In an effort to contain the coronavirus disease 2019 (COVID-19) pandemic, the United Kingdom initiated its vaccination campaign on December 8, 2020. To date, more than 77% of the adult population in the U.K. have received at least one dose of the COVID-19 vaccine.
Study: Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study. Image Credit: Melinda Nagy / Shutterstock.com
Several COVID-19 vaccines have received emergency use approval (EUA) from the Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K., which has allowed many researchers to evaluate the efficacy of these vaccines in real-world settings. For instance, both messenger ribonucleic acid (mRNA) vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have demonstrated 95% efficacy rates, whereas the Oxford-AstraZeneca vaccine (ChAdOx1) has been reported to have lower efficacy of about 70%.
Assessing the effectiveness of these vaccines is essential in determining the impact of the vaccination program. Previous studies have estimated the effectiveness of vaccines by comparing the number of hospitalizations, susceptibility to infection, and mortality rates between vaccinated and unvaccinated individuals. However, these studies have often failed to consider certain confounding factors and temporal changes that have influenced the calculations on vaccine effectiveness, which has subsequently resulted in a biased overestimation of the effects of the vaccine.
RDD to evaluate COVID-19 vaccine efficacy
Many researchers believe that under certain conditions, such as the eligibility to get a vaccine based on a continuous variable, the regression discontinuity design (RDD) can be applied to obtain impartial estimates of vaccine effectiveness. In fact, RDD can be applied even in the presence of unmeasured confounding factors.
For example, RDD approaches have recently been used to reveal that the Bacillus Calmette-Guérin (BCG) vaccine has no impact on the COVID-19 disease. More specifically, the RDD approach helped to determine that the relationship between BCG vaccination coverage and reduction in COVID-19 cases in different countries was the result of unmeasured confounding factors.
Taken together, researchers believe that the RDD approach can be used to accurately calculate COVID-19 vaccine efficacy, as many countries across the globe have adopted an age-based vaccine roll-out strategy.
Estimation of vaccine efficacy
A new study published on the preprint server medRxiv* estimates vaccine effectiveness against COVID-19 mortality in England using the RDD approach. In their work, a fuzzy RDD method was used to estimate the impact of vaccination on the risk of death due to COVID-19.
Herein, the deaths that occurred due to COVID-19 disease were compared to the deaths due to non-COVID-19 factors in people between the ages of 75–79 and 80–84. The RDD exploited the discontinuity in vaccination rates that was generated owing to the U.K.’s strategy of age-based vaccination of priority groups.
The researchers found a reduction in the mortality rates due to COVID-19 for people above the age of 80 years. This result reassured the scientists that the reduction in the mortality rate in the older age group was largely due to the availability of vaccines, rather than the result of residual confounding factors.
Additionally, using eligibility as a criterion for being vaccinated, the RDD approach used herein indicated seropositivity in individuals who received a single dose of vaccine. As a result, a decrease in the COVID-19 mortality rate was observed. Notably, a similar trend was not observed in the unvaccinated group.
The researchers estimated vaccine effectiveness to be 70.5% for the vaccinated group who were of or above 80 years and were seropositive. Further, the scientists also found that a single dose of the COVID-19 vaccine provided a robust protective effect against COVID-19 mortality in the older age group.
Strengths and limitations of the study
The main strength of this study is the use of the RDD method to estimate COVID-19 vaccine effectiveness, which minimizes the risk of bias. The RDD approach is useful when analyzing cases that include many confounding factors, while also reducing the impact of temporal and geographical differences. Another strength of this study was the fact the approximately 93.9% of England’s population who is in the age group of 75–84 years had received the first dose of a COVID-19 vaccine.
An important limitation of this study is that it has only estimated the effectiveness of the first dose of the COVID-19 vaccine. This method also did not consider immune responses that may have occurred because of previous COVID-19 infection.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.