Drug Safety Still Seen as Lagging

More than a year after the Food and Drug Administration announced it had strengthened its drug safety system, the agency still lacks a reliable system for keeping track of emerging problems, congressional investigators concluded in a report to be released today.

The Government Accountability Office found that a new Drug Safety Oversight Board and other FDA initiatives were “unlikely to address all the gaps” in the agency’s system for monitoring the long-term safety of prescription drugs approved for market.

Although the board may help straighten out high-profile cases, the GAO said, day-to-day oversight of safety issues is still hampered by poor information, lack of legal authority to order drug company studies, and bickering between the powerful FDA bureau that reviews drugs for approval and a smaller safety office depicted in the report as a bureaucratic stepchild.

The safety office “serves primarily as a consultant” to the Office of New Drugs “and does not have any independent decision-making responsibility,” the report said. In some cases, it found, the new-drugs bureau has excluded safety officers from presenting their findings to scientific panels that the FDA relies on for advice.

With eight directors of its safety office in the last 10 years, the FDA “has not effectively overseen post-market drug-safety issues, and as a result, it is unclear how [the agency] can know that important safety concerns have been addressed and resolved in a timely manner,” the report said.

It is too early to tell whether the report will provide a boost for stalled legislation to beef up the FDA’s safety office and make it an independent center within the agency.

Although GAO investigators outlined a long list of unresolved problems, they also credited the FDA for working to make improvements. In a statement, the FDA vigorously disputed the finding that its safety office plays a secondary role.

Two key lawmakers who had requested the GAO inquiry were divided in their reactions to the report.

“The GAO report shows that the drug-safety system is not in crisis, but the FDA’s process may need some fine-tuning,” said Rep. Joe L. Barton (R-Texas), chairman of the House Energy and Commerce Committee, which oversees the pharmaceutical industry.

A spokesman said Barton would wait for a National Academy of Sciences report due this summer before deciding whether to pursue legislation.

But Sen. Charles E. Grassley (R-Iowa), a co-author of the FDA reform bill, said the findings by the GAO’s nonpartisan investigators bolstered his proposal.

Grassley had held widely publicized hearings into the FDA’s failure to identify the heart risks of Vioxx, despite warnings from its safety office. The hearings followed an unexpected decision by manufacturer Merck to withdraw the painkiller, which had racked up blockbuster sales and profits.

“At the Vioxx hearing, some said there was a crisis at the FDA and others said everything is all right,” Grassley said. “This report provides solid evidence that everything is not all right.... The FDA’s problems are systemic and cultural, not isolated or easily fixed.”

In preparing their report, GAO investigators interviewed FDA scientists and managers and reviewed internal documents usually not provided to the public. Meetings of the drug safety board, for example, are closed.

The FDA’s oversight problems begin with spotty data, investigators found. The agency’s Adverse Event Reporting System, which relies heavily on voluntary reports from doctors, captures only a tiny fraction of bad reactions to drugs.

And in most cases, the agency lacks legal authority to order manufacturers to conduct follow-up safety studies once a drug is approved. (Grassley’s bill would grant the agency such authority.)

Drug data should soon start becoming more complete, investigators said, because the FDA has obtained $10 million in funding from Congress to tap into health insurer databases and other sources. Better information, however, is no guarantee that oversight will improve.

GAO investigators found that the new-drugs bureau and the safety office repeatedly got bogged down in bickering over what the data mean. These scientific disputes can continue for months, even years.

The FDA’s drug-safety decision-making process is complex, investigators said, involving a repetitive back-and-forth between the two offices, often over the same points.

“Several [safety office] staff characterized this as ... falling into a ‘black hole’ or ‘abyss,’ ” the GAO report said.

It depicted the safety office -- with 106 employees and a $27-million budget -- as a junior bureaucratic partner, sometimes ignored or dismissed by the new-drugs bureau, with 715 employees and a $111-million budget.

The chief of the new-drugs bureau reports directly to the head of the FDA’s Center for Drug Evaluation and Research. The director of the safety office must go through another supervisory level before reaching the head of the center.

The FDA disputed the finding that the safety office played merely a consultant role, saying that the two offices are equally respected and that 51% of the work of the new-drugs bureau involves safety.

The GAO looked closely at four cases in which the FDA encountered safety problems after a drug had been approved for use by patients. Not surprisingly, it took longer to resolve instances in which the two offices disagreed.

One drug for rheumatoid arthritis, Sanofi Aventis’ Arava, remains on the market nearly four years after the safety office recommended that it be withdrawn because of concerns it could cause serious liver problems and even death.

Reviewers at the new-drugs bureau strongly disagreed that reported cases of liver injury among patients were linked to the drug. At a 2003 scientific advisory panel meeting, the new-drugs bureau refused to let the safety office present its data, questioning their scientific merit, the report said.

Arava remains on the market, albeit with stronger warnings about liver risk.

Congressional investigators said the FDA needed to set up a more effective system for settling such disputes between the two offices.