Pragmatic applications of implementation science frameworks to regulatory science: an assessment of FDA Risk Evaluation and Mitigation Strategies (REMS) (2014\u20132018)

Linda Huynh,Gita A Toyserkani,Elaine H Morrato

doi:10.1186/s12913-021-06808-3

Abstract

BackgroundA Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program for certain medications with serious safety concerns required by the U.S. Food and Drug Administration (FDA) of manufacturers to implement to help ensure the benefits of the medication outweigh its risks. FDA is encouraging “the research community to develop novel methods for assessing REMS,” conveying the unmet need for a standardized evaluation method of these regulatory-mandated healthcare programs. The objective of this research is to evaluate FDA REMS assessment plans using established implementation science frameworks and identify opportunities for strengthening REMS evaluation.MethodsA content analysis was conducted of publicly available assessment plans for all REMS programs (N = 23) approved 1/1/2014–12/31/2018 for new drug applications (NDAs) and biologics license applications (BLAs) requiring FDA-mandated Elements to Assure Safe Use (ETASU). Blinded reviewers critically appraised REMS assessment measures (n = 674) using three established implementation science frameworks: RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance); PRECEDE-PROCEED (Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation – Policy, Regulatory, and Organizational Constructs in Educational and Environmental Development); and CFIR (Consolidated Framework for Implementation Research). Framework constructs were mapped to REMS Assessment categories as defined by FDA Guidance for Industry to evaluate congruence.ResultsREMS assessment measures demonstrated strong congruence (> 90% mapping rate) with the evaluative constructs of RE-AIM, PRECEDE-PROCEED, and CFIR. Application of the frameworks revealed that REMS assessment measures heavily emphasize implementation and operations, focus less on health outcomes, and do not evaluate program context and design assumptions.ConclusionsImplementation science frameworks have utility for evaluating FDA-mandated drug safety programs including the selection of primary measures to determine whether REMS goals are being met and of secondary measures to evaluate contextual factors affecting REMS effectiveness in varying organizational settings.

Highlights

A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program for certain medications with serious safety concerns required by the U.S Food and Drug Administration (FDA) of manufacturers to implement to help ensure the benefits of the medication outweigh its risks
Risk Evaluation and Mitigation Strategies (REMS) are a drug safety program required by the US Food and Drug Administration (FDA) for certain medications with serious safety concerns to help ensure that the benefits of a medication outweigh its risks [1]
A total of 23 REMS programs consisting of nine Biologics License Applications (BLA), nine new drug applications (NDAs), and five Shared Systems were selected for analysis based on the eligibility criteria (Additional file 3)

Summary

Introduction

A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program for certain medications with serious safety concerns required by the U.S Food and Drug Administration (FDA) of manufacturers to implement to help ensure the benefits of the medication outweigh its risks. Risk Evaluation and Mitigation Strategies (REMS) are a drug safety program required by the US Food and Drug Administration (FDA) for certain medications with serious safety concerns to help ensure that the benefits of a medication outweigh its risks [1]. REMS are required when additional strategies beyond product labeling are needed to reduce the occurrence and/or severity of a specific risk to reinforce the medication’s safe use conditions and behaviors [2]. In addition to ETASU, other REMS strategies include dissemination of information such as materials in patient-friendly language delivered to patients

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