ReviewMuscle & nerve2020
Addressing heterogeneity in amyotrophic lateral sclerosis CLINICAL TRIALS.
Review in Muscle & nerve, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- What can we learn on ALS pathophysiology from iPSC-derived motor neurons harbouring TARBDP mutations: a systematic review.Translational neurodegeneration · 2026Pooled it
- MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review.CNS neuroscience & therapeutics · 2024Pooled it
- The landscape of neurophysiological outcome measures in ALS interventional trials: A systematic review.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2022Pooled it
- Respiratory Function Improvement and Lifespan Extension Following Immunotherapy with NP001 Support the Concept That Amyotrophic Lateral Sclerosis (ALS) Is an Immuno-Neurologic Disease.International journal of molecular sciences · 2025Trial
- Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses.Muscle & nerve · 2022Trial
- A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis.Muscle & nerve · 2022Trial
- Cerebrospinal fluid inflammatory proteomic profiling identifies biomarkers linked to disease progression in amyotrophic lateral sclerosis.Journal of neurology · 2026Article
- Data-Driven SuStaIn Model of Disability Progression in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Combination Pharmacology for ALS: A Mechanistic Rationale.International journal of molecular sciences · 2026Review
- Article
- Artificial intelligence revolutionizing CNS drug discovery and development.Drug discovery today · 2026Review
- Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits.Biomolecules · 2026Article
- Imaging-derived neuromuscular ultrasound phenotypes are associated with functional status in amyotrophic lateral sclerosis.Journal of neurology · 2026Article
- My Amyotrophic Lateral Sclerosis (ALS) Journey from Weakness to Diagnosis: A Journey of Hope.Healthcare (Basel, Switzerland) · 2025Article
- Machine learning predicts distinct biotypes of amyotrophic lateral sclerosis.European journal of human genetics : EJHG · 2025Article
- Comparison of Demographics: National Amyotrophic Lateral Sclerosis Registry and Clinical Trials Data.Journal of racial and ethnic health disparities · 2025Article
- Meta-Analysis of Gene Expression in Bulk-Processed Post-Mortem Spinal Cord from ALS Patients and Normal Controls.NeuroSci · 2025Article
- Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.Life (Basel, Switzerland) · 2025Review
- Population-Based Versus Hospital-Based Data in Amyotrophic Lateral Sclerosis-A Factor to Consider?European journal of neurology · 2025Article
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.