2026 American Academy of Neurology Abstract Website

Objective:

To examine patterns in disease progression of newly diagnosed Parkinson’s disease (PD) participants enrolled in clinical trials vs natural history.

Background:

Differences in disease progression among PD participants enrolled in clinical trials vs natural history studies are hypothesized, partially based on a potential for expectation bias. Understanding differences in PD progression is important for interpreting results generated from such datasets.

Design/Methods:

Data were obtained from the multicenter natural history cohort Parkinson’s Progression Markers Initiative (PPMI) and the Critical Path for Parkinson’s (CPP) dataset of clinical trial placebo arms. Subjects with confirmed PD within the previous two years and naïve to dopaminergic treatment were included in the analysis. Baseline demographics and clinical characteristics were examined. Changes in MDS-UPDRS scores (Parts I, II and III) over 24-months were compared by examining change from baseline (CFB) and mean CFB to standard deviation ratios (MSDRs). CFB and MSDRs were also calculated for individual items at 12-months.

Results:

A total of 430 and 183 participants from the PPMI and CPP databases, respectively, met inclusion criteria for this analysis. At the aggregate level baseline characteristics were similar across datasets. When MDS-UPDRS trajectories were examined, Part 1 was observed to improve over the first 12-months for subjects in CPP (MSDR: -0.21) followed by a reversion to baseline by 24-month. Subjects in PPMI consistently declined over the 24-month period (MSDRs of 0.23 and 0.36, at 12- and 24-months, respectively). Aggregate level differences in progression on Part 2 and 3 were less apparent, however at the item level there were differences in which items progressed over 12-months.

Conclusions:

Participants enrolled in placebo arms demonstrated less decline on MDS-UPDRS Part 1 compared to natural history, which may be indicative of expectation bias.