Drug warnings can be risky, too, doctor says

Vioxx, the painkiller pulled from the market in 2004 after it was shown to double the risk of heart attack and stroke, has become the poster child for reforming drug-safety oversight. The 2007 Food and Drug Administration Amendments Act is intended to give the agency more authority to gather information about problems caused by drugs, before and after approval.

But what if the only safety data available comes from company-sponsored trials or small studies comparing competing drugs? That can mean the FDA is issuing warnings about drug side effects based on sometimes incomplete or unreliable data, Dr. Jerry Avorn of Harvard Medical School and Brigham and Women's Hospital writes in the New England Journal of Medicine.

He cites concern about case reports of suicide by patients taking anticonvulsant medications to control their seizures. The FDA asked the makers of 11 anticonvulsant drugs to turn over data from trials they had conducted. The pooled data showed that nearly two additional patients per thousand people would have suicidal thoughts or behaviors caused by the drugs. That is a real but modest effect, Avorn said, but one that needs to be balanced with the potential harm of not taking the drug.

FDA staff and an advisory committee couldn't agree on whether the evidence was strong enough to warrant a black-box warning -- the highest-level alert for physicians -- or just a mention on the label and in the medication guide for patients.

"The anticonvulsant-suicidality controversy reveals the limits of our capacity to ascertain adverse events in preapproval studies as well as the challenges inherent in risk communication and management," he writes. "Our current approaches require the FDA, clinicians, patients, and payers to make decisions about drug use in a data-poor environment."

The solution is to collect more rigorous data in trials before and after a drug is approved, Avorn suggests, or "settle for an unsatisfying mixture of unduly scary alarms and false reassurances."