Ethics and international research
Authors: E C O Edi-Osagie, N E Edi-Osagie, P. Lurie, S. M Wolfe, J. Burdon, R. Baraza, M. J Landray, N. A Halsey, A. Sommer, R. E Black, P. Godfrey-Faussett, A. Mwinga, M. Hosp, R. Baggaley, M. Quigley, J. Porter
Journal: BMJ (1998)

Editor—In their editorial Halsey et al defended their placebo controlled trials of effective interventions to prevent maternal-fetal HIV transmission in developing countries.1 Their arguments in defence of these trials are weak. They cite the guidelines of the Council for International Organisations of Medical Sciences, which “call for universal principles of ethical research, not universal standards of medical care.”1,2 This does not, however, justify their exposing pregnant women with HIV infection to placebo treatment in a trial that also offers appropriate treatment. Although prevailing economic circumstances in developing countries may preclude such women from routinely receiving effective treatment, this is no justification to deny the control arm in the trial of Halsey et al effective treatment because it would act as an undue incentive. We also do not agree with Lurie and Wolfe’s counterarguments that studies supported by the American government should provide all participants with the same level of care that is available to Americans.3 Although this suggestion is ethically sound and desirable, it is highly impracticable. 

We believe that any intervention in a research trial that deliberately sets out not to prevent an anticipated deleterious health condition (maternal-fetal HIV transmission in this case) is unethical and goes against the guidelines of the Council for International Organisations of Medical Sciences.2 Examples abound in contemporary medicine of established but untested interventions whose effectiveness cannot now be tested because subjecting people to placebo controlled trials of their effectiveness is considered to be unethical and unacceptable. Lurie and Wolfe’s suggestion of comparing the new short course zidovudine regimens against the established ACTG 076 regimen is ethical and statistically sound. Perhaps more appropriate would be a three arm trial, with the new regimens and ACTG 076 making up two arms and the local population of pregnant women infected with HIV who are not actively recruited to the study making up the third (control) arm. The data for this third arm should be readily available locally, and comparisons with the active treatment arms will be valid because they all belong to the same population cohort in which the biological behaviour of the infection is similar. The use of multiple logistic regression, with appropriate adjustments, will enable valid comparisons and conclusions to be made. 

It is simplistic of Halsey et al to assert that none of the subjects in their trials are being denied the care that they would otherwise have had. The challenge the trialists have brought themselves is to prove to the world that anyone with understanding would willingly submit themselves to a deleterious health condition in a trial which alternatively offers treatment for that condition. We find the thought that these poor women have been used as human guinea pigs disturbing. If Halsey et al believe that any positive results from their trials in the developing world (to identify cheaper effective treatment to reduce vertical transmission of HIV) will not be exported for the benefit of the developed world, they are probably the only ones on this planet who do.