| First Author | Kleikers PW | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 13428 | PubMed ID | 26310318 |
| Mgi Jnum | J:355440 | Mgi Id | MGI:6217572 |
| Doi | 10.1038/srep13428 | Citation | Kleikers PW, et al. (2015) A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation. Sci Rep 5:13428 |
| abstractText | 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. |
