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Title: A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
Authors: Kleikers, Pamela WM;Hooijmans, Carlijn;Göb, Eva;Langhauser, Friederike;Rewell, Sarah SJ;Radermacher, Kim;Ritskes-Hoitinga, Merel;Howells, David W;Kleinschnitz, Christoph;Schmidt, Harald HHW
Issue Date: 27-Aug-2015
Citation: Scientific Reports 2015; 5: 13428
Abstract: Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.
DOI: 10.1038/srep13428
PubMed URL:
Type: Journal Article
Subjects: Molecular Targeted Therapy
NADPH Oxidase
Randomized Controlled Trials as Topic
Appears in Collections:Journal articles

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