Joint modeling of multiple repeated measures and survival data using multidimensional latent trait linear mixed model.

Journal Article (Journal Article)

Impairment caused by Amyotrophic lateral sclerosis (ALS) is multidimensional (e.g. bulbar, fine motor, gross motor) and progressive. Its multidimensional nature precludes a single outcome to measure disease progression. Clinical trials of ALS use multiple longitudinal outcomes to assess the treatment effects on overall improvement. A terminal event such as death or dropout can stop the follow-up process. Moreover, the time to the terminal event may be dependent on the multivariate longitudinal measurements. In this article, we develop a joint model consisting of a multidimensional latent trait linear mixed model (MLTLMM) for the multiple longitudinal outcomes, and a proportional hazards model with piecewise constant baseline hazard for the event time data. Shared random effects are used to link together two models. The model inference is conducted using a Bayesian framework via Markov chain Monte Carlo simulation implemented in Stan language. Our proposed model is evaluated by simulation studies and is applied to the Ceftriaxone study, a motivating clinical trial assessing the effect of ceftriaxone on ALS patients.

Full Text

Duke Authors

Cited Authors

  • Wang, J; Luo, S

Published Date

  • 2019

Published In

Volume / Issue

  • 28 / 10-11

Start / End Page

  • 3392 - 3403

PubMed ID

  • 30306833

Pubmed Central ID

  • PMC6478574

Electronic International Standard Serial Number (EISSN)

  • 1477-0334

Digital Object Identifier (DOI)

  • 10.1177/0962280218802300


  • eng

Conference Location

  • England