Utility-weighted modified Rankin Scale: Still too crude to be a truly patient-centric primary outcome measure?

Rethnam, Venesha; Bernhardt, Julie; Dewey, Helen M; Moodie, Marj; Johns, Hannah; Gao, Lan; Collier, Janice; Ellery, Fiona; Чурилов, Леонид

doi:10.1177/1747493019830583

Cited by 13 publications

(18 citation statements)

References 21 publications

(42 reference statements)

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“…Only 1 study had the necessary data available for hypothesis testing for each of the following instruments: SF-36-PF, 27 SF-36-SF, 27 World Health Organization Global Burden of Disease Project, 28 Patient-Reported Outcomes Measurement Information System-Physical Function, 29 Quality of Life in Neurological Disorders, 29 Health-Related Quality of Life in Stroke Patients, 30 and Assessment of Quality of Life. 15 For these health utility scales, an F test was conducted to compare the mean utility weights at each mRS score, and Tukey tests for pairwise differences were conducted to compare pairwise differences at all mRS scores.…”

Section: Discussionmentioning

confidence: 99%

Health Utility Weighting of the Modified Rankin Scale

Rebchuk

O’Neill

Szefer³

et al. 2020

JAMA Netw Open

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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 (continued) Key Points Question Is a preexisting health utilityweighted outcome scale suitable for use in a clinical trial, or is a study-specific approach more appropriate? Findings Among 24 studies including 22 389 individuals, this systematic review and meta-analysis found statistically significant between-study differences for studies reporting utility weighting of the modified Rankin Scale. When applied to the results of major acute stroke trials, different studysp...

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Section: Discussionmentioning

confidence: 99%

Health Utility Weighting of the Modified Rankin Scale

Rebchuk

O’Neill

Szefer³

et al. 2020

JAMA Netw Open

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“…Despite the advantages of the UW-mRS, patients with a given mRS may exhibit a wide range of utility values, and patients with different mRS scores can have similar utility values, making the UW-mRS not sufficiently granular to represent post-stroke burden. 18…”

Section: Introductionmentioning

confidence: 99%

Look closer: The multidimensional patterns of post-stroke burden behind the modified Rankin Scale

Rethnam

Bernhardt

Johns

et al. 2020

International Journal of Stroke

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Background The utility-weighted modified Rankin Scale, representing patient perspectives of quality of life, is a newly proposed measure to improve the interpretability of the modified Rankin Scale. Despite obvious advantages, such weighting imperfectly reflects the multidimensional patterns of post-stroke burden. Aims To investigate multidimensional patterns of post-stroke burden formed by individual domains of Assessment of Quality of Life and Barthel Index for each modified Rankin Scale category. Methods In the A Very Early Rehabilitation Trial (n = 2104), modified Rankin Scale scores and modified Rankin Scale-stratified Barthel Index scores of Self-care and Mobility, and Assessment of Quality of Life scores of Independent Living, Senses, Mental Health and Relationships were collected at three months. The multivariate relationship between individual Assessment of Quality of Life and Barthel Index domains, and modified Rankin Scale was investigated using random effects linear regression models with respective interaction terms. Results Of 2104 patients, simultaneously collected Assessment of Quality of Life, Barthel Index and modified Rankin Scale scores at three months were available in 1870 patients. While individual Assessment of Quality of Life and Barthel Index domain scores decreased significantly as modified Rankin Scale increased (p < 0.0001), the patterns of decrease differed by domains (p < 0.0001). Patients with modified Rankin Scale 0–1 had the largest post-stroke burden in the Mental Health and Relationship domains, while patients with modified Rankin Scale >3 showed the greatest burden in Independent Living, Mobility and Self-care domains. Conclusions Across the modified Rankin Scale, individual domains are varyingly impacted demonstrating unique patterns of post-stroke burden, which facilitates appropriate assessment, articulation and interpretation of the modified Rankin Scale and utility-weighted modified Rankin Scale.

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“…The estimate of treatment effect using such weights would be a single easily understood value for the difference in QALE between the two trial strategies. An important limitation of the UW-mRS, as discussed in recent publications, is the high variability in utility values within each mRS category and across time poststroke [40,41]. By aggregating utility assessments from multiple time-points up to 5-year follow-up from a population-based cohort, our QALE weights may mitigate this limitation by accounting for some of the utility variability over time.Even if the QALE (or other) weights are used for secondary or tertiary analyses in stroke trials, they could add to the meaningful interpretation of the trial results, including in otherwise neutral trials, where they may suggest potential treatment effects worthy of further study.…”

Section: Discussionmentioning

confidence: 99%

Weights for ordinal analyses of the modified Rankin Scale in stroke trials: A population-based cohort study

et al. 2020

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Background: Ordinal/shift analyses of ordered measures like the modified Rankin Scale(mRS) are underused as primary trial outcomes for neurological disorders À despite statistical advantages À potentially hindered by poor clinical interpretability versus dichotomies, and by valuing state-transitions equally (linear scale). Weighted ordinal analyses incorporating step-changes at key transitions might have greater statistical validity and clinical applicability. Methods: In a prospective population-based cohort of ischaemic stroke (Oxford Vascular Study, recruited 2002-2014, we stratified 5-year outcomes of death, dementia, and/or institutionalization, health/social-care costs, and EuroQol-derived quality-adjusted life-expectancy(QALE) by 3-month mRS. We compared root-mean-square errors(RMSEs) from linear regressions for these outcomes with the mRS coded as a linear scale versus incorporating a spline at transitions 1-2, 2-3, or 3-4. We derived 3-month mRS weights for probability of 5-year death/ dementia/institutionalization using age/sex-adjusted logistic regressions, and cost and QALE weights from 1000bootstraps. We applied these weights to analyse recent trials of thrombectomy for acute ischaemic stroke. Findings: Among 1,607 patients, a non-linear (S-shaped) relationship was observed between 3-month mRS and each 5-year outcome, with RMSEs 18-73% lower using a spline at mRS 2-3 versus a linear representation. Age/ sex-adjusted probability weights for 5-year death/dementia/institutionalization were: mRS 0=0.19; 1=0.27; 2=0.41; 3=0.73; 4=0.77; 5=0.94 (mRS 6=1 by definition). Similar trends were seen with costs; estimated 5-year QALEs were: mRS 0=3.88; 1=3.49; 2=3.01; 3=1.87; 4=1.30; 5=0.06; 6=0. Results were similar stratifying by age/ sex, and excluding pre-morbidly disabled patients. Using a weighted ordinal approach, estimates of thrombectomy impact were more favourable than estimates with dichotomous approaches, 5-year cost reductions being 29% higher than with 0-2/3-6, and over three-fold higher than with 0-1/2-6 dichotomy. Interpretation: Our findings favour weighting the mRS in ordinal analyses for stroke and other neurological disorders, as state-transitions differ in clinical prognosis, quality-of-life, and costs. These weights could also be used for prognostication and cost-effectiveness analyses.

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Utility-weighted modified Rankin Scale: Still too crude to be a truly patient-centric primary outcome measure?

Cited by 13 publications

References 21 publications

Health Utility Weighting of the Modified Rankin Scale

Health Utility Weighting of the Modified Rankin Scale

Look closer: The multidimensional patterns of post-stroke burden behind the modified Rankin Scale

Weights for ordinal analyses of the modified Rankin Scale in stroke trials: A population-based cohort study

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