Jones Michael P
Department of Biostatistics, University of Iowa, Iowa City, IA 52242, U.S.A.
Environmetrics. 2018 Dec;29(8). doi: 10.1002/env.2536. Epub 2018 Oct 3.
Environmental toxicology studies often involve sample values that fall below a laboratory procedure's limit of quantification. Such left-censored data give rise to several problems for regression analyses. First, both covariates and outcome may be left censored. Second, the transformed toxicant levels may not be normal but mixtures of normals because of differences in personal characteristics, e.g. exposure history and demographic factors. Third, the outcome and covariates may be linear functions of left-censored variates, such as averages and differences. Fourth, some toxicant levels may be functions of other toxicant levels resulting in a recursive system. In this paper marginal and pseudo-likelihood based methods are proposed for estimation of the means and covariance matrix of variates found in these four settings. Next, linear regression methods are developed allowing outcomes and covariates to be linear combinations of left-censored measures. This is extended to a recursive system of modeling equations. Bootstrap standard errors and confidence intervals are used. Simulation studies demonstrate the proposed methods are accurate for a wide range of study designs and left-censoring probabilities. The proposed methods are illustrated through the analysis of an on-going community-based study of polychlorinated biphenyls, which motivated the proposed methodology.
环境毒理学研究常常涉及低于实验室程序定量限的样本值。这种左删失数据给回归分析带来了几个问题。首先,协变量和结果变量都可能被左删失。其次,由于个人特征(如接触史和人口统计学因素)的差异,转化后的毒物水平可能不是正态分布,而是正态分布的混合。第三,结果变量和协变量可能是左删失变量的线性函数,如均值和差值。第四,一些毒物水平可能是其他毒物水平的函数,从而导致一个递归系统。本文提出了基于边际和拟似然的方法,用于估计在这四种情况下发现的变量的均值和协方差矩阵。接下来,开发了线性回归方法,使结果变量和协变量能够成为左删失测量值的线性组合。这被扩展到一个建模方程的递归系统。使用了自助法标准误差和置信区间。模拟研究表明,所提出的方法对于广泛的研究设计和左删失概率都是准确的。通过对一项正在进行的基于社区的多氯联苯研究的分析说明了所提出的方法,该研究推动了所提出方法的发展。