Clinical trial data: Getting the complete picture

When it comes to the data pharmaceutical companies gather from clinical trials, physicians and patients now don't know if they have all the information they need to guide treatment plans and drug safety risk-benefit decisions. This concern drives continuing interest in the development of a comprehensive clinical trial registry -- a critical element in ensuring that physicians and patients have access to the best evidence science has to offer.

Recent controversies about antidepressant use by children and teens underscore the need for such a database. They also point to the systemic nature of the problem.

The American Medical Association's Council on Scientific Affairs concluded in a June 2004 report that the existence of publication bias in pharmaceutical research distorts medical literature and therefore could affect the validity of subsequent reviews. This can lead to flawed decisions by government agencies and health plans.

Supporters of a comprehensive repository of trial data say such a mechanism is the answer. Physicians need access to information that would allow them to view the entire picture of how medicines work and they need it in a user-friendly, one-stop shopping, electronically searchable resource.

The AMA has been working toward this goal. Last year the Association called for the creation of a national clinical trial registry operated by the Dept. of Health and Human Services to list all drug trials and link to their results -- both positive and negative. The AMA also urges hospital and university institutional review boards to consider registration of clinical trials as a condition for approval.

Meanwhile, the International Committee of Medical Journal Editors, which includes the editor of the Journal of the American Medical Association, has taken actions of its own.

In September 2004, this group published a joint editorial in JAMA making clear that a trial would be considered for their publications only if it had been registered before the enrollment of the first patient. Last month, the group renewed and refined this position in a second editorial, setting Sept. 13 as the date before which ongoing trials must be registered to gain consideration. Their message was clear. "Our goal then and now is to foster a comprehensive, publicly available database of clinical trials."

In a related matter, the AMA House of Delegates this month will examine a new Council on Scientific Affairs report addressing physician access to Food and Drug Administration data. This document, which stems from issues concerning antidepressants and pediatric patients, grew into a broad discussion about clinical trial data, drug safety issues, and how drug risks are communicated to physicians. In this context, the report serves as a reminder of the central role that a comprehensive clinical trial registry would have in addressing these issues.

While the problem of undisclosed trial data is obvious to many, the finer points of disclosure have yet to be fully ironed out.

The journal editor committee has outlined a minimal registration data set of 20 items, including funding sources and a description of the intervention that includes the generic name of a registered drug or the generic name or company serial number of an unregistered drug. The World Health Organization, too, has made progress toward developing a worldwide standard for data collection.

But industry cooperation is key and by no means guaranteed. As it stands, many entries in the government's online database (link), a service of the National Institutes of Health developed by the National Library of Medicine, do not provide the most necessary information. Certain companies, for instance, use phrases such as "investigational drug" instead of the drug's actual name.

Ultimately, the challenge of revealing all that should be known about the clinical trial process is complex. Some maintain that legislative action will be necessary. Already governments around the world, including the United States, are beginning to wrestle with mandating disclosure requirements.

These proposals will continue to emerge and evolve, and the details will prove to be an important variable in gaining success. With it, patients and physicians will know that all the facts are on the table when they make their treatment choices. Also, clinical trial participants will be assured that their altruism will contribute to improved medical understanding. Letting light shine on the the data is the right way to achieve those important goals.