Interim Analysis, Adaptations and Master Protocols

In this lecture, we will focus on the role of interim analysis to react to new data emerging from inside and outside the trial. How to incorporate an interim analysis in a confirmatory clinical trial without inflating the risk of declaring a treatment as efficient when it is not. Regulatory guidelines document stresses that for confirmatory clinical trials one of the key features is the strict control of the type 1 error risk. The concept of group sequential designs will be explained which allow both early stopping for efficacy and futility. Adaptive designs will be discussed which allow the adaptations such as sample size reassessment, treatment selection or change of allocation ratio. Both regulatory guidance documents and the Consort extension on adaptive design (Dimairo et al. 2020) will be presented. The latter includes several adaptive case studies in its explanatory document.

Finally, the concept of master protocols will be presented highlighting some of the key statistical concepts (Koenig et al. 2024, Meyer et al 2020), especially how to increase efficiency by data sharing concepts.