Keywords: ongoing aggregate safety evaluation, safety monitoring, safety profile
A Program Safety Analysis Plan (PSAP) has been used by some pharmaceutical companies for planning the analyses of aggregated safety data during product development. An enhanced program-level aggregate safety evaluation process has recently been developed with the ultimate goal of systematically characterizing the safety profile of a compound in an ongoing manner, beginning earlier in clinical development and continuing throughout the entire product life-cycle. This aggregate safety assessment process is a 2-tiered approach that involves a broad, cross-functional group of contributors (e.g., from Pharmacovigilance/Safety, Statistics, Late- and Early-stage Clinical Development, Epidemiology, Regulatory, etc.). The first tier focuses on authoring an aggregate safety assessment plan (AgSAP), an internal document that contains the high-level strategic planning for program-level, ongoing aggregate safety evaluation (OASE) and monitoring for a compound. The AgSAP may be updated at any time based on the evolving data and safety profile. The second tier focuses on documenting methods and technical implementation plans for each specific OASE. Each OASE may be performed using either blinded data aggregated across ongoing trials or with unblinded data aggregated across trials as they are completed. Multiple OASEs and types may be planned and performed based on emerging data and knowledge. Advantages of this new AgSAP approach include the following: improved collaboration and advanced planning for aggregate analyses of safety data; more comprehensive, cross-functional input; improved identification, documentation and understanding of important safety topics and populations of interest; and ongoing evaluation and communication of results to all key stakeholders. In summary, this approach will help improve the scientific evaluation of accumulating safety data and the ongoing characterization of the safety profile for compounds throughout their life-cycle.