Abstract Details

Title Re-weighting MDS-UPDRS Part II Items for Optimal Sensitivity to Parkinson’s Disease Progression Using Parkinson’s Progression Markers Initiative Natural History Data

Topic Movement Disorders

Presentation(s) P11 - Poster Session 11 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-012

Objective This work examines how composite scores (CS) of re-weighted combinations of the MDS-UPDRS PART II items can better detect meaningful changes and increase success for efficacious disease-modifying treatments.

Background Parkinson’s disease (PD) clinical trials require careful planning to progress beyond Phase 2. Many in the PD community recognize the need for improvements in communication, education, funding, recruitment, and compliance, but the need to measure disease with optimized outcome is underappreciated.

Design/Methods

This study analyzed Parkinson’s Progression Markers Initiative data in subjects with confirmed PD. Three cohorts were defined based on use of levodopa or dopamine agonists (lev/DA) and presence of motor complications: untreated, early-lev/DA (motor complications absent), and later-lev/DA with motor complications (≥25% time of waking day in OFF-state and/or dyskinesia assessed on MDS-UPDRS). Sensitivity of individual items to disease progression was assessed using partial least square regression. Selected items were weighted using model coefficients and summed to create the CS. CS responsiveness to change was assessed using a 2-year mean to standard deviation ratio (MSDR) for treated and 1-year for untreated (due to data limitations).

Results CS were generated for untreated (n=428), early-lev/DA (n=424), and later-lev/DA (n=536) cohorts separately. The three most responsive items (with their combined weights) were: turning in bed, getting out of bed/car/chair, tremor (45%); turning in bed, getting out of bed, and speech (56%); and turning in bed, speech, and handwriting (53%) respectively. The MSDRs increased from 0.5431 to 0.5647, 0.4265 to 0.4994, and 0.3128 to 0.3849, respectively. Corresponding sample size decreases were ~7%, 27%, and 34%, reflecting powering improvements of ~3%, 11% and 13%.

Conclusions Endpoints derived from the three CS presented can measure clinically meaningful progression with greater sensitivity compared to existing tools.

Authors/Disclosures
Samuel Dickson (Pentara Corporation) PRESENTER	Mr. Dickson has nothing to disclose.
Basia Rogula	Basia Rogula has received personal compensation for serving as an employee of Broadstreet HEOR.
Jordan S. Dubow, MD	Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Revalesio .
Nick Kozauer (Biohaven Pharmaceuticals)	Dr. Kozauer has received personal compensation for serving as an employee of Biohaven. Dr. Kozauer has stock in Biohaven.
Lauren Powell (Broadstreet HEOR)	Lauren Powell has nothing to disclose.
Michele Potashman, PhD (Biohaven)	Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Kim Crimin	No disclosure on file
Patrick O'Keefe (Pentara)	Patrick O'Keefe has received personal compensation for serving as an employee of Pentara.
Ellen Korol (Broadstreet HEOR)	Ellen Korol has received personal compensation for serving as an employee of Broadstreet HEOR.
Madeleine Crabtree (Broadstreet HEOR)	Madeleine Crabtree has nothing to disclose.
Fernanda Nagase (Broadstreet HEOR)	Fernanda Nagase has nothing to disclose.
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Suzanne Hendrix, PhD (Pentara)	Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has or had stock in Pentara.
Gilbert J. L'Italien	Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has stock in biohaven pharmaceuticals.

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