Assessing the Performance of Major Congenital Malformations as a Composite Outcome in Signal Detection and Evaluation

On September 30, 2022, the President signed into law the FDA User Fee Reauthorization Act of 2022. This 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 an effort to optimize the Sentinel Initiative and describe a focus on supporting FDA’s monitoring of safety of medical products during pregnancy.

As part of these enhancements, FDA is developing a framework addressing how to optimize use of postapproval pregnancy safety studies. The Sentinel System is conducting six demonstration projects to inform this pregnancy framework and address gaps in knowledge about performance characteristics of different study designs. Project four aims to assess the performance and usefulness of major congenital malformations (MCM) as a composite outcome in signal detection and signal evaluation when there is true risk for some but not all specific malformations.