The shared frailty model and the power for heterogeneity tests in multicenter trials

Heterogeneity between centers in multicenter trials with time to event outcome can be modeled by the frailty proportional hazards model. The majority of the different approaches that have been used to fit frailty models assume either the gamma or the lognormal frailty density and are based on simila...

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Main Authors: Duchateau, L., Janssen, P., Lindsey, P., Legrand, C., Nguti, R., Sylvester-Bradley, Rosemary
Format: Journal Article
Language:Inglés
Published: Elsevier 2002
Subjects:
Online Access:https://hdl.handle.net/10568/28432
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author Duchateau, L.
Janssen, P.
Lindsey, P.
Legrand, C.
Nguti, R.
Sylvester-Bradley, Rosemary
author_browse Duchateau, L.
Janssen, P.
Legrand, C.
Lindsey, P.
Nguti, R.
Sylvester-Bradley, Rosemary
author_facet Duchateau, L.
Janssen, P.
Lindsey, P.
Legrand, C.
Nguti, R.
Sylvester-Bradley, Rosemary
author_sort Duchateau, L.
collection Repository of Agricultural Research Outputs (CGSpace)
description Heterogeneity between centers in multicenter trials with time to event outcome can be modeled by the frailty proportional hazards model. The majority of the different approaches that have been used to fit frailty models assume either the gamma or the lognormal frailty density and are based on similar log likelihood expressions. These approaches are briefly reviewed and their specific features described; simulations further demonstrate that the different techniques lead to virtually the same estimates for the heterogeneity parameter. An important issue is the relationship between the size of a multicenter trial, in terms of number of centers and number of patients per center, and the bias and the spread of estimates of the heterogeneity parameter around its true value. Based on simulation results (restricted to constant hazard rate and the gamma frailty density), it becomes clear how the number of centers and the number of patients per center influence the quality of the estimates in the particular setting of breast cancer clinical trials. This insight is important in treatment outcome research, where one tries to relate differences with respect to clinical practice to differences in outcome in the various centers.
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spelling CGSpace284322024-04-25T06:00:29Z The shared frailty model and the power for heterogeneity tests in multicenter trials Duchateau, L. Janssen, P. Lindsey, P. Legrand, C. Nguti, R. Sylvester-Bradley, Rosemary models genetic variation experimentation morbidity Heterogeneity between centers in multicenter trials with time to event outcome can be modeled by the frailty proportional hazards model. The majority of the different approaches that have been used to fit frailty models assume either the gamma or the lognormal frailty density and are based on similar log likelihood expressions. These approaches are briefly reviewed and their specific features described; simulations further demonstrate that the different techniques lead to virtually the same estimates for the heterogeneity parameter. An important issue is the relationship between the size of a multicenter trial, in terms of number of centers and number of patients per center, and the bias and the spread of estimates of the heterogeneity parameter around its true value. Based on simulation results (restricted to constant hazard rate and the gamma frailty density), it becomes clear how the number of centers and the number of patients per center influence the quality of the estimates in the particular setting of breast cancer clinical trials. This insight is important in treatment outcome research, where one tries to relate differences with respect to clinical practice to differences in outcome in the various centers. 2002-09 2013-05-06T07:00:36Z 2013-05-06T07:00:36Z Journal Article https://hdl.handle.net/10568/28432 en Limited Access Elsevier Computational Statistics & Data Analysis;40(30): 603-620
spellingShingle models
genetic variation
experimentation
morbidity
Duchateau, L.
Janssen, P.
Lindsey, P.
Legrand, C.
Nguti, R.
Sylvester-Bradley, Rosemary
The shared frailty model and the power for heterogeneity tests in multicenter trials
title The shared frailty model and the power for heterogeneity tests in multicenter trials
title_full The shared frailty model and the power for heterogeneity tests in multicenter trials
title_fullStr The shared frailty model and the power for heterogeneity tests in multicenter trials
title_full_unstemmed The shared frailty model and the power for heterogeneity tests in multicenter trials
title_short The shared frailty model and the power for heterogeneity tests in multicenter trials
title_sort shared frailty model and the power for heterogeneity tests in multicenter trials
topic models
genetic variation
experimentation
morbidity
url https://hdl.handle.net/10568/28432
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