The Phase 2 Endpoint Dilemma: Bridging Subjective Scales and Objective Measures in Neurodegenerative Trials

Phase 2 neurodegenerative trials are increasingly challenged by slow disease trajectories, heterogeneous patient populations, and blunt legacy endpoints that struggle to detect treatment-related change over typical study durations. Traditional scales such as ADAS-Cog and MDS-UPDRS, while well-established, often lack sensitivity in early disease, are vulnerable to rater and practice effects, and may insufficiently capture subtle but clinically meaningful benefits.

This webinar will examine when and how to move beyond single-scale approaches toward more informative composite strategies, highlighting circumstances in which composites enhance signal detection versus when they introduce additional noise, complexity, and interpretability risk. We will explore practical frameworks for integrating functional, cognitive, and biomarker measures into coherent endpoint hierarchies that support both mechanistic insight and regulatory relevance. Finally, we will discuss how real-world evidence and natural history data can be leveraged to select, calibrate, and power Phase 2 endpoints capable of detecting meaningful change within shorter trial timeframes, improving go/no-go decision quality for emerging neurodegenerative therapies.

Key Learning Objectives:
– Evaluate the strengths and limitations of traditional subjective scales (e.g., ADAS-Cog, MDS-UPDRS) in Phase 2 neurodegenerative trials and identify when alternative or composite strategies are warranted

– Apply practical frameworks to integrate cognitive, functional, and biomarker endpoints into coherent, regulator-ready hierarchies that enhance signal detection while minimizing interpretability risk

– Leverage real-world evidence and natural history datasets to inform endpoint selection, calibration, and powering strategies that improve Phase 2 go/no-go decision-making