BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of 
the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke 
trials: a shift toward good functional outcome on the 7-category modified Rankin 
scale (mRS).
METHODS: We used the Cochran-Mantel-Haenszel shift test to analyze the 
distribution of the 90-day mRS outcomes in the NINDS and ECASS-II databases and 
compared the results with a dichotomized mRS outcome by logistic regression (0 
to 2 vs 3 to 6, or 0 to 1 vs 2 to 6). We also stratified each dataset based on 
National Institutes of Health Stroke Scale baseline severity.
RESULTS: Each dataset showed a statistically significant shift in the 90-day mRS 
distributions favoring tissue plasminogen activator (odds ratio, 1.6 for NINDS, 
1.3 for ECASS-II). For ECASS-II, larger shift effects appeared in National 
Institutes of Health Stroke Scale 0 to 6 and 16 to 40 strata. Similarly, the mRS 
0 to 2 analysis but not mRS 0 to 1 found similar treatment effects in both 
datasets (odds ratio, 1.6 for NINDS, 1.5 for ECASS-II) and similar variations in 
the low and high strata in the ECASS-II trial. NINDS found no significant 
treatment effects across the strata. After removing the strata at the fringes, 
the shift test lost significance in both datasets.
CONCLUSIONS: Tissue plasminogen activator causes a beneficial shift toward 
wellness on the mRS in both the NINDS and ECASS-II trials, and ECASS-II would 
have been a positive trial according to the shift approach. However, the shift 
effect is not global for all treated patients and does not outperform the 
dichotomized 0 to 2 outcome. Patients with mild and severe deficits also shifted 
favorably on the mRS in the ECASS-II trial.