• James Heyward, Lily Olson, Joshua M Sharfstein, Elizabeth A Stuart, Peter Lurie, and G Caleb Alexander.
• Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
• JAMA Intern Med. 2020 Feb 1; 180 (2): 301-309.

ImportanceExtended-release/long-acting (ER/LA) opioids have caused substantial morbidity and mortality in the United States, yet little is known about the efforts of the US Food and Drug Administration (FDA) and drug manufacturers to reduce adverse outcomes associated with inappropriate prescribing or use. This review of 9739 pages of FDA documents obtained through a Freedom of Information Act request aimed to investigate whether the FDA and ER/LA manufacturers were able to assess the effectiveness of the ER/LA Risk Evaluation and Mitigation Strategy (REMS) program by evaluating manufacturer REMS assessments and FDA oversight of these assessments.ObservationsThe REMS program was implemented largely as planned. The FDA's goal was for 60% of ER/LA prescribers to take REMS-adherent continuing education (CE) between 2012 and 2016; 27.6% (88 316 of 320 000) of prescribers had done so by 2016. Audits of REMS programs indicated close adherence to FDA content guidelines except for financial disclosures. Nonrepresentative cross-sectional surveys of self-selected prescribers suggested modestly greater ER/LA knowledge among CE completers than noncompleters, and claims-based surveillance indicated slowly declining ER/LA prescribing, although the contribution of the REMS to these trends could not be assessed. The effectiveness of the REMS program for reducing adverse outcomes also could not be assessed because the analyses used nonrepresentative samples, lacked adequate controls for confounding, and did not link prescribing or clinical outcomes to prescribers' receipt of CE training. Although the FDA had requested studies tracking adverse outcomes as a function of CE training, the FDA concluded that these studies had not been performed as of the 60-month report in 2017.Conclusions And RelevanceFive years after initiation, the FDA and ER/LA manufacturers could not conclude whether the ER/LA REMS had reduced inappropriate prescribing or improved patient outcomes. Alternative observational study designs would have allowed for more rigorous estimates of the program's effectiveness.

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