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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2053

Title: A Bayesian approach to jointly estimate centre and treatment by centre heterogeneity in a proportional hazards model
Authors: LEGRAND, Catherine
Ducrocq, V
JANSSEN, Paul
SYLVESTER, Richard
DUCHATEAU, Luc
Issue Date: 2005
Publisher: JOHN WILEY & SONS LTD
Citation: STATISTICS IN MEDICINE, 24(24). p. 3789-3804
Abstract: When multicentre clinical trial data are analysed, it has become more and more popular to look for possible heterogeneity in outcome between centres. However, beyond the investigation of such heterogeneity, it is also interesting to consider heterogeneity in treatment effect over centres. For time-to-event outcomes, this may be investigated by including a random centre effect and a random treatment by centre interaction in a Cox proportional hazards model. Assuming independence between the random effects, we propose a Bayesian approach to fit our proposed model. The parameters of interest are the variance components sigma(0)(2) and a; of these random effects, which can be interpreted as a measure of centre and treatment effect over centres heterogeneity of the hazard. These variance components are estimated from their marginal posterior density after integrating out the fixed treatment effect and the random effects. As this integration cannot be performed analytically, the marginal posterior density is approximated using the Laplace integration technique. Statistical inference is then based on the characteristics of the posterior marginal density, such as the mode and the standard deviation. We demonstrate the proposed technique using data from a pooled database of seven EORTC bladder cancer clinical trials. Substantial centre and treatment effect over centres heterogeneity in disease-free interval was found. Copyright (c) 2005 John Wiley & Sons, Ltd.
Notes: European Inst Res & Treatment Canc, B-1200 Brussels, Belgium. Inst Natl Rech Agron, Genet Quantitat & Appl Stn, Jouy En Josas, France. Hasselt Univ, Ctr Stat, B-3590 Diepenbeek, Belgium. State Univ Ghent, Fac Vet Med, Dept Physiol Biochem & Biometr, B-9000 Ghent, Belgium.Legrand, C, European Inst Res & Treatment Canc, Av E Mounier 83-11, B-1200 Brussels, Belgium.catherine.legrand@eortc.be
URI: http://hdl.handle.net/1942/2053
DOI: 10.1002/sim.2475
ISI #: 000234284800009
ISSN: 0277-6715
Category: A1
Type: Journal Contribution
Validation: ecoom, 2007
Appears in Collections: Research publications

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