Flexible Bayesian additive joint models with an application to type 1 diabetes research

Biom J. 2017 Nov;59(6):1144-1165. doi: 10.1002/bimj.201600224. Epub 2017 Aug 10.

Abstract

The joint modeling of longitudinal and time-to-event data is an important tool of growing popularity to gain insights into the association between a biomarker and an event process. We develop a general framework of flexible additive joint models that allows the specification of a variety of effects, such as smooth nonlinear, time-varying and random effects, in the longitudinal and survival parts of the models. Our extensions are motivated by the investigation of the relationship between fluctuating disease-specific markers, in this case autoantibodies, and the progression to the autoimmune disease type 1 diabetes. Using Bayesian P-splines, we are in particular able to capture highly nonlinear subject-specific marker trajectories as well as a time-varying association between the marker and event process allowing new insights into disease progression. The model is estimated within a Bayesian framework and implemented in the R-package bamlss.

Keywords: Anisotropic smoothing; Biomarkers; Longitudinal data; P-splines; Time-to-event data.

MeSH terms

  • Bayes Theorem
  • Biometry / methods*
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Humans
  • Longitudinal Studies
  • Models, Statistical*