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On the record about off-label drug use

By Jennifer Durgin

When a doctor says "take two and call me in the morning," patients tend to assume there's sound evidence backing up the recommendation. But that may not be the case, according to a study led by David Radley, M.P.H., a Ph.D. student at DMS's Center for the Evaluative Clinical Sciences.

Uses: Using a national database, Radley and colleagues analyzed 725 million prescriptions written in 2001. They found that 79% were for uses approved by the Food and Drug Administration (FDA), while 21% were "off-label"—for uses not approved by the FDA.

Off-label prescribing is not necessarily cause for alarm, notes a DMS pharmacologist. "A lot of the time, using a drug in a way that's not FDA-approved is very good treatment," says David Nierenberg, M.D, who was not involved in the study. But there must be "good papers in the peer-reviewed journals that are unbiased that show that the drug is safe and effective" for the off-label use. Herein lies the most disconcerting finding of Radley's study.

Of the 725 million prescriptions he analyzed, 15% were written without evidence of safety or effectiveness. In other words, these drugs were not approved by the FDA for the condition they were prescribed for and there were few or no reports in the scientific literature supporting the use. Psychiatric and allergy drugs were the most common ones in this category. "This issue of sneaking off of FDA approval into another area can be very dangerous," observes Nierenberg.

"By definition, off-label uses receive less scrutiny then labeled ones do," Radley says. "This doesn't mean that all of them are bad. This doesn't mean that they are not carefully considered by the physician prescribing the drug. But it does imply that off-label uses may carry greater unknown risks compared to approved uses."

Concerns about patient safety are what first inspired Radley to begin researching prescribing patterns, when he was an M.P.H. student at Yale. Although his study—published in Archives of Internal Medicine—does not assess patient safety, it provides a foundation for further inquiry. "Our study was innovative in that it was the first" to comprehensively examine off-label prescribing, says Radley.

He is also concerned about the wastefulness of prescribing practices with little or no scientific evidence. "The efficiency with which we provide care," says Radley, "is something that everybody should be thinking a lot about."

To address both concerns, he and his coauthors call for "more extensive postmarketing surveillance to identify non-evidence- based prescribing practices that lack FDA approval."

Evidence: And at the individual level, Radley encourages patients to ask their doctors about the evidence behind prescriptions they write. "Patients should be asking their doctors, 'Is this going to work for me? Is it going to put me at risk?' " Radley advises. "That holds not just for off-label medication use, but for all medication use."

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