1 00:00:12,579 --> 00:00:13,013 It's always 2 00:00:13,013 --> 00:00:17,017 a pleasure to, talk in this, course. 3 00:00:17,017 --> 00:00:20,020 And I'm very sorry that I can't be there in person. 4 00:00:21,088 --> 00:00:24,091 But greetings to everyone from Scotland. 5 00:00:25,859 --> 00:00:29,183 So Robert has discussed, the issue of the standard of 6 00:00:29,183 --> 00:00:29,496 care 7 00:00:29,763 --> 00:00:31,743 that should be used in research studies 8 00:00:31,743 --> 00:00:33,267 in resource limited settings. 9 00:00:34,468 --> 00:00:37,704 One of the other key issues he introduced concerned 10 00:00:37,704 --> 00:00:40,951 the types of trials that one can do in resource poor 11 00:00:40,951 --> 00:00:41,575 settings. 12 00:00:41,575 --> 00:00:45,212 And the associated issue of post-trial access 13 00:00:45,212 --> 00:00:48,591 to treatments that are used or that are tested in those 14 00:00:48,591 --> 00:00:49,082 trials. 15 00:00:49,616 --> 00:00:52,141 And that's what I'm going to focus on 16 00:00:52,141 --> 00:00:52,619 today. 17 00:00:54,721 --> 00:00:58,959 I'm start by briefly outlining two cases. 18 00:00:59,793 --> 00:01:01,929 These are based on real studies. 19 00:01:01,929 --> 00:01:04,932 But I've somewhat simplified the details. 20 00:01:07,801 --> 00:01:09,236 The first case concerns 21 00:01:09,236 --> 00:01:13,440 access to antiretroviral therapy for patients with HIV Aids. 22 00:01:15,642 --> 00:01:17,611 Millions of people around the world, 23 00:01:17,611 --> 00:01:19,861 including in sub-Saharan Africa, South America and 24 00:01:19,861 --> 00:01:20,580 Southeast Asia, 25 00:01:21,648 --> 00:01:24,651 have access to antiretroviral therapy. 26 00:01:25,085 --> 00:01:28,531 The lifespan of people who are successfully maintained 27 00:01:28,531 --> 00:01:28,722 on 28 00:01:29,022 --> 00:01:32,702 T is now close to that of people who don't have 29 00:01:32,702 --> 00:01:33,093 HIV, 30 00:01:34,094 --> 00:01:37,810 but thousands of patients end up having to move to 31 00:01:37,810 --> 00:01:38,999 different types 32 00:01:38,999 --> 00:01:42,359 of antiretroviral as their strain of HIV virus, 33 00:01:42,359 --> 00:01:43,003 develops 34 00:01:43,003 --> 00:01:46,006 resistance to the r t. 35 00:01:46,673 --> 00:01:49,676 This study was carried out with patients 36 00:01:49,910 --> 00:01:53,080 who, already on second line antiretrovirals 37 00:01:53,613 --> 00:01:56,450 and whose second line regimens were now failing 38 00:01:56,450 --> 00:01:59,453 due to resistant strains of HIV. 39 00:02:00,420 --> 00:02:03,190 And the study sought to test a strategy 40 00:02:03,190 --> 00:02:06,226 for optimizing alternative treatment 41 00:02:06,226 --> 00:02:09,229 combinations for these patients. 42 00:02:11,898 --> 00:02:15,464 It was an open label phase for prospective interventional 43 00:02:15,464 --> 00:02:15,902 study, 44 00:02:15,902 --> 00:02:17,927 enrolling 500 adults with HIV one 45 00:02:17,927 --> 00:02:20,073 whose treatment with a second line 46 00:02:20,073 --> 00:02:22,776 regimen contained a protease inhibitor 47 00:02:22,776 --> 00:02:25,795 that is a particular type of antiretroviral, which 48 00:02:25,795 --> 00:02:26,580 was failing. 49 00:02:27,581 --> 00:02:29,645 The goal of the study was to test 50 00:02:29,645 --> 00:02:30,584 a novel method 51 00:02:30,584 --> 00:02:33,587 for assessing, resistance, 52 00:02:34,688 --> 00:02:36,657 and assignments 53 00:02:36,657 --> 00:02:39,084 then of the patient to a new treatment 54 00:02:39,084 --> 00:02:39,659 regimen. 55 00:02:40,293 --> 00:02:42,329 Study had sites in Brazil, India, Kenya, 56 00:02:42,329 --> 00:02:44,831 Malawi, Peru, South Africa, Thailand and 57 00:02:44,831 --> 00:02:45,332 Uganda. 58 00:02:46,666 --> 00:02:49,936 Then all of the drugs that we used in 59 00:02:49,936 --> 00:02:52,939 the trial were licensed in the US. 60 00:02:53,440 --> 00:02:56,003 They weren't all licensed in the countries 61 00:02:56,003 --> 00:02:58,078 where the trial was taking place. 62 00:02:59,112 --> 00:03:02,447 And this meant that participants might have been put on a 63 00:03:02,447 --> 00:03:03,150 lifesaving, 64 00:03:03,784 --> 00:03:06,250 treatment regimen, but then they wouldn't be able 65 00:03:06,250 --> 00:03:06,753 to obtain 66 00:03:06,753 --> 00:03:10,023 the same combination of drugs once they left the trial. 67 00:03:11,191 --> 00:03:13,593 And the researchers who designed the study, 68 00:03:13,593 --> 00:03:16,563 this seemed unethical. 69 00:03:18,031 --> 00:03:20,067 So that's the first case. 70 00:03:20,067 --> 00:03:22,396 Second case concerns a research study 71 00:03:22,396 --> 00:03:23,970 on Huntington's disease. 72 00:03:24,971 --> 00:03:27,472 Huntington's disease is a hereditary brain 73 00:03:27,472 --> 00:03:28,008 disease, 74 00:03:28,008 --> 00:03:31,011 caused by an autosomal dominant mutation, 75 00:03:31,011 --> 00:03:33,327 which means that if someone has Huntington's, 76 00:03:33,327 --> 00:03:34,047 then normally 77 00:03:34,347 --> 00:03:36,794 her children have a 50% chance of inheriting 78 00:03:36,794 --> 00:03:37,350 the gene. 79 00:03:37,617 --> 00:03:39,453 And so developing the disease as well. 80 00:03:40,654 --> 00:03:41,955 Symptoms of Huntington's 81 00:03:41,955 --> 00:03:45,692 usually start between, ages of 30 and 50. 82 00:03:46,126 --> 00:03:48,428 Causes uncoordinated, jerky body movements 83 00:03:48,428 --> 00:03:49,196 and a decline 84 00:03:49,196 --> 00:03:52,365 of mental capacity and adventure. 85 00:03:52,365 --> 00:03:54,401 Most Huntington's patients die 86 00:03:54,401 --> 00:03:57,404 within 20 years of onset of symptoms. 87 00:04:00,807 --> 00:04:02,509 There's a rural community 88 00:04:02,509 --> 00:04:05,512 on Lake Maracaibo in northwest Venezuela 89 00:04:05,912 --> 00:04:07,327 that has the highest concentration 90 00:04:07,327 --> 00:04:08,949 of Huntington's carriers in the world. 91 00:04:09,783 --> 00:04:11,574 This made it an ideal community for 92 00:04:11,574 --> 00:04:13,620 carrying out research into the disease. 93 00:04:14,221 --> 00:04:17,524 So in 1993, US researchers used, 94 00:04:17,791 --> 00:04:20,861 samples of blood and semen from people in Maracaibo 95 00:04:21,528 --> 00:04:23,876 to identify the gene that was responsible 96 00:04:23,876 --> 00:04:25,365 for causing Huntington's. 97 00:04:26,800 --> 00:04:30,137 As a result of that research, a genetic test was developed 98 00:04:30,137 --> 00:04:31,880 that could determine whether or not 99 00:04:31,880 --> 00:04:33,773 someone was a carrier of the disease. 100 00:04:34,441 --> 00:04:36,977 And that test is now available in many health care systems 101 00:04:36,977 --> 00:04:39,855 around the world, but it's not available 102 00:04:39,855 --> 00:04:41,581 to people in Maracaibo. 103 00:04:42,482 --> 00:04:44,818 And to some, that seems unfair. 104 00:04:48,121 --> 00:04:49,623 So Anastrozole is, 105 00:04:49,623 --> 00:04:51,898 a physician working in the community, 106 00:04:51,898 --> 00:04:53,927 expressed the concern like this. 107 00:04:54,594 --> 00:04:57,764 He said in the US or Europe, 108 00:04:57,764 --> 00:04:59,366 whoever has the disease in their family 109 00:04:59,366 --> 00:05:00,433 has the option to decide. 110 00:05:00,433 --> 00:05:01,701 I want to get the test. 111 00:05:01,701 --> 00:05:03,303 I don't want to know. 112 00:05:03,303 --> 00:05:05,739 The people of Maracaibo don't have that option. 113 00:05:05,739 --> 00:05:08,742 Even after they collaborated in the research. 114 00:05:11,011 --> 00:05:13,980 That these cases illustrate two ethical issues 115 00:05:13,980 --> 00:05:17,050 that are salient in research in populations 116 00:05:17,851 --> 00:05:19,965 that lack access to good quality care 117 00:05:19,965 --> 00:05:21,621 outside of research studies, 118 00:05:22,289 --> 00:05:24,826 which includes many populations in low and middle income 119 00:05:24,826 --> 00:05:25,325 countries. 120 00:05:26,259 --> 00:05:28,562 It can also include 121 00:05:28,562 --> 00:05:31,464 groups in high income countries who lack access to affordable 122 00:05:31,464 --> 00:05:34,248 health care, including in countries like the 123 00:05:34,248 --> 00:05:34,501 US. 124 00:05:34,501 --> 00:05:37,550 But I'm not going to focus on those cases 125 00:05:37,550 --> 00:05:38,071 today. 126 00:05:39,139 --> 00:05:42,142 The first is the issue of personal access. 127 00:05:42,142 --> 00:05:45,231 What care should participants receive after a 128 00:05:45,231 --> 00:05:45,712 study? 129 00:05:46,613 --> 00:05:48,117 So if they have a chronic condition 130 00:05:48,117 --> 00:05:49,449 that still requires treatment, 131 00:05:49,449 --> 00:05:51,651 are they entitled to continued treatment? 132 00:05:52,652 --> 00:05:55,922 Second, the issue of reasonable availability 133 00:05:57,090 --> 00:05:59,504 should host communities have access to study 134 00:05:59,504 --> 00:06:00,327 interventions? 135 00:06:01,561 --> 00:06:04,531 After a successful study? 136 00:06:06,533 --> 00:06:07,067 So I'm going to start 137 00:06:07,067 --> 00:06:10,937 by discussing, post-trial access to care for trial participants. 138 00:06:11,271 --> 00:06:13,995 And note I'm going to primarily focus 139 00:06:13,995 --> 00:06:15,542 on post-trial access 140 00:06:15,842 --> 00:06:18,812 to the intervention that's being tested in a study. 141 00:06:19,546 --> 00:06:21,540 Now, of course, that's not the only some 142 00:06:21,540 --> 00:06:23,583 participants might need a trial meeting. 143 00:06:24,084 --> 00:06:26,697 It has, however, been the focus of a lot of the 144 00:06:26,697 --> 00:06:27,087 debate 145 00:06:27,087 --> 00:06:30,090 over post-trial access. 146 00:06:30,523 --> 00:06:32,559 So first, what do the guidelines 147 00:06:32,559 --> 00:06:35,562 and the regulations say about this issue? 148 00:06:36,463 --> 00:06:38,975 The Declaration of Helsinki is, the World 149 00:06:38,975 --> 00:06:40,200 Medical Association 150 00:06:40,200 --> 00:06:41,990 statement of the ethical principles 151 00:06:41,990 --> 00:06:44,037 that they think should govern research. 152 00:06:44,704 --> 00:06:47,489 Extremely influential document used by research ethics 153 00:06:47,489 --> 00:06:48,108 committees. 154 00:06:48,742 --> 00:06:50,143 These, 155 00:06:50,143 --> 00:06:53,146 all around the world mentioned in regulations. 156 00:06:53,613 --> 00:06:57,083 The 2024 version of the declaration states 157 00:06:57,751 --> 00:06:59,418 in advance of the clinical trial, 158 00:06:59,418 --> 00:07:01,388 post-trial provisions must be arranged 159 00:07:01,388 --> 00:07:04,424 by sponsors and researchers to be provided by themselves, 160 00:07:04,858 --> 00:07:07,124 healthcare systems or governance for all 161 00:07:07,124 --> 00:07:07,861 participants 162 00:07:08,061 --> 00:07:09,899 who still need the intervention identified 163 00:07:09,899 --> 00:07:11,431 as beneficial and reasonably safe. 164 00:07:11,431 --> 00:07:11,965 In the trial. 165 00:07:12,932 --> 00:07:14,167 Exceptions to this requirement 166 00:07:14,167 --> 00:07:16,452 must be approved by Research Ethics 167 00:07:16,452 --> 00:07:17,170 Committee. 168 00:07:18,438 --> 00:07:21,441 Okay. 169 00:07:21,741 --> 00:07:25,312 At the national level, things are much less clear 170 00:07:25,312 --> 00:07:27,887 cut than they are with the Declaration of 171 00:07:27,887 --> 00:07:28,515 Helsinki. 172 00:07:29,983 --> 00:07:32,205 Most national regulations for human 173 00:07:32,205 --> 00:07:34,554 subjects research are silent on this 174 00:07:34,554 --> 00:07:35,889 question. 175 00:07:35,889 --> 00:07:38,667 So the common rule, for example, says nothing about post-trial 176 00:07:38,667 --> 00:07:39,025 access. 177 00:07:39,826 --> 00:07:41,603 Other regulations might encourage 178 00:07:41,603 --> 00:07:42,195 provision, 179 00:07:42,195 --> 00:07:43,988 require researchers to make efforts 180 00:07:43,988 --> 00:07:45,832 to transition participants to care, 181 00:07:46,132 --> 00:07:49,135 or simply require the provision of information. 182 00:07:50,236 --> 00:07:53,673 There is a legal requirement to provide post-trial access 183 00:07:53,673 --> 00:07:56,181 for participants in Argentina, Brazil, 184 00:07:56,181 --> 00:07:56,643 Chile, 185 00:07:58,211 --> 00:08:00,947 Peru, and recently India. 186 00:08:00,947 --> 00:08:04,551 I've not seen much data on, how that has been implemented 187 00:08:04,551 --> 00:08:08,021 in, Argentina, Chile, India and Peru. 188 00:08:08,788 --> 00:08:10,990 It's pretty recent in most countries. 189 00:08:10,990 --> 00:08:13,460 In Brazil, the entity 190 00:08:13,460 --> 00:08:15,176 that has the legal duty to provide 191 00:08:15,176 --> 00:08:17,297 post-trial access is frequently disputed. 192 00:08:17,630 --> 00:08:19,999 So pharmaceutical companies end up suing the government, 193 00:08:19,999 --> 00:08:22,669 and the government ends up suing pharmaceutical companies. 194 00:08:25,105 --> 00:08:27,374 Finally, post-trial access to successful 195 00:08:27,374 --> 00:08:30,377 interventions is also recommended by some, 196 00:08:31,311 --> 00:08:33,740 national guidelines in low and middle income 197 00:08:33,740 --> 00:08:34,347 countries. 198 00:08:34,681 --> 00:08:36,933 So, for example, in South Africa, 199 00:08:36,933 --> 00:08:37,684 in Uganda, 200 00:08:37,684 --> 00:08:40,987 those sorts of recommendations are not legally binding. 201 00:08:40,987 --> 00:08:42,822 But like the Declaration of Helsinki, 202 00:08:42,822 --> 00:08:45,825 they might be relied upon by research ethics committees 203 00:08:46,626 --> 00:08:48,995 who then have the power to disapprove 204 00:08:48,995 --> 00:08:51,998 research. 205 00:08:52,966 --> 00:08:55,869 Various sponsors of research, have policies that relate to 206 00:08:55,869 --> 00:08:58,089 post-trial access to, I'm going to mention 207 00:08:58,089 --> 00:08:59,305 just one, which is NIH 208 00:08:59,305 --> 00:09:02,308 has guidance. 209 00:09:03,042 --> 00:09:06,046 The NIH guidance applies very narrowly. 210 00:09:06,346 --> 00:09:08,508 It's written only for the provision of, 211 00:09:08,508 --> 00:09:09,949 antiretroviral treatment. 212 00:09:10,250 --> 00:09:14,354 It applies only to the provision of treatment to participants 213 00:09:14,354 --> 00:09:15,688 in treatment trials. 214 00:09:15,688 --> 00:09:18,585 So not, for example, participants 215 00:09:18,585 --> 00:09:19,726 who contract 216 00:09:19,726 --> 00:09:21,970 HIV during studies of interventions 217 00:09:21,970 --> 00:09:23,830 to prevent HIV transmission. 218 00:09:24,664 --> 00:09:27,300 And it applies only to developing countries. 219 00:09:27,300 --> 00:09:30,040 So not, for example, two studies that take place in 220 00:09:30,040 --> 00:09:30,470 the US. 221 00:09:33,740 --> 00:09:35,642 The guidance states 222 00:09:35,642 --> 00:09:37,980 that the NIH expects investigators 223 00:09:37,980 --> 00:09:39,012 or contractors 224 00:09:39,012 --> 00:09:42,115 to address the provision of antiretroviral treatment 225 00:09:42,115 --> 00:09:44,755 to trial participants after their completion of the 226 00:09:44,755 --> 00:09:45,118 trial. 227 00:09:45,819 --> 00:09:48,071 The NIH recommends that investigators 228 00:09:48,071 --> 00:09:49,289 or contractors work 229 00:09:49,956 --> 00:09:52,592 with host countries, authorities and other stakeholders 230 00:09:52,592 --> 00:09:55,595 to identify available sources of antiretroviral treatment. 231 00:09:56,229 --> 00:09:59,699 Priority may be given to sites where sources are identified. 232 00:09:59,966 --> 00:10:01,728 The provision of antiretroviral treatment 233 00:10:01,728 --> 00:10:02,802 following the completion 234 00:10:02,802 --> 00:10:05,805 of the trial. 235 00:10:06,973 --> 00:10:07,273 Okay. 236 00:10:07,273 --> 00:10:09,976 So, that's what some of the guidance and 237 00:10:09,976 --> 00:10:12,745 regulations say about post-trial access. 238 00:10:13,480 --> 00:10:15,949 What should we make of it from 239 00:10:15,949 --> 00:10:18,952 the point of view of ethics? 240 00:10:21,955 --> 00:10:24,224 Well, many researchers, 241 00:10:24,224 --> 00:10:27,132 trial participants, IRB members, ethicists 242 00:10:27,132 --> 00:10:29,762 think that there is a duty to provide 243 00:10:29,762 --> 00:10:31,852 post-trial access to effective treatment 244 00:10:31,852 --> 00:10:33,366 to participants who need it. 245 00:10:34,200 --> 00:10:38,329 Providing a justification for that duty has proven more 246 00:10:38,329 --> 00:10:39,305 challenging. 247 00:10:40,640 --> 00:10:41,341 Multiple rounds have 248 00:10:41,341 --> 00:10:44,878 been suggested, and I'm going to quickly discuss 249 00:10:45,345 --> 00:10:47,877 four important grants that have been raised by 250 00:10:47,877 --> 00:10:48,648 bioethicists. 251 00:10:48,915 --> 00:10:50,955 And I'll note some of the challenges 252 00:10:50,955 --> 00:10:51,918 with using them. 253 00:10:52,118 --> 00:10:55,121 I'll then say something about how post-trial access 254 00:10:55,121 --> 00:10:58,124 plays out in practice. 255 00:11:00,994 --> 00:11:03,062 The first justification is based on 256 00:11:03,062 --> 00:11:06,065 avoiding harm to participants. 257 00:11:07,000 --> 00:11:08,768 So if someone has a chronic disease 258 00:11:08,768 --> 00:11:10,959 and is benefiting from the treatment 259 00:11:10,959 --> 00:11:12,906 that they're on during a trial, 260 00:11:13,506 --> 00:11:16,943 taking them off the treatment will harm them. 261 00:11:18,077 --> 00:11:20,651 And this, it's argued, will violate the duty of normal 262 00:11:20,651 --> 00:11:21,080 absence. 263 00:11:21,748 --> 00:11:24,751 The case of antiretroviral therapy makes this clear. 264 00:11:24,984 --> 00:11:28,555 If someone's HIV is controlled by, regimen, 265 00:11:28,955 --> 00:11:31,039 taking it off that regimen will lead 266 00:11:31,039 --> 00:11:32,892 to a resurgence of her disease. 267 00:11:33,993 --> 00:11:35,636 And this sort of justification in terms 268 00:11:35,636 --> 00:11:37,363 of harm to participants is quite common. 269 00:11:39,199 --> 00:11:40,533 I think, though, 270 00:11:40,533 --> 00:11:43,736 it's usually a mistaken justification. 271 00:11:46,406 --> 00:11:49,275 The reason that it's mistaken 272 00:11:49,275 --> 00:11:52,412 is that in many, maybe most of the cases 273 00:11:52,412 --> 00:11:54,302 in which post-trial access to care 274 00:11:54,302 --> 00:11:55,415 would be desirable. 275 00:11:56,215 --> 00:11:58,779 Participating in the trial in the first place benefited 276 00:11:58,779 --> 00:11:59,385 participants 277 00:11:59,385 --> 00:12:02,388 relative to how they would otherwise have been. 278 00:12:02,822 --> 00:12:05,358 So suppose, we're evaluating a proposed 279 00:12:05,358 --> 00:12:08,656 trial of antihypertensive drug that's unapproved and so 280 00:12:08,656 --> 00:12:09,195 unlikely 281 00:12:09,195 --> 00:12:12,198 to be available soon to participants in a study. 282 00:12:13,066 --> 00:12:15,136 Assume that the drug turns out to be 283 00:12:15,136 --> 00:12:15,768 beneficial 284 00:12:15,768 --> 00:12:19,038 and there aren't alternatives available outside the trial. 285 00:12:19,305 --> 00:12:20,737 Otherwise, we wouldn't have these 286 00:12:20,737 --> 00:12:22,342 ethical concerns in the first place. 287 00:12:23,209 --> 00:12:26,373 In that case, if the participants were not in 288 00:12:26,373 --> 00:12:27,146 the trial, 289 00:12:27,847 --> 00:12:30,850 they would be without access to this beneficial treatment. 290 00:12:31,050 --> 00:12:32,918 Being in the trial provided access 291 00:12:32,918 --> 00:12:34,621 to that treatment for a while. 292 00:12:35,488 --> 00:12:38,256 So it's plausible that they're therefore better 293 00:12:38,256 --> 00:12:38,491 off 294 00:12:38,791 --> 00:12:40,793 even if they don't get access after the trial. 295 00:12:41,761 --> 00:12:44,494 And that implies that trial participation itself doesn't 296 00:12:44,494 --> 00:12:45,031 harm them. 297 00:12:45,031 --> 00:12:48,434 And so the duty of non Maleficent's is not violated. 298 00:12:53,106 --> 00:12:55,108 A second and I think more plausible 299 00:12:55,108 --> 00:12:55,908 justification 300 00:12:55,908 --> 00:12:59,178 grounds post-trial obligations and the special relationship 301 00:12:59,379 --> 00:13:00,647 between researchers 302 00:13:00,647 --> 00:13:02,378 and their participants that develops 303 00:13:02,378 --> 00:13:03,916 during the course of the study. 304 00:13:04,851 --> 00:13:06,986 And the idea is that this is analogous 305 00:13:06,986 --> 00:13:09,443 to the relationship between doctors and their 306 00:13:09,443 --> 00:13:09,989 patients. 307 00:13:10,189 --> 00:13:12,692 So just as a doctor has, 308 00:13:12,692 --> 00:13:15,695 a special duty with regard to the well-being of a patient. 309 00:13:15,895 --> 00:13:17,630 So a researcher has a special duty 310 00:13:17,630 --> 00:13:19,852 with regards to the well-being of the 311 00:13:19,852 --> 00:13:20,633 participant. 312 00:13:21,734 --> 00:13:24,055 And that's because in any clinical 313 00:13:24,055 --> 00:13:24,737 research, 314 00:13:25,238 --> 00:13:28,041 participants entrust aspects of their health 315 00:13:28,041 --> 00:13:30,627 to the researchers, providing information 316 00:13:30,627 --> 00:13:32,078 about their condition, 317 00:13:32,345 --> 00:13:35,181 receiving clinical care, and so on. 318 00:13:35,181 --> 00:13:36,883 Now, clearly, 319 00:13:36,883 --> 00:13:39,185 that suggests that the duty would be greater 320 00:13:39,185 --> 00:13:41,480 when a study has been long and has involved lots of 321 00:13:41,480 --> 00:13:42,155 clinical care. 322 00:13:43,690 --> 00:13:45,725 But then that fits with how 323 00:13:45,725 --> 00:13:48,277 researchers tend to feel that the participants have 324 00:13:48,277 --> 00:13:48,828 developed. 325 00:13:49,562 --> 00:13:52,532 The longer and deeper the relationship, the greater 326 00:13:52,532 --> 00:13:55,635 the felt obligation. 327 00:13:55,635 --> 00:13:57,825 And there are two related challenges 328 00:13:57,825 --> 00:13:58,738 that I see in, 329 00:13:59,272 --> 00:14:00,861 appealing to a special relationship 330 00:14:00,861 --> 00:14:02,542 between researchers and participants 331 00:14:02,542 --> 00:14:04,974 in order to ground the duty of researchers 332 00:14:04,974 --> 00:14:05,611 to provide 333 00:14:05,611 --> 00:14:08,581 post-trial, access to care. 334 00:14:09,515 --> 00:14:11,763 One of them is that the role morality of a 335 00:14:11,763 --> 00:14:12,351 researcher 336 00:14:12,351 --> 00:14:15,621 might be different than that of a clinician. 337 00:14:16,489 --> 00:14:18,813 After all, the primary goal of research 338 00:14:18,813 --> 00:14:20,660 is to conduct rigorous science 339 00:14:20,660 --> 00:14:23,171 that can generate knowledge that can benefit future 340 00:14:23,171 --> 00:14:23,663 patients. 341 00:14:24,697 --> 00:14:26,753 The well-being of research participants 342 00:14:26,753 --> 00:14:28,334 is normally a secondary goal, 343 00:14:28,334 --> 00:14:30,488 or maybe a constraint on the pursuit 344 00:14:30,488 --> 00:14:31,804 of that primary goal. 345 00:14:34,173 --> 00:14:35,308 By contrast, 346 00:14:35,308 --> 00:14:36,902 the primary goal of clinical care 347 00:14:36,902 --> 00:14:38,544 is in general to help the patient 348 00:14:38,544 --> 00:14:40,213 who is currently in front of the clinician. 349 00:14:41,781 --> 00:14:44,784 So, insofar as the two audience analysis, 350 00:14:45,384 --> 00:14:47,208 we'd expect the special obligations 351 00:14:47,208 --> 00:14:49,188 of the researcher to her participants 352 00:14:49,188 --> 00:14:52,759 to be weaker than those, of the clinician, 353 00:14:53,159 --> 00:14:56,162 to her patients. 354 00:14:57,296 --> 00:15:00,700 The other challenge is that in any case, I'm not convinced 355 00:15:00,700 --> 00:15:03,974 that clinicians have open ended obligations to their 356 00:15:03,974 --> 00:15:04,604 patients, 357 00:15:05,805 --> 00:15:07,206 at least in the United States. 358 00:15:07,206 --> 00:15:09,890 It seems as though when someone loses their 359 00:15:09,890 --> 00:15:10,576 insurance, 360 00:15:11,110 --> 00:15:13,012 their primary care physician 361 00:15:13,012 --> 00:15:14,773 doesn't have an obligation to continue 362 00:15:14,773 --> 00:15:16,349 to provide care to them for free. 363 00:15:16,883 --> 00:15:17,216 Right? 364 00:15:17,216 --> 00:15:19,975 That most there's a duty not to abandon one's patient to 365 00:15:19,975 --> 00:15:20,319 ensure 366 00:15:20,319 --> 00:15:23,322 a transition to some other source of care. 367 00:15:24,390 --> 00:15:26,592 So I think 368 00:15:26,592 --> 00:15:28,821 the relationship is, a possible ground 369 00:15:28,821 --> 00:15:30,463 for post-trial obligations, 370 00:15:31,030 --> 00:15:33,666 of researchers, but potentially quite a weak 371 00:15:33,666 --> 00:15:36,669 grand. 372 00:15:37,804 --> 00:15:38,704 Third, 373 00:15:38,704 --> 00:15:42,341 some ethicists cite a duty of reciprocation. 374 00:15:44,076 --> 00:15:45,745 So research participants contribute 375 00:15:45,745 --> 00:15:47,809 to medical knowledge when they take part 376 00:15:47,809 --> 00:15:49,048 in medical experiments. 377 00:15:49,315 --> 00:15:51,524 It seems plausible they deserve something 378 00:15:51,524 --> 00:15:53,786 in return for the contribution they make. 379 00:15:54,320 --> 00:15:56,260 But one appropriate way, to provide 380 00:15:56,260 --> 00:15:57,757 this might be by providing 381 00:15:57,757 --> 00:16:01,227 additional medical care to them after the trial is complete. 382 00:16:03,095 --> 00:16:05,698 Now, again, I think this is a plausible 383 00:16:05,698 --> 00:16:06,165 ground 384 00:16:06,165 --> 00:16:09,168 for post-trial obligations. 385 00:16:09,602 --> 00:16:12,196 One important challenge, though, is it's not going to 386 00:16:12,196 --> 00:16:12,538 ground 387 00:16:12,538 --> 00:16:15,780 open ended obligations, and it won't grant the same 388 00:16:15,780 --> 00:16:16,542 obligations 389 00:16:16,542 --> 00:16:19,545 in every case. 390 00:16:19,545 --> 00:16:21,147 If what we're doing is, 391 00:16:21,147 --> 00:16:23,460 reciprocating for the contribution of the 392 00:16:23,460 --> 00:16:24,250 participants, 393 00:16:24,250 --> 00:16:25,801 then the extent of the obligation 394 00:16:25,801 --> 00:16:27,587 to benefit them, it's going to depend 395 00:16:27,587 --> 00:16:30,590 on the extent of their contribution. 396 00:16:31,624 --> 00:16:34,129 And this, we might think, would be analyzed in terms of 397 00:16:34,129 --> 00:16:34,493 factors 398 00:16:34,493 --> 00:16:38,024 like, the burden they took on in participating, the risks they 399 00:16:38,024 --> 00:16:38,764 took on. So. 400 00:16:41,267 --> 00:16:43,202 Note also 401 00:16:43,202 --> 00:16:45,517 that it's not just or even mostly 402 00:16:45,517 --> 00:16:46,639 the researchers 403 00:16:46,639 --> 00:16:50,176 who would have this obligation, since other parties also benefit 404 00:16:50,176 --> 00:16:53,279 for the contribution of research participants. 405 00:16:53,279 --> 00:16:55,181 The very least sponsors of research, 406 00:16:55,181 --> 00:16:57,814 like pharmaceutical companies, would share the obligation to 407 00:16:57,814 --> 00:16:58,384 reciprocate. 408 00:16:58,985 --> 00:17:01,986 And so might governments who make use of the products of 409 00:17:01,986 --> 00:17:02,521 research, 410 00:17:02,788 --> 00:17:04,590 within healthcare systems. 411 00:17:04,590 --> 00:17:07,660 So this is not just going to be then an obligation 412 00:17:07,660 --> 00:17:10,663 that falls on researchers. 413 00:17:11,731 --> 00:17:15,440 For a duty to provide post-trial access might be 414 00:17:15,440 --> 00:17:16,135 grounded 415 00:17:16,135 --> 00:17:18,237 in a duty of beneficence. 416 00:17:18,237 --> 00:17:21,340 That's called the duty to rescue. 417 00:17:21,340 --> 00:17:22,275 That's classic case. 418 00:17:22,275 --> 00:17:25,444 To, illustrate this duty is as follows. 419 00:17:25,444 --> 00:17:25,645 Yeah. 420 00:17:25,645 --> 00:17:28,581 Imagine I'm on my way to give a talk, 421 00:17:28,581 --> 00:17:31,584 and I walk past, a large pond. 422 00:17:32,051 --> 00:17:34,854 And in the pond, I notice, a child drowning. 423 00:17:34,854 --> 00:17:35,821 No one else is around. 424 00:17:36,822 --> 00:17:39,992 Now, I could wade into the pond 425 00:17:39,992 --> 00:17:42,461 and save the child, but 426 00:17:42,461 --> 00:17:45,531 I'm wearing a rather nice white suit, 427 00:17:46,532 --> 00:17:49,535 so it's going to be ruined if I rescue the child. 428 00:17:49,535 --> 00:17:52,538 And that is several hundred dollars. 429 00:17:53,873 --> 00:17:54,907 Here's the point. 430 00:17:54,907 --> 00:17:57,910 Even if it's going to ruin my suit, 431 00:17:58,644 --> 00:18:01,580 I have a moral duty to wade in and rescue 432 00:18:01,580 --> 00:18:04,584 the child. 433 00:18:05,618 --> 00:18:06,586 The ethicist Peter 434 00:18:06,586 --> 00:18:10,708 Singer provides a succinct statement of the duty 435 00:18:10,708 --> 00:18:11,223 here. 436 00:18:11,691 --> 00:18:15,618 He writes, if it's in our power to prevent something bad from 437 00:18:15,618 --> 00:18:16,262 happening 438 00:18:16,262 --> 00:18:18,030 without thereby sacrificing anything 439 00:18:18,030 --> 00:18:21,033 morally significant, we ought thoroughly to do it. 440 00:18:22,168 --> 00:18:25,705 So apply this, principle to the case of hand 441 00:18:26,806 --> 00:18:27,239 research. 442 00:18:27,239 --> 00:18:29,710 This might be in a position to give urgently needed 443 00:18:29,710 --> 00:18:30,242 treatment. 444 00:18:30,242 --> 00:18:33,245 So, for example, continued care might be lifesaving 445 00:18:33,579 --> 00:18:36,048 and research participants may not have access 446 00:18:36,048 --> 00:18:39,051 to other sources of treatment outside of the trial. 447 00:18:39,385 --> 00:18:42,491 So the duty to rescue could ground post-trial 448 00:18:42,491 --> 00:18:43,389 obligations. 449 00:18:46,058 --> 00:18:48,160 Two challenges should be mentioned, 450 00:18:48,160 --> 00:18:51,163 regarding the duty to rescue in this context. 451 00:18:51,364 --> 00:18:53,132 First, 452 00:18:53,132 --> 00:18:54,734 it's going to apply only in cases 453 00:18:54,734 --> 00:18:56,335 where providing the intervention 454 00:18:56,335 --> 00:18:59,706 is relatively low cost and the benefit it provides is 455 00:18:59,706 --> 00:19:00,406 very high. 456 00:19:01,007 --> 00:19:04,010 Those are going to be the rescue cases 457 00:19:04,343 --> 00:19:06,245 for really expensive, 458 00:19:06,245 --> 00:19:08,839 interventions or interventions that provide only marginal 459 00:19:08,839 --> 00:19:09,248 benefit. 460 00:19:09,615 --> 00:19:11,884 That's not going to justify a duty 461 00:19:11,884 --> 00:19:12,618 to rescue. 462 00:19:14,020 --> 00:19:15,421 Second, 463 00:19:15,421 --> 00:19:18,424 the duty to rescue applies any time that someone 464 00:19:18,991 --> 00:19:21,558 can provide a great benefit to another at low cost to 465 00:19:21,558 --> 00:19:21,994 herself. 466 00:19:22,762 --> 00:19:25,765 It's not specific to researchers or research subjects. 467 00:19:26,065 --> 00:19:28,534 For example, if, 468 00:19:28,534 --> 00:19:30,636 the researchers in a particular 469 00:19:30,636 --> 00:19:33,739 country are studying heart disease, 470 00:19:33,739 --> 00:19:36,208 but the local community is in desperate 471 00:19:36,208 --> 00:19:39,211 need of, say, antimalarials. 472 00:19:39,979 --> 00:19:41,113 The fact that the researchers 473 00:19:41,113 --> 00:19:42,643 could provide those antimalarials 474 00:19:42,643 --> 00:19:44,450 could mean they have a duty to rescue, 475 00:19:45,317 --> 00:19:48,745 even to people who are not in that research 476 00:19:48,745 --> 00:19:49,622 study. And 477 00:19:50,923 --> 00:19:53,759 clinicians, NGOs, government agencies, 478 00:19:53,759 --> 00:19:55,777 anyone else in a position to provide 479 00:19:55,777 --> 00:19:57,963 aid can equally have a duty to rescue. 480 00:20:00,366 --> 00:20:02,401 So this table 481 00:20:02,401 --> 00:20:05,404 summarizes, foregrounds that have been suggested for why 482 00:20:05,404 --> 00:20:08,140 there might be an ethical duty to provide 483 00:20:08,140 --> 00:20:10,342 post-trauma care to participants 484 00:20:10,843 --> 00:20:13,198 who wouldn't be able to access that care 485 00:20:13,198 --> 00:20:13,846 otherwise. 486 00:20:15,281 --> 00:20:17,917 I've suggested that, the duty to avoid harm 487 00:20:17,917 --> 00:20:19,813 will normally not apply in the cases 488 00:20:19,813 --> 00:20:20,920 we're interested in. 489 00:20:21,954 --> 00:20:24,537 The special relationship between researchers and 490 00:20:24,537 --> 00:20:25,291 participants, 491 00:20:26,125 --> 00:20:28,232 and the duty of reciprocity might ground 492 00:20:28,232 --> 00:20:30,129 duties of care for the researchers. 493 00:20:30,896 --> 00:20:33,899 But those duties will be limited in their extent. 494 00:20:34,900 --> 00:20:37,636 The duty to rescue may occasionally apply, 495 00:20:37,636 --> 00:20:40,322 but it won't be limited to the urgent needs of 496 00:20:40,322 --> 00:20:41,140 participants. 497 00:20:44,743 --> 00:20:47,313 So some key points I'd like to emphasize 498 00:20:47,313 --> 00:20:49,381 from this ethical analysis of post-trial access. 499 00:20:50,950 --> 00:20:52,651 None of the justifications 500 00:20:52,651 --> 00:20:55,233 that I've discussed imply an open ended obligation for 501 00:20:55,233 --> 00:20:55,855 researchers. 502 00:20:56,889 --> 00:20:59,795 The researchers themselves don't have an obligation to 503 00:20:59,795 --> 00:21:00,226 provide 504 00:21:00,226 --> 00:21:03,229 care for the next step. Yes. 505 00:21:04,497 --> 00:21:05,364 Further, 506 00:21:05,364 --> 00:21:10,078 none of the justifications imply that the best or the only way to 507 00:21:10,078 --> 00:21:10,803 discharge 508 00:21:10,803 --> 00:21:12,551 researchers post-trial obligations 509 00:21:12,551 --> 00:21:14,607 is by providing the study intervention. 510 00:21:15,674 --> 00:21:18,338 It might be in some cases, like with the antiretroviral 511 00:21:18,338 --> 00:21:18,677 study, 512 00:21:19,378 --> 00:21:23,185 but in other cases, especially, with studies where the standard 513 00:21:23,185 --> 00:21:23,849 of care in 514 00:21:23,849 --> 00:21:26,431 the trial is higher than the standard of care 515 00:21:26,431 --> 00:21:27,119 outside it, 516 00:21:28,320 --> 00:21:29,758 other care beside the experimental 517 00:21:29,758 --> 00:21:31,323 intervention might be more valuable. 518 00:21:32,858 --> 00:21:34,827 And finally, 519 00:21:34,827 --> 00:21:37,730 this is not just a matter for the researchers. 520 00:21:37,730 --> 00:21:40,633 We need to consider the duties of multiple parties, 521 00:21:40,633 --> 00:21:43,858 including the researchers, but also sponsors and national 522 00:21:43,858 --> 00:21:44,537 governments 523 00:21:44,537 --> 00:21:47,048 who are responsible for providing care to the 524 00:21:47,048 --> 00:21:47,606 citizens. 525 00:21:50,009 --> 00:21:53,012 Current practice with regard to, 526 00:21:53,345 --> 00:21:55,741 providing post-trial access to effective experimental 527 00:21:55,741 --> 00:21:56,148 products 528 00:21:56,148 --> 00:21:59,151 is highly variable. 529 00:21:59,418 --> 00:22:01,654 Many research sites, 530 00:22:01,654 --> 00:22:04,056 the focus is on transitioning 531 00:22:04,056 --> 00:22:06,531 participants who still need cat other sources 532 00:22:06,531 --> 00:22:07,026 of care. 533 00:22:07,026 --> 00:22:09,595 So these might be national health systems. 534 00:22:09,595 --> 00:22:12,185 They might be other studies for which participants are now 535 00:22:12,185 --> 00:22:12,631 eligible. 536 00:22:14,466 --> 00:22:16,911 Research sites in these cases, may 537 00:22:16,911 --> 00:22:18,637 then provide short term 538 00:22:18,637 --> 00:22:21,749 care during a transition period, but not for extended periods of 539 00:22:21,749 --> 00:22:22,041 time. 540 00:22:22,441 --> 00:22:25,835 Some companies have ensured continued access to beneficial 541 00:22:25,835 --> 00:22:26,478 treatments 542 00:22:26,478 --> 00:22:29,919 for serious conditions by running, open label extension 543 00:22:29,919 --> 00:22:30,482 studies. 544 00:22:31,016 --> 00:22:33,405 And again, this is not a consistent 545 00:22:33,405 --> 00:22:34,019 practice 546 00:22:35,221 --> 00:22:37,223 in high income countries. 547 00:22:37,223 --> 00:22:39,558 It's more likely participants will get access, to 548 00:22:39,558 --> 00:22:41,876 continue treatment through expanded 549 00:22:41,876 --> 00:22:43,862 access programs or in the US, 550 00:22:44,330 --> 00:22:47,333 compassionate use programs until drugs get licensed. 551 00:22:48,767 --> 00:22:49,201 Finally. 552 00:22:51,737 --> 00:22:53,906 Perceived obligations 553 00:22:53,906 --> 00:22:57,576 to ensure post-trial access have also led, in some cases, 554 00:22:57,576 --> 00:23:00,737 public and private sponsors, to avoid carrying out research 555 00:23:00,737 --> 00:23:01,380 in contexts 556 00:23:01,847 --> 00:23:04,558 where patients don't have access to effective care outside of the 557 00:23:04,558 --> 00:23:04,850 trial. 558 00:23:05,618 --> 00:23:07,661 I don't want to flag this because I think 559 00:23:07,661 --> 00:23:09,555 it's a potentially unfortunate effect 560 00:23:09,555 --> 00:23:11,605 of demanding that researchers and sponsors 561 00:23:11,605 --> 00:23:12,825 provide post-trial care. 562 00:23:12,825 --> 00:23:14,093 You're getting into this, 563 00:23:14,093 --> 00:23:15,860 I think also in the end of the question 564 00:23:15,860 --> 00:23:17,129 period in the last session. 565 00:23:18,631 --> 00:23:21,860 So there's potential for people who already lack access to care 566 00:23:21,860 --> 00:23:22,167 to be 567 00:23:22,167 --> 00:23:24,287 penalized, again by not getting access 568 00:23:24,287 --> 00:23:25,738 to care through research. 569 00:23:26,071 --> 00:23:29,261 So pushing for post-trial access cuts 570 00:23:29,261 --> 00:23:30,209 both ways. 571 00:23:31,377 --> 00:23:34,380 Let me return now to the case with which we began. 572 00:23:35,047 --> 00:23:38,150 The drugs in question were made by multiple private companies, 573 00:23:38,150 --> 00:23:40,319 and those companies agreed to provide the drugs 574 00:23:40,319 --> 00:23:42,388 that were not licensed in country for free. 575 00:23:44,623 --> 00:23:47,312 They didn't want to be involved with the distribution of the 576 00:23:47,312 --> 00:23:47,626 drugs. 577 00:23:47,626 --> 00:23:50,296 That would have to be done by the research team. 578 00:23:50,296 --> 00:23:52,264 The sponsor, on the other hand, 579 00:23:52,264 --> 00:23:54,673 was not allowed to provide clinical care outside of a 580 00:23:54,673 --> 00:23:55,401 research study. 581 00:23:55,968 --> 00:23:58,704 So after considerable negotiation, 582 00:23:58,704 --> 00:24:01,407 the following arrangement was reached. 583 00:24:01,407 --> 00:24:04,410 The researchers designed an extension study, 584 00:24:05,978 --> 00:24:07,721 which would provide the manufacturers 585 00:24:07,721 --> 00:24:09,181 drugs with the goal of testing 586 00:24:09,181 --> 00:24:11,965 whether the participants remain virally suppressed for two 587 00:24:11,965 --> 00:24:12,685 further years. 588 00:24:13,452 --> 00:24:15,672 And the thought was that two years 589 00:24:15,672 --> 00:24:18,023 should be enough time for the drugs 590 00:24:18,023 --> 00:24:19,719 to be licensed in country and provided 591 00:24:19,719 --> 00:24:21,460 to patients through national programs. 592 00:24:22,962 --> 00:24:25,397 I'll leave you to decide whether you think 593 00:24:25,397 --> 00:24:28,400 that was a sufficient arrangement. 594 00:24:29,968 --> 00:24:31,369 Okay, so I'm not going to leave behind 595 00:24:31,369 --> 00:24:31,737 the issue 596 00:24:31,737 --> 00:24:33,274 of what carries out to participants 597 00:24:33,274 --> 00:24:35,074 who leave a trial still in need of care. 598 00:24:35,341 --> 00:24:36,753 And I'm going to turn to the issue 599 00:24:36,753 --> 00:24:37,376 of what's owed 600 00:24:37,376 --> 00:24:39,545 to the communities that host research. 601 00:24:41,280 --> 00:24:43,489 To a large extent, this discussion is focused on 602 00:24:43,489 --> 00:24:43,949 the issue 603 00:24:43,949 --> 00:24:46,366 of making, again, study interventions 604 00:24:46,366 --> 00:24:47,019 available 605 00:24:47,019 --> 00:24:50,022 to host communities. 606 00:24:51,557 --> 00:24:52,691 Now, there are fewer 607 00:24:52,691 --> 00:24:55,327 guidelines and regulations that speak to this issue. 608 00:24:55,327 --> 00:24:58,597 Two of the most important sets of international guidelines 609 00:24:58,997 --> 00:25:02,101 have relevant clauses. 610 00:25:02,101 --> 00:25:05,104 So the Declaration of Helsinki says that 611 00:25:06,372 --> 00:25:08,287 medical research with individuals, groups 612 00:25:08,287 --> 00:25:09,641 or communities in situations 613 00:25:09,842 --> 00:25:12,811 of particular vulnerability is only justified 614 00:25:13,045 --> 00:25:16,048 if it's responsive to the health needs and priorities, 615 00:25:16,315 --> 00:25:18,717 and the individual, group or community stands to benefit 616 00:25:18,717 --> 00:25:20,772 from the resulting knowledge, practices 617 00:25:20,772 --> 00:25:21,720 or interventions. 618 00:25:22,821 --> 00:25:25,174 The second piece of extremely influential 619 00:25:25,174 --> 00:25:27,126 international guidance comes from 620 00:25:27,126 --> 00:25:29,133 the Council of International Organizations 621 00:25:29,133 --> 00:25:30,662 of Medical Sciences or Science. 622 00:25:32,297 --> 00:25:35,300 Their 2002 guidelines set 623 00:25:36,602 --> 00:25:39,171 before undertaking research in a population or community 624 00:25:39,171 --> 00:25:40,906 with limited resources. 625 00:25:40,906 --> 00:25:44,097 The sponsor and the investigator must make every effort to ensure 626 00:25:44,097 --> 00:25:44,343 that 627 00:25:45,344 --> 00:25:46,678 the research is responsive 628 00:25:46,678 --> 00:25:48,213 to the health needs and the priorities 629 00:25:48,213 --> 00:25:51,183 of the population, community, and which is to be carried out 630 00:25:51,183 --> 00:25:55,513 and any intervention or product developed or knowledge generated 631 00:25:55,513 --> 00:25:56,054 will be 632 00:25:56,054 --> 00:25:58,534 made reasonably available for the benefit of that 633 00:25:58,534 --> 00:25:59,091 population 634 00:25:59,324 --> 00:26:02,327 or community. 635 00:26:03,295 --> 00:26:05,597 Okay, so what's the ethical reasoning 636 00:26:05,597 --> 00:26:08,634 behind these recommendations that the group population 637 00:26:08,634 --> 00:26:11,637 communities should get access to the products of research? 638 00:26:13,071 --> 00:26:16,074 I think that the underlying concern 639 00:26:16,442 --> 00:26:19,111 about conducting research, where it's not expected 640 00:26:19,111 --> 00:26:21,211 that the host community would get access 641 00:26:21,211 --> 00:26:23,415 to the products of research, is a concern 642 00:26:23,649 --> 00:26:26,652 about exploitation. 643 00:26:28,353 --> 00:26:29,655 Now, what does it mean 644 00:26:29,655 --> 00:26:31,837 for one party to exploit another, 645 00:26:31,837 --> 00:26:33,225 or for a transaction 646 00:26:33,659 --> 00:26:36,462 to be exploitative? 647 00:26:36,462 --> 00:26:39,465 The standard analysis defines exploitation like this 648 00:26:40,232 --> 00:26:44,269 x exploit Y when X takes unfair advantage of y situation. 649 00:26:44,670 --> 00:26:47,773 So the party doing the exploiting 650 00:26:48,974 --> 00:26:50,108 takes advantage of some 651 00:26:50,108 --> 00:26:53,597 vulnerability of the other party in order to get more out of 652 00:26:53,597 --> 00:26:53,946 them. 653 00:26:54,313 --> 00:26:56,982 That is deserved. 654 00:26:56,982 --> 00:26:59,985 So, for example, suppose my car gets stuck in the mud. 655 00:27:00,252 --> 00:27:03,255 Phyllis is the only person with a tow truck. 656 00:27:03,956 --> 00:27:06,625 I might be vulnerable because I have no other way to get out 657 00:27:06,625 --> 00:27:07,159 of the mud. 658 00:27:07,693 --> 00:27:10,362 I suppose it's miles to the nearest town. 659 00:27:10,362 --> 00:27:13,365 I won't be able to make it there without my car. 660 00:27:13,665 --> 00:27:16,662 Suppose she charges me a thousand bucks for ten 661 00:27:16,662 --> 00:27:17,236 minutes. 662 00:27:17,236 --> 00:27:20,239 Work. 663 00:27:20,506 --> 00:27:23,487 So I might be willing to pay that much to get pulled out of 664 00:27:23,487 --> 00:27:23,942 the mud. 665 00:27:24,343 --> 00:27:26,178 If I'm in a desperate situation. 666 00:27:26,178 --> 00:27:28,914 But she's surely treating me wrongly. 667 00:27:28,914 --> 00:27:31,250 And the wrong here, I think, is that she's 668 00:27:31,250 --> 00:27:32,084 exploiting me. 669 00:27:32,084 --> 00:27:35,087 She takes unfair advantage of my situation 670 00:27:35,087 --> 00:27:38,323 to get more out of our interaction than she should. 671 00:27:42,661 --> 00:27:44,630 Now, looking at this sort of, 672 00:27:44,630 --> 00:27:48,767 simple example helps us to see some key 673 00:27:48,767 --> 00:27:51,770 characteristics of exploitation. 674 00:27:52,905 --> 00:27:54,644 Does exploitation have to be harmful 675 00:27:54,644 --> 00:27:56,141 to the person who's exploited? 676 00:27:56,441 --> 00:28:01,213 No, I'm not harmed in this, case by, exploiting me. 677 00:28:01,213 --> 00:28:02,347 I'm benefited. 678 00:28:02,347 --> 00:28:04,158 That's why I agreed to pay the thousand 679 00:28:04,158 --> 00:28:04,483 bucks. 680 00:28:04,483 --> 00:28:07,562 Because it's better for me to be pulled out of the mud and 681 00:28:07,562 --> 00:28:07,986 survive 682 00:28:08,220 --> 00:28:11,223 than it is to be left there with my thousand bucks. 683 00:28:11,890 --> 00:28:14,159 Does exploitation involve invalid consent? 684 00:28:14,159 --> 00:28:14,826 Again, no. 685 00:28:14,826 --> 00:28:16,395 I might understand what I'm agreeing to 686 00:28:16,395 --> 00:28:19,398 and do it voluntarily, but still be exploited. 687 00:28:20,232 --> 00:28:23,268 So we can have what Alan Wertheimer called 688 00:28:23,268 --> 00:28:26,338 mutually advantageous consensual exploitation. 689 00:28:29,174 --> 00:28:31,476 Okay, so return now to the question 690 00:28:31,476 --> 00:28:33,598 of the exploitation of communities 691 00:28:33,598 --> 00:28:34,846 that host research. 692 00:28:36,548 --> 00:28:38,162 They'll be exploited if they receive 693 00:28:38,162 --> 00:28:39,418 an unfair level of benefits 694 00:28:39,418 --> 00:28:42,888 from the research relative to the burdens 695 00:28:42,888 --> 00:28:44,699 of hosting the research and relative 696 00:28:44,699 --> 00:28:46,258 to the gains to other parties. 697 00:28:48,093 --> 00:28:48,927 So gains to other 698 00:28:48,927 --> 00:28:51,411 parties might be, companies who profit 699 00:28:51,411 --> 00:28:53,699 from developing a successful drug, 700 00:28:53,699 --> 00:28:56,702 or maybe patients in other countries 701 00:28:56,702 --> 00:28:59,671 who benefit from the drug being developed. 702 00:29:00,305 --> 00:29:03,041 So we need to think about the burdens 703 00:29:03,041 --> 00:29:06,044 and the benefits to those communities. 704 00:29:06,612 --> 00:29:09,514 So what sort of burdens might that be? 705 00:29:09,514 --> 00:29:12,050 Over and above 706 00:29:12,050 --> 00:29:14,309 the risks and burdens faced by, research 707 00:29:14,309 --> 00:29:15,721 participants themselves? 708 00:29:16,888 --> 00:29:18,390 Well, 709 00:29:18,390 --> 00:29:21,023 the research might make use of clinical services that are 710 00:29:21,023 --> 00:29:21,393 scarce. 711 00:29:22,361 --> 00:29:22,561 Right. 712 00:29:22,561 --> 00:29:24,413 So if local health care practitioners 713 00:29:24,413 --> 00:29:26,064 are hired for the research, then 714 00:29:26,064 --> 00:29:28,006 it might attract them away from the public 715 00:29:28,006 --> 00:29:29,901 health system and thereby contribute to, 716 00:29:30,902 --> 00:29:33,905 an internal brain drain. 717 00:29:34,673 --> 00:29:36,274 There's a limit to how much research 718 00:29:36,274 --> 00:29:39,277 can take place at any one site. 719 00:29:40,412 --> 00:29:42,547 So research that doesn't have 720 00:29:42,547 --> 00:29:45,745 high social value may crowd out that more valuable 721 00:29:45,745 --> 00:29:46,385 research. 722 00:29:47,919 --> 00:29:49,554 There are, of course, 723 00:29:49,554 --> 00:29:52,557 also benefits potentially to host communities. 724 00:29:52,791 --> 00:29:55,794 And so a research study might answer questions 725 00:29:55,994 --> 00:29:58,518 about local health problems that are important to the host 726 00:29:58,518 --> 00:29:58,997 community. 727 00:29:59,731 --> 00:30:01,900 But so answering questions 728 00:30:01,900 --> 00:30:03,772 about the epidemiology of a disease 729 00:30:03,772 --> 00:30:05,804 might help with local vector control, 730 00:30:06,405 --> 00:30:08,674 efforts or with public information 731 00:30:08,674 --> 00:30:09,408 campaigns. 732 00:30:10,842 --> 00:30:14,046 The research may be, part of the process 733 00:30:14,046 --> 00:30:16,590 of developing new interventions that are going to benefit the 734 00:30:16,590 --> 00:30:17,049 population 735 00:30:17,983 --> 00:30:20,540 rather than taking away from the 736 00:30:20,540 --> 00:30:21,420 facilities 737 00:30:21,420 --> 00:30:25,190 and the trained clinicians, that will be providing care. 738 00:30:26,391 --> 00:30:27,970 It's possible that the infrastructure 739 00:30:27,970 --> 00:30:29,761 that's used for the research could expand 740 00:30:30,062 --> 00:30:31,730 local facilities, and local health care 741 00:30:31,730 --> 00:30:33,398 workers might get additional training. 742 00:30:35,634 --> 00:30:36,935 Now, think 743 00:30:36,935 --> 00:30:39,938 back to the reasonable availability requirement 744 00:30:40,806 --> 00:30:43,775 requiring that research, 745 00:30:43,775 --> 00:30:46,645 only be conducted when the products of research 746 00:30:46,645 --> 00:30:48,215 will be made reasonably available 747 00:30:48,215 --> 00:30:49,881 for patients and host communities. 748 00:30:51,783 --> 00:30:54,088 Avoids exploitation by ensuring that 749 00:30:54,088 --> 00:30:54,920 the benefits 750 00:30:54,920 --> 00:30:57,494 those communities are fair given the benefits that other parties 751 00:30:57,494 --> 00:30:57,856 receive. 752 00:30:57,856 --> 00:30:59,565 Given the burdens that have taken 753 00:30:59,565 --> 00:31:00,859 on hosting the research. 754 00:31:01,193 --> 00:31:03,347 The idea, I take it, is that the benefits 755 00:31:03,347 --> 00:31:05,397 of getting access to new interventions 756 00:31:05,397 --> 00:31:06,834 that are important for the health 757 00:31:06,834 --> 00:31:08,533 of people in the community is normally 758 00:31:08,533 --> 00:31:10,934 thought to be a sufficient benefit 759 00:31:10,934 --> 00:31:11,570 to avoid 760 00:31:11,570 --> 00:31:14,573 exploitation. 761 00:31:15,841 --> 00:31:18,543 However. 762 00:31:18,543 --> 00:31:19,511 The requirement of reasonable 763 00:31:19,511 --> 00:31:22,514 availability has come in for some criticism. 764 00:31:22,514 --> 00:31:24,164 For one, it's not going to be relevant 765 00:31:24,164 --> 00:31:25,250 to some research, right? 766 00:31:25,250 --> 00:31:27,241 For example, it's not going to apply 767 00:31:27,241 --> 00:31:29,287 to phase one, trials, since normally 768 00:31:29,287 --> 00:31:30,960 the products that make it through phase 769 00:31:30,960 --> 00:31:32,290 one of not yet shown efficacy. 770 00:31:34,092 --> 00:31:36,695 Is going to apply to epidemiological studies 771 00:31:36,695 --> 00:31:39,264 because they have no associated product. 772 00:31:39,264 --> 00:31:42,367 Sometimes there are no benefits to be provided, right? 773 00:31:43,101 --> 00:31:45,937 If the study doesn't show an intervention to be effective, 774 00:31:45,937 --> 00:31:48,540 then there's no beneficial intervention to provide 775 00:31:50,108 --> 00:31:52,110 further. 776 00:31:52,110 --> 00:31:53,979 The requirement, has been criticized 777 00:31:53,979 --> 00:31:56,982 for putting an excessive burden on researchers and sponsors. 778 00:31:57,916 --> 00:31:59,484 It's not their job. 779 00:31:59,484 --> 00:32:00,986 It's argued 780 00:32:00,986 --> 00:32:02,574 to provide drugs to everyone in the 781 00:32:02,574 --> 00:32:04,389 population who would benefit from them. 782 00:32:04,890 --> 00:32:07,526 Nor is it their job to ensure that the, local 783 00:32:07,526 --> 00:32:10,529 health care system provides the drugs. 784 00:32:11,263 --> 00:32:12,464 And finally, 785 00:32:12,464 --> 00:32:14,380 the reasonable availability, requirement 786 00:32:14,380 --> 00:32:16,201 has been criticized for taking a view 787 00:32:16,601 --> 00:32:19,604 of the benefits that count that's too narrow 788 00:32:20,806 --> 00:32:22,879 according to the amount of exploitation 789 00:32:22,879 --> 00:32:23,942 we're working with. 790 00:32:23,942 --> 00:32:26,444 Whether or not someone is exploited 791 00:32:26,444 --> 00:32:28,748 by a transaction depends on the amount 792 00:32:28,748 --> 00:32:30,081 to which she benefits 793 00:32:30,081 --> 00:32:31,983 relative to her contribution, benefits 794 00:32:31,983 --> 00:32:33,084 to others, and so on. 795 00:32:34,052 --> 00:32:35,253 Nothing in the account 796 00:32:35,253 --> 00:32:38,256 relies on the benefits to her being of a particular type, 797 00:32:39,191 --> 00:32:41,827 and insisting that the benefits be in the form of providing 798 00:32:41,827 --> 00:32:43,328 experimental interventions. 799 00:32:43,328 --> 00:32:45,564 That leads to the problems with research that doesn't, 800 00:32:46,565 --> 00:32:49,568 produce a product. 801 00:32:49,801 --> 00:32:51,937 Now, some of these objections have been addressed 802 00:32:51,937 --> 00:32:55,184 in the most recent revisions to the CMS guidelines, which 803 00:32:55,184 --> 00:32:55,640 clarify 804 00:32:56,041 --> 00:32:59,044 the reasonable availability requirement, say 805 00:32:59,277 --> 00:33:01,314 as part of their obligation, sponsors 806 00:33:01,314 --> 00:33:03,515 researchers must also make every effort 807 00:33:03,915 --> 00:33:06,918 in cooperation with government and other relevant stakeholders 808 00:33:07,252 --> 00:33:08,770 to make available as soon as possible, 809 00:33:08,770 --> 00:33:10,288 any intervention or product developed 810 00:33:10,622 --> 00:33:12,588 and knowledge generated for the population 811 00:33:12,588 --> 00:33:14,226 or community in which the research 812 00:33:14,226 --> 00:33:16,671 is carried out, and to assist in building 813 00:33:16,671 --> 00:33:18,163 local research capacity. 814 00:33:19,531 --> 00:33:22,500 But this clearly doesn't deal with the objection 815 00:33:22,500 --> 00:33:26,137 that what matters is the amount, not the type of benefits 816 00:33:27,772 --> 00:33:28,573 on this. 817 00:33:28,573 --> 00:33:30,375 There is a debate. 818 00:33:30,375 --> 00:33:32,114 Some ethicists think we should allow 819 00:33:32,114 --> 00:33:33,612 a much wider range of benefits 820 00:33:33,612 --> 00:33:35,113 to host communities to account. 821 00:33:35,113 --> 00:33:37,804 So, for example, they think exploitation 822 00:33:37,804 --> 00:33:39,217 could be avoided by, 823 00:33:40,785 --> 00:33:43,421 supporting a clinic to provide additional health 824 00:33:43,421 --> 00:33:45,959 care to community members or improving the supply of 825 00:33:45,959 --> 00:33:46,691 potable water. 826 00:33:47,959 --> 00:33:50,262 Others think once we loosen 827 00:33:50,262 --> 00:33:53,265 requirements on, what benefits count, 828 00:33:53,531 --> 00:33:56,534 there's a risk of communities getting a raw deal. 829 00:33:57,168 --> 00:33:58,946 But there are big power disparities 830 00:33:58,946 --> 00:34:00,572 between the high income country 831 00:34:00,572 --> 00:34:03,890 institutions and companies that, fund international 832 00:34:03,890 --> 00:34:04,476 research 833 00:34:04,876 --> 00:34:06,517 and the host communities in low and middle 834 00:34:06,517 --> 00:34:08,079 income countries where they take place. 835 00:34:09,114 --> 00:34:11,883 If we don't have a standard for what's fair, 836 00:34:11,883 --> 00:34:13,636 and if research sponsors are allowed 837 00:34:13,636 --> 00:34:15,487 to, shop around different communities 838 00:34:15,487 --> 00:34:18,019 for a good deal, then we risk a race to the 839 00:34:18,019 --> 00:34:18,490 bottom. 840 00:34:18,857 --> 00:34:21,366 We risk that is the powerful sponsors of 841 00:34:21,366 --> 00:34:21,993 research, 842 00:34:22,227 --> 00:34:24,647 bargaining down the benefits that they provide to host 843 00:34:24,647 --> 00:34:25,230 communities. 844 00:34:26,231 --> 00:34:28,459 Now, there are also middle positions 845 00:34:28,459 --> 00:34:29,634 between these two. 846 00:34:30,502 --> 00:34:32,863 Recall that the reasonable availability 847 00:34:32,863 --> 00:34:34,739 requirement was originally one 848 00:34:34,739 --> 00:34:37,580 half of a two part requirement, but that research should be 849 00:34:37,580 --> 00:34:38,109 responsive 850 00:34:38,843 --> 00:34:42,213 to host population needs, that the products of research should 851 00:34:42,213 --> 00:34:42,647 be made 852 00:34:42,881 --> 00:34:43,915 reasonably available. 853 00:34:45,383 --> 00:34:46,818 If you're convinced 854 00:34:46,818 --> 00:34:49,948 by the criticisms of reasonable availability, but you're not 855 00:34:49,948 --> 00:34:50,522 convinced, 856 00:34:50,822 --> 00:34:52,397 we should allow just any benefits 857 00:34:52,397 --> 00:34:53,925 to host communities to account. 858 00:34:54,659 --> 00:34:57,438 Then you might turn to the first of these requirements to help 859 00:34:57,438 --> 00:34:57,662 out, 860 00:34:58,797 --> 00:35:01,800 no matter what else you might say, 861 00:35:02,267 --> 00:35:03,001 no matter what else. 862 00:35:03,001 --> 00:35:05,678 Research should be responsive to the health needs of the 863 00:35:05,678 --> 00:35:06,204 population 864 00:35:06,204 --> 00:35:09,207 in which the research is carried out. 865 00:35:10,275 --> 00:35:12,277 Here's how I like to think about 866 00:35:12,277 --> 00:35:13,278 responsiveness. 867 00:35:13,278 --> 00:35:16,548 I like to think about it in terms of local social value. 868 00:35:18,149 --> 00:35:20,033 So you already have learned about the social value 869 00:35:20,033 --> 00:35:20,485 requirement 870 00:35:20,485 --> 00:35:23,289 for research, according to which the knowledge 871 00:35:23,289 --> 00:35:23,655 that, 872 00:35:23,655 --> 00:35:25,987 a research study is expected to generate 873 00:35:25,987 --> 00:35:28,493 should be sufficiently valuable to justify 874 00:35:28,493 --> 00:35:31,313 asking the participants to take on the risks and burdens of 875 00:35:31,313 --> 00:35:32,030 participation. 876 00:35:33,898 --> 00:35:34,766 The idea here 877 00:35:34,766 --> 00:35:37,454 is that we can also think in terms of the local social 878 00:35:37,454 --> 00:35:37,802 value, 879 00:35:37,802 --> 00:35:40,815 which is the value of, the knowledge that the research 880 00:35:40,815 --> 00:35:41,373 generates 881 00:35:41,573 --> 00:35:44,576 to the community that hosts the research. 882 00:35:45,977 --> 00:35:49,114 If the value of that knowledge, whether it be from 883 00:35:49,114 --> 00:35:51,012 epidemiological research or implementation 884 00:35:51,012 --> 00:35:52,684 research or developing new products, 885 00:35:53,251 --> 00:35:55,920 the value of that knowledge is sufficiently great. 886 00:35:55,920 --> 00:35:58,590 The research won't be exploitative. 887 00:35:58,590 --> 00:36:01,359 So I think it may be easier to work out 888 00:36:01,359 --> 00:36:05,363 whether research has sufficient local social value than whether 889 00:36:05,663 --> 00:36:09,467 a particular amount of benefits offered to a community is fair. 890 00:36:10,368 --> 00:36:12,198 If that's right, that's a reason to think 891 00:36:12,198 --> 00:36:14,072 that we should care about responsiveness. 892 00:36:15,607 --> 00:36:18,043 On the other hand, if we think that in principle 893 00:36:18,043 --> 00:36:20,311 any type of benefit should count, 894 00:36:20,311 --> 00:36:21,585 but deciding whether the benefits 895 00:36:21,585 --> 00:36:22,781 to a community are sufficient, 896 00:36:23,848 --> 00:36:24,182 that's a 897 00:36:24,182 --> 00:36:27,152 reason to be more liberal about what benefits count, 898 00:36:27,419 --> 00:36:30,221 and then to try to put in place protections to, 899 00:36:30,221 --> 00:36:33,224 make sure that it doesn't lead to exploitation in practice. 900 00:36:34,592 --> 00:36:36,000 Now, there's much more to be said 901 00:36:36,000 --> 00:36:37,195 about this discussion, but, 902 00:36:37,195 --> 00:36:39,436 I should wrap up to take home points 903 00:36:39,436 --> 00:36:41,366 about reasonable availability. 904 00:36:42,600 --> 00:36:46,404 First, it's hard to justify requiring that researchers or 905 00:36:46,404 --> 00:36:47,005 sponsors 906 00:36:47,005 --> 00:36:49,442 ensure that study products that are shown 907 00:36:49,442 --> 00:36:50,809 effective must be made 908 00:36:50,809 --> 00:36:52,778 reasonably available to the communities 909 00:36:52,778 --> 00:36:54,546 or populations that host research. 910 00:36:55,146 --> 00:36:59,190 Secondly, I think it's hard to justify research that's not 911 00:36:59,190 --> 00:36:59,818 relevant 912 00:37:00,485 --> 00:37:02,192 to the health of host communities 913 00:37:02,192 --> 00:37:04,055 in low and middle income countries. 914 00:37:04,956 --> 00:37:07,219 In practice, asking the question, 915 00:37:07,219 --> 00:37:08,660 what's the relevance 916 00:37:08,660 --> 00:37:10,231 of this research to the population 917 00:37:10,231 --> 00:37:11,663 in which it's been carried out 918 00:37:11,863 --> 00:37:15,900 turns out to be a good way to avoid exploitative research, 919 00:37:16,301 --> 00:37:19,237 and a good way to identify ways in which a research project 920 00:37:19,237 --> 00:37:22,700 should be changed in order to give it more local social 921 00:37:22,700 --> 00:37:23,141 value. 922 00:37:26,878 --> 00:37:27,612 Okay, we're turning now 923 00:37:27,612 --> 00:37:30,615 to the second case, with which I started this talk. 924 00:37:31,382 --> 00:37:33,940 Most people in Maracaibo don't know about the 925 00:37:33,940 --> 00:37:35,019 Huntington's test. 926 00:37:35,453 --> 00:37:38,456 As far as I know, none of them have access to it. 927 00:37:38,957 --> 00:37:43,140 At the, time, a radio program that reported on 928 00:37:43,140 --> 00:37:43,595 this 929 00:37:43,595 --> 00:37:46,765 said that the test was available privately in Caracas at, 930 00:37:47,732 --> 00:37:50,135 a cost of about $1,000. 931 00:37:50,135 --> 00:37:53,138 I don't know whether that's still the case, 932 00:37:53,471 --> 00:37:55,140 that the original goal of the research, 933 00:37:55,140 --> 00:37:57,295 which was finding a cure for Huntington's 934 00:37:57,295 --> 00:37:58,977 disease, has not been achieved. 935 00:37:58,977 --> 00:38:03,047 So the host community doesn't have a new treatment, 936 00:38:03,047 --> 00:38:05,657 and it doesn't have the test that was developed for the 937 00:38:05,657 --> 00:38:06,084 research 938 00:38:06,084 --> 00:38:09,087 with members of the community. 939 00:38:09,287 --> 00:38:11,389 On the other hand, the researcher who led 940 00:38:11,389 --> 00:38:13,264 the project in Maracaibo has raised 941 00:38:13,264 --> 00:38:15,460 a large amount of money about $6 million 942 00:38:15,760 --> 00:38:18,048 to support the Huntington's disease 943 00:38:18,048 --> 00:38:18,963 clinic there. 944 00:38:19,364 --> 00:38:21,157 So one might think that this benefit 945 00:38:21,157 --> 00:38:23,001 to members of the community is large 946 00:38:23,001 --> 00:38:24,536 enough that we should not say 947 00:38:25,737 --> 00:38:27,071 that doing the research there 948 00:38:27,071 --> 00:38:30,074 was exploitative. 949 00:38:32,810 --> 00:38:33,077 Okay. 950 00:38:33,077 --> 00:38:35,580 To conclude, 951 00:38:35,580 --> 00:38:38,360 there's widespread agreement that both participants in 952 00:38:38,360 --> 00:38:39,184 clinical trials 953 00:38:39,184 --> 00:38:40,552 and the communities 954 00:38:40,552 --> 00:38:42,584 that host research studies should benefit 955 00:38:42,584 --> 00:38:44,022 from research participation. 956 00:38:44,822 --> 00:38:47,197 And I've talked about some of the ways 957 00:38:47,197 --> 00:38:47,759 in which 958 00:38:47,759 --> 00:38:50,929 people think they should benefit and why 959 00:38:50,929 --> 00:38:54,098 there's disagreement about the type of benefit 960 00:38:54,098 --> 00:38:56,768 that's got to be provided and the extent of that benefit. 961 00:38:56,768 --> 00:38:59,109 So, for example, how long a sponsor should 962 00:38:59,109 --> 00:39:01,339 pay for X participants to receive care? 963 00:39:02,106 --> 00:39:04,997 There's also disagreement about who has the duty to provide the 964 00:39:04,997 --> 00:39:05,410 benefit, 965 00:39:05,944 --> 00:39:07,469 whether it's governments, whether it's 966 00:39:07,469 --> 00:39:08,913 the researchers and their sponsors. 967 00:39:13,685 --> 00:39:15,453 Finally, 968 00:39:15,453 --> 00:39:18,723 I want to sound a cautionary note 969 00:39:18,723 --> 00:39:21,540 about the ethical issues that we've been discussing this 970 00:39:21,540 --> 00:39:21,993 morning. 971 00:39:22,794 --> 00:39:25,541 I think conducting research in environments where many 972 00:39:25,541 --> 00:39:25,897 people 973 00:39:25,897 --> 00:39:28,700 lack access to affordable, quality care is ethically 974 00:39:28,700 --> 00:39:29,400 challenging. 975 00:39:30,368 --> 00:39:31,803 I don't think 976 00:39:31,803 --> 00:39:34,772 that should put us off doing it. 977 00:39:35,073 --> 00:39:38,076 As the examples that, Robert described showed, 978 00:39:38,276 --> 00:39:40,278 conducting this research is also vitally 979 00:39:40,278 --> 00:39:40,778 important 980 00:39:40,778 --> 00:39:42,334 for improving the health of people 981 00:39:42,334 --> 00:39:43,982 in low and middle income countries. 982 00:39:43,982 --> 00:39:45,984 So the ethical challenges are challenges 983 00:39:45,984 --> 00:39:46,985 that should be met, 984 00:39:47,585 --> 00:39:50,588 not challenges that should be avoided. 985 00:39:51,756 --> 00:39:52,156 Thank you.