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A Two-Stage Joint Model for Nonlinear Longitudinal Response and a Time-to-Event with Application in Transplantation Studies.pdf
Hindawi Publishing Corporation
Journal of Probability and Statistics
Volume 2012, Article ID 194194, 18 pages
doi:10.1155/2012/194194
Research Article
A Two-Stage Joint Model for Nonlinear
Longitudinal Response and a Time-to-Event with
Application in Transplantation Studies
Magdalena Murawska,1 Dimitris Rizopoulos,1
and Emmanuel Lesaffre1, 2
1 Department of Biostatistics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam,
The Netherlands
2 I-Biostat, Catholic University of Leuven, B-3000 Leuven, Belgium
Correspondence should be addressed to Magdalena Murawska, m.murawska@erasmusmc.nl
Received 7 July 2011; Revised 27 October 2011; Accepted 6 November 2011
Academic Editor: Grace Y. Yi
Copyright q 2012 Magdalena Murawska et al. This is an open access article distributed under
the Creative Commons Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
In transplantation studies, often longitudinal measurements are collected for important markers
prior to the actual transplantation. Using only the last available measurement as a baseline
covariate in a survival model for the time to graft failure discards the whole longitudinal evolution.
We propose a two-stage approach to handle this type of data sets using all available information.
At the first stage, we summarize the longitudinal information with nonlinear mixed-effects model,
and at the second stage, we include the Empirical Bayes estimates of the subject-specific parameters
as predictors in the Cox model for the time to allograft failure. To take into account that the
estimated subject-specific parameters are included in the model, we use a Monte Carlo
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