Protections for clinical trials in low and middle income countries need strengthening not weakeningBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4254 (Published 04 July 2014) Cite this as: BMJ 2014;349:g4254
All rapid responses
Today we are confronted with new ethical issues in relation to research at the molecular level and the forms of production of generalizable knowledge. Pharmacogenetics and pharmacogenomics try to determine how genetic differences among individuals modify the response to a drug, as variations of DNA sequences and different variants of gene expression. They require samples and population groups living together for generations and gene sequencers and biobanks. North and South again. Development and underdevelopment.
Many discussions and debates recently published in the indexed literature on research ethics refer to regulatory and legal problems. Scientific research and its ways need to be recognized as social needs. (1)
To communities, research is not a good word, it creates distrust, evokes bad memories, it raises suspicions. This is not a casual social susceptibility. Recent history and current times are plethoric in aberrant cases. It is necessary to regain the respect of the communities for medical research and public health research. (2)
Once upon a time a Global Forum... Universities and UN agencies needs a global forum to interact with researchers and bioethicists from around the world, from the developed to developing world, where freely discuss emerging issues in the ethics of research and find joint solutions. It is necessary to re-create the Global Forum on Bioethics in Research (GFBR), to provide a venue for dialogue between representatives of the four cardinal points, interested in the challenges of investigating and the ethical boundaries. (3)
(1) Riis P. Ethical principles for project collaboration between academic professionals or institutions and the biomedical industry. Clin Epidemiol. 2012;4:95-7.
(2) Garattini S, Chalmers I. Patients and the public deserve big changes in evaluation of drugs. BMJ, 2009; 338:804–806.
(3) Littler K. The Global Forum for Bioethics in Research: Past, present and future. S Afr J BL, 2014;7(1):5-8.
Competing interests: No competing interests
Dal-Ré and collaborators presents an interesting critique to the disappearance of “other appropriate care and benefits” from the text of the Declaration of Helsinki 2013 dealing with post-trial provisions.
I agree with the authors that the reference to “other appropriate care” that has disappeared from the text of the Declaration is regrettable. If one of the core ethical concerns of post-trial provision in the Declaration of Helsinki 2013 is the health needs of participants after research, then it should have included both the beneficial intervention identified in the trial and any other essential healthcare that the participants may need after the study. For instance, in prevention trials of vaccines for HIV/AIDS, participants who get infected during the trial may need and should receive antiretroviral therapy after research and a comprehensive clinical care package (Schucklenk 2001, Macklin 2006). This kind of healthcare is not covered in any plausible interpretation of “intervention identified as beneficial in the trial” (DoH 2013, para. 34). A similar position has also been recently defended by the National Research Ethics Service of the UK in their document on post-trial provision where the authors state that: “care after research includes  the study intervention when supplied or funded by the sponsor or otherwise as well as  standard healthcare that the participant may need after the study” (NRES 2012:2, edited, Sofaer et al. 2014)
However, the disappearance of “other appropriate benefits” is not as problematic. Although Dal-Ré and collaborators give some examples of what could constitute other appropriate benefits, the criteria of what constitutes a “fair benefit” remain unclear. Furthermore, the fairness criteria behind the fair benefits framework have been criticized as “fundamentally wrong” by one of its own proponents (Lie 2010). As noted by Lie, to determine the fairness of research studies is not analogous to determining the fair price of a product or service through negotiation between the parties, as you are supposed to do in a flea market or when bargaining with a plumber. At the very least, the unjust background conditions of the participants and the relevance of the knowledge for the society should also be considered (Lie 2010:3).
I agree with Dal-Ré and collaborators that other basic needs of research participants or host societies should be taken into account besides health needs. Maybe, to avoid further confusion it should be stated that the requirement of post-trial provisions “does not preclude the provision of any additional benefits” either to research participants, their community or host society (Macklin, personal communication 14th June 2014). However, many of the fair benefits we care about are already captured by the provision that clinical trials are “responsive to the health needs or priorities” (DoH 2013, para. 20), such as “training of healthcare staff, or development of research and medical care capacity” (Dal-Ré et al 2014). If there’s something to criticize DoH 2013 is that the responsiveness requirement should be applied not only when doing research with vulnerable groups but in all trials (London 2008, Macklin 2009).
Finally, the assessment of the authors that “Declaration of Helsinki weakens protections for trial participants in low and middle income countries” needs further discussion and qualification. I believe that despite the limitations mention above, DoH 2013 formulation is an improved version of paragraph 30 of the DoH 2008 for the following reasons: (1) the language of the contentious fair benefit framework in which post-trial obligations were presented was removed; (2) the ethical requirement has been reformulated in terms of post-trial access provisions based on the health needs of participants; (3) it explicitly identifies the main agents responsible for post-trial obligations (the “sponsors” , “researchers” and “governments of the host countries”), whose absence was one of the main criticisms in the formulations of post-trial obligations since DoH 2000; and (4) it requires that plans or arrangements for post-trial provisions be disclosed to the participants during the informed consent process for the first time in DoH.
Strengthening protections for LMICs is not straight forward and the expressions “fair level of benefits” or “other appropriate benefits” in the DoH were a blank check that could be easily dishonored by interested parties playing semantic tricks on the meaning of “fairness” and “exploitation”.
Dal-Ré, R., Ndebele, P., Higgs, E., Sewankambo, N., & Wendler, D. (2014). Protections for clinical trials in low and middle income countries need strengthening not weakening. BMJ, 349, g4254.
London, A (2008). Responsiveness to host community health needs. In Emanuel, Ezekiel et al (eds.), The Oxford Textbook of Clinical Research Ethics, 737-744, New York: Oxford University Press.
Lie, R. K. (2010). The Fair Benefits Approach Revisited. Hastings Center Report, 40(4), 3-3.
Macklin, R. (2006). Changing the presumption: providing ART to vaccine research participants. The American Journal of Bioethics, 6(1), W1-W5.
Macklin, R. (2009). The Declaration of Helsinki: another revision. Indian J Med Ethics, 6(1), 2-4.
National Research Ethics Service (NRES) (2012), "Care after research: a framework for NHS RECs", Health Research Authority (HRA), http://www.nres.nhs.uk/applications/guidance/guidance-and-good-practice/..., version 19 December.
Schuklenk, U. (2001). Helsinki Declaration revisions. Indian Journal of Medical Ethics, (9)1, 29.
Sofaer, N., Lewis, P., & Davies, H. (2014). Forthcoming practical framework for ethics committees and researchers on post-trial access to the trial intervention and healthcare. Journal of medical ethics, 40(4), 217-218.
I would like to thank Ruth Macklin for helpful comments on this letter.
Competing interests: No competing interests