Characterizing Anchoring Bias in Vaccine Comparator Selection Due to Health Care Utilization With COVID-19 and Influenza: Observational Cohort Study

Abstract

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Observational data enables large-scale vaccine safety surveillance but requires careful evaluation of potential sources of bias. One potential source of bias is an index date selection procedure for the unvaccinated cohort or unvaccinated comparison time (“anchoring”). Objective: Here, we evaluate different index date selection procedures for two vaccinations: against COVID-19 and influenza. Methods: For each vaccine, we extracted patient baseline characteristics on the index date and up to 450 days prior and then compared them to the characteristics of the unvaccinated patients indexed on (a) an arbitrary date or (b) a date of a visit. Additionally, we compared vaccinated patients indexed on the date of vaccination and the same patients indexed on a prior date or visit. Results: COVID-19 vaccination and influenza vaccination differ drastically from each other in terms of populations vaccinated and their status on the day of vaccination. When compared to indexing on a visit in unvaccinated population, influenza vaccination had markedly higher covariate proportions and COVID-19 vaccination had lower proportions of most covariates on the index date. In contrast, COVID-19 vaccination had similar covariate proportions when compared to an arbitrary date. These effects attenuated but were still present with a longer lookback period. The effect of day 0 was present even when patients served as their own controls. Conclusions: Patient baseline characteristics are sensitive to the choice of the index date. In vaccine safety studies, unexposed index event should represent vaccination settings. Study designs previously used to assess influenza vaccination must be reassessed for COVID-19 to account for a potentially healthier population and lack of medical activity on the day of vaccination.