The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries

ABSTRACT. The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.