Abstract Details

Title Re-weighting MDS-UPDRS Part II and PDQ-39 Items to Detect Maximal Decline in Activities of Daily Living in Untreated Parkinson's disease

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (5:00 PM-6:00 PM)

Poster/Presentation
Number 5-015

Objective This work used established methods to generate a composite scale from MDS-UPDRS-Part II and PDQ-39 items optimized for sensitivity to detect functional decline over 1-year.

Background Traditional measures used in clinical trials of disease-modifying treatments (DMTs) in early Parkinson’s disease (PD) may fail to detect treatment effects on patients’ daily functioning over feasible study timeframes for otherwise effective treatments.

Design/Methods Data from 140 subjects with confirmed early PD who were naïve to dopaminergic therapies were selected from the placebo groups of five DMT trials within the Critical Path for Parkinson’s dataset. Patients were censored at PD treatment initiation. Partial least squares regression was used to select and weight items from MDS-UPDRS-Part II and PDQ-39 that maximize the observable signal of disease progression in early unmedicated PD (PARCOMS-Function). PARCOMS-Function’s ability to detect change was measured using a 1-year mean-to-standard-deviation ratio (MSDR), a ratio of signal-to-noise with higher values indicating better sensitivity.

Results This method selected 15 of the 52 possible items to form PARCOMS-Function – seven from MDS-UPDRS-Part II and eight from PDQ-39. The items with the highest contribution (indicating responsiveness to change in this population) were hygiene (17.2%), speech (12.6%), and handwriting (11.2%) from Part II and walking half a mile (8.7%), muscle cramps (8.3%), and buttons and shoelaces (6.3%) from PDQ-39. The 1-year MSDR of PARCOMS-Function was 0.6534, reflecting increases in the ability to detect change of 12.3% compared to Part II alone, and 339.1% compared to PDQ-39 alone.

Conclusions PARCOMS-Function is a re-weighted optimized version of existing measures, with greater sensitivity to detect functional decline in early unmedicated patients with PD. Use of PARCOMS-Function could increase trial efficiency and power to detect meaningful delay in disease progression with DMTs.

Authors/Disclosures
Gilbert J. L'Italien PRESENTER	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.
Samuel Dickson (Pentara Corporation)	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.
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.
Vlad Coric	No disclosure on file
Liana Rosenthal, MD (Johns Hopkins School of Medicine)	Dr. Rosenthal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Rosenthal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reata Pharmaceuticals. Dr. Rosenthal has received research support from NIH. Dr. Rosenthal has received research support from Gordon and Marilyn Macklin Foundation. Dr. Rosenthal has received research support from The Daniel B. and Florence E. Green Foundation. Dr. Rosenthal has received research support from National Ataxia Foundation. Dr. Rosenthal has received research support from Michael J. Fox Foundation. Dr. Rosenthal has received research support from Pfizer. Dr. Rosenthal has received research support from Biohaven Pharmaceuticals. Dr. Rosenthal has a non-compensated relationship as a Medical Director, ex-officio Member of the Board with National Ataxia Foundation that is relevant to AAN interests or activities.
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.

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