A new approach for sizing trials with composite binary endpoints using anticipated marginal values and accounting for the correlation between components
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Cita com:
hdl:2117/171418
Tipus de documentArticle
Data publicació2019-05-20
Condicions d'accésAccés obert
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ProjecteBarcelona Graduate School of Mathematics (BGSMath) (MINECO-MDM-2014-0445)
METODOS ESTADISTICOS PARA ENSAYOS CLINICOS, PATRONES DE CENSURA COMPLEJOS Y ANALISIS INTEGRADO DE DATOS OMICOS (MINECO-MTM2015-64465-C2-1-R)
METODOS ESTADISTICOS PARA ENSAYOS CLINICOS, PATRONES DE CENSURA COMPLEJOS Y ANALISIS INTEGRADO DE DATOS OMICOS (MINECO-MTM2015-64465-C2-1-R)
Abstract
Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for the primary endpoint. As shown in this work, when using a composite binary endpoint to size a trial, one needs to specify the event rates and the effect sizes of the composite components as well as the correlation between them. In practice, the marginal parameters of the components can be obtained from previous studies or pilot trials; however, the correlation is often not previously reported and thus usually unknown. We first show that the sample size for composite binary endpoints is strongly dependent on the correlation and, second, that slight deviations in the prior information on the marginal parameters may result in underpowered trials for achieving the study objectives at a pre-specified significance level. We propose a general strategy for calculating the required sample size when the correlation is not specified and accounting for uncertainty in the marginal parameter values. We present the web platform CompARE to characterize composite endpoints and to calculate the sample size just as we propose in this paper. We evaluate the performance of the proposal with a simulation study and illustrate it by means of a real case study using CompARE.
Descripció
This is the peer reviewed version of the following article: Bofill, M.; Gómez Melis, G. A new approach for sizing trials with composite binary endpoints using anticipated marginal values and accounting for the correlation between components. "Statistics in medicine", 20 Maig 2019, vol. 38, núm. 11, p. 1935-1956, which has been published in final form at https://doi.org/10.1002/sim.8092. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
CitacióBofill, M.; Gómez Melis, G. A new approach for sizing trials with composite binary endpoints using anticipated marginal values and accounting for the correlation between components. "Statistics in medicine", 20 Maig 2019, vol. 38, núm. 11, p. 1935-1956.
ISSN0277-6715
Versió de l'editorhttps://onlinelibrary.wiley.com/doi/full/10.1002/sim.8092
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