Confidence Intervals Following Group Sequential Tests in Clinical Trails with Multivariate Observations

Abstract

Several authors ( e.g. Kim and DeMets, 1987a, Biometrics) have developed methods for estimation following group sequential tests in clinical trials when each patient has only one response. In many long-term clinical trials, the subjects enter the study sequentially and yield repeated measurements or other types of multivariate observations at successive follow-up visits. Typically, investigators want to compare a parameter of interest such as the slope over time in a repeated measures trial etc. In this article, we propose an exact confidence interval for these parameters in a repeated measures trial, and compare it with a naive confidence interval using Monte Carlo simulation. This method is illustrated with a real example for bone density measurements.