Enhancing REMS program evaluations: A strategic approach for life sciences partners

Moving from compliance to competitive advantage

Risk Evaluation and Mitigation Strategy (REMS) programs are FDA-mandated safety programs required of manufacturers of certain high-risk medications. These programs aim to ensure that the therapeutic benefits of a drug outweigh its risks by outlining safe use conditions and often require the development and use of educational materials such as medication guides (MGs) or patient counseling guides (PCGs).

Despite their regulatory importance, many REMS programs face well-documented challenges when it comes to effective implementation, stakeholder adoption, and real-world impact. At Carelon Research, we partner with life sciences organizations to evaluate complex programs such as REMS by applying scientific knowledge and rigor to real-world data.

The value of the REMS logic model

Logic models offer a structured, conceptual framework to make programmatic design assumptions explicit and identify relevant measures that evaluate the outcomes and impact of the program. The FDA introduced a REMS logic model in 2024 to help stakeholders design and evaluate future REMS programs more effectively. This article highlights the REMS logic model as a useful tool to help visualize which components are contributing to progress and where strategic adjustments may be needed in the Opioid Analgesics REMS (OA REMS) program.

Risk evaluation and mitigation strategies (REMS) logic model

Toyserkani, G.A., Robottom, S.B. & Morrato, E.H. REMS Logic Model: A Pragmatic Framework for Incorporating Drug Safety into Clinical Practice. Drug Saf 48, 715–718 (2025). DOI: 10.1007/s40264-025-01542-9.

Case study: Opioid analgesic REMS survey study

Since 2014, Carelon Research has conducted five REMS knowledge surveys for the OA REMS program assessing the knowledge of opioid pain medications among patients prescribed opioid analgesic medications and their caregivers.

As part of the REMS logic model, identifying the primary goal of the program is an important part of program planning. The primary goal of the OA REMS program is to educate patients about the serious risks and safe use of opioid analgesics. In order to achieve this goal, MGs are provided by pharmacists with every prescription fill and PCGs are provided to clinicians for use with their patients to support communication about the safe use and disposal of these drugs.

In collaboration with Clinical Directors Network, Inc., we surveyed more than 1,070 respondents across Medicare Advantage, commercially insured, and Medicaid populations and their caregivers. We constructed a survey instrument based on the material in the MG and PCG and tested the questions with a small sample of patients for clarity.

While the average patient knowledge score (79% correct answers) approached the prespecified success threshold of 80%, our findings highlighted critical knowledge gaps around safe medication disposal and overdose response. Respondents correctly answered 59% of questions about storing the drug in a safe place, and only 56% of questions about what to do if they take too much drug.

The REMS logic model emphasizes the iterative nature of program improvement, and the sequential steps needed to improve the processes. A new OA REMS modification was recently implemented to include mail-back envelopes for safe medication disposal. An additional opportunity exists for improvement in patient knowledge of existing tools that are safe and effective at reversing opioid overdose.

These results gave our life sciences partners not just an assessment of current REMS effectiveness, but a strategic path forward on where to enhance patient education to maximize patient safety.

Collaboration for smarter REMS strategies

REMS programs have evolved — and so must the way we evaluate and optimize them. The FDA logic model provides an actionable roadmap for implementing and evaluating REMS programs and improving safety outcomes.

Carelon Research is proud to serve as a trusted research and strategy partner to the life sciences industry. We help organizations navigate REMS program complexity with confidence, ensuring their safety commitments are not only met but meaningfully measured.

See the results from the most recent REMS knowledge survey for the Opioid Analgesic REMS program presented at ISPE 2025 in Washington, D.C.

Sunday, August 24, 2025
12:00 - 1:30 PM
(A-019) Patients’ and Caregivers’ Understanding of the Serious Risks of Opioid Analgesics and How to Use These Products Safely: A Patient/Caregiver Survey 

References for further reading
Carelon Research authors are inidicated in bold.

Cepeda MS, Coplan PM, Kopper NW, Maziere JY, Wedin GP, Wallace LE. ER/LA Opioid Analgesics REMS: Overview of ongoing assessments of its progress and its impact on health outcomes. Pain Med 2017 Jan 1;18(1):78-85. DOI: 10.1093/pm/pnw129.

Esposito DB, Desai VCA, Stephenson JJ, Cepeda MS, Lyons JG, Holick CN, Wedin GP, Lanes S; members of the REMS Program Companies Metrics Subteam. Patient knowledge of safe use of ER/LA opioid analgesics following Implementation of the class-wide REMS: A survey study. Patient Prefer Adherence 2021 Feb 24; 15:431-442. DOI: 10.2147/PPA.S286935. 

Huynh L, Toyserkani GA, Morrato EH. Pragmatic applications of implementation science frameworks to regulatory science: an assessment of FDA Risk Evaluation and Mitigation Strategies (REMS) (2014–2018). BMC Health Serv Res 2021; 21:779. DOI: 10.1186/s12913-021-06808-3.

Toyserkani GA, Robottom SB, Morrato EH. REMS logic model: A pragmatic framework for incorporating drug safety into clinical practice. Drug Saf 2025 Jul; 48(7):715-718. DOI: 10.1007/s40264-025-01542-9.

Toyserkani GA, Huynh L, Morrato EH. Adaptation for regulatory application: A content analysis of FDA Risk Evaluation and Mitigation Strategies assessment plans (2014-2018) using RE-AIM. Front Public Health. 2020 Feb 25; 8:43. DOI: 10.3389/fpubh.2020.00043.

U.S. Food and Drug Administration. REMS logic model: a framework to link program design with assessment. Guidance for industry DRAFT GUIDANCE. Office of Communications, Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration. Silver Spring, MD. May 2024.