Credit: Shiela Foran

Two new proposals for the ethical conduct of medical research will push hundreds of clinical trials beyond the bounds of ethical acceptability. The World Medical Association's (WMA) revision of the Declaration of Helsinki and the US National Bioethics Advisory Committee (NBAC) have both called for an end to placebo-controlled trials in developing countries where an alternative standard of care exists. The latter also states that Western researchers and their sponsors have an obligation to provide care to study participants even after trials have ended.

The new declaration language was introduced at a meeting of the WMA in Scotland, UK, last month. The section on placebo-controlled studies now reads that every patient should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods. Placebos are only acceptable when no proven treatment exists.

The change has been prompted by a debate that began in 1997 when Peter Lurie, the deputy director of the Public Citizen Health Research Group, and others challenged the ethics of using a placebo arm in a Ugandan study of mother-to-child human immunodeficiency virus transmission when AZT (3′-azido-3′-deoxythymidine) is used in developed countries to lower transmission rates. The study's defenders argued that placebo studies speed up research—and therefore cures—and that the Ugandan study was appropriate considering that host country's standard of care.

The same study also spurred the NBAC to examine the issue. Its report recommends against the use of a placebo arm in studies of conditions where an effective therapy already exists. Although some have called that approach bad science, the idea received a boost last month with the publication of an equivalence study without a placebo arm that produced new information about mother-to-child HIV-1 (NEJM. 343, 982; 2000).

The report's most striking recommendation states that researchers should “continue to provide to all participants . . . any research intervention that was proven successful along with other interventions that were provided to participants during the research, if these participants would not otherwise have access to an established, effective treatment.”

US researchers told the NBAC that “funding agencies would never be willing to sponsor research that entailed provision of treatment at the end of the study.” If cost is the issue, it shouldn't be, says Lurie. “These are multimillion dollar trials funded by enormous government agencies or multibillion dollar pharmaceutical companies,” he said. “They can well afford to provide these interventions to the very people who have put their health on the line for the companies.”

Money is not the only issue, says Sara Radcliffe of the Pharmaceutical Research and Manufacturers Association, an industry lobbying group. In the right situation, pharmaceutical manufacturers are willing to continue providing treatment, and some do, she says. But if that were a requirement, it might do more harm than good. For example, many countries won't be able to ensure antibiotics are used in a way that prevents an increase in resistance. Ultimately, she says, “It seems problematic to make drug companies responsible for making up for shortfalls in health care delivery.”

Although highly respected as guiding principles for medical research, neither the NBAC report nor the declaration is legally binding.