Crucial data ignored in justifying placebo studies
In an article in the September 18, 1997 New England Journal of Medicine, two Public Citizen Health Research Group physicians attack the U.S. Government for funding unethical HIV experiments in some of the world’s poorest countries and assert that safer alternative research methods have been largely ignored.
The Sounding Board article, “Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries”, addresses 15 studies conducted on HIV-positive pregnant women in Cote d’Ivoire, Uganda, Tanzania, South Africa, Malawi, Thailand, Ethiopia, Burkina Faso, Zimbabwe, Kenya and the Dominican Republic in which some women are not given AZT even though the drug has been proved to reduce transmission of HIV from mother to infant by two-thirds. Nine of the 15 studies are funded by the U.S. Government, through the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), although such experiments would never be tolerated if attempted in the U.S. Indeed, both studies being conducted in the U.S. provide AZT or similar drugs for all women.
The article presents a previously unpublished analysis of data from the 1994 placebo-controlled study which established the standard AZT treatment for reducing mother-to-infant HIV transmission. This analysis suggests that shorter regimens of AZT treatment may be as effective as longer ones. This makes it very likely that the shorter regimens are more effective than a placebo, undermining any ethical basis for the trials. “Those who gave the go-ahead for the unethical placebo trials appear to have missed or ignored these vital data. These findings undermine the rationale for continuing these lethal experiments,” said Dr. Sidney Wolfe, co-author of the article and Director of Public Citizen’s Health Research Group.
“These studies, despite the fact that most are being funded by Western governments, deny women access to the kind of effective treatment that has been available for several years in developed countries. Comparing the shorter regimen to nothing (a placebo) is the wrong comparison and needlessly places patients’ lives at risk. Instead, the shorter regimens should be compared with a treatment similar to the AZT regimen already proved effective,” said Dr. Peter Lurie of Public Citizen’s Health Research Group, co-author of the article.
Some of those defending the placebo studies suggest that experiments should only meet the standard of care offered in the developing countries. The article strongly rejects this double standard: “Residents of impoverished, postcolonial countries, the majority of whom are people of color, must be protected from potential exploitation in research. Otherwise, the abominable state of health care in these countries can be used to justify studies that could never pass ethical muster in the sponsoring country,” it says.
The NIH and CDC have responded to Public Citizen’s complaint by saying that “our decision to support these trials rest (sic) heavily on local support and approval.” Yet an internal CDC memo dated January 27, 1995 states that “Despite detailed discussions … justifying the use of placebo, it has become evident that some of the Ivoirian physicians working at [the CDC research project in Cote d’Ivoire], several of our important Ivoirian collaborators, and a number of international researchers involved in [perinatal HIV transmission], do not feel comfortable with the use of placebo.” If developing countries’ scientists did support the trials, it may be because they were offered the wrong choice: given a choice between a placebo-controlled trial and no trial at all, it is not surprising that some opted for the placebo-controlled trial, said Lurie.
The authors urge that future studies should adhere to a single international ethical standard that does not discriminate between patients’ countries of residence. “Tragically, for the hundreds of infants who have needlessly contracted HIV infection in the perinatal-transmission studies that have already been completed, any such protection will have come too late,” the article concludes.