Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16297
Title: A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
Austin 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
Affiliation: Department of Pharmacology, CARIM, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
SYRCLE at Central Animal Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands
Neurologische Klinik und Poliklinik der Universitätsklinik Würzburg, Würzburg, Germany
Florey Institute of Neuroscience and Mental Health, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 27-Aug-2015
Publication information: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16297
DOI: 10.1038/srep13428
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/26310318
Type: Journal Article
Subjects: Molecular Targeted Therapy
NADPH Oxidase
Randomized Controlled Trials as Topic
Appears in Collections:Journal articles

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