Navigating the quagmire: Comparison and interpretation of COVID-19 vaccine phase 1/2 clinical trials

Abstract

Vaccines against Coronavirus Disease 2019 Originated-19) have been developed with unprecedented rapidity, many utilizing novel strategies. As of November 2020, a series of publications have outlined the results of phase 1/2 studies of nine different vaccines planned to move forward to phase 3 trials. The results are encouraging, demonstrating a paucity of severe or serious adverse events and robust induction of antibody titers. Determination of the vaccine candidates with the highest protective efficacy and best adverse event profiles will be essential in refining public health strategies. However, differences in study design and reporting of data make comparisons of existing phase 1/2 studies difficult. With respect to safety, studies have variable follow-up times and may use different definitions for adverse events. Immunogenicity outcomes are even more inconsistent, with variations in timepoints and critical differences in the types of antibodies studied as well as methodological differences in assays. Furthermore, the correlates of protection in COVID-19 are not known. Harmonization of phase 3 trial designs and use of objective and meaningful clinical outcomes will be crucial in streamlining future global responses to the pandemic.