Evaluation of an Adaptive Seamless Design for a Phase II/III Clinical Trial in Recurrent Events Data to Demonstrate Reduction in Number of Acute Exacerbations in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Abstract

–The aim of this work is to present an adaptive two-stage seamless design for a Phase II/III clinical trial in chronic obstructive pulmonary disease (COPD). This approach implies sample size re-estimation based on the primary outcome efficacy variable, namely the annual acute exacerbation rate. Patient recruitment in COPD trials can be slow; the proposed statistical approach may allow for a faster completion of the trial by reducing the time between interim analysis (IA) (Phase II) and new recruitment (Phase III). In addition, an adaptive design with re-estimation of the sample size during the study may increase its likelihood of success, especially in cases where estimated interim vaccine efficacy is lower than expected. By applying the proposed approach, at the time of the IA (end of Phase II), a decision can be taken to stop the trial for futility, to continue the trial (by advancing to Phase III) with the planned sample size or to continue the study and increase the sample size. We carried out simulations to evaluate the performance of the method.