eCite Digital Repository

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]


Preview
PDF
1Mb
  

Copyright Statement

Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/srep13428

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

Repository Staff Only: item control page