Bayesian estimation of logistic regression with misclassified covariates and response

Measurement error is a commonly addressed problem in psychometrics and the behavioral sciences, particularly where gold standard data either does not exist or are too expensive. The Bayesian approach can be utilized to adjust for the bias that results from measurement error in tests. Bayesian methods offer other practical advantages for the analysis of epidemiological data including the possibility of incorporating relevant prior scientific information and the ability to make inferences that do not rely on large sample assumptions. In this paper we consider a logistic regression model where both the response and a binary covariate are subject to misclassification. We assume both a continuous measure and a binary diagnostic test are available for the response variable but no gold standard test is assumed available. We consider a fully Bayesian analysis that affords such adjustments, accounting for the sources of error and correcting estimates of the regression parameters. Based on the results from our example and simulations, the models that account for misclassification produce more statistically significant results, than the models that ignore misclassification. A real data example on math disorders is considered.     

Regression analysis of competing risks data via semi-parametric additive hazard model

When the subjects in a study possess different demographic and disease characteristics and are exposed to more than one types of failure, a practical problem is to assess the covariate effects on each type of failure as well as on all-cause failure. The most widely used method is to employ the Cox models on each cause-specific hazard and the all-cause hazard. It has been pointed out that this method causes the problem of internal inconsistency. To solve such a problem, the additive hazard models have been advocated. In this paper, we model each cause-specific hazard with the additive hazard model that includes both constant and time-varying covariate effects. We illustrate that the covariate effect on all-cause failure can be estimated by the sum of the effects on all competing risks. Using data from a longitudinal study on breast cancer patients, we show that the proposed method gives simple interpretation of the final results, when the primary covariate effect is constant in the additive manner on each cause-specific hazard. Based on the given additive models on the cause-specific hazards, we derive the inferences for the adjusted survival and cumulative incidence functions.     

A generalized estimating equation approach to modelling incompatible data formats with covariate measurement error: application to human immunodeficiency virus immune markers

The integration of technological advances into research studies often raises an issue of incompatibility of data. This problem is common to longitudinal and multicentre studies, taking the form of changes in the definitions, acquisition of data or measuring instruments of some study variables. In our case of studying the relationship between a marker of immune response to human immunodeficiency virus and human immunodeficiency virus infection status, using data from the Multi-Center AIDS Cohort Study, changes in the manufactured tests used for both variables occurred throughout the study, resulting in data with different manufactured scales. In addition, the latent nature of the immune response of interest necessitated a further consideration of a measurement error component. We address the general issue of incompatibility of data, together with the issue of covariate measurement error, in a unified, generalized linear model setting with inferences based on the generalized estimating equation framework. General conditions are constructed to ensure consistent estimates and their variances for the primary model of interest, with the asymptotic behaviour of resulting estimates examined under a variety of modelling scenarios. The approach is illustrated by modelling a repeated ordinal response with incompatible formats, as a function of a covariate with incompatible formats and measurement error, based on the Multi-Center AIDS Cohort Study data.     

Inference for cumulative incidence on discrete failure times with competing risks

In the competing risks analysis, most inferences have been developed based on continuous failure time data. However, failure times are sometimes observed as being discrete. We propose nonparametric inferences for the cumulative incidence function for pure discrete data with competing risks. When covariate information is available, we propose semiparametric inferences for direct regression modelling of the cumulative incidence function for grouped discrete failure time data with competing risks. Simulation studies show that the procedures perform well. The proposed methods are illustrated with a study of contraceptive use in Indonesia.     

Inference on local average treatment effects for misclassified treatment

We develop point-identification for the local average treatment effect when the binary treatment contains a measurement error. The standard instrumental variable estimator is inconsistent for the parameter since the measurement error is nonclassical by construction. We correct the problem by identifying the distribution of the measurement error based on the use of an exogenous variable that can even be a binary covariate. The moment conditions derived from the identification lead to generalized method of moments estimation with asymptotically valid inferences. Monte Carlo simulations and an empirical illustration demonstrate the usefulness of the proposed procedure.     

A Better Alternative to Non-parametric Approaches for Adjusting for Covariate Measurement Errors in Logistic Regression

In this article, we propose a flexible parametric (FP) approach for adjusting for covariate measurement errors in regression that can accommodate replicated measurements on the surrogate (mismeasured) version of the unobserved true covariate on all the study subjects or on a sub-sample of the study subjects as error assessment data. We utilize the general framework of the FP approach proposed by Hossain and Gustafson in 2009 for adjusting for covariate measurement errors in regression. The FP approach is then compared with the existing non-parametric approaches when error assessment data are available on the entire sample of the study subjects (complete error assessment data) considering covariate measurement error in a multiple logistic regression model. We also developed the FP approach when error assessment data are available on a sub-sample of the study subjects (partial error assessment data) and investigated its performance using both simulated and real life data. Simulation results reveal that, in comparable situations, the FP approach performs as good as or better than the competing non-parametric approaches in eliminating the bias that arises in the estimated regression parameters due to covariate measurement errors. Also, it results in better efficiency of the estimated parameters. Finally, the FP approach is found to perform adequately well in terms of bias correction, confidence coverage, and in achieving appropriate statistical power under partial error assessment data.     

Survival model of a parallel system with dependent failures and time varying covariates

In this paper, we extended a parallel system survival model based on the bivariate exponential to incorporate a time varying covariate. We calculated the bias, standard error and rmse of the parameter estimates of this model at different censoring levels using simulated data. We then compared the difference in the total error when a fixed covariate model was used instead of the true time varying covariate model. Following that, we studied three methods of constructing confidence intervals for such models and conclusions were drawn based on the results of the coverage probability study. Finally, the results obtained by fitting the diabetic retinopathy study data to the model were analysed.     

Estimation with unbalanced panel data having covariate measurement error

Panel data with covariate measurement error appear frequently in various studies. Due to the sampling design and/or missing data, panel data are often unbalanced in the sense that panels have different sizes. For balanced panel data (i.e., panels having the same size), there exists a generalized method of moments (GMM) approach for adjusting covariate measurement error, which does not require additional validation data. This paper extends the GMM approach of adjusting covariate measurement error to unbalanced panel data. Two health related longitudinal surveys are used to illustrate the implementation of the proposed method.     

Combining information from multiple surveys for assessing health disparities

Despite advances in public health practice and medical technology, the disparities in health among the various racial/ethnic and socioeconomic groups remain a concern which has prompted the Department of Human and Health Services to designate the elimination of disparities in health as an overarching goal of Healthy People 2010. To assess the progress towards this goal, suitable measures are needed at the population level that can be tracked over time; Statistical inferential procedures have to be developed for these population level measures; and the data sources have to be identified to allow for such inferences to be conducted. Popular data sources for health disparities research are large surveys such the National Health and Interview Survey (NHIS) or the Behavior Risk Factor Surveillance System (BRFSS). The self-report disease status collected in these surveys may be inaccurate and the errors may be correlated with variables used in defining the groups. This article uses the National Health and Nutritional Examination Survey (NHANES) 99-00 to assess the extent of error in the self-report disease status; uses a Bayesian framework develop corrections for the self-report disease status in the National Health Interview Survey (NHIS) 99-00; and compares inferences about various measures of health disparities, with and without correcting for measurement error. The methodology is illustrated using the disease outcome hypertension, a common risk factor for cardiovascular disease.     

Combining information from multiple surveys for assessing health disparities

Despite advances in public health practice and medical technology, the disparities in health among the various racial/ethnic and socioeconomic groups remain a concern which has prompted the Department of Human and Health Services to designate the elimination of disparities in health as an overarching goal of Healthy People 2010. To assess the progress towards this goal, suitable measures are needed at the population level that can be tracked over time; Statistical inferential procedures have to be developed for these population level measures; and the data sources have to be identified to allow for such inferences to be conducted. Popular data sources for health disparities research are large surveys such the National Health and Interview Survey (NHIS) or the Behavior Risk Factor Surveillance System (BRFSS). The self-report disease status collected in these surveys may be inaccurate and the errors may be correlated with variables used in defining the groups. This article uses the National Health and Nutritional Examination Survey (NHANES) 99-00 to assess the extent of error in the self-report disease status; uses a Bayesian framework develop corrections for the self-report disease status in the National Health Interview Survey (NHIS) 99-00; and compares inferences about various measures of health disparities, with and without correcting for measurement error. The methodology is illustrated using the disease outcome hypertension, a common risk factor for cardiovascular disease. JEL classification C1 (C11, C13, C15), C4 (C42) and I3 (I31, I38)     

基于贝叶斯推断的HIV非线性混合效应联合模型研究

 在纵向数据研究中,混合效应模型的随机误差通常采用正态性假设。而诸如病毒载量和CD4细胞数目等病毒性数据通常呈现偏斜性,因此正态性假设可能影响模型结果甚至导致错误的结论。在HIV动力学研究中,病毒响应值往往与协变量相关,且协变量的测量值通常存在误差,为此论文中联立协变量过程建立具有偏正态分布的非线性混合效应联合模型,并用贝叶斯推断方法估计模型的参数。由于协变量能够解释个体内的部分变化,因此协变量过程的模型选择对病毒载量的拟合效果有重要的影响。该文提出了一次移动平均模型作为协变量过程的改进模型,比较后发现当协变量采用移动平均模型时,病毒载量模型的拟合效果更好。该结果对协变量模型的研究具有重要的指导意义。     

Overcoming biases and misconceptions in ecological studies

The aggregate data study design provides an alternative group level analysis to ecological studies in the estimation of individual level health risks. An aggregate model is derived by aggregating a plausible individual level relative rate model within groups, such that population-based disease rates are modelled as functions of individual level covariate data. We apply an aggregate data method to a series of fictitious examples from a review paper by Greenland and Robins which illustrated the problems that can arise when using the results of ecological studies to make inference about individual health risks. We use simulated data based on their examples to demonstrate that the aggregate data approach can address many of the sources of bias that are inherent in typical ecological analyses, even though the limited between-region covariate variation in these examples reduces the efficiency of the aggregate study. The aggregate method has the potential to estimate exposure effects of interest in the presence of non-linearity, confounding at individual and group levels, effect modification, classical measurement error in the exposure and non-differential misclassification in the confounder.     

Estimation and Prediction in the Presence of Spatial Confounding for Spatial Linear Models

In studies that produce data with spatial structure, it is common that covariates of interest vary spatially in addition to the error. Because of this, the error and covariate are often correlated. When this occurs, it is difficult to distinguish the covariate effect from residual spatial variation. In an i.i.d. normal error setting, it is well known that this type of correlation produces biased coefficient estimates, but predictions remain unbiased. In a spatial setting, recent studies have shown that coefficient estimates remain biased, but spatial prediction has not been addressed. The purpose of this paper is to provide a more detailed study of coefficient estimation from spatial models when covariate and error are correlated and then begin a formal study regarding spatial prediction. This is carried out by investigating properties of the generalized least squares estimator and the best linear unbiased predictor when a spatial random effect and a covariate are jointly modelled. Under this setup, we demonstrate that the mean squared prediction error is possibly reduced when covariate and error are correlated.     

Censored regression with the multistate accelerated sojourn times model

Many disease processes are characterized by two or more successive health states, and it is often of interest and importance to assess state-specific covariate effects. However, with incomplete follow-up data such inference has not been satisfactorily addressed in the literature. We model the logarithm-transformed sojourn time in each state as linearly related to the covariates; however, neither the distributional form of the error term nor the dependence structure of the states needs to be specified. We propose a regression procedure to accommodate incomplete follow-up data. Asymptotic theory is presented, along with some tools for goodness-of-fit diagnostics. Simulation studies show that the proposal is reliable for practical use. We illustrate it by application to a cancer clinical trial.     

Composite conditional likelihood for sparse clustered data

Summary.  Sparse clustered data arise in finely stratified genetic and epidemiologic studies and pose at least two challenges to inference. First, it is difficult to model and interpret the full joint probability of dependent discrete data, which limits the utility of full likelihood methods. Second, standard methods for clustered data, such as pairwise likelihood and the generalized estimating function approach, are unsuitable when the data are sparse owing to the presence of many nuisance parameters. We present a composite conditional likelihood for use with sparse clustered data that provides valid inferences about covariate effects on both the marginal response probabilities and the intracluster pairwise association. Our primary focus is on sparse clustered binary data, in which case the method proposed utilizes doubly discordant quadruplets drawn from each stratum to conduct inference about the intracluster pairwise odds ratios.     

On Confounding, Prediction and Efficiency in the Analysis of Longitudinal and Cross-sectional Clustered Data

Abstract.  In the analysis of clustered and/or longitudinal data, it is usually desirable to ignore covariate information for other cluster members as well as future covariate information when predicting outcome for a given subject at a given time. This can be accomplished through con-ditional mean models which merely condition on the considered subject's covariate history at each time. Pepe & Anderson (Commun. Stat. Simul. Comput. 23, 1994 , 939) have shown that ordinary generalized estimating equations may yield biased estimates for the parameters in such models, but that valid inferences can be guaranteed by using a diagonal working covariance matrix in the equations. In this paper, we provide insight into the nature of this problem by uncovering substantive data-generating mechanisms under which such biases will result. We then propose a class of asymptotically unbiased estimators for the parameters indexing the suggested conditional mean models. In addition, we provide a representation for the efficient estimator in our class, which attains the semi-parametric efficiency bound under the model, along with an efficient algorithm for calculating it. This algorithm is easy to apply and may realize major efficiency improvements as demonstrated through simulation studies. The results suggest ways to improve the efficiency of inverse-probability-of-treatment estimators which adjust for time-varying confounding, and are used to estimate the effect of discontinuing highly active anti-retroviral therapy (HAART) on viral load in HIV-infected patients.     

A Comparison of Analysis of Covariate-Adjusted Residuals and Analysis of Covariance

Various methods to control the influence of a covariate on a response variable are compared. These methods are ANOVA with or without homogeneity of variances (HOV) of errors and Kruskal–Wallis (K–W) tests on (covariate-adjusted) residuals and analysis of covariance (ANCOVA). Covariate-adjusted residuals are obtained from the overall regression line fit to the entire data set ignoring the treatment levels or factors. It is demonstrated that the methods on covariate-adjusted residuals are only appropriate when the regression lines are parallel and covariate means are equal for all treatments. Empirical size and power performance of the methods are compared by extensive Monte Carlo simulations. We manipulated the conditions such as assumptions of normality and HOV, sample size, and clustering of the covariates. The parametric methods on residuals and ANCOVA exhibited similar size and power when error terms have symmetric distributions with variances having the same functional form for each treatment, and covariates have uniform distributions within the same interval for each treatment. In such cases, parametric tests have higher power compared to the K–W test on residuals. When error terms have asymmetric distributions or have variances that are heterogeneous with different functional forms for each treatment, the tests are liberal with K–W test having higher power than others. The methods on covariate-adjusted residuals are severely affected by the clustering of the covariates relative to the treatment factors when covariate means are very different for treatments. For data clusters, ANCOVA method exhibits the appropriate level. However, such a clustering might suggest dependence between the covariates and the treatment factors, so makes ANCOVA less reliable as well.     

A new class of measurement-error models,with applications to dietary data

Measurement-error modelling occurs when one cannot observe a covariate, but instead has possibly replicated surrogate versions of this covariate measured with error. The vast majority of the literature in measurement-error modelling assumes (typically with good reason) that given the value of the true but unobserved (latent) covariate, the replicated surrogates are unbiased for latent covariate and conditionally independent. In the area of nutritional epidemiology, there is some evidence from biomarker studies that this simple conditional independence model may break down due to two causes: (a) systematic biases depending on a person's body mass index, and (b) an additional random component of bias, so that the error structure is the same as a one-way random-effects model. We investigate this problem in the context of (1) estimating distribution of usual nutrient intake, (2) estimating the correlation between a nutrient instrument and usual nutrient intake, and (3) estimating the true relative risk from an estimated relative risk using the error-prone covariate. While systematic bias due to body mass index appears to have little effect, the additional random effect in the variance structure is shown to have a potentially important effect on overall results, both on corrections for relative risk estimates and in estimating the distribution of usual nutrient intake. However, the effect of dietary measurement error on both factors is shown via examples to depend strongly on the data set being used. Indeed, one of our data sets suggests that dietary measurement error may be masking a strong risk of fat on breast cancer, while for a second data set this masking is not so clear. Until further understanding of dietary measurement is available, measurement-error corrections must be done on a study-specific basis, sensitivity analyses should be conducted, and even then results of nutritional epidemiology studies relating diet to disease risk should be interpreted cautiously.     

Non‐parametric Maximum Likelihood Estimation for Cox Regression with Subject‐Specific Measurement Error

Abstract. Many epidemiological studies have been conducted to identify an association between nutrient consumption and chronic disease risk. To this problem, Cox regression with additive covariate measurement error has been well developed in the literature. However, researchers are concerned with the validity of the additive measurement error assumption for self‐report nutrient data. Recently, some study designs using more reliable biomarker data have been considered, in which the additive measurement error assumption is more likely to hold. Biomarker data are often available in a subcohort. Self‐report data often encounter with a variety of serious biases. Complications arise primarily because the magnitude of measurement errors is often associated with some characteristics of a study subject. A more general measurement error model has been developed for self‐report data. In this paper, a non‐parametric maximum likelihood (NPML) estimator using an EM algorithm is proposed to simultaneously adjust for the general measurement errors.     

Amplification of Sensitivity Analysis in Matched Observational Studies

A sensitivity analysis displays the increase in uncertainty that attends an inference when a key assumption is relaxed. In matched observational studies of treatment effects, a key assumption in some analyses is that subjects matched for observed covariates are comparable, and this assumption is relaxed by positing a relevant covariate that was not observed and not controlled by matching. What properties would such an unobserved covariate need to have to materially alter the inference about treatment effects? For ease of calculation and reporting, it is convenient that the sensitivity analysis be of low dimension, perhaps indexed by a scalar sensitivity parameter, but for interpretation in specific contexts, a higher dimensional analysis may be of greater relevance. An amplification of a sensitivity analysis is defined as a map from each point in a low dimensional sensitivity analysis to a set of points, perhaps a 'curve,' in a higher dimensional sensitivity analysis such that the possible inferences are the same for all points in the set. Possessing an amplification, an investigator may calculate and report the low dimensional analysis, yet have available the interpretations of the higher dimensional analysis.