A recent study recommends clinicians use caution when prescribing drugs for off-label uses that lack strong scientific evidence.

Off-label use of prescription drugs is a proven contributor to preventable adverse drug events (ADEs) in children, and this study confirms a similar association in adult patients. The study was published online ahead of print in JAMA Internal Medicine.1

The researchers analyzed data from a cohort of 46 021 patients who received 151 305 incident prescribed drugs, using the Medical Office of the XXIst Century electronic health record.

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Analysis was via multivariate marginal Cox proportional hazards regression for clustered data with the drug as the unit of analysis. Main outcome was ADEs in off-label use with and without strong scientific evidence.

The prescriptions were dispensed from January 1, 2005, through December 30, 2009, and follow up was from the date of prescription to the discontinuation of the drug, the end of treatment, or the end of follow-up (December 30, 2010).

Among the 46 021 study patients, a total of 3484 ADEs were found. Study results show rate of ADEs was higher for off-label use (19.7 per 10 000 person-months) than for on-label use (12.5 per 10 000 person-months).

Off-label use lacking strong scientific evidence (21.7 per 10 000 person-months) had a higher rate of ADEs; however, off-label use with strong scientific evidence had a similar rate of ADEs as on-label use.

Additional findings show the risks for ADEs were higher for drugs approved from 1981 to 1995, drugs used by women, patients receiving 5 to 7 drugs, and patients receiving cardiovascular drugs and anti-infectives (14.4, 14.3, 12.1, 15.9, 66.2, respectively, per 10 000 person-months). A 19% increase in ADEs was seen in patients with a 1-unit increase in the continuity of care index.

“Future electronic health records should be designed to enable postmarket surveillance of treatment indications and treatment outcomes to monitor the safety of on- and off-label uses of drugs,” recommend the researchers.


1. Eguale T, Buckeridge DL, Verma A, et al. Association of off-label drug use and adverse drug events in an adult population [published online ahead of print November 2, 2015]. JAMA Intern Med. Doi:10.1001/jamainternmed.2015.6058.