The win ratio approach to analyzing composite outcomes: An application to the EVOLVE trial

Unlike conventional time-to-event analysis of composite endpoints in clinical trials, the “win ratio” method allows for flexibility in prioritizing their components. Here, we compare the EVOLVE trial findings using the win ratio with those from time-to-event analysis. Exposure: Randomization to cina...

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Bibliographic Details
Published in:Contemporary clinical trials Vol. 48; pp. 119 - 124
Main Authors: Abdalla, Safa, Montez-Rath, Maria E., Parfrey, Patrick S., Chertow, Glenn M.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.05.2016
Subjects:
Aged
Angina, Unstable - epidemiology
Calcimimetic Agents - therapeutic use
Cardiovascular
Cause of Death
Cinacalcet
Cinacalcet Hydrochloride - therapeutic use
Composite endpoints
EVOLVE trial
Female
Heart Failure - epidemiology
Hematology, Oncology and Palliative Medicine
Hospitalization - statistics & numerical data
Humans
Kidney Failure, Chronic - drug therapy
Male
Middle Aged
Mortality
Myocardial Infarction - epidemiology
Peripheral Vascular Diseases - epidemiology
Proportional Hazards Models
Randomized Controlled Trials as Topic
Treatment Outcome
Win ratio
Cinacalcet
EVOLVE trial
Composite endpoints
Win ratio
ISSN:1551-7144, 1559-2030, 1559-2030
Online Access:Get full text
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Summary:Unlike conventional time-to-event analysis of composite endpoints in clinical trials, the “win ratio” method allows for flexibility in prioritizing their components. Here, we compare the EVOLVE trial findings using the win ratio with those from time-to-event analysis. Exposure: Randomization to cinacalcet or placebo. Outcome: The primary composite endpoint combining all-cause mortality and non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, and peripheral vascular events. Analysis: In an unadjusted analysis, we paired each participant from the cinacalcet arm with every participant from the placebo arm within randomization strata. Pairs were classified as “winners” or “losers,” according to which participant died first during the shared follow-up time, or experienced the next ranked event first. We ranked non-fatal events in two ways: 1) all ranked evenly; and 2) prioritized by their effect on health-related quality of life. The win ratio equaled the total winners divided by total losers. Further analyses were conducted where the win ratio was stratified by, or adjusted for, age. The unadjusted win ratio for the primary composite endpoint was 1.09 (95% CI 0.97 to 1.21), a statistically non-significant result which supports the primary trial result — unadjusted hazard ratio 0.93 (95% CI 0.85 to 1.02). Age-stratified analyses showed a nominally significant benefit of cinacalcet (win ratio 1.14, 95% CI 1.04 to 1.26). Ranking of non-fatal outcomes by their relative effects on quality of life did not materially alter the results. The win ratio method corroborated the findings of EVOLVE based on conventional time-to-event analysis. EVOLVE ClinicalTrials.gov number: NCT00345839.
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ISSN:1551-7144
1559-2030
1559-2030
DOI:10.1016/j.cct.2016.04.001