August 27, 2009

Some Doctors in the Dark About Off-Label Drugs

A number of physicians erroneously believed that certain off-label uses of prescription drugs were approved by the Food and Drug Administration (FDA), according to a recent national survey. "Off-label use" refers to prescribing a drug for a purpose outside the scope of a drug's approved label.

The FDA makes it clear that they regulate the marketing of prescription drugs, not prescribing. The agency approves drugs for marketing with an official "label" that stipulates an indication, dose, intended population and duration of use. However, physicians and other licensed prescribers are free to prescribe any approved drug for any indication, whether or not the indication is included on the drug's FDA-approved label.

"Our research shows that some off-label prescribing might be driven by mistaken beliefs about FDA approval and the level of evidence supporting off-label drug use," G. Caleb Alexander, MD, MS, Assistant Professor of Medicine at the University of Chicago Medical Center and corresponding author of the research is quoted as saying. "The results indicate an urgent need for more effective methods of informing physicians about the level of evidence supporting off-label drug use"”especially for common off-label uses that are ineffective or carry unacceptable risks of harm."

The 2007-2008 survey of 1,199 physicians -- 599 primary care physicians and 600 psychiatrists -- included 22 drug-indication pairs. The indications varied in their FDA approval status from on-label use to off-label use supported by medical evidence to off-label use deemed to be ineffective.

Overall, physicians were able to correctly identify the FDA-approval status of just over half of the 22 drug-indication pairs -- i.e., a particular drug prescribed for a particular condition.

In many cases, the proportion of physicians who erroneously believed a particular drug was FDA approved for a specific use was higher among physicians who had prescribed the drug for that indication. For example, 26 percent of  physician respondents erroneously believed that lorazepam was FDA approved for chronic anxiety. That figure rose to 33 percent for physicians who had prescribed lorazepam for chronic anxiety.

Thirteen percent of physician respondents erroneously believed that quetiapine (Seroquel®) was FDA approved for dementia with agitation. That figure rose to 19 percent for physicians who had prescribed quetiapine for dementia with agitation. At the time of the study there was an FDA-advisory specifically urging caution regarding the off-label use of quetiapine in patients with dementia.
"Some physicians and health care experts maintain that physicians should know the evidence, not the FDA labeling. However, knowledge about FDA labeling can be important, because FDA approval of a drug for a specific indication indicates a clear threshold of evidence supporting that use," Donna Chen, MD, Assistant Professor of Biomedical Ethics, Public Health Sciences, and Psychiatry at the University of Virginia is quoted as saying.

A study by other investigators published in 2006 indicated that approximately 21 percent of drug uses in the United States occur for off-label purposes, with 73 percent of those cases lacking scientific evidence of the drug's effectiveness. The highest rates of off-label use were for anticonvulsants (74 percent), antipsychotics (60 percent) and antibiotics (41 percent).

"We hope our research will increase awareness of off-label prescribing and highlight the pressing need for more evidence-based use of prescription drugs," Alexander said. "Although some off-label uses are well-supported, many are not. New ways are needed to help physicians tap the scientific evidence supporting various prescription drug uses."

SOURCE: Pharmacoepidemiology and Drug Safety, August 21, 2009