Literature DB >> 19664136

Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice.

Ulrich Dirnagl1, Malcolm R Macleod.   

Abstract

In this issue, Bath et al. use state of the art meta-analytical tools to address the pressing question of why NXY-059, a compound at the time considered to fulfil all the recommendations for the evaluation of preclinical data regarding neuroprotective drugs, has failed clinically. They demonstrate quantitatively that a negative publication bias existed, that the compound was indeed neuroprotective in experimental stroke, but that bias may have resulted in an overestimation of efficacy, and that efficacy in healthy, male, adolescent animals is a poor predictor of success in clinical trial. The study contains important messages for researchers, journal editors, the pharmaceutical industry and science policy makers. Bias is both prevalent and relevant in experiments modelling human stroke. Simple measures can reduce, perhaps substantially, the impact of such bias. The decision to proceed to clinical trial should be based on a thorough and systematic review of the animal data.

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Year:  2009        PMID: 19664136      PMCID: PMC2743833          DOI: 10.1111/j.1476-5381.2009.00211.x

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN: 0007-1188            Impact factor:   8.739


  11 in total

Review 1.  Recommendations for standards regarding preclinical neuroprotective and restorative drug development.

Authors: 
Journal:  Stroke       Date:  1999-12       Impact factor: 7.914

Review 2.  Bench to bedside: the quest for quality in experimental stroke research.

Authors:  Ulrich Dirnagl
Journal:  J Cereb Blood Flow Metab       Date:  2006-03-08       Impact factor: 6.200

3.  Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach.

Authors:  Nicolas A Crossley; Emily Sena; Jos Goehler; Jannekke Horn; Bart van der Worp; Philip M W Bath; Malcolm Macleod; Ulrich Dirnagl
Journal:  Stroke       Date:  2008-01-31       Impact factor: 7.914

Review 4.  A critical appraisal of the NXY-059 neuroprotection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke.

Authors:  Sean I Savitz
Journal:  Exp Neurol       Date:  2007-03-12       Impact factor: 5.330

Review 5.  Improving outcome after stroke: overcoming the translational roadblock.

Authors:  Matthias Endres; Britta Engelhardt; Jari Koistinaho; Olle Lindvall; Stephen Meairs; Jay P Mohr; Anna Planas; Nancy Rothwell; Markus Schwaninger; Martin E Schwab; Denis Vivien; Tadeusz Wieloch; Ulrich Dirnagl
Journal:  Cerebrovasc Dis       Date:  2008-02-22       Impact factor: 2.762

6.  Effects of NXY-059 in experimental stroke: an individual animal meta-analysis.

Authors:  P M W Bath; L J Gray; A J G Bath; A Buchan; T Miyata; A R Green
Journal:  Br J Pharmacol       Date:  2009-04-27       Impact factor: 8.739

Review 7.  Reprint: Good laboratory practice: preventing introduction of bias at the bench.

Authors:  Malcolm R Macleod; Marc Fisher; Victoria O'Collins; Emily S Sena; Ulrich Dirnagl; Philip M W Bath; Alastair Buchan; Alistair Buchan; H Bart van der Worp; Richard J Traystman; Kazuo Minematsu; Geoffrey A Donnan; David W Howells
Journal:  J Cereb Blood Flow Metab       Date:  2008-09-17       Impact factor: 6.200

8.  Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality.

Authors:  Malcolm R Macleod; H Bart van der Worp; Emily S Sena; David W Howells; Ulrich Dirnagl; Geoffrey A Donnan
Journal:  Stroke       Date:  2008-07-17       Impact factor: 7.914

9.  NXY-059 for the treatment of acute ischemic stroke.

Authors:  Ashfaq Shuaib; Kennedy R Lees; Patrick Lyden; James Grotta; Antonio Davalos; Stephen M Davis; Hans-Christoph Diener; Tim Ashwood; Warren W Wasiewski; Ugochi Emeribe
Journal:  N Engl J Med       Date:  2007-08-09       Impact factor: 91.245

10.  Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.

Authors:  Irving Kirsch; Brett J Deacon; Tania B Huedo-Medina; Alan Scoboria; Thomas J Moore; Blair T Johnson
Journal:  PLoS Med       Date:  2008-02       Impact factor: 11.069

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  32 in total

1.  The two pathophysiologies of focal brain ischemia: implications for translational stroke research.

Authors:  Konstantin-Alexander Hossmann
Journal:  J Cereb Blood Flow Metab       Date:  2012-01-11       Impact factor: 6.200

2.  International, multicenter randomized preclinical trials in translational stroke research: it's time to act.

Authors:  Ulrich Dirnagl; Marc Fisher
Journal:  J Cereb Blood Flow Metab       Date:  2012-04-18       Impact factor: 6.200

3.  Improving the quality of biomedical research: guidelines for reporting experiments involving animals.

Authors:  Ulrich Dirnagl; Martin Lauritzen
Journal:  J Cereb Blood Flow Metab       Date:  2011-01-05       Impact factor: 6.200

4.  Animal models in today's translational medicine world.

Authors:  Abhishek Choudhary; Jamal A Ibdah
Journal:  Mo Med       Date:  2013 May-Jun

5.  Translational neuropharmacology and the appropriate and effective use of animal models.

Authors:  A R Green; J Gabrielsson; K C F Fone
Journal:  Br J Pharmacol       Date:  2011-10       Impact factor: 8.739

6.  Data Standardization and Quality Management.

Authors:  Paul A Lapchak; John H Zhang
Journal:  Transl Stroke Res       Date:  2017-03-10       Impact factor: 6.829

7.  Neuroprotection by valproic Acid in mouse models of permanent and transient focal cerebral ischemia.

Authors:  Yong Ri Qian; Mu-Jin Lee; Shinae Hwang; Ji Hyun Kook; Jong-Keun Kim; Choon Sang Bae
Journal:  Korean J Physiol Pharmacol       Date:  2010-12-31       Impact factor: 2.016

8.  Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage.

Authors:  Seung-Hoon Baek; Ah Reum Noh; Kyeong-A Kim; Muhammad Akram; Young-Jun Shin; Eun-Sun Kim; Seong Woon Yu; Arshad Majid; Ok-Nam Bae
Journal:  Stroke       Date:  2014-06-17       Impact factor: 7.914

9.  A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia.

Authors:  Yu-Yo Sun; Chia-Yi Kuan
Journal:  J Vis Exp       Date:  2015-08-18       Impact factor: 1.355

10.  Effect of Danshen aqueous extract on serum hs-CRP, IL-8, IL-10, TNF-α levels, and IL-10 mRNA, TNF-α mRNA expression levels, cerebral TGF-β1 positive expression level and its neuroprotective mechanisms in CIR rats.

Authors:  Xue-Yun Liang; Hai-Ning Li; Xiao-Yan Yang; Wen-Yan Zhou; Jian-Guo Niu; Ben-Dong Chen
Journal:  Mol Biol Rep       Date:  2013-02-02       Impact factor: 2.316

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