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.     

Flexible modeling of conditional distributions using smooth mixtures of asymmetric student t densities

A general model is proposed for flexibly estimating the density of a continuous response variable conditional on a possibly high-dimensional set of covariates. The model is a finite mixture of asymmetric student t densities with covariate-dependent mixture weights. The four parameters of the components, the mean, degrees of freedom, scale and skewness, are all modeled as functions of the covariates. Inference is Bayesian and the computation is carried out using Markov chain Monte Carlo simulation. To enable model parsimony, a variable selection prior is used in each set of covariates and among the covariates in the mixing weights. The model is used to analyze the distribution of daily stock market returns, and shown to more accurately forecast the distribution of returns than other widely used models for financial data.     

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.     

A Profile Conditional Likelihood Approach for the Semiparametric Transformation Regression Model with Missing Covariates

We propose a profile conditional likelihood approach to handle missing covariates in the general semiparametric transformation regression model. The method estimates the marginal survival function by the Kaplan-Meier estimator, and then estimates the parameters of the survival model and the covariate distribution from a conditional likelihood, substituting the Kaplan-Meier estimator for the marginal survival function in the conditional likelihood. This method is simpler than full maximum likelihood approaches, and yields consistent and asymptotically normally distributed estimator of the regression parameter when censoring is independent of the covariates. The estimator demonstrates very high relative efficiency in simulations. When compared with complete-case analysis, the proposed estimator can be more efficient when the missing data are missing completely at random and can correct bias when the missing data are missing at random. The potential application of the proposed method to the generalized probit model with missing continuous covariates is also outlined.     

Polynomials for classification trees and applications

This paper relates computational commutative algebra to tree classification with binary covariates. With a single classification variable, properties of uniqueness of a tree polynomial are established. In a binary multivariate context, it is shown how trees for many response variables can be made into a single ideal of polynomials for computations. Finally, a new sequential algorithm is proposed for uniform conditional sampling. The algorithm combines the lexicographic Groebner basis with importance sampling and it can be used for conditional comparisons of regulatory network maps. The binary state space leads to an explicit form for the design ideal, which leads to useful radical and extension properties that play a role in the algorithms.     

Boosted coefficient models

Regression methods typically construct a mapping from the covariates into the real numbers. Here, however, we consider regression problems where the task is to form a mapping from the covariates into a set of (univariate) real-valued functions. Examples are given by conditional density estimation, hazard regression and regression with a functional response. Our approach starts by modeling the function of interest using a sum of B-spline basis functions. To model dependence on the covariates, the coefficients of this expansion are each modeled as functions of the covariates. We propose to estimate these coefficient functions using boosted tree models. Algorithms are provided for the above three situations, and real data sets are used to investigate their performance. The results indicate that the proposed methodology performs well. In addition, it is both straightforward, and capable of handling a large number of covariates.     

Comparisons of the Unbiased Ridge Estimation to the Other Estimations

In this article, we employ the method of empirical likelihood to construct confidence intervals of conditional density for a left-truncation model. It is proved that the empirical likelihood ratio admits a limiting chi-square distribution with one degree of freedom when the lifetime observations with multivariate covariates form a stationary α-mixing sequence.     

Missing covariates in generalized linear models when the missing data mechanism is non-ignorable

We propose a method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. We use a multinomial model for the missing data indicators and propose a joint distribution for them which can be written as a sequence of one-dimensional conditional distributions, with each one-dimensional conditional distribution consisting of a logistic regression. We allow the covariates to be either categorical or continuous. The joint covariate distribution is also modelled via a sequence of one-dimensional conditional distributions, and the response variable is assumed to be completely observed. We derive the E- and M-steps of the EM algorithm with non-ignorable missing covariate data. For categorical covariates, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For continuous covariates, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. Computational techniques for Gibbs sampling are proposed and implemented. The parametric form of the assumed missing data mechanism itself is not `testable' from the data, and thus the non-ignorable modelling considered here can be viewed as a sensitivity analysis concerning a more complicated model. Therefore, although a model may have `passed' the tests for a certain missing data mechanism, this does not mean that we have captured, even approximately, the correct missing data mechanism. Hence, model checking for the missing data mechanism and sensitivity analyses play an important role in this problem and are discussed in detail. Several simulations are given to demonstrate the methodology. In addition, a real data set from a melanoma cancer clinical trial is presented to illustrate the methods proposed.     

Polynomial Spline Estimation for a Generalized Additive Coefficient Model

Abstract.  We study a semiparametric generalized additive coefficient model (GACM), in which linear predictors in the conventional generalized linear models are generalized to unknown functions depending on certain covariates, and approximate the non-parametric functions by using polynomial spline. The asymptotic expansion with optimal rates of convergence for the estimators of the non-parametric part is established. Semiparametric generalized likelihood ratio test is also proposed to check if a non-parametric coefficient can be simplified as a parametric one. A conditional bootstrap version is suggested to approximate the distribution of the test under the null hypothesis. Extensive Monte Carlo simulation studies are conducted to examine the finite sample performance of the proposed methods. We further apply the proposed model and methods to a data set from a human visceral Leishmaniasis study conducted in Brazil from 1994 to 1997. Numerical results outperform the traditional generalized linear model and the proposed GACM is preferable.     

Bayesian Methods for Missing Covariates in Cure Rate Models

We propose methods for Bayesian inference for missing covariate data with a novel class of semi-parametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.     

Confidence intervals for the difference between two median survival times for clustered survival data

Clustered survival data arise often in clinical trial design, where the correlated subunits from the same cluster are randomized to different treatment groups. Under such design, we consider the problem of constructing confidence interval for the difference of two median survival time given the covariates. We use Cox gamma frailty model to account for the within-cluster correlation. Based on the conditional confidence intervals, we can identify the possible range of covariates over which the two groups would provide different median survival times. The associated coverage probability and the expected length of the proposed interval are investigated via a simulation study. The implementation of the confidence intervals is illustrated using a real data set.     

A Bayesian analysis of clustered discrete and continuous outcomes

Many study designs yield a variety of outcomes from each subject clustered within an experimental unit. When these outcomes are of mixed data types, it is challenging to jointly model the effects of covariates on the responses using traditional methods. In this paper, we develop a Bayesian approach for a joint regression model of the different outcome variables and show that the fully conditional posterior distributions obtained under the model assumptions allow for estimation of posterior distributions using Gibbs sampling algorithm.     

Calibrating covariate informed product partition models

Covariate informed product partition models incorporate the intuitively appealing notion that individuals or units with similar covariate values a priori have a higher probability of co-clustering than those with dissimilar covariate values. These methods have been shown to perform well if the number of covariates is relatively small. However, as the number of covariates increase, their influence on partition probabilities overwhelm any information the response may provide in clustering and often encourage partitions with either a large number of singleton clusters or one large cluster resulting in poor model fit and poor out-of-sample prediction. This same phenomenon is observed in Bayesian nonparametric regression methods that induce a conditional distribution for the response given covariates through a joint model. In light of this, we propose two methods that calibrate the covariate-dependent partition model by capping the influence that covariates have on partition probabilities. We demonstrate the new methods’ utility using simulation and two publicly available datasets.     

Semiparametric inference for estimating equations with nonignorably missing covariates

We consider statistical inference of unknown parameters in estimating equations (EEs) when some covariates have nonignorably missing values, which is quite common in practice but has rarely been discussed in the literature. When an instrument, a fully observed covariate vector that helps identifying parameters under nonignorable missingness, is available, the conditional distribution of the missing covariates given other covariates can be estimated by the pseudolikelihood method of Zhao and Shao [(2015), ‘Semiparametric pseudo likelihoods in generalised linear models with nonignorable missing data’, Journal of the American Statistical Association, 110, 1577–1590)] and be used to construct unbiased EEs. These modified EEs then constitute a basis for valid inference by empirical likelihood. Our method is applicable to a wide range of EEs used in practice. It is semiparametric since no parametric model for the propensity of missing covariate data is assumed. Asymptotic properties of the proposed estimator and the empirical likelihood ratio test statistic are derived. Some simulation results and a real data analysis are presented for illustration.     

Inferences in dynamic logit models in semi-parametric setup for repeated binary data

Binary dynamic fixed and mixed logit models are extensively studied in the literature. These models are developed to examine the effects of certain fixed covariates through a parametric regression function as a part of the models. However, there are situations where one may like to consider more covariates in the model but their direct effect is not of interest. In this paper we propose a generalization of the existing binary dynamic logit (BDL) models to the semi-parametric longitudinal setup to address this issue of additional covariates. The regression function involved in such a semi-parametric BDL model contains (i) a parametric linear regression function in some primary covariates, and (ii) a non-parametric function in certain secondary covariates. We use a simple semi-parametric conditional quasi-likelihood approach for consistent estimation of the non-parametric function, and a semi-parametric likelihood approach for the joint estimation of the main regression and dynamic dependence parameters of the model. The finite sample performance of the estimation approaches is examined through a simulation study. The asymptotic properties of the estimators are also discussed. The proposed model and the estimation approaches are illustrated by reanalysing a longitudinal infectious disease data.     

Estimation with Interval Censored Data and Covariates

In biostatistical applications interest often focuses on the estimation of the distribution of time T between two consecutive events. If the initial event time is observed and the subsequent event time is only known to be larger or smaller than an observed monitoring time C, then the data conforms to the well understood singly-censored current status model, also known as interval censored data, case I. Additional covariates can be used to allow for dependent censoring and to improve estimation of the marginal distribution of T. Assuming a wrong model for the conditional distribution of T, given the covariates, will lead to an inconsistent estimator of the marginal distribution. On the other hand, the nonparametric maximum likelihood estimator of FT requires splitting up the sample in several subsamples corresponding with a particular value of the covariates, computing the NPMLE for every subsample and then taking an average. With a few continuous covariates the performance of the resulting estimator is typically miserable. In van der Laan, Robins (1996) a locally efficient one-step estimator is proposed for smooth functionals of the distribution of T, assuming nothing about the conditional distribution of T, given the covariates, but assuming a model for censoring, given the covariates. The estimators are asymptotically linear if the censoring mechanism is estimated correctly. The estimator also uses an estimator of the conditional distribution of T, given the covariates. If this estimate is consistent, then the estimator is efficient and if it is inconsistent, then the estimator is still consistent and asymptotically normal. In this paper we show that the estimators can also be used to estimate the distribution function in a locally optimal way. Moreover, we show that the proposed estimator can be used to estimate the distribution based on interval censored data (T is now known to lie between two observed points) in the presence of covariates. The resulting estimator also has a known influence curve so that asymptotic confidence intervals are directly available. In particular, one can apply our proposal to the interval censored data without covariates. In Geskus (1992) the information bound for interval censored data with two uniformly distributed monitoring times at the uniform distribution (for T has been computed. We show that the relative efficiency of our proposal w.r.t. this optimal bound equals 0.994, which is also reflected in finite sample simulations. Finally, the good practical performance of the estimator is shown in a simulation study. This revised version was published online in July 2006 with corrections to the Cover Date.     

Extension of a Two-Stage Conditionally Unbiased Estimator of the Selected Population to the Bivariate Normal Case

A useful parameterization of the exponential failure model with imperfect signalling, under random censoring scheme, is considered to accommodate covariates. Simple sufficient conditions for the existence, uniqueness, consistency, and asymptotic normality of maximum likelihood estimators for the parameters in these models are given. The results are then applied to derive the asymptotic properties of the likelihood ratio test for a difference between failure signalling proportions between groups in a ‘one-way’ classification.     

MODEL SELECTION FOR PENALIZED SPLINE SMOOTHING USING AKAIKE INFORMATION CRITERIA

Two different forms of Akaike's information criterion (AIC) are compared for selecting the smooth terms in penalized spline additive mixed models. The conditional AIC (cAIC) has been used traditionally as a criterion for both estimating penalty parameters and selecting covariates in smoothing, and is based on the conditional likelihood given the smooth mean and on the effective degrees of freedom for a model fit. By comparison, the marginal AIC (mAIC) is based on the marginal likelihood from the mixed‐model formulation of penalized splines which has recently become popular for estimating smoothing parameters. To the best of the authors' knowledge, the use of mAIC for selecting covariates for smoothing in additive models is new. In the competing models considered for selection, covariates may have a nonlinear effect on the response, with the possibility of group‐specific curves. Simulations are used to compare the performance of cAIC and mAIC in model selection settings that have correlated and hierarchical smooth terms. In moderately large samples, both formulations of AIC perform extremely well at detecting the function that generated the data. The mAIC does better for simple functions, whereas the cAIC is more sensitive to detecting a true model that has complex and hierarchical terms.     

Cure rate survival models with missing covariates: a simulation study

In this paper we study the cure rate survival model involving a competitive risk structure with missing categorical covariates. A parametric distribution that can be written as a sequence of one-dimensional conditional distributions is specified for the missing covariates. We consider the missing data at random situation so that the missing covariates may depend only on the observed ones. Parameter estimates are obtained by using the EM algorithm via the method of weights. Extensive simulation studies are conducted and reported to compare estimates efficiency with and without missing data. As expected, the estimation approach taking into consideration the missing covariates presents much better efficiency in terms of mean square errors than the complete case situation. Effects of increasing cured fraction and censored observations are also reported. We demonstrate the proposed methodology with two real data sets. One involved the length of time to obtain a BS degree in Statistics, and another about the time to breast cancer recurrence.     

Estimating a Marginal Causal Odds Ratio Subject to Confounding

Odds ratios are frequently used to describe the relationship between a binary treatment or exposure and a binary outcome. An odds ratio can be interpreted as a causal effect or a measure of association, depending on whether it involves potential outcomes or the actual outcome. An odds ratio can also be characterized as marginal versus conditional, depending on whether it involves conditioning on covariates. This article proposes a method for estimating a marginal causal odds ratio subject to confounding. The proposed method is based on a logistic regression model relating the outcome to the treatment indicator and potential confounders. Simulation results show that the proposed method performs reasonably well in moderate-sized samples and may even offer an efficiency gain over the direct method based on the sample odds ratio in the absence of confounding. The method is illustrated with a real example concerning coronary heart disease.