The off-label use of prescription drugs is common and legal but not necessarily risk-free. A patient's risk of suffering an adverse event, according to a new study, is 44% higher when they're prescribed drugs in ways that diverge from their originally approved use.
About 80% of the nearly 18,000 off-label prescriptions studied were given despite a lack of strong scientific evidence supporting the non-approved uses. Whether or not off-label support data existed, however, the rate of adverse events remained high, according to the findings published Monday in JAMA Internal Medicine.
Better tracking is needed to systematically gauge the real-world impact of off-label drug use, said lead researcher Dr. Tewodros Eguale, formerly of the McGill University in Montreal, Canada. “We have to at least monitor what's going on,” he said, noting that not all electronic health record systems require physicians include the clinical purpose for a prescription.
The system used in Canada allowed for such tracking. Researchers analyzed electronic health-record data for a total 46,021 patients prescribed 151,305 drugs at primary care clinics between January 2005 and December 2009. Patients were followed from the date the prescription was dispensed until either the drug's use was discontinued or through the end of 2010.
The findings may add fuel to an already heated debate over prescription drug marketing in which some safety advocates are seeking stricter requirements. While doctors can prescribe drugs off-label, the Food and Drug Administrations prohibits marketing by drug manufacturers for off-label uses. Still, it is still not an uncommon tactic to boost sales amid expiring patents. When a New York federal judge cited freedom-of-speech in an August ruling that determined the FDA cannot bar “truthful” off-label marketing, critics feared laws were becoming too lax.
There are many clinical circumstances for which an off-label prescription is best for a patient. But in many cases when clinicians move “beyond the carefully devised confines of the labeled indication, they enter an arena of the unknown,” according to an accompanying commentary in JAMA Internal Medicine by University of Pittsburgh researchers Dr. Chester Good—also co-director of the department of Veteran Affairs' Center for Medication Safety—and Dr. Walid Gellad of the Center for Health Equity Research and Promotion.
They note ongoing concerns over subpar post-market surveillance for flagging adverse events. Safety leaders argue voluntary reporting systems do not provide the rigorous tracking needed to capture adverse events before problems become widespread. It takes years of evidence collection before warnings are issued about treatments which millions of patients already use.
Hood and Gellad point out that even in situations where an off-label indication has been studied, drug interactions and other safety issues are not likely to have undergone the same rigorous level of study as required during the approval process.
“These circumstances threaten the safe, effective and informed use of medications by patients,” they wrote. The new study provides “compelling evidence that off-label prescribing is frequently inappropriate.”
