Evidence map›Paper›PMID 34476128›Full record

ArticleNeurology. Clinical practice2021

Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design.

James Berry, Benjamin Brooks, Angela Genge, Terry Heiman-Patterson, Stanley Appel, Michael Benatar, Robert Bowser, Merit Cudkowicz, Clifton Gooch, Jeremy Shefner and 5 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Clinical practice, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04259255 (Radicava®), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 52% 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.

NCT04259255 completednot on this map

Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)

TypeobservationalSponsorShionogiRan2019 to 2024Enrolled74ConditionsAmyotrophic Lateral Sclerosis, ALSArmsEdaravone (Radicava®/Radicava ORS®)
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. ACS omega · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 3 countries.

James BerryMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Benjamin BrooksMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.ORCID 0000-0002-1914-5061
Angela GengeMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Terry Heiman-PattersonMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Stanley AppelMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Michael BenatarMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Robert BowserMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Merit CudkowiczMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Clifton GoochMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Jeremy ShefnerMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Jurjen WestraMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Wendy AgneseMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Charlotte MerrillMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Sally NelsonMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Stephen AppleMassachusetts General Hospital (JB), Boston; Atrium Health Neurosciences Institute (BB), Carolinas Medical Center, University of North Carolina School of Medicine-Charlotte Campus; Montreal Neurological Institute and Hospital (AG), QC, Canada; Lewis Katz School of Medicine (TH-P), Temple University, Philadelphia, PA; Houston Methodist (S. Appel), TX; University of Miami (MB), FL; Barrow Neurological Institute (RB, JS), Phoenix, AZ; Harvard Medical School (MC), Boston, MA; University of South Florida (CG), Tampa; Oxford BioDynamics Inc. (JW), Wilmington, DE; and Mitsubishi Tanabe Pharma America (WA, CM, SN, S. Apple), Inc., Jersey City, NJ.
Montreal Neurological Institute and Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo identify putative biomarkers that may serve as quantifiable, biological, nonclinical measures of the pharmacodynamic effect of edaravone in amyotrophic lateral sclerosis (ALS) and to report real-world treatment outcomes.

methodsThis is a prospective, observational, longitudinal, multicenter (up to 40 sites) US study (Clinicaltrials.gov; NCT04259255) with at least 200 patients with ALS who will receive edaravone for 24 weeks (6 cycles; Food and Drug Administration-approved regimen). All participants must either be treatment naive for edaravone or be more than 1 month without receiving any edaravone dose before screening. Biomarker quantification and other assessments will be performed at baseline (before cycle 1) and during cycles 1, 3, and 6. Selected biomarkers of oxidative stress, inflammation, neuronal injury and death, and muscle injury, as well as biomarker discovery panels (EpiSwitch and SOMAscan), will be evaluated and, when feasible, compared with biobanked samples. Clinical efficacy assessments will include the ALS Functional Rating Scale-Revised, King's clinical staging, ALS Assessment Questionnaire-40, Appel ALS Score (Rating Scale), slow vital capacity, hand-held dynamometry and grip strength, and time to specified states of disease progression or death. DNA samples will also be collected for potential genomic evaluation. The predicted rates of progression and survival, and their potential correlations with biomarkers, will be evaluated. Adverse events related to the study will be reported.

resultsThe study is estimated to be completed in 2022 with an interim analysis planned.

conclusionsFindings may help to further the understanding of the pharmacodynamic effect of edaravone, including changes in biomarkers, in response to treatment.

Identifiers

PMID34476128
PMCPMC8382414
OpenAlexW3088555433

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.