Comparative effectiveness of three common SARS-COV-2 vaccines: A network meta-analysis of randomized trials

Abstract

Background

Moderna, Pfizer, and AstraZeneca SARS-CoV-2 vaccines for preventing COVID-19 have regulatory approval in most countries. We conducted a network meta-analysis to compare their effectiveness.

Methods

We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ICTRP, and Clinicaltrials.gov for the randomized controlled trials (RCTs) published between 1st January 2020 and 1st February 2024. Eligible RCTs evaluated the Moderna, Pfizer or AstraZeneca vaccines among healthy individuals and reported the effectiveness of vaccination versus control measured with the outcome occurrence of COVID-19. We performed study selection, data extraction, and quality (risk of bias) assessment in duplicate. Network meta-analysis with random effects models was used to generate odds ratios (OR) with 95% confidence intervals (CI), evaluating heterogeneity statistically using I² for direct comparisons and ranking vaccines hierarchically using the surface under the cumulative ranking curve (SUCRA). This study was registered on PROSPERO, CRD42023457957.

Findings

Of the 1954 initial citation, 18 RCTs (272,724 participants; 151,034 received one of the vaccines and 121,690 controls) that reported the outcome occurrence of COVID-19 were selected. Of these, 2 (11%) were moderate and 5 (28%) were high in quality. In network meta-analysis, all three vaccines were effective compared directly with control (Moderna OR 0.13, 95% CI 0.07–0.26, I² 97%; Pfizer OR 0.10, 95% CI 0.05–0.19, I² 78%; AstraZeneca OR 0.38, 95% CI 0.25–0.59, I² 63%). Indirect comparison of vaccines using control as the common comparator showed that AstraZeneca was less effective than Moderna (OR 2.84, 95% CI 1.32–6.12) and Pfizer (OR 3.94, 95% CI 1.80–8.60), while Moderna versus Pfizer showed no difference (OR 1.39, 95% CI 0.56–3.46). Vaccine SUCRA probabilities were higher for Pfizer than Moderna and AstraZeneca (92%, 75% and 33% respectively compared to control).

Interpretations

Pfizer ranks highest followed by Moderna (without a statistically significant difference) and AstraZeneca vaccines for preventing symptomatic COVID-19.