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Outcome heterogeneity and bias in acute experimental spinal cord injury: A meta-analysis


Watzlawick, R and Antonic, A and Sena, ES and Kopp, MA and Rind, J and Dirnagl, U and Macleod, M and Howells, DW and Schwab, JM, Outcome heterogeneity and bias in acute experimental spinal cord injury: A meta-analysis, Neurology, 93, (1) pp. E40-E51. ISSN 0028-3878 (2019) [Refereed Article]

Copyright Statement

Copyright 2019 American Academy of Neurology.

DOI: doi:10.1212/WNL.0000000000007718


Objective To determine whether and to what degree bias and underestimated variability undermine the predictive value of preclinical research for clinical translation.

Methods We 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.

Results Overall, the included interventions reported a neurobehavioral outcome improvement of 26.3% (95% confidence interval 24.328.4). 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bias, which extrapolates to identify likely missing data, suggested that between 2% and 41% of experiments remain unpublished.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%.

Conclusions We 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.

Item Details

Item Type:Refereed Article
Keywords:spinal cord, injury, bias
Research Division:Health Sciences
Research Group:Other health sciences
Research Field:Other health sciences not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Howells, DW (Professor David Howells)
ID Code:151351
Year Published:2019
Web of Science® Times Cited:17
Deposited By:College Office - CHM
Deposited On:2022-07-27
Last Modified:2022-09-29

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