In the wake of the withdrawal of rofecoxib and the addition of a black box warning for antidepressants, the Food and Drug Administration last month announced a plan aimed at strengthening its safety program for drugs.
A main component of the plan is an FDA-sponsored study by the Institute of Medicine that will evaluate the current drug safety system, with emphasis on the postmarketing phase. The IOM study will assess what additional steps could be taken to learn more about the adverse effects of drugs once they are on the market. The FDA also plans to create a system to adjudicate differences of professional opinion within its Center for Drug Evaluation and Research (CDER) concerning a particular drug, a situation that was widely reported to be an issue with the rofecoxib and antidepressant safety reviews. Workshops and advisory committee meetings where drug safety and risk management issues will be discussed are also planned for next year, including an advisory panel meeting next February on the safety of the cyclooxygenase-2 (COX-2) inhibitors.
These efforts are aimed at "keeping the agency on the cutting edge of public health protection, with regard to the risks of pharmaceutical products," and to "enhance the confidence" of Americans in the safety of the drugs they are prescribed, Steven Galson, M.D., acting CDER director, Rockville, Md., said during a telephone press briefing held to announce the FDA's plans.
Postmarketing drug safety has become a prominent issue. The FDA has been widely criticized for not acting quickly enough on these issues.
Using the selective serotonin reuptake inhibitors (SSRIs) and rofecoxib as recent examples of drugs with serious adverse events that emerged after marketing, Dr. Galson said that, clearly, the FDA does not always understand the "full magnitude" of a particular drug's risks before approval. When adverse events are identified in postapproval clinical trials, or by spontaneous reporting of the events to the FDA and/or pharmaceutical manufacturers, the agency takes a proactive approach, he said, with experts in clinical medicine and epidemiology evaluating the new data and determining the impact on the risk-benefit balance of the products.
Responding to the criticism that the agency acted too slowly on these two major safety issues, Dr. Galson said that "there will always be discussions in the health care community about the speed with which we make postmarketing regulatory decisions," and the methods used to make those decisions.
He said that no particular issue instigated the decision to contract with the IOM for a study of the FDA's drug safety program—the study has been under consideration for years.
The effort to adjudicate differences in professional opinion is geared toward ensuring that the opinions of all FDA reviewers are incorporated into its decision-making process when there are disagreements.
With both rofecoxib and antidepressants, attention has focused on a particular reviewer who raised safety questions, which reportedly were not given sufficient weight. These cases are "extremely rare," and the amount of publicity they received are disproportional to the number of drug safety consultations "that go really, really well," Dr. Galson said.
And in response to criticism that rofecoxib should have been withdrawn much earlier, he added, "we think what happened to Vioxx is a demonstration that the system worked well," and that the public and health care professionals were notified when concerns about cardiovascular safety emerged. He said it would be too difficult to comment on how these two cases would have been different if the new measures had been in place.
Asked to comment on the plans, Curt Furberg, M.D., a member of the FDA's drug safety advisory committee, said that it was "a step in the right direction," but does not go far enough to ensure the safety of drugs once they are marketed.
This will remain a problem as long as the review of postmarketing drug safety remains within the FDA, where the same people who approve a drug then judge whether it should remain on the market, said Dr. Furberg, professor of public health sciences at Wake Forest University, Winston-Salem, N.C.