Sensitivity analyses
EVENT
The sample size calculation (“Sample size” section) assumed a 15% rate of the composite safety outcome in the control group. Because the non-inferiority margin is defined using a fixed risk difference, deviations from the assumed control group rate could cause a reduction in power (if > 15%) or an inflation of the tolerable relative risk in the treatment group (if < 15%). We will therefore repeat the primary analysis with the non-inferiority margin modified according to the power-stabilising arcsine transformation [We will use CACE [We will use SACE [To assess the impact of missing composite safety outcome data, we will compare the results of the primary analysis (complete cases, as defined in the “Missing data” section) with estimates from two simple imputation models. We will treat all missing components as negative (no event) in the “best-case” imputation, and as positive in the “worst-case” imputation, providing upper and lower bounds on the composite safety outcome.