title: Are placebo and drug-specific effects additive? Questioning basic assumptions of double-blinded randomized clinical trials and presenting novel study designs.
abstract: Double-blinded randomized clinical trials (RCTs) assume that pharmacological interventions have drug-specific and unspecific components. Traditional RCTs postulate an additivity of these two components. In this review, we provide evidence from both clinical trials and experimental studies that questions this 'additive model'. Given that the evaluation of drug treatments in RCTs is based on the assumption of additivity, its violation has far-reaching consequences. Therefore, we discuss an interactive model that, in contrast to the additive model, considers interactions between placebo and drug-specific effects. Moreover, we discuss implications for future clinical trials and present novel study designs enabling researchers to consider the complex interplay of drug-specific and unspecific effects.
authors.affiliation: Philipps-University of Marburg, Department of Clinical Psychology and Psychotherapy, Gutenbergstrabe 18, D-35032 Marburg, Germany. Electronic address: tobias.kube@uni-marburg.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kube
authors.affiliation: Philipps-University of Marburg, Department of Clinical Psychology and Psychotherapy, Gutenbergstrabe 18, D-35032 Marburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Rief
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
chemical_list: D004364:Pharmaceutical Preparations