Anyone who’s been prescribed a drug at a doctor’s office has wondered, “But why this particular medicine?”
According to a recent study led by Randall S. Stafford of the Stanford School of Medicine, doctors often select medications without adequate research on their effectiveness and safety.
When the Food and Drug Administration (FDA) approves a medication, it approves it for specific indications and uses.
However, “It is well-known that medications are often used for conditions or diseases not covered by the FDA indication,” Stafford said in an interview with The Daily. “We term that use ‘off-label.’”
In an analysis of the top 100 drugs prescribed and 60 other commonly-used, randomly-selected drugs, Stafford found that 21 percent of prescriptions were off-label.
Off-label prescribing — while offering doctors flexibility and innovation in treating patients — may carry unknown risks. Furthermore, Stafford explained that there are several different types of off-label prescribing.
“Some of these uses are virtually standard practice but for one reason or another, the FDA has not approved them for a secondary indication,” he said. “On the other hand, there are other off-label uses which often are based off scant information, where we have concerns about the safety and efficacy of these drugs.”
In these cases, Stafford determined that three-quarters of the off-label uses lacked substantial scientific data to support the drug’s use.
This means that the vast majority of prescribing physicians lacked strong scientific evidence to justify the medicine’s use for that specific purpose, he said.
Stafford is quick to point out, however, that FDA approval is not the be-all-end-all on the appropriateness of a drug’s prescription. Sometimes, drug companies are reluctant to undergo the expensive process of gaining FDA approval for secondary uses of a drug — particularly if its use for such purposes is already prevalent. In addition, if a drug has gone to generic production, it lacks a “corporate advocate” who has the resources to go back to the FDA for additional approval.
According to Stafford, this means that both physicians and patients are now “practicing in an area where they have less data to provide reassurance that the drugs are safe and effective.”
In recent years, there have been significant problems even with FDA-approved drugs. For example, in 2004 the administration recalled the prescription drug Vioxx due to safety concerns.
Stafford pointed out that in such cases, there had been “rigorous review” because of the need for FDA approval. But in considering off-label prescriptions, even less information exists, and the same concerns about effectiveness and safety persist. Stafford added that there is a “misperception that the newest drug is the best drug.”
Stafford emphasized that his study does not discourage off-label prescribing altogether. He said he believes that if physicians have tried standard therapy first and the patient seems unresponsive, then off-label prescribing can be a reasonable and innovative solution to the problem.
“Some types of off-label uses are beneficial, giving physicians the opportunity to innovate and solve difficult clinical problems,” he added.
Stafford’s study appeared on May 8 in the Archives of Internal Medicine and was conducted in collaboration with David C. Radley of Dartmouth Medical School’s Center for Evaluative Clinical Sciences and Stan N. Finkelstein of the Massachusetts Institute of Technology.