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

Sophie Graham*, Elise Tessier, Julia Stowe, Jamie Lopez Bernal, Edward P.K. Parker, Dorothea Nitsch, Elizabeth Miller, Nick Andrews, Jemma L. Walker, Helen I. McDonald

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3984
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
This work uses data provided by patients and collected by the NHS as part of their care and support ( ). In addition, we would like to thank participants of the questionnaire who provided valuable data that enabled the conduct of this study. S.G., E.M., N.A., J.L.W. and N.A. and H.I.M. are funded by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (grant reference NIHR200929), a partnership between UK Health Security Agency and London School of Hygiene & Tropical Medicine. EPKP received funding from the UKRI COVID-19 Longitudinal Health and Wellbeing National Core Study (Phase 1 LHW-NCS, MC_PC-20059). The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency or the Department of Health and Social Care.

Publisher Copyright:
© 2023, The Author(s).


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