Estimation of a secondary parameter in a group sequential clinical trial.

In this article, we investigate estimation of a secondary parameter in group sequential tests. We study the model in which the secondary parameter is the mean of the normal distribution in a subgroup of the subjects. The bias of the naive secondary parameter estimator is studied. It is shown that the sampling proportions of the subgroup have a crucial effect on the bias: As the sampling proportion of the subgroup at or just before the stopping time increases, the bias of the naive subgroup parameter estimator increases as well. An unbiased estimator for the subgroup parameter and an unbiased estimator for its variance are derived. Using simulations, we compare the mean squared error of the unbiased estimator to that of the naive estimator, and we show that the differences are negligible. As an example, the methods of estimation are applied to an actual group sequential clinical trial, The Beta-Blocker Heart Attack Trial.