“Various academics within our University are strongly against our position of promoting off-label prescribing of DMTs to pwMS in resource-poor settings; the most outspoken person being Professor Allyson Pollock. If any of you have met Allyson, and debated with her, you simply don’t want to be in her firing line. The paper below highlights yet another issue with off-label prescribing, preventable serious adverse events (ADEs), which supports her, and her department’s, position. The study below using electronic patient records shows that preventable adverse drug events (ADEs) are more common with off-label prescribing compared to on-label prescribing. What protects our position, apart from the unmet need, is that ADEs in relation to off-label use with strong scientific evidence had a lower ADE rates than off-label use lacking strong scientific evidence. The latter depends on if you agree with our position on the evidence supporting off-label use of DMTs. Please keep in mind that the majority of pwMS in resource poor settings, for whom we are recommending off-label DMTs, are not on any DMT; in other words they are left to ravages of MS. When prescribing DMTs you also need to consider what the impact of untreated MS is. What does the natural history of MS look like? My infographic below tries to capture the headlines in relation to the impact of MS. The data on which this infographic is based is from studies in resource-rich countries. I suspect the impact may be worse in resource poor settings where there are no social safety nets. I have stated many times in the past that if I worked in a resource-poor setting I would have no hesitation in using cheaper off-label drugs to treat MS. At the end of the day I would have a commitment to look after pwMS with the best tools at hand and with the evidence at hand. I would still treat-2-target of NEDA, simply using different DMTs.”
IMPORTANCE: Off-label use of prescription drugs has been identified as an important contributor to preventable adverse drug events (ADEs) in children. Despite concerns regarding adverse outcomes, to date, no systematic investigation of the effects of off-label drug use in adult populations has been performed.
OBJECTIVE: To monitor and evaluate off-label use of prescription drugs and its effect on ADEs in an adult population.
DESIGN, SETTING, AND PARTICIPANTS: A cohort of 46 021 patients who received 151 305 incident prescribed drugs was assembled from primary care clinics in Quebec, Canada, using the Medical Office of the XXIst Century electronic health record, which supports documentation of treatment indications and treatment outcomes. Prescriptions dispensed from January 1, 2005, through December 30, 2009, were followed up from the date of the prescription to the date the drug use was discontinued, the end of treatment, or the end of follow-up (December 30, 2010). Data were analyzed from January 5, 2012, to March 15, 2015.
EXPOSURES: Off-label prescription drug use with and without strong scientific evidence.
MAIN OUTCOMES AND MEASURES: Adverse drug events in off-label use with and without strong scientific evidence. Analysis used multivariate marginal Cox proportional hazards regression for clustered data with the drug as the unit of analysis.
RESULTS: A total of 3484 ADEs were found in the 46 021 study patients, with an incidence rate of 13.2 per 10 000 person-months. The rate of ADEs for off-label use (19.7 per 10 000 person-months) was higher than that for on-label use (12.5 per 10 000 person-months) (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.30-1.60). Off-label use lacking strong scientific evidence had a higher ADE rate (21.7 per 10 000 person-months) compared with on-label use (AHR, 1.54; 95% CI, 1.37-1.72). However, off-label use with strong scientific evidence had the same risk for ADEs as on-label use (AHR, 1.10; 95% CI, 0.88-1.38). The risks for ADEs were higher for drugs approved from 1981 to 1995 (14.4 per 10 000 person-months; AHR, 1.62; 95% CI, 1.45-1.80) and for those used by women (14.3 per 10 000 person-months; AHR, 1.17; 95% CI, 1.06-1.28), patients receiving 5 to 7 drugs (12.1 per 10 000 person-months; AHR, 3.23; 95% CI, 2.66-3.92), and patients receiving cardiovascular drugs (15.9 per 10 000 person-months; AHR, 3.30; 95% CI, 2.67-4.08) and anti-infectives (66.2 per 10 000 person-months; AHR, 6.33; 95% CI, 4.58-8.76). Patients with a 1-unit increase in the continuity of care index had a 19% increase in ADEs (AHR, 1.19; 95% CI, 1.12-1.26).
CONCLUSIONS AND RELEVANCE: Off-label use of prescription drugs is associated with ADEs. Caution should be exercised in prescribing drugs for off-label uses that lack strong scientific evidence. 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.