Ethical riddles in HIV research Boghuma Kabisen Titanji

I’d like to share with you the story of

one of my patients called Selene Selene

is a housewife and leaves in a rural

district of Cameroon in West Central

Africa six years ago at the time of her

HIV diagnosis she was recruited to

participate in the clinical trial which

was running in her health district at

the time when I first met Celine a

little over a year ago she had gone for

18 months without any antiretroviral

therapy and she was very ill she told me

that she stopped coming to the clinic

when the trial ended because she had no

money for the bus fare and was too ill

to walk the 35 kilometers now during the

clinical trial she’d been given all her

antiretroviral drugs free of charge and

her transportation cost had been covered

by the research funds all of these ended

once the trial was completed leading

Celine with no alternatives she was

unable to tell me the names of the drugs

should receive during the trial or even

what the trial had been about I didn’t

bother to ask her what the results of

the trial we’re because it seemed

obvious to me that she would have no

clue yet what puzzled me most was Celine

had given her informed consent to be a

part of this trial yet she clearly did

not understand the implications of being

a participant or what would happen to

her once the trial had been completed

now I have shared this story with you as

an example of what can happen to

participants in the clinical trial when

it is poorly conducted maybe this

particular trial yielded exciting

results maybe it even got published in a

high-profile scientific journal maybe it

would inform clinicians around the world

on how to improve on the HIV of the on

the clinical management of HIV patients

but it would have done

so at a price to hundreds of patients

who like Celine were left to their own

devices once the research had been

completed I do not stand here today to

suggest in any way that conducting HIV

clinical trials in developing countries

is bad on the contrary clinical trials

are extremely useful tools and a much

needed to address the burden of disease

in developing countries however the

inequalities that exists between richer

countries and developing countries in

terms of funding pose a real risk for

exploitation especially in a context of

externally funded research sadly enough

the fact remains that a lot of the

studies that are conducted in developing

countries could never be authorized in

the richer countries which fund the

research I am sure you must be asking

yourselves what makes developing

countries especially those in

sub-saharan Africa so attractive for

these HIV clinical trials well in order

for a clinical trial to generate valid

and widely applicable results they need

to be conducted with large numbers of

study participants and preferably on a

population with a high incidence of new

HIV infections sub-saharan Africa

largely fits this description with 22

million people living with HIV an

estimated 70% of the 30 million people

who are infected worldwide also research

within the continent is a lot easier to

conduct due to widespread poverty

endemic diseases and inadequate health

care systems a clinical trial that is

considered to be potentially beneficial

to the population is more likely to be

authorized and in the absence of good

health care systems almost any offer of

medical assistance is accepted as better

than nothing even more problematic

reasons include lower risk of litigation

less rigorous ethical reviews and

populations that are willing to

participate in almost any study that

hints at a cure

as funding for HIV research increases in

developing countries an ethical review

in richer countries become more strict

you can see why this context becomes

very very attractive the high prevalence

of HIV drives researchers to conduct

research that is sometimes

scientifically acceptable but on many

levels ethically questionable how then

can we ensure that in our search for the

Cure we do not take an unfair advantage

of those who are already most affected

by the pandemic I invite you to consider

four areas I think we can focus on in

order to improve the way in which things

are done the first phase is informed

consent now in order for a clinical

trial to be ethically considered

ethically acceptable participants must

be given the relevant information in a

way in which they can understand and

must freely consent to participate in

the trial this is especially important

in developing countries well a lot of

participants consent to research because

they believe it is the only way in which

they can receive medical care or other

benefits consent procedures that are

used in richer countries are often

inappropriate or ineffective in a lot of

developing countries for example it is

counterintuitive to have an illiterate

study participant like Celine sign a

lengthy consent form that they unable to

read let alone understand local

communities need to be more involved in

establishing the criteria for recruiting

participants in clinical trials as well

as the incentives for participation the

information on these trials need to be

given to the potential participants in

linguistically and culturally acceptable

formats the second point I would like

for you to consider is the standard of

care that is provided to participants

within any clinical trial now this is

subject to a lot of debate and

controversy should the control group in

the clinical trial be given the best

current treatment which is available

anywhere in the world or should they be

given an altar

relative standard of care such as the

best current treatment available in the

country in which the research is being

conducted is it fair to evaluate a

treatment regimen which may not be

affordable or accessible to the study

participants once the research has been

completed now in a situation where the

best current treatment is inexpensive

and simple to deliver the answer is

straightforward however the best current

treatment available anywhere in the

world is often very difficult to provide

in developing countries it is important

to assess the potential risk and

benefits of the standard of care which

is to be provided to participants in any

clinical trial and establish one which

is relevant for the study but for the

context of the study and most beneficial

for the participants within the study

that brings us to the third point I

wanted to think about the ethical review

of research an effective system for

reviewing the ethical suitability of

clinical trials is primordial to

safeguard participants within any

clinical trial unfortunately this is

often lacking or inefficient in a lot of

developing countries local governments

need to to set up effective systems for

reviewing the ethical issues around the

clinical trials which are authorized in

different developing countries and they

need to do this by setting up ethical

review committees that are independent

of the government and research sponsors

public accountability needs to be

promoted through transparency an

independent review by non-governmental

and international organizations as

appropriate the final point I’d like for

you to consider tonight is what happens

to participants in the clinical trial

once the research has been completed I

think it is absolutely wrong for

research to begin in the first place

without a clear plan for what would

happen to the participants once the

trial has ended now researchers need to

make every effort to ensure that an

intervention that has been shown to be

beneficial

during a clinical trial is as accessible

to the participant of the child once the

trial has been completed in addition

they should be able to consider the

possibility of introducing and

maintaining effective treatments in the

wider community once the trial ends if

for any reason they feel that this might

not be possible then I think they should

have to ethically justify why the

clinical trial should be conducted in

the first place

now fortunately for Saline our meeting

did not end in my office I was able to

get her enrolled into a free HIV

treatment program closer to her home and

with a support group to help her cope

her story has a positive ending but

there are thousands of others in similar

situations who are much less fortunate

although she may not know this my

encounter with saline has completely

changed the way in which I view HIV

clinical trials in developing countries

and made me even more determined to be

part of the movement to change the way

in which things are done I believe that

every single person listening to me

tonight can be part of that change if

your researcher I hold you to a higher

standard of moral conscience to remain

ethical in your research and not

compromise human welfare in your search

for answers if you work for a funding

agency or from a suitable company I

challenge you to hold your employer’s to

fund research that is ethically sound if

you come from a developing country like

myself I urge you to hold your

government to a more thorough review of

the clinical trials which are authorized

in your country yes the reason need for

us to find a cure for HIV to find an

effective vaccine for malaria to find a

diagnostic tool that works for TB but I

believe that we owe it to those who

willingly and selflessly consent to

participate in these clinical trials to

do this in a humane way thank you

you

我想与大家分享

我的一位名叫 Selene 的患者的故事,Selene

是一名家庭主妇,

六年前在她被诊断出艾滋病毒时,她离开了中非西部喀麦隆的一个农村地区,

她被招募

参加了 一年多前我第一次见到席琳

时,她的健康区正在进行临床试验,

她已经

18 个月没有接受任何抗逆转录病毒

治疗,她病得很重,她告诉我

当 试验结束,因为她没有

钱支付巴士车费,

现在临床试验期间她病得不能步行 35 公里,

她所有的

抗逆转录病毒药物都被免费提供,

她的交通费用已

全部由研究基金支付。

一旦试验完成,这些就结束了,导致

席琳别无选择,她

无法告诉我在试验期间应该接受的药物名称,甚至无法告诉

我试验的内容我不

知道 然后问她我们的试验结果是什么,

因为

对我来说很明显她不

知道但最让我困惑的是席琳

已经同意她

参与这项试验,但她显然

不明白 成为参与者的意义

一旦试验完成后她会发生什么

现在我已经与您分享了这个故事,作为

临床试验参与者可能发生的事情的一个例子,如果

它进行得不好,也许这个

特定的试验会产生令人兴奋的结果

结果也许它甚至发表在了一个

备受瞩目的科学期刊上也许它

会告诉世界各地的临床医生

如何改善

艾滋病毒患者的临床管理,

但它会

为此付出数百名患者的代价

像 Celine 一样的人

在研究

完成后就只能

自生自灭了

相反,临床试验

是非常有用的工具,是

解决

发展中国家

疾病负担的急需工具

外部资助的研究 可悲

的是,

在发展中国家进行的许多研究

永远无法在

资助研究的较

富裕国家获得

授权 撒哈拉非洲对

这些 HIV 临床试验非常有吸引力,

以便临床试验产生有效

和广泛适用的结果,它们需要

与大量

研究参与者一起进行,最好是在撒哈拉以南

地区新 HIV 感染高发人群中进行

非洲

有 2200 万人生活在很大程度上符合这一描述

在全球 3000 万感染者中,估计有 70% 的艾滋病毒

由于普遍存在的贫困

地方病和不完善的医疗

保健系统,在非洲大陆进行的研究更容易进行一项被

认为可能

对人群有益的临床试验 更有可能获得

授权,并且在没有良好的医疗保健系统的情况下,

几乎任何提供的

医疗援助都被接受

总比没有好 甚至更多问题的

原因包括诉讼风险较低

不太严格的伦理审查以及

愿意

参与几乎任何

随着发展中国家对艾滋病毒研究的资助增加,研究暗示了一种治愈方法

富裕国家的伦理审查变得更加严格

你可以看到为什么这种情况变得

非常有吸引力 艾滋病毒的高流行

促使

研究人员进行有时在

科学上可以接受的研究,但 在许多

层面上都存在道德问题

我们能否确保在寻求

治疗的过程中,我们不会不公平地

利用那些已经受疫情影响最严重

的人?我邀请您考虑

我认为我们可以关注的四个领域,

以改善事情的发展

方式 第一阶段

现在是知情同意,为了使临床

试验在伦理上被认为是

伦理上可接受的,参与者必须

以他们可以理解的方式获得相关信息,

并且

必须自由同意

参与试验,这

对于开发 很多

参与者同意研究,因为

他们认为这是

他们获得医疗保健或其他

福利的唯一方式。

在富裕国家使用的同意程序在许多发展中国家通常是

不合适或无效的,

例如它是

让像 Celine 这样不识字的

研究参与者签署一份

冗长的同意书,他们无法阅读,这违反直觉

仅了解当地

社区需要更多地参与

制定招募

临床试验参与者的标准

以及参与的激励措施

这些试验的信息需要以

语言和文化上可接受的

格式提供给潜在的参与者 第二点 我会

让您考虑的是

在任何临床试验中向参与者提供的护理标准,如果临床试验

中的对照组

得到

目前任何地方可用的最佳治疗,这会引起很多争论和争议

。 或者是否应该

给他们一个祭坛

相关的护理标准,例如进行研究

的国家目前可用的最佳

治疗方法,评估研究参与者可能无法负担或无法获得的治疗方案是否公平?

研究已经

完成,目前

最好的 t 治疗费用低廉

且易于提供 答案很

简单,但是目前世界上

任何地方可用的最佳治疗

通常很难在发展中国家提供

评估将提供的护理标准的潜在风险和益处很重要

给任何

临床试验的参与者,并建立一个

与研究相关但与研究

背景相关且对研究中的参与者最有利

的第三点,我

想考虑

对研究进行伦理审查是一种有效的方法

审查临床试验的伦理适用性的系统对于

在任何

临床试验中保护参与者来说是最重要的,不幸的是,这

在许多发展中国家往往缺乏或效率低下,

地方政府

需要建立有效的系统来

审查围绕临床试验的伦理问题,

这 在

不同的发展中国家获得授权,并且 他们

需要通过建立

独立

于政府和研究赞助商的伦理审查委员会来做到这一点

需要通过透明度促进公共问责制

由非政府

组织和国际组织

酌情进行独立审查 最后一点我想

请你 考虑今晚是研究完成

后临床试验参与者会发生什么

认为

首先开始研究

而没有明确计划

一旦

试验结束参与者会发生什么现在研究人员需要

尽一切努力确保在临床试验

中被证明有益的干预措施

在试验完成后对儿童参与者来说是可及的

,此外,

他们应该能够

考虑引入和

保持有效的干预措施的可能性

试验结束后在更广泛的社区进行治疗,如果

出于任何原因 你觉得这可能

是不可能的,那么我认为他们

应该在道德上证明为什么

首先应该

进行临床试验,幸运的是,对于 Saline,我们的会议

没有在我的办公室结束,我能够

让她参加一个免费的

离她家更近的艾滋病毒治疗计划

和一个支持小组帮助她应对

她的故事有一个积极的结局,但

还有成千上万处于类似

情况的人不幸得多,

尽管她可能不知道我

与生理盐水的相遇完全

改变了 我

对发展中国家 HIV 临床试验的看法,

并让我更加坚定地成为

改变做事方式的运动的一部分

研究员我要求你保持更高

的道德良心标准,

在你的研究中保持道德,

如果你为你工作,在寻找答案的过程中不损害人类福祉 如果您来自像我这样的发展中国家,我敦促

您让您的雇主

为符合道德的研究提供资金,

我敦促您让您的

政府对授权的临床试验进行更彻底的审查

在您的国家,是的,

我们需要找到治愈艾滋病毒的方法,找到

有效的疟疾疫苗,找到

对结核病有效的诊断工具,但我

相信我们应该感谢那些

自愿和无私地同意

参与这些临床试验的人 尝试

以人道的方式做到这一点,谢谢