Estimation following group-sequential response-adaptive clinical trials

A sequential clinical trial model is considered in which two treatments with immediate normally distributed responses are to be compared. The class of one-sided group-sequential tests with response-adaptive sampling developed by Jennison and Turnbull is used to investigate which of the treatments has the larger mean response. The power function for this class of tests is the same as that under nonadaptive sampling, and significant decreases in the inferior treatment number can be achieved with only minor increases in the average total sample number. Two inferential methods are considered following the design. Approximate confidence intervals for the treatment mean difference and the individual means are constructed using the pivotal method of Woodroofe, and an approximation to the bias of the maximum likelihood estimator of the treatment mean difference is studied based on the work of Whitehead. Simulation is used to assess the accuracy of both methods for various stopping boundaries and numbers of interim analyses. (C) 2003 Elsevier Inc. All rights reserved.