Estimation of semiparametric regression model with longitudinal data

In a longitudinal study, an individual is followed up over a period of time. Repeated measurements on the response and some time-dependent covariates are taken at a series of sampling times. The sampling times are often irregular and depend on covariates. In this paper, we propose a sampling adjusted procedure for the estimation of the proportional mean model without having to specify a sampling model. Unlike existing procedures, the proposed method is robust to model misspecification of the sampling times. Large sample properties are investigated for the estimators of both regression coefficients and the baseline function. We show that the proposed estimation procedure is more efficient than the existing procedures. Large sample confidence intervals for the baseline function are also constructed by perturbing the estimation equations. A simulation study is conducted to examine the finite sample properties of the proposed estimators and to compare with some of the existing procedures. The method is illustrated with a data set from a recurrent bladder cancer study.     

Multiple imputation of censored survival data in the presence of missing covariates using restricted mean survival time

Missing covariates data with censored outcomes put a challenge in the analysis of clinical data especially in small sample settings. Multiple imputation (MI) techniques are popularly used to impute missing covariates and the data are then analyzed through methods that can handle censoring. However, techniques based on MI are available to impute censored data also but they are not much in practice. In the present study, we applied a method based on multiple imputation by chained equations to impute missing values of covariates and also to impute censored outcomes using restricted survival time in small sample settings. The complete data were then analyzed using linear regression models. Simulation studies and a real example of CHD data show that the present method produced better estimates and lower standard errors when applied on the data having missing covariate values and censored outcomes than the analysis of the data having censored outcome but excluding cases with missing covariates or the analysis when cases with missing covariate values and censored outcomes were excluded from the data (complete case analysis).     

Fast Bayesian variable screenings for binary response regressions with small sample size

Screening procedures play an important role in data analysis, especially in high-throughput biological studies where the datasets consist of more covariates than independent subjects. In this article, a Bayesian screening procedure is introduced for the binary response models with logit and probit links. In contrast to many screening rules based on marginal information involving one or a few covariates, the proposed Bayesian procedure simultaneously models all covariates and uses closed-form screening statistics. Specifically, we use the posterior means of the regression coefficients as screening statistics; by imposing a generalized g-prior on the regression coefficients, we derive the analytical form of their posterior means and compute the screening statistics without Markov chain Monte Carlo implementation. We evaluate the utility of the proposed Bayesian screening method using simulations and real data analysis. When the sample size is small, the simulation results suggest improved performance with comparable computational cost.     

A comparison of methods for the fitting of generalized additive models

There are several procedures for fitting generalized additive models, i.e. regression models for an exponential family response where the influence of each single covariates is assumed to have unknown, potentially non-linear shape. Simulated data are used to compare a smoothing parameter optimization approach for selection of smoothness and of covariates, a stepwise approach, a mixed model approach, and a procedure based on boosting techniques. In particular it is investigated how the performance of procedures is linked to amount of information, type of response, total number of covariates, number of influential covariates, and extent of non-linearity. Measures for comparison are prediction performance, identification of influential covariates, and smoothness of fitted functions. One result is that the mixed model approach returns sparse fits with frequently over-smoothed functions, while the functions are less smooth for the boosting approach and variable selection is less strict. The other approaches are in between with respect to these measures. The boosting procedure is seen to perform very well when little information is available and/or when a large number of covariates is to be investigated. It is somewhat surprising that in scenarios with low information the fitting of a linear model, even with stepwise variable selection, has not much advantage over the fitting of an additive model when the true underlying structure is linear. In cases with more information the prediction performance of all procedures is very similar. So, in difficult data situations the boosting approach can be recommended, in others the procedures can be chosen conditional on the aim of the analysis.     

Explained Variation and Predictive Accuracy in General Parametric Statistical Models: The Role of Model Misspecification

When studying a regression model measures of explained variation are used to assess the degree to which the covariates determine the outcome of interest. Measures of predictive accuracy are used to assess the accuracy of the predictions based on the covariates and the regression model. We give a detailed and general introduction to the two measures and the estimation procedures. The framework we set up allows for a study of the effect of misspecification on the quantities estimated. We also introduce a generalization to survival analysis.     

Additive hazards regression of current status data with auxiliary covariates

This paper discusses the regression analysis of current status failure time data arising from the additive hazards model with auxiliary covariates. As often occurs in practice, it is impossible or impractical to measure the exact magnitude of covariates for all subjects in a study. To compensate the missing information, some auxiliary covariates are utilized instead. We propose two easy-to-implement procedures for estimation of regression parameters by making use of auxiliary information. The asymptotic properties of the resulting estimators are established and extensive numerical studies indicate that both procedures work well in practice.     

Power of double-sampling tests for General Linear Hypotheses

In this paper, testing procedures based on double-sampling are proposed that yield gains in terms of power for the tests of General Linear Hypotheses. The distribution of a test statistic, involving both the measurements of the outcome on the smaller sample and of the covariates on the wider sample, is first derived. Then, approximations are provided in order to allow for a formal comparison between the powers of double-sampling and single-sampling strategies. Furthermore, it is shown how to allocate the measurements of the outcome and the covariates in order to maximize the power of the tests for a given experimental cost.     

A Partially Linear Regression Model for Data from an Outcome-Dependent Sampling Design

The outcome dependent sampling scheme has been gaining attention in both the statistical literature and applied fields. Epidemiological and environmental researchers have been using it to select the observations for more powerful and cost-effective studies. Motivated by a study of the effect of in utero exposure to polychlorinated biphenyls on children's IQ at age 7, in which the effect of an important confounding variable is nonlinear, we consider a semi-parametric regression model for data from an outcome-dependent sampling scheme where the relationship between the response and covariates is only partially parameterized. We propose a penalized spline maximum likelihood estimation (PSMLE) for inference on both the parametric and the nonparametric components and develop their asymptotic properties. Through simulation studies and an analysis of the IQ study, we compare the proposed estimator with several competing estimators. Practical considerations of implementing those estimators are discussed.     

Covariate adjustment and estimation of mean response in randomised trials

Analyses of randomised trials are often based on regression models which adjust for baseline covariates, in addition to randomised group. Based on such models, one can obtain estimates of the marginal mean outcome for the population under assignment to each treatment, by averaging the model‐based predictions across the empirical distribution of the baseline covariates in the trial. We identify under what conditions such estimates are consistent, and in particular show that for canonical generalised linear models, the resulting estimates are always consistent. We show that a recently proposed variance estimator underestimates the variance of the estimator around the true marginal population mean when the baseline covariates are not fixed in repeated sampling and provide a simple adjustment to remedy this. We also describe an alternative semiparametric estimator, which is consistent even when the outcome regression model used is misspecified. The different estimators are compared through simulations and application to a recently conducted trial in asthma.     

Model checks for nonparametric regression with missing data: a comparative study

ABSTRACT

This paper analyses the behaviour of the goodness-of-fit tests for regression models. To this end, it uses statistics based on an estimation of the integrated regression function with missing observations either in the response variable or in some of the covariates. It proposes several versions of one empirical process, constructed from a previous estimation, that uses only the complete observations or replaces the missing observations with imputed values. In the case of missing covariates, a link model is used to fill the missing observations with other complete covariates. In all the situations, Bootstrap methodology is used to calibrate the distribution of the test statistics. A broad simulation study compares the different procedures based on empirical regression methodology, with smoothed tests previously studied in the literature. The comparison reflects the effect of the correlation between the covariates in the tests based on the imputed sample for missing covariates. In addition, the paper proposes a computational binning strategy to evaluate the tests based on an empirical process for large data sets. Finally, two applications to real data illustrate the performance of the tests.     

Bayesian LASSO-Regularized quantile regression for linear regression models with autoregressive errors

Quantile regression (QR) is a natural alternative for depicting the impact of covariates on the conditional distributions of a outcome variable instead of the mean. In this paper, we investigate Bayesian regularized QR for the linear models with autoregressive errors. LASSO-penalized type priors are forced on regression coefficients and autoregressive parameters of the model. Gibbs sampler algorithm is employed to draw the full posterior distributions of unknown parameters. Finally, the proposed procedures are illustrated by some simulation studies and applied to a real data analysis of the electricity consumption.     

Confidence Bands for Comparison of Transition Probabilities in a Markov Chain Model

We consider graphs, confidence procedures and tests that can be used to compare transition probabilities in a Markov chain model with intensities specified by a Cox proportional hazard model. Under assumptions of this model, the regression coefficients provide information about the relative risks of covariates in one–step transitions, however, they cannot in general be used to to assess whether or not the covariates have a beneficial or detrimental effect on the endpoint events. To alleviate this problem, we consider graphical tests based on confidence procedures for a generalized Q–Q plot and for the difference between transition probabilities. The procedures are illustrated using data of the International Bone Marrow Transplant Registry.     

Estimation of group means using Bayesian generalized linear mixed models

Generalized linear mixed models (GLMM) are commonly used to model the treatment effect over time while controlling for important clinical covariates. Standard software procedures often provide estimates of the outcome based on the mean of the covariates; however, these estimates will be biased for the true group means in the GLMM. Implementing GLMM in the frequentist framework can lead to issues of convergence. A simulation study demonstrating the use of fully Bayesian GLMM for providing unbiased estimates of group means is shown. These models are very straightforward to implement and can be used for a broad variety of outcomes (eg, binary, categorical, and count data) that arise in clinical trials. We demonstrate the proposed method on a data set from a clinical trial in diabetes.     

Imputation for semiparametric transformation models with biased-sampling data

Widely recognized in many fields including economics, engineering, epidemiology, health sciences, technology and wildlife management, length-biased sampling generates biased and right-censored data but often provide the best information available for statistical inference. Different from traditional right-censored data, length-biased data have unique aspects resulting from their sampling procedures. We exploit these unique aspects and propose a general imputation-based estimation method for analyzing length-biased data under a class of flexible semiparametric transformation models. We present new computational algorithms that can jointly estimate the regression coefficients and the baseline function semiparametrically. The imputation-based method under the transformation model provides an unbiased estimator regardless whether the censoring is independent or not on the covariates. We establish large-sample properties using the empirical processes method. Simulation studies show that under small to moderate sample sizes, the proposed procedure has smaller mean square errors than two existing estimation procedures. Finally, we demonstrate the estimation procedure by a real data example.     

Non-parametric Evaluation of Biomarker Accuracy under Nested Case-control Studies

To evaluate the clinical utility of new risk markers, a crucial step is to measure their predictive accuracy with prospective studies. However, it is often infeasible to obtain marker values for all study participants. The nested case-control (NCC) design is a useful cost-effective strategy for such settings. Under the NCC design, markers are only ascertained for cases and a fraction of controls sampled randomly from the risk sets. The outcome dependent sampling generates a complex data structure and therefore a challenge for analysis. Existing methods for analyzing NCC studies focus primarily on association measures. Here, we propose a class of non-parametric estimators for commonly used accuracy measures. We derived asymptotic expansions for accuracy estimators based on both finite population and Bernoulli sampling and established asymptotic equivalence between the two. Simulation results suggest that the proposed procedures perform well in finite samples. The new procedures were illustrated with data from the Framingham Offspring study.     

Optimal design for epidemiological studies subject to designed missingness

In large epidemiological studies, budgetary or logistical constraints will typically preclude study investigators from measuring all exposures, covariates and outcomes of interest on all study subjects. We develop a flexible theoretical framework that incorporates a number of familiar designs such as case control and cohort studies, as well as multistage sampling designs. Our framework also allows for designed missingness and includes the option for outcome dependent designs. Our formulation is based on maximum likelihood and generalizes well known results for inference with missing data to the multistage setting. A variety of techniques are applied to streamline the computation of the Hessian matrix for these designs, facilitating the development of an efficient software tool to implement a wide variety of designs.     

Improving precision and power in randomized trials with a two-stage study design: Stratification using clustering method

In a randomized controlled trial (RCT), it is possible to improve precision and power and reduce sample size by appropriately adjusting for baseline covariates. There are multiple statistical methods to adjust for prognostic baseline covariates, such as an ANCOVA method. In this paper, we propose a clustering-based stratification method for adjusting for the prognostic baseline covariates. Clusters (strata) are formed only based on prognostic baseline covariates, not outcome data nor treatment assignment. Therefore, the clustering procedure can be completed prior to the availability of outcome data. The treatment effect is estimated in each cluster, and the overall treatment effect is derived by combining all cluster-specific treatment effect estimates. The proposed implementation of the procedure is described. Simulations studies and an example are presented.     

Bayesian density regression for discrete outcomes

We develop Bayesian models for density regression with emphasis on discrete outcomes. The problem of density regression is approached by considering methods for multivariate density estimation of mixed scale variables, and obtaining conditional densities from the multivariate ones. The approach to multivariate mixed scale outcome density estimation that we describe represents discrete variables, either responses or covariates, as discretised versions of continuous latent variables. We present and compare several models for obtaining these thresholds in the challenging context of count data analysis where the response may be over‐ and/or under‐dispersed in some of the regions of the covariate space. We utilise a nonparametric mixture of multivariate Gaussians to model the directly observed and the latent continuous variables. The paper presents a Markov chain Monte Carlo algorithm for posterior sampling, sufficient conditions for weak consistency, and illustrations on density, mean and quantile regression utilising simulated and real datasets.     

An Accelerated Model for Recurrence Data

Recurrence data usually come from sampling a system in different ages. It is common in areas of manufacturing, reliability, medicine, and risk analysis. In this article, an accelerated model for recurrence data is proposed. The model is based on the time between failures (TBFs) for an accelerated time regression method using the number of failures as a dummy covariate. Using this model, the repair (or cure) effect can also be studied. A graphical display of recurrence data created by plotting the log-TBFs versus the number of failures is proposed to detect any linear or nonlinear trend for log-TBFs. The model is then extended to incorporate covariates and/or time factors. Two data sets are used to demonstrate the usefulness of the proposed model.     

Mixture models in measurement error problems, with reference to epidemiological studies

Summary. The paper focuses on a Bayesian treatment of measurement error problems and on the question of the specification of the prior distribution of the unknown covariates. It presents a flexible semiparametric model for this distribution based on a mixture of normal distributions with an unknown number of components. Implementation of this prior model as part of a full Bayesian analysis of measurement error problems is described in classical set-ups that are encountered in epidemiological studies: logistic regression between unknown covariates and outcome, with a normal or log-normal error model and a validation group. The feasibility of this combined model is tested and its performance is demonstrated in a simulation study that includes an assessment of the influence of misspecification of the prior distribution of the unknown covariates and a comparison with the semiparametric maximum likelihood method of Roeder, Carroll and Lindsay. Finally, the methodology is illustrated on a data set on coronary heart disease and cholesterol levels in blood.