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The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
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) support...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700608/ https://www.ncbi.nlm.nih.gov/pubmed/31306141 http://dx.doi.org/10.3233/JPD-191648 |
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author | Stephenson, Diane Hill, Derek Cedarbaum, Jesse M. Tome, Maria Vamvakas, Spiros Romero, Klaus Conrado, Daniela J. Dexter, David T. Seibyl, John Jennings, Danna Nicholas, Timothy Matthews, Dawn Xie, Zhiyong Imam, Syed Maguire, Paul Russell, David Gordon, Mark Forrest Stebbins, Glenn T. Somer, Ed Gallagher, Jill Roach, Arthur Basseches, Peter Grosset, Donald Marek, Kenneth |
author_facet | Stephenson, Diane Hill, Derek Cedarbaum, Jesse M. Tome, Maria Vamvakas, Spiros Romero, Klaus Conrado, Daniela J. Dexter, David T. Seibyl, John Jennings, Danna Nicholas, Timothy Matthews, Dawn Xie, Zhiyong Imam, Syed Maguire, Paul Russell, David Gordon, Mark Forrest Stebbins, Glenn T. Somer, Ed Gallagher, Jill Roach, Arthur Basseches, Peter Grosset, Donald Marek, Kenneth |
author_sort | Stephenson, Diane |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6700608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67006082019-09-03 The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease Stephenson, Diane Hill, Derek Cedarbaum, Jesse M. Tome, Maria Vamvakas, Spiros Romero, Klaus Conrado, Daniela J. Dexter, David T. Seibyl, John Jennings, Danna Nicholas, Timothy Matthews, Dawn Xie, Zhiyong Imam, Syed Maguire, Paul Russell, David Gordon, Mark Forrest Stebbins, Glenn T. Somer, Ed Gallagher, Jill Roach, Arthur Basseches, Peter Grosset, Donald Marek, Kenneth J Parkinsons Dis Review 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. IOS Press 2019-07-30 /pmc/articles/PMC6700608/ /pubmed/31306141 http://dx.doi.org/10.3233/JPD-191648 Text en © 2019 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Stephenson, Diane Hill, Derek Cedarbaum, Jesse M. Tome, Maria Vamvakas, Spiros Romero, Klaus Conrado, Daniela J. Dexter, David T. Seibyl, John Jennings, Danna Nicholas, Timothy Matthews, Dawn Xie, Zhiyong Imam, Syed Maguire, Paul Russell, David Gordon, Mark Forrest Stebbins, Glenn T. Somer, Ed Gallagher, Jill Roach, Arthur Basseches, Peter Grosset, Donald Marek, Kenneth The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title_full | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title_fullStr | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title_full_unstemmed | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title_short | The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease |
title_sort | qualification of an enrichment biomarker for clinical trials targeting early stages of parkinson’s disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700608/ https://www.ncbi.nlm.nih.gov/pubmed/31306141 http://dx.doi.org/10.3233/JPD-191648 |
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