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) 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

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) 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

Practices Of Psychological Inquiry: The Global Challenge

The preceding chapter challenged the guiding assumptions and values underpinning the major practices of Western psychology. If such practices are potentially inimical to dealing with global challenges, what alternatives are invited? Here we turn attention to practices of inquiry. In a globally responsible psychology, how are we to conceptualize the practice of research? As we find, this question cannot be treated separately from assumptions concerning the nature of knowledge. As we propose, to realize the potentials of a value-based progressivism, we must replace an outworn positivism with a social epistemology. In what follows, we explore this epistemological transition, and outline major forms of inquiry thus favored

Climate policy conflict in the U.S. states: a critical review and way forward

Abstract Many U.S. states have taken significant action on climate change in recent years, demonstrating their commitment despite federal policy gridlock and rollbacks. Yet, there is still much we do not know about the agents, discourses, and strategies of those seeking to delay or obstruct state-level climate action. We first ask, what are the obstacles to strong and effective climate policy within U.S. states? We review the political structures and interest groups that slow action, and we examine emerging tensions between climate justice and the technocratic and/or market-oriented approaches traditionally taken by many mainstream environmental groups. Second, what are potential solutions for overcoming these obstacles? We suggest strategies for overcoming opposition to climate action that may advance more effective and inclusive state policy, focusing on political strategies, media framing, collaboration, and leveraging the efforts of ambitious local governments