Outcome Assessment in Parkinson Disease Prevention Trials

Abstract

Background and ObjectivesThe prodromal phase of Parkinson disease (PD) is accompanied by subtle clinical signs that are not sufficient for diagnosis but could potentially be measured in the context of clinical trials of therapies intended to delay or prevent more definitive clinical features. The objective of this study was to review the available literature on the presence and time course of subtle motor features in prodromal PD in the context of planning for possible clinical trials.MethodsWe reviewed the available literature based on expert opinion. We considered a range of outcomes including measurement of clinical features, patient-reported outcomes, digital markers, and clinical diagnosis.ResultsWe considered these features and measures in the context of patient stratification, intermediate outcomes, and clinically relevant end points, including phenoconversion.DiscussionSubstantial progress has been made in understanding how motor features evolve in the period immediately before a PD diagnosis. Digital measures hold substantial progress for measurement precision and may be additionally relevant because they can be used in naturalistic environments outside the clinic. Future studies should focus on advancing digital sensor technology and analysis and developing methods to implement available methods, particularly determination of a clinical diagnosis of PD, in a clinical trial context.

Path to Parkinson Disease Prevention

“…Although a number of observational studies comprehensively summarized by Mirelman et al 39 have provided substantial data on the risk of phenoconversion in prodromal cohorts to clinically defined PD, definition of endpoints for clinical trials still remains challenging. Possible endpoints for trials in the prodromal phase follow different concepts, each with inherent limitations.1) Phenoconversion, that is, a clinical diagnosis of PD: Although this endpoint seems most relevant, operationalization of this subjective clinical outcome is difficult, and standardization of phenoconversion as an outcome measure remains a major challenge.…”

“…Although a number of observational studies comprehensively summarized by Mirelman et al 39 have provided substantial data on the risk of phenoconversion in prodromal cohorts to clinically defined PD, definition of endpoints for clinical trials still remains challenging. Possible endpoints for trials in the prodromal phase follow different concepts, each with inherent limitations.…”

Isolation and Characterization of Cell-Free DNA from Cerebral Organoids

“…Effective treatments for a wide range of neurological disorders, including epilepsy, neurodegenerative diseases (Dementia, Alzheimer's, and Parkinson's), and neurodevelopmental disorders such as autism spectrum disorder (ASD), share a common feature: establishing early and accurate diagnoses [1][2][3][4][5][6]. However, this is particularly difficult in the presence of comorbidities, as neurological symptoms can result from many underlying causes [7].…”