Shift analysis versus dichotomization of the modified Rankin scale outcome scores in the NINDS and ECASS-II trials
Department of Neurology
Activities of Daily Living; Aged; *Clinical Trials as Topic; Data Interpretation, Statistical; Databases, Factual; *Disability Evaluation; Female; Humans; Male; Middle Aged; National Institutes of Health (U.S.); Odds Ratio; Outcome Assessment (Health Care); Quality Assurance, Health Care; Quality of Life; Self-Evaluation Programs; Stroke; Tissue Plasminogen Activator; United States
Nervous System Diseases | Neurology
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.
DOI of Published Version
Stroke. 2007 Dec;38(12):3205-12. Epub 2007 Nov 1. Link to article on publisher's site
Stroke; a journal of cerebral circulation
Savitz SI, Lew RA, Bluhmki E, Hacke W, Fisher M. (2007). Shift analysis versus dichotomization of the modified Rankin scale outcome scores in the NINDS and ECASS-II trials. Neurology Publications. https://doi.org/10.1161/STROKEAHA.107.489351. Retrieved from https://escholarship.umassmed.edu/neuro_pp/70