The Lessebo Effect in Disease Modification Trials in Parkinson's Disease

Abstract

AbstractBackgroundThe impact of expectation of benefit on outcomes is well established in Parkinson's disease (PD). A reduction of a treatment effect due to a perceived placebo allocation (lessebo effect) in randomized controlled trials (RCTs) was documented for symptomatic treatments.ObjectivesTo evaluate the lessebo effect in disease modification RCTs (DMT) in PD.MethodsSubject‐level meta‐analyses of active treatment arms of DMT (n = 1149 subjects): FS‐1, FS‐TOO (probability of placebo allocation/P(placebo) = 0.33) and DATATOP, PRECEPT, QE2 (P(placebo) = 0.25). We tested the association between P(placebo) and time to dopaminergic treatment initiation using a marginal Cox proportional hazards model.ResultsThe adjusted hazard ratio (P(placebo) = 0.25 vs. 0.33) for initiation of dopaminergic treatment was 1.15 (95% CI: 0.92–1.43).ConclusionsWe did not observe the lessebo effect in DMT. The necessary use of a placebo (and no active comparator) is a limitation. The prospective measurement of expectation of benefit could help to evaluate the many impacts of placebo use. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.