SCPRT: A Sequential Procedure That Gives Another Reason to Stop Clinical Trials Early

摘要

A sequential clinical trial is designed with given significance level and power to detect a certain difference in the parameter of interest and the trial will be stopped early when data collected at an early stage of the trial have produced enough, in one sense or another, evidence for the conclusion of the hypotheses. Different sequential test designs are available for a same requirement of significance level and power. On the other hand, a same set of observed data can be interpreted as outcomes of different sequential designs with the same significance level and power. Therefore for same observed data, the conclusion of a test may be significant by one sequential design but insignificant by another sequential test design. This phenomenon may lead to the question of whether applying sequential test design to clinical trials is rational. Withstanding this challenge, the sequential conditional probability ratio test (SCPRT) offers a special feature such that a conclusion made at an early stopping is unlikely to be reversed if the trial were not stopped but continued to the planned end. The SCPRT gives a sound reason to stop a trial early; that is, if the trial were not stopped as it should, then adding more data and continuing the trial by the planned end would not change the conclusion. With an SCPRT procedure, a sequential clinical trial is designed not only with given significance level and power, but also with a given probability of discordance which controls the chance that conclusion at an early stage would differ from that at the final stage of the trial. In particular, the SCPRT procedure based on Brownian motion on information time is simple to use and can be applied to clinical trials with different endpoints and different distributions.