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Addressing heterogeneity in amyotrophic lateral sclerosis CLINICAL TRIALS
Author(s) -
Goyal Namita A.,
Berry James D.,
Windebank Anthony,
Staff Nathan P.,
Maragakis Nicholas J.,
Berg Leonard H.,
Genge Angela,
Miller Robert,
Baloh Robert H.,
Kern Ralph,
Gothelf Yael,
Lebovits Chaim,
Cudkowicz Merit
Publication year - 2020
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26801
Subject(s) - amyotrophic lateral sclerosis , clinical trial , medicine , disease , biomarker , precision medicine , drug development , personalized medicine , bioinformatics , pathology , drug , biology , pharmacology , biochemistry
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder with complex biology and significant clinical heterogeneity. Many preclinical and early phase ALS clinical trials have yielded promising results that could not be replicated in larger phase 3 confirmatory trials. One reason for the lack of reproducibility may be ALS biological and clinical heterogeneity. Therefore, in this review, we explore sources of ALS heterogeneity that may reduce statistical power to evaluate efficacy in ALS trials. We also review efforts to manage clinical heterogeneity, including use of validated disease outcome measures, predictive biomarkers of disease progression, and individual clinical risk stratification. We propose that personalized prognostic models with use of predictive biomarkers may identify patients with ALS for whom a specific therapeutic strategy may be expected to be more successful. Finally, the rapid application of emerging clinical and biomarker strategies may reduce heterogeneity, increase trial efficiency, and, in turn, accelerate ALS drug development.