ArticleAmyotrophic lateral sclerosis & frontotemporal degeneration
The ALSFRS as an outcome measure in therapeutic trials and its relationship to symptom onset.
Article in Amyotrophic lateral sclerosis & frontotemporal degeneration. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: A systematic review and meta-analysis.Brain and behavior · 2022Pooled it
- Study 19 (MCI186-19) Post Hoc Analyses.Muscle & nerve · 2026Trial
- Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.JAMA neurology · 2026Trial
- A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS.Annals of clinical and translational neurology · 2022Trial
- Long-term edaravone efficacy in amyotrophic lateral sclerosis: Post-hoc analyses of Study 19 (MCI186-19).Muscle & nerve · 2020Trial
- Transplantation of Mesenchymal Stromal Cells in Patients With Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial.Cell transplantation · 2017Trial
- Data-Driven SuStaIn Model of Disability Progression in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 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
- Associations of cognitive and behavioural impairment in ALS with brain pathology: pTDP-43 versus microglial activation.Journal of neurology · 2026Article
- Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial.Scientific reports · 2026Article
- Greek Registry for Amyotrophic Lateral Sclerosis (ALS-GR): An Observational Cohort of Individuals With ALS Across 11 Specialized Centers in Greece.European journal of neurology · 2025Observational
- Analytical and clinical validation of step counting method in people living with amyotrophic lateral sclerosis.Scientific reports · 2025Article
- Antisense oligonucleotide depletion ofmedRxiv : the preprint server for health sciences · 2025Article
- Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.Journal of comparative effectiveness research · 2025Observational
- Phosphorylated neurofilament heavy chain (pNfH) concentration in cerebrospinal fluid predicts overall disease aggressiveness (D50) in amyotrophic lateral sclerosis.Frontiers in neuroscience · 2025Article
- Glymphatic dysfunction in amyotrophic lateral sclerosis: a multimodal MRI investigation of brain-CSF functional and structural dynamics.Frontiers in neuroscience · 2025Article
- Prognostic factors affecting ALS progression through disease tollgates.Journal of neurology · 2024Article
- Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.Journal of neurology · 2024Article
- Prognostic Factors and Epidemiology of Amyotrophic Lateral Sclerosis in Southeastern United States.Mayo Clinic proceedings. Innovations, quality & outcomes · 2024Article
- Multimodal speech biomarkers for remote monitoring of ALS disease progression.Computers in biology and medicine · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The reduction in ALS Functional Rating Score (ALSFRS) from reported symptom onset to diagnosis is used to estimate rate of disease progression. ALSFRS decline may be non-linear or distorted by drop-outs in therapeutic trials, reducing the reliability of change in slope as an outcome measure. The PRO-ACT database uniquely allows such measures to be explored using historical data from negative therapeutic trials. The decline of functional scores was analysed in 18 pooled trials, comparing rates of decline based on symptom onset with rates calculated between interval assessments. Strategies to mitigate the effects of trial drop-out were considered. Results showed that progression rate calculated by symptom onset underestimated the subsequent rate of disability accumulation, although it predicted survival more accurately than four-month interval estimates of δALSFRS or δFVC. Individual ALSFRS and FVC progression within a typical trial duration were linear. No simple solution to correct for trial drop-out was identified, but imputation using δALSFRS appeared least disruptive. In conclusion, there is a trade-off between the drive to recruit trial participants soon after symptom onset, and reduced reliability of the ALSFRS-derived progression rate at enrolment. The need for objective markers of disease activity as an alternative to survival-based end-points is clear and pressing.
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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.