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Stat Med. 2018 Jan 15;37(1):167-178. doi: 10.1002/sim.7515. Epub 2017 Oct 16.

A mechanistic nonlinear model for censored and mismeasured covariates in longitudinal models, with application in AIDS studies.

Author information

1
Department of Epidemiology and Biostatistics, School of Public Health, City University of New York, 55 West 125th Street, New York, NY 10027, USA.
2
CIHR Canadian HIV Trials Network, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
3
Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Abstract

When modeling longitudinal data, the true values of time-varying covariates may be unknown because of detection-limit censoring or measurement error. A common approach in the literature is to empirically model the covariate process based on observed data and then predict the censored values or mismeasured values based on this empirical model. Such an empirical model can be misleading, especially for censored values since the (unobserved) censored values may behave very differently than observed values due to the underlying data-generation mechanisms or disease status. In this paper, we propose a mechanistic nonlinear covariate model based on the underlying data-generation mechanisms to address censored values and mismeasured values. Such a mechanistic model is based on solid scientific or biological arguments, so the predicted censored or mismeasured values are more reasonable. We use a Monte Carlo EM algorithm for likelihood inference and apply the methods to an AIDS dataset, where viral load is censored by a lower detection limit. Simulation results confirm that the proposed models and methods offer substantial advantages over existing empirical covariate models for censored and mismeasured covariates.

KEYWORDS:

AIDS; censoring; joint model; measurement error; nonlinear mixed effects model

PMID:
29034494
DOI:
10.1002/sim.7515
[Indexed for MEDLINE]

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