Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study

Background: Estimating real-world vaccine effectiveness is vital to assess the impact of the vaccination programme on the pandemic and inform the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the non-randomised design and the potential for unmeasured confounding. Methods: We used a Regression Discontinuity Design (RDD) to estimate vaccine effectiveness against COVID-19 mortality in England, exploiting the discontinuity in vaccination rates resulting from the UK's age-based vaccination priority groups. We used the fact that people aged 80 or over were prioritised for the vaccine roll-out in the UK to compare the risk of COVID-19 and non-COVID-19 death in people aged 75-79 and 80-84. Findings: The prioritisation of vaccination of people aged 80 or above led to a large discrepancy in vaccination rates in people 80-84 compared to those 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality, but not in non-COVID-19 mortality, suggesting that our approach appropriately addresses the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 70.5% (95% CI 18.2-117.7) in those aged 80. Interpretations: Our results support existing evidence that a first dose of a COVID-19 vaccine has a strong protective effect against COVID-19 mortality in older adults. The RDD estimate of vaccine effectiveness is comparable to previously published studies using different methods, suggesting that unmeasured confounding factors are unlikely to substantially bias these studies.