P-1949. The Self-Controlled Risk Interval: An Evolving Method for Vaccine Effectiveness Estimation in Complex Real-World Data

Abstract Background Post-marketing assessments of vaccine effectiveness (VE) are critical to informing health policy, understanding real-world vaccine performance, and ensuring confidence in vaccination efforts, though imperfect comparator groups can limit the accuracy of VE assessments. The self-controlled risk interval (SCRI) design, a case-only analytic method historically used in safety studies, controls for time-invariant confounding using within-person comparisons and has recently been used to assess VE. This targeted review identifies and characterizes SCRI’s growing role in VE research.Table 1:Vaccine Effectiveness Studies that Used the Self-Controlled Risk Interval Design Methods Targeted database searches were conducted in Medline, Embase®, Embase Preprints, and BIOSIS Previews®, and the preprint servers: medRxiv, preprints with The Lancet, and Research Square. Key terms (and related variations) included: vaccine effectiveness, COVID-19 vaccines, and self-controlled risk interval. Results Two VE studies that used the SCRI design were identified (Table 1). Both were retrospective database studies (one using electronic health records and the other insurance claims data), evaluated SARS-CoV-2 infection, and used similar post-vaccination control windows, but featured different post-vaccination risk windows and were conducted among notably different populations. An additional 10 identified studies included post-vaccination person-time in the comparison group but did not make within-person comparisons to address important potential confounding, acknowledging that post-vaccination benefits are not appreciated immediately. These studies varied in the study populations, outcomes assessed, comparison group composition, and analytic methods. Conclusion Use of SCRI for VE estimation has been limited; however, the increasing inclusion of post-vaccination control arm person-time in other COVID-19 VE studies merits the broadening of its application. The results of this review suggest that, in the context of COVID-19, SCRI VE evaluation is a promising tool where there are no suitable comparison groups, increasingly complex individual backgrounds (e.g., infection history, number and timing of doses, or heterologous vaccination), or insufficient information for confounding control. Disclosures Jonathan Fix, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Hadi Beyhaghi, MD, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Matthew D. Rousculp, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)