Published online before print April 1, 2004, doi: 10.1161/01.STR.0000125719.25853.20
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2004;35:1203.)
© 2004 American Heart Association, Inc.
Original Contributions |
Pooling of Animal Experimental Data Reveals Influence of Study Design and Publication Bias
From National Stroke Research Institute, Melbourne, Australia (M.R.M., T.O., D.W.H., G.A.D.); School of Molecular and Clinical Medicine, University of Edinburgh, UK (M.R.M.); Department of Medicine, University of Melbourne, Australia (D.W.H.).
Correspondence to Dr Malcolm Macleod, Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom. E-mail malcolm{at}apoptosis.freeserve.co.uk
Background and Purpose— The extensive neuroprotective literature describing the efficacy of candidate drugs in focal ischemia has yet to lead to the development of effective stroke treatments. Ideally, the choice of drugs taken forward to clinical trial should be based on an unbiased assessment of all available data. Such an assessment might include not only the efficacy of a drug but also the in vivo characteristics and limits—in terms of time window, dose, species, and model of ischemia used—to that efficacy. To our knowledge, such assessments have not been made. Nicotinamide is a candidate neuroprotective drug with efficacy in experimental stroke, but the limits to and characteristics of that efficacy have not been fully described.
Methods— Systematic review and modified meta-analysis of studies of experimental stroke describing the efficacy of nicotinamide. The search strategy ensured ascertainment of studies published in full and those published in abstract only. DerSimonian and Laird random effects meta-analysis was used to account for heterogeneity between studies.
Results— Nicotinamide improved outcome by 0.287 (95% confidence interval 0.227 to 0.347); it was more effective in temporary ischemia models, after intravenous administration, in animals without comorbidities, and in studies published in full rather than in abstract. Studies scoring highly on a quality measure gave more precise estimates of the global effect.
Conclusions— Meta-analysis provides an effective technique for the aggregation of data from experimental stroke studies. We propose new standards for reporting such studies and a systematic approach to aggregating data from the neuroprotective literature.
Key Words: meta-analysis • stroke • animal models • neuroprotection • nicotinamide
This article has been cited by other articles:
 |
|
 |
|
  S. I. Savitz Cosmic Implications of NXY-059 Stroke, March 1, 2009; 40(3_suppl_1): S115 - S118. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Macleod, H. B. van der Worp, E. S. Sena, D. W. Howells, U. Dirnagl, and G. A. Donnan Evidence for the Efficacy of NXY-059 in Experimental Focal Cerebral Ischaemia Is Confounded by Study Quality Stroke, October 1, 2008; 39(10): 2824 - 2829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Zivin Identifying Low-Quality Preclinical Studies Stroke, October 1, 2008; 39(10): 2697 - 2698. [Full Text] [PDF]
|
|
|
|
|
|
J. Minnerup, J. Heidrich, J. Wellmann, A. Rogalewski, A. Schneider, and W.-R. Schabitz Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia Stroke, June 1, 2008; 39(6): 1855 - 1861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Crossley, E. Sena, J. Goehler, J. Horn, B. van der Worp, P. M.W. Bath, M. Macleod, and U. Dirnagl Empirical Evidence of Bias in the Design of Experimental Stroke Studies: A Metaepidemiologic Approach Stroke, March 1, 2008; 39(3): 929 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Gibson, L. J. Gray, P. M. W. Bath, and S. P. Murphy Progesterone for the treatment of experimental brain injury; a systematic review Brain, February 1, 2008; 131(2): 318 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Donnan The 2007 Feinberg Lecture: A New Road Map for Neuroprotection Stroke, January 1, 2008; 39(1): 242 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B. van der Worp, E. S. Sena, G. A. Donnan, D. W. Howells, and M. R. Macleod Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis Brain, December 1, 2007; 130(12): 3063 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ali, P. M.W. Bath, J. Curram, S. M. Davis, H.-C. Diener, G. A. Donnan, M. Fisher, B. A. Gregson, J. Grotta, W. Hacke, et al. The Virtual International Stroke Trials Archive Stroke, June 1, 2007; 38(6): 1905 - 1910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sena, P. Wheble, P. Sandercock, and M. Macleod Systematic Review and Meta-Analysis of the Efficacy of Tirilazad in Experimental Stroke Stroke, February 1, 2007; 38(2): 388 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G Hackam Translating animal research into clinical benefit BMJ, January 27, 2007; 334(7586): 163 - 164. [Full Text] [PDF]
|
|
|
|
|
|
M. Kaste Use of Animal Models Has Not Contributed to Development of Acute Stroke Therapies: Pro Stroke, October 1, 2005; 36(10): 2323 - 2324. [Full Text] [PDF]
|
|
|
|
|
|
H. Yao, F. Sadanaga-Akiyoshi, S. Ibayashi, M. Iida, M. Macleod, T. O'Collins, D. Howells, and G. Donnan Nicotinamide Attenuates Focal Ischemic Brain Injury: Meta-Analysis or Mechanism of Protection * Response: Stroke, December 1, 2004; 35(12): 2757 - 2758. [Full Text] [PDF]
|
|