In 2005, CIOMS VI (Management of Safety Information from Clinical Trials) started to bridge the gap between pre- and post-approval activities to understand and manage risk. Pharmacovigilance had traditionally focused on detection and evaluation of signals in the post-approval environment to secure early detection of new adverse reactions or high risk subgroups, and to introduce measures to manage those risks. They called for sponsors to develop a process to assess, evaluate, and act upon safety information on a continuous basis throughout development. A systematic, reproducible approach to detect, classify, and document AEs would enable sponsors and investigators to develop clinical as well as statistical understanding of the safety profile.
CIOMS VI provided the basis for the Program Safety Analysis Plan (PSAP). PhRMA Safety Planning, Evaluation and Reporting Team (SPERT) proposed the PSAP as a tool to proactively plan for meta-analysis of the program safety data for new product submissions and during early post-marketing. They provided recommendations for the planning of repeated, cumulative meta-analyses of the safety data obtained from the studies conducted within the development program.
More recently the DIA-ASA Interdisciplinary Safety Evaluation (DAISE) scientific working group (now one of the Safety working groups of ASA Biopharm) has developed the Aggregate Safety Assessment Planning (ASAP) process, which builds on the PSAP and addresses the IND safety reporting final rule. It describes the operational framework within which accumulating safety data are to be monitored and strengthens cross-disciplinary communication and collaboration. It enables ongoing recognition and prioritization of key safety topics of interest and characterization of the emerging safety profile for a given compound; planning and execution for ongoing aggregate monitoring (including for blinded trials), especially focused on these topics of interest; preparation for regulatory filing activities and responses to regulatory queries; and consistent and authoritative communication of the safety story in scientific evaluations and public disclosures. Also, importantly, it streamlines the process – saving time, energy, and resources.