Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm

Background and aims The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Methods Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. Results SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78-0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91-1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87-1.11; P = 0.02 for non-inferiority), similar to those using mRS. Conclusions This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke.National Health and Medical Research Council of Australia 1020462 1101113 Stroke Association of the United Kingdom TSA 2012/01 2015/01 Ministry of Health - Turkey National Council for Scientific and Technological Development (CNPq) 467322/2014-7 402388/2013-5 Ministry for Health, Welfare and Family Affairs of the Republic of Korea HI14C1985 National Health and Medical Research Council of Australia APP1141328 National Health and Medical Research Council of Australi