Real-Time Pharmacovigilance: Transforming Population-Based Monitoring of Post-Approval Vaccine Safety Through Rapid Cycle Analysis (RCA)-A Review of the Published Literature.

Abstract

Background/Objectives: Rapid cycle analysis (RCA) is an established and efficient methodology that has been traditionally utilized by United States health authorities to monitor post-approval vaccine safety. Initially developed in the Vaccine Safety Datalink (VSD) in early 2000s, RCA has evolved into a valuable approach for timely post-approval signal detection. Due to the availability of additional near real-time data sources and enhanced analytic approaches, the use of RCA has expanded. This narrative review provides an in-depth assessment of studies that utilized RCA for safety surveillance to detect and evaluate safety signals in post-approval vaccine monitoring. Methods: Embase and Medline were searched on 8 August 2024 to identify post-approval non-interventional vaccine safety studies using RCA or other near real-time surveillance methods published from 1 January 2018 to 31 July 2024. Data on study characteristics (e.g., study population, data source, outcomes) and RCA methodological characteristics (e.g., type of comparator, sequential testing method, confounding control method) were extracted from the eligible RCA studies. Results: Of 1128 articles screened, 18 RCA vaccine safety studies were included, of which 17 (94.4%) were conducted in the United States (US). Twelve (67%) aimed at signal detection and six (33%) conducted further signal evaluation. Over 60% examined COVID-19 vaccine safety, with half using VSD. Over 80% conducted the RCA weekly or monthly and about 78% of the studies used a database-specific historical comparator group. Conclusions: This review indicates that most of the published articles on the application of the RCA methodology in vaccine safety studies are based on research conducted in the US. With increasing availability of near real-time data sources and advanced analytic methods capabilities, RCA is expected to be more widely deployed as an active surveillance tool to complement traditional pharmacovigilance. Future studies should explore the extension of vaccine RCA methodology for non-vaccine medicinal products.