Comparison of Signal Detection and Evaluation Study Designs to Inform Development of the Pregnancy Safety Framework

On September 30, 2022, the President signed into law the FDA User Fee Reauthorization Act of 2022. This new law includes the sixth reauthorization of the Prescription Drug User Fee Act (PDUFA) that provides FDA with the necessary resources to maintain a predictable and efficient review process for human drug and biologic products. FDA committed to the “Enhancement and modernization of the FDA drug safety system.” The enhancement and modernization include the development of a consistent and transparent approach to help decide when and what postapproval pregnancy safety studies might optimally be used to obtain timely evidence of safety for regulatory decision making.

In the September 2023 Public Workshop, FDA presented a preliminary framework addressing how to select viable and optimal study approaches in various scenarios. As a follow-up, the Sentinel System will conduct three demonstration projects to inform this pregnancy framework and address gaps in knowledge about performance characteristics of different study approaches. Through the use of existing pregnancy registry data and electronic healthcare data, project one compares signal detection study approaches when the exposure to medication in pregnancy is relatively common, project two compares signal evaluation study approaches when the exposure to medication in pregnancy is relatively common, and project three compares signal detection approaches when the exposure to medication in pregnancy is relatively low. The projects collectively have four aims: 1) protocol development, 2) data acquisition, 3) analysis execution, and 4) dissemination.