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

ABSTRACT

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. Key messagesO_LIReal world evidence generated using weighting (overlapping weights and inverse probability of treatment weights) and propensity score matching all methods successfully replicate the findings of Phase 3 trials for COVID-19 vaccine effectiveness. C_LIO_LIOverlap weighting provides the least biased estimates in our study and should be considered amongst the most suitable methods for future COVID-19 vaccine effectiveness research. C_LIO_LIDespite a lack of trial data, our findings suggest that first-dose BNT162b2 provides effective protection against SARS-COV-2 infection for up to 12 weeks, in line with UKs Joint Committee on Vaccination and Immunisation modelling and subsequent vaccination strategies. C_LI