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(Stroke. 2008;39:2824.)
© 2008 American Heart Association, Inc.

Original Contributions

Evidence for the Efficacy of NXY-059 in Experimental Focal Cerebral Ischaemia Is Confounded by Study Quality

Malcolm R. Macleod, PhD, FRCP; H. Bart van der Worp, MD, PhD; Emily S. Sena, BSc; David W. Howells, PhD; Ulrich Dirnagl, MD, PhD Geoffrey A. Donnan, MD, FRACP

From Clinical Neurosciences (M.R.M., E.S.S.), University of Edinburgh, Scotland, UK; the Department of Neurology (H.B.v.d.W.), Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands; the National Stroke Research Institute (E.S.S., D.W.H., G.A.D.), Melbourne, Australia; and the Department Neurology (U.D.), Charite Hospital, Berlin, Germany.

Correspondence to Malcolm R. Macleod, PhD, FRCP, Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK. E-mail malcolm.macleod{at}ed.ac.uk

Background and Purpose— The neutral results of the SAINT II trial have again highlighted difficulties translating neuroprotective efficacy from bench to bedside. Animal studies are susceptible to study quality biases, which may lead to overstatement of efficacy. We report the impact of study quality on published estimates of the efficacy of NXY-059 in animal models of stroke.

Methods— We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia.

Results— Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies.

Conclusions— The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.

Key Words: neuroprotection • NXY-059 • study quality

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