Two-step and likelihood methods for HIV viral dynamic models with covariate measurement errors and missing data |
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Authors: | Wei Liu Lang Wu |
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Institution: | 1. Department of Mathematics and Statistics , York University , Toronto , Ontario , Canada , M3J 1P3;2. Department of Statistics , University of British Columbia , Vancouver , British Columbia , Canada , V6T 1Z2 |
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Abstract: | HIV viral dynamic models have received much attention in the literature. Long-term viral dynamics may be modelled by semiparametric nonlinear mixed-effect models, which incorporate large variation between subjects and autocorrelation within subjects and are flexible in modelling complex viral load trajectories. Time-dependent covariates may be introduced in the dynamic models to partially explain the between-individual variations. In the presence of measurement errors and missing data in time-dependent covariates, we show that the commonly used two-step method may give approximately unbiased estimates but may under-estimate standard errors. We propose a two-stage bootstrap method to adjust the standard errors in the two-step method and a likelihood method. |
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Keywords: | cubic spline basis HIV viral dynamic model longitudinal data measurement error missing data |
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