Informed consent for national registration of COVID-19 vaccination caused information bias of vaccine effectiveness estimates mostly in older adults: a bias correction study

Objectives: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of nonconsenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in vaccine effectiveness (VE) estimates. Study Design and Setting: National data were used for the period dominated by the SARS-CoV-2 Delta variant (July 11 to November 15, 2021). VE ((1-relative risk)∗100%) against COVID-19 hospitalization and intensive care unit (ICU) admission was estimated for individuals 12 to 49, 50 to 69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iteratively imputing corrected vaccination status. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected/corrected relative risk. Results: A total of 8804 COVID-19 hospitalizations and 1692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the nonconsent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5–77.4) before to 85.9% (95% CI 84.7–87.1) after correction (absolute bias −10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2–90.8) before and 93.7% (95% CI 92.2–94.9) after correction (absolute bias −5.0 percentage point, relative bias 1.79). Conclusion: VE estimates can be substantially biased with modest nonconsent percentages for vaccination data registration. Data on covariate-specific nonconsent percentages should be available to correct this bias.