Bioethics and Local Circumstances

The ethics of the design of clinical trials to prevent transmission of HIV-1 from mother to child in developing countries have been criticized.* However, a discussion of ethical principles in biomedical research that ignores the socioeconomic heterogeneity of society is not ethical and not worth holding. Policies regarding health management differ within and between industrialized and developing countries because of their different economic capabilities. Whereas it is established policy that all HIV-positive pregnant women in the United States and other developed countries are offered azidothymidine (AZT), this is not achievable in many developing countries because the costs of the drug and logistical support are prohibitive. For example, Uganda (with 156,600 pregnancies per year) spends $6 annually in health care per person.

In the ACTG 076 trial of AZT's ability to prevent maternal transmission of HIV-frequently used as the "gold standard" against which other trials are measured-AZT treatment was started in a hospital setting between 14 and 34 weeks of gestation and continued (through delivery) until the newborn infant was 6 weeks of age. Yet in Uganda, fewer than 10% of all pregnant women have prenatal care for the first time during the first trimester, 30% during the second trimester, and 60% during the third trimester; only 40% deliver in a health facility. So to conduct research in Uganda based on such a regimen would produce results applicable only in a research setting.

The future of clinical trials in Africa could depend on two factors. First, sponsoring agencies might slow down or stop the trials because of the ongoing debate about how best to conduct them. This would leave Africa in a terrible position because resources are not available there to do the trials. For maternal transmission studies, the results of testing alternative treatment regimens could lower the cost of therapy dramatically, to a point where it would be feasible for the governments to subsidize treatment. Evaluation of HIV vaccines is essential for Africa because the resources required for highly active antiretroviral treatment (HAART) are not available and other preventive interventions have their own limitations. The second factor is the extent to which the people in developing countries will be influenced by the debate. Discussions that ignore the magnitude of the problem, gloss over the socioeconomic circumstances of poor nations, and apply previously developed ethical guidelines too literally may lead individuals to reduce their participation in future trials. So far, policy-makers and politicians have not interfered with ongoing trials because of the current debate.

Following the atrocities committed by Nazi research physicians, ethical guidelines to protect research subjects were laid down in the Nuremberg Code, the Declaration of Helsinki, and the "International Ethical Guidelines for Biomedical Research Involving Human Subjects" (issued in 1982 and revised in 1993). The 1993 guidelines were designed to be of use, particularly to developing countries, in defining national policies on the ethics of biomedical research, applying ethical standards in local circumstances, and establishing or redefining adequate mechanisms for ethical review of research involving humans. In their present form these guidelines will delay development of badly needed vaccines and treatment regimens. For example, they state that phase I drug studies and phase I and II vaccine studies should only be conducted in "developed communities of the country of the sponsor." Likewise, the guidelines say that phase III vaccine trials and phase II and III drug trials should be conducted simultaneously in the host and sponsoring countries. Barry R. Bloom discusses other ethical issues in this issue. Regional meetings are being convened in Africa, Asia, Latin America, North America, and Europe early in the year to address the obstacles posed by the guidelines in their current form. Resulting improvements are expected to make the guidelines more specific so that there will be no roadblocks in the way of conducting ethical clinical trials.

F. X. Miiro, personal communication.

E. K. Mbidde, J. Intl. Assoc. Physicians AIDS Care 3 (no. 11), 26 (1997).

CIOMS in collaboration with WHO, International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, Geneva, Switzerland, 1982; revised in 1993).

B. R. Bloom, Science 278, 186 (1998).

The author is director of the Uganda Cancer Institute at Makerere University in Uganda, Africa.