Shift analysis versus dichotomization of the modified Rankin scale outcome scores in the NINDS and ECASS-II trials

Stroke. 2007 Dec;38(12):3205-12. doi: 10.1161/STROKEAHA.107.489351. Epub 2007 Nov 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / methods*
  • Outcome Assessment, Health Care / standards
  • Outcome Assessment, Health Care / statistics & numerical data
  • Quality Assurance, Health Care / methods*
  • Quality Assurance, Health Care / standards
  • Quality Assurance, Health Care / statistics & numerical data
  • Quality of Life
  • Self-Evaluation Programs / methods*
  • Self-Evaluation Programs / standards
  • Self-Evaluation Programs / statistics & numerical data
  • Stroke / epidemiology*
  • Stroke Rehabilitation
  • Tissue Plasminogen Activator / metabolism
  • United States


  • Tissue Plasminogen Activator