A simple and efficient bias-reduced estimator of response probability following a group sequential phase II trial.

A phase II clinical trial evaluating the rate of response of a new therapeutic treatment is often designed to have one or two interim analyses, allowing possible termination of the trial at an early stage if lack of treatment efficacy is evident. Due to the sequential nature of such a trial, the sample proportion yields biased estimation for the rate of response. In this paper we propose an estimator of response rate by subtracting the estimated bias directly from the sample proportion. The proposed estimator is simple, intuitive, and easy to compute. When the bias of the sample proportion is of concern to the investigators, the proposed estimator is an efficient alternative to other estimators in the literature in terms of bias and mean squared error.