Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

Estimating curves and derivatives with parametric penalized spline smoothing

Accurate estimation of an underlying function and its derivatives is one of the central problems in statistics. Parametric forms are often proposed based on the expert opinion or prior knowledge of the underlying function. However, these strict parametric assumptions may result in biased estimates when they are not completely accurate. Meanwhile, nonparametric smoothing methods, which do not impose any parametric form, are quite flexible. We propose a parametric penalized spline smoothing method, which has the same flexibility as the nonparametric smoothing methods. It also uses the prior knowledge of the underlying function by defining an additional penalty term using the distance of the fitted function to the assumed parametric function. Our simulation studies show that the parametric penalized spline smoothing method can obtain more accurate estimates of the function and its derivatives than the penalized spline smoothing method. The parametric penalized spline smoothing method is also demonstrated by estimating the human height function and its derivatives from the real data.     

Semiparametric multiple kernel estimators and model diagnostics for count regression functions

Abstract

This study concerns semiparametric approaches to estimate discrete multivariate count regression functions. The semiparametric approaches investigated consist of combining discrete multivariate nonparametric kernel and parametric estimations such that (i) a prior knowledge of the conditional distribution of model response may be incorporated and (ii) the bias of the traditional nonparametric kernel regression estimator of Nadaraya-Watson may be reduced. We are precisely interested in combination of the two estimations approaches with some asymptotic properties of the resulting estimators. Asymptotic normality results were showed for nonparametric correction terms of parametric start function of the estimators. The performance of discrete semiparametric multivariate kernel estimators studied is illustrated using simulations and real count data. In addition, diagnostic checks are performed to test the adequacy of the parametric start model to the true discrete regression model. Finally, using discrete semiparametric multivariate kernel estimators provides a bias reduction when the parametric multivariate regression model used as start regression function belongs to a neighborhood of the true regression model.     

Testing homogeneity in clustered (longitudinal) count data regression model with over-dispersion

Clustered (longitudinal) count data arise in many bio-statistical practices in which a number of repeated count responses are observed on a number of individuals. The repeated observations may also represent counts over time from a number of individuals. One important problem that arises in practice is to test homogeneity within clusters (individuals) and between clusters (individuals). As data within clusters are observations of repeated responses, the count data may be correlated and/or over-dispersed. For over-dispersed count data with unknown over-dispersion parameter we derive two score tests by assuming a random intercept model within the framework of (i) the negative binomial mixed effects model and (ii) the double extended quasi-likelihood mixed effects model (Lee and Nelder, 2001). These two statistics are much simpler than a statistic derived by Jacqmin-Gadda and Commenges (1995) under the framework of the over-dispersed generalized linear model. The first statistic takes the over-dispersion more directly into the model and therefore is expected to do well when the model assumptions are satisfied and the other statistic is expected to be robust. Simulations show superior level property of the statistics derived under the negative binomial and double extended quasi-likelihood model assumptions. A data set is analyzed and a discussion is given.     

ESTIMATING A RATIO OF MEANS FROM BIVARIATE COUNTS WITH APPLICATIONS IN STEREOLOGY

In survey sampling and in stereology, it is often desirable to estimate the ratio of means θ= E(Y)/E(X) from bivariate count data (X, Y) with unknown joint distribution. We review methods that are available for this problem, with particular reference to stereological applications. We also develop new methods based on explicit statistical models for the data, and associated model diagnostics. The methods are tested on a stereological dataset. For point‐count data, binomial regression and bivariate binomial models are generally adequate. Intercept‐count data are often overdispersed relative to Poisson regression models, but adequately fitted by negative binomial regression.     

A flexible semiparametric regression model for bimodal,asymmetric and censored data

In this paper, we propose a new semiparametric heteroscedastic regression model allowing for positive and negative skewness and bimodal shapes using the B-spline basis for nonlinear effects. The proposed distribution is based on the generalized additive models for location, scale and shape framework in order to model any or all parameters of the distribution using parametric linear and/or nonparametric smooth functions of explanatory variables. We motivate the new model by means of Monte Carlo simulations, thus ignoring the skewness and bimodality of the random errors in semiparametric regression models, which may introduce biases on the parameter estimates and/or on the estimation of the associated variability measures. An iterative estimation process and some diagnostic methods are investigated. Applications to two real data sets are presented and the method is compared to the usual regression methods.     

A new local estimation method for single index models for longitudinal data

Single index models are natural extensions of linear models and overcome the so-called curse of dimensionality. They are very useful for longitudinal data analysis. In this paper, we develop a new efficient estimation procedure for single index models with longitudinal data, based on Cholesky decomposition and local linear smoothing method. Asymptotic normality for the proposed estimators of both the parametric and nonparametric parts will be established. Monte Carlo simulation studies show excellent finite sample performance. Furthermore, we illustrate our methods with a real data example.     

Semi-parametric modelling and likelihood estimation with estimating equations

This paper proposes a semi-parametric modelling and estimating method for analysing censored survival data. The proposed method uses the empirical likelihood function to describe the information in data, and formulates estimating equations to incorporate knowledge of the underlying distribution and regression structure. The method is more flexible than the traditional methods such as the parametric maximum likelihood estimation (MLE), Cox's (1972) proportional hazards model, accelerated life test model, quasi-likelihood (Wedderburn, 1974) and generalized estimating equations (Liang & Zeger, 1986). This paper shows the existence and uniqueness of the proposed semi-parametric maximum likelihood estimates (SMLE) with estimating equations. The method is validated with known cases studied in the literature. Several finite sample simulation and large sample efficiency studies indicate that when the sample size is larger than 100 the SMLE is compatible with the parametric MLE; and in all case studies, the SMLE is about 15% better than the parametric MLE with a mis-specified underlying distribution.     

Analyzing clustered count data with a cluster-specific random effect zero-inflated Conway–Maxwell–Poisson distribution

Count data analysis techniques have been developed in biological and medical research areas. In particular, zero-inflated versions of parametric count distributions have been used to model excessive zeros that are often present in these assays. The most common count distributions for analyzing such data are Poisson and negative binomial. However, a Poisson distribution can only handle equidispersed data and a negative binomial distribution can only cope with overdispersion. However, a Conway–Maxwell–Poisson (CMP) distribution [4] can handle a wide range of dispersion. We show, with an illustrative data set on next-generation sequencing of maize hybrids, that both underdispersion and overdispersion can be present in genomic data. Furthermore, the maize data set consists of clustered observations and, therefore, we develop inference procedures for a zero-inflated CMP regression that incorporates a cluster-specific random effect term. Unlike the Gaussian models, the underlying likelihood is computationally challenging. We use a numerical approximation via a Gaussian quadrature to circumvent this issue. A test for checking zero-inflation has also been developed in our setting. Finite sample properties of our estimators and test have been investigated by extensive simulations. Finally, the statistical methodology has been applied to analyze the maize data mentioned before.     

Mixed Correlated Bivariate Ordinal and Negative Binomial Longitudinal Responses with Nonignorable Missing Values

Regression models with random effects are proposed for joint analysis of negative binomial and ordinal longitudinal data with nonignorable missing values under fully parametric framework. The presented model simultaneously considers a multivariate probit regression model for the missing mechanisms, which provides the ability of examining the missing data assumptions and a multivariate mixed model for the responses. Random effects are used to take into account the correlation between longitudinal responses of the same individual. A full likelihood-based approach that allows yielding maximum likelihood estimates of the model parameters is used. The model is applied to a medical data, obtained from an observational study on women, where the correlated responses are the ordinal response of osteoporosis of the spine and negative binomial response is the number of joint damage. A sensitivity of the results to the assumptions is also investigated. The effect of some covariates on all responses are investigated simultaneously.     

Nonparametric Bayes Stochastically Ordered Latent Class Models

Latent class models (LCMs) are used increasingly for addressing a broad variety of problems, including sparse modeling of multivariate and longitudinal data, model-based clustering, and flexible inferences on predictor effects. Typical frequentist LCMs require estimation of a single finite number of classes, which does not increase with the sample size, and have a well-known sensitivity to parametric assumptions on the distributions within a class. Bayesian nonparametric methods have been developed to allow an infinite number of classes in the general population, with the number represented in a sample increasing with sample size. In this article, we propose a new nonparametric Bayes model that allows predictors to flexibly impact the allocation to latent classes, while limiting sensitivity to parametric assumptions by allowing class-specific distributions to be unknown subject to a stochastic ordering constraint. An efficient MCMC algorithm is developed for posterior computation. The methods are validated using simulation studies and applied to the problem of ranking medical procedures in terms of the distribution of patient morbidity.     

Semiparametric estimation for count data through weighted distributions

This paper is concerned with semiparametric discrete kernel estimators when the unknown count distribution can be considered to have a general weighted Poisson form. The estimator is constructed by multiplying the Poisson estimate with a nonparametric discrete kernel-type estimate of the Poisson weight function. Comparisons are then carried out with the ordinary discrete kernel probability mass function estimators. The Poisson weight function is thus a local multiplicative correction factor, and is considered as the uniform measure to detect departures from the equidispersed Poisson distribution. In this way, the effects of dispersion and zero-proportion with respect to the standard Poisson distribution are also minimized. This method of estimation is also applied to the weighted binomial form for the count distribution having a finite support. The proposed estimators, in addition to being simple, easy-to-implement and effective, also outperform the competing nonparametric and parametric estimators in finite-sample situations. Two examples illustrate this new semiparametric estimation.     

Efficient regression modeling for correlated and overdispersed count data

Abstract

The objective of this paper is to propose an efficient estimation procedure in a marginal mean regression model for longitudinal count data and to develop a hypothesis test for detecting the presence of overdispersion. We extend the matrix expansion idea of quadratic inference functions to the negative binomial regression framework that entails accommodating both the within-subject correlation and overdispersion issue. Theoretical and numerical results show that the proposed procedure yields a more efficient estimator asymptotically than the one ignoring either the within-subject correlation or overdispersion. When the overdispersion is absent in data, the proposed method might hinder the estimation efficiency in practice, yet the Poisson regression based regression model is fitted to the data sufficiently well. Therefore, we construct the hypothesis test that recommends an appropriate model for the analysis of the correlated count data. Extensive simulation studies indicate that the proposed test can identify the effective model consistently. The proposed procedure is also applied to a transportation safety study and recommends the proposed negative binomial regression model.     

Modelling Survival Events with Longitudinal Covariates Measured with Error

In survival analysis, time-dependent covariates are usually present as longitudinal data collected periodically and measured with error. The longitudinal data can be assumed to follow a linear mixed effect model and Cox regression models may be used for modelling of survival events. The hazard rate of survival times depends on the underlying time-dependent covariate measured with error, which may be described by random effects. Most existing methods proposed for such models assume a parametric distribution assumption on the random effects and specify a normally distributed error term for the linear mixed effect model. These assumptions may not be always valid in practice. In this article, we propose a new likelihood method for Cox regression models with error-contaminated time-dependent covariates. The proposed method does not require any parametric distribution assumption on random effects and random errors. Asymptotic properties for parameter estimators are provided. Simulation results show that under certain situations the proposed methods are more efficient than the existing methods.     

Prediction bands for the EDF of a future sample

We develop both nonparametric and parametric methods for obtaining prediction bands for the empirical distribution function (EDF) of a future sample. These methods yield simultaneous prediction intervals for all order statistics of the future sample, and they also correspond to tests for the two-sample problem. The nonparametric prediction bands correspond to the two-sample Kolmogorov-Smirnov test and related nonparametric tests, but the parametric prediction bands correspond to entirely new parametric two-sample tests. The parametric prediction bands tend to outperform the nonparametric bands when the parametric assumptions hold, but they may have true coverage probabilities well below their nominal levels when the parametric assumptions fail. A new computational algorithm is used to obtain critical values in the nonparametric case.     

Bayesian latent variable models for clustered mixed outcomes

A general framework is proposed for modelling clustered mixed outcomes. A mixture of generalized linear models is used to describe the joint distribution of a set of underlying variables, and an arbitrary function relates the underlying variables to be observed outcomes. The model accommodates multilevel data structures, general covariate effects and distinct link functions and error distributions for each underlying variable. Within the framework proposed, novel models are developed for clustered multiple binary, unordered categorical and joint discrete and continuous outcomes. A Markov chain Monte Carlo sampling algorithm is described for estimating the posterior distributions of the parameters and latent variables. Because of the flexibility of the modelling framework and estimation procedure, extensions to ordered categorical outcomes and more complex data structures are straightforward. The methods are illustrated by using data from a reproductive toxicity study.     

Discrete Nonparametric Kernel and Parametric Methods for the Modeling of Pavement Deterioration

This article is concerned with one discrete nonparametric kernel and two parametric regression approaches for providing the evolution law of pavement deterioration. The first parametric approach is a survival data analysis method; and the second is a nonlinear mixed-effects model. The nonparametric approach consists of a regression estimator using the discrete associated kernels. Some asymptotic properties of the discrete nonparametric kernel estimator are shown as, in particular, its almost sure consistency. Moreover, two data-driven bandwidth selection methods are also given, with a new theoretical explicit expression of optimal bandwidth provided for this nonparametric estimator. A comparative simulation study is realized with an application of bootstrap methods to a measure of statistical accuracy.     

Modelling forces of infection by using monotone local polynomials

Summary. On the basis of serological data from prevalence studies of rubella, mumps and hepatitis A, the paper describes a flexible local maximum likelihood method for the estimation of the rate at which susceptible individuals acquire infection at different ages. In contrast with parametric models that have been used before in the literature, the local polynomial likelihood method allows this age-dependent force of infection to be modelled without making any assumptions about the parametric structure. Moreover, this method allows for simultaneous nonparametric estimation of age-specific incidence and prevalence. Unconstrained models may lead to negative estimates for the force of infection at certain ages. To overcome this problem and to guarantee maximal flexibility, the local smoother can be constrained to be monotone. It turns out that different parametric and nonparametric estimates of the force of infection can exhibit considerably different qualitative features like location and the number of maxima, emphasizing the importance of a well-chosen flexible statistical model.     

A semi-parametric approach to robust parameter design

Parameter design or robust parameter design (RPD) is an engineering methodology intended as a cost-effective approach for improving the quality of products and processes. The goal of parameter design is to choose the levels of the control variables that optimize a defined quality characteristic. An essential component of RPD involves the assumption of well estimated models for the process mean and variance. Traditionally, the modeling of the mean and variance has been done parametrically. It is often the case, particularly when modeling the variance, that nonparametric techniques are more appropriate due to the nature of the curvature in the underlying function. Most response surface experiments involve sparse data. In sparse data situations with unusual curvature in the underlying function, nonparametric techniques often result in estimates with problematic variation whereas their parametric counterparts may result in estimates with problematic bias. We propose the use of semi-parametric modeling within the robust design setting, combining parametric and nonparametric functions to improve the quality of both mean and variance model estimation. The proposed method will be illustrated with an example and simulations.     

Semiparametric statistical inferences for longitudinal data with nonparametric covariance modelling

In this paper, semiparametric modelling for longitudinal data with an unstructured error process is considered. We propose a partially linear additive regression model for longitudinal data in which within-subject variances and covariances of the error process are described by unknown univariate and bivariate functions, respectively. We provide an estimating approach in which polynomial splines are used to approximate the additive nonparametric components and the within-subject variance and covariance functions are estimated nonparametrically. Both the asymptotic normality of the resulting parametric component estimators and optimal convergence rate of the resulting nonparametric component estimators are established. In addition, we develop a variable selection procedure to identify significant parametric and nonparametric components simultaneously. We show that the proposed SCAD penalty-based estimators of non-zero components have an oracle property. Some simulation studies are conducted to examine the finite-sample performance of the proposed estimation and variable selection procedures. A real data set is also analysed to demonstrate the usefulness of the proposed method.