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 in the UK. A questionnaire was sent to participants from the first published TNCC COVID-19 vaccine effectiveness 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 08/12/2020 and 21/02/2021. A questionnaire was sent to cases and controls tested from 1–21 February 2021. In this study, 8648 individuals responded to the questionnaire (36.5% response). Using information from the questionnaire to produce a combined estimate that accounted for all potential biases decreased the original vaccine effectiveness estimate after two doses of BNT162b2 from 88% (95% CI: 79–94%) to 85% (95% CI: 68–94%). Self-reported behaviour demonstrated minimal evidence of riskier behaviour after vaccination. These findings offer reassurance to policy makers and clinicians making decisions based on COVID-19 vaccine effectiveness TNCC studies.

Test-negative case control studies have been widely used to estimate COVID-19 vaccine effectiveness, but the accuracy of estimates may be impacted by bias and unmeasured confounding. Here, the authors investigate the these impacts by collecting additional data from individuals included in the first UK COVID-19 test negative study.