Joint longitudinal and time-to-event models for multilevel hierarchical data

Joint modelling of longitudinal and time-to-event data has received much attention recently. Increasingly, extensions to standard joint modelling approaches are being proposed to handle complex data structures commonly encountered in applied research. In this paper, we propose a joint model for hierarchical longitudinal and time-to-event data. Our motivating application explores the association between tumor burden and progression-free survival in non-small cell lung cancer patients. We define tumor burden as a function of the sizes of target lesions clustered within a patient. Since a patient may have more than one lesion, and each lesion is tracked over time, the data have a three-level hierarchical structure: repeated measurements taken at time points (level 1) clustered within lesions (level 2) within patients (level 3). We jointly model the lesion-specific longitudinal trajectories and patient-specific risk of death or disease progression by specifying novel association structures that combine inform...