Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper

Citation

Rosenfeld J, Abrahams S, McHutchinson C, Ajroud-Driss S, Weber M, Paganoni S, Mitsumoto H, Genge A, Grosskreutz J, Van Den Berg L, Andrews J & Kiernan MC (2025) Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. https://doi.org/10.1080/21678421.2025.2593308

Abstract
The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.

Keywords
ALS heterogeneity; clinical trial design; ALS subtypes; stratification; subgrouping

Journal
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

• Utility Of Patient Subgrouping In ALS Clinical Trials A World Federation Of Neurology White Paper