Differential anchoring effects of vaccination comparator selection: characterizing a potential bias due to healthcare utilization in COVID-19 versus influenza

  1. Anna Ostropolets
  2. Patrick B. Ryan
  3. Martijn J. Schuemie
  4. George Hripcsak

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Abstract

Introduction

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. Here, we evaluate different index date selection procedures for two vaccines: 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 an arbitrary date or indexed on 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.

Conclusion

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.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.07.21264711: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.10.07.21264711v1 on medRxiv