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.…
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 |
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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): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |