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.