Re-weighting MDS-UPDRS Motor Items for Optimal Sensitivity to Parkinson’s Disease Progression in Untreated Patients Using Parkinson’s Progression Markers Initiative Data
Gilbert L'Italien1, Samuel Dickson2, Basia Rogula3, Jordan Dubow4, Nick Kozauer1, Lauren Powell3, Michele Potashman1, Kim Crimin1, Patrick O'Keefe2, Ellen Korol3, Madeline Crabtree3, Fernanda Nagase3, Vladimir Coric1, Suzanne Hendrix2
1Biohaven Pharmaceuticals, Inc., 2Pentara Corporation, 3Broadstreet HEOR, 4Clintrex
Objective:
Examine composite scores (CS) of re-weighted combinations the MDS-UPDRS items as a more sensitive measure of meaningful changes in motor progression.
Background:
As a complex degenerative disease, Parkinson’s disease (PD) affects motor abilities across diverse domains, even prior to initiation of dopaminergic therapy (DT). This work demonstrates how CS consisting of re-weighted combinations of the items from MDS-UPDRS Parts II and III can better detect meaningful changes in motor progression.
Design/Methods:
This study analyzed the Parkinson’s Progression Markers Initiative MDS-UPDRS data Parts II and III in subjects with confirmed PD naïve to DT. Patients were censored from the analysis once DT was initiated. The sensitivity of individual items to disease progression was assessed using partial least square regression. Selected items were weighted using the model coefficients and summed to create the CS. CS responsiveness to change was assessed using a 1-year mean-to-standard-deviation ratio (MSDR).
Results:
CS were generated for untreated subjects (n=428) across items from Parts II and III individually, and as a combined motor composite score (MCS). The three most responsive items (with their combined weights) were: turning in bed, getting out of bed/car/chair, and tremor (45%) for Part II, and leg agility (left) and rest tremor amplitude – left and right (34%) for Part III. The MSDRs increased from 0.5431 to 0.5647, and 0.6341 to 0.7040, which increases power 3% and 8%, respectively. Items from Part II and III contributed to 37.4% and 62.6% of the weighed MCS. Similar items were retained in the MCS as in the individual CSs, and the MSDR increased from 0.7615 to 0.8591, increasing power 8%.
Conclusions:
Endpoints derived from the CS reflecting items from combined domains can measure clinically meaningful progression of motor symptoms and the impacts with greater sensitivity compared to using the totality of items from existing tools.