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Abstract Details

Exploring Expectation Bias in Parkinson’s Disease Clinical Trials by Comparing Placebo Arm Progression on MDS-UPDRS to a Natural History Dataset
Movement Disorders
P9 - Poster Session 9 (5:00 PM-6:00 PM)
16-010
To examine patterns in disease progression of newly diagnosed Parkinson’s disease (PD) participants enrolled in clinical trials vs natural history.
Differences in disease progression among PD participants enrolled in clinical trials vs natural history studies are hypothesized, partially based on a potential for expectation bias. Understanding differences in PD progression is important for interpreting results generated from such datasets.

Data were obtained from the multicenter natural history cohort Parkinson’s Progression Markers Initiative (PPMI) and the Critical Path for Parkinson’s (CPP) dataset of clinical trial placebo arms. Subjects with confirmed PD within the previous two years and naïve to dopaminergic treatment were included in the analysis. Baseline demographics and clinical characteristics were examined.  Changes in MDS-UPDRS scores (Parts I, II and III) over 24-months were compared by examining change from baseline (CFB) and mean CFB to standard deviation ratios (MSDRs). CFB and MSDRs were also calculated for individual items at 12-months.

A total of 430 and 183 participants from the PPMI and CPP databases, respectively, met inclusion criteria for this analysis. At the aggregate level baseline characteristics were similar across datasets. When MDS-UPDRS trajectories were examined, Part 1 was observed to improve over the first 12-months for subjects in CPP (MSDR: -0.21) followed by a reversion to baseline by 24-month. Subjects in PPMI consistently declined over the 24-month period (MSDRs of 0.23 and 0.36, at 12- and 24-months, respectively). Aggregate level differences in progression on Part 2 and 3 were less apparent, however at the item level there were differences in which items progressed over 12-months.

Participants enrolled in placebo arms demonstrated less decline on MDS-UPDRS Part 1 compared to natural history, which may be indicative of expectation bias.
Authors/Disclosures
Michele Potashman, PhD (Biohaven)
PRESENTER
Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Lauren Powell (Broadstreet HEOR) Lauren Powell has nothing to disclose.
Basia Rogula Basia Rogula has received personal compensation for serving as an employee of Broadstreet HEOR.
Fernanda Nagase (Broadstreet HEOR) Fernanda Nagase has nothing to disclose.
Ciara S. de Brun, MSci Ms. de Brun has received personal compensation for serving as an employee of Broadstreet HEOR.
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.
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 .
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.
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.