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Development of an Individual-Tree Basal Area Increment Model using a Linear Mixed-Effects Approach
Published on: July 3, 2020
Shared parameter modeling of longitudinal data allowing for possibly informative visiting process and terminal event
Christos Thomadakis1,2, Loukia Meligkotsidou2, Nikos Pantazis1
1Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 115 27, Greece.
Abstract:
Joint modeling of longitudinal and time-to-event data, particularly through shared parameter models (SPMs), is a common approach for handling longitudinal marker data with an informative terminal event. A critical but often neglected assumption in this context is that the visiting/observation process is noninformative, depending solely on past marker values and visit times. When this assumption fails, the visiting process becomes informative, resulting potentially to biased SPM estimates. Existing methods generally rely on a conditional independence assumption, positing that the marker model, visiting process, and time-to-event model are independent given shared or correlated random effects. Moreover, they are typically built on an intensity-based visiting process using calendar time. This study introduces a unified approach for jointly modeling a normally distributed marker, the visiting process, and time-to-event data in the form of competing risks. Our model conditions on the history of observed marker values, prior visit times, the marker's random effects, and possibly a frailty term independent of the random effects. While our approach aligns with the shared-parameter framework, it does not presume conditional independence between the processes. Additionally, the visiting process can be defined on either a gap time scale, via proportional hazard models, or a calendar time scale, via proportional intensity models. Through extensive simulation studies, we assess the performance of our proposed methodology. We demonstrate that disregarding an informative visiting process can yield significantly biased marker estimates. However, misspecification of the visiting process can also lead to biased estimates. The gap time formulation exhibits greater robustness compared to the intensity-based model when the visiting process is misspecified. In general, enriching the visiting process with prior visit history enhances performance. We further apply our methodology to real longitudinal data from HIV, where visit frequency varies substantially among individuals.
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