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A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation

Please always quote using this URN: urn:nbn:de:bvb:20-opus-151401
  • 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 NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) studies revealed a positiveBiomedical 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 NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) 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 NOX\(_{2}\) 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.show moreshow less

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Metadaten
Author: Pamela W. M. Kleikers, Carlijn Hooijmans, Eva Göb, Friederike Langhauser, Sarah S. J. Rewell, Kim Radermacher, Merel Ritskes-Hoitinga, David W. Howells, Christoph Kleinschnitz, Harald H. H. W. Schmidt
URN:urn:nbn:de:bvb:20-opus-151401
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurologische Klinik und Poliklinik
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2015
Volume:5
Issue:13428
Source:Scientific Reports 5, 13428 (2015). DOI: 10.1038/srep13428
DOI:https://doi.org/10.1038/srep13428
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:NADPH oxidase inhibitors; chronic kidney disease; colony-stimulating factor; darbepoetin alpha; diabetes mellitus; focal cerebral ischemia; mice; oxidative stress; search filter; translational stroke research
Release Date:2017/10/12
EU-Project number / Contract (GA) number:294683
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International