Abstract
Background: The measures used to assess Parkinson’s disease (PD) in clinical trials were developed for a broad spectrum of disease severity, limiting their ability to detect meaningful changes in early PD over a feasible study period. Objective: To develop PD composite scales (PARCOMS) using clinical trials data with increased responsiveness to clinical decline in patients with early untreated disease. Methods: Subjects from the placebo arms of clinical trials (Critical Path for Parkinson’s [CPP] dataset), diagnosed with PD within the previous two years, with no current or prior use of dopaminergic therapies were included. Partial least squares (PLS) regression was used to develop two composite scales: PARCOMS-Function using items from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and Parkinson’s Disease Questionnaire (PDQ-39) scales, and PARCOMS-Motor using items from MDS-UPDRS Parts II and III. Scale responsiveness was estimated using mean to standard deviation ratios (MSDRs) for change from baseline at 12-months. Results: The MSDR for PARCOMS-Function (n = 140) was 12.3 % higher vs MDS-UPDRS Part II alone and 339 % higher vs PDQ-39 alone. The MSDR for PARCOMS-Motor (n = 181) was 27.5 % higher vs the combined MDS- UPDRS Parts II and III. PARCOMS-Function retained 15-items (34.1 %) from Part II and PDQ-39. PARCOMS-motor retained 23-items (50.0 %) from Part II and III. Items that were not responsive to change or that were correlated with more responsive items were omitted. Conclusions: Clinical trial data were used to develop two PARCOMS scales which demonstrated greater sensitivity to disease progression in patients with early PD over 12-months compared to the original scales.