Generalized linear models with covariate measurement error and unknown link function

Generalized linear models (GLMs) with error-in-covariates are useful in epidemiological research due to the ubiquity of non-normal response variables and inaccurate measurements. The link function in GLMs is chosen by the user depending on the type of response variable, frequently the canonical link function. When covariates are measured with error, incorrect inference can be made, compounded by incorrect choice of link function. In this article we propose three flexible approaches for handling error-in-covariates and estimating an unknown link simultaneously. The first approach uses a fully Bayesian (FB) hierarchical framework, treating the unobserved covariate as a latent variable to be integrated over. The second and third are approximate Bayesian approach which use a Laplace approximation to marginalize the variables measured with error out of the likelihood. Our simulation results show support that the FB approach is often a better choice than the approximate Bayesian approaches for adjusting for measurement error, particularly when the measurement error distribution is misspecified. These approaches are demonstrated on an application with binary response.     

A bivariate generalized linear model with an application to meteorological data analysis

A bivariate generalized linear model is developed as a mixture distribution with one component of the mixture being discrete with probability mass only at the origin. The use of the proposed model is illustrated by analyzing local area meteorological measurements with constant correlation structure that incorporates predictor variables. The Monte Carlo study is performed to evaluate the inferential efficiency of model parameters for two types of true models. These results suggest that the estimates of regression parameters are consistent and the efficiency of the inference increases for the proposed model for ρ≥0.50 especially in larger samples. As an illustration of a bivariate generalized linear model, we analyze a precipitation monitoring data of adjacent local stations for Tokyo and Yokohama.     

Parametric relative survival regression using generalized linear models with application to Hodgkin's lymphoma

Changes in survival rates during 1940–1992 for patients with Hodgkin's disease are studied by using population-based data. The aim of the analysis is to identify when the breakthrough in clinical trials of chemotherapy treatments started to increase population survival rates, and to find how long it took for the increase to level off, indicating that the full population effect of the breakthrough had been realized. A Weibull relative survival model is used because the model parameters are easily interpretable when assessing the effect of advances in clinical trials. However, the methods apply to any relative survival model that falls within the generalized linear models framework. The model is fitted by using modifications of existing software (SAS, GLIM) and profile likelihood methods. The results are similar to those from a cause-specific analysis of the data by Feuer and co-workers. Survival started to improve around the time that a major chemotherapy breakthrough (nitrogen mustard, Oncovin, prednisone and procarbazine) was publicized in the mid 1960s but did not level off for 11 years. For the analysis of data where the cause of death is obtained from death certificates, the relative survival approach has the advantage of providing the necessary adjustment for expected mortality from causes other than the disease without requiring information on the causes of death.     

Testing serial correlation in partially linear models with validation data

This article investigates the testing for serial correlation in partially linear models with validation data and applies the empirical likelihood methods to construct serial tests statistics, and then we derive the asymptotic distribution of the test statistics under null hypothesis. Simulation results show that our method performs well.     

Penalized contrast estimation in functional linear models with circular data

Our aim is to estimate the unknown slope function in the functional linear model when the response Y is real and the random function X is a second-order stationary and periodic process. We obtain our estimator by minimizing a standard (and very simple) mean-square contrast on linear finite dimensional spaces spanned by trigonometric bases. Our approach provides a penalization procedure which allows to automatically select the adequate dimension, in a non-asymptotic point of view. In fact, we can show that our penalized estimator reaches the optimal (minimax) rate of convergence in the sense of the prediction error. We complete the theoretical results by a simulation study and a real example that illustrates how the procedure works in practice.     

Conditionally gaussian distributions and an application to kalman filtering with stochastic regressors

The work reviews theory of conditionally Gaussian distributions, especially so called theorems on normal correlation. Three theorems are given: the basic, the recursive, and the conditional theorem on normal correlation. They assume that (a,y), (a,x,y), or (a,y,z) has a Gaussian distribution, ussert that (a,y), (a,x,y), and (a,y,z), respectively, are Gaussian, and give formulas for the corresponding conditional mean vectors and variance covariance matrices. A proof is presented for the recursive and the conditional theorem.     

Dynamic approach to linear statistical calibration with an application in microwave radiometry

The problem of statistical calibration of a measuring instrument can be framed both in a statistical context as well as in an engineering context. In the first, the problem is dealt with by distinguishing between the ‘classical’ approach and the ‘inverse’ regression approach. Both of these models are static models and are used to estimate exact measurements from measurements that are affected by error. In the engineering context, the variables of interest are considered to be taken at the time at which you observe it. The Bayesian time series analysis method of Dynamic Linear Models can be used to monitor the evolution of the measures, thus introducing a dynamic approach to statistical calibration. The research presented employs a new approach to performing statistical calibration. A simulation study in the context of microwave radiometry is conducted that compares the dynamic model to traditional static frequentist and Bayesian approaches. The focus of the study is to understand how well the dynamic statistical calibration method performs under various signal-to-noise ratios, r.     

Admissible linear estimation in singular linear models with respect to a restricted parameter set

The admissibility results of Hoffmann (1977), proved in the context of a nonsingular covariance matrix are extended to the situation where the covariance matrix is singular. Admissible linear estimators in the Gauss-Markoff model are characterised and admissibility of the Best Linear Unbiased Estimator is investigated.     

An evaluation of ridge estimator in linear mixed models: an example from kidney failure data

This paper is concerned with the ridge estimation of fixed and random effects in the context of Henderson's mixed model equations in the linear mixed model. For this purpose, a penalized likelihood method is proposed. A linear combination of ridge estimator for fixed and random effects is compared to a linear combination of best linear unbiased estimator for fixed and random effects under the mean-square error (MSE) matrix criterion. Additionally, for choosing the biasing parameter, a method of MSE under the ridge estimator is given. A real data analysis is provided to illustrate the theoretical results and a simulation study is conducted to characterize the performance of ridge and best linear unbiased estimators approach in the linear mixed model.     

A Bayesian approach for generalized linear models with explanatory biomarker measurement variables subject to detection limit: an application to acute lung injury

Biomarkers have the potential to improve our understanding of disease diagnosis and prognosis. Biomarker levels that fall below the assay detection limits (DLs), however, compromise the application of biomarkers in research and practice. Most existing methods to handle non-detects focus on a scenario in which the response variable is subject to the DL; only a few methods consider explanatory variables when dealing with DLs. We propose a Bayesian approach for generalized linear models with explanatory variables subject to lower, upper, or interval DLs. In simulation studies, we compared the proposed Bayesian approach to four commonly used methods in a logistic regression model with explanatory variable measurements subject to the DL. We also applied the Bayesian approach and other four methods in a real study, in which a panel of cytokine biomarkers was studied for their association with acute lung injury (ALI). We found that IL8 was associated with a moderate increase in risk for ALI in the model based on the proposed Bayesian approach.     

Influence in covariance structure analysis: with an application to confirmatory factor analysis

Influence functions are derived for the parameters in covariance structure analysis, where the parameters are estimated by minimizing a discrepancy function between the assumed covariance matrix and the sample covariance matrix. The case of confirmatory factor analysis is studied precisely with a numerical example. Comparing with a general procedure called one-step estimation, the proposed procedure has two advantages:1) computing cost is cheaper, 2) the property that arbitrary influence can be decomposed into a fi-nite number of components discussed by Tanaka and Castano-Tostado(1990) can be used for efficient computing and the characterization of a covariance structure model from the sensitivity perspective. A numerical comparison is made among the confirmatory factor analysis and some procedures of ex-ploratory factor analysis by using the decomposition mentioned above.     

Bayesian analysis of linear models exhibiting changes in mean and precisionat an unknown time point

This paper analyses a linear model in which both the mean and the precision change exactly once at an unknown point in time. Posterior distributions are found for the unknown time point at which the changes occurred and for the ratio of the precisions. The Bayesian predictive distribution of k future observations is also derived. It is shown that the unconditional posterior distribution of the ratio of precisions is a mixture of F-type distributions and the predictive distribution is a mixture of multivariate t distributions.     

On the accuracy in high‐dimensional linear models and its application to genomic selection

Genomic selection is today a hot topic in genetics. It consists in predicting breeding values of selection candidates, using the large number of genetic markers now available owing to the recent progress in molecular biology. One of the most popular methods chosen by geneticists is ridge regression. We focus on some predictive aspects of ridge regression and present theoretical results regarding the accuracy criteria, that is, the correlation between predicted value and true value. We show the influence of singular values, the regularization parameter, and the projection of the signal on the space spanned by the rows of the design matrix. Asymptotic results in a high‐dimensional framework are given; in particular, we prove that the convergence to optimal accuracy highly depends on a weighted projection of the signal on each subspace. We discuss on how to improve the prediction. Last, illustrations on simulated and real data are proposed.     

Estimation of patterned covariance in the multivariate linear models: an outer product least-squares approach

In this article, we present a framework of estimating patterned covariance of interest in the multivariate linear models. The main idea in it is to estimate a patterned covariance by minimizing a trace distance function between outer product of residuals and its expected value. The proposed framework can provide us explicit estimators, called outer product least-squares estimators, for parameters in the patterned covariance of the multivariate linear model without or with restrictions on regression coefficients. The outer product least-squares estimators enjoy the desired properties in finite and large samples, including unbiasedness, invariance, consistency and asymptotic normality. We still apply the framework to three special situations where their patterned covariances are the uniform correlation, a generalized uniform correlation and a general q-dependence structure, respectively. Simulation studies for three special cases illustrate that the proposed method is a competent alternative of the maximum likelihood method in finite size samples.     

Non parametric regression analysis for longitudinal data with time-depending autoregressive error process

This paper considers a non parametric longitudinal model, where the within-subject correlation structure is represented by a time-depending autoregressive error process. An initial estimator without taking into account the within-subject correlation is obtained to fit the time-depending autoregressive error process. With the initial estimator, we construct a two-stage local linear estimator of the mean function. According to the asymptotic normality of the initial and two-stage estimators, it is discovered that the two-stage estimator has a smaller asymptotic variance. The simulation results show us that the two-stage estimation has some good properties. The analysis of a data set demonstrates its application.     

Unbiased estimation of a nonlinear function a normal mean with application to measurement err oorf models

Let W be a normal random variable with mean μand known variance σ². Conditions on the function f(·) are given under which there exists an unbiased estimator, f(W), of f(μ) for all real μ. In particular it is shown that f(·) must be an entire function over the complex plane. Infinite series solutions for F(·) are obtained which are shown to be valid under growth conditions of the derivatives, f^k( ·), of f(·). Approximate solutions are given for the cases in which no exact solution exists. The theory is applied to nonlinear measurement-error models as a means of finding unbiased score functions when measurement error is normally distributed. Relative efficiencies comparing the proposed method to the use of conditional scores (Stefanski and Carroll, 1987) are given for the Poisson regression model with canonical link.     

Doubly robust estimation of partially linear models for longitudinal data with dropouts and measurement error in covariates

In longitudinal studies, missing responses and mismeasured covariates are commonly seen due to the data collection process. Without cautiousness in data analysis, inferences from the standard statistical approaches may lead to wrong conclusions. In order to improve the estimation for longitudinal data analysis, a doubly robust estimation method for partially linear models, which can simultaneously account for the missing responses and mismeasured covariates, is proposed. Imprecisions of covariates are corrected by taking advantage of the independence between replicate measurement errors, and missing responses are handled by the doubly robust estimation under the mechanism of missing at random. The asymptotic properties of the proposed estimators are established under regularity conditions, and simulation studies demonstrate desired properties. Finally, the proposed method is applied to data from the Lifestyle Education for Activity and Nutrition study.     

Bayes linear analysis for graphical models: The geometric approach to local computation and interpretive graphics

This paper concerns the geometric treatment of graphical models using Bayes linear methods. We introduce Bayes linear separation as a second order generalised conditional independence relation, and Bayes linear graphical models are constructed using this property. A system of interpretive and diagnostic shadings are given, which summarise the analysis over the associated moral graph. Principles of local computation are outlined for the graphical models, and an algorithm for implementing such computation over the junction tree is described. The approach is illustrated with two examples. The first concerns sales forecasting using a multivariate dynamic linear model. The second concerns inference for the error variance matrices of the model for sales, and illustrates the generality of our geometric approach by treating the matrices directly as random objects. The examples are implemented using a freely available set of object-oriented programming tools for Bayes linear local computation and graphical diagnostic display.     

Continuous threshold models with two-way interactions in survival analysis

Proportional hazards model with the biomarker–treatment interaction plays an important role in the survival analysis of the subset treatment effect. A threshold parameter for a continuous biomarker variable defines the subset of patients who can benefit or lose from a certain new treatment. In this article, we focus on a continuous threshold effect using the rectified linear unit and propose a gradient descent method to obtain the maximum likelihood estimation of the regression coefficients and the threshold parameter simultaneously. Under certain regularity conditions, we prove the consistency, asymptotic normality and provide a robust estimate of the covariance matrix when the model is misspecified. To illustrate the finite sample properties of the proposed methods, we simulate data to evaluate the empirical biases, the standard errors and the coverage probabilities for both the correctly specified models and misspecified models. The proposed continuous threshold model is applied to a prostate cancer data with serum prostatic acid phosphatase as a biomarker.     

A class of semiparametric transormation frailty models with application to estimating treatment effects and heterogenity in aids clinical traials

Muitivariate failure time data are common in medical research; com¬monly used statistical models for such correlated failure-time data include frailty and marginal models. Both types of models most often assume pro¬portional hazards (Cox, 1972); but the Cox model may not fit the data well This article presents a class of linear transformation frailty models that in¬cludes, as a special case, the proportional hazards model with frailty. We then propose approximate procedures to derive the best linear unbiased es¬timates and predictors of the regression parameters and frailties. We apply the proposed methods to analyze results of a clinical trial of different dose levels of didansine (ddl) among HIV-infected patients who were intolerant of zidovudine (ZDV). These methods yield estimates of treatment effects and of frailties corresponding to patient groups defined by clinical history prior to entry into the trial.