Unmeasured confounding and misclassification in studies estimating vaccine effectiveness against hospitalisation and death using electronic health records (EHRs): an evaluation of a multi-country European retrospective cohort study

We observed some evidence of unmeasured confounding when using non-COVID-19 deaths as a negative outcome, though the specificity of our negative control must be considered. This result may suggest overestimation of VE, but also the need for further analysis with more specific negative control outcomes and confounding-adjustment techniques. Addressing such confounding using richer data sources and more refined approaches remains critical to ensure accurate, timely VE estimates based on retrospective cohorts constructed using registry data. Extending the delay between the end of observation and data extraction modestly improves the completeness of exposure and outcome data, with limited effect on pooled VE estimates.