Properties of preliminary test estimators and shrinkage estimators for evaluating multiple exposures - Application to questionnaire data from the SONIC study

Epidemiology studies increasingly examine multiple exposures in relation to disease by selecting the exposures of interest in a thematic manner. For example, sun exposure, sunburn, and sun protection behavior could be themes for an investigation of sun-related exposures. Several studies now use pre-defined linear combinations of the exposures pertaining to the themes to estimate the effects of the individual exposures. Such analyses may improve the precision of the exposure effects, but they can lead to inflated bias and type I errors when the linear combinations are inaccurate. We investigate preliminary test estimators and empirical Bayes type shrinkage estimators as alternative approaches when it is desirable to exploit the thematic choice of exposures, but the accuracy of the pre-defined linear combinations is unknown. We show that the two types of estimator are intimately related under certain assumptions. The shrinkage estimator derived under the assumption of an exchangeable prior distribution gives precise estimates and is robust to misspecifications of the user-defined linear combinations. The precision gains and robustness of the shrinkage estimation approach are illustrated using data from the SONIC study, where the exposures are the individual questionnaire items and the outcome is (log) total back nevus count.     

Measuring and estimating the interaction between exposures on a dichotomous outcome for observational studies

In observational studies for the interaction between exposures on a dichotomous outcome of a certain population, usually one parameter of a regression model is used to describe the interaction, leading to one measure of the interaction. In this article we use the conditional risk of an outcome given exposures and covariates to describe the interaction and obtain five different measures of the interaction, that is, difference between the marginal risk differences, ratio of the marginal risk ratios, ratio of the marginal odds ratios, ratio of the conditional risk ratios, and ratio of the conditional odds ratios. These measures reflect different aspects of the interaction. By using only one regression model for the conditional risk, we obtain the maximum-likelihood (ML)-based point and interval estimates of these measures, which are most efficient due to the nature of ML. We use the ML estimates of the model parameters to obtain the ML estimates of these measures. We use the approximate normal distribution of the ML estimates of the model parameters to obtain approximate non-normal distributions of the ML estimates of these measures and then confidence intervals of these measures. The method can be easily implemented and is presented via a medical example.     

Predictive control of posterior robustness for sample size choice in a Bernoulli model

In this article we consider the sample size determination problem in the context of robust Bayesian parameter estimation of the Bernoulli model. Following a robust approach, we consider classes of conjugate Beta prior distributions for the unknown parameter. We assume that inference is robust if posterior quantities of interest (such as point estimates and limits of credible intervals) do not change too much as the prior varies in the selected classes of priors. For the sample size problem, we consider criteria based on predictive distributions of lower bound, upper bound and range of the posterior quantity of interest. The sample size is selected so that, before observing the data, one is confident to observe a small value for the posterior range and, depending on design goals, a large (small) value of the lower (upper) bound of the quantity of interest. We also discuss relationships with and comparison to non robust and non informative Bayesian methods.     

A Statistical Model for Social Network Labeling

We consider a social network from which one observes not only network structure (i.e., nodes and edges) but also a set of labels (or tags, keywords) for each node (or user). These labels are self-created and closely related to the user’s career status, life style, personal interests, and many others. Thus, they are of great interest for online marketing. To model their joint behavior with network structure, a complete data model is developed. The model is based on the classical p₁ model but allows the reciprocation parameter to be label-dependent. By focusing on connected pairs only, the complete data model can be generalized into a conditional model. Compared with the complete data model, the conditional model specifies only the conditional likelihood for the connected pairs. As a result, it suffers less risk from model misspecification. Furthermore, because the conditional model involves connected pairs only, the computational cost is much lower. The resulting estimator is consistent and asymptotically normal. Depending on the network sparsity level, the convergence rate could be different. To demonstrate its finite sample performance, numerical studies (based on both simulated and real datasets) are presented.     

Logistic regression analysis of epidemiologic data: theory and practice

The use of logistic regression analysis is widely applicable to epidemiologic studies concerned with quantifying an association between a study factor (i.e., an exposure variable) and a health outcome (i.e., disease status). This paper reviews the general characteristics of the logistic model and illustrates its use in epidemiologic inquiry. Particular emphasis is given to the control of extraneous variables in the context of follow-up and case-control studies. Techniques for both unconditional and conditional maximum likelihood estimation of the parameters in the logistic model are described and illustrated. A general analysis strategy is also presented which incorporates the assessment of both interaction and confounding in quantifying an exposure-disease association of interest.     

Opportunities for minimization of confounding in observational research

Observational epidemiological studies are increasingly used in pharmaceutical research to evaluate the safety and effectiveness of medicines. Such studies can complement findings from randomized clinical trials by involving larger and more generalizable patient populations by accruing greater durations of follow-up and by representing what happens more typically in the clinical setting. However, the interpretation of exposure effects in observational studies is almost always complicated by non-random exposure allocation, which can result in confounding and potentially lead to misleading conclusions. Confounding occurs when an extraneous factor, related to both the exposure and the outcome of interest, partly or entirely explains the relationship observed between the study exposure and the outcome. Although randomization can eliminate confounding by distributing all such extraneous factors equally across the levels of a given exposure, methods for dealing with confounding in observational studies include a careful choice of study design and the possible use of advanced analytical methods. The aim of this paper is to introduce some of the approaches that can be used to help minimize the impact of confounding in observational research to the reader working in the pharmaceutical industry.     

Asymptotic Normality of a Kernel Conditional Quantile Estimator Under Strong Mixing Hypothesis and Left-Truncation

We consider the estimation of the conditional quantile when the interest variable is subject to left truncation. Under regularity conditions, it is shown that the kernel estimate of the conditional quantile is asymptotically normally distributed, when the data exhibit some kind of dependence. We use asymptotic normality to construct confidence bands for predictors based on the kernel estimate of the conditional median.     

Identification of longitudinal biomarkers for survival by a score test derived from a joint model of longitudinal and competing risks data

In this paper, we consider joint modelling of repeated measurements and competing risks failure time data. For competing risks time data, a semiparametric mixture model in which proportional hazards model are specified for failure time models conditional on cause and a multinomial model for the marginal distribution of cause conditional on covariates. We also derive a score test based on joint modelling of repeated measurements and competing risks failure time data to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data.     

Two-stage hierarchical modeling for analysis of subpopulations in conditional distributions

In this work, we develop modeling and estimation approach for the analysis of cross-sectional clustered data with multimodal conditional distributions where the main interest is in analysis of subpopulations. It is proposed to model such data in a hierarchical model with conditional distributions viewed as finite mixtures of normal components. With a large number of observations in the lowest level clusters, a two-stage estimation approach is used. In the first stage, the normal mixture parameters in each lowest level cluster are estimated using robust methods. Robust alternatives to the maximum likelihood estimation are used to provide stable results even for data with conditional distributions such that their components may not quite meet normality assumptions. Then the lowest level cluster-specific means and standard deviations are modeled in a mixed effects model in the second stage. A small simulation study was conducted to compare performance of finite normal mixture population parameter estimates based on robust and maximum likelihood estimation in stage 1. The proposed modeling approach is illustrated through the analysis of mice tendon fibril diameters data. Analyses results address genotype differences between corresponding components in the mixtures and demonstrate advantages of robust estimation in stage 1.     

Constructing non-regular robust parameter designs

In recent years there has been considerable attention paid to robust parameter design as a strategy for variance reduction. Of particular concern is the selection of a good experimental plan in light of the two different types of factors in the experiment (control and noise) and the asymmetric manner in which effects of the same order are treated. Recent work has focussed on the selection of regular fractional factorial designs in this setting. In this article, we consider the construction and selection of optimal non-regular experiment plans for robust parameter design. Our approach defines the word-length pattern for non-regular fractional factorial designs with two different types of factors which allows for the choice of optimal design to emphasize the estimation of the effects of interest. We use this new word-length pattern to rank non-regular robust parameter designs. We show that one can easily find minimum aberration robust parameter designs from existing orthogonal arrays. The methodology is demonstrated by finding optimal assignments for control and noise factors for 12, 16 and 20-run orthogonal arrays.     

Factor Stochastic Volatility in Mean Models: A GMM Approach

This paper provides a semiparametric framework for modeling multivariate conditional heteroskedasticity. We put forward latent stochastic volatility (SV) factors as capturing the commonality in the joint conditional variance matrix of asset returns. This approach is in line with common features as studied by Engle and Kozicki (1993), and it allows us to focus on identication of factors and factor loadings through first- and second-order conditional moments only. We assume that the time-varying part of risk premiums is based on constant prices of factor risks, and we consider a factor SV in mean model. Additional specification of both expectations and volatility of future volatility of factors provides conditional moment restrictions, through which the parameters of the model are all identied. These conditional moment restrictions pave the way for instrumental variables estimation and GMM inference.     

Estimation and inference of the joint conditional distribution for multivariate longitudinal data using nonparametric copulas

In this paper we study estimating the joint conditional distributions of multivariate longitudinal outcomes using regression models and copulas. For the estimation of marginal models, we consider a class of time-varying transformation models and combine the two marginal models using nonparametric empirical copulas. Our models and estimation method can be applied in many situations where the conditional mean-based models are not good enough. Empirical copulas combined with time-varying transformation models may allow quite flexible modelling for the joint conditional distributions for multivariate longitudinal data. We derive the asymptotic properties for the copula-based estimators of the joint conditional distribution functions. For illustration we apply our estimation method to an epidemiological study of childhood growth and blood pressure.     

Optimal estimation in surrogate outcome regression problems

The authors consider a double robust estimation of the regression parameter defined by an estimating equation in a surrogate outcome set‐up. Under a correct specification of the propensity score, the proposed estimator has smallest trace of asymptotic covariance matrix whether the “working outcome regression model” involved is specified correct or not, and it is particularly meaningful when it is incorrectly specified. Simulations are conducted to examine the finite sample performance of the proposed procedure. Data on obesity and high blood pressure are analyzed for illustration. The Canadian Journal of Statistics 38: 633–646; 2010 © 2010 Statistical Society of Canada     

Regression analysis of longitudinal data with outcome‐dependent sampling and informative censoring

We consider a regression analysis of longitudinal data in the presence of outcome‐dependent observation times and informative censoring. Existing approaches commonly require a correct specification of the joint distribution of longitudinal measurements, the observation time process, and informative censoring time under the joint modeling framework and can be computationally cumbersome due to the complex form of the likelihood function. In view of these issues, we propose a semiparametric joint regression model and construct a composite likelihood function based on a conditional order statistics argument. As a major feature of our proposed methods, the aforementioned joint distribution is not required to be specified, and the random effect in the proposed joint model is treated as a nuisance parameter. Consequently, the derived composite likelihood bypasses the need to integrate over the random effect and offers the advantage of easy computation. We show that the resulting estimators are consistent and asymptotically normal. We use simulation studies to evaluate the finite‐sample performance of the proposed method and apply it to a study of weight loss data that motivated our investigation.     

Screening procedures using quadratic forms

In quality control, a performance variable having a two-sided specification limit is common for assessing lot quality. Sometimes it is difficult or impossible to measure the performance variable directly; for example, when testing is destructive, expensive, or when the performance variable is related to the lifetime of the product. However, it may happen that there are several concomitant variables which are easily measured and which correlate highly with the variable of interest. Thus, one may use measurements on these variables to select or screen product which will have a high conditional probability of meeting product specification. We consider this situation when all variables have a joint multivariate normal distribution and the specification limits on the performance variable are two-sided.     

A statistical framework for ecological and aggregate studies

Inference from studies that make use of data at the level of the area, rather than at the level of the individual, is more difficult for a variety of reasons. Some of these difficulties arise because frequently exposures (including confounders) vary within areas. In the most basic form of ecological study the outcome measure is regressed against a simple area level summary of exposure. In the aggregate data approach a survey of exposures and confounders is taken within each area. An alternative approach is to assume a parametric form for the within-area exposure distribution. We provide a framework within which ecological and aggregate data studies may be viewed, and we review some approaches to inference in such studies, clarifying the assumptions on which they are based. General strategies for analysis are provided including an estimator based on Monte Carlo integration that allows inference in the case of a general risk–exposure model. We also consider the implications of the introduction of random effects, and the existence of confounding and errors in variables.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Disaggregated spatial modelling for areal unit categorical data

Summary.  We consider joint spatial modelling of areal multivariate categorical data assuming a multiway contingency table for the variables, modelled by using a log-linear model, and connected across units by using spatial random effects. With no distinction regarding whether variables are response or explanatory, we do not limit inference to conditional probabilities, as in customary spatial logistic regression. With joint probabilities we can calculate arbitrary marginal and conditional probabilities without having to refit models to investigate different hypotheses. Flexible aggregation allows us to investigate subgroups of interest; flexible conditioning enables not only the study of outcomes given risk factors but also retrospective study of risk factors given outcomes. A benefit of joint spatial modelling is the opportunity to reveal disparities in health in a richer fashion, e.g. across space for any particular group of cells, across groups of cells at a particular location, and, hence, potential space–group interaction. We illustrate with an analysis of birth records for the state of North Carolina and compare with spatial logistic regression.     

A linear model-based test for the heterogeneity of conditional correlations

Current methods of testing the equality of conditional correlations of bivariate data on a third variable of interest (covariate) are limited due to discretizing of the covariate when it is continuous. In this study, we propose a linear model approach for estimation and hypothesis testing of the Pearson correlation coefficient, where the correlation itself can be modeled as a function of continuous covariates. The restricted maximum likelihood method is applied for parameter estimation, and the corrected likelihood ratio test is performed for hypothesis testing. This approach allows for flexible and robust inference and prediction of the conditional correlations based on the linear model. Simulation studies show that the proposed method is statistically more powerful and more flexible in accommodating complex covariate patterns than the existing methods. In addition, we illustrate the approach by analyzing the correlation between the physical component summary and the mental component summary of the MOS SF-36 form across a fair number of covariates in the national survey data.     

Conditional Stochastic Dominance Testing

This article proposes bootstrap-based stochastic dominance tests for nonparametric conditional distributions and their moments. We exploit the fact that a conditional distribution dominates the other if and only if the difference between the marginal joint distributions is monotonic in the explanatory variable at each value of the dependent variable. The proposed test statistic compares restricted and unrestricted estimators of the difference between the joint distributions, and it can be implemented under minimal smoothness requirements on the underlying nonparametric curves and without resorting to smooth estimation. The finite sample properties of the proposed test are examined by means of a Monte Carlo study. We illustrate the test by studying the impact on postintervention earnings of the National Supported Work Demonstration, a randomized labor training program carried out in the 1970s.