Analysis of Combination Trials with No Placebo Arm *

Abstract

When two drug products are combined together, the traditional design of a trial to investigate the efficacy of the combination product usually includes four arms: a placebo arm, both monotherapy arms, and the combination arm. For ethical reasons, it is sometimes not possible to include a placebo arm in the study when one drug has already been shown to be effective. In this article, we will specifically look at the case when drug A has already been shown to have a mortality effect relative to placebo from an historical study. A new drug is believed to have a similar effect to drug A, and the effect of the combination of the two drugs is believed to be more effective than drug A alone. A clinical trial is designed with three arms to show these conclusions, but no placebo arm is present.