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A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
Citation
Kleikers, PWM and Hooijmans, C and Gob, E and Langhauser, F and Rewell, SSJ and Radermacher, K and Ritskes-Hoitinga, M and Howells, DW and Kleinschnitz, C and Schmidt, HHHW, A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation, Scientific Reports, 5 pp. 1-12. ISSN 2045-2322 (2015) [Refereed Article]
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Copyright Statement
Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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 metaanalysis
(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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Central Nervous System |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Cardiovascular System and Diseases |
| Author: | Howells, DW (Professor David Howells) |
| ID Code: | 109482 |
| Year Published: | 2015 |
| Deposited By: | Office of the School of Medicine |
| Deposited On: | 2016-06-20 |
| Last Modified: | 2016-09-06 |
| Downloads: | 29 View Download Statistics |
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