Indiana University-Purdue University Indianapolis (IUPUI) / Time-to-event outcomes are widely utilized in medical research. Assessing the cumulative
effects of time-varying exposures on time-to-event outcomes poses challenges in
statistical modeling. First, exposure status, intensity, or duration may vary over time.
Second, exposure effects may be delayed over a latent period, a situation that is not considered
in traditional survival models. Third, exposures that occur within a time window
may cumulatively in
uence an outcome. Fourth, such cumulative exposure effects may
be non-linear over exposure latent period. Lastly, exposure-outcome dynamics may differ
among groups defined by individuals' characteristics. These challenges have not been adequately
addressed in current statistical models. The objective of this dissertation is to
provide a novel approach to modeling group-specific dynamics between cumulative timevarying
exposures and a time-to-event outcome.
A framework of group-specific dynamic models is introduced utilizing functional
time-dependent cumulative exposures within an etiologically relevant time window. Penalizedspline
time-dependent Cox models are proposed to evaluate group-specific outcome-exposure
dynamics through the associations of a time-to-event outcome with functional cumulative
exposures and group-by-exposure interactions. Model parameter estimation is achieved
by penalized partial likelihood. Hypothesis testing for comparison of group-specific exposure
effects is performed by Wald type tests. These models are extended to group-specific
non-linear exposure intensity-latency-outcome relationship and group-specific interaction
effect from multiple exposures. Extensive simulation studies are conducted and demonstrate satisfactory model performances. The proposed methods are applied to the analyses
of group-specific associations between antidepressant use and time to coronary artery disease
in a depression-screening cohort using data extracted from electronic medical records.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/30878 |
| Date | 12 1900 |
| Creators | Tong, Yan |
| Contributors | Gao, Sujuan, Bakoyannis, Giorgos, Tu, Wanzhu, Han, Jiali |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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