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Optimizing the Predictive Value of Pre-Clinical Research Session 3: Reviewer Perspective Malcolm Macleod Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and Centre for Clinical Brain Sciences, University of Edinburgh. Quality is important. EAE. AD.
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Optimizing the Predictive Value of Pre-Clinical ResearchSession 3: Reviewer PerspectiveMalcolm MacleodCollaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies andCentre for Clinical Brain Sciences, University of Edinburgh
Quality is important EAE AD PD
Prevalence of reporting of some measures to improve validity
Quality by Journal • 4584 full publications curated on CAMARADES • Reporting the efficacy of an intervention in an animal disease model • Journals contributing more than 100 publications • Brain Research • Experimental Neurology • JCBFM* • Journal of Immunology • Journal of Neuroimmunology • Journal of Neuroscience • Neuroscience • PNAS • Stroke
Does high Impact Factor reflect high quality research? • 563 publications in focal cerebral ischaemia • Weak association between Impact Factor and quality (adjusted r2 = 0.06) • Weaker association between number of citations received by that publication and quality (adjusted r2 = 0.004)
Randomisation Blinded outcome assessment Blinded conduct of experiment Concealment of allocation sequence Sample size calculation Conflict of Interest statement Change over time • EAE: some improvement over time: 26 years per point increment in quality • AD: some improvement over time: 24 years per point improvement in study quality Study quality of in vivo studies selected from random sample of 1000 publications from PubMed
Publication bias 20% - 32%
Dimensions of assessment Internal validity Efficacy Generalisability Exemplar heat map of 30 experiments testing an intervention in EAE Generalisability Validity Generalisability Efficacy Validity Efficacy
Experimental Studies Evidence based translational medicine Clinical trial • Multi Centre Animal Studies • confirm efficacy • robust and monitored conduct of experiments • transparent analysis and reporting • deliberate heterogeneity • Systematic review and meta-analysis • how powerful is the treatment? • what is the quality of evidence? • what is the range of evidence? • is there evidence of a publication bias? • What are the conditions of maximum efficacy?