SynthesisNeurology2019
Outcome heterogeneity and bias in acute experimental spinal cord injury: A meta-analysis.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 9 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 9 pooled it
–field-weighted citation impact
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.
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
26 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments.Scientific reports · 2023Pooled it
- Systematic Evaluation of Spinal Cord Injury Animal Models in the Field of Biomaterials.Tissue engineering. Part B, Reviews · 2022Pooled it
- A methodological review with meta-epidemiological analysis of preclinical systematic reviews with meta-analyses.Scientific reports · 2022Pooled it
- What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies.Frontiers in immunology · 2022Pooled it
- Developing a core outcome set for traumatic brachial plexus injuries: a systematic review of outcomes.BMJ open · 2021Pooled it
- Investigating the blood-spinal cord barrier in preclinical models: a systematic review of in vivo imaging techniques.Spinal cord · 2021Pooled it
- The rodent object-in-context task: A systematic review and meta-analysis of important variables.PloS one · 2021Pooled it
- Pooled it
- Effects of drinking natural hydrogen sulfide (HInternational journal of biometeorology · 2020Pooled it
- Exploring the Regenerative Role of Exosomes as a Potential Therapy for Peripheral Nerve Injury: A Systematic Review.Biomolecules & therapeutics · 2026Review
- Lost in translation: why pharmacological trials keep failing in acute spinal cord injury.Arquivos de neuro-psiquiatria · 2026Review
- Preclinical evaluation of repositioned non-antibiotic agents against Staphylococcus aureus: a network meta-analysis of survival outcomes.World journal of microbiology & biotechnology · 2025Article
- Systematic review and meta-analysis use in the field of spinal cord injury research: A bibliometric analysis.The journal of spinal cord medicine · 2025Article
- Age and Sex Affect the Chronic Trajectory of Plasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels in a Murine Thoracic Contusion Spinal Cord Injury Model.Topics in spinal cord injury rehabilitation · 2025Article
- Stepwise Imperatives for Improving the Protection of Animals in Research and Education in Canada.Animals : an open access journal from MDPI · 2024Article
- Effect-Size Discrepancies in Literature Versus Raw Datasets from Experimental Spinal Cord Injury Studies: A CLIMBER Meta-Analysis.Neurotrauma reports · 2024Article
- The potential of gene therapies for spinal cord injury repair: a systematic review and meta-analysis of pre-clinical studies.Neural regeneration research · 2023Article
- Compounds co-targeting kinases in axon regulatory pathways promote regeneration and behavioral recovery after spinal cord injury in mice.Experimental neurology · 2022Article
- Harmonization-Information Trade-Offs for Sharing Individual Participant Data in Biomedicine.Harvard data science review · 2022Article
- Promoting FAIR Data Through Community-driven Agile Design: the Open Data Commons for Spinal Cord Injury (odc-sci.org).Neuroinformatics · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Ralf WatzlawickFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.ORCID 0000-0001-7886-3314
Ana AntonicFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.
Emily S SenaFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.ORCID 0000-0002-3282-8502
Marcel A KoppFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.
Julian RindFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.
Ulrich DirnaglFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.
Malcolm MacleodFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.ORCID 0000-0001-9187-9839
David W HowellsFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus.
Jan M SchwabFrom Charité-Universitätsmedizin Berlin (R.W., M.A.K., J.R., U.D., J.M.S.), corporate member of the Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurology and Experimental Neurology (R.W., M.A.K., J.R., J.M.S.), Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin; Department of Neurosurgery (R.W.), Freiburg University Medical Center, Germany; Department of Neuroscience (A.A.), Central Clinical School, Monash University, Melbourne; Stroke Division (E.S.S., M.M., D.W.H.), Melbourne, Victoria, Australia; Departments of Neurology and Clinical Neurosciences (E.S.S., M.M.), University of Edinburgh, UK; Center for Stroke Research Berlin (U.D.) and Excellence Cluster Neurocure (U.D.), Charité-Universitätsmedizin, Berlin, Germany; German Center for Neurodegenerative Diseases (U.D.), Bonn; Berlin Institute of Health (M.A.K., U.D.), Germany; University of Tasmania (D.W.H.), School of Medicine, Faculty of Health, Medical Sciences Precinct, Hobart, Australia; Department of Neurology (J.M.S.), Spinal Cord Injury Medicine (Paraplegiology), and Belford Center for Spinal Cord Injury (J.M.S.), Departments of Neuroscience and Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus. jan.schwab@osumc.edu.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine whether and to what degree bias and underestimated variability undermine the predictive value of preclinical research for clinical translation.
methodsWe investigated experimental spinal cord injury (SCI) studies for outcome heterogeneity and the impact of bias. Data from 549 preclinical SCI studies including 9,535 animals were analyzed with meta-regression to assess the effect of various study characteristics and the quality of neurologic recovery.
resultsOverall, the included interventions reported a neurobehavioral outcome improvement of 26.3% (95% confidence interval 24.3-28.4). Response to treatment was dependent on experimental modeling paradigms (neurobehavioral score, site of injury, and animal species). Applying multiple outcome measures was consistently associated with smaller effect sizes compared with studies applying only 1 outcome measure. More than half of the studies (51.2%) did not report blinded assessment, constituting a likely source of evaluation bias, with an overstated effect size of 7.2%. Assessment of publication bias, which extrapolates to identify likely missing data, suggested that between 2% and 41% of experiments remain unpublished. Inclusion of these theoretical missing studies suggested an overestimation of efficacy, reducing the effect sizes by between 0.9% and 14.3%.
conclusionsWe provide empirical evidence of prevalent bias in the design and reporting of experimental SCI studies, resulting in overestimation of the effectiveness. Bias compromises the internal validity and jeopardizes the successful translation of SCI therapies from the bench to bedside.
Indexed as
Disease Models, AnimalAnimalsPublication BiasRecovery of FunctionSpinal Cord InjuriesTranslational Research, Biomedical
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
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.