Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials
UMass Chan Affiliations
Department of NeurologyDocument Type
Journal ArticlePublication Date
2008-12-17Keywords
Acute DiseaseAnimals
Benzenesulfonates
Brain Ischemia
Cardiovascular Agents
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
*Disease Models, Animal
Humans
Neuroprotective Agents
Research
Research Design
Risk
Stroke
Neurology
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
BACKGROUND AND PURPOSE: Numerous neuroprotective agents have proven effective in animal stroke studies, but every drug has failed to achieve its primary outcome when brought forward to clinical trials. We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials. METHODS: We conducted a systematic search of all neuroprotective drugs in Phase II or III trials and collected data from animal studies of focal cerebral ischemia testing agents systemically administered within 24 hours of occlusion. The methodological rigor of each individual study was evaluated using 5 criteria derived from the STAIR guidelines. The adequacy of the preclinical "package" for each drug was then evaluated by combining the results of all studies for each drug to determine which of a further 5 STAIR criteria were met before moving forward from animal to human studies. RESULTS: Our search yielded 13 agents of which 10 had published data in peer-reviewed journals. There is substantial within-drug variability in the quality of preclinical studies as well as substantial variation in the completeness of the collective preclinical literature for different drugs. There has been little or no improvement in the quality of animal studies since NXY-059, and current agents have not been subjected to a more complete preclinical evaluation. CONCLUSIONS: There is significant heterogeneity in the quality of animal testing for neuroprotective agents in stroke. Drugs in the post-SAINT era have not been subjected to more thorough preclinical evaluation.Source
Stroke. 2009 Feb;40(2):577-81. Epub 2008 Dec 12. Link to article on publisher's siteDOI
10.1161/STROKEAHA.108.524330Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37692PubMed ID
19074479Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1161/STROKEAHA.108.524330