1,026 Experimental treatments in acute stroke
Article first published online: 1 FEB 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 3, pages 467–477, March 2006
How to Cite
O'Collins, V. E., Macleod, M. R., Donnan, G. A., Horky, L. L., van der Worp, B. H. and Howells, D. W. (2006), 1,026 Experimental treatments in acute stroke. Ann Neurol., 59: 467–477. doi: 10.1002/ana.20741
- Issue published online: 17 FEB 2006
- Article first published online: 1 FEB 2006
- Manuscript Revised: 10 OCT 2005
- Manuscript Accepted: 10 OCT 2005
- Manuscript Received: 25 JUL 2005
Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally.
We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically.
There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 ± 16.7% versus 24.4 ± 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy.
The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside. Ann Neurol 2006