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.
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