TY - JOUR

T1 - Utility-Weighted Modified Rankin Scale as Primary Outcome in Stroke Trials

T2 - A Simulation Study

AU - Dijkland, Simone A

AU - Voormolen, Daphne C

AU - Venema, Esmee

AU - Roozenbeek, Bob

AU - Polinder, Suzanne

AU - Haagsma, Juanita A

AU - Nieboer, Daan

AU - Chalos, Vicky

AU - Yoo, Albert J

AU - Schreuders, Jennifer

AU - van der Lugt, Aad

AU - Majoie, Charles B L M

AU - Roos, Yvo B W E M

AU - van Zwam, Wim H

AU - van Oostenbrugge, Robert J

AU - Steyerberg, Ewout W

AU - Dippel, Diederik W J

AU - Lingsma, Hester F

AU - MR CLEAN Investigators

AU - Bot, JCJ

N1 - © 2018 The Authors.

PY - 2018/4

Y1 - 2018/4

N2 - BACKGROUND AND PURPOSE: The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a new patient-centered primary outcome in stroke trials. We aimed to describe utility weights for the mRS health states and to evaluate the statistical efficiency of the UW-mRS to detect treatment effects in stroke intervention trials.METHODS: We used data of the 500 patients enrolled in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Utility values were elicited from the EuroQol Group 5-Dimension Self-Report Questionnaire assessed at 90 days after inclusion, simultaneously with the mRS. Utility weights were determined by averaging the utilities of all patients within each mRS category. We performed simulations to evaluate statistical efficiency. The simulated treatment effect was an odds ratio of 1.65 in favor of the treatment arm, similar for all mRS cutoffs. This treatment effect was analyzed using 3 approaches: linear regression with the UW-mRS as outcome, binary logistic regression with a dichotomized mRS (0-1/2-6, 0-2/3-6, and 0-4/5-6), and proportional odds logistic regression with the ordinal mRS. The statistical power of the 3 approaches was expressed as the proportion of 10 000 simulations that resulted in a statistically significant treatment effect (P≤0.05).RESULTS: The mean utility values (SD) for mRS categories 0 to 6 were: 0.95 (0.08), 0.93 (0.13), 0.83 (0.21), 0.62 (0.27), 0.42 (0.28), 0.11 (0.28), and 0 (0), respectively, but varied substantially between individual patients within each category. The UW-mRS approach was more efficient than the dichotomous approach (power 85% versus 71%) but less efficient than the ordinal approach (power 85% versus 87%).CONCLUSIONS: The UW-mRS as primary outcome does not capture individual variation in utility values and may reduce the statistical power of a randomized trial.

AB - BACKGROUND AND PURPOSE: The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a new patient-centered primary outcome in stroke trials. We aimed to describe utility weights for the mRS health states and to evaluate the statistical efficiency of the UW-mRS to detect treatment effects in stroke intervention trials.METHODS: We used data of the 500 patients enrolled in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Utility values were elicited from the EuroQol Group 5-Dimension Self-Report Questionnaire assessed at 90 days after inclusion, simultaneously with the mRS. Utility weights were determined by averaging the utilities of all patients within each mRS category. We performed simulations to evaluate statistical efficiency. The simulated treatment effect was an odds ratio of 1.65 in favor of the treatment arm, similar for all mRS cutoffs. This treatment effect was analyzed using 3 approaches: linear regression with the UW-mRS as outcome, binary logistic regression with a dichotomized mRS (0-1/2-6, 0-2/3-6, and 0-4/5-6), and proportional odds logistic regression with the ordinal mRS. The statistical power of the 3 approaches was expressed as the proportion of 10 000 simulations that resulted in a statistically significant treatment effect (P≤0.05).RESULTS: The mean utility values (SD) for mRS categories 0 to 6 were: 0.95 (0.08), 0.93 (0.13), 0.83 (0.21), 0.62 (0.27), 0.42 (0.28), 0.11 (0.28), and 0 (0), respectively, but varied substantially between individual patients within each category. The UW-mRS approach was more efficient than the dichotomous approach (power 85% versus 71%) but less efficient than the ordinal approach (power 85% versus 87%).CONCLUSIONS: The UW-mRS as primary outcome does not capture individual variation in utility values and may reduce the statistical power of a randomized trial.

U2 - 10.1161/STROKEAHA.117.020194

DO - 10.1161/STROKEAHA.117.020194

M3 - Article

C2 - 29535271

VL - 49

SP - 965

EP - 971

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 4

ER -