(016) FDA REMS: Characterizing Burdens and Case Application of a Novel Integrated Ethical Framework

Background: FDA Risk Evaluation and Mitigation Strategy (REMS) programs aim to promote responsible use of certain medications with safety risk concerns. However, burdens on REMS participants – such as patients, health care providers, pharmacists, and healthcare institutions – persist. These burdens remain poorly characterized in the literature, and no ethical framework exists for the evaluation and reduction of REMS burdens.

Objectives: To inform the existing regulatory scientific gap, a novel integrated framework was developed for understanding the ethical implications of REMS burdens.

Methods: A literature search was conducted in February 2024 on three online databases (PubMed (MEDLINE), JSTOR, and Embase) using MeSH terms to scope for existing ethical frameworks specific to FDA REMS and program burdens. Relevant frameworks from Public Health (Kass, 6 main questions), Clinical Ethics (Jonsen et al., 4-quadrant method), and Health Equity (Dover and Belon, 21 domains) were identified, evaluated, and synthesized to inform a novel REMS ethical framework for assessing burden. The resulting model was tested using Clozapine REMS as a case example.

Results: None of the abstracts reviewed had any ethical frameworks to examine REMS burdens. The following domains were identified as relevant to REMS burden reduction based on analysis of key ethical frameworks: (1) Macro Legal Landscape, composed of existing policy that affects adequate implementation and provision of REMS; (2) Program-level Healthcare Delivery Factors, such as access to healthcare settings, available economic resources and patient experience of financial distress/toxicity, and related influences on health and participation in REMS; (3) Interpersonal Competing Interests and Preferences, between REMS participants; and (4) Individual Net Quality of Life, which includes individual benefit-risk assessment of medication safety and REMS participation as well as personal moral injury experienced by healthcare professionals and patient individual-level burdens due to provisionary gaps in care. Applying the Clozapine REMS program as a case example across these domains revealed that contextual and time-variant factors affect continuity of patient access and appropriate oversight of medication administration.

Conclusions: An integrated ethical framework that provides a systematic, structured approach for reflection and incorporation of participant perspectives may be integrated in routine REMS assessment reports for burden reduction. Application of this framework may facilitate a dynamic evaluation process that considers how risk management changes over time along with emerging scientific evidence within the broader socioecological and health policy landscape.