Abstract
Background: Risk Evaluation and Mitigation Strategies (REMS) are safety programs that U.S. Food and Drug Administration can require to ensure a drug's benefits outweigh its risks and can be considered public health interventions. FDA's 2019 draft Guidance for Industry on REMS Assessments encourages the development of “novel methods for assessing REMS [to] help advance the science of post-market assessment of effectiveness of risk mitigation strategies.”Objective: To characterize REMS assessment plans using RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework and identify areas for advancing methods for evaluating REMS programs. RE-AIM was selected for its wide application evaluating the translation of scientific advances into practice for public health impact.Methods: A content analysis of REMS assessment plans (N = 18) and measures(n = 540) was conducted for REMS programs approved by FDA between 1/1/2014–12/31/2018. Eligibility criteria were: a new drug application or biologic license application, included FDA-mandated mitigation strategies called elements to assure safe use (ETASU), and represented a single product REMS program. Assessment plans were collected from publicly available regulatory approval letters from REMS@FDA website. Blinded reviewers categorized each REMS assessment measure to a RE-AIM dimension, adjudicated their application (average IRR 75%), and refined the adapted dimensions' definitions. Dimensions were also mapped to REMS Assessment guidance categories.Results: The median number of assessment measures per REMS assessment plan was 31 (IQR: 21–36). Frequency of measures per RE-AIM criteria per REMS program was: Reach (median = 2; IQR: 2–4); Effectiveness (median = 2.5; IQR:1–4); Adoption (median = 3.5; IQR: 2–5); Implementation (median = 18; IQR: 15–24); Maintenance (median = 0; IQR: 0–1). Adoption (among prescriber, health system agents of implementation) was more commonly assessed than Reach (population-attributable number of patients affected). Assessment of heterogeneity of Adoption and Reach was generally absent. Implementation assessment measures were most common among drugs requiring evidence of safe-use conditions before dispensing or administering the drug. Patient-level Effectiveness and Maintenance assessments were most common among drugs requiring patient monitoring.Discussion: Implementation science frameworks, such as RE-AIM, can be applied to characterize REMS assessment measures and identify opportunities for standardizing and strengthening their evaluation. Methods to measure Maintenance are needed to provide real-world evidence of REMS integration into the healthcare system.
Highlights
The U.S Food and Drug Administration (FDA) is responsible for protecting the public health of Americans by assuring the safety and efficacy of human drugs and biological products [1]
Shared system Risk Evaluation and Mitigation Strategies (REMS) were excluded because we wanted to focus on new programs, and shared system REMS programs reflect sustaining programs that have been adapted for generic products
The drug products carried a variety of risks intended to be mitigated by the REMS, ranging from cancers such as lymphoma and osteosarcoma, immune system disorders such as autoimmune conditions and cytokine release syndrome, and psychiatric disorders such as suicidal ideation and behavior
Summary
The U.S Food and Drug Administration (FDA) is responsible for protecting the public health of Americans by assuring the safety and efficacy of human drugs and biological products [1]. Over the past two decades, modernization of post marketing drug safety and risk management has received increasing attention [2, 3]. The Food and Drug Administration Amendments Act (FDAAA) of 2007 granted FDA authority to require risk evaluation and mitigation strategies (REMS) to ensure that the benefits of a drug outweigh its risks [6]. Risk Evaluation and Mitigation Strategies (REMS) are safety programs that U.S Food and Drug Administration can require to ensure a drug’s benefits outweigh its risks and can be considered public health interventions. FDA’s 2019 draft Guidance for Industry on REMS Assessments encourages the development of “novel methods for assessing REMS [to] help advance the science of post-market assessment of effectiveness of risk mitigation strategies.”
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