The 2021 IND safety reporting guidance highlights the importance of maintaining a Safety Surveillance Plan (SSP) that describes the approach for monitoring serious anticipated events requiring aggregate analysis. Decisionmaking for this approach needs to be supported by an ongoing systematic assessment of the product’s safety data from all sources. The Aggregate Safety Assessment Planning (ASAP) process empowers the multidisciplinary Safety Management Team (SMT) to plan and coordinate aggregate assessments of accumulating safety data across ongoing and completed trials throughout the product development life cycle. It strengthens cross-disciplinary communication and collaboration and facilitates a scientific evaluation of accumulating program-level safety data; to support ongoing characterization of the product safety profile and to prepare for regulatory filing activities and responses to regulatory queries.
The ASAP process provides the foundation for the aggregate analyses required by the SSP. Safety Topics of Interest (STOIs) facilitate the use of consistent safety endpoint definitions across studies in the program and ensure alignment between aggregate safety assessment and study level monitoring and evaluation of safety data. The more comprehensive ASAP specified outputs can inform IND reporting decisions by providing aggregate data about the occurrence of related nonserious adverse events or informative laboratory findings. Importantly, the STOIs requiring special data collection, monitoring, or analyses may assist in IND safety reporting decisions. The SSP could be a stand-alone appendix in the ASAPlanning document, which could be provided to FDA (separately, if requested) to show the sponsor processes for IND safety reporting decisions about SAEs from ongoing studies requiring aggregate analyses and possible unblinded review.