Abstract Details
Activity Number:
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367
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Type:
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Contributed
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Date/Time:
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Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
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Sponsor:
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Biometrics Section
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Abstract #315853
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Title:
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Proportional Hazards Regression Modeling with Dichotomized Longitudinal Biomarkers Measured with Error
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Author(s):
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Rong Fu* and Peter B. Gilbert
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Companies:
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University of Washington and Fred Hutchinson Cancer Research Center
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Keywords:
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Longitudinal biomarkers ;
Measurement error ;
Proportional hazards model ;
Random effects model
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Abstract:
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In cohort studies and clinical trials, a common objective is to assess time-varying longitudinal biomarkers as correlates of the instantaneous hazard of a study endpoint. We are interested in studying a typical practice where biomarker levels are dichotomized at fixed thresholds. The biomarker values are often measured intermittently and with error, which undermines the validity/asymptotic consistency from the standard Cox model. We address this problem via joint models. The underlying continuous biomarker trajectories are characterized by random effects models, while the relationship between the dichotomized trajectories and the instantaneous risk is characterized by a Cox model. The estimation is made via the risk set regression calibration method to reduce the asymptotic bias due to measurement errors. We compared our method to the naive two-stage method through simulation studies under various event rates and numbers of measuring time points. Our method retains very small level of bias in most settings. The application to real data is illustrated on the ACTG 175 antiretroviral therapy trial.
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Authors who are presenting talks have a * after their name.
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