Choice of Delta: A Special Case

Abstract

From a scientific point of view the proof of efficacy of a new investigational (test) treatment is persuasively established by demonstrating superiority to a concurrent placebo group in a randomized double-blind clinical trial. However, in the case where a standard treatment (reference) has already proved effective the comparison against placebo may be considered unethical and efficacy can only be derived in a randomized active control study by showing noninferiority or equivalence. Inherent for these trials is the necessity of an a priori specification of what constitutes an irrelevant difference. The purpose of this paper is to derive a methodology when this difference is defined as a fraction of the reference mean.