Standardized mean differences in adaptive group sequential trials

Abstract

For studies comparing two independent groups, experimental E and control C, with normally distributed response variables, the outcome measure standardized differences of means is considered that is scale and translation invariant. This effect measure enables a convenient specification of a noninferiority margin in a concrete application. The present paper provides in particular a group sequential confidence interval approach to noninferiority trials and to switching between noninferiority and superiority for the effect size measure standardized mean difference. During the course of the trial, the sample size can be calculated in a completely adaptive way, based on the unblinded data of previously performed stages. Concrete rules for sample size updating are provided in this paper. Moreover, in each interim analysis, it is possible to change the planning from showing noninferiority to showing superiority or vice versa. A real data example is worked out in detail and the change in the planning from showing noninferiority to showing superiority is considered during the ongoing trial.