Joint models for the longitudinal analysis of measurement scales in the presence of informative dropout

TL;DR

This paper extends joint models to handle latent variables measured by various indicators over time, accounting for informative dropout, and demonstrates its application in studying disease progression in a neurodegenerative disease.

Contribution

It introduces a novel joint modeling framework for latent measurement scales with mixed indicator types, incorporating informative dropout and risk of multi-cause events.

Findings

Validated estimation method via simulations

Applied to MSA cohort to study dysphagia progression

Implemented in R-package JLPM

Abstract

In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work,we explain how joint models can be extended to the framework of a latent quantity measured over time by indicators of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each observation of the indicators through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time stopped by the occurrence of death.