Bias assessment of a test-negative design study of COVID-19 vaccine effectiveness used in national policymaking

Abstract National test-negative-case-control (TNCC) studies are used to monitor COVID-19 vaccine effectiveness (VE) in the UK. A questionnaire was sent to participants from the first published TNCC COVID-19 VE study conducted by the UK Health Security Agency, to assess for potential biases and changes in behaviour related to vaccination. The original study included symptomatic adults aged ≥70 years testing for COVID-19 between 8 December 2020 and 21 February 2021. The questionnaire was sent to cases and controls tested from 1-21 February 2021. 8,648 individuals responded to the questionnaire (36.5% response). Self-reported timing of vaccination and infection onset was consistent with routinely recorded data. Additional adjustment of vaccine effectiveness estimates for high-risk conditions and household size or type found no evidence of confounding by these factors. Self-reported behaviour demonstrated some deferral of vaccination while unwell, but no or minimal evidence of riskier behaviour after vaccination. These findings offer reassurance to policy makers and clinicians making decisions based on COVID-19 VE TNCC studies.