1 00:00:01,577 --> 00:00:03,573 I'd like to share with you 2 00:00:03,573 --> 00:00:07,410 the story of one of my patients called Celine. 3 00:00:07,410 --> 00:00:10,563 Celine is a housewife and lives in a rural district 4 00:00:10,563 --> 00:00:13,635 of Cameroon in west Central Africa. 5 00:00:13,635 --> 00:00:17,322 Six years ago, at the time of her HIV diagnosis, 6 00:00:17,322 --> 00:00:20,323 she was recruited to participate in the clinical trial 7 00:00:20,323 --> 00:00:23,394 which was running in her health district at the time. 8 00:00:23,394 --> 00:00:27,098 When I first met Celine, a little over a year ago, 9 00:00:27,098 --> 00:00:28,782 she had gone for 18 months 10 00:00:28,782 --> 00:00:31,069 without any antiretroviral therapy, 11 00:00:31,069 --> 00:00:33,806 and she was very ill. 12 00:00:33,806 --> 00:00:36,204 She told me that she stopped coming to the clinic 13 00:00:36,204 --> 00:00:37,755 when the trial ended 14 00:00:37,755 --> 00:00:40,466 because she had no money for the bus fare 15 00:00:40,466 --> 00:00:44,194 and was too ill to walk the 35-kilometer distance. 16 00:00:44,194 --> 00:00:45,938 Now during the clinical trial, 17 00:00:45,938 --> 00:00:50,323 she'd been given all her antiretroviral drugs free of charge, 18 00:00:50,323 --> 00:00:52,354 and her transportation costs 19 00:00:52,354 --> 00:00:54,961 had been covered by the research funds. 20 00:00:54,961 --> 00:00:58,315 All of these ended once the trial was completed, 21 00:00:58,315 --> 00:01:01,307 leaving Celine with no alternatives. 22 00:01:01,307 --> 00:01:03,983 She was unable to tell me the names of the drugs 23 00:01:03,983 --> 00:01:06,010 she'd received during the trial, 24 00:01:06,010 --> 00:01:08,767 or even what the trial had been about. 25 00:01:08,767 --> 00:01:12,316 I didn't bother to ask her what the results of the trial were 26 00:01:12,316 --> 00:01:16,723 because it seemed obvious to me that she would have no clue. 27 00:01:16,723 --> 00:01:18,992 Yet what puzzled me most 28 00:01:18,992 --> 00:01:22,099 was Celine had given her informed consent 29 00:01:22,099 --> 00:01:25,931 to be a part of this trial, yet she clearly did not understand 30 00:01:25,931 --> 00:01:28,401 the implications of being a participant 31 00:01:28,401 --> 00:01:32,810 or what would happen to her once the trial had been completed. 32 00:01:32,810 --> 00:01:36,205 Now, I have shared this story with you as an example 33 00:01:36,205 --> 00:01:39,134 of what can happen to participants in the clinical trial 34 00:01:39,134 --> 00:01:41,593 when it is poorly conducted. 35 00:01:41,593 --> 00:01:45,458 Maybe this particular trial yielded exciting results. 36 00:01:45,458 --> 00:01:49,147 Maybe it even got published in a high-profile scientific journal. 37 00:01:49,147 --> 00:01:51,954 Maybe it would inform clinicians around the world 38 00:01:51,954 --> 00:01:57,489 on how to improve on the clinical management of HIV patients. 39 00:01:57,489 --> 00:02:00,275 But it would have done so at a price 40 00:02:00,275 --> 00:02:03,222 to hundreds of patients who, like Celine, 41 00:02:03,222 --> 00:02:05,466 were left to their own devices 42 00:02:05,466 --> 00:02:08,537 once the research had been completed. 43 00:02:08,537 --> 00:02:11,875 I do not stand here today to suggest in any way 44 00:02:11,875 --> 00:02:13,888 that conducting HIV clinical trials 45 00:02:13,888 --> 00:02:16,103 in developing countries is bad. 46 00:02:16,103 --> 00:02:20,470 On the contrary, clinical trials are extremely useful tools, 47 00:02:20,470 --> 00:02:22,768 and are much needed to address the burden 48 00:02:22,768 --> 00:02:25,239 of disease in developing countries. 49 00:02:25,239 --> 00:02:28,098 However, the inequalities that exist between 50 00:02:28,098 --> 00:02:31,800 richer countries and developing countries in terms of funding 51 00:02:31,800 --> 00:02:34,957 pose a real risk for exploitation, 52 00:02:34,957 --> 00:02:38,842 especially in the context of externally-funded research. 53 00:02:38,842 --> 00:02:41,448 Sadly enough, the fact remains that 54 00:02:41,448 --> 00:02:45,432 a lot of the studies that are conducted in developing countries 55 00:02:45,432 --> 00:02:48,008 could never be authorized in the richer countries 56 00:02:48,008 --> 00:02:50,256 which fund the research. 57 00:02:50,256 --> 00:02:52,503 I'm sure you must be asking yourselves 58 00:02:52,503 --> 00:02:54,419 what makes developing countries, 59 00:02:54,419 --> 00:02:56,963 especially those in sub-Saharan Africa, 60 00:02:56,963 --> 00:03:00,530 so attractive for these HIV clinical trials? 61 00:03:00,530 --> 00:03:03,802 Well, in order for a clinical trial to generate 62 00:03:03,802 --> 00:03:06,918 valid and widely applicable results, 63 00:03:06,918 --> 00:03:10,918 they need to be conducted with large numbers of study participants 64 00:03:10,918 --> 00:03:13,561 and preferably on a population 65 00:03:13,561 --> 00:03:17,342 with a high incidence of new HIV infections. 66 00:03:17,342 --> 00:03:20,813 Sub-Saharan Africa largely fits this description, 67 00:03:20,813 --> 00:03:24,015 with 22 million people living with HIV, 68 00:03:24,015 --> 00:03:27,655 an estimated 70 percent of the 30 million people 69 00:03:27,655 --> 00:03:30,136 who are infected worldwide. 70 00:03:30,136 --> 00:03:32,566 Also, research within the continent 71 00:03:32,566 --> 00:03:36,678 is a lot easier to conduct due to widespread poverty, 72 00:03:36,678 --> 00:03:40,529 endemic diseases and inadequate health care systems. 73 00:03:40,529 --> 00:03:43,318 A clinical trial that is considered to be 74 00:03:43,318 --> 00:03:46,068 potentially beneficial to the population 75 00:03:46,068 --> 00:03:48,375 is more likely to be authorized, 76 00:03:48,375 --> 00:03:51,175 and in the absence of good health care systems, 77 00:03:51,175 --> 00:03:54,129 almost any offer of medical assistance 78 00:03:54,129 --> 00:03:57,047 is accepted as better than nothing. 79 00:03:57,047 --> 00:03:59,633 Even more problematic reasons include 80 00:03:59,633 --> 00:04:01,920 lower risk of litigation, 81 00:04:01,920 --> 00:04:04,387 less rigorous ethical reviews, 82 00:04:04,387 --> 00:04:06,943 and populations that are willing to participate 83 00:04:06,943 --> 00:04:11,607 in almost any study that hints at a cure. 84 00:04:11,607 --> 00:04:15,232 As funding for HIV research 85 00:04:15,232 --> 00:04:17,488 increases in developing countries 86 00:04:17,488 --> 00:04:21,495 and ethical review in richer countries become more strict, 87 00:04:21,495 --> 00:04:23,580 you can see why this context becomes 88 00:04:23,580 --> 00:04:26,141 very, very attractive. 89 00:04:26,141 --> 00:04:29,821 The high prevalence of HIV drives researchers 90 00:04:29,821 --> 00:04:34,305 to conduct research that is sometimes scientifically acceptable 91 00:04:34,305 --> 00:04:37,584 but on many levels ethically questionable. 92 00:04:37,584 --> 00:04:41,023 How then can we ensure that, in our search for the cure, 93 00:04:41,023 --> 00:04:43,343 we do not take an unfair advantage 94 00:04:43,343 --> 00:04:46,847 of those who are already most affected by the pandemic? 95 00:04:46,847 --> 00:04:50,703 I invite you to consider four areas I think we can focus on 96 00:04:50,703 --> 00:04:54,278 in order to improve the way in which things are done. 97 00:04:54,278 --> 00:04:57,105 The first of these is informed consent. 98 00:04:57,105 --> 00:04:59,473 Now, in order for a clinical trial to be 99 00:04:59,473 --> 00:05:03,154 considered ethically acceptable, 100 00:05:03,154 --> 00:05:05,978 participants must be given the relevant information 101 00:05:05,978 --> 00:05:08,413 in a way in which they can understand, 102 00:05:08,413 --> 00:05:12,630 and must freely consent to participate in the trial. 103 00:05:12,630 --> 00:05:15,308 This is especially important in developing countries, 104 00:05:15,308 --> 00:05:18,210 where a lot of participants consent to research 105 00:05:18,210 --> 00:05:20,898 because they believe it is the only way in which 106 00:05:20,898 --> 00:05:24,468 they can receive medical care or other benefits. 107 00:05:24,468 --> 00:05:27,435 Consent procedures that are used in richer countries 108 00:05:27,435 --> 00:05:30,237 are often inappropriate or ineffective 109 00:05:30,237 --> 00:05:32,590 in a lot of developing countries. 110 00:05:32,590 --> 00:05:35,563 For example, it is counterintuitive to have 111 00:05:35,563 --> 00:05:38,562 an illiterate study participant, like Celine, 112 00:05:38,562 --> 00:05:41,889 sign a lengthy consent form that they are unable to read, 113 00:05:41,889 --> 00:05:43,996 let alone understand. 114 00:05:43,996 --> 00:05:47,076 Local communities need to be more involved 115 00:05:47,076 --> 00:05:50,349 in establishing the criteria for recruiting participants 116 00:05:50,349 --> 00:05:55,050 in clinical trials, as well as the incentives for participation. 117 00:05:55,050 --> 00:05:56,866 The information in these trials 118 00:05:56,866 --> 00:05:59,817 needs to be given to the potential participants 119 00:05:59,817 --> 00:06:04,245 in linguistically and culturally acceptable formats. 120 00:06:04,245 --> 00:06:07,066 The second point I would like for you to consider 121 00:06:07,066 --> 00:06:09,504 is the standard of care that is provided 122 00:06:09,504 --> 00:06:12,450 to participants within any clinical trial. 123 00:06:12,450 --> 00:06:16,147 Now, this is subject to a lot of debate and controversy. 124 00:06:16,147 --> 00:06:19,128 Should the control group in the clinical trial 125 00:06:19,128 --> 00:06:22,401 be given the best current treatment which is available 126 00:06:22,401 --> 00:06:24,481 anywhere in the world? 127 00:06:24,481 --> 00:06:27,449 Or should they be given an alternative standard of care, 128 00:06:27,449 --> 00:06:30,337 such as the best current treatment available 129 00:06:30,337 --> 00:06:33,649 in the country in which the research is being conducted? 130 00:06:33,649 --> 00:06:36,989 Is it fair to evaluate a treatment regimen 131 00:06:36,989 --> 00:06:40,065 which may not be affordable or accessible 132 00:06:40,065 --> 00:06:44,035 to the study participants once the research has been completed? 133 00:06:44,035 --> 00:06:47,776 Now, in a situation where the best current treatment 134 00:06:47,776 --> 00:06:50,415 is inexpensive and simple to deliver, 135 00:06:50,415 --> 00:06:52,443 the answer is straightforward. 136 00:06:52,443 --> 00:06:55,593 However, the best current treatment available 137 00:06:55,593 --> 00:06:58,480 anywhere in the world is often very difficult 138 00:06:58,480 --> 00:07:01,167 to provide in developing countries. 139 00:07:01,167 --> 00:07:04,719 It is important to assess the potential risks and benefits 140 00:07:04,719 --> 00:07:07,496 of the standard of care which is to be provided 141 00:07:07,496 --> 00:07:09,977 to participants in any clinical trial, 142 00:07:09,977 --> 00:07:15,425 and establish one which is relevant for the context of the study 143 00:07:15,425 --> 00:07:18,922 and most beneficial for the participants within the study. 144 00:07:18,922 --> 00:07:22,173 That brings us to the third point I want you think about: 145 00:07:22,173 --> 00:07:25,024 the ethical review of research. 146 00:07:25,024 --> 00:07:28,823 An effective system for reviewing the ethical suitability 147 00:07:28,823 --> 00:07:32,951 of clinical trials is primordial to safeguard participants 148 00:07:32,951 --> 00:07:35,064 within any clinical trial. 149 00:07:35,064 --> 00:07:37,976 Unfortunately, this is often lacking 150 00:07:37,976 --> 00:07:41,504 or inefficient in a lot of developing countries. 151 00:07:41,504 --> 00:07:45,867 Local governments need to set up effective systems 152 00:07:45,867 --> 00:07:48,744 for reviewing the ethical issues around the clinical trials 153 00:07:48,744 --> 00:07:52,661 which are authorized in different developing countries, 154 00:07:52,661 --> 00:07:54,935 and they need to do this by setting up 155 00:07:54,935 --> 00:07:57,445 ethical review committees that are independent 156 00:07:57,445 --> 00:08:00,830 of the government and research sponsors. 157 00:08:00,830 --> 00:08:03,240 Public accountability needs to be promoted 158 00:08:03,240 --> 00:08:06,473 through transparency and independent review 159 00:08:06,473 --> 00:08:09,512 by nongovernmental and international organizations 160 00:08:09,512 --> 00:08:11,083 as appropriate. 161 00:08:11,083 --> 00:08:14,593 The final point I would like for you to consider tonight 162 00:08:14,593 --> 00:08:17,816 is what happens to participants in the clinical trial 163 00:08:17,816 --> 00:08:20,591 once the research has been completed. 164 00:08:20,591 --> 00:08:24,065 I think it is absolutely wrong for research to begin 165 00:08:24,065 --> 00:08:26,577 in the first place without a clear plan 166 00:08:26,577 --> 00:08:28,656 for what would happen to the participants 167 00:08:28,656 --> 00:08:31,096 once the trial has ended. 168 00:08:31,096 --> 00:08:36,224 Now, researchers need to make every effort to ensure that 169 00:08:36,224 --> 00:08:39,208 an intervention that has been shown to be beneficial 170 00:08:39,208 --> 00:08:40,940 during a clinical trial 171 00:08:40,940 --> 00:08:44,552 is accessible to the participants of the trial 172 00:08:44,552 --> 00:08:47,100 once the trial has been completed. 173 00:08:47,100 --> 00:08:50,624 In addition, they should be able to consider the possibility 174 00:08:50,624 --> 00:08:54,225 of introducing and maintaining effective treatments 175 00:08:54,225 --> 00:08:58,066 in the wider community once the trial ends. 176 00:08:58,066 --> 00:09:01,489 If, for any reason, they feel that this might not be possible, 177 00:09:01,489 --> 00:09:04,456 then I think they should have to ethically justify 178 00:09:04,456 --> 00:09:08,483 why the clinical trial should be conducted in the first place. 179 00:09:08,483 --> 00:09:10,799 Now, fortunately for Celine, 180 00:09:10,799 --> 00:09:13,474 our meeting did not end in my office. 181 00:09:13,474 --> 00:09:17,848 I was able to get her enrolled into a free HIV treatment program 182 00:09:17,848 --> 00:09:19,236 closer to her home, 183 00:09:19,236 --> 00:09:23,010 and with a support group to help her cope. 184 00:09:23,010 --> 00:09:25,344 Her story has a positive ending, 185 00:09:25,344 --> 00:09:29,047 but there are thousands of others in similar situations 186 00:09:29,047 --> 00:09:31,344 who are much less fortunate. 187 00:09:31,344 --> 00:09:33,768 Although she may not know this, 188 00:09:33,768 --> 00:09:37,633 my encounter with Celine has completely changed the way 189 00:09:37,633 --> 00:09:41,904 in which I view HIV clinical trials in developing countries, 190 00:09:41,904 --> 00:09:45,624 and made me even more determined to be part of the movement 191 00:09:45,624 --> 00:09:48,481 to change the way in which things are done. 192 00:09:48,481 --> 00:09:50,849 I believe that every single person 193 00:09:50,849 --> 00:09:55,224 listening to me tonight can be part of that change. 194 00:09:55,224 --> 00:09:57,821 If you are a researcher, I hold you 195 00:09:57,821 --> 00:10:00,391 to a higher standard of moral conscience, 196 00:10:00,391 --> 00:10:02,818 to remain ethical in your research, 197 00:10:02,818 --> 00:10:06,306 and not compromise human welfare in your search for answers. 198 00:10:06,306 --> 00:10:09,984 If you work for a funding agency or pharmaceutical company, 199 00:10:09,984 --> 00:10:13,014 I challenge you to hold your employers 200 00:10:13,014 --> 00:10:16,189 to fund research that is ethically sound. 201 00:10:16,189 --> 00:10:19,375 If you come from a developing country like myself, 202 00:10:19,375 --> 00:10:22,447 I urge you to hold your government 203 00:10:22,447 --> 00:10:25,063 to a more thorough review of the clinical trials 204 00:10:25,063 --> 00:10:27,976 which are authorized in your country. 205 00:10:27,976 --> 00:10:31,644 Yes, there is a need for us to find a cure for HIV, 206 00:10:31,644 --> 00:10:34,296 to find an effective vaccine for malaria, 207 00:10:34,296 --> 00:10:38,138 to find a diagnostic tool that works for T.B., 208 00:10:38,138 --> 00:10:41,713 but I believe that we owe it to those who willingly 209 00:10:41,713 --> 00:10:45,768 and selflessly consent to participate in these clinical trials 210 00:10:45,768 --> 00:10:47,994 to do this in a humane way. 211 00:10:47,994 --> 00:10:50,321 Thank you.