A Frailty Model in Crossover Studies with Time-to-Event Response Variable |
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Authors: | Ilya Shvartsman Vernon M. Chinchilli Hsiao-pin Liu |
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Affiliation: | 1. Department of Mathematics and Computer Science , Penn State Harrisburg , Middletown , Pennsylvania , USA ius13@psu.edu;3. Department of Public Health Sciences , Penn State College of Medicine , Hershey , Pennsylvania , USA |
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Abstract: | In this article, we develop a model to study treatment, period, carryover, and other applicable effects in a crossover design with a time-to-event response variable. Because time-to-event outcomes on different treatment regimens within the crossover design are correlated for an individual, we adopt a proportional hazards frailty model. If the frailty is assumed to have a gamma distribution, and the hazard rates are piecewise constant, then the likelihood function can be determined via closed-form expressions. We illustrate the methodology via an application to a data set from an asthma clinical trial and run simulations that investigate sensitivity of the model to data generated from different distributions. |
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Keywords: | Crossover design Frailty Maximum likelihood Proportional hazards |
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