Inconsistent Safety Outcome Reporting in Randomized Clinical Trials of COVID-19 Vaccines Complicates Informed Medical Decisions

Abstract

In recent months, there has been extensive reporting of interim efficacy results of several COVID-19 vaccine randomized clinical trials. Considerably less attention has been placed on the safety outcomes of these trials. Before largescale observational studies became available, individual patients and clinicians needed to make indirect comparisons between COVID-19 vaccines in regions, such as Hong Kong, where patients may choose among vaccine products. The early results of COVID-19 vaccines trials published in top medical journals [1–4] were some of the first publicly available data reporting vaccine safety outcomes, yet the reporting of these outcomes in journal articles should be more consistent, comprehensive, and transparent to allow for informed comparisons between different vaccines. Ramasamy et al. reported local and systemic adverse reactions for Vaxzevria (COVID-19 Vaccine [ChAdOx1-S (recombinant)]; AstraZeneca AB, Stockholm, Sweden) vs the control (MenACWY vaccine) [3]. However, we note that the detailed adverse reaction data for the controls appear to be missing from the supplementary tables. In their studies of CoronaVac (COVID-19 Vaccine [Vero Cell], Inactivated; Sinovac Life Sciences, Beijing, China), Wu et al. and Zhang et al. define the primary safety endpoint as adverse reactions [1, 2]. The International Conference on Harmonisation defines adverse events as “Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment” [5]. In contrast, an adverse reaction is an event that is judged to be caused by the vaccine under study. In the published papers by Wu et al. and Zhang et al., there appears to be a lack of clarity in the reporting as both terms are used somewhat interchangeably. There are also discrepancies between the primary outcome of adverse reactions in the study protocols and adverse events in the statistical analysis plans. To date, the Government of Hong Kong has purchased three COVID-19 vaccines that use three different vaccine platform technologies: Comirnaty (COVID-19 mRNA Vaccine [nucleoside-modified]; BioNTech Manufacturing GmbH, Mainz, Germany), CoronaVac, and Vaxzevria. To emphasize the importance of consistent, clear, and transparent reporting of safety outcomes in published articles of COVID-19 vaccine randomized clinical trials, a summary of the frequency of adverse events or reactions reported in clinical trials after the first dose of these three vaccines is shown in Table 1. Published rates of adverse reactions for CoronaVac appear to be lower when compared with Comirnaty and Vaxzevria. It is not clear to us whether the investigators of CoronaVac used different definitions or different processes to ascertain whether an adverse event qualified as an adverse reaction, which could have resulted in a much lower frequency of reported adverse reactions when compared with Comirnaty and Vaxzevria, but this is difficult to ascertain from the published article. Tools created by the Brighton Collaboration [6], which establishes consistent definitions for adverse events following immunization, * Ian C. K. Wong [email protected]