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FDA Is Criticized Over Drugs' Safety Problems
Response to Approved Medications Cited

By Marc Kaufman
Washington Post Staff Writer
Monday, April 24, 2006

The Food and Drug Administration is sometimes too slow in picking up safety problems once drugs are on the market and in responding to emerging danger signals, a federal study concluded in a report to be released today.

The review by the Government Accountability Office found that the FDA does not have clear policies for addressing drug safety issues and that it sometimes excludes its best safety experts from important meetings.

The report also calls on Congress to consider expanding the FDA's authority to require that drug companies conduct studies of already-approved products. The agency's ability to order post-market studies is now limited, and many drug companies have been slow to conduct studies that they had agreed to undertake as a condition of gaining FDA approval.

The GAO inquiry was requested by Congress in 2004 after the sudden withdrawal of the blockbuster painkiller Vioxx, which was found to increase the risk of heart attacks and strokes in long-term users. Several bills that would toughen the FDA's safety oversight were introduced after the Vioxx withdrawal, and the report offers their sponsors new ammunition.

The FDA was widely criticized for moving too slowly in its review of the potential health problems with Vioxx, which was taken by millions, but the GAO report took the criticism a major step forward: It concluded that the agency's entire system for reviewing the safety of drugs already on the market is too limited and broadly flawed.

GAO's examiners studied the agency's handling of four controversial drugs -- the cholesterol-lowering drug Baycol, the painkiller Bextra, the rheumatoid arthritis drug Arava, and the nighttime heartburn medication Propulsid -- and concluded that "there is a lack of criteria for determining what safety actions to take and when to take them."

All but Arava were ultimately taken off the market because of safety concerns, but the GAO found that disputes between two arms of the FDA's Center for Drug Evaluation and Research slowed the process. Since 2000, 10 drugs have been withdrawn by their manufacturers for safety reasons.

The report found that the Office of Drug Safety, which monitors reports of emerging safety risks, at times made recommendations that were ignored by the larger and more influential Office of New Drugs. The GAO also criticized the way experts in the Office of Drug Safety were kept from speaking at important advisory committee meetings on drugs they were studying. The drug safety office has seen considerable turnover, with eight directors in the past 10 years.

"This report provides solid evidence that everything is not all right at the FDA and calls for long-overdue reform," said Sen. Charles E. Grassley (R-Iowa), who requested the GAO report with Rep. Joe Barton (R-Tex.). Grassley and Sen. Christopher J. Dodd (D-Conn.) have introduced a bill that Grassley said would give the post-market review process "real teeth."

Barton said that "the GAO report shows that the drug safety system is not in crisis, but the FDA's process may need some fine-tuning."

In its formal response, the FDA said the report was "well done" and that the "conclusions reached are reasonable and consistent with actions we already have underway or planned."

Caroline Loew, senior vice president of the Pharmaceutical Research and Manufacturers of America, said the industry group "believes that the FDA takes the post-market surveillance of prescription drugs seriously and has taken additional steps over the past couple of years to help ensure that patient safety cannot be compromised." She added that only 3 percent of all approved drugs were later withdrawn.

In the aftermath of the Vioxx withdrawal, the FDA created the Drug Safety Oversight Board, with expanded ability to act on emerging safety issues. The GAO report makes clear, however, that its reviewers consider FDA's actions insufficient. The new board may help provide greater oversight of high-level safety decisions, the report said, but "it does not address the lack of systematic tracking of ongoing safety issues."

To gain approval of a new drug, companies generally conduct clinical trials with hundreds or thousands of volunteers to determine whether the product is safe and effective. But some safety risks may not surface until it has been taken by millions of people.

Since the Vioxx controversy, the FDA has begun posting previously withheld preliminary information about possible drug safety problems and has been quicker to highlight potential risks. But the GAO said the information available to the FDA on potential problems is still limited.

Its system for collecting reports of "adverse events," for instance, is a voluntary one that does not require doctors to report drug-related problems they encounter. Experts estimate that only about 10 percent are reported.

Alastair Wood of Vanderbilt University, a prominent voice on the FDA's advisory panel on drug safety and risk management, said the GAO report "confirmed a lot of what people have been saying for some time."

Wood said the FDA is still refusing to take the bold steps he believes are necessary to ensure drug safety. "Frankly, it doesn't look right now as if much has changed," he said.

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