Abstract Details

Title The Coalition Against Major Diseases: Dopamine Transporter Neuroimaging as an Enrichment Biomarker To Enable Parkinson's Disease Clinical Trials

Topic Aging and Dementia

Presentation(s) P06 - (-)

Poster/Presentation
Number 049

Objective

Background BACKGROUND: The Coalition Against Major Diseases (CAMD) was formed by the Critical Path Institute in response to FDA's Critical Path Initiative. Reduced levels of DAT by SPECT neuroimaging correlate with known PD pathology and functional impairment.

Design/Methods DESIGN/METHODS: A literature review was conducted to identify observational and clinical studies of first diagnosed PD patients that utilized DAT imaging with longitudinal follow up, blinded imaging assessments, relevant statistics, and defined ligand. Four studies were identified that fulfilled the criteria and each study was further analyzed to define DAT imaging's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), calculated with 95% confidence intervals (Clopper and Pearson method). Nine separate comparisons of DAT imaging in patients with PD vs. essential tremor, or vascular, drug-induced, or other secondary parkinsonisms, were evaluated with visual or quantitative interpretation of DAT images vs. the "gold standard" clinical diagnosis by movement disorder experts.

Results RESULTS: Statistical parameters of DAT neuroimaging identified patients with PD and other primary parkinsonian syndromes and supported a robust and stable method for discriminating PD from essential tremor, and from cases of vascular, drug-induced, or other secondary parkinsonisms, that may have scans without evidence of dopamine deficiency (SWEDDs). Sensitivity ranged from 68-96% and specificity from 74-100% (with one outlier). Differences in the study design (e.g. length of follow-up) and neurobiology likely contributed to this heterogeneity.

Conclusions CONCLUSIONS: These analyses suggest that in early PD patients, reduced levels of DAT assessed by SPECT can discriminate PD from essential tremor and certain secondary parkinsonisms without nigrostriatal degeneration (possible SWEDD cases). Such data support the use of DAT imaging to enable identification of a target patient population for enrichment of clinical trials with idiopathic PD patients.

Authors/Disclosures
Mark F. Gordon, MD, FAAN (Teva Pharmaceuticals) PRESENTER	Dr. Gordon has received personal compensation for serving as an employee of Teva. Dr. Gordon has stock in Teva.
Diane Stephenson	No disclosure on file
Christopher Coffey, PhD, FAAN (University of Iowa)	Dr. Coffey has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Coffey has received research support from NIH. The institution of Dr. Coffey has received research support from Michael J Fox Foundation.
Patricia Cole	No disclosure on file
	No disclosure on file
Igor Grachev	No disclosure on file
Donald Grosset	Donald Grosset has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Glasgow Memory Clinic. Donald Grosset has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Donald Grosset has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for AbbVie. Donald Grosset has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Britannia. Donald Grosset has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GE Healthcare. The institution of Donald Grosset has received research support from Parkinson's UK. Donald Grosset has received personal compensation in the range of $10,000-$49,999 for serving as a Clinical Director Excellence Network with Parkinson's UK.
	No disclosure on file
Mikko Kuoppamaki (Orion Pharma)	No disclosure on file
	No disclosure on file
Kenneth L. Marek, MD (IND)	Dr. Marek has received personal compensation for serving as an employee of IND. Dr. Marek has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for invicro. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for takeda. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Koneksa. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Xingimaging. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Marek has received research support from Michael J Fox Foundation.
Dawn C. Matthews, MS (Abiant, Inc.)	No disclosure on file
Bradford Dickerson, MD, FAAN	Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lantheus. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Dickerson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Dickerson has received publishing royalties from a publication relating to health care. Dr. Dickerson has received publishing royalties from a publication relating to health care.
	No disclosure on file
David S. Russell, MD, PhD (Invicro)	Dr. Russell has received personal compensation for serving as an employee of Invicro. Dr. Russell has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine. The institution of Dr. Russell has received research support from Biogen. The institution of Dr. Russell has received research support from Roche. The institution of Dr. Russell has received research support from Voyager. The institution of Dr. Russell has received research support from Eisai. The institution of Dr. Russell has received research support from Neuraly. The institution of Dr. Russell has received research support from Michael J. Fox Foundation. The institution of Dr. Russell has received research support from National Institutes for Health. The institution of Dr. Russell has received research support from Eli Lilly. The institution of Dr. Russell has received research support from Aprinoia.
John P. Seibyl, MD	Dr. Seibyl has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Invicro. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Life Molecular Imaging. Dr. Seibyl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Seibyl has received stock or an ownership interest from Invicro.
	No disclosure on file
Yafit Stark, PhD (Teva Pharmaceutical Industries, Ltd)	No disclosure on file
	No disclosure on file

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