Box 9 Exemplar on reporting item 3c elements

Example. Inferentially seamless phase 2/3 (5-arm 2-stage) AD allowing for regimen selection, SSR and futility early stopping

Although this should ideally have been referenced in the main report, Léauté-Labrèze et al. [94] (on pages 17–18 of supplementary material) summarise important changes to the trial design including an explanation and discussion of implications. These changes include a reduction in the number of patients assigned to the placebo across stages—randomisation was changed from 1:1:1:1:1 to 2:2:2:2:1 (each of the 4 propranolol regimens: placebo) for stage 1 and from 1:1 to 2:1 for stage 2 in favour of the selected regimen; revised complete or nearly complete resolution success rates for certain treatment regimens. As a result, total sample size was revised to 450 (excluding possible SSR); and a slight increase in the number of patients (from 175 to 180) to be recruited for the interim analysis.