Non-inferiority Trial on Monoclonal Antibodies in COVID-19

Sample size. The parameters for the sample size estimation were derived from the only double‐blind, randomised, placebo‐controlled trial assessing the clinical efficacy of casirivimab/imdevimab (reference standard) [3]. Hospitalisation related to COVID‐19 or all‐cause mortality in this study occurred in 7 of 736 patients in the casirivimab/imdevimab 1200‐mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomisation concurrently (3.2%) (relative risk reduction, 70.4%; P=0.002). Assuming a non‐inferiority margin of 5%, 420 patients per group were needed to achieve 90% power with a 1‐sided α level of .025, allowing for 5% dropout. A 5% non‐inferiority margin was chosen as the maximal difference between treatments in COVID‐19 progression that would be clinically acceptable by consultation with Infectious Diseases and clinical trial specialists involved in the protocol development.