Joint modeling of longitudinal and repeated time-to-event data using nonlinear mixed-effects models and the SAEM algorithm

Cyprien Mbogning (1, 2) , Kevin Bleakley (1) , Marc Lavielle (1, 2)

1 POPIX - Modélisation en pharmacologie de population
2 LM-Orsay - Laboratoire de Mathématiques d'Orsay

We propose a nonlinear mixed-effects framework to jointly model longitudinal and repeated time-to-event data. A parametric nonlin-ear mixed-effects model is used for the longitudinal observations and a parametric mixed-effects hazard model for repeated event times. We show the importance for parameter estimation of properly calculating the conditional density of the observations (given the individual parameters) in the presence of interval and/or right censoring. Parameters are estimated by maximizing the exact joint likelihood with the Stochastic Approximation Expectation-Maximization algorithm. This workflow for joint models is now implemented in the Monolix software, and illustrated here on five simulated and two real data sets.

Mots clés: Joint models; Mixed-effects models; Repeated time-to-events; Maximum likelihood; SAEM algorithm

Domaines: Statistiques [math.ST]

Cyprien Mbogning, Kevin Bleakley, Marc Lavielle. Joint modeling of longitudinal and repeated time-to-event data using nonlinear mixed-effects models and the SAEM algorithm. Journal of Statistical Computation and Simulation, 2015, 85 (8), pp.1512--1528. ⟨10.1080/00949655.2013.878938⟩. ⟨hal-01122140⟩