arXiv subjects

Catherine Legrand

Publications and source records attributed to Catherine Legrand.

3 recordsLinked to original sources

arXiv2026

A Bias-Corrected Two-Stage Approach for Joint Modelling of Multidimensional Longitudinal HRQoL and Survival Data

Health-related quality-of-life (HRQoL) outcomes are increasingly incorporated into oncology research to complement traditional survival endpoints by capturing patients' well-being over time. These outcomes are typically collected through multidimensional questionnaires yielding longitudinal ordinal data, and are often subject to dropout due to disease progression or death. In this context, joint models provide a well-established framework to account for the dependence between longitudinal HRQoL trajectories and time-to-event outcomes, but fully joint estimation rapidly becomes computationally prohibitive when multiple latent dimensions and random effects are involved. We propose a novel slope-corrected two-stage (SC2S) approach for the joint analysis of multivariate ordinal HRQoL data and survival outcomes within a multidimensional latent trait framework. The proposed approach propagates longitudinal information to the survival model through informative priors on the random effects, while additionally re-estimating longitudinal slope parameters. This strategy substantially reduces bias in both longitudinal and survival submodels while preserving much of the computational efficiency of two-stage procedures. Through simulation studies and an application to HRQoL data from patients with progressive glioblastoma, we show that the proposed method closely approximates fully joint Bayesian estimation while requiring notably less computation time.

stat.ME↗

arXiv2025

Joint modeling of longitudinal HRQoL data accounting for the risk of competing dropouts

In cancer clinical trials, health-related quality of life (HRQoL) is an important endpoint, providing information about patients' well-being and daily functioning. However, missing data due to premature dropout can lead to biased estimates, especially when dropouts are informative. This paper introduces the extJMIRT approach, a novel tool that efficiently analyzes multiple longitudinal ordinal categorical data while addressing informative dropout. Within a joint modeling framework, this approach connects a latent variable, derived from HRQoL data, to cause-specific hazards of dropout. Unlike traditional joint models, which treat longitudinal data as a covariate in the survival submodel, our approach prioritizes the longitudinal data and incorporates the log baseline dropout risks as covariates in the latent process. This leads to a more accurate analysis of longitudinal data, accounting for potential effects of dropout risks. Through extensive simulation studies, we demonstrate that extJMIRT provides robust and unbiased parameter estimates and highlight the importance of accounting for informative dropout. We also apply this methodology to HRQoL data from patients with progressive glioblastoma, showcasing its practical utility.

stat.AP↗

arXiv2025

Tutorial for Surrogate Endpoint Validation Using Joint modeling and Mediation Analysis

The use of valid surrogate endpoints is an important stake in clinical research to help reduce both the duration and cost of a clinical trial and speed up the evaluation of interesting treatments. Several methods have been proposed in the statistical literature to validate putative surrogate endpoints. Two main approaches have been proposed: the meta-analytic approach and the mediation analysis approach. The former uses data from meta-analyses to derive associations measures between the surrogate and the final endpoint at the individual and trial levels. The latter rather uses the proportion of the treatment effect on the final endpoint through the surrogate as a measure of surrogacy in a causal inference framework. Both approaches have remained separated as the meta-analytic approach does not estimate the treatment effect on the final endpoint through the surrogate while the mediation analysis approach have been limited to single-trial setting. However, these two approaches are complementary. In this work we propose an approach that combines the meta-analytic and mediation analysis approaches using joint modeling for surrogate validation. We focus on the cases where the final endpoint is a time-to-event endpoint (such as time-to-death) and the surrogate is either a time-to-event or a longitudinal biomarker. Two new joint models were proposed depending on the nature of the surrogate. These model are implemented in the R package frailtypack. We illustrate the developed approaches in three applications on real datasets in oncology.

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