AUTHOR=Toyserkani Gita A. , Huynh Linda , Morrato Elaine H. 

TITLE=Adaptation for Regulatory Application: A Content Analysis of FDA Risk Evaluation and Mitigation Strategies Assessment Plans (2014–2018) Using RE-AIM

JOURNAL=Frontiers in Public Health

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2020.00043

DOI=10.3389/fpubh.2020.00043

ISSN=2296-2565

ABSTRACT=<p><bold>Background:</bold> 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 <italic>draft Guidance for Industry on REMS Assessments</italic> encourages the development of “novel methods for assessing REMS [to] help advance the science of post-market assessment of effectiveness of risk mitigation strategies.”</p><p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> A content analysis of REMS assessment plans (<italic>N</italic> = 18) and measures(<italic>n</italic> = 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 <italic>REMS Assessment guidance</italic> categories.</p><p><bold>Results:</bold> 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.</p><p><bold>Discussion:</bold> 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.</p>