Are placebo and drug-specific effects additive? Questioning basic assumptions of double-blinded randomized clinical trials and presenting novel study designs

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...