Observational methods for COVID-19 vaccine effectiveness research: a trial emulation and empirical evaluation

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

Despite much research on the topic, little work has been done comparing the use of methods to control for confounding in the estimation of COVID-19 vaccine effectiveness in routinely collected medical record data. We conducted a trial emulation study to replicate the ChAdOx1 (Oxford/AstraZeneca) and BNT162b2 (BioNTech/Pfizer) COVID-19 phase 3 efficacy studies. We conducted a cohort study including individuals aged 75+ from UK CPRD AURUM (N = 916,128) in early 2021. Three different methods were assessed: Overlap weighting, inverse probability treatment weighting, and propensity score matching. All three methods successfully replicated the findings from both phase 3 trials, and overlap weighting performed best in terms of confounding, systematic error, and precision. Despite lack of trial data beyond 3 weeks, we found that even 1 dose of BNT162b2 was effective against SARS-CoV-2 infection for up to 12 weeks before a second dose was administered. These results support the UK Joint Committee on Vaccination and Immunisation modelling and related UK vaccination strategies implemented in early 2021.

Author list



  1. Center for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK 
  2. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands


Martí Català, Edward Burn, Trishna Rathod-Mistry, Junqing Xie, Antonella Delmestri, Daniel Prieto-Alhambra, Annika M. Jödicke

Novel Coronavirus SARS-CoV-2