Development and performance of npde for the evaluation of time-to-event models

Marc Cerou 1, 2, 3, * Marc Lavielle 4, 5 Karl Brendel 3 Marylore Chenel 3 Emmanuelle Comets 1, 2
* Corresponding author
1 CIC - Centre d'Investigation Clinique [Rennes]
2 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
3 IRIS - Institut de Recherches Internationales Servier [Suresnes]
4 CMAP - Centre de Mathématiques Appliquées - Ecole Polytechnique
5 XPOP - Modélisation en pharmacologie de population
CMAP - Centre de Mathématiques Appliquées - Ecole Polytechnique, Inria Saclay - Ile de France
Abstract : Purpose - Normalised prediction distribution errors (npde) are used to graphically and statistically evaluate mixed-effect models for continuous responses. In this study, our aim was to extend npde to time-to-event (TTE) models and evaluate their performance.

Methods - Let V denote a dataset with censored TTE observations. The null hypothesis (H) is that observations in V can be described by model M. We extended npde to TTE models using imputations to take into account censoring. We then evaluated their performance in terms of type I error and power to detect model misspecifications for TTE data by means of a simulation study with different sample sizes.

Results - Type I error was found to be close to the expected 5% significance level for all sample sizes tested. The npde were able to detect misspecifications in the baseline hazard as well as in the link between the longitudinal variable and the survival function. The ability to detect model misspecifications increased as the difference in the shape of the survival function became more apparent. As expected, the power also increased as the sample size increased. Imputing the censored events tended to decrease the percentage of rejections.

Conclusions - We have shown that npde can be readily extended to TTE data and that they perform well with an adequate type I error.

Keywords : npde model evaluation PSA time-to-event
Document type :
Journal articles
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https://www.hal.inserm.fr/inserm-01695500
Contributor : Laurent Jonchère <>
Submitted on : Thursday, July 5, 2018 - 11:40:44 AM
Last modification on : Saturday, February 15, 2020 - 2:02:36 AM

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CNRS | UNIV-PARIS7 | X-CMAP | X-DEP-MATHA | CMAP | UNIV-RENNES1 | CIC | CIC203 | UNIV-PARIS13 | X | INRIA | USPC | UNIV-PARIS-SACLAY | PARISTECH | BIOSIT | UR1-UFR-SVE | UNIV-RENNES | IAME

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Marc Cerou, Marc Lavielle, Karl Brendel, Marylore Chenel, Emmanuelle Comets. Development and performance of npde for the evaluation of time-to-event models. Pharmaceutical Research, American Association of Pharmaceutical Scientists, 2018, 35 (2), pp.30. ⟨10.1007/s11095-017-2291-3⟩. ⟨inserm-01695500v2⟩

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