New Evidence That Off-Label Drug Use Increases Risk of Harm

Marketing drugs for uses that have not been approved by the Food and Drug Administration (FDA) — a practice known as off-label promotion — poses significant threats to patient and public health. This is particularly the case when there is a lack of evidence from well-designed clinical trials demonstrating that the medicine is safe and effective for the off-label use.

For many years, off-label promotion has been rife within the pharmaceutical industry. As documented in Public Citizen’s 2012 report, Pharmaceutical Industry Criminal and Civil Penalties: An Update, pharmaceutical companies since 1991 had paid more than $30 billion in penalties to federal and state governments to settle 239 cases involving charges of illegal conduct.[1] Unlawful promotion of drugs — which includes illegal off-label promotion — has resulted in the largest penalties. Just about every major pharmaceutical company has been found guilty of illegal off-label promotion, with many being repeat offenders.

A study published online in JAMA Internal Medicine in November 2015 provided new evidence of the dangers of off-label promotion.[2] Researchers examined medical records for a group of 46,000 patients in Quebec, who received a new drug prescription from 2005 through 2009. The researchers then determined whether the drug was prescribed for an approved use or an off-label use and whether the drug subsequently was stopped because of an adverse reaction. Patients were followed for up to six years.

The patients in the study received more than 151,000 new prescriptions. Twelve percent of the prescriptions were for an off-label use, and for 80 percent of these, strong scientific evidence from clinical trials supporting that use was lacking. Patients who received a prescription for an off-label use lacking such evidence were 54 percent more likely to experience an adverse drug reaction that resulted in stopping the drug than those who were prescribed a drug for an on-label use.

Drug companies increasingly have been challenging FDA rules prohibiting off-label promotion in federal courts, and, unfortunately, they often have found a sympathetic ear. Hopefully, evidence like that from the new Canadian study will prompt judges to give more deference to the FDA's arguments that off-label promotion threatens public health. Otherwise, companies will engage in ever-more-aggressive off-label marketing, and that will be bad for patients.

References

[1] Public Citizen. Pharmaceutical Industry Criminal and Civil Penalties: An Update. September 27, 2012. http://www.citizen.org/hrg2073. Accessed November 13, 2015.

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