A general statistical principle for changing a design any time during the course of a trial.

Abstract

A general method is presented that allows the researcher to change statistical design elements such as the residual sample size during the course of an experiment, to include an interim analysis for early stopping when no formal rule for early stopping was foreseen, to increase or reduce the number of planned interim analyses, to change time points and the type I error spending function for the further design of interim analyses, or to change the test statistic, the outcome measure, etc. At the time of a pre-planned interim analysis for early stopping or at any time of an interim look without spending part of the type I error level the method offers the option to completely redesign the remaining part of the trial, without affecting the type I error level. The method is described in the usual Brownian motion model and extended to the general context of statistical decision functions. It is based on the conditional rejection probability of a decision variable.