Recent Developments in Group-Sequential Designs BT - Developments in Statistical Evaluation of Clinical Trials

Abstract

In a group-sequential trial, patients are recruited in groups, and their response to treatment is assessed. After each group is assessed, an interim analysis is conducted. At each interim analysis, the trial can stop for futility, stop for efficacy, or continue. The main advantage of group-sequential designs is that the expected number of patients is reduced compared to a design without interim analyses. There are infinitely many possible group-sequential designs to use, and the choice strongly affects the operating characteristics of the trial. This chapter discusses optimal and admissible group-sequential designs. Optimal designs minimise the expected sample size at some specified treatment effect; admissible designs optimise a weighted sum of trial properties of interest, such as expected sample size and maximum sample size. Methods for finding such designs are discussed, including a detailed description of an R package that implements a quick search procedure. Recent applications of group-sequential methodology to trials with multiple experimental treatments being tested against a single control treatment are also described.