Revising the Declaration of HelsinkiBMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2837 (Published 08 May 2013) Cite this as: BMJ 2013;346:f2837
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As pointed in the BMJ Editorial, the public consultation of the World Medical Association provided researchers with a unique opportunity to influence research governance, based on real-life experience. As a group of clinical ad social sciences researchers active in North-South collaborative research, we would like to draw the attention to the concept of “vulnerability” in medical research, on how it is currently defined in the Declaration, and on how it could be refined.
“Vulnerability” is explicitly addressed in the Article 19 and Article 20 of the Draft Version for Public Consultation of the Declaration. In the Article 19, it is described as being unable to give or refuse consent, or as being at risk of coercion or undue influence, and is defined in terms of age, mental capacity or autonomy. For instance, young children and the mentally incapacitated are not in the position to consent for themselves; and prisoners and other persons living in highly hierarchized environments are potentially subject to some form of coercion or undue influence. Thus, these categories of people should always be considered as [potentially] vulnerable in the context of medical research: they have “an increased likelihood of incurring additional and greater harm”, and they need “specifically considered protection”. The concepts of coercion or undue influence, and of inability to consent, are retaken in the Articles 27 and 28, which require appropriate measures for consent if “the potential subject is in a dependent relationship with the physician or may consent under duress”, and if the potential research subject is incompetent.
But nowadays, we face situations where identifying vulnerable individuals or communities in medical research is less straightforward than Article 19 seems to portray. In fact, the substantial increase in the number of commercial and non-commercial clinical studies conducted in limited-resources settings has brought new opportunities as well as new challenges (1). In particular, research participants are more and more frequently recruited from [severely] socio-economically disadvantaged populations, whose status could be described in terms of poverty (i.e. the lack of physical necessities, assets and income) (2) and/or social exclusion. Social exclusion consists of dynamic, multi-dimensional processes driven by unequal power relationships interacting across an economic, political, social and cultural dimension and operating at different levels, including individual, household, group, community, country and global levels. It results in a continuum of inclusion/exclusion characterized by unequal access to resources, capabilities and rights, which leads to health inequalities (3). Patients recruited in these settings may have diminished autonomy and be vulnerable to exploitation (4) due to more subtle reasons than those traditionally considered (5), something which may directly impair their freedom to consent and expose them to exploitation. The lack of/limited access to quality health care, for example, may push these populations towards participation in research, simply because it is a way to get free access to quality health care. Noteworthy, the proposed Article 20 of the Declaration refers to “disadvantaged or vulnerable population or community”, but does not give defining criteria for them.
We acknowledge the WMA workgroup’s statement that specific vulnerable groups should not be mentioned explicitly in the Declaration and that a general regulation on vulnerability is more appropriate, to avoid misinterpretation. Nonetheless, in order to avoid such misinterpretation and ambiguity when defining vulnerable study populations, we propose that the general regulation should include at least a clear definition/defining criteria of the categories of people that constitute vulnerable groups (i.e. age, autonomy, poverty). In fact, the causes and features of vulnerability may vary, and the ways and tools to ensure protection of different vulnerable persons/communities will vary accordingly (i.e. assuring ethical research conduct for socially excluded/stigmatized persons will require different protective measures then for those who are poor but fully participating members of society). In light of the above, we suggest that both poverty and social exclusion are explicitly acknowledged in the Declaration of Helsinki as criteria to define vulnerable groups.
Noteworthy, vulnerability due to poverty and/or social exclusion should never in itself lead to exclusion from medical research, as research in socio-economically vulnerable populations is most often badly needed to address the specific health problems of these communities. Excluding them from pertinent medical research would result in a breach of the ethical principles of fairness and justice. And fortunately, in recent years there has been an increase in medical research on e.g. neglected tropical diseases addressing health needs of the most neglected patients (6,7). These additional criteria in the Declaration should be seen as a reason for taking special care to avoid both exploitation and neglect. We hope that this would contribute to achieve the best protection of research subjects and their communities, irrespectively of their socio-economic status, and in a timeless manner.
1. Halidou Tinto, Ramadhani A. Noor, Charles L. Wanga, Innocent Valea, Maimouna Ndour Mbaye, Umberto D'Alessandro, and Raffaella M. Ravinetto. Good Clinical Practice in Resource-Limited Settings: Translating Theory into Practice. Am J Trop Med Hyg 2013;88 608-613
2. Chambers R. Poverty and livelihoods: whose reality counts? Environ Urban 1995; 7:173-204. SAGE Publications. Available online at http://eau.sagepub.com/content/7/1/173
3. Popay J, Escorel S, Hernández M, Johnston H, Mathieson J, Rispel L. Understanding and tackling social exclusion. Final report to the WHO Commission on Social Determinants of Health. From the Social Exclusion Knowledge Network WHO, 2008. Available at: www.who.int/social_determinants/knowledge_networks/final_reports/sekn_fi...
4. Editorial: Strengthening clinical research in India. The Lancet 2007; 369 (9569): 1233
5. Kipnis K. Vulnerability in research subjects: a bioethical taxonomy. In: National Bioethics Advisory Commission. Ethical and policy issues in research involving human participants. Vol. II. Washington, DC: US Government Printing Office, 2001.
6. Boelaert M, Meheus F, Robays J, Lutumba P. Socio-economic aspects of neglected diseases: sleeping sickness and visceral leishmaniasis. Ann Trop Med Parasitol. 2010 Oct;104(7):535-42. doi: 10.1179/136485910X12786389891641. Review. PubMed PMID: 21092391.
7. Picado A, Rijal S, Sundar S, Boelaert M. Visceral leishmaniasis treatment in the Indian subcontinent: how to reach the most vulnerable. Expert Rev Anti Infect Ther. 2012 Aug;10(8):839-41. doi: 10.1586/eri.12.71. PubMed PMID: 23030320.
Competing interests: No competing interests
I would have some concerns about the introduction of 'exceptional' in 'There may be exceptional situations where consent would be impossible or impracticable to obtain for such research ...'.
For large data collections or re-use of older data this will frequently be the case, so 'exceptional' is the wrong term to use.
There is the check that such studies should be subject to REC review, though I note that current UK NRES guidance would suggest not (at least where de-identified data is used). From personal experience, REC review on data re-use can be highly variable depending on the experience of the REC members with data protection issues.
Frankly, this paragraph seems to be an area where the Helsinki Agreement is moving into data protection rather than ethical research behaviour; fundamental human rights rather than prevention of inappropriate 'research'.
Clearly, research participants should know that their data is being collected (so odd that this is now dropped), retained, and will be re-used for research purposes when they agree to participate. There is already the protection of privacy and confidentiality in para. 24 (previously para 23) to limit or eliminate potential harm.
There seems little reason to shackle 'research' more than other areas of data re-use (of which there is far too little in healthcare in comparison with other industries), which is why aspects of general data protection should be left to data protection law - 'render unto Caesar the things that are Caesar's'
Competing interests: No competing interests
Surely we need to be more nuanced about the term 'vulnerable' - all of us may be 'vulnerable' to different things at different points in time. Poor pregnant women and sex-workers may be vulnerable in terms of their health or exploitation by others, but in no way compromised in their ability to choose whether to be in a research project or not, provided it is properly explained and there are no other coercive factors in play.
It would be patronising indeed to consider that their vulnerability in one area made them vulnerable in all aspects and removed their right to choose for themselves.
'Vulnerability' is a rather over-exploited term and is itself vulnerable to misuse.
Competing interests: No competing interests
As this editorial has aptly summarised, "research on vulnerable people should be carried out only if the same answers cannot be obtained another way".
Indeed, vulnerable populations need protection from harm and exploitation and at first sight, this new requirement might sound like a good idea. For instance, who would want to argue that a refugee in a war-torn country or a terminally ill infant should be enrolled in a clinical trial that can be undertaken on non-vulnerable participants?
One would assume that a ban on such research would provide added protection to the already disadvantaged. However, such a ban would also create new injustices at least for those vulnerable populations that are able to consent as the following two examples show.
The case of direct health benefits
Poor, pregnant women with HIV in Africa are probably one of the best examples of a vulnerable population in need of protection. Yet, in the complex ethical debates about the HIV transmission prevention studies, nobody demanded that these women should be stopped from taking part in the studies because they had not yet been conducted on a non-vulnerable population. However, this is what the draft revision of the Declaration of Helsinki would require.
Even research with a very high likelihood of immediate direct health benefit could not be conducted on a vulnerable population unless it had already been carried out on a non-vulnerable population. This would disadvantage vulnerable populations twice. First they are disadvantaged already due to the source of their vulnerability, and second they would now be blocked from accessing a research study with immediate health benefits. This would be unjust for those vulnerable populations who are able to consent as the women in the HIV transmission prevention studies.
The case of minimal risk and minimal burden research
Some types of research carry minimal risk and minimal burden, for instance, genetic studies with reliable procedures for data protection. Another example of a highly vulnerable population would be sex workers working in a slum with no access to health care. What would happen, if the new draft of the Declaration of Helsinki were accepted with regard to minimal risk and minimal burden research on vulnerable populations?
In collaboration between the University of Nairobi and the University of Manitoba, a clinic in the Majengo slums of Nairobi has been conducting genetic and epidemiological studies on sexually transmitted diseases for several decades. Access to the clinic is restricted to sex workers who – in return for sample donation – receive comprehensive and long-term health care, including anti-retrovirals [1, 2]. Women interviewed at the clinic all expressed their appreciation for the clinic, the services and the personnel. ("Whatever kind of sickness I get, I am treated. So this clinic has a lot of benefits") .
Research on sexually transmitted diseases does not have to be undertaken in the slums of Nairobi, it could be undertaken on non-vulnerable populations. And it would have to be if the latest draft revision of the Declaration of Helsinki were implemented. Yet, it would be highly patronizing to tell the clinic's research participants that their individual informed consent will now be overruled - for their own protection - by a ban on the kind of studies they are enrolled in. The research is minimally burdensome and minimally risky, yet carries considerable indirect health benefits for the participants.
Looking at these two examples, one has to conclude that the new requirement added to the Declaration of Helsinki could be unfair in the case of research with direct health benefits and patronizing in the case of research, which carries minimal risk and minimal burden. In both cases, those participants who are able to give informed consent should continue to be given the opportunity to decide for themselves.
(1) Lavery JV, Bandewar SVS, Kimani J, Upshur REG, Plummer FA, Singer PA. Relief of oppression: An organizing principle for researchers’ obligations to participants in observational studies in the developing world. BMC Public Health, 2010, 10(384). http://www.biomedcentral.com/1471-2458/10/384.
(2) Schroeder D, Gefenas E, Chennells R, Fournier V, Feinholz D, Sirugo G. Realizing Benefit Sharing: Is there a Role forEthics Review? In: Schroeder D, Lucas CJ (eds) Benefit Sharing – From Biodiversity to Human Genetics, 179-201, 2013; Springer, Dordrecht.
Competing interests: No competing interests