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

The 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.

To evaluate the lessebo effect in disease modification RCTs (DMT) in PD.

Subject-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.

The adjusted hazard ratio (P_(placebo)  = 0.25 vs. 0.33) for initiation of dopaminergic treatment was 1.15 (95% CI: 0.92-1.43).

We 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.