Tamoxifen and Informed Consent Dissent: Congress, outside Advisers Cite Reservations about NIH Cancer-Prevention Trial

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Congress, outside advisers cite reservations about NIH cancer-prevention trial

Medical research relies on human trials to test the safety and efficacy of new treatments. But all drugs -- even aspirin -- pose some risk. For example, a $68 million National Cancer Institute (NCI) trial now in its early stages will attempt to prevent breast cancer in 8,000 healthy women by giving them daily doses of tamoxifen for five years. Yet this synthetic hormone can itself induce cancer and fatal blood clots in a small percentage of women.

Have the designers of the trial done everything they can to minimize the risks to these 8,000 volunteers? Is it even ethical to expose healthy recruits to a drug with such serious side effects (SN: 4/25/92, p.266)?

These were among the questions raised last month at a hearing before the House Subcommittee on Human Resources and Intergovernmental Relations. And though officials at the National Institutes of Health (NIH) promised some changes, including major revisions in their informed-consent process, subcommittee chairman Rep. Donald M. Payne (D-N.J.) says he was not reassured by what he learned: "I remain very concerned."

Not all medical centers involved in the trial are providing potential recruits with an up-to-date synopsis of the risks that may be associated with tamoxifen, one panel of medical witnesses testified. And an analysis by the subcommittee of 268 different informed-consent forms being used by the medical centers participating in this trial found that most contained one or more potentially serious omissions of risk data. State and federal laws require that volunteers sign such consent forms before taking part in medical experiments. The aim is to establish that each recruit understands -- and accepts -- the specific known risks associated with an experiment.

The Oct. 22 hearing also turned up evidence that two federally impaneled groups of independent medical experts had unsuccessfully challenged the trial's design before it began. The panels charged that the trial's entry criteria permitted the recruitment of women whose risk of developing breast cancer was unacceptably low.

How NIH responds to charges leveled at the hearing may affect medical research well beyond the tamoxifen trial. This is the first major disease-prevention study to use a drug "that carries such serious risks," asserts Arthur L. Caplan, director of the Center for Biomedical Ethics at the University of Minnesota in Minneapolis. As such, he maintains, this trial "is a watershed, in terms of ethics" and may set a precedent for risk disclosure in future disease-prevention trials.

Moreover, says Seattle attorney Leonard W. Schroeter, "there's more to this than the ethics. There is a human rights issue.

Ever since the Nuremberg trials of Nazis accused of war crimes, Western law has prohibited medical experimentation on humans without the participants' full and informed consent, he notes. So "any person who is harmed as a consequence of these trials, without first having been fully informed of [tamoxifen's] risks, most probably has an appropriate lawsuit against both the dispensing doctor and the government," says Schroeter, the immediate past chairman of the environmental, toxic, and pharmaceutical torts section of the Association of Trial Lawyers of America.

Since disease sufferers may well accept side effects and risks that healthy people will not, "prevention clinical trials are very different from treatment trials," notes Peter Greenwald, director of NCI's Division of Cancer Prevention and Control in Bethesda, Md.

A woman's risk of breast cancer increases with age and several other factors, such as having a mother or sister with the disease. To ensure that only those women most likely to benefit from tamoxifen will face its risks, the new study is restricting entry to women who are at least as likely as a normal 60-year-old woman to develop breast cancer. …