Rethinking Digital Outcome Measures for Amyotrophic Lateral Sclerosis Trials: Consensus Priorities for Actigraphy Harmonization, Validation, and Regulatory Readiness.

Abstract

Amyotrophic lateral sclerosis (ALS) clinical trials need outcome measures that complement established end points while capturing how people function in daily life. In this viewpoint, we draw on our collective experience in ALS research, clinical trials, digital-measure development, and regulatory science, together with published evidence, a preliminary patient survey, stakeholder discussions, and experience from multisite actigraphy studies. We argue that the field now has a substantial base of longitudinal data and candidate measures, but lacks the coordinated framework needed to compare, prioritize, and validate them across studies. We identify 4 linked priorities: adopt fit-for-purpose measures in stages and within defined contexts of use; harmonize data collection and analysis; use data to shortlist and validate measures across cohorts; and prepare actigraphy methods for trial adoption through early industry and regulatory engagement. Across these priorities, actigraphy should complement rather than replace established clinical outcomes, with its integration guided by patient relevance, ALS phenotypic heterogeneity, participant, and caregiver burden, and the intended context of use. Our central message is that progress now depends less on generating additional isolated datasets or measures than on coordinating the evaluation of existing assets, and aligning future evidence generation.