Group sequential trials revisited: Simple implementation using SAS

Abstract

The methodology of group sequential trials is now well established and widely implemented. The benefits of the group sequential approach are generally acknowledged, and its use, when applied properly, is accepted by researchers and regulators. This article describes how a wide range of group sequential designs can easily be implemented using two accessible SAS functions. One of these, PROBBNRM is a standard function, while the other, SEQ, is part of the interactive matrix language of SAS, PROC IML. The account focuses on the essentials of the approach and reveals how straightforward it can be. The design of studies is described, including their evaluation in terms of the distribution of final sample size. The conduct of the interim analyses is discussed, with emphasis on the consequences of inevitable departures from the planned schedule of information accrual. The computations required for the final analysis, allowing for the sequential design, are closely related to those conducted at the design stage. Illustrative examples are given and listings of suitable of SAS code are provided.