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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Group Specific Dynamic Models of Time Varying Exposures on a Time-to-Event Outcome

Tong, Yan 12 1900 (has links)
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.

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