Ordinal vs dichotomous analyses of modified Rankin Scale, 5-year outcome, and cost of stroke

Abstract

Objective: To compare how 3 common representations (ordinal vs dichotomized as 0-1/2-6 or 0-2/3-6) of the modified Rankin Scale (mRS)-a commonly used trial outcome measure-relate to long-term outcomes, and quantify trial ineligibility rates based on premorbid mRS.

Methods: In consecutive patients with ischemic stroke in a population-based, prospective, cohort study (Oxford Vascular Study; 2002-2014), we related 3-month mRS to 1-year and 5-year disability and death (logistic regressions), and health/social care costs (generalized linear model), adjusted for age/sex, and compared goodness-of-fit values (C statistic, mean absolute error). We also calculated the proportion of patients in whom premorbid mRS score >1 or >2 would result in exclusion from trials using dichotomous analysis.

Results: Among 1,607 patients, the ordinal mRS was more strongly related to 5-year mortality than both the 0-1/2-6 and 0-2/3-6 dichotomies (all p < 0.0001). Results were similar for 5-year disability, and 5-year care costs were also best captured by the ordinal model (change in mean absolute error vs age/sex: -$3,059 for ordinal, -$2,805 for 0-2/3-6, -$1,647 for 0-1/2-6). Two hundred forty-four (17.1%) 3-month survivors had premorbid mRS score >2 and 434 (30.5%) had mRS score >1; both proportions increased with female sex, socioeconomic deprivation, and age (all p < 0.0001).

Conclusion: The ordinal form of the 3-month mRS relates better to long-term outcomes and costs in survivors of ischemic stroke than either dichotomy. This finding favors using ordinal approaches in trials analyzing the mRS. Exclusion of patients with higher premorbid disability by use of dichotomous primary outcomes will also result in unrepresentative samples.

Figure 1. Proportion of 3-month survivors of ischemic stroke with premorbid disability

Premorbid disability was defined as a prestroke modified Rankin Scale (mRS) score of >2 (blue) or >1 (red) and is presented by (A) age, (B) sex, and (C) socioeconomic deprivation index. Bars represent 95% confidence intervals.

Figure 2. Five-year disability and death/disability outcomes in survivors of ischemic stroke, stratified by 3-month mRS scores

The graphs show the proportion of 3-month survivors, also alive at 5 years, who were disabled at 5 years (A–C), and the proportion of 3-month survivors who were dead/disabled at 5 years (B–D), with disability defined as 5-year mRS score >2 (A and B) or mRS score >1 (C and D). Significant differences between mRS grades are indicated using p values from χ² analysis. Bars represent 95% confidence intervals. mRS = modified Rankin Scale.

Figure 3. Deaths and health and social care costs in survivors of ischemic stroke, stratified by 3-month mRS scores

The graphs show the proportion of 3-month survivors with full 5 years of follow-up who were dead at 1 year (A), dead at 5 years (B), and the cumulative 5-year health care costs for all survivors (C). Significant differences between mRS grades are indicated using p values from χ² analysis (A and B) and mean cost differences with 95% CIs (C). CI = confidence interval; mRS = modified Rankin Scale; USD = US dollars.