RUSTAND, Denis; BRIOLLAIS, Laurent; RONDEAU, Virginie

doi:10.1002/pst.2338

Bordeaux population health [BPH]

BRIOLLAIS, Laurent

RONDEAU, Virginie

Bordeaux population health [BPH]

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Article de revue

Ce document a été publié dans

Pharmaceutical Statistics. 2023-09-17

Résumé en anglais

The sum of the longest diameter (SLD) of the target lesions is a longitudinal biomarker used to assess tumor response in cancer clinical trials, which can inform about early treatment effect. This biomarker is semicontinuous, often characterized by an excess of zeros and right skewness. Conditional two-part joint models were introduced to account for the excess of zeros in the longitudinal biomarker distribution and link it to a time-to-event outcome. A limitation of the conditional two-part model is that it only provides an effect of covariates, such as treatment, on the conditional mean of positive biomarker values, and not an overall effect on the biomarker, which is often of clinical relevance. As an alternative, we propose in this article, a marginalized two-part joint model (M-TPJM) for the repeated measurements of the SLD and a terminal event, where the covariates affect the overall mean of the biomarker. Our simulation studies assessed the good performance of the marginalized model in terms of estimation and coverage rates. Our application of the M-TPJM to a randomized clinical trial of advanced head and neck cancer shows that the combination of panitumumab in addition with chemotherapy increases the odds of observing a disappearance of all target lesions compared to chemotherapy alone, leading to a possible indirect effect of the combined treatment on time to death.< Réduire

Mots clés en anglais

Conditional two-part

Joint model

Left-censoring

Marginalized two-part

Randomized clinical trial

Semicontinuous

Solid tumors

URI

https://oskar-bordeaux.fr/handle/20.500.12278/184636

DOI

http://dx.doi.org/10.1002/pst.2338

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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A marginalized two-part joint model for a longitudinal biomarker and a terminal event with application to advanced head and neck cancers

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Résumé en anglais

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