One in Ten Prescription Drugs Either Pulled from Market, Get Label Warning After FDA Approval, Study Finds
More than 10% of prescription drugs approved by the FDA between 1975 and 1999 were either withdrawn from the market or required a label change to warn against dangerous adverse reactions, according to a study in today's Journal of the American Medical Association. The Washington Post reports that the study recommends that because of the risk posed by newly approved drugs, doctors prescribe older, "long-used" medications whenever possible. "Based on our results and those of others, clinicians should avoid using new drugs when older, similarly (effective drugs) are available," the authors wrote, adding, "Patients who must use new drugs should be informed of the drug's limited experience and safety record" (Kaufman, Washington Post, 5/1). Using 25 editions of the Physicians' Desk Reference, an annual compendium of information from the FDA on all approved drugs used by most physicians, researchers reviewed 548 drugs approved from 1975 to 1999. Here are some of the findings:
- Sixteen drugs, or 2.9%, were withdrawn because they turned out to be unsafe. Of these, 50% were withdrawn within two years.
- Forty-five drugs, or 8.2%, had "black box" warnings added to their labels alerting physicians and patients to dangerous adverse reactions that could lead to serious injury or death. Fifty percent of adverse reactions were detected within seven years of approval.
- Seven drugs approved since 1993 and later withdrawn have been "reported as possibly contributing to 1,002 deaths." And almost 20 million Americans used at least one of five drugs banned between September 1997 and September 1998 (Grady, New York Times, 5/1).
Because many of the 548 drugs were approved recently, the authors used a probability analysis to estimate the number of future black box warnings and withdrawals. They estimated that 20% of all drugs would eventually be withdrawn or given a new black box warning within a 25-year period (Washington Post, 5/1).
Presenting the study findings at a press conference, Dr. Sidney Wolfe, director of the consumer organization Public Citizen's Health Research Group and a co-author of the report, said that doctors should prescribe new medications that represent "breakthroughs" in areas such as cancer and AIDS with confidence. But for drugs that have older and equally effective alternatives, such as obesity and anxiety treatments, patients should use the older versions until the efficacy of the drugs is proven, he said (Pelton, Baltimore Sun, 5/1). One reason that withdrawals and adverse reaction warnings can come many years after a drug is approved is that clinical trials are not large enough to capture all of a drug's side effects, which become apparent when millions of people start using a medication. Also, the study found that physicians report only 10% of adverse reactions to the FDA, inhibiting its ability to track drugs' side effects (Rubin, USA Today, 5/1). Wolfe said that drug companies contribute to the problem of withdrawals and warnings by "rushing ahead with approving and marketing lucrative new products" and through their heavy use of direct-to-consumer advertising, which "often give[s] the false impression that new drugs are better than older medications."
Both the FDA and the drug industry questioned the study's conclusions. In an accompanying JAMA editorial, Drs. Robert Temple and Martin Himmel of the FDA Center for Drug Evaluation and Research wrote, "It is incorrect to describe the introduction of unsafe drugs as frequent. If there is a sound reason to use a recently approved drug, the physicians need not deny the patient this treatment" (Baltimore Sun, 5/1). Temple said that most of the drugs cited in the study were in fact breakthrough medications, including AIDS, cancer and transplant treatments (USA Today, 5/1). He also said that many of the label changes cited "did not fundamentally change the way drugs were used," such as cases in which pregnant women were warned not to take a medication (Burling, Philadelphia Inquirer, 5/1). The Pharmaceutical Research and Manufacturers of America released a statement calling the study "misinformed and misleading," adding, "We note that [the authors] state that the benefit/risk ratio of new medicines sometimes shifts as new information is acquired after marketing, but they fail to state that it often shifts to the benefit side. For example, cholesterol-lowering drugs have been found after marketing to have significant additional benefits" (Washington Post, 5/1). Curtis Meinert, director of Johns Hopkins' center for clinical trials, questioned the study's recommendation that patients wait years before taking new, non-breakthrough drugs. If all doctors delayed prescribing a new drug, there would be no safety data to collect that could indicate potential side effects, thereby defeating the purpose of waiting to see if a drug is safe, he said (Baltimore Sun, 5/1). The study is available online. Temple's and Himmel's editorial is available online.