Nocebo responses in randomized controlled trials of COVID-19 vaccines.

Abstract

OBJECTIVE\nThe aim of this study was to evaluate the frequency and magnitude of nocebo responses in -COVID-19 vaccine trials.\n\n\nMATERIALS AND METHODS\nWe performed a meta-analysis of adverse effects (AEs), severe adverse effects (SAEs), withdrawal due to AEs, death, and immune-mediated SAEs observed in randomized controlled trials (RCTs) of COVID-19 vaccines.\n\n\nRESULTS\nFour RCTs with a total of 119,110 participants (65,254 from the vaccine group and 53,856 from the placebo group) were considered. The pooled estimate of AEs in the placebo and vaccine groups was 16.4% (95% confidence interval (CI), 9.1\xa0-\xa027.7%) and 25.3% (95% CI, 22.7\xa0-\xa028.1%), respectively. The pooled SAE rate in the placebo and vaccine groups was 0.7% (95% CI, 0.5\xa0-\xa01.0%) and 0.6% (95% CI, 0.4\xa0-\xa00.9%), respectively. The pooled estimate of participants who withdrew from treatment due to AEs in the placebo and vaccine groups was 0.3% (95% CI, 0.1\xa0-\xa01.0%) and 0.2% (95% CI, 0.1\xa0-\xa00.5%), respectively. The pooled death rate in the placebo and vaccine groups was 0.02% (95% CI, 0.01\xa0-\xa00.04%) and 0.01% (95% CI, 0.01\xa0-\xa00.03%), respectively. The pooled estimate of immune-mediated SAEs in the placebo and vaccine groups was 0.01% (95% CI, 0.01\xa0-\xa00.04%) and 0.02% (95% CI, 0.01\xa0-\xa00.05%), respectively. There were no differences observed in the pooled risk of AEs, SAEs, withdrawal due to AEs, death, and immune-mediated SAEs between placebo and vaccine groups.\n\n\nCONCLUSION\nThe frequency and magnitude of nocebo responses were 16.4% and 0.3%, respectively. Therefore, the incidence of nocebo responses was high, but their magnitude was low in COVID-19 vaccine trials.