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Pharm Stat. 2014 Mar-Apr;13(2):145-52. doi: 10.1002/pst.1612. Epub 2014 Feb 12.

Adjusting for centre heterogeneity in multicentre clinical trials with a time-to-event outcome.

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Institute of Statistics, Biostatistics and Actuarial Sciences (ISBA), Université catholique de Louvain, Louvain-la-Neuve, Belgium.


Conducting a clinical trial at multiple study centres raises the issue of whether and how to adjust for centre heterogeneity in the statistical analysis. In this paper, we address this issue for multicentre clinical trials with a time-to-event outcome. Based on simulations, we show that the current practice of ignoring centre heterogeneity can be seriously misleading, and we illustrate the performances of the frailty modelling approach over competing methods. A special attention is paid to the problem of misspecification of the frailty distribution. The appendix provides sample codes in R and in SAS to perform the analyses in this paper.


frailty distribution misspecification; frailty model; multicentre clinical trial; time-to-event outcome

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