Beyond aggregate estimates: stratified self-controlled case series analyses and insights into COVID-19 vaccine safety

Assessing vaccine safety profiles and potential adverse effects is fundamental to maintaining high safety standards and sustaining public confidence in vaccination programs, particularly in the context of vaccine hesitancy [Citation1,Citation2]. The self-controlled case series (SCCS) design is a key and widely used methodological approach for evaluating adverse events following vaccination [Citation3,Citation4]. SCCS offers a rigorous framework for assessing temporal associations between transient exposures and acute outcomes by comparing incidence rates within predefined risk and control periods in the same individual [Citation3,Citation4]. By relying on within-person comparisons, SCCS inherently controls for time-invariant confounders, such as genetic predisposition, underlying chronic conditions, and stable patterns of healthcare access, thereby enhancing internal validity [Citation3,Citation4]. These features make SCCS particularly well suited for vaccine safety assessments using routinely collected data in real-world populations [Citation5–7].