FDA Officials Divided Over Need for Policy Change

To paraphrase Freud, “What does the FDA want?” For a couple of days in early March, the answer was unclear as the U.S. Food and Drug Administration (FDA) tried to sort out its message on the best ways to ensure drug safety.

In testimony before a Senate committee delivered two days apart, two FDA officials offered contradictory statements on the approach to drug-safety oversight.

First, Sandra L. Kweder, M.D., deputy director of the Office of New Drugs at the FDA, told the panel that the FDA needed additional powers to require new clinical trials and to order label changes for drugs when safety questions arise following approval.

“Stronger authority to change labeling would be helpful,” she said, addressing the Senate Committee on Health, Education, Labor, and Pensions on March 1.

But 48 hours later, Janet Woodcock, M.D., acting director for operations at the FDA, addressing the same committee, said that new legislation granting such authority was unneeded. The FDA will not have an official position on these issues until the Institute of Medicine completes its study of postapproval drug-safety monitoring, she said. Woodcock outranks Kweder at the FDA so her statement was taken as superseding Kweder's earlier remarks.

Woodcock also placed greater emphasis on the FDA's proposed “Drug Watch” Web page, which would get “information directly out to people who need it in a timely manner.”

Other witnesses supported the FDA's February announcement of the formation of an independent Drug Safety Oversight Board, saying it was an important first step, but they also called for greater transparency in clinical-trials data and controls on direct-to-consumer advertising.

“This is a time for re-evaluation of the FDA,” said committee chair Sen. Michael Enzi (R-Wyo.), referring to controversies like the Vioxx recall and warning labeling for SSRIs. “It's appropriate to react to recent events, but not to overreact.”

The hearings, held on two days, served as the opening of a fact-finding process intended to guide a congressional response to concerns about drug safety, according to a joint statement by Enzi and ranking minority member Sen. Edward Kennedy (D-Mass.).

“Since 1992, more funds have been available to speed approval, but drug safety checks have not kept pace,” added Kennedy at the hearing.“ The FDA needs clear authority to assess risk and change labeling, conflicts of interest must be addressed in advance, and patients need information in understandable language.”

The FDA's approval process is still the “gold standard” for evaluating drugs, Kweder said, adding that no one could identify in advance all risk from a drug. “You can't anticipate how a drug will be marketed or used.”

The agency cannot evaluate a drug in terms of only risks or only benefits, she said. A drug whose side effects included itching would have to be considered in a different light from one that caused liver failure, for instance. Even if a drug carried serious risks, the FDA might recommend continued sale if there were also major benefits to some patient groups.

Currently, the FDA can only persuade, not force, drug companies to change label content or take a drug off the market, said Kweder. Labeling changes often require lengthy back-and-forth negotiations between the companies and the agency, leading to long delays in remedial action, as occurred in the Vioxx case.

A separate, outside safety panel is not needed because postmarketing drug safety analysis would benefit from in-house expertise, and conflict-of-interest issues would be fewer, she said.

“The data safety board will include FDA staff not involved in the original review of the drug, as well as medical experts from other agencies like the National Institutes of Health and the Department of Veterans Affairs,” she said. “Our goal is to create a source of consumer-friendly information for health professionals and patients on emerging health risks.”

Representing APA, Vermont psychiatrist and APA Trustee David Fassler, M.D., put forth three proposals for improved safety.

In the light of recent concerns about SSRIs and suicidal ideation, the FDA should create a new drug advisory committee focusing only on central nervous system drugs for children and adolescents, he said. In addition, registration of clinical trials is essential to allow physicians and patients access all to data from both published and unpublished studies. Congress should also enact new educational incentives and federal support for mental health training programs to increase the number of health professionals available to treat young people.

Calls for a drug-safety board do not mean that the FDA is broken, said Thomas Fleming, Ph.D., a professor of biostatistics at the University of Washington who has served on several FDA drug advisory committees. There is no need for a separate outside group to monitor safety once a drug is on the market.

“The FDA staff is familiar with the regulatory process, serious conflict-of-interest issues would arise with an outside board, and there would be problems incorporating outside recommendations into the workings of the agency,” he said.

Not every product would require randomized controlled trials to test safety, said Fleming. A surveillance system based on adverse-event reports by clinicians and data from large, linked databases could signal safety issues, he said. That safety signal would trigger the FDA's authority to require new trials from manufacturers.

Another panelist, William B. Schultz, J.D., agreed that recent recalls and labeling changes do not require a wholesale overhaul of the FDA.

“The fact that a drug has serious safety problems doesn't mean that the FDA made a mistake [in the approval stage],” said Schultz, a former FDA deputy commissioner for policy, now in private practice. Because of the limited number of patients recruited, clinical trials conducted as part of the premarket approval process were unlikely to detect either rare or common adverse reactions, he said. Thousands of patients were included in those clinical trials, but millions might take a new drug in its first years on the market. The FDA should educate patients about the inherent risks of all prescription drugs, he added.

“The FDA should remind physicians and patients about the additional risks of newly approved drugs, and it should advise caution in taking drugs to which large numbers of patients have not yet been exposed,” he said.

The agency also needs sufficient money and staff to monitor drugs following approval and should have authority to order changes in labeling or to require postmarketing clinical trials to gauge safety. The FDA already can require postmarket surveillance for medical devices but not for drugs.

Better disclosure about the safety of new drugs and a ban on direct-to-consumer advertising for one or two years following approval could reduce the pressure to prescribe new drugs before their risks are well known. Finally, said Schultz, the the FDA should have the power to restrict physicians' use of drugs to their stated indications or to limit distribution of some drugs to certain specialists. Traditionally, the FDA has drawn a line between approving drugs and regulating the practice of medicine.

Prepared statements by witnesses at the Senate hearing are posted online at<http://help.senate.gov/bills/hlh_66_bill.html> and at<http://help.senate.gov/bills/hlh_67_bill.html>.▪