Chapter 19 - Role of novel endpoints and evaluations of response in Parkinson disease

Abstract

With progress in our understanding of Parkinson disease (PD) and other neurodegenerative disorders, from clinical features to imaging, genetic, and molecular characterization comes the opportunity to refine and revise how we measure these diseases and what outcome measures are used as endpoints in clinical trials. While several rater-, patient-, and milestone-based outcomes for PD exist that may serve as clinical trial endpoints, there remains an unmet need for endpoints that are clinically meaningful, patient centric while also being more objective and quantitative, less susceptible to effects of symptomatic therapy (for disease-modification trials), and that can be measured over a short period and yet accurately represent longer-term outcomes. Several novel outcomes that may be used as endpoints in PD clinical trials are in development, including digital measures of signs and symptoms, as well a growing array of imaging and biospecimen biomarkers. This chapter provides an overview of the state of PD outcome measures as of 2022, including considerations for selection of clinical trial endpoints in PD, advantages and limitations of existing measures, and emerging potential novel endpoints.