Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research and for those for whom the research is combined with care.

Declaration of Helsinki. Principle 8

This requirement for the ethical conduct of research concerns the strategy whereby research participants will be recruited. Generalizability of research results to the population at large depends, in part, on the appropriate choice of eligibility criteria, the latter declared in the section addressing the requirement of scientific validity. Once eligibility criteria are formulated, recruitment should not be restricted to certain populations of potential participants simply on the basis of convenience or efficiency, or by exploiting vulnerable individuals or communities. Many possible vulnerabilities may be identified: cognitive (including impaired decisional capacity); deferential; institutional; social; economic; and medical. Because clinical trials are often international in scope, research ethics committees in each country involved should evaluate proposed recruitment practices in its local and regional communities, mindful that the aforementioned vulnerabilities are inherently contextual, and will vary across regional and national boundaries.

Research ethics committees should also evaluate whether there will be an equitable distribution of potential benefits and burdens -- those who bear the potential risks of the trial, and the communities from which they are drawn, should not be systematically excluded from realizing the potential benefits of the research. The presence of clinical equipoise (1) at the inception of the trial ensures that potential participants are not disadvantaged by participating, but meaningful benefits may depend on continued access to the drug or intervention after completion of the trial. In addition, the judgment of clinical equipoise at the inception of the trial may be difficult, and contentious, when research is conducted in poor, developing nations by researchers from wealthy, industrialized countries. The interventions studied may not ordinarily be available in the countries concerned. This also bears on the notion of social value, a separate requirement for the ethical conduct of research. A full discussion of this important consideration is beyond the scope of this document, and the reader is referred to reports issued by the National Bioethics Advisory Commission in the U.S. (2), and the Nuffield Council on Bioethics in the U.K. (3), for additional elaboration.

The applicable notion of (distributive) justice is also elaborated on in the Belmont Report (4) which guides the deliberations of Institutional Review Boards in the U.S. The report also discusses two other ethical principles applicable to human subjects research: beneficence, and respect for persons.

Individuals from specific groups, such as women, should not be inappropriately excluded from the potential benefits of clinical trial participation. Such exclusion has traditionally arisen from concerns about the possible teratogenic effects of investigational agents, but is no longer considered justifiable (5). Similarly, the presence of clinical equipoise permits the ethical enrollment of children in clinical trials. Because drugs are typically utilized "off-label" in the pediatric population (6), appropriately conducted controlled trials in this age group are indispensible.

References

References available online are hyperlinked

1. Freedman B. Equipoise and the ethics of clinical research. NEJM 1987; 317:141.

2. National Bioethics Advisory Commission. Report on Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries. 2001.

3. Nuffield Council on Bioethics. The ethics of clinical research in developing countries. 2000.

4. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. 1979.

5. F.D.A. Guidelines for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs. 1993.

6. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label use in pediatric wards in European countries. BMJ 2000; 320:79-82.