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(Stroke. 2007;38:3205.)
© 2007 American Heart Association, Inc.

Original Contributions

Shift Analysis Versus Dichotomization of the Modified Rankin Scale Outcome Scores in the NINDS and ECASS-II Trials

Sean I. Savitz, MD; Robert Lew, PhD; Erich Bluhmki, PhD; Werner Hacke, MD Marc Fisher, MD

From the Department of Neurology (S.I.S.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass; Veterans Administration (R.L.), Jamaica Plains, Mass; Boehringer Ingelheim Pharma (E.B.), Ingelheim, Germany; Department of Neurology (W.H.), University of Heidelberg, Heidelberg, Germany; and Department of Neurology (M.F.), University of Massachusetts Medical Center, Worcester, Mass.

Correspondence to Sean I. Savitz, MD, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030. E-mail sean.i.savitz{at}uth.tmc.edu

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.

Key Words: outcome • shift analysis • thrombolysis