Alexander D Rebchuk1, Zoe R O'Neill2, Elena K Szefer3, Michael D Hill4,5, Thalia S Field1,6,7. 1. Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. 2. Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 3. Emmes Canada, Vancouver, British Columbia, Canada. 4. Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 5. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 6. Djavad Mowafaghian Centre for Brain Health, The University of British Columbia, Vancouver, British Columbia, Canada. 7. Vancouver Stroke Program, The University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
Importance: The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a patient-centered alternative primary outcome for stroke clinical trials. However, to date, there is no clear consensus on an approach to weighting the mRS. Objective: To characterize the between-study variability in utility weighting of the mRS in a population of patients who experienced stroke and its implications when applied to the results of a clinical trial. Data Sources: In this systematic review and meta-analysis, MEDLINE, Embase, and PsycINFO were searched from January 1987 through May 2019 using major search terms for stroke, health utility, and mRS. Study Selection: Original research articles published in English were reviewed. Included were studies with participants 18 years or older with ischemic or hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage, with mRS scores and utility weights evaluated concurrently. A total of 5725 unique articles were identified. Of these, 283 met criteria for full-text review, and 24 were included in the meta-analysis. Data Extraction and Synthesis: PRISMA guidelines for systematic review were followed. Data extraction was performed independently by multiple researchers. Data were pooled using mixed models. Main Outcomes and Measures: The mean utility weights and 95% CIs were calculated for each mRS score and health utility scale. Geographic differences in weighting for the EuroQoL 5-dimension (EQ-5D) and Stroke Impact Scale-based UW-mRS were explored using inverse variance-weighted linear models. The results of 18 major acute stroke trials cited in current guidelines were then reanalyzed using the UW-mRS weighting scales identified in the systematic review. Results: The meta-analysis included 22 389 individuals; the mean (SD) age of participants was 65.9 (4.0) years, and the mean (SD) proportion of male participants was 58.2% (7.5%). For all health utility scales evaluated, statistically significant differences were observed between the mean utility weights by mRS score. For studies using an EQ-5D-weighted mRS, between-study variance was higher for worse (mRS 2-5) compared with better (mRS 0-1) scores. Of the 18 major acute stroke trials with reanalyzed results, 3 had an unstable outcome when using different UW-mRSs. Conclusions and Relevance: Multiple factors, including cohort-specific characteristics and health utility scale selection, can influence mRS utility weighting. If the UW-mRS is selected as a primary outcome, the approach to weighting may alter the results of a clinical trial. Researchers using the UW-mRS should prospectively and concurrently obtain mRS scores and utility weights to characterize study-specific outcomes.
Importance: The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a patient-centered alternative primary outcome for stroke clinical trials. However, to date, there is no clear consensus on an approach to weighting the mRS. Objective: To characterize the between-study variability in utility weighting of the mRS in a population of patients who experienced stroke and its implications when applied to the results of a clinical trial. Data Sources: In this systematic review and meta-analysis, MEDLINE, Embase, and PsycINFO were searched from January 1987 through May 2019 using major search terms for stroke, health utility, and mRS. Study Selection: Original research articles published in English were reviewed. Included were studies with participants 18 years or older with ischemic or hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage, with mRS scores and utility weights evaluated concurrently. A total of 5725 unique articles were identified. Of these, 283 met criteria for full-text review, and 24 were included in the meta-analysis. Data Extraction and Synthesis: PRISMA guidelines for systematic review were followed. Data extraction was performed independently by multiple researchers. Data were pooled using mixed models. Main Outcomes and Measures: The mean utility weights and 95% CIs were calculated for each mRS score and health utility scale. Geographic differences in weighting for the EuroQoL 5-dimension (EQ-5D) and Stroke Impact Scale-based UW-mRS were explored using inverse variance-weighted linear models. The results of 18 major acute stroke trials cited in current guidelines were then reanalyzed using the UW-mRS weighting scales identified in the systematic review. Results: The meta-analysis included 22 389 individuals; the mean (SD) age of participants was 65.9 (4.0) years, and the mean (SD) proportion of male participants was 58.2% (7.5%). For all health utility scales evaluated, statistically significant differences were observed between the mean utility weights by mRS score. For studies using an EQ-5D-weighted mRS, between-study variance was higher for worse (mRS 2-5) compared with better (mRS 0-1) scores. Of the 18 major acute stroke trials with reanalyzed results, 3 had an unstable outcome when using different UW-mRSs. Conclusions and Relevance: Multiple factors, including cohort-specific characteristics and health utility scale selection, can influence mRS utility weighting. If the UW-mRS is selected as a primary outcome, the approach to weighting may alter the results of a clinical trial. Researchers using the UW-mRS should prospectively and concurrently obtain mRS scores and utility weights to characterize study-specific outcomes.
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