Please use this identifier to cite or link to this item:
|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|
|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.|
|Subjects:||Molecular Targeted Therapy|
Randomized Controlled Trials as Topic
|Appears in Collections:||Journal articles|
Files in This Item:
There are no files associated with this item.
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.