ArticleEBioMedicine2024
Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02327845 (Phenotype, Genotype & Biomarkers in ALS and Related Disorders), which is not on this map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Phenotype, Genotype & Biomarkers in ALS and Related Disorders
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diagnostic and Prognostic Value of Blood and Cerebrospinal Fluid Biomarkers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.European journal of neurology · 2025Pooled it
- TRICALS risk score augments but cannot replace neurofilament as a prognostic biomarker in ALS.Journal of neurology · 2026Trial
- Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.JAMA neurology · 2026Trial
- Article
- Plasma Proteomic Signatures Predict Incident Amyotrophic Lateral Sclerosis: A Prospective Study Stratified by C9orf72 Expansion.Journal of cachexia, sarcopenia and muscle · 2026Article
- Proteomic profile of CSF obtained at the time of diagnosis determines amyotrophic lateral sclerosis progression and survival: CXCL7 levels in disease prognosis and survival.Brain pathology (Zurich, Switzerland) · 2026Article
- Powering Neurology Drug Development Trials to Reduce False Negative Results.Clinical and translational science · 2026Review
- Data-Driven SuStaIn Model of Disability Progression in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Development of a machine learning-based survival prediction model for ALS inclusive of the advanced-stage population.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2026Article
- Troponin T and Neurofilament Light Chain Levels as Complementary Biomarkers of Disease Accumulation and Aggressiveness in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Anchoring ALS Prognosis: Neurofilament Light Chain Outperforms Inflammatory, Metabolic, and CNS Barrier Biomarkers in the METABALS Cohort.Molecular neurobiology · 2026Article
- The role of adiponectin and cytokines in Amyotrophic lateral sclerosis: assessment of disease progression and survival status.Scientific reports · 2026Article
- Small RNA sequencing identifies serum tDR-1:34-Gly-GCC tiRNA levels as a biomarker for survival in amyotrophic lateral sclerosis.iScience · 2026Article
- Correlations of cerebrospinal fluid neurofilament light chain levels with clinical and electromyography findings in amyotrophic lateral sclerosis.Irish journal of medical science · 2026Article
- Plasma isomiRs as Candidate Biomarkers for Amyotrophic Lateral Sclerosis.Neurology. Genetics · 2026Article
- Skeletal Muscle Biomarkers of Amyotrophic Lateral Sclerosis: A Large-Scale, Multi-Cohort Proteomic Study.Annals of neurology · 2026Article
- Measuring neurofilament light in human plasma and cerebrospinal fluid: a comparison of five analytical immunoassays.Clinical chemistry and laboratory medicine · 2026Article
- Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026Review
- The role of neurofilament light chain and other fluid biomarkers in cerebellar ataxias.Brain communications · 2026Review
- miRNA Biomarkers Diagnose Amyotrophic Lateral Sclerosis in Circulating Blood.Molecular neurobiology · 2025Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
backgroundWith increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used.
methodsA subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as "trial-like" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75
findingsBaseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40 pg/mL and >100 pg/mL correspond to future ALSFRS-R slopes of ∼0.5 and ∼1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ∼25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75
interpretationAmong the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency.
fundingNIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).
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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.