Ethics of healthcare research in developing countries

Medical and scientific research is now cross-national and cross-cultural. The relentless progress of globalization poses complex ethical questions for those wishing to do healthcare research in developing countries^1,2,3,4. While some forms of research sponsorship are altruistic, much research is driven by economic or academic interests that may or may not reflect the needs of the host country. There is also the delicate matter of double standards. Does informed consent have the same meaning in a poor illiterate population as it does in, say, Basingstoke? What is an acceptable standard of clinical care in a resource-poor community? And there is the economic dilemma of whether and how to sustain an intervention, if the trial shows it to be effective, after the research is over. Perhaps most important of all is the issue of how to develop an ethical model for research and training partnerships between developed and developing countries— an approach with long-term advantage for the latter⁵. Happily, the era of ‘safari research’ is now gone, but the typical funding agency still pays scant attention to the audit of collaborative partnerships, especially with regard to development of the host country's research capacity.

A report from the Nuffield Council on Bioethics, The Ethics of Research Related to Healthcare in Developing Countries⁶, is a timely contribution to the debate and a useful resource for governments, policy-makers and researchers. Its ethical framework is based on four sound principles of duty—the duty to alleviate suffering, to show respect for human beings, to be sensitive to cultural differences, and not to exploit the vulnerable. In the application of these principles, the social, cultural and economic context must be taken into account. The report recommends that:

• Countries should set national priorities related to provision of healthcare and to enhance their capacity to conduct research relevant to their needs

• When externally sponsored research is proposed which falls outside the national priorities, its relevance must be justified to the appropriate research ethics committees

• All countries should establish an effective system for the ethical review of research, which includes the establishment and maintenance of research ethics committees, independent of government and sponsors

• National and international sponsors of research should ensure that adequate provision is made for training in the ethics of research for professionals involved in research related to healthcare

• Development of local expertise in provision of health-care research should be an integral component of any proposed research.

None of these ideas is drastically new. Among the most widely used existing international guidelines on research ethics are the Declaration of Helsinki, the Council for International Organisations of Medical Sciences Guidelines, and the Guidance on Good Clinical Practice. However, researchers do not always follow guidelines, and, if they do, their interpretations vary. Many developed countries have specific guidelines on research ethics, mainly tailored towards their own national research⁴. For example, guidelines in the USA are legally binding and American investigators are supposed to follow them no matter where the research is conducted. This poses a dilemma for American investigators working in developing countries since the regulations may not fit in with the host country's own regulations, standards of care, consent procedures and cultural expectations. Several developing countries, among them Uganda, Gambia, India, Nepal and Brazil, now have in place well established ethical review committees with experienced and well trained members. Others, such as Myanmar and Laos, have no functional ethics committees at all. Even where there is commitment to ethical review, meagre resources and poor infrastructure will make research projects hard to monitor. In the UK, the running costs of an ethics committee are about £36 000 a year and in the USA they can be as high as $500 000. Many developing countries lack regulatory mechanisms and a legal framework for biomedical research; moreover, poverty, poor pay and ignorance breed corrupt practices. The Nuffield report recommends international initiatives to establish research ethics committees, to train their members and to monitor their development. More controversially, it also declares that ‘Funding should be provided for these purposes by those who sponsor research in developing countries’. The worry about this last recommendation is that ethics committee members might not be clearly impartial when assessing the pros and cons of a trial proposed by their sponsor.

What of informed consent? In general, the principle is that genuinely informed consent should be obtained from every participant in a study, perhaps sometimes preceded by the agreement of a senior member of the family or community member. So no news here either. The report has little to say on the matter of cluster-randomized trials, where communities rather than individuals are randomized to particular public health interventions. A dilemma that does attract close attention is the definition of a legitimate standard of care. This issue, when it arose in relation to clinical trials of antiretroviral agents in Africa, sharply divided the scientific community^7,8,9. Angell, editorializing in the New England Journal of Medicine, declared that ‘our ethical standards should not depend on where the research is performed’ and that there is no justification for taking into account local economic conditions so as to provide ‘a lower standard of care for some subjects than they would have received... in a different place’. But African researchers hotly dismissed this stance—which takes no account of local conditions and resource constraints—as imperialist¹⁰. The Nuffield report sides with the Africans, drawing upon the arguments of the philosopher Bernard Williams that what we mean by equality is not that people must always be treated identically, but that ‘for every difference in the way men [sic] are treated, a reason should be given’ that is relevant¹¹. The working party recommends that the ‘standards of care’ provided to members of the control group in a research project should be developed in consultation with those who work within the country, and that the local ethics committee must be satisfied.

What does the working party say about the researcher's obligations if a controlled trial shows a treatment to be effective? Whatever happens, it declares, the decision must be made in principle before the research gets underway. Ideally, when the trial is completed, all participants who might benefit should be offered access to the intervention; and, if this is judged impossible, the ethics committee will need to be presented with strong reasons. This sounds fine in theory, but the reality is that the purpose of a trial is to test an unproven intervention, and a commitment to long-term provision of the intervention by the researchers, after the trial is over, is usually beyond the resources of the research team.

On the crucial questions of resources and capacity in developing countries, the working party can do little more than beg donors and funding agencies to take these recommendations forward. But the track record of these bodies offers little hope of stable funding for these activities. The progress made so far has come largely from developing countries—enlightened governments or academics. Perhaps the biggest disappointment of the report is the lack of specific advice on how to shift the balance from international (expatriate) to national agendas. Developing countries require institutions that are capable of high-quality research; it is on national rather than international staff that the sustainability of research findings and new interventions will depend. Although the report pleads eloquently ‘we recommend that external sponsors of research should require that the development of expertise in research be an integral component of all research in developing countries’, there are no detailed recommendations on the component of funding that should go to local infrastructure and how this might be monitored. None of the questions raised by this new report will come afresh to people conducting serious research in the developing world. For them, the important issues are resources, trained staff and infrastructure. On the special ethical issues raised by healthcare research, the ideal solution is for developing countries to take the lead and become self-sufficient. Programmes to advance this process would be a worthy object for outside funding.