Call for Clinical Trials Registry Gaining Momentum

For years, most clinical investigators working with experimental drugs have had some discretion about publishing their research findings regardless of the outcome.

But after a lawsuit involving depressed minors reached a New York court and the front pages of major newspapers last month, the public started questioning the ethics of selective publication of research results.

Last month, New York State Attorney General Eliot Spitzer filed a suit charging the pharmaceutical company GlaxoSmithKline (GSK) with "repeated persistent fraud" by not publicizing unfavorable studies of one of its drugs, Paxil, that was tested on depressed children and adolescents.

The British firm had tested the efficacy of Paxil in at least five different studies, four of which yielded findings linking the use of Paxil to suicidal thoughts children experienced. GSK only published the study containing positive results.

Partly as a result of the ensuing controversy, the American Medical Association (AMA) announced this summer that it would call on the Department of Health and Human Services to create a comprehensive, centralized clinical trials registry.

"Several members of Congress have indicated interest in pursuing legislation to create the registry," the AMA said in a statement. "Merck & Co. has said it supports expanding an existing government clinical trial registry to include all drugs. GlaxoSmithKline announced it will post the results of all its drug trials on the Internet."

The AAMC also supports the creation of a public registry.

"The association believes a mandatory public clinical trials registry would be a significant step toward strengthening the reliability and credibility of clinical research, which is so vital to advancing medicine and improving health," said AAMC President Jordan J. Cohen, M.D. "A registry will ensure that all scientifically valid results reach the public arena and that members of the medical profession and patients, as well as federal decision makers, will have access to more than just the select findings published in medical journals or the press."

Making a Case

A federal database for open clinical trials already exists and drug manufacturers are required by law to post some of their studies in it. However, enforcement of the law is weak. A 1997 law requires the pharmaceutical industry to disclose its open clinical trials for serious or life-threatening diseases to the federal government, but according to the Food and Drug Administration it has repeatedly failed to do so. The federal statute does not list penalties for non-compliance or give the FDA authority to punish violators.

Some members of academia were pleased with the recent attention given to the public registry proposal.

"It is fantastic that the AMA has supported this idea," said Kay Dickersin, Ph.D., an associate professor at Brown University. "Academic investigators and others have wanted this for a long time."

However, one medical school department chair who requested anonymity, expressed concern about the implementation of a public registry, saying that it would represent a major administrative burden on institutions doing clinical trials. Medical schools already invest a substantial amount of money in research and the administrative requirements a public registry might impose would likely result in financial strain.

A Pharmaceutical Research and Manufacturers of America (PhRMA) representative said that revealing early phase clinical trial information would create a financial disincentive to drug manufacturers. The industry contends that the cost to bring a new drug to market averages $820 million, and the time required for its introduction is usually a decade.

"A public registry containing information of early phase clinical trials would disclose companies' proprietary information to competitors, creating a risk for manufacturers trying to develop new, very expensive medications," said Court Rosen, a spokesman for PhRMA.

Various data indicate that investigators tend not to publish negative findings, according to Dr. Dickersin.

"What we know from the literature about what works and what doesn't is biased in favor of things working," she said.

An important ethical consideration in favor of a registry is the fact that patients participating in experiments are often told they are making a contribution to scientific knowledge when signing informed consents, she added.

"If that knowledge is never published, they are not making a contribution," said Dr. Dickersin. "What is happening then is unethical, since the covenant between the investigator and the patient is broken."

Having a public registry will enhance patient trust and avoid the breach of contract Dr. Dickersin describes, according to Dr. Cohen. "Implementing a registry will require careful thought, planning, and management, as well as adequate funding, but will greatly enhance the public's trust in the clinical research enterprise," he said.

-Suria Santana

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