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A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
Zitieren Sie bitte immer diese 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.…
Autor(en): | 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 |
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URN: | urn:nbn:de:bvb:20-opus-151401 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Scientific Reports |
Erscheinungsjahr: | 2015 |
Band / Jahrgang: | 5 |
Heft / Ausgabe: | 13428 |
Originalveröffentlichung / Quelle: | Scientific Reports 5, 13428 (2015). DOI: 10.1038/srep13428 |
DOI: | https://doi.org/10.1038/srep13428 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Freie Schlagwort(e): | NADPH oxidase inhibitors; chronic kidney disease; colony-stimulating factor; darbepoetin alpha; diabetes mellitus; focal cerebral ischemia; mice; oxidative stress; search filter; translational stroke research |
Datum der Freischaltung: | 12.10.2017 |
EU-Projektnummer / Contract (GA) number: | 294683 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |