A robust method for comparing two treatments in a confirmatory clinical trial via multivariate time‐to‐event methods that jointly incorporate information from longitudinal and time‐to‐event data |
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Authors: | Benjamin R Saville Amy H Herring Gary G Koch |
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Institution: | 1. Department of Biostatistics, Vanderbilt University School of Medicine, S‐2323 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232‐2158, U.S.A.;2. Department of Biostatistics, University of North Carolina at Chapel Hill, CB #7420, Chapel Hill, NC 27599, U.S.A.;3. Carolina Population Center, Chapel Hill, NC 27599, U.S.A. |
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Abstract: | We consider regulatory clinical trials that require a prespecified method for the comparison of two treatments for chronic diseases (e.g. Chronic Obstructive Pulmonary Disease) in which patients suffer deterioration in a longitudinal process until death occurs. We define a composite endpoint structure that encompasses both the longitudinal data for deterioration and the time‐to‐event data for death, and use multivariate time‐to‐event methods to assess treatment differences on both data structures simultaneously, without a need for parametric assumptions or modeling. Our method is straightforward to implement, and simulations show that the method has robust power in situations in which incomplete data could lead to lower than expected power for either the longitudinal or survival data. We illustrate the method on data from a study of chronic lung disease. Copyright © 2009 John Wiley & Sons, Ltd. |
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Keywords: | composite endpoint structure Wei– Lin– Weissfeld nonparametric ANCOVA for logrank scores confirmatory clinical trial correlated survival and longitudinal data |
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