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.