In randomized controlled trials, should subjects in both placebo and drug groups be expected to guess that they are taking drug 50% of the time?

Part of the design of some randomized controlled trials has included asking patients to guess whether they are taking placebo or active drug. Some authors have stated that in randomized, double-blind placebo-controlled clinical trials patients in each group should guess that they are taking placebo half the time. However, this pattern should occur only under a limited set of circumstances. This paper explores the factors that affect the guess and the role of the guess in understanding both the establishment and the maintenance of the blind. It suggests that more than half of those in the treatment group should guess they are taking active drug if treatment or side-effects are powerful. Though the randomized controlled trial has become the paradigmatic tool to assess treatment efficacy, studies are still needed to validate key assumptions make by investigators and the effect of violation of these assumptions on study outcomes.