Re-weighting MDS-UPDRS Parts II and III Items to Improve Assessment of Motor Decline in Untreated Parkinson’s Disease
Samuel Dickson1, Basia Rogula2, Jordan Dubow3, Nick Kozauer4, Lauren Powell2, Michele Potashman4, Patrick O'Keefe1, Ellen Korol2, Madeleine Crabtree2, Fernanda Nagase2, Vlad Coric4, Liana Rosenthal5, Suzanne Hendrix1, Gilbert L'Italien4
1Pentara Corporation, 2Broadstreet HEOR, 3Clintrex, 4Biohaven Pharmaceuticals, 5Department of Neurology, Johns Hopkins School of Medicine
Objective:

PARCOMS-Motor was developed using two different datasets (natural history and clinical trial placebo arms) to optimize motor decline assessment in patients with untreated PD.

Background:

There is considerable interest in improving the sensitivity of Parkinson’s disease (PD) measures to adequately capture the effect of disease modifying therapies.

Design/Methods:

Subjects with confirmed PD naïve to dopaminergic treatment from the Parkinson’s Progression Markers Initiative (PPMI) and the Critical Path for Parkinson’s (CPP) datasets were included in the analysis. Items from MDS-UPDRS Parts II and III were selected and weighted based on responsiveness to clinical decline using partial least square regression. The responsiveness of PARCOMS-Motor 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:

In PARCOMS-Motor, 34 of the 46 items from the MDS-UPDRS Parts II and III were retained in either the CPP or PPMI derived composite scales: 17 (50%) were retained in both the PPMI and the CPP derived composite scales; six (18%) were included only in the CPP composite scale; and 11 (32%) were retained only in the PPMI scale. Items retained in both PPMI and CPP derived scales predominantly measured irregular/involuntary movement (including items capturing bradykinesia, tremor and rigidity) concepts. In both scales, activities of daily living and oral dysfunction items had similar weights. In PARCOMS-Motor there was a 13.1% and 27.5% increase in the MSDR compared to the original scales, for PPMI and CPP respectively.

Conclusions:

More responsive scales were derived from the MDS-UPDRS motor items using two distinct data sources. The two PARCOMS-Motor scales were not entirely consistent, which may be explained by differences in disease characteristics of patients enrolled in clinical trials versus natural history datasets.

10.1212/WNL.0000000000208766
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