Assessment of the U.S. Food and Drug Administration's risk evaluation and mitigation strategy (REMS) for prasugrel (EFFIENT): A narrative review.

Background: Prasugrel, first approved in 2009, was subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to mitigate the risk of bleeding associated with its use. Methods: We performed a narrative review of FDA documents obtained through a Freedom of Information Act request. Document classification and primary evidence extraction was performed by three authors (TM, JC, and SL). Results: The prasugrel REMS consists of a medication guide and a communication plan. Assessment of the REMS was via patient and clinician surveys. 1560 patients were invited to participate and 212 individuals (13.6 %) completed the survey. Rates of awareness among respondents varied across key messages and were highest for those examining the risks of premature discontinuation (96 % and 88 % of respondents), while lower for those regarding the importance of perioperative discontinuation (66 %) and contraindications posed by a history of stroke (16 %) or transient ischemic attack (17 %). Of the 6000 clinicians invited to participate in the survey, 201 (3.4 %) agreed to take part. Four of 11 key risk messages did not meet prespecified acceptable levels of comprehension. No prespecified levels of patient or provider knowledge were required for the retirement of the REMS, which took place on March 23, 2012 based on the sponsor's request. Conclusions: The prasugrel REMS consisted of passive educational materials whose adequacy was evaluated using highly limited, one-time, cross-sectional surveys. Our assessment adds to evidence suggesting the importance of improving the quality and impact of the FDA's post-approval activities to maximize drug safety.