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

Stephenson, Diane; Hill, Derek L. G.; Cedarbaum, Jesse M.; Tome, Maria; Vamvakas, Spiros; Romero, Klaus; Conrado, Daniela J.; Dexter, David T.; Seibyl, John; Jennings, Danna; Nicholas, Timothy; Matthews, Dawn; Xie, Zhihui; Imam, Syed H.; Maguire, R. Paul; Russell, David H.; Gordon, Mark Forrest; Stebbins, Glenn T.; Somer, Ed; Gallagher, Jill; Roach, Arthur; Basseches, Peter J.; Grosset, Donald; Marek, Kenneth

doi:10.3233/jpd-199003

Cited by 15 publications

(26 citation statements)

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“…Critical Path for Parkinson's (CPP), one of several Critical Path Institute consortia, was established as an international consortium of academic institutions, pharmaceutical companies, patient advocacy organizations, and regulators to collectively advance the development of effective treatments for PD by aligning with regulatory agencies and promoting excellence in data science using a data-driven research approach [42]. The progress of CPP to date includes qualification of dopamine transporter imaging as an enrichment biomarker for PD clinical trials in patients with early Parkinsonian symptoms [43], and the development of a global integrated unified database of standardized patient level data from clinical studies conducted around the world [42]. When CPP was launched, the concept of focusing on digital technology was envisioned as a future strategy [42].…”

Section: Case Study: Engagement Of Regulatory Agencies By Multidiscipmentioning

confidence: 99%

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

et al. 2020

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Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies.

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Section: Case Study: Engagement Of Regulatory Agencies By Multidiscipmentioning

confidence: 99%

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

et al. 2020

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“…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.…”

Section: Drug Development Toolsmentioning

confidence: 99%

Open Data Revolution in Clinical Research: Opportunities and Challenges

Shahin

Bhattacharya

Silva

et al. 2020

Clinical Translational Sci

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Efforts for sharing individual clinical data are gaining momentum due to a heightened recognition that integrated data sets can catalyze biomedical discoveries and drug development. Among the benefits are the fact that data sharing can help generate and investigate new research hypothesis beyond those explored in the original study. Despite several accomplishments establishing public systems and guidance for data sharing in clinical trials, this practice is not the norm. Among the reasons are ethical challenges, such as privacy of individuals, data ownership, and control. This paper creates awareness of the potential benefits and challenges of sharing individual clinical data, how to overcome these challenges, and how as a clinical pharmacology community we can shape future directions in this field.

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“…9 In this context, DAT imaging serves as a secondary outcome measure for treatment effects 10,11 and has recently qualified as enrichment biomarker. 12 Several radioligands targeting the DAT have been developed over the last decades, but only few SPECT ligands have reached a broad clinical application. 13 To take advantage of the higher resolution and sensitivity of modern PET systems, the novel radioligand [ 18 F]-(E)-N-(3-iodoprop-2-enyl)-2b-carbofluoroethoxy-3b-(4-methylphenyl)nortropane ([ 18 F]-FE-PE2I) was recently evaluated in humans.…”

Section: Introductionmentioning

confidence: 99%

Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

Brumberg

Kerstens

Cselényi

et al. 2020

J Cereb Blood Flow Metab

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Quantification of dopamine transporter (DAT) availability with [18F]FE-PE2I PET enables the detection of presynaptic dopamine deficiency and provides a potential progression marker for Parkinson`s disease (PD). Simplified quantification is feasible, but the time window of short acquisition protocols may have a substantial impact on the reliability of striatal binding estimates. Dynamic [18F]FE-PE2I PET data of cross-sectional (33 PD patients, 24 controls), test–retest (9 patients), and longitudinal (12 patients) cohorts were used to assess the variability and reliability of specific binding ratios (SBR) measured during early peak and late pseudo-equilibrium. Receiver operating characteristics area under the curve (PD vs. controls) was high for early (0.996) and late (0.991) SBR. Early SBR provided more favourable effect size, absolute variability, and standard error of measurement than late SBR (caudate: 1.29 vs. 1.23; 6.9% vs. 9.8%; 0.09 vs. 0.20; putamen: 1.75 vs. 1.67; 7.7% vs. 14.0%; 0.08 vs. 0.17). The annual percentage change was comparable for both time windows (−7.2%–8.5%), but decline was significant only for early SBR. Whereas early and late [18F]FE-PE2I PET acquisitions have similar discriminative power to separate PD patients and controls, the early peak equilibrium acquisition can be recommended if [18F]FE-PE2I is used to measure longitudinal changes of DAT availability.

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

Cited by 15 publications

References 0 publications

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Open Data Revolution in Clinical Research: Opportunities and Challenges

Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

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

Cited by 15 publications

References 0 publications

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Open Data Revolution in Clinical Research: Opportunities and Challenges

Simplified quantification of [18F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

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Product

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Simplified quantification of [¹⁸F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium