Box 21.

Exemplars on reporting item 14c elements

Example 1. Bayesian adaptive-enrichment AD with futility and superiority early stopping; stage of results “Enrolment in the trial was stopped at 31 months, because the results of an interim analysis met the pre-specified criterion for trial discontinuation, which was a predictive probability of superiority of thrombectomy of at least 95% for the first primary endpoint (the mean score for disability on the utility-weighted modified Rankin scale at 90 days). This was the first pre-specified interim analysis that permitted stopping for this reason, and it was based on the enrolment of 200 patients. Because enrichment thresholds had not been crossed, the analysis included the full population of patients enrolled in the trial, regardless of infarct volume.” [96] Example 2. Dose-selection decisions for an inferentially seamless phase 2/3 AD “The two doses of indacaterol selected against the two reference efficacy criteria were 150 μg (as the lowest dose exceeding both criteria) and 300 μg (as the next highest dose). The safety results, together with the safety data from the other 1-year study, led the DMC to conclude that there was no safety signal associated with indacaterol at any dose. Thus, the two doses selected (at stage 1) to continue into stage 2 of the study were indacaterol 150 and 300 μg.” [141]