Poster presented at the 38th Annual International Society for Pharmacoepidemiology Conference
Background: Using real-world data to assess COVID-19 vaccine safety is challenging due to evolving vaccine recommendations, potential incomplete capture of COVID-19 vaccines in data sources, and emerging safety signals.
Objective: To describe critical study design considerations in the design of a Pfizer-BioNTech COVID-19 vaccine postauthorization safety study (PASS) in the United States in a rapidly changing COVID-19 environment.
Methods: This PASS uses primarily claims data from partners in the Sentinel System, with a total source population of ~65 million people. Three study designs and their strengths and limitations were considered in the COVID-19 environment: cohort design with concurrent unexposed comparators, cohort design with historical comparators, and self-controlled risk interval (SCRI) design.
Key exposure-related considerations were potential incomplete capture of COVID-19 vaccines, multidose schedule, introduction of booster doses, potential high vaccine uptake, prioritizing of high-risk groups, and changing vaccine eligibility criteria over time. Key outcome-related factors were changing healthcare utilization during the pandemic, and relatively limited knowledge of the safety profile at study initiation, which led to including numerous safety events of interest and adding others with emerging safety signals.
Results: Contingent on completeness of COVID-19 vaccine data and availability of unexposed comparators, the study will use a cohort design with unexposed comparators as it is appropriate for both acute and nonacute events. Concurrent rather than historical comparators were chosen because changes in healthcare utilization during the pandemic could impact outcome ascertainment. Confounding will be addressed by matching exposed to unexposed comparators on time-specific propensity scores. To address potential misclassification of unexposed status, sensitivity analysis will incorporate a SCRI design and a cohort design with historical unexposed comparators.
Discussion: Flexibility is critical in designing this PASS for Pfizer-BioNTech COVID-19 Vaccine using real-world data. Although a cohort design with concurrent comparators is planned, the primary study design may be converted to SCRI (for acute events) and cohort with historical comparators (for nonacute events) if vaccine capture is incomplete or if there are insufficient unexposed comparators.
