Multiplicity adjustments in trials with two correlated comparisons of interest

Abstract

Clinical trials investigating the efficacy of two or more doses of an experimental treatment compared to a single reference arm are not uncommon. In such situations, if each dose is compared to the reference arm using an un-adjusted significance level, consideration of the Type I familywise error is likely to be required. Furthermore, in trials where two or more comparisons are performed using the same reference arm, the comparisons are inherently correlated. The correlation between comparisons can be utilised to remove some of the conservativeness of some commonly used procedures. This article is intended as a practical guide that should enable calculation of significance levels that fully conserve Type I error and provides graphical presentation that could facilitate their description to non-statisticians.