Clinical trials are designed as uncontrolled or controlled studies. Controlled studies, with the highest quality and level of evidence coming from randomized controlled studies, judge the efficacy of an experimental treatment against an alternative treatment, or control. Controls may be broadly categorized as placebo, active treatment, or best available therapy.1 A placebo, by definition, has no therapeutic benefit and is intended to provide only a psychological treatment effect. In comparison, active treatment or best available therapy controls have intrinsic therapeutic benefit.