Title: Adaptive designs: Methods and applications

Abstract: Adaptive designs for clinical trials were identified as a means to make the clinical development of therapies more efficient. Furthermore, adaptive designs can be used to make trials more robust against misspecifications in the planning phase. Focusing on confirmatory trials, an overview of adaptive design methodology will be provided. 

We start by considering nuisance-parameter-based sample size re-estimation, also known as internal pilot study designs. We demonstrate that re-estimating the sample size based on blinded (noncomparative) data has in most situations no practically relevant effect on the Type I error rate and maintains the power at a desired level for the planning alternative independent of the size of the nuisance parameter. In the second part of the presentation, adaptive seamless designs with treatment or subgroup selection are considered. 

We show how the Type I error rate can be controlled in very flexible designs. Practically relevant aspects such as the use of early outcomes to inform the interim decision on the adaptation while testing treatment effects on clinically relevant long-term outcomes are discussed. The methods will be motivated and illustrated using clinical trial examples.