Group sequential methods in the design and analysis of clinical trials

TLDR

Fixed sample size designs are ethically unjustified in sequential patient entry trials, making sequential designs impractical. The study addresses how to determine the required sample size and number of groups in a group sequential design. They propose a group sequential design that partitions patients into equal‑sized groups and applies repeated significance tests on accumulated data, while also exploring how to choose the sample size and number of groups. Exact results for two‑treatment normal‑response trials with known variance were derived, simulations indicated these results extend to other response types, and an example demonstrated that group sequential designs can be statistically superior to standard sequential designs.

Abstract

In clinical trials with sequential patient entry, fixed sample size designs are unjustified on ethical grounds and sequential designs are often impracticable. One solution is a group sequential design dividing patient entry into a number of equal-sized groups so that the decision to stop the trial or continue is based on repeated significance tests of the accumulated data after each group is evaluated. Exact results are obtained for a trial with two treatments and a normal response with known variance. The design problem of determining the required size and number of groups is also considered. Simulation shows that these normal results may be adapted to other types of response data. An example shows that group sequential designs can sometimes be statistically superior to standard sequential designs.