Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials Using a Utility-Weighted Modified Rankin Scale

Abstract

Background and Purpose Although the modified Rankin Scale (mRS) is the most commonly employed primary endpoint in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect size challenging to interpret when analyzed ordinally. Weighting the seven Rankin levels by utilities may improve scale interpretability while preserving statistical power. Methods A utility weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta-analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions. Results Utility values were: mRS 0–1.0; mRS 1 - 0.91; mRS 2 - 0.76; mRS 3 - 0.65; mRS 4 - 0.33; mRS 5 & 6 - 0. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in six of eight unidirectional effect trials, while dichotomous analyses were statistically significant in two to four of eight. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249. Conclusion A utility-weighted mRS performs similarly to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits.

Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

“…Imprecision in estimates of the treatment effect may have arisen from interobserver variability in determining the scores on the modified Rankin scale, 15,25 which was administered principally by telephone. Analysis of the net change in functional outcome was based on equal weights assigned to each score (0 through 6) on the modified Rankin scale, but patient and provider assessments can vary across health transitions, 26 and functional recovery can continue beyond 90 days. 27 In our trial, selection bias was due to the inclusion of patients who had a predominantly mild severity of neurologic impairment and who were treated at a later time point after symptom onset than in other trials 1,3,4 and than in quality-assurance studies 12,16,28 of the use of alteplase in patients with acute ischemic stroke.…”

Benefits of Stroke Treatment Using a Mobile Stroke Unit Compared With Standard Management

“…Furthermore, we need to consider using an outcome measure such as the utility weighted mRS that will be more sensitive to improvements in outcomes in this subset of patients. 14 Fourth, we are reassured that remote telemedicine assessment independent of the decision being made by the on-site VN is possible. Recently, we demonstrated the feasibility and accuracy of telemedicine assessment of actors stimulating patients with stroke in ambulances using existing technology.…”

Comparison of 3-Month Stroke Disability and Quality of Life across Modified Rankin Scale Categories

“…Therefore, the development and increasing use of ordinal mRS “shift” analysis and weighted mRS schema represent significant advances in the stroke research field [11,12,13,14]. As shown recently, utility-weighted mRS performed similarly to ordinal mRS in detecting treatment effects in published stroke trials and outperformed dichotomous mRS-based analyses [12]. However, the interpretation of effect size using the ordinal mRS shift analysis, as well as application of results using these approaches to an individual patient, can be quite challenging.…”