Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease

Abstract

The Critical Path for Parkinson's ( CPP ) Imaging Biomarker and Modeling and Simulation working groups aimed to achieve qualification opinion by the European Medicines Agency ( EMA ) Committee for Medical Products for Human Use ( CHMP ) for the use of baseline dopamine transporter neuroimaging for patient selection in early Parkinson's disease clinical trials. This paper describes the regulatory science strategy to achieve this goal. CPP is an international consortium of three Parkinson's charities and nine pharmaceutical partners, coordinated by the Critical Path Institute.

The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease

“…The full qualification document including details of the data analyses and imaging methodology recommendations can be found on the EMA website [50]. The analyses that supported the qualification opinion has been published [50,62] and was accepted for publication prior to the final regulatory qualification. The qualification document contains the operational details required to employ DAT SPECT imaging in a clinical trial of patients with early motor PD.…”

“…This review highlights the formal qualification opinion issued by the European Medicines Agency (EMA) for the use of molecular neuroimaging of the dopamine transporter (DAT) as an enrichment biomarker for use in PD clinical trials. A manuscript focused on highlighting the data analyses and regulatory aspects of this project was recently published [62].…”

Open Data Revolution in Clinical Research: Opportunities and Challenges

“…This effort followed a similar approach to the one used before in the context of early-stage Parkinson's disease, demonstrating the utility of dopamine transporter neuroimaging as enrichment biomarker for clinical trials. [34][35][36] Such effort was led by the Critical Path for Parkinson's consortium, and used individual-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the disease in the Parkinson's Progression Markers Initiative observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial. The analysis served as the basis for the EMA qualification of the dopamine transporter as an enrichment biomarker in that patient population.…”

Hippocampal Neuroimaging‐Informed Clinical Trial Enrichment Tool for Amnestic Mild Cognitive Impairment Using Open Data

“…As a second step, this model was used to develop a user‐friendly web‐based application, which allows the simulation of different clinical trial designs and estimates statistical power. We used an approach similar to the one used before in the context of early‐stage Parkinson’s disease demonstrating the utility of dopamine transporter neuroimaging as an enrichment biomarker for clinical trials . The analysis served as the basis for the European Medicines Agency (EMA) qualification of the dopamine transporter as an enrichment biomarker in that patient population .…”

“…We used an approach similar to the one used before in the context of early-stage Parkinson's disease demonstrating the utility of dopamine transporter neuroimaging as an enrichment biomarker for clinical trials. [3][4][5] The analysis served as the basis for the European Medicines Agency (EMA) qualification of the dopamine transporter as an enrichment biomarker in that patient population. 6 It constitutes a "model-informed biomarker qualification, " to our knowledge, presented for the first time in the literature.…”