In choosing which drugs to prescribe, doctors often select medications for patients despite a lack of conclusive medical evidence of their effects and safety, according to a new study led by a researcher at the Stanford University School of Medicine.
Of a wide sampling of prescriptions dispensed to patients in 2001, 21 percent were intended to treat medical conditions for which the drugs lacked specific approval from the U.S. Food and Drug Administration, though other published research suggested possible benefits. Furthermore, about three of every four of those prescriptions were for conditions for which there were little or no evidence of the drugs' effectiveness.
This practice of "off-label prescribing" offers doctors flexibility and innovation in treating patients but also carries unknown risks. The findings, which will be published May 8 in the Archives of Internal Medicine, are believed to be the first estimate based on a sizeable data base of the actual number of off-label prescriptions among the 100 most-used drugs and 60 other randomly-selected, commonly used medications.
The results show scientific evidence plays only a partial role in a physician's treatment decisions, said Randall Stafford, MD, PhD, associate professor of medicine at the Stanford Prevention Research Center and senior author of the study. Indeed, many doctors might be unaware if a drug has been FDA-approved for a specific use or how much research supports its use, he added.
"Many doctors prescribed a drug when there is little or no evidence supporting its efficacy and safety," Stafford said. "The study can't tell us why doctors prescribe drugs off label. Some uses are more reasonable than others, but, by definition, off-label uses receive less scrutiny than FDA-approved indications."
It is unclear how off-label uses become established within the medical community in cases where limited or no scientific evidence backs up their use. Informal communication between physicians, promising or preliminary scientific studies, and marketing by the pharmaceutical industry could play roles, Stafford commented.
Of course, just because a drug is unapproved by the FDA doesn't mean it's ineffective. The FDA approves drugs for treating specific indications only, and there are many reasons why a drug might not have been approved for treating a particular condition, Stafford said. Undergoing the trials necessary for approval, for instance, can be time-consuming and expensive. If a drug's patent has expired, a pharmaceutical company is unlikely to pursue approval for another indication.
What's more, many drugs belong to classes of pharmaceuticals that work in similar ways, though each might have different side effects. It would be logical to assume that a drug in a particular class would have the same effect as others in that class. Other off-label use may represent an extension of labeled uses or evolving new uses that have not been evaluated stringently. Greater caution is advised in such circumstances, Stafford said.
"These off-label uses have not been scrutinized the way FDA-approved uses have been," Stafford explained. "While this situation is more risky, some patients might have conditions where taking such risks might be warranted."
For patients with severe medical conditions, the potential benefits of treatment might outweigh the increased risk associated with off-label use. A physician might choose to prescribe a drug off-label to adjust for a patient's sensitivities, to avoid interactions with other drugs or to try a different approach if FDA-approved drugs haven't worked. While nothing prevents a doctor's prescribing a drug off-label, pharmaceutical companies are prohibited from directly promoting such uses.