The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
| العنوان: | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
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| المؤلفون: | Arthur Roach, Ed Somer, Klaus Romero, Glenn T. Stebbins, John Seibyl, Daniela J. Conrado, Maria B. Tome, Timothy Nicholas, Donald G. Grosset, Peter Basseches, Paul Maguire, Kenneth Marek, David T Dexter, David S. Russell, Diane Stephenson, Syed Z. Imam, Derek L. G. Hill, Dawn Matthews, Jill Gallagher, Zhiyong Xie, Danna Jennings, Mark Forrest Gordon, Jesse M. Cedarbaum, Spiros Vamvakas |
| المصدر: | Journal of Parkinson's Disease |
| بيانات النشر: | IOS Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Parkinson's disease, enrichment biomarker, Review, Disease, 01 natural sciences, Motor symptoms, SWEDD, 03 medical and health sciences, Cellular and Molecular Neuroscience, PPMI, 0302 clinical medicine, Physical medicine and rehabilitation, Neuroimaging, EMA, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, PRECEPT, Societies, Medical, Tomography, Emission-Computed, Single-Photon, Clinical Trials as Topic, Dopamine Plasma Membrane Transport Proteins, business.industry, Clinical Studies as Topic, 010102 general mathematics, Dopaminergic, Parkinson Disease, medicine.disease, Corpus Striatum, 3. Good health, Clinical trial, Observational Studies as Topic, 030104 developmental biology, Dopamine transporter, Biomarker (medicine), Observational study, Neurology (clinical), Erratum, business, Biomarkers, 030217 neurology & neurosurgery |
| الوصف: | As therapeutic trials target early stages of Parkinson's disease (PD), appropriate patient selection based purely on clinical criteria poses significant challenges. Members of the Critical Path for Parkinson's Consortium formally submitted documentation to the European Medicines Agency (EMA) supporting the use of Dopamine Transporter (DAT) neuroimaging in early PD. Regulatory documents included a comprehensive literature review, a proposed analysis plan of both observational and clinical trial data, and an assessment of biomarker reproducibility and reliability. The research plan included longitudinal analysis of the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) and the Parkinson's Progression Markers Initiative (PPMI) study to estimate the degree of enrichment achieved and impact on future trials in subjects with early motor PD. The presence of reduced striatal DAT binding based on visual reads of single photon emission tomography (SPECT) scans in early motor PD subjects was an independent predictor of faster decline in UPDRS Parts II and III as compared to subjects with scans without evidence of dopaminergic deficit (SWEDD) over 24 months. The EMA issued in 2018 a full Qualification Opinion for the use of DAT as an enrichment biomarker in PD trials targeting subjects with early motor symptoms. Exclusion of SWEDD subjects in future clinical trials targeting early motor PD subjects aims to enrich clinical trial populations with idiopathic PD patients, improve statistical power, and exclude subjects who are unlikely to progress clinically from being exposed to novel test therapeutics. |
| وصف الملف: | application/pdf |
| تدمد: | 1877-718X 1877-7171 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43f8abaa6c630687f90f70ba6c3641c6Test https://doi.org/10.3233/jpd-191648Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....43f8abaa6c630687f90f70ba6c3641c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1877718X 18777171 |
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