Toward Rapproachment in the Placebo Control Debate

Abstract

In an effort to minimize risk to participants, some investigators avoid using placebo controls in randomized controlled clinical trials (RCT) if an effective treatment is available. An unintended consequence of this approach is that substantially more participants remain acutely ill (i.e., nonresponders) throughout an active-comparator trial than a placebo-controlled trial. This is due to the increased sample size required to detect smaller differences between investigational and proven active agents. The objective of this article is to identify an RCT design that will minimize both the number assigned to placebo and the number of nonresponders. To do so, two aspects of clinical trial design are manipulated: choice of comparator and treatment allocation ratio. Several examples illustrate empirically that placebo-controlled trials that are designed to randomize twice as many participants to the investigational cell could appeal to potential study participants, clinical researchers, and Institutional Review Boards alike.