Quantifying Placebo Effects in Hereditary Ataxia Trials: A Meta-Analysis of Scale for the Assessment and Rating of...

The Scale for the Assessment and Rating of Ataxia (SARA) is the primary outcome most frequently used in clinical trials involving hereditary ataxia patients. This systematic review and meta-analysis aimed to quantify changes in SARA scores within placebo arms of these trials to better understand the placebo effect.

Placebo arm data were collected from clinical trials on hereditary ataxias via PubMed and ClinicalTrials.gov. Heterogeneity was assessed with funnel plots. A random-effects meta-analysis was conducted on trials providing variance data. The influence of covariates such as trial duration, continent, intervention type, publication date, and trial result was evaluated.

Thirty-four trials with placebo arms, including patients with spinocerebellar ataxias and Friedreich's ataxia, were identified. Trial durations ranged from 1 to 52 weeks. Thirty-seven assessment points were included in the meta-analysis, revealing substantial heterogeneity (I² = 94%). Placebo response differed significantly by continent, with European trials showing minimal effect (0.01 [-0.35; 0.37]) and Asian trials the largest effect (-0.85 [-1.13; -0.58]). Intervention type also impacted placebo response, with device interventions exhibiting the strongest effect (-0.84 [-1.60; -0.08]). Trial duration showed no statistically significant effect; however, a trend of decreasing placebo effect over time was observed.

The analysis indicates a measurable placebo effect on SARA scores. Both intervention type and geographic region significantly influenced the strength of this effect, suggesting roles for patient expectations and cultural factors. Additionally, there was a trend toward reduction of placebo response as trial duration increased. © 2026 International Parkinson and Movement Disorder Society.