Evidence map›Paper›PMID 35321926›Full record

ArticleNeurology2022

Designing Multi-arm Multistage Adaptive Trials for Neuroprotection in Progressive Multiple Sclerosis.

Vivien Li, Baptiste Leurent, Frederik Barkhof, Marie Braisher, Fay Cafferty, Olga Ciccarelli, Arman Eshaghi, Emma Gray, Jennifer M Nicholas, Mahesh Parmar and 5 more

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In one paragraph

Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Towards primary prevention of multiple sclerosis.Nature reviews. Neurology · 2026
    Review
  3. Article
  4. Neuroprotection in Parkinson Disease.Neurology and therapy · 2025
    Review
  5. Review
  6. The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024
    Review
  7. Article
  8. Enhancing involvement of people with multiple sclerosis in clinical trial design.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023
    Review
  9. Quantifying Patient Investment in Novel Neurological Drug Development.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 3 countries.

Vivien LiFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0001-9889-971X
Baptiste LeurentFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0001-6420-6567
Frederik BarkhofFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0003-3543-3706
Marie BraisherFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
Fay CaffertyFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
Olga CiccarelliFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0001-7485-1367
Arman EshaghiFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0002-6652-3512
Emma GrayFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
Jennifer M NicholasFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
Mahesh ParmarFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0003-0166-1700
Guy PeryerFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0003-0425-6911
Jenny RobertsonFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
Nigel StallardFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.
James WasonFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0002-4691-126X
Jeremy ChatawayFrom the Florey Institute of Neuroscience and Mental Health (V.L.), University of Melbourne; Department of Neurology (V.L.), Royal Melbourne Hospital, Australia; Department of Medical Statistics (B.L., J.M.N.) and International Statistics and Epidemiology Group (B.L.), London School of Hygiene and Tropical Medicine, UK; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (F.B.), VU University Medical Center, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre (M.B., O.C.), and NMR Unit, Department of Neuroinflammation (A.E.), Faculty of Brain Sciences, UCL Queen Square Institute of Neurology; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology (F.C., M.P., J.C.), and Department of Computer Science, Centre for Medical Image Computing (A.E.), University College London; National Institute for Health Research (F.B., O.C., J.C.), University College London Hospitals Biomedical Research Centre; UK Multiple Sclerosis Society (E.G., G.P., J.R.), London; Faculty of Medicine and Health Sciences (G.P.), University of East Anglia, Norwich; Statistics and Epidemiology, Division of Health Sciences (N.S.), Warwick Medical School, University of Warwick, Coventry; and Population Health Sciences Institute (J.W.), Newcastle University, UK.ORCID 0000-0001-7286-6901
University of East Anglia · GB

Funding

Medical Research Council MC_UU_00002/6Medical Research Council MR/N028171/1
6 · The paper itself

Abstract

There are few treatments shown to slow disability progression in progressive multiple sclerosis (PMS). One challenge has been efficiently testing the pipeline of candidate therapies from preclinical studies in clinical trials. Multi-arm multistage (MAMS) platform trials may accelerate evaluation of new therapies compared to traditional sequential clinical trials. We describe a MAMS design in PMS focusing on selection of interim and final outcome measures, sample size, and statistical considerations. The UK MS Society Expert Consortium for Progression in MS Clinical Trials reviewed recent phase II and III PMS trials to inform interim and final outcome selection and design measures. Simulations were performed to evaluate trial operating characteristics under different treatment effect, recruitment rate, and sample size assumptions. People with MS formed a patient and public involvement group and contributed to the trial design, ensuring it would meet the needs of the MS community. The proposed design evaluates 3 experimental arms compared to a common standard of care arm in 2 stages. Stage 1 (interim) outcome will be whole brain atrophy on MRI at 18 months, assessed for 123 participants per arm. Treatments with sufficient evidence for slowing brain atrophy will continue to the second stage. The stage 2 (final) outcome will be time to 6-month confirmed disability progression, based on a composite clinical score comprising the Expanded Disability Status Scale, Timed 25-Foot Walk test, and 9-Hole Peg Test. To detect a hazard ratio of 0.75 for this primary final outcome with 90% power, 600 participants per arm are required. Assuming one treatment progresses to stage 2, the trial will recruit ≈1,900 participants and last ≈6 years. This is approximately two-thirds the size and half the time of separate 2-arm phase II and III trials. The proposed MAMS trial design will substantially reduce duration and sample size compared to traditional clinical trials, accelerating discovery of effective treatments for PMS. The design was well-received by people with multiple sclerosis. The practical and statistical principles of MAMS trial design may be applicable to other neurodegenerative conditions to facilitate efficient testing of new therapies.

Indexed as

Multiple SclerosisMultiple Sclerosis, Chronic ProgressiveAdaptive Clinical Trials as TopicAtrophyHumansNeuroprotectionResearch DesignTreatment Outcome

Identifiers

PMID35321926
PMCPMC9109150
OpenAlexW4221106369

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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.