Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects
Abstract
Many of the available disability outcome measures used in clinical trials of multiple sclerosis are insensitive to change over time, inadequately validated, or insensitive to patient-perceived health status or quality of life. Increasing focus on therapies that slow or reverse disability progression makes it essential to refine existing measures or to develop new tools. Major changes to the expanded disability status scale should be avoided to prevent the loss of acceptance by regulators as a measure for primary outcomes in trials that provide substantial evidence of effectiveness. Rather, we recommend practical refinements. Conversely, although substantial data support the multiple sclerosis functional composite as an alternative measure, changes to its component tests and scoring method are needed. Novel approaches, including the use of composite endpoints, patient-reported outcomes, and measurement of biomarkers, show promise as adjuncts to the current disability measures, but are insufficiently validated to serve as substitutes. A collaborative approach that involves academic experts, regulators, industry representitives, and funding agencies is needed to most effectively develop disability outcome measures.
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EDSS has several shortcomings including its non-linear ordinal nature, variability between raters, overemphasis on ambulation, and inadequate capture of cognitive impairment.
“Despite its widespread use and regulatory precedent, the EDSS has several shortcomings including its non-linear ordinal nature, variability between raters, overemphasis on ambulation, and inadequate capture of cognitive impairment52.”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [52]
EDSS is the most frequently used disability measure in people with multiple sclerosis, but has major limitations, and does not specifically measure balance problems.
“Expanded Disability Status Scale (EDSS) (10) is the most frequently used disability measure in pwMS, but has major limitations, and does not specifically measure balance problems (11).”
From The instrumented single leg stance test detects early balance impairment in people with multiple sclerosis (2023) · cites this paper as [11]
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- Authors
- Cohen, J. A., Reingold, S. C., Polman, C. H., & Wolinsky, J. S.
- Affiliations
- Cleveland Clinic (US)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Cohen, Jeffrey A
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 11
- Issue
- 5
- Pages
- 467-476
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2072013430
- Cited by
- 233
- References
- 6
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 14 · 2021: 13 · 2020: 12 · 2019: 24 · 2018: 17 · 2017: 22 · 2016: 25 · 2015: 20 · 2014: 30 · 2013: 18 · 2012: 7
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- multiple sclerosis, Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, disability progression, patient-reported outcomes, composite endpoints, biomarkers, outcome measure validation, clinical trial endpoints, regulatory acceptance
- MeSH terms
- Activities of Daily Living, Brain, Disability Evaluation, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Neurologic Examination, Retina, Biomarkers, Randomized Controlled Trials as Topic, Disease Progression, Tomography, Optical Coherence
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