GAO report criticizes FDA drug safety oversight.

Amid public concern about dangerous drugs, the Government Accountability Office (GAO) recently released a report saying that the FDA "lacks a clear and effective process for making decisions about, and providing management oversight of, postmarket drug safety issues." (Gov't Accountability Office, Improvement Needed in FDA's Postmarket Decision-Making and Oversight Process, GAO-06-402 (Mar. 31, 2006).)

The report found that there was "a lack of criteria for determining what safety actions to take and when to take them" and that, without such criteria, decisions "are often based on the case-by-case judgments of the individuals reviewing the data."

Senate Finance Committee Chairman Charles Grassley (R-Iowa) requested the inquiry in 2004, after the painkiller Vioxx was withdrawn from the market. Since 2000, only 10 drugs have been withdrawn for safety reasons, and their manufacturers withdrew them voluntarily.

James Gotz, a Boston lawyer and chair of ATLA's Section on Toxic, Environmental, and Pharmaceutical Torts, noted that the GAO report brings to light the limits of the FDA's legal authority: "its inability to compel or leverage pharmaceutical manufacturers to conduct large-scale postmarket studies" and its "limited ability to compel drug companies to take remedial action, be it label changes or drug withdrawal."

The FDA developed the Drug Safety Oversight Board last year to address some of these problems. (See Allison Torres Burtka, FDA's New Drug-Safety Board Is an Imperfect Solution, Critics Say, TRIAL, Apr. 2005, at 78.) But the report says the board hasn't done enough: It "may help provide high-level oversight of safety issues, but it does not address the lack of systematic tracking of safety issues and their resolution."

Part of the problem, the report says, is insufficient communication between two offices within the agency's Center for Drug Evaluation and Research (CDER): the Office of New Drugs (OND) and the Office of Drug Safety (ODS). OND both approves drugs and has the authority to take regulatory action concerning postmarket safety. ODS is smaller, focuses on postmarket safety, and "serves primarily as a consultant to OND and does not have independent decision-making responsibility," according to the report.

When a safety concern arises, ODS produces a report for OND, but ODS sometimes does not know how OND responds to it. Several ODS staff said their reports fall into a "black hole" or "abyss," the GAO noted.

When the two offices disagree, OND may seek guidance from advisory board committees made up of outside experts and consumer representatives. But ODS's role in these meetings is unclear, and some ODS staff have been excluded from them, according to the report.

Members of the advisory committees often have financial conflicts of interest but are rarely recused, according to a study published in the Journal of the American Medical Association in April. In 73 percent of the meetings studied, at least one member or voting consultant disclosed a conflict. (Peter Lurie et al., Financial Conflict of Interest Disclosure and Voting Patterns at Food and Drug Administration Drug Advisory Committee Meetings, 295 JAMA 1921 (2006) .)

The GAO report recommends that Congress expand the FDA's authority "to require drug sponsors to conduct postmarket studies when additional data are needed." It also urges the FDA to establish "a mechanism for systematically tracking postmarket drug safety issues, revising and implementing FDA's draft policy on major postmarket drug safety decisions, improving CDER's dispute resolution process, and clarifying ODS's role in FDA's scientific advisory committee meetings."

Beyond giving the FDA authority to require postmarket studies, Gotz said, "there needs to be meat on this new bone." He questioned how the agency will enforce calls for postmarket studies ("Will they suspend marketing if the company does not comply?") and whether the agency will approve the studies' design or monitor them ("Will the FDA be permitted access to the studies' raw data for independent interpretation of the results?").

Grassley said in a statement that the report "provides solid evidence that everything is not all right at the FDA," adding that its problems "are systemic and cultural, not isolated or easily fixed." Last year, Grassley cosponsored a bill (S. 930) to set up a new, independent center within the agency for postmarket review.

According to the report, the FDA stated that the GAO's conclusions were "reasonable and consistent with actions that it has already begun or planned."

Still, critics are skeptical that the agency will do enough to ensure consumer safety after a drug reaches the market.

"These conclusions don't recommend serious enough changes," said Sidney Wolfe, a physician and director of the Public Citizen Health Research Group, and an author of the JAMA report. The GAO report contains "nothing critical or sharp enough to make the FDA uncomfortable."

Wolfe called for removing ODS from under CDER so it can make independent decisions. He also said the Prescription Drug User Fee Act, which established the system the FDA uses to collect fees from companies whose products it evaluates, should be repealed so that the industry does not fund the agency regulating it.

Gotz agreed, pointing to "inherent biases in the process that favor the pharmaceutical industry. The drug companies fund more than 50 percent of the OND budget and 25 percent of the ODS budget."

In pharmaceutical litigation, the GAO report will help rebut drug makers' so-called FDA defense, which argues that FDA-approved drugs should not be subject to products liability claims, Gotz said.

"The report should be deemed admissible to preempt or rebut any such defense assertion," he said. "I intend to offer it in evidence in all my cases."