(A-032) REMS Registries: The Role They Play & How They Operate

Background: In 2007, FDA received authority to require a risk evaluation and mitigation strategy (REMS) for certain drugs with serious safety concerns to help ensure the benefits outweigh its risks. FDA may require a REMS registry as a strategy to support safe use and characterize long-term safety of a drug. Recent guidance for industry on use of real-world data from registries recommends “…assessing the reliability of registry data include whether the data were collected in accordance with the prespecified protocol.”

Objectives: To characterize REMS registries on the type and extent of data collection, including comparing registries with and without a submitted protocol, and to identify if REMS registries have informed regulatory decision-making.

Methods: A retrospective analysis of current REMS registries was conducted using 1) REMS@FDA data (publicly accessible website for REMS information) and 2) internal reviews and documents submitted by applicants to the FDA (2018-2024). Descriptive analysis of the characteristics of REMS registries for risks addressed, registry objective, enrollment type, data collection, and regulatory impact and comparison of registries with and without a protocol (i.e., discontinuation information, and statistical analysis) was conducted.

Results: A total of 17 REMS programs (14 drug moieties) with a registry were identified. The most common risk (n=8) was embryo-fetal toxicity, with voluntary enrollment pregnancy exposure registries. The remaining registries (n=9) had the objective of supporting safe use and may have also included further risk characterization. Seven of the 14 moieties had orphan designation.

Less than half (n=8) of the REMS registries had a protocol submitted. Of these, majority were pregnancy exposure registries with similar data collection protocols. All registries with a protocol included a statistical analysis plan of which three also included potential reasons for registry discontinuation while all registries without a protocol did not address this.

Registry data supported labeling changes for 2 REMS-covered products, which led to updated safety information in the Boxed Warning of the Prescribing Information. REMS registries (n=4) also supported post-marketing requirements by enabling patient recruitment and providing data

Conclusions: Registries to support safe use can be a valuable tool for risk characterization; however, challenges remain for utilizing registries to clarify safety concerns and provide surveillance. Despite the FDA recommending a prespecified protocol for registries as a factor of reliability, less than half of REMS registries had a protocol. Further research on best practices for REMS registries may be warranted.