A note on randomization and selection bias in maintenance therapy clinical trials

Abstract

In this article we demonstrate that even in randomized controlled clinical trials, unobserved confounding variables can bias the outcome of a study. For the case of a two-phase maintenance therapy trial where patients who respond to treatment during the acute phase are then randomized to a maintenance therapy, we show explicitly the role that confounding may play in biasing the interpretation of the results of such a trial. We suggest an alternative design to deal with the problem of a selection effect for treatment responders in the acute phase of the trial by randomizing patients at the outset of the study to both an acute and maintenance therapy.