IOM Recommendations Fall Short

Recommendations in an Institute of Medicine (IOM) report on reforming the U.S. Food and Drug Administration's (FDA) drug safety process may be a good start (see page 1), but the IOM's report does not go far enough, a group of experts in brain, behavior, and neuropsychopharmacology concluded last month.

In a statement issued by the American College of Neuropsychopharmacology (ACNP) in response to the report, Charles O'Brien, M.D., Ph.D., vice chair of the Department of Psychiatry at the University of Pennsylvania and chair of ACNP's Human Research Committee, and Donald Klein, M.D., a professor of psychiatry at Columbia University, said, “The current postmarketing surveillance process only accidentally detects rare but serious harmful effects of prescription medications, including legal off-label use of drugs prescribed for illnesses that were not studied in premarketing trials, as well as toxic drug interactions.”

While applauding the IOM's call for expanding the FDA's legislated authority to mandate postmarketing studies, O'Brien and Klein said,“ [T]his is not enough. In order to adequately detect late, rare, and off-label toxicities, a new cross-linked computerized database should be created.”

A week before the release of the IOM report, ACNP convened a panel of experts at a forum examining the FDA's tracking of adverse drug events related to medications already on the market. The panel, noting recent high-profile cases of serious adverse events that were not detected in the clinical-trials stage of drug development, explored ways to improve pharmacovigilance.

The ACNP panel asserted the need for a computerized surveillance system that integrates medical, laboratory, and pharmacy records. A computerized database linked to a person's medical records “will reduce medical errors and help physicians identify side effects that weren't detected during clinical trials, which are often too short and too small to identify rare or late events.”

Under the current system, 51 percent of drugs have significant label changes due to major safety issues discovered after the drug goes on the market. Nearly 20 percent of drugs go on to receive black-box warnings, and 3 percent to 4 percent are ultimately withdrawn from the market for safety reasons.

The group outlined three specific areas to explore. One was the implementation of “provisional approval” from the FDA in which drugs are allowed to come to market sooner but their marketing is highly restricted.

“This type of program will enable the people who need the drugs the most to get them, while encouraging industry to continue to collect data and monitor side effects,” said O'Brien.

Second, the computerized drug-surveillance system needs to integrate medical records and pharmacy records so that side effects can be quickly identified and researched. A cross-linked computerized surveillance system similar to that being suggested by the ACNP is already in use in the Netherlands. Known as the PHARMO Institute, the system integrates input from practitioner, hospital, pharmacy, and laboratory records. Another example of integrated databases is the General Practice Research Database in the United Kingdom.

Finally, the ACNP panel recommended that the organization itself should consider establishing fellowships in pharmacoepidemiology to promote the field and facilitate training of a new generation of scientists dedicated to pharmacovigilance. The group agreed that individuals with solid methodological expertise will be essential to collecting data and using the data wisely.

More information on the ACNP is posted at<www.acnp.org>. Information on the Netherlands' PHARMO Institute and the U.K.'s GPRD is posted at, respectively,<www.pharmo.nl/> and<www.gprd.com/home/>.▪