University Of Tasmania
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A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation

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journal contribution
posted on 2023-05-18, 20:03 authored by Kleikers, PWM, Hooijmans, C, Gob, E, Langhauser, F, Rewell, SSJ, Radermacher, K, Ritskes-Hoitinga, M, David Howells, Kleinschnitz, C, Schmidt, HHHW
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.


Publication title

Scientific Reports








Tasmanian School of Medicine


Nature Publishing Group

Place of publication

United Kingdom

Rights statement

Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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