Literature DB >> 24247324

Bringing rigour to translational medicine.

David W Howells1, Emily S Sena2, Malcolm R Macleod2.   

Abstract

Translational neuroscience is in the doldrums. The stroke research community was among the first to recognize that the motivations inherent in our system of research can cause investigators to take shortcuts, and can introduce bias and reduce generalizability, all of which leads ultimately to the recurrent failure of apparently useful drug candidates in clinical trials. Here, we review the evidence for these problems in stroke research, where they have been most studied, and in other translational research domains, which seem to be bedevilled by the same issues. We argue that better scientific training and simple changes to the way that we fund, assess and publish research findings could reduce wasted investment, speed drug development, and create a healthier research environment. For 'phase III' preclinical studies--that is, those studies that build the final justification for conducting a clinical trial--we argue for a need to apply the same attention to detail, experimental rigour and statistical power in our animal experiments as in the clinical trials themselves.

Entities:  

Mesh:

Year:  2013        PMID: 24247324     DOI: 10.1038/nrneurol.2013.232

Source DB:  PubMed          Journal:  Nat Rev Neurol        ISSN: 1759-4758            Impact factor:   42.937


  59 in total

1.  Replication and reproducibility in spinal cord injury research.

Authors:  Oswald Steward; Phillip G Popovich; W Dalton Dietrich; Naomi Kleitman
Journal:  Exp Neurol       Date:  2011-11-10       Impact factor: 5.330

Review 2.  Factors affecting the apparent efficacy and safety of tissue plasminogen activator in thrombotic occlusion models of stroke: systematic review and meta-analysis.

Authors:  Emily S Sena; Catherine L Briscoe; David W Howells; Geoffrey A Donnan; Peter A G Sandercock; Malcolm R Macleod
Journal:  J Cereb Blood Flow Metab       Date:  2010-07-21       Impact factor: 6.200

Review 3.  Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke.

Authors:  Malcolm R Macleod; Tori O'Collins; Laura L Horky; David W Howells; Georey A Donnan
Journal:  J Pineal Res       Date:  2005-01       Impact factor: 13.007

Review 4.  Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.

Authors:  Terence J O'Brien; Elinor Ben-Menachem; Edward H Bertram; Stephen D Collins; Merab Kokaia; Holger Lerche; Henrik Klitgaard; Kevin J Staley; Elisabetta Vaudano; Matthew C Walker; Michele Simonato
Journal:  Epilepsia       Date:  2013-08       Impact factor: 5.864

5.  The economic cost of brain disorders in Europe.

Authors:  J Olesen; A Gustavsson; M Svensson; H-U Wittchen; B Jönsson
Journal:  Eur J Neurol       Date:  2012-01       Impact factor: 6.089

6.  Publication bias in reports of animal stroke studies leads to major overstatement of efficacy.

Authors:  Emily S Sena; H Bart van der Worp; Philip M W Bath; David W Howells; Malcolm R Macleod
Journal:  PLoS Biol       Date:  2010-03-30       Impact factor: 8.029

7.  Design, power, and interpretation of studies in the standard murine model of ALS.

Authors:  Sean Scott; Janice E Kranz; Jeff Cole; John M Lincecum; Kenneth Thompson; Nancy Kelly; Alan Bostrom; Jill Theodoss; Bashar M Al-Nakhala; Fernando G Vieira; Jeyanthi Ramasubbu; James A Heywood
Journal:  Amyotroph Lateral Scler       Date:  2008

8.  Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models.

Authors:  K A Reimer; R B Jennings; F R Cobb; R H Murdock; J C Greenfield; L C Becker; B H Bulkley; G M Hutchins; R P Schwartz; K R Bailey
Journal:  Circ Res       Date:  1985-05       Impact factor: 17.367

9.  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

10.  Differences in the evolution of the ischemic penumbra in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.

Authors:  Christopher McCabe; Lindsay Gallagher; Willy Gsell; Delyth Graham; Anna F Dominiczak; I Mhairi Macrae
Journal:  Stroke       Date:  2009-09-24       Impact factor: 7.914

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  48 in total

1.  Two-kidney one-clip is a pertinent approach to integrate arterial hypertension in animal models of stroke: Serial magnetic resonance imaging studies of brain lesions before and during cerebral ischemia.

Authors:  Benjamin Ménard; Laurent Chazalviel; Simon Roussel; Myriam Bernaudin; Omar Touzani
Journal:  J Cereb Blood Flow Metab       Date:  2017-06-15       Impact factor: 6.200

2.  Outcome heterogeneity and bias in acute experimental spinal cord injury: A meta-analysis.

Authors:  Ralf Watzlawick; Ana Antonic; Emily S Sena; Marcel A Kopp; Julian Rind; Ulrich Dirnagl; Malcolm Macleod; David W Howells; Jan M Schwab
Journal:  Neurology       Date:  2019-06-07       Impact factor: 9.910

3.  Discovery reliability.

Authors:  Anders Hånell
Journal:  J Cereb Blood Flow Metab       Date:  2019-03-13       Impact factor: 6.200

Review 4.  Dispositional negativity: An integrative psychological and neurobiological perspective.

Authors:  Alexander J Shackman; Do P M Tromp; Melissa D Stockbridge; Claire M Kaplan; Rachael M Tillman; Andrew S Fox
Journal:  Psychol Bull       Date:  2016-10-10       Impact factor: 17.737

Review 5.  Variability of functional outcome measures used in animal models of stroke and vascular cognitive impairment - a review of contemporary studies.

Authors:  Tuuli M Hietamies; Caroline Ostrowski; Zhong Pei; Luyang Feng; Christopher McCabe; Lorraine M Work; Terence J Quinn
Journal:  J Cereb Blood Flow Metab       Date:  2018-09-11       Impact factor: 6.200

6.  Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

Authors:  Holger Langhof; William Wei Lim Chin; Susanne Wieschowski; Carole Federico; Jonathan Kimmelman; Daniel Strech
Journal:  Br J Pharmacol       Date:  2018-10-01       Impact factor: 8.739

7.  Oral administration of a novel lipophilic PPARδ agonist is not neuroprotective after rodent cerebral ischemia.

Authors:  Samuel Knauss; Matthias Endres; Florian Blaschke; Claudia Hindinger; Alexander Kunz
Journal:  J Cereb Blood Flow Metab       Date:  2017-11-21       Impact factor: 6.200

Review 8.  Improving the predictive value of interventional animal models data.

Authors:  Caroline J Zeiss
Journal:  Drug Discov Today       Date:  2014-11-04       Impact factor: 7.851

Review 9.  Behavioral testing in animal models of spinal cord injury.

Authors:  K Fouad; C Ng; D M Basso
Journal:  Exp Neurol       Date:  2020-07-28       Impact factor: 5.330

10.  Influence of metabolic syndrome on post-stroke outcome, angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI.

Authors:  Jesús M Pradillo; Macarena Hernández-Jiménez; María E Fernández-Valle; Violeta Medina; Juan E Ortuño; Stuart M Allan; Spencer D Proctor; Juan M Garcia-Segura; María J Ledesma-Carbayo; Andrés Santos; María A Moro; Ignacio Lizasoain
Journal:  J Cereb Blood Flow Metab       Date:  2020-12-01       Impact factor: 6.200

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