often lack lacking the capacity 69 00:02:49,032 --> 00:02:50,470 to give their own consent. 70 00:02:51,138 --> 00:02:53,042 There are lots of reasons you might want 71 00:02:53,042 --> 00:02:54,708 to study adults first in research. 72 00:02:55,776 --> 00:02:57,424 First is that in general, children 73 00:02:57,424 --> 00:02:59,413 are more vulnerable to harm than adults. 74 00:02:59,813 --> 00:03:02,264 It's better not to expose them to unknown 75 00:03:02,264 --> 00:03:02,682 risks. 76 00:03:02,682 --> 00:03:04,718 And this is both because, 77 00:03:04,718 --> 00:03:08,106 there may be certain risks that could compound over the 78 00:03:08,106 --> 00:03:08,722 lifespan, 79 00:03:09,056 --> 00:03:13,223 and also because, children may have less 80 00:03:13,223 --> 00:03:14,161 immunity 81 00:03:14,161 --> 00:03:17,464 to things or be more fragile in certain respects than adults. 82 00:03:18,698 --> 00:03:20,946 Additionally, because children cannot give their own 83 00:03:20,946 --> 00:03:21,334 consent, 84 00:03:21,334 --> 00:03:23,712 they can't protect their own interests 85 00:03:23,712 --> 00:03:24,337 directly. 86 00:03:25,305 --> 00:03:27,674 And then finally, there's a greater potential 87 00:03:27,674 --> 00:03:29,637 for negative attention if something goes 88 00:03:29,637 --> 00:03:31,011 wrong in a pediatric trial. 89 00:03:31,411 --> 00:03:33,563 There's often this concern that if you're 90 00:03:33,563 --> 00:03:35,715 relying really only on parental consent, 91 00:03:36,550 --> 00:03:39,553 for permission to enroll a child in research, 92 00:03:39,553 --> 00:03:42,522 you may not be getting at, 93 00:03:42,522 --> 00:03:46,000 the the same level of moral transformation 94 00:03:46,000 --> 00:03:46,993 that occurs 95 00:03:46,993 --> 00:03:49,121 when somebody consents to research 96 00:03:49,121 --> 00:03:49,996 for their own 97 00:03:50,330 --> 00:03:52,999 participation. 98 00:03:52,999 --> 00:03:54,692 However, there are lots of reasons 99 00:03:54,692 --> 00:03:56,036 to enroll children sooner. 100 00:03:56,303 --> 00:03:58,375 So sometimes children can receive 101 00:03:58,375 --> 00:04:01,074 important benefits directly from research, 102 00:04:01,074 --> 00:04:03,473 especially if there are few alternatives, 103 00:04:03,473 --> 00:04:05,579 and this is often the case in later 104 00:04:05,579 --> 00:04:09,266 stage treatment trials, particularly trials and rare 105 00:04:09,266 --> 00:04:10,117 conditions. 106 00:04:10,984 --> 00:04:13,720 Some diseases or conditions also only affect 107 00:04:13,720 --> 00:04:16,857 children or affect children differently. 108 00:04:16,857 --> 00:04:19,893 So for instance, tuberculosis 109 00:04:19,893 --> 00:04:22,963 is in children under ten very different 110 00:04:22,963 --> 00:04:24,931 from adult tuberculosis. 111 00:04:24,931 --> 00:04:27,234 And once children reach the ten, it's 112 00:04:27,234 --> 00:04:29,334 essentially similar, a similar condition 113 00:04:29,334 --> 00:04:31,171 to how it's experienced in adults. 114 00:04:32,873 --> 00:04:34,908 But there's also the issue of 115 00:04:34,908 --> 00:04:37,089 things like malaria, which is a condition 116 00:04:37,089 --> 00:04:38,845 that affects people of all ages. 117 00:04:38,845 --> 00:04:42,682 But, children under five can have more severe cases. 118 00:04:43,150 --> 00:04:45,886 So there are lots of reasons based on that. 119 00:04:45,886 --> 00:04:49,526 But sometimes you have to study a condition by studying it in 120 00:04:49,526 --> 00:04:50,123 children. 121 00:04:51,258 --> 00:04:53,193 Finally, there's, 122 00:04:53,193 --> 00:04:57,977 if you delay pediatric testing, that can lead to a sort of 123 00:04:57,977 --> 00:04:59,132 domino effect 124 00:04:59,132 --> 00:05:02,135 for ultimately licensure or availability of the test. 125 00:05:02,135 --> 00:05:05,272 Intervention is also delayed for children. 126 00:05:06,606 --> 00:05:08,814 So when you turn to ethical guidance 127 00:05:08,814 --> 00:05:10,777 to figure out how do we balance 128 00:05:10,777 --> 00:05:12,427 these different reasons for and against 129 00:05:12,427 --> 00:05:13,780 enrolling children in research? 130 00:05:15,348 --> 00:05:17,250 The World Health Organization 131 00:05:17,250 --> 00:05:18,821 has the Council for International 132 00:05:18,821 --> 00:05:20,487 Organizations of Medical Sciences, 133 00:05:20,487 --> 00:05:22,317 and you've probably heard of this 134 00:05:22,317 --> 00:05:24,257 talk about this guidance in other, 135 00:05:25,358 --> 00:05:26,059 sessions. 136 00:05:26,059 --> 00:05:28,298 This is really influential guidance, 137 00:05:28,298 --> 00:05:30,163 actually, in 2016 said adults 138 00:05:30,163 --> 00:05:33,200 should be first in research in all cases. 139 00:05:33,200 --> 00:05:36,670 And the Declaration of Helsinki, the 2013 version said 140 00:05:36,670 --> 00:05:39,987 that people who cannot consent, which includes children by 141 00:05:39,987 --> 00:05:40,674 definition, 142 00:05:40,674 --> 00:05:42,492 should not be enrolled in research 143 00:05:42,492 --> 00:05:44,044 unless there's a prospective 144 00:05:44,044 --> 00:05:46,649 direct benefit or the research is designed 145 00:05:46,649 --> 00:05:48,014 to promote the health 146 00:05:48,014 --> 00:05:50,283 of the group, involves minimal risk 147 00:05:50,283 --> 00:05:52,552 or burden, and cannot be performed 148 00:05:52,752 --> 00:05:55,822 with people who can consent. 149 00:05:55,822 --> 00:05:58,827 So, you know, many of the existing guidance 150 00:05:58,827 --> 00:05:59,526 documents 151 00:05:59,526 --> 00:06:01,361 are actually somewhat restrictive 152 00:06:01,361 --> 00:06:03,363 about when children can be enrolled 153 00:06:03,363 --> 00:06:06,499 in research. 154 00:06:06,499 --> 00:06:08,505 There is, I think, the sort of most 155 00:06:08,505 --> 00:06:09,135 systematic 156 00:06:09,135 --> 00:06:13,272 approach that I found on this was from as far back as 157 00:06:13,272 --> 00:06:13,740 2004. 158 00:06:14,074 --> 00:06:17,304 So this was a group, the European specialists in 159 00:06:17,304 --> 00:06:18,111 pediatrics, 160 00:06:18,111 --> 00:06:21,079 who came together to say, when should we enroll children 161 00:06:21,079 --> 00:06:21,715 in research 162 00:06:21,715 --> 00:06:24,451 and think, try to think about it somewhat more systematically 163 00:06:24,451 --> 00:06:26,194 from the perspective of phases and, 164 00:06:26,194 --> 00:06:27,787 of course, phases and research, 165 00:06:28,421 --> 00:06:30,624 which you've probably heard about in other classes as well. 166 00:06:30,624 --> 00:06:34,794 They're not always, applicable to all types of research, but 167 00:06:35,228 --> 00:06:38,231 they the way they thought about it was, is 168 00:06:39,099 --> 00:06:41,568 the disease was only affecting children. 169 00:06:42,602 --> 00:06:43,203 Then you 170 00:06:43,203 --> 00:06:45,767 needed to have preclinical safety data 171 00:06:45,767 --> 00:06:46,239 first, 172 00:06:46,239 --> 00:06:48,797 but you could go directly to enrolling children in 173 00:06:48,797 --> 00:06:49,309 research. 174 00:06:51,611 --> 00:06:53,700 The second category would be diseases 175 00:06:53,700 --> 00:06:55,282 that mainly affect children 176 00:06:55,282 --> 00:06:56,922 or that are very serious in children, 177 00:06:56,922 --> 00:06:58,785 or where there's no or limited treatment. 178 00:06:59,252 --> 00:07:02,856 And there there was a need for some preclinical safety data 179 00:07:02,856 --> 00:07:06,426 and some adult efficacy data before enrolling children. 180 00:07:07,494 --> 00:07:10,500 Now, when you turn to diseases in adults and kids where there 181 00:07:10,500 --> 00:07:10,697 are 182 00:07:10,697 --> 00:07:12,907 treatment options, then the idea was 183 00:07:12,907 --> 00:07:15,302 that you would actually go all the way 184 00:07:15,302 --> 00:07:17,241 through all the research on adults 185 00:07:17,241 --> 00:07:18,838 before turning to children. 186 00:07:20,006 --> 00:07:22,642 And this, I think, is really at least 187 00:07:22,642 --> 00:07:25,812 one of the most sustained efforts 188 00:07:25,812 --> 00:07:28,768 to be more systematic about when to enroll children in 189 00:07:28,768 --> 00:07:29,316 research. 190 00:07:30,250 --> 00:07:32,852 However, these recommendations 191 00:07:32,852 --> 00:07:34,969 don't focus directly on the risks 192 00:07:34,969 --> 00:07:36,956 and benefits of a given trial. 193 00:07:36,956 --> 00:07:39,559 They sort of assume the risks and benefits based on, 194 00:07:40,794 --> 00:07:43,797 whether there are treatment options and 195 00:07:44,064 --> 00:07:45,804 and whether the disease only affects 196 00:07:45,804 --> 00:07:47,400 children or also affects adults. 197 00:07:48,268 --> 00:07:50,849 They also don't focus directly on the importance of the 198 00:07:50,849 --> 00:07:51,271 research 199 00:07:51,271 --> 00:07:52,505 or the social value, 200 00:07:52,505 --> 00:07:54,318 which I think you've also heard about in this 201 00:07:54,318 --> 00:07:54,641 course. 202 00:07:54,641 --> 00:07:57,367 And then they don't focus on the differences between 203 00:07:57,367 --> 00:07:57,944 prevention 204 00:07:57,944 --> 00:07:58,411 and treatment. 205 00:07:58,411 --> 00:08:00,483 They're really just focused on treatment 206 00:08:00,483 --> 00:08:01,881 for an existing condition. 207 00:08:02,115 --> 00:08:05,118 And not on research on things like vaccines to prevent 208 00:08:05,118 --> 00:08:05,618 children 209 00:08:05,618 --> 00:08:08,922 from being infected with a particular disease. 210 00:08:10,023 --> 00:08:12,267 So I think it really may make more sense 211 00:08:12,267 --> 00:08:13,893 to focus on the risk benefit 212 00:08:13,893 --> 00:08:16,140 ratio of research, given the available 213 00:08:16,140 --> 00:08:18,565 alternatives for a particular condition. 214 00:08:18,865 --> 00:08:22,302 And get more granular to decide when to enroll children. 215 00:08:23,336 --> 00:08:26,339 I think this is a helpful piece of, 216 00:08:27,240 --> 00:08:28,950 guidance that can help when you're 217 00:08:28,950 --> 00:08:30,810 thinking about treatment trials and, 218 00:08:32,045 --> 00:08:33,742 at least I think was one of the first 219 00:08:33,742 --> 00:08:34,247 approaches 220 00:08:34,247 --> 00:08:37,250 to approach this systematically. 221 00:08:37,751 --> 00:08:39,780 There's also an additional protection 222 00:08:39,780 --> 00:08:40,987 that people sometimes 223 00:08:41,588 --> 00:08:43,611 talk about, which is called age 224 00:08:43,611 --> 00:08:44,591 de-escalation. 225 00:08:44,791 --> 00:08:48,361 And this is sort of the idea is that first you have to decide 226 00:08:48,361 --> 00:08:50,750 when do enroll children in general, 227 00:08:50,750 --> 00:08:51,364 and then 228 00:08:51,865 --> 00:08:53,518 how do you additionally protect them 229 00:08:53,518 --> 00:08:55,035 when you start to your children. 230 00:08:55,035 --> 00:08:57,001 And the idea is really that in a stepwise 231 00:08:57,001 --> 00:08:58,872 fashion, you start with older children 232 00:08:59,139 --> 00:09:02,142 and then work your way down to the youngest children. 233 00:09:02,542 --> 00:09:06,268 This has been used in research on treatments for malaria, 234 00:09:06,268 --> 00:09:07,313 cancer and flu, 235 00:09:07,580 --> 00:09:11,418 and vaccine trials on anthrax, typhoid, enterovirus 236 00:09:11,418 --> 00:09:14,421 and a number of other conditions. 237 00:09:14,654 --> 00:09:17,357 What's interesting is that this is often 238 00:09:17,357 --> 00:09:20,894 presumed to be a valuable safeguard. 239 00:09:20,894 --> 00:09:23,804 And, the president's commission environment, there's some 240 00:09:23,804 --> 00:09:24,264 thinking 241 00:09:24,264 --> 00:09:29,030 about research and biomedical countermeasures really focused 242 00:09:29,030 --> 00:09:29,269 on 243 00:09:29,536 --> 00:09:32,639 de-escalation is one of the ways to justify research in children. 244 00:09:32,939 --> 00:09:36,543 So there are many special cases where it's really important. 245 00:09:36,876 --> 00:09:38,945 But what's interesting, I think, is that 246 00:09:38,945 --> 00:09:41,014 for a long time, people sort of treated 247 00:09:41,548 --> 00:09:43,282 glaceon as if it was just generally 248 00:09:43,282 --> 00:09:44,918 the approach that you should use 249 00:09:44,918 --> 00:09:47,720 without questioning it. And more recently, 250 00:09:48,822 --> 00:09:49,522 during especially 251 00:09:49,522 --> 00:09:52,625 during the Covid pandemic, people started to question 252 00:09:52,625 --> 00:09:55,628 whether de-escalation was always the best idea. 253 00:09:56,029 --> 00:09:58,281 So this paper really nicely talks 254 00:09:58,281 --> 00:09:59,032 about how, 255 00:10:00,099 --> 00:10:03,103 de-escalation used during the Covid pandemic 256 00:10:03,403 --> 00:10:07,006 led to particular farms and really didn't 257 00:10:07,407 --> 00:10:09,309 address the potential benefits of research 258 00:10:09,309 --> 00:10:10,577 for certain groups of kids. 259 00:10:11,110 --> 00:10:13,512 They noted that although young children had 260 00:10:13,512 --> 00:10:13,847 lower 261 00:10:13,847 --> 00:10:16,850 risks from Covid 19 infection than many other groups, 262 00:10:17,150 --> 00:10:20,987 there were still 651 deaths and over 263 00:10:20,987 --> 00:10:24,691 2000 cases of a multi, a systemic, 264 00:10:25,692 --> 00:10:28,820 inflammatory syndrome in children under the age of 265 00:10:28,820 --> 00:10:29,195 five. 266 00:10:30,063 --> 00:10:32,251 And due to the use of de-escalation, 267 00:10:32,251 --> 00:10:34,501 the vaccines for children under five 268 00:10:34,501 --> 00:10:37,670 were not available during one of the biggest surges 269 00:10:37,670 --> 00:10:40,635 that occurred, the Omicron sort of Omicron surge in 270 00:10:40,635 --> 00:10:41,508 December 2021. 271 00:10:42,742 --> 00:10:45,255 And children had the largest increase 272 00:10:45,255 --> 00:10:46,613 in hospitalizations 273 00:10:46,613 --> 00:10:50,750 and at that time, for children under five specifically. 274 00:10:51,718 --> 00:10:52,418 So what 275 00:10:52,418 --> 00:10:55,296 these authors conclude is that we really should think 276 00:10:55,296 --> 00:10:55,622 about 277 00:10:56,222 --> 00:10:59,492 collection more carefully and recognize 278 00:10:59,492 --> 00:11:01,583 that it can be particularly problematic 279 00:11:01,583 --> 00:11:02,762 in a number of cases. 280 00:11:02,762 --> 00:11:06,499 But I think the one that really is the important to learn 281 00:11:06,866 --> 00:11:08,879 Covid 19 example is that if you have 282 00:11:08,879 --> 00:11:11,171 an unduly narrow conception of the risks 283 00:11:11,171 --> 00:11:14,173 and benefits for children to be involved in research, 284 00:11:14,440 --> 00:11:17,443 then you may find that, 285 00:11:18,945 --> 00:11:19,512 de-escalation 286 00:11:19,512 --> 00:11:22,134 actually prevents children from accessing important 287 00:11:22,134 --> 00:11:22,649 benefits. 288 00:11:22,649 --> 00:11:24,284 I think there are at least two ways 289 00:11:24,284 --> 00:11:25,919 that this played out during Covid. 290 00:11:26,252 --> 00:11:28,655 One was there was, 291 00:11:28,655 --> 00:11:32,759 a lack of appreciation that even young children 292 00:11:32,759 --> 00:11:35,044 could have serious risks from Covid 293 00:11:35,044 --> 00:11:35,762 infection. 294 00:11:36,863 --> 00:11:39,832 And the second is that children, 295 00:11:39,832 --> 00:11:42,101 the fact that children could become infected 296 00:11:42,101 --> 00:11:45,325 within their families and infect their parents and miss time from 297 00:11:45,325 --> 00:11:45,672 school 298 00:11:45,972 --> 00:11:48,975 not being daycare, and all of those things, 299 00:11:49,642 --> 00:11:52,111 were significant 300 00:11:52,111 --> 00:11:55,682 indirect forms that could apply to children 301 00:11:55,682 --> 00:11:57,507 that weren't just the standard ways 302 00:11:57,507 --> 00:11:59,385 that we calculate benefit and risk. 303 00:12:00,153 --> 00:12:01,988 And those things were pretty much 304 00:12:01,988 --> 00:12:04,324 neglected as people considered when to in 305 00:12:04,324 --> 00:12:05,525 children in research. 306 00:12:07,126 --> 00:12:07,594 So I think 307 00:12:07,594 --> 00:12:11,517 the lesson from Covid 19 is that in general, children 308 00:12:11,517 --> 00:12:12,332 were often 309 00:12:12,332 --> 00:12:14,814 an afterthought in these research and policy 310 00:12:14,814 --> 00:12:15,435 decisions, 311 00:12:15,802 --> 00:12:18,037 and we need to do a better job of trying 312 00:12:18,037 --> 00:12:20,273 to benefit children in future pandemics 313 00:12:20,273 --> 00:12:22,191 and to think more comprehensively 314 00:12:22,191 --> 00:12:24,110 about the kinds of benefits that 315 00:12:24,477 --> 00:12:26,824 enrollment and research can lead to for individual 316 00:12:26,824 --> 00:12:27,246 children 317 00:12:27,246 --> 00:12:29,148 and children in this group. 318 00:12:29,148 --> 00:12:31,684 And with several of my colleagues from, 319 00:12:31,684 --> 00:12:33,186 former colleagues from the Department 320 00:12:33,186 --> 00:12:34,687 of Bioethics who wrote this paper on 321 00:12:35,021 --> 00:12:37,964 and went to enroll minors in Covid vaccine 322 00:12:37,964 --> 00:12:38,524 trials, 323 00:12:38,925 --> 00:12:41,514 learning as an attempt to really learn from that 324 00:12:41,514 --> 00:12:42,161 experience. 325 00:12:44,430 --> 00:12:46,766 Okay, so we've talked about the importance 326 00:12:46,766 --> 00:12:48,835 of really focusing on the risks and benefits. 327 00:12:48,835 --> 00:12:50,169 So what does that mean? 328 00:12:50,169 --> 00:12:53,379 How do we focus on risks and benefits in research with 329 00:12:53,379 --> 00:12:53,973 children. 330 00:12:55,208 --> 00:12:57,277 So most regulations including 331 00:12:57,277 --> 00:12:59,498 the Council of Europe Uganda CMS, 332 00:12:59,498 --> 00:13:01,114 as I mentioned earlier, 333 00:13:02,548 --> 00:13:04,904 the legislation in South Africa, Canada, 334 00:13:04,904 --> 00:13:05,551 Australia, 335 00:13:05,852 --> 00:13:09,989 they all permit research that in sort of two categories. 336 00:13:09,989 --> 00:13:13,613 First, research that offers a prospect of direct benefit to 337 00:13:13,613 --> 00:13:14,227 the child 338 00:13:14,560 --> 00:13:16,591 that outweighs the risks, especially 339 00:13:16,591 --> 00:13:18,564 in comparison to the alternatives. 340 00:13:19,165 --> 00:13:21,732 And then the second category is research 341 00:13:21,732 --> 00:13:23,336 that poses minimal risk. 342 00:13:24,070 --> 00:13:26,109 So this is research that's not supposed 343 00:13:26,109 --> 00:13:27,573 to be to benefit the child, 344 00:13:27,573 --> 00:13:30,134 but the amount of risk that it poses 345 00:13:30,134 --> 00:13:31,344 is just minimal. 346 00:13:33,312 --> 00:13:36,382 U.S. federal regulation or 347 00:13:36,382 --> 00:13:39,352 a lot of other regulations around the world. 348 00:13:39,352 --> 00:13:42,014 Except in cases where I think there are countries that have 349 00:13:42,014 --> 00:13:42,555 essentially 350 00:13:42,555 --> 00:13:44,935 just adopted our regulations and, 351 00:13:44,935 --> 00:13:47,460 codified them into their own laws. 352 00:13:47,760 --> 00:13:50,122 So our regulations have four categories 353 00:13:50,122 --> 00:13:51,030 of protection, 354 00:13:51,264 --> 00:13:55,034 which include the first two that we talked about that exist 355 00:13:55,034 --> 00:13:58,171 around the world, and two others that are much less common. 356 00:13:58,171 --> 00:14:00,516 So we can do research into minimal risk 357 00:14:00,516 --> 00:14:03,042 research that offers a prospect of direct 358 00:14:03,042 --> 00:14:06,640 benefit that outweighs the risk as pretty much anywhere in the 359 00:14:06,640 --> 00:14:07,046 world. 360 00:14:07,613 --> 00:14:10,616 And you can also do research in the United States 361 00:14:11,017 --> 00:14:13,341 if it's approved by an institutional review 362 00:14:13,341 --> 00:14:13,720 board, 363 00:14:13,720 --> 00:14:17,457 because it poses a minor increase of mental over minimal 364 00:14:17,457 --> 00:14:17,857 risk. 365 00:14:17,857 --> 00:14:19,933 And that's okay, even if there's no 366 00:14:19,933 --> 00:14:21,594 prospect of direct benefit. 367 00:14:21,961 --> 00:14:25,531 However, in this category, the research has to benefit the, 368 00:14:26,599 --> 00:14:27,667 group of 369 00:14:27,667 --> 00:14:29,979 participants from which the participants 370 00:14:29,979 --> 00:14:30,903 are coming from 371 00:14:31,571 --> 00:14:34,574 and benefit their condition or disorder. 372 00:14:35,007 --> 00:14:37,637 And finally, there's a sort of catchall 373 00:14:37,637 --> 00:14:38,244 category 374 00:14:38,244 --> 00:14:41,380 where if research doesn't fit into any of these categories, 375 00:14:41,681 --> 00:14:43,836 it can be taken to a special panel 376 00:14:43,836 --> 00:14:46,119 and approved by that special panel, 377 00:14:46,119 --> 00:14:47,736 which is appointed by the Secretary 378 00:14:47,736 --> 00:14:49,122 of Health and Human Services. 379 00:14:50,957 --> 00:14:52,425 So when we look 380 00:14:52,425 --> 00:14:53,947 at these regulations, an important 381 00:14:53,947 --> 00:14:55,828 question is what do all these words mean? 382 00:14:55,828 --> 00:14:58,862 How are they defined and their definitions 383 00:14:58,862 --> 00:15:01,534 are not as robust as you might like. 384 00:15:02,001 --> 00:15:03,703 So minimal risk. 385 00:15:03,703 --> 00:15:06,405 I think this definition is, 386 00:15:06,405 --> 00:15:09,837 helpful and has been really operationalized by many 387 00:15:09,837 --> 00:15:10,510 scholars. 388 00:15:10,843 --> 00:15:12,378 So minimal risks 389 00:15:12,378 --> 00:15:16,096 involves the risks of daily life or of routine examinations or 390 00:15:16,096 --> 00:15:16,516 tests. 391 00:15:16,516 --> 00:15:18,355 That's how it's defined in the 392 00:15:18,355 --> 00:15:19,152 regulations. 393 00:15:19,152 --> 00:15:21,621 But there's no definition for what a minor 394 00:15:21,621 --> 00:15:23,858 increase over a minimal risk is in the 395 00:15:23,858 --> 00:15:24,624 regulations. 396 00:15:25,291 --> 00:15:28,494 And we did a survey of us 397 00:15:28,494 --> 00:15:30,296 chairpersons of institutional review 398 00:15:30,296 --> 00:15:31,798 boards or in other countries. 399 00:15:31,798 --> 00:15:33,832 This will be referred to as research ethics 400 00:15:33,832 --> 00:15:34,400 committees. 401 00:15:34,400 --> 00:15:37,737 Many years ago now and this was back in 2004. 402 00:15:37,737 --> 00:15:42,535 And we published these data and found a wide variability on 403 00:15:42,535 --> 00:15:42,942 how, 404 00:15:44,510 --> 00:15:46,012 people on our reviews 405 00:15:46,012 --> 00:15:48,262 interpreted what counted as minimal risk 406 00:15:48,262 --> 00:15:49,949 or greater than minimal risk. 407 00:15:50,183 --> 00:15:53,586 So they could only really agree on the extremes. 408 00:15:53,586 --> 00:15:57,128 Both ends of the spectrum attend CC blood draw and a healthy 11 409 00:15:57,128 --> 00:15:57,690 year old. 410 00:15:57,957 --> 00:15:59,574 Most people said that's minimal risk, 411 00:15:59,574 --> 00:16:01,060 but not even everybody said that. 412 00:16:01,427 --> 00:16:04,063 And a lumbar puncture in that team healthy 413 00:16:04,063 --> 00:16:07,066 11 year old would be considered more of a minimal risk. 414 00:16:07,533 --> 00:16:10,703 People with their 2% who said it. 415 00:16:11,971 --> 00:16:13,439 Was just minimal risk. 416 00:16:13,439 --> 00:16:16,023 And then everywhere else, there was 417 00:16:16,023 --> 00:16:16,909 variability 418 00:16:16,909 --> 00:16:19,574 is pretty much split for memorize and sexual 419 00:16:19,574 --> 00:16:20,179 activity. 420 00:16:20,613 --> 00:16:22,896 And we also found that our just in testing 421 00:16:22,896 --> 00:16:23,983 people were sort of 422 00:16:24,217 --> 00:16:27,050 I don't didn't show this here, but there's about a third of 423 00:16:27,050 --> 00:16:27,386 people 424 00:16:27,386 --> 00:16:28,221 in each category 425 00:16:28,221 --> 00:16:30,206 minimal risk, minor increase over minimal 426 00:16:30,206 --> 00:16:32,191 risk and more than a minor increase over 427 00:16:32,191 --> 00:16:32,859 minimal risk. 428 00:16:34,594 --> 00:16:35,361 So what 429 00:16:35,361 --> 00:16:37,794 I think this tells us is that often review 430 00:16:37,794 --> 00:16:38,431 committees 431 00:16:38,431 --> 00:16:40,553 assess risks based on their intuition 432 00:16:40,553 --> 00:16:41,701 and their judgment, 433 00:16:42,034 --> 00:16:45,037 and this may lead to inaccurate estimations of risk 434 00:16:45,538 --> 00:16:48,941 and also incorporating bias into their judgments. 435 00:16:49,308 --> 00:16:50,997 It also can lead to wide variability, 436 00:16:50,997 --> 00:16:52,411 especially if you have a study 437 00:16:52,411 --> 00:16:53,312 that's being done. 438 00:16:53,312 --> 00:16:55,449 Multiple sites and different sites 439 00:16:55,449 --> 00:16:57,083 have different assessment 440 00:16:57,083 --> 00:16:59,218 of what the risks entail. 441 00:16:59,218 --> 00:17:01,367 This also then leads into other issues 442 00:17:01,367 --> 00:17:02,555 where the permission 443 00:17:02,555 --> 00:17:05,791 that's required, can be different sites. 444 00:17:06,158 --> 00:17:08,629 So if a study is in that third category 445 00:17:08,629 --> 00:17:09,896 of a minor increase 446 00:17:09,896 --> 00:17:11,802 of a minimal risk, you need both parents 447 00:17:11,802 --> 00:17:12,899 to give their consent. 448 00:17:13,232 --> 00:17:15,070 And that may lead to complications 449 00:17:15,070 --> 00:17:17,069 in trying to plan out their studies. 450 00:17:18,271 --> 00:17:21,407 So it's better to use data on the risks of research 451 00:17:21,407 --> 00:17:23,209 procedures and the risks to daily life, 452 00:17:23,209 --> 00:17:24,410 and then compare the two. 453 00:17:24,744 --> 00:17:28,328 And Dave Wendler and others have worked on trying 454 00:17:28,328 --> 00:17:28,547 to 455 00:17:28,948 --> 00:17:32,485 do this more systematically and show how it can be done. 456 00:17:32,485 --> 00:17:36,187 So they've done it for a range of procedures and really sort of 457 00:17:36,187 --> 00:17:36,422 use 458 00:17:36,422 --> 00:17:38,758 that as a proof of concept, that this could be done 459 00:17:38,758 --> 00:17:41,024 for a much wider range of procedures 460 00:17:41,024 --> 00:17:42,662 that IRBs need to review. 461 00:17:44,397 --> 00:17:47,667 Okay, so let's turn now to decision. 462 00:17:50,670 --> 00:17:52,935 First, when you think about parental 463 00:17:52,935 --> 00:17:53,439 consent 464 00:17:53,439 --> 00:17:55,207 and child assent, 465 00:17:55,207 --> 00:17:58,353 it's really important that children should be enrolled 466 00:17:58,353 --> 00:17:58,644 only 467 00:17:58,644 --> 00:18:00,479 with the permission of their legal guardian, 468 00:18:00,479 --> 00:18:02,078 which is typically their parents, 469 00:18:02,078 --> 00:18:03,482 but can be other caregivers. 470 00:18:03,783 --> 00:18:07,753 And who can consent is typically set by local law. 471 00:18:09,255 --> 00:18:12,029 There are many exceptions to parental consent 472 00:18:12,029 --> 00:18:12,892 requirements. 473 00:18:13,159 --> 00:18:15,252 So most guidelines around the world 474 00:18:15,252 --> 00:18:17,763 allow waiving parental consent sometimes. 475 00:18:18,097 --> 00:18:20,306 And the most common example that's given 476 00:18:20,306 --> 00:18:21,300 is that sometimes 477 00:18:21,300 --> 00:18:23,979 parental consent or permission is not a 478 00:18:23,979 --> 00:18:24,804 protection. 479 00:18:24,804 --> 00:18:27,807 So if you think about a case where a child, 480 00:18:28,240 --> 00:18:30,647 where there's research being done on, 481 00:18:30,647 --> 00:18:33,379 parents who are suspected of child abuse, 482 00:18:34,046 --> 00:18:35,181 there may be concerns 483 00:18:35,181 --> 00:18:37,441 that a parent doesn't want to be involved 484 00:18:37,441 --> 00:18:38,985 in that research, partially 485 00:18:38,985 --> 00:18:42,828 because they aren't keeping their kids interests at 486 00:18:42,828 --> 00:18:43,356 heart. 487 00:18:44,323 --> 00:18:44,790 And they 488 00:18:44,790 --> 00:18:46,605 really aren't protecting their children 489 00:18:46,605 --> 00:18:48,094 in the way that they should be. 490 00:18:48,561 --> 00:18:51,110 So that might be an example where waiver 491 00:18:51,110 --> 00:18:53,532 of parental consent can be justified. 492 00:18:54,333 --> 00:18:58,237 There also are a number of state and local laws that allow minors 493 00:18:58,237 --> 00:18:59,638 to consent for themselves. 494 00:18:59,638 --> 00:19:02,408 And these are in three main categories, can be based 495 00:19:02,408 --> 00:19:05,411 on the status 496 00:19:05,611 --> 00:19:06,245 of the minor. 497 00:19:06,245 --> 00:19:06,779 For instance, 498 00:19:06,779 --> 00:19:09,299 if that minors married their maturity, 499 00:19:09,299 --> 00:19:12,151 if they're determined to be a mature minor 500 00:19:12,151 --> 00:19:15,414 with different processes depending on the state or their 501 00:19:15,414 --> 00:19:16,055 condition. 502 00:19:16,055 --> 00:19:17,890 So for, 503 00:19:17,890 --> 00:19:19,441 treatment for sexually transmitted 504 00:19:19,441 --> 00:19:20,626 infections, for instance. 505 00:19:20,626 --> 00:19:23,329 And I'll talk a little bit more about this later. 506 00:19:23,329 --> 00:19:25,585 I've provided a map here of the Guttmacher 507 00:19:25,585 --> 00:19:26,499 Institute, which 508 00:19:27,400 --> 00:19:31,437 lays out when minors can obtain contraceptive services 509 00:19:31,437 --> 00:19:32,438 without a parent's involvement. 510 00:19:32,438 --> 00:19:34,774 And they've done a great job of, in general, 511 00:19:36,308 --> 00:19:37,043 highlighting the 512 00:19:37,043 --> 00:19:40,146 variability across states and providing, 513 00:19:40,146 --> 00:19:43,583 reliable information for what the current law is in various 514 00:19:43,583 --> 00:19:44,050 states. 515 00:19:44,050 --> 00:19:47,053 So it's a good resource to have in mind. 516 00:19:48,054 --> 00:19:50,523 So in the US, regulations require 517 00:19:50,523 --> 00:19:52,504 that both parents give consent in risky 518 00:19:52,504 --> 00:19:53,926 or non beneficial research, 519 00:19:53,926 --> 00:19:56,929 like the third category I was just talking about, 520 00:19:57,997 --> 00:19:59,899 a lot of ethicists however, really 521 00:19:59,899 --> 00:20:02,517 want to point out something which is not in the federal 522 00:20:02,517 --> 00:20:03,135 regulations. 523 00:20:03,135 --> 00:20:05,278 That probably should be that really, 524 00:20:05,278 --> 00:20:07,540 when we're talking about what parents 525 00:20:07,540 --> 00:20:09,418 are doing, they're giving permission 526 00:20:09,418 --> 00:20:11,610 and that's different from giving consent. 527 00:20:11,610 --> 00:20:14,246 So when you think about it, if a child is going to school, 528 00:20:14,246 --> 00:20:15,781 parents sign a permission form. 529 00:20:15,781 --> 00:20:17,516 They don't sign a consent form. 530 00:20:17,516 --> 00:20:20,186 And consent is typically thought to be 531 00:20:20,186 --> 00:20:21,966 when you give consent for somebody 532 00:20:21,966 --> 00:20:23,222 to do something to you. 533 00:20:23,756 --> 00:20:27,632 So really what parents are doing is they're giving their 534 00:20:27,632 --> 00:20:28,394 permission 535 00:20:28,727 --> 00:20:29,695 for their children 536 00:20:29,695 --> 00:20:31,739 to be engaged in some sort of activity 537 00:20:31,739 --> 00:20:33,299 or in research in this case. 538 00:20:33,699 --> 00:20:36,302 And the reason that I think this is really like 539 00:20:36,302 --> 00:20:39,271 to make this distinction is that there's 540 00:20:39,839 --> 00:20:43,008 the notion that consent itself is only 541 00:20:43,008 --> 00:20:45,811 is is more and morally transformative. 542 00:20:45,811 --> 00:20:47,546 So it takes something that could be wrong 543 00:20:47,546 --> 00:20:50,549 and turns it into something that's morally permissible. 544 00:20:50,549 --> 00:20:51,484 Then permission. 545 00:20:51,484 --> 00:20:54,987 So parents have less discretion and less authority, 546 00:20:55,621 --> 00:20:58,469 to consent for their children to be involved in a range of 547 00:20:58,469 --> 00:20:59,058 activities. 548 00:20:59,058 --> 00:21:00,693 And especially, I think, 549 00:21:00,693 --> 00:21:02,341 because parents are supposed to keep 550 00:21:02,341 --> 00:21:04,263 their children's best interests at heart, 551 00:21:04,763 --> 00:21:07,366 they cannot give permission 552 00:21:07,366 --> 00:21:11,470 for children to be exposed to, substantial risk and research. 553 00:21:13,539 --> 00:21:14,440 With it, 554 00:21:14,440 --> 00:21:16,105 in addition to this notion that parents 555 00:21:16,105 --> 00:21:17,643 have to give permission or consent, 556 00:21:18,577 --> 00:21:21,452 the regulations also require that institutional 557 00:21:21,452 --> 00:21:21,881 review 558 00:21:21,881 --> 00:21:24,834 boards make provisions for assent from children who are 559 00:21:24,834 --> 00:21:25,317 capable. 560 00:21:25,784 --> 00:21:29,221 Now, the regulations only define assent in this way. 561 00:21:29,221 --> 00:21:31,212 Affirmative agreement to participate 562 00:21:31,212 --> 00:21:33,092 in research, not just the failure 563 00:21:33,092 --> 00:21:35,859 to how this is not the most helpful 564 00:21:35,859 --> 00:21:36,729 definition 565 00:21:36,729 --> 00:21:39,061 because it's basically defining assent 566 00:21:39,061 --> 00:21:40,166 as what it's not. 567 00:21:40,766 --> 00:21:42,401 However, 568 00:21:42,401 --> 00:21:45,020 I think a better way to think about it 569 00:21:45,020 --> 00:21:45,571 is that 570 00:21:45,571 --> 00:21:47,506 there should be agreement based on the child 571 00:21:47,506 --> 00:21:49,900 understanding as much as she's capable of 572 00:21:49,900 --> 00:21:50,776 understanding, 573 00:21:51,110 --> 00:21:53,166 even if that child cannot understand 574 00:21:53,166 --> 00:21:54,880 enough to give valid consent. 575 00:21:55,347 --> 00:21:57,606 And in some cases it might be really, really 576 00:21:57,606 --> 00:21:58,017 limited 577 00:21:58,017 --> 00:22:01,084 information like, you know, you'll have to come to this 578 00:22:01,084 --> 00:22:01,921 research site, 579 00:22:03,022 --> 00:22:04,490 three times 580 00:22:04,490 --> 00:22:08,093 and that's pretty much all that the child understands. 581 00:22:08,093 --> 00:22:12,031 But in other cases, it may be more substantial. 582 00:22:13,699 --> 00:22:15,808 Now, it's important to recognize, 583 00:22:15,808 --> 00:22:17,469 however, that the reasons 584 00:22:17,703 --> 00:22:20,084 for requiring assent can also shape 585 00:22:20,084 --> 00:22:23,008 what it is that asks is being asked of it. 586 00:22:23,776 --> 00:22:25,802 So when we involve children in decision 587 00:22:25,802 --> 00:22:27,880 making in sort of different directions, 588 00:22:27,880 --> 00:22:29,995 it can be giving them a sense of control 589 00:22:29,995 --> 00:22:31,951 over what's about to happen to them, 590 00:22:32,451 --> 00:22:34,342 having giving them the opportunity 591 00:22:34,342 --> 00:22:35,955 to prepare for what they are 592 00:22:35,955 --> 00:22:36,856 going to have to do. 593 00:22:36,856 --> 00:22:39,265 So if we're trying to stay overnight in the 594 00:22:39,265 --> 00:22:39,825 hospital, 595 00:22:39,825 --> 00:22:41,442 it might be important for the child 596 00:22:41,442 --> 00:22:42,828 to know that that's coming up 597 00:22:42,828 --> 00:22:46,030 and to be able to pack a bag and bring along their favorite 598 00:22:46,030 --> 00:22:46,899 stuffed animal. 599 00:22:48,467 --> 00:22:49,635 It's also important 600 00:22:49,635 --> 00:22:52,671 for to show respect for the growing astronomy. 601 00:22:52,671 --> 00:22:54,948 So over time, children are increasing in 602 00:22:54,948 --> 00:22:55,574 astronomy. 603 00:22:55,574 --> 00:22:59,372 And as a parent of a pre-teen, I can tell you that I can't get 604 00:22:59,372 --> 00:22:59,678 away 605 00:22:59,678 --> 00:23:01,974 with making decisions for my pre-teen 606 00:23:01,974 --> 00:23:03,649 in the way that I used to. 607 00:23:03,649 --> 00:23:06,377 I have to engage her because she wants 608 00:23:06,377 --> 00:23:08,387 she has increasing capacity 609 00:23:08,387 --> 00:23:10,953 to make decisions, and also just a concern 610 00:23:10,953 --> 00:23:12,358 for her own authority. 611 00:23:12,358 --> 00:23:16,128 She doesn't like to be engaged in things 612 00:23:16,395 --> 00:23:19,965 without some, ability to weigh in. 613 00:23:22,067 --> 00:23:25,237 So a respectful assent process, therefore, would involve 614 00:23:25,237 --> 00:23:27,527 different stages that can be informed 615 00:23:27,527 --> 00:23:29,508 in a child's about information. 616 00:23:29,508 --> 00:23:32,019 Engaging them, seeing if they have any questions or 617 00:23:32,019 --> 00:23:32,511 concerns, 618 00:23:32,511 --> 00:23:35,514 asking for their assent, and finally, 619 00:23:36,215 --> 00:23:38,150 respecting any dissent. 620 00:23:38,150 --> 00:23:40,719 So this could involve monitoring discomfort 621 00:23:40,719 --> 00:23:42,266 if they're experiencing any problems 622 00:23:42,266 --> 00:23:43,856 that they're having in the research, 623 00:23:44,189 --> 00:23:47,026 any objections that they know. 624 00:23:47,026 --> 00:23:49,862 All of these things are important 625 00:23:49,862 --> 00:23:52,865 to the extent a child has full capacity. 626 00:23:53,198 --> 00:23:55,490 However, if a child has less capacity, 627 00:23:55,490 --> 00:23:56,635 it may be that not 628 00:23:56,635 --> 00:23:58,203 all of these things need to be done. 629 00:23:58,203 --> 00:24:00,122 So if a child really can't understand 630 00:24:00,122 --> 00:24:02,041 the importance of benefiting others, 631 00:24:02,574 --> 00:24:04,687 asking them to to participate in research 632 00:24:04,687 --> 00:24:06,078 is essentially asking them 633 00:24:06,078 --> 00:24:08,174 a question that doesn't make any sense to 634 00:24:08,174 --> 00:24:08,480 them. 635 00:24:08,480 --> 00:24:10,983 So it may be more important in such case 636 00:24:10,983 --> 00:24:13,741 to for young children to really focus on 637 00:24:13,741 --> 00:24:16,155 informing them about the research, 638 00:24:16,355 --> 00:24:18,872 engaging them and seeing if they have any questions or 639 00:24:18,872 --> 00:24:19,291 worries, 640 00:24:19,291 --> 00:24:21,586 and then checking for their discomfort 641 00:24:21,586 --> 00:24:23,095 as the studies going on, 642 00:24:23,095 --> 00:24:25,157 to see if there's a way in which that's 643 00:24:25,157 --> 00:24:27,166 increasing the risks of the research. 644 00:24:29,868 --> 00:24:30,169 When we 645 00:24:30,169 --> 00:24:33,288 think about who can assent to most guidelines don't specify 646 00:24:33,288 --> 00:24:33,605 this. 647 00:24:34,006 --> 00:24:36,076 The US federal regulations only stipulate 648 00:24:36,076 --> 00:24:37,743 that the determination of assent 649 00:24:37,743 --> 00:24:39,896 should take into account the age, maturity and 650 00:24:39,896 --> 00:24:40,879 psychological state. 651 00:24:44,583 --> 00:24:47,386 We did a study looking at this and found 652 00:24:47,386 --> 00:24:50,656 that many IRBs use the rule of seven. 653 00:24:51,557 --> 00:24:54,560 But it's interesting because I think 654 00:24:54,927 --> 00:24:57,733 this rule is essentially that a child under the age of 655 00:24:57,733 --> 00:24:58,097 seven, 656 00:24:59,264 --> 00:25:03,469 can't really give a child from 7 to 14 can give assent, 657 00:25:03,469 --> 00:25:07,196 and a child from 14 and above is essentially capable of 658 00:25:07,196 --> 00:25:07,806 consent. 659 00:25:08,207 --> 00:25:10,802 But individual children can have very different 660 00:25:10,802 --> 00:25:11,410 capacities 661 00:25:11,410 --> 00:25:13,262 for decision making depending on various 662 00:25:13,262 --> 00:25:13,679 factors. 663 00:25:13,679 --> 00:25:15,647 So if you consider chronically ill children, 664 00:25:15,647 --> 00:25:18,203 one thing that I've seen in our children's 665 00:25:18,203 --> 00:25:18,751 hospital 666 00:25:18,751 --> 00:25:19,017 is that 667 00:25:19,017 --> 00:25:20,819 there are some chronically ill children 668 00:25:20,819 --> 00:25:22,621 who fit in, in and out of the hospital 669 00:25:22,921 --> 00:25:25,594 for many years, and that leads to them 670 00:25:25,594 --> 00:25:27,493 really understanding a lot 671 00:25:27,493 --> 00:25:29,862 about condition, about different procedures 672 00:25:29,862 --> 00:25:32,030 that they might have experienced in the past 673 00:25:32,030 --> 00:25:34,900 that could be used in research in the future. And 674 00:25:35,934 --> 00:25:38,036 really being able to engage and talk a lot 675 00:25:38,036 --> 00:25:40,357 about whether research makes sense 676 00:25:40,357 --> 00:25:41,039 for them. 677 00:25:41,407 --> 00:25:43,342 On the other hand, there are other children 678 00:25:43,342 --> 00:25:44,343 who've been chronically ill 679 00:25:44,343 --> 00:25:45,911 in and out of a hospital, and that's 680 00:25:45,911 --> 00:25:47,479 kind of had an infantilizing effect 681 00:25:47,813 --> 00:25:51,183 for even a child who's above the age of consent 682 00:25:51,617 --> 00:25:53,317 can't actually make that many decisions, 683 00:25:53,317 --> 00:25:54,253 and they're much more 684 00:25:54,253 --> 00:25:57,256 accustomed to their parents helping make those decisions. 685 00:25:57,456 --> 00:26:00,125 So it really is interesting 686 00:26:00,125 --> 00:26:02,440 how even one factor can cut in either 687 00:26:02,440 --> 00:26:03,128 direction. 688 00:26:04,863 --> 00:26:06,901 So when we did the study asking IRBs 689 00:26:06,901 --> 00:26:09,334 about what they did, about half of the IRB 690 00:26:09,334 --> 00:26:11,457 chairs we talked to required investigators 691 00:26:11,457 --> 00:26:12,871 to use a particular method. 692 00:26:13,172 --> 00:26:15,407 And most of those used to age cut off. 693 00:26:15,407 --> 00:26:17,342 The majority use the age of seven, 694 00:26:17,342 --> 00:26:20,349 where assent was required after the age of seven, and the 695 00:26:20,349 --> 00:26:20,612 rest 696 00:26:20,612 --> 00:26:22,933 of the other half of of our vicars 697 00:26:22,933 --> 00:26:25,117 left it up to the investigator. 698 00:26:27,853 --> 00:26:28,353 But this really 699 00:26:28,353 --> 00:26:30,853 raises the question, I think, as we think 700 00:26:30,853 --> 00:26:33,292 about different ones that give children 701 00:26:33,292 --> 00:26:36,124 consent, the ability to consent at different ages for different 702 00:26:36,124 --> 00:26:36,528 reasons. 703 00:26:37,329 --> 00:26:40,232 Should someone be giving assent or consent? 704 00:26:40,232 --> 00:26:42,417 Once children grow, they develop capacity 705 00:26:42,417 --> 00:26:43,802 to reason and understand. 706 00:26:43,802 --> 00:26:47,606 And it's definitely the case that children might even become 707 00:26:47,606 --> 00:26:50,776 legally able to consent during the course of research. 708 00:26:50,776 --> 00:26:52,975 So the guidance I referred to earlier 709 00:26:52,975 --> 00:26:54,580 shown says that if a child 710 00:26:54,580 --> 00:26:56,114 becomes capable of giving independent, 711 00:26:56,114 --> 00:26:57,649 informed consent during the research, 712 00:26:58,016 --> 00:26:59,878 researchers should obtain their consent 713 00:26:59,878 --> 00:27:01,787 to continue participation at that time, 714 00:27:02,454 --> 00:27:05,290 and this might occur instance in children, 715 00:27:05,290 --> 00:27:08,339 if a child samples are held in a database 716 00:27:08,339 --> 00:27:10,496 for storage sample research, 717 00:27:11,330 --> 00:27:13,866 they might become 18 over the course of the research. 718 00:27:13,866 --> 00:27:15,434 And, you know, in general, 719 00:27:15,434 --> 00:27:18,273 a lot of guidance suggests they should be reconsidered at 720 00:27:18,273 --> 00:27:18,871 that point. 721 00:27:19,671 --> 00:27:21,363 There are some people who have argued 722 00:27:21,363 --> 00:27:22,140 to the contrary. 723 00:27:22,140 --> 00:27:25,466 For instance, Ben Bergman, has argued 724 00:27:25,466 --> 00:27:26,545 that really 725 00:27:26,545 --> 00:27:29,047 there are a lot of things that parents decisions 726 00:27:29,047 --> 00:27:30,517 that parents make about their children, 727 00:27:30,517 --> 00:27:31,083 and they don't 728 00:27:31,083 --> 00:27:33,183 children don't necessarily get to revisit 729 00:27:33,183 --> 00:27:34,720 all of them at the age of 18. 730 00:27:35,020 --> 00:27:38,557 So it's not clear in his view that this is one of those cases 731 00:27:38,557 --> 00:27:40,977 where we should always go back and ask children for their 732 00:27:40,977 --> 00:27:41,360 consent. 733 00:27:43,862 --> 00:27:46,198 And additionally, as mentioned earlier, 734 00:27:46,198 --> 00:27:49,868 different states and countries allow minors to legally consent 735 00:27:49,868 --> 00:27:53,005 to treatment or prevention based on different things. 736 00:27:53,005 --> 00:27:54,801 So those can include age, status, 737 00:27:54,801 --> 00:27:56,108 maturity or conditions. 738 00:27:56,508 --> 00:27:59,845 So some places will have different ages. 739 00:28:01,880 --> 00:28:03,615 And as I mentioned, this can vary 740 00:28:03,615 --> 00:28:06,618 quite a bit between the ages of 14 and 21. 741 00:28:07,019 --> 00:28:11,223 Status a miner who's married, who's pregnant, who's, 742 00:28:11,924 --> 00:28:14,040 in the military can have the ability 743 00:28:14,040 --> 00:28:15,627 to consent for themselves. 744 00:28:15,861 --> 00:28:18,830 Some students have these really funny works 745 00:28:18,830 --> 00:28:22,301 so they can have it so that a miner gets to consent 746 00:28:22,734 --> 00:28:25,737 for their own medical care and their child and, 747 00:28:26,605 --> 00:28:28,607 their own medical care when they are pregnant. 748 00:28:28,607 --> 00:28:32,511 But once the child's born and they are no longer pregnant, 749 00:28:32,945 --> 00:28:36,164 then that minor parent gives the consent for their 750 00:28:36,164 --> 00:28:36,615 child, 751 00:28:36,615 --> 00:28:37,950 but can't consent themselves. 752 00:28:39,952 --> 00:28:41,553 There also is this issue of maturity. 753 00:28:41,553 --> 00:28:43,752 So can some states have laws allowing 754 00:28:43,752 --> 00:28:45,891 for mature minors to make decisions 755 00:28:45,891 --> 00:28:49,103 for themselves, and that can be based on 756 00:28:49,103 --> 00:28:50,629 either a clinician 757 00:28:51,296 --> 00:28:54,159 evaluating the minor and deciding that they have this 758 00:28:54,159 --> 00:28:54,700 maturity, 759 00:28:55,000 --> 00:28:57,076 or it can be based on a court process 760 00:28:57,076 --> 00:28:58,704 where court determines this. 761 00:28:59,338 --> 00:29:01,980 And finally, there are many cases 762 00:29:01,980 --> 00:29:04,142 where children can consent 763 00:29:04,409 --> 00:29:08,313 to researching care for having certain conditions. 764 00:29:09,181 --> 00:29:11,817 For instance, there are laws that are based on the concern 765 00:29:11,817 --> 00:29:14,253 that adolescents who fail to receive needed 766 00:29:14,253 --> 00:29:14,820 treatment 767 00:29:15,854 --> 00:29:17,606 because it would reveal sexual risk 768 00:29:17,606 --> 00:29:18,156 behaviors. 769 00:29:18,156 --> 00:29:19,791 For instance, 770 00:29:19,791 --> 00:29:22,775 should be able to get treatment for sexually transmitted 771 00:29:22,775 --> 00:29:23,362 infections 772 00:29:23,362 --> 00:29:26,365 without getting parental permission first. 773 00:29:26,732 --> 00:29:28,686 And this is something that really is 774 00:29:28,686 --> 00:29:30,369 a public health justification. 775 00:29:30,369 --> 00:29:33,522 It's not necessarily about, oh, this minor has greater 776 00:29:33,522 --> 00:29:34,106 autonomy. 777 00:29:34,840 --> 00:29:37,509 But it's that as a public health matter, 778 00:29:37,509 --> 00:29:37,909 if we 779 00:29:38,543 --> 00:29:40,657 let parental permission be a barrier here, 780 00:29:40,657 --> 00:29:41,613 then we would have 781 00:29:41,880 --> 00:29:44,082 sexually transmitted infections that go untreated, 782 00:29:44,082 --> 00:29:46,018 and that might be likely to be transmitted. 783 00:29:48,720 --> 00:29:49,554 When we're asking this 784 00:29:49,554 --> 00:29:52,858 question of whether children can give assent or consent. 785 00:29:53,358 --> 00:29:56,728 There have been several studies now of adolescent participation 786 00:29:56,728 --> 00:29:58,982 in HIV research, and these studies 787 00:29:58,982 --> 00:30:01,767 have shown that there are lots of reasons 788 00:30:01,767 --> 00:30:04,450 to sort of question the default assumption 789 00:30:04,450 --> 00:30:07,005 that children can't give consent until, 790 00:30:07,739 --> 00:30:10,409 they reach that legal age where they are 791 00:30:10,409 --> 00:30:12,878 now able to consent for many things. 792 00:30:13,345 --> 00:30:17,382 So first, one study involved using a simplified assent form 793 00:30:17,649 --> 00:30:20,719 and then testing adolescents to understand, to see how 794 00:30:20,719 --> 00:30:23,955 well they understood, what they needed to know. 795 00:30:23,955 --> 00:30:27,133 And over half of the adolescents answered all the questions 796 00:30:27,133 --> 00:30:27,726 correctly. 797 00:30:28,360 --> 00:30:31,142 Another study, that I participated in 798 00:30:31,142 --> 00:30:33,999 did something to this a step further. 799 00:30:33,999 --> 00:30:36,632 So we compared adolescents to adults 800 00:30:36,632 --> 00:30:37,803 and tested them 801 00:30:37,803 --> 00:30:39,771 on their comprehension for research. 802 00:30:39,771 --> 00:30:41,531 And we found no significant difference 803 00:30:41,531 --> 00:30:42,874 in comprehension of research 804 00:30:42,874 --> 00:30:46,244 between adults and adolescents, each over the age of 14. 805 00:30:46,812 --> 00:30:48,945 We did find that when analysts were a little 806 00:30:48,945 --> 00:30:49,381 younger, 807 00:30:49,381 --> 00:30:52,117 there were certain differences in their comprehension. 808 00:30:52,117 --> 00:30:56,354 So this sort of suggested that having a occur 809 00:30:56,755 --> 00:30:59,491 could work, at least in this case. 810 00:30:59,491 --> 00:31:01,341 Although the tests were pretty simple, 811 00:31:01,341 --> 00:31:03,095 so they weren't really delving deep 812 00:31:03,095 --> 00:31:04,830 into understanding. 813 00:31:04,830 --> 00:31:08,741 Finally, adolescents understood placebo and clinical 814 00:31:08,741 --> 00:31:09,267 trials 815 00:31:09,267 --> 00:31:11,091 pretty well across a range of studies, but 816 00:31:11,091 --> 00:31:12,871 didn't last well with things like risks, 817 00:31:13,238 --> 00:31:17,817 randomization, and a particular risk that occurs in HIV vaccine 818 00:31:17,817 --> 00:31:18,543 research. 819 00:31:18,543 --> 00:31:20,612 For if you receive an HIV vaccine, 820 00:31:22,013 --> 00:31:23,348 you may have 821 00:31:23,348 --> 00:31:26,885 a future false positive, uncertain HIV tests that are 822 00:31:26,885 --> 00:31:27,285 done. 823 00:31:27,686 --> 00:31:30,509 And that false positive may mean that it looks like you 824 00:31:30,509 --> 00:31:31,022 have HIV. 825 00:31:31,022 --> 00:31:34,459 But really, unless a better test is done, 826 00:31:35,494 --> 00:31:37,996 you don't know whether or not you have HIV. 827 00:31:37,996 --> 00:31:39,503 So that type of risk was something 828 00:31:39,503 --> 00:31:41,099 that adolescents didn't necessarily 829 00:31:41,099 --> 00:31:44,102 understand very well. 830 00:31:44,369 --> 00:31:49,193 So we did a study on policy stakeholders on adolescent 831 00:31:49,193 --> 00:31:49,908 consent 832 00:31:49,908 --> 00:31:52,944 to try and understand how do we make sense 833 00:31:52,944 --> 00:31:55,947 of all of these rules and laws, 834 00:31:56,381 --> 00:31:58,884 to really do a better job 835 00:31:58,884 --> 00:32:01,887 of addressing adolescent needs and research. 836 00:32:02,087 --> 00:32:04,289 We did semi-structured interviews 837 00:32:04,289 --> 00:32:07,092 with the purpose of sampling of 15 policy 838 00:32:07,092 --> 00:32:09,060 stakeholders, which included lawyers, 839 00:32:09,060 --> 00:32:11,052 institutional review board members, school 840 00:32:11,052 --> 00:32:12,664 administrators and policy makers. 841 00:32:13,064 --> 00:32:16,067 And then we conducted thematic analysis. 842 00:32:16,735 --> 00:32:19,004 And we found three themes. 843 00:32:19,004 --> 00:32:21,502 The first was that age is a poor proxy 844 00:32:21,502 --> 00:32:23,475 for decision making capacity. 845 00:32:23,942 --> 00:32:27,245 And people think that factors like maternity and context 846 00:32:27,579 --> 00:32:30,582 and the risk and benefit ratio matter more. 847 00:32:30,982 --> 00:32:33,518 The second theme was that policies should evolve 848 00:32:33,518 --> 00:32:36,555 with changing societal views about adolescent autonomy, 849 00:32:37,122 --> 00:32:40,458 and the third is that adults should be focused on empowering 850 00:32:40,458 --> 00:32:42,335 and involving adolescents in decision 851 00:32:42,335 --> 00:32:44,262 making to move them towards ownership 852 00:32:44,262 --> 00:32:46,531 over their own health. Over time. 853 00:32:48,533 --> 00:32:49,734 So for the first theme, I 854 00:32:49,734 --> 00:32:52,572 just want to give you a couple representative quotes for these 855 00:32:52,572 --> 00:32:52,938 themes. 856 00:32:53,738 --> 00:32:57,075 One person pointed out, people don't mature the same way 857 00:32:57,075 --> 00:32:59,604 that there are adults who aren't very mature and 858 00:32:59,604 --> 00:33:00,078 they're, 859 00:33:00,712 --> 00:33:02,781 younger adolescents who can be quite mature. 860 00:33:02,781 --> 00:33:04,482 And it just depends. 861 00:33:04,482 --> 00:33:08,494 So their view is that age in general is a poor proxy for 862 00:33:08,494 --> 00:33:09,354 determining 863 00:33:09,354 --> 00:33:12,077 if somebody has the capacity to make a decision about 864 00:33:12,077 --> 00:33:12,591 research. 865 00:33:14,125 --> 00:33:15,835 The second theme that I had mentioned 866 00:33:15,835 --> 00:33:16,528 is that policy 867 00:33:16,528 --> 00:33:18,196 should evolve with societal views. 868 00:33:18,196 --> 00:33:19,998 And I really liked this quote. 869 00:33:19,998 --> 00:33:21,666 This person said, who is it helping? 870 00:33:21,666 --> 00:33:23,627 Is the policy in place for us to feel 871 00:33:23,627 --> 00:33:25,270 right and religious and moral, 872 00:33:25,503 --> 00:33:27,727 or isn't the policy in place to protect 873 00:33:27,727 --> 00:33:29,608 and to work for our adolescents? 874 00:33:30,075 --> 00:33:33,010 So for me, I just feel the policies need to completely 875 00:33:33,010 --> 00:33:33,445 change. 876 00:33:33,812 --> 00:33:37,182 Even the laws need to change to reflect current society. 877 00:33:37,682 --> 00:33:40,218 And this person also pointed out that 878 00:33:40,218 --> 00:33:42,782 with access to the internet and social 879 00:33:42,782 --> 00:33:43,255 media, 880 00:33:43,521 --> 00:33:47,430 the things that adolescents know and understand really have 881 00:33:47,430 --> 00:33:48,026 evolved. 882 00:33:48,026 --> 00:33:50,128 Their view was adolescents know a lot more 883 00:33:50,128 --> 00:33:52,030 now than adolescents might have known 884 00:33:52,264 --> 00:33:53,832 in previous generations. 885 00:33:55,767 --> 00:33:58,603 Finally, with the third theme, 886 00:33:58,603 --> 00:34:01,439 there was really this sense that it's important 887 00:34:01,439 --> 00:34:03,811 for adults to still be involved in 888 00:34:03,811 --> 00:34:04,509 decisions 889 00:34:04,509 --> 00:34:07,007 about adolescents when that's possible 890 00:34:07,007 --> 00:34:08,847 and when it's a protection. 891 00:34:09,614 --> 00:34:12,250 But that it's really a shift from 892 00:34:12,250 --> 00:34:14,540 making decisions in authoritative way 893 00:34:14,540 --> 00:34:16,087 to fighting adolescents. 894 00:34:16,087 --> 00:34:18,195 So one person's that you guide them, 895 00:34:18,195 --> 00:34:19,424 but ultimately they, 896 00:34:19,424 --> 00:34:22,427 the adolescents, make decision. 897 00:34:23,228 --> 00:34:25,430 So with the study, I think one important 898 00:34:25,430 --> 00:34:27,632 limitation is that it was a qualitative 899 00:34:27,632 --> 00:34:29,863 study, primarily hypothesis generating 900 00:34:29,863 --> 00:34:32,270 and focused on the East African context. 901 00:34:33,204 --> 00:34:35,707 But I think what we found might have broader 902 00:34:35,707 --> 00:34:38,710 implications and really suggest a need for further research. 903 00:34:39,010 --> 00:34:41,560 So first, laws without strict age cutoffs and 904 00:34:41,560 --> 00:34:42,013 greater 905 00:34:42,013 --> 00:34:45,183 flexibility, such as mid term minor laws, 906 00:34:45,183 --> 00:34:48,153 where a clinician can determine whether a minor has 907 00:34:48,653 --> 00:34:52,055 the ability to make decisions for themselves that may help 908 00:34:52,055 --> 00:34:52,524 address 909 00:34:52,524 --> 00:34:55,181 diverse decision making capacities 910 00:34:55,181 --> 00:34:58,463 and allow clinicians to really, determine 911 00:34:58,697 --> 00:35:01,129 that he has a lot more maturity than you 912 00:35:01,129 --> 00:35:03,501 might think or even less maturity than 913 00:35:04,803 --> 00:35:06,237 based on their age. 914 00:35:06,237 --> 00:35:08,390 Additionally, there's a need for continued 915 00:35:08,390 --> 00:35:09,774 research on how to support 916 00:35:09,774 --> 00:35:12,796 caregivers and adolescents in working together to make 917 00:35:12,796 --> 00:35:13,411 decisions. 918 00:35:14,579 --> 00:35:16,571 So this could involve training caregivers 919 00:35:16,571 --> 00:35:17,349 or other adults 920 00:35:17,349 --> 00:35:19,279 and how to guide adolescent decision 921 00:35:19,279 --> 00:35:20,352 making effectively, 922 00:35:20,819 --> 00:35:23,492 and figuring out ways to support adolescents with 923 00:35:23,492 --> 00:35:24,255 interventions 924 00:35:24,255 --> 00:35:27,392 to address their particular developmental limitations. 925 00:35:27,392 --> 00:35:30,962 So a lot of research has shown that adolescents can understand 926 00:35:31,262 --> 00:35:34,248 some of the important concepts, but there may be other 927 00:35:34,248 --> 00:35:34,966 limitations. 928 00:35:36,001 --> 00:35:38,291 We know that the adolescent brain is one 929 00:35:38,291 --> 00:35:40,638 that has trouble resisting peer pressure 930 00:35:40,638 --> 00:35:42,440 and is really susceptible to it, 931 00:35:42,440 --> 00:35:44,934 or tends to focus on short term risks over 932 00:35:44,934 --> 00:35:45,944 long term risks. 933 00:35:46,344 --> 00:35:49,814 And maybe there's a way to really just address those 934 00:35:49,814 --> 00:35:53,386 developmental limitations to help adolescents make better 935 00:35:53,386 --> 00:35:54,953 decisions by themselves. 936 00:35:56,588 --> 00:35:57,055 So this is 937 00:35:57,055 --> 00:36:00,225 a paper that tries to it illustrates, 938 00:36:01,026 --> 00:36:04,029 the research that I was just talking about. 939 00:36:04,496 --> 00:36:07,553 So finally, dissent is another important 940 00:36:07,553 --> 00:36:08,700 consideration. 941 00:36:08,700 --> 00:36:12,628 And many guidelines mention that a child's dissent should 942 00:36:12,628 --> 00:36:12,904 be, 943 00:36:14,439 --> 00:36:16,041 noted and that a child 944 00:36:16,041 --> 00:36:18,710 or their parents have a right to withdraw at any 945 00:36:18,710 --> 00:36:19,044 time. 946 00:36:19,444 --> 00:36:22,180 And this raises a challenge, which is how can we tell 947 00:36:22,180 --> 00:36:25,183 when a child is dissenting from research? 948 00:36:26,384 --> 00:36:28,353 Age is a factor, right? 949 00:36:28,353 --> 00:36:31,923 So a crying child who's three might 950 00:36:31,923 --> 00:36:35,694 just be having a tantrum or upset or hungry. 951 00:36:36,061 --> 00:36:38,043 And that doesn't necessarily mean 952 00:36:38,043 --> 00:36:40,565 that the child is dissenting to research. 953 00:36:41,633 --> 00:36:43,742 But we should respect sustained dissent 954 00:36:43,742 --> 00:36:45,203 by a child who understands 955 00:36:45,203 --> 00:36:47,278 what he or she doing for them is doing, 956 00:36:47,278 --> 00:36:48,873 for the most part, obviously, 957 00:36:49,507 --> 00:36:51,806 there might be very contrary teenagers 958 00:36:51,806 --> 00:36:54,045 who would just say no to everything. 959 00:36:54,045 --> 00:36:55,844 And maybe it's worth figuring out 960 00:36:55,844 --> 00:36:57,916 how to have a conversation with them. 961 00:36:58,783 --> 00:37:01,953 That doesn't automatically get them to know 962 00:37:02,187 --> 00:37:03,657 simply because they want to be 963 00:37:03,657 --> 00:37:04,589 contradictory. But 964 00:37:06,057 --> 00:37:06,991 we also may not 965 00:37:06,991 --> 00:37:09,994 want to force children to undergo research procedures. 966 00:37:09,994 --> 00:37:13,331 So if a child doesn't have capacity 967 00:37:13,331 --> 00:37:14,666 or is making, 968 00:37:15,633 --> 00:37:17,498 contrary decisions, really doesn't 969 00:37:17,498 --> 00:37:19,637 want to do something, we have to think 970 00:37:19,637 --> 00:37:21,503 about the practicality of getting 971 00:37:21,503 --> 00:37:23,708 that child to participate in research. 972 00:37:23,708 --> 00:37:25,710 They have to be dragged to the site, 973 00:37:25,710 --> 00:37:28,713 and they have to be held down to get a research procedure. 974 00:37:28,980 --> 00:37:30,215 And that's not something 975 00:37:30,215 --> 00:37:32,484 that I think isn't good for either 976 00:37:32,484 --> 00:37:34,752 the research staff or that child. 977 00:37:34,752 --> 00:37:39,157 So there may be cases where even if there's not an autonomy 978 00:37:39,157 --> 00:37:42,946 based reason to respect dissent or there's not a reason based 979 00:37:42,946 --> 00:37:43,194 on, 980 00:37:44,262 --> 00:37:47,268 the thinking that the child is necessarily 981 00:37:47,268 --> 00:37:48,700 going to be harmed. 982 00:37:49,300 --> 00:37:52,897 The actual practicality of it's just that you just don't know 983 00:37:52,897 --> 00:37:53,605 that child. 984 00:37:53,605 --> 00:37:54,038 Anything 985 00:37:55,940 --> 00:37:57,942 and decision is different from distrust. 986 00:37:57,942 --> 00:38:00,078 So dissent may reflect things like a desire 987 00:38:00,078 --> 00:38:02,611 for control or to express one's developing 988 00:38:02,611 --> 00:38:03,214 autonomy. 989 00:38:03,815 --> 00:38:06,618 But distress is when a child is experiencing 990 00:38:06,618 --> 00:38:09,621 psychological firm from research persuasion. 991 00:38:09,621 --> 00:38:12,005 So for instance, if you if there's a child 992 00:38:12,005 --> 00:38:13,992 is really terrified of injections, 993 00:38:14,993 --> 00:38:18,429 and the research involves an injection 994 00:38:18,730 --> 00:38:21,363 that may actually increase the risks 995 00:38:21,363 --> 00:38:24,435 of research participation for that child, 996 00:38:24,435 --> 00:38:26,125 because of the psychological harm 997 00:38:26,125 --> 00:38:28,173 that they would be likely to experience 998 00:38:28,439 --> 00:38:30,858 that may be different or higher than what 999 00:38:30,858 --> 00:38:31,743 other children 1000 00:38:31,743 --> 00:38:34,779 experience. 1001 00:38:34,779 --> 00:38:37,428 Importantly, there are times where, even in 1002 00:38:37,428 --> 00:38:37,982 research 1003 00:38:37,982 --> 00:38:42,086 could be ethically justifiable to override dissent or distress. 1004 00:38:42,420 --> 00:38:44,622 For instance, if a child could obtain benefit 1005 00:38:44,622 --> 00:38:47,014 from the research that they couldn't obtain 1006 00:38:47,014 --> 00:38:47,625 otherwise, 1007 00:38:47,892 --> 00:38:51,196 and the harms of proceeding are outweighed by that sense. 1008 00:38:52,530 --> 00:38:53,064 But it's 1009 00:38:53,064 --> 00:38:56,067 really important to think about what the level of, 1010 00:38:57,001 --> 00:38:59,083 for distress at the level of risk 1011 00:38:59,083 --> 00:39:00,471 is that's being added 1012 00:39:00,471 --> 00:39:04,669 to the research and determining whether the firms from that 1013 00:39:04,669 --> 00:39:05,310 research 1014 00:39:05,310 --> 00:39:08,313 participation are outweighed by a potential that. 1015 00:39:09,848 --> 00:39:10,582 Okay. 1016 00:39:10,582 --> 00:39:13,618 So in some research with children, 1017 00:39:13,618 --> 00:39:16,621 fires balancing protection with individuals with the needs, 1018 00:39:17,822 --> 00:39:20,592 data about treating children as a group. 1019 00:39:20,592 --> 00:39:22,060 And most guidelines strike 1020 00:39:22,060 --> 00:39:24,170 this balance by allowing children 1021 00:39:24,170 --> 00:39:25,897 to participate in research 1022 00:39:25,897 --> 00:39:28,036 that benefits them and minimal research 1023 00:39:28,036 --> 00:39:29,901 if there's no prospect of direct, 1024 00:39:30,101 --> 00:39:32,809 minimal risk research, if there's no prospect to direct 1025 00:39:32,809 --> 00:39:33,104 them. 1026 00:39:35,607 --> 00:39:37,475 I really wanted to encourage you 1027 00:39:37,475 --> 00:39:39,606 to recognize that although there's long 1028 00:39:39,606 --> 00:39:41,246 been this default of thinking 1029 00:39:41,246 --> 00:39:43,011 about the protection of children, 1030 00:39:43,011 --> 00:39:44,882 there are many cases where we need 1031 00:39:44,882 --> 00:39:47,980 to give consideration to enrolling children in 1032 00:39:47,980 --> 00:39:48,653 research. 1033 00:39:49,120 --> 00:39:52,169 Earlier, and the Covid 19 pandemic 1034 00:39:52,169 --> 00:39:54,859 really taught us that lesson. 1035 00:39:54,859 --> 00:39:57,469 That sort of thinking reflexively 1036 00:39:57,469 --> 00:39:59,130 and not specifically 1037 00:39:59,130 --> 00:40:02,294 about children can really hurt them in pandemic 1038 00:40:02,294 --> 00:40:02,967 response. 1039 00:40:04,235 --> 00:40:06,671 But in many cases, the 1040 00:40:06,671 --> 00:40:09,707 however, to ensure that earlier inclusion of children 1041 00:40:09,707 --> 00:40:12,710 is ethical, it's important to ensure that there's a strong 1042 00:40:13,311 --> 00:40:15,833 and there's a respectful permission 1043 00:40:15,833 --> 00:40:16,915 and a process. 1044 00:40:17,882 --> 00:40:20,805 Finally, we really do need clear guidance 1045 00:40:20,805 --> 00:40:21,019 on 1046 00:40:21,019 --> 00:40:22,909 when children should decide on their own 1047 00:40:22,909 --> 00:40:24,422 about participating in research 1048 00:40:24,789 --> 00:40:27,314 and how caregivers can help support them 1049 00:40:27,314 --> 00:40:29,460 and make good research decisions. 1050 00:40:30,161 --> 00:40:32,473 And this is something I think a lot of caregivers 1051 00:40:32,473 --> 00:40:32,897 struggle 1052 00:40:32,897 --> 00:40:35,633 with as children gain increasing autonomy 1053 00:40:35,633 --> 00:40:37,235 and become adolescents. 1054 00:40:37,235 --> 00:40:39,852 And I think need for sustained attention 1055 00:40:39,852 --> 00:40:42,273 to figure out how to get that right. 1056 00:40:43,308 --> 00:40:44,208 Thank you very much.