Two-Stage Estimation in Copula Models Used in Family Studies

In this paper register based family studies provide the motivation for studying a two-stage estimation procedure in copula models for multivariate failure time data. The asymptotic properties of the estimators in both parametric and semi-parametric models are derived, generalising the approach by Shih and Louis (Biometrics vol. 51, pp. 1384–1399, 1995b) and Glidden (Lifetime Data Analysis vol. 6, pp. 141–156, 2000). Because register based family studies often involve very large cohorts a method for analysing a sampled cohort is also derived together with the asymptotic properties of the estimators. The proposed methods are studied in simulations and the estimators are found to be highly efficient. Finally, the methods are applied to a study of mortality in twins.     

AN APPROACH FOR JOINTLY MODELING MULTIVARIATE LONGITUDINAL MEASUREMENTS AND DISCRETE TIME-TO-EVENT DATA

In many medical studies, patients are followed longitudinally and interest is on assessing the relationship between longitudinal measurements and time to an event. Recently, various authors have proposed joint modeling approaches for longitudinal and time-to-event data for a single longitudinal variable. These joint modeling approaches become intractable with even a few longitudinal variables. In this paper we propose a regression calibration approach for jointly modeling multiple longitudinal measurements and discrete time-to-event data. Ideally, a two-stage modeling approach could be applied in which the multiple longitudinal measurements are modeled in the first stage and the longitudinal model is related to the time-to-event data in the second stage. Biased parameter estimation due to informative dropout makes this direct two-stage modeling approach problematic. We propose a regression calibration approach which appropriately accounts for informative dropout. We approximate the conditional distribution of the multiple longitudinal measurements given the event time by modeling all pairwise combinations of the longitudinal measurements using a bivariate linear mixed model which conditions on the event time. Complete data are then simulated based on estimates from these pairwise conditional models, and regression calibration is used to estimate the relationship between longitudinal data and time-to-event data using the complete data. We show that this approach performs well in estimating the relationship between multivariate longitudinal measurements and the time-to-event data and in estimating the parameters of the multiple longitudinal process subject to informative dropout. We illustrate this methodology with simulations and with an analysis of primary biliary cirrhosis (PBC) data.     

Random regression models for human immunodeficiency virus ribonucleic acid data subject to left censoring and informative drop-outs

Objectives in many longitudinal studies of individuals infected with the human immunodeficiency virus (HIV) include the estimation of population average trajectories of HIV ribonucleic acid (RNA) over time and tests for differences in trajectory across subgroups. Special features that are often inherent in the underlying data include a tendency for some HIV RNA levels to be below an assay detection limit, and for individuals with high initial levels or high ranges of change to drop out of the study early because of illness or death. We develop a likelihood for the observed data that incorporates both of these features. Informative drop-outs are handled by means of an approach previously published by Schluchter. Using data from the HIV Epidemiology Research Study, we implement a maximum likelihood procedure to estimate initial HIV RNA levels and slopes within a population, compare these parameters across subgroups of HIV-infected women and illustrate the importance of appropriate treatment of left censoring and informative drop-outs. We also assess model assumptions and consider the prediction of random intercepts and slopes in this setting. The results suggest that marked bias in estimates of fixed effects, variance components and standard errors in the analysis of HIV RNA data might be avoided by the use of methods like those illustrated.     

Sampling from the posterior distribution in generalized linear mixed models

Generalized linear mixed models provide a unified framework for treatment of exponential family regression models, overdispersed data and longitudinal studies. These problems typically involve the presence of random effects and this paper presents a new methodology for making Bayesian inference about them. The approach is simulation-based and involves the use of Markov chain Monte Carlo techniques. The usual iterative weighted least squares algorithm is extended to include a sampling step based on the Metropolis–Hastings algorithm thus providing a unified iterative scheme. Non-normal prior distributions for the regression coefficients and for the random effects distribution are considered. Random effect structures with nesting required by longitudinal studies are also considered. Particular interests concern the significance of regression coefficients and assessment of the form of the random effects. Extensions to unknown scale parameters, unknown link functions, survival and frailty models are outlined.     

On the Ghoudi,Khoudraji, and Rivest test for extreme‐value dependence

Ghoudi, Khoudraji & Rivest [The Canadian Journal of Statistics 1998;26:187–197] showed how to test whether the dependence structure of a pair of continuous random variables is characterized by an extreme‐value copula. The test is based on a U‐statistic whose finite‐ and large‐sample variance are determined by the present authors. They propose estimates of this variance which they compare to the jackknife estimate of Ghoudi, Khoudraji & Rivest ( 1998 ) through simulations. They study the finite‐sample and asymptotic power of the test under various alternatives. They illustrate their approach using financial and geological data. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

A general joint model for longitudinal measurements and competing risks survival data with heterogeneous random effects

This article studies a general joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the competing risks survival data, and a regression sub-model for the variance–covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. The model provides a useful approach to adjust for non-ignorable missing data due to dropout for the longitudinal outcome, enables analysis of the survival outcome with informative censoring and intermittently measured time-dependent covariates, as well as joint analysis of the longitudinal and survival outcomes. Unlike previously studied joint models, our model allows for heterogeneous random covariance matrices. It also offers a framework to assess the homogeneous covariance assumption of existing joint models. A Bayesian MCMC procedure is developed for parameter estimation and inference. Its performances and frequentist properties are investigated using simulations. A real data example is used to illustrate the usefulness of the approach.     

The partial Koziol–Green model with covariates

Two important models in survival analysis are that of general random censorship and the proportional hazards submodel of Koziol and Green. The difference between the two models is the way in which the lifetime variable is censored (informative versus non-informative censoring). In this paper the two viewpoints are combined into a new model which allows the lifetimes to be censored by two types of variables, one of which censors in an informative way and the other one in a non-informative way. The lifetimes and the censoring times are also allowed to depend on covariates in a very general way. The estimator for the conditional distribution of the lifetimes generalizes that of Gather and Pawlitschko (1998. Metrika 48, 189–209), who recently studied the situation without covariate information. Results obtained are the uniform strong consistency (with rate), an almost sure asymptotic representation and the weak convergence of the process.     

Mixture of linear mixed models using multivariate t distribution

Linear mixed models are widely used when multiple correlated measurements are made on each unit of interest. In many applications, the units may form several distinct clusters, and such heterogeneity can be more appropriately modelled by a finite mixture linear mixed model. The classical estimation approach, in which both the random effects and the error parts are assumed to follow normal distribution, is sensitive to outliers, and failure to accommodate outliers may greatly jeopardize the model estimation and inference. We propose a new mixture linear mixed model using multivariate t distribution. For each mixture component, we assume the response and the random effects jointly follow a multivariate t distribution, to conveniently robustify the estimation procedure. An efficient expectation conditional maximization algorithm is developed for conducting maximum likelihood estimation. The degrees of freedom parameters of the t distributions are chosen data adaptively, for achieving flexible trade-off between estimation robustness and efficiency. Simulation studies and an application on analysing lung growth longitudinal data showcase the efficacy of the proposed approach.     

Books on probability ideas are reviewed

In this paper, semiparametric methods are applied to estimate multivariate volatility functions, using a residual approach as in [J. Fan and Q. Yao, Efficient estimation of conditional variance functions in stochastic regression, Biometrika 85 (1998), pp. 645–660; F.A. Ziegelmann, Nonparametric estimation of volatility functions: The local exponential estimator, Econometric Theory 18 (2002), pp. 985–991; F.A. Ziegelmann, A local linear least-absolute-deviations estimator of volatility, Comm. Statist. Simulation Comput. 37 (2008), pp. 1543–1564], among others. Our main goal here is two-fold: (1) describe and implement a number of semiparametric models, such as additive, single-index and (adaptive) functional-coefficient, in volatility estimation, all motivated as alternatives to deal with the curse of dimensionality present in fully nonparametric models; and (2) propose the use of a variation of the traditional cross-validation method to deal with model choice in the class of adaptive functional-coefficient models, choosing simultaneously the bandwidth, the number of covariates in the model and also the single-index smoothing variable. The modified cross-validation algorithm is able to tackle the computational burden caused by the model complexity, providing an important tool in semiparametric volatility estimation. We briefly discuss model identifiability when estimating volatility as well as nonnegativity of the resulting estimators. Furthermore, Monte Carlo simulations for several underlying generating models are implemented and applications to real data are provided.     

An explanation of generalized profile likelihoods

Let X, T, Y be random vectors such that the distribution of Y conditional on covariates partitioned into the vectors X = x and T = t is given by f(y; x, ), where = (, (t)). Here is a parameter vector and (t) is a smooth, real–valued function of t. The joint distribution of X and T is assumed to be independent of and . This semiparametric model is called conditionally parametric because the conditional distribution f(y; x, ) of Y given X = x, T = t is parameterized by a finite dimensional parameter = (, (t)). Severini and Wong (1992. Annals of Statistics 20: 1768–1802) show how to estimate and (·) using generalized profile likelihoods, and they also provide a review of the literature on generalized profile likelihoods. Under specified regularity conditions, they derive an asymptotically efficient estimator of and a uniformly consistent estimator of (·). The purpose of this paper is to provide a short tutorial for this method of estimation under a likelihood–based model, reviewing results from Stein (1956. Proceedings of the Third Berkeley Symposium on Mathematical Statistics and Probability, vol. 1, University of California Press, Berkeley, pp. 187–196), Severini (1987. Ph.D Thesis, The University of Chicago, Department of Statistics, Chicago, Illinois), and Severini and Wong (op. cit.).     

Factor stochastic volatility with time varying loadings and Markov switching regimes

We generalize the factor stochastic volatility (FSV) model of Pitt and Shephard [1999. Time varying covariances: a factor stochastic volatility approach (with discussion). In: Bernardo, J.M., Berger, J.O., Dawid, A.P., Smith, A.F.M. (Eds.), Bayesian Statistics, vol. 6, Oxford University Press, London, pp. 547–570.] and Aguilar and West [2000. Bayesian dynamic factor models and variance matrix discounting for portfolio allocation. J. Business Econom. Statist. 18, 338–357.] in two important directions. First, we make the FSV model more flexible and able to capture more general time-varying variance–covariance structures by letting the matrix of factor loadings to be time dependent. Secondly, we entertain FSV models with jumps in the common factors volatilities through So, Lam and Li's [1998. A stochastic volatility model with Markov switching. J. Business Econom. Statist. 16, 244–253.] Markov switching stochastic volatility model. Novel Markov Chain Monte Carlo algorithms are derived for both classes of models. We apply our methodology to two illustrative situations: daily exchange rate returns [Aguilar, O., West, M., 2000. Bayesian dynamic factor models and variance matrix discounting for portfolio allocation. J. Business Econom. Statist. 18, 338–357.] and Latin American stock returns [Lopes, H.F., Migon, H.S., 2002. Comovements and contagion in emergent markets: stock indexes volatilities. In: Gatsonis, C., Kass, R.E., Carriquiry, A.L., Gelman, A., Verdinelli, I. Pauler, D., Higdon, D. (Eds.), Case Studies in Bayesian Statistics, vol. 6, pp. 287–302].     

An Estimator of the Survival Function Basedon the Semi-Markov Model Under Dependent Censorship

Lee and Wolfe (Biometrics vol. 54 pp. 1176–1178, 1998) proposed the two-stage sampling design for testing the assumption of independent censoring, which involves further follow-up of a subset of lost-to-follow-up censored subjects. They also proposed an adjusted estimator for the survivor function for a proportional hazards model under the dependent censoring model. In this paper, a new estimator for the survivor function is proposed for the semi-Markov model under the dependent censorship on the basis of the two-stage sampling data. The consistency and the asymptotic distribution of the proposed estimator are derived. The estimation procedure is illustrated with an example of lung cancer clinical trial and simulation results are reported of the mean squared errors of estimators under a proportional hazards and two different nonproportional hazards models.     

Robust transformation mixed‐effects models for longitudinal continuous proportional data

The authors propose a robust transformation linear mixed‐effects model for longitudinal continuous proportional data when some of the subjects exhibit outlying trajectories over time. It becomes troublesome when including or excluding such subjects in the data analysis results in different statistical conclusions. To robustify the longitudinal analysis using the mixed‐effects model, they utilize the multivariate t distribution for random effects or/and error terms. Estimation and inference in the proposed model are established and illustrated by a real data example from an ophthalmology study. Simulation studies show a substantial robustness gain by the proposed model in comparison to the mixed‐effects model based on Aitchison's logit‐normal approach. As a result, the data analysis benefits from the robustness of making consistent conclusions in the presence of influential outliers. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

A skew-normal random effects model for longitudinal ordinal categorical responses with missing data

Missing values are common in longitudinal data studies. The missing data mechanism is termed non-ignorable (NI) if the probability of missingness depends on the non-response (missing) observations. This paper presents a model for the ordinal categorical longitudinal data with NI non-monotone missing values. We assumed two separate models for the response and missing procedure. The response is modeled as ordinal logistic, whereas the logistic binary model is considered for the missing process. We employ these models in the context of so-called shared-parameter models, where the outcome and missing data models are connected by a common set of random effects. It is commonly assumed that the random effect follows the normal distribution in longitudinal data with or without missing data. This can be extremely restrictive in practice, and it may result in misleading statistical inferences. In this paper, we instead adopt a more flexible alternative distribution which is called the skew-normal distribution. The methodology is illustrated through an application to Schizophrenia Collaborative Study data [19 D. Hedeker, Generalized linear mixed models, in Encyclopedia of Statistics in Behavioral Science, B. Everitt and D. Howell, eds., John Wiley, London, 2005, pp. 729–738. [Google Scholar]] and a simulation.     

Small area estimation of the mean using non-parametric M-quantile regression: a comparison when a linear mixed model does not hold

The demand for reliable statistics in subpopulations, when only reduced sample sizes are available, has promoted the development of small area estimation methods. In particular, an approach that is now widely used is based on the seminal work by Battese et al. [An error-components model for prediction of county crop areas using survey and satellite data, J. Am. Statist. Assoc. 83 (1988), pp. 28–36] that uses linear mixed models (MM). We investigate alternatives when a linear MM does not hold because, on one side, linearity may not be assumed and/or, on the other, normality of the random effects may not be assumed. In particular, Opsomer et al. [Nonparametric small area estimation using penalized spline regression, J. R. Statist. Soc. Ser. B 70 (2008), pp. 265–283] propose an estimator that extends the linear MM approach to the case in which a linear relationship may not be assumed using penalized splines regression. From a very different perspective, Chambers and Tzavidis [M-quantile models for small area estimation, Biometrika 93 (2006), pp. 255–268] have recently proposed an approach for small-area estimation that is based on M-quantile (MQ) regression. This allows for models robust to outliers and to distributional assumptions on the errors and the area effects. However, when the functional form of the relationship between the qth MQ and the covariates is not linear, it can lead to biased estimates of the small area parameters. Pratesi et al. [Semiparametric M-quantile regression for estimating the proportion of acidic lakes in 8-digit HUCs of the Northeastern US, Environmetrics 19(7) (2008), pp. 687–701] apply an extended version of this approach for the estimation of the small area distribution function using a non-parametric specification of the conditional MQ of the response variable given the covariates [M. Pratesi, M.G. Ranalli, and N. Salvati, Nonparametric m-quantile regression using penalized splines, J. Nonparametric Stat. 21 (2009), pp. 287–304]. We will derive the small area estimator of the mean under this model, together with its mean-squared error estimator and compare its performance to the other estimators via simulations on both real and simulated data.     

Likelihood analysis of joint marginal and conditional models for longitudinal categorical data

The authors develop a Markov model for the analysis of longitudinal categorical data which facilitates modelling both marginal and conditional structures. A likelihood formulation is employed for inference, so the resulting estimators enjoy the optimal properties such as efficiency and consistency, and remain consistent when data are missing at random. Simulation studies demonstrate that the proposed method performs well under a variety of situations. Application to data from a smoking prevention study illustrates the utility of the model and interpretation of covariate effects. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

A flexible approach for multivariate mixed-effects models with non-ignorable missing values

We propose a flexible model approach for the distribution of random effects when both response variables and covariates have non-ignorable missing values in a longitudinal study. A Bayesian approach is developed with a choice of nonparametric prior for the distribution of random effects. We apply the proposed method to a real data example from a national long-term survey by Statistics Canada. We also design simulation studies to further check the performance of the proposed approach. The result of simulation studies indicates that the proposed approach outperforms the conventional approach with normality assumption when the heterogeneity in random effects distribution is salient.     

Analysis of structural break models based on the evolutionary spectrum: Monte Carlo study and application

We investigate the instability problem of the covariance structure of time series by combining the non-parametric approach based on the evolutionary spectral density theory of Priestley [Evolutionary spectra and non-stationary processes, J. R. Statist. Soc., 27 (1965), pp. 204–237; Wavelets and time-dependent spectral analysis, J. Time Ser. Anal., 17 (1996), pp. 85–103] and the parametric approach based on linear regression models of Bai and Perron [Estimating and testing linear models with multiple structural changes, Econometrica 66 (1998), pp. 47–78]. A Monte Carlo study is presented to evaluate the performance of some parametric testing and estimation procedures for models characterized by breaks in variance. We attempt to see whether these procedures perform in the same way as models characterized by mean-shifts as investigated by Bai and Perron [Multiple structural change models: a simulation analysis, in: Econometric Theory and Practice: Frontiers of Analysis and Applied Research, D. Corbea, S. Durlauf, and B.E. Hansen, eds., Cambridge University Press, 2006, pp. 212–237]. We also provide an analysis of financial data series, of which the stability of the covariance function is doubtful.     

A Comparative Study of Approaches for Predicting Prostate Cancer from Longitudinal Data

Disease prediction based on longitudinal data can be done using various modeling approaches. Alternative approaches are compared using data from a longitudinal study to predict the onset of disease. The data are modeled using linear mixed-effects models. Posterior probabilities of group membership are computed starting with the first observation and sequentially adding observations until the subject is classified as developing the disease or until the last measurement is used. Individuals are classified by computing posterior probabilities using the marginal distributions of the mixed-effects models, the conditional distributions (conditional on the group-specific random effects), and the distributions of the random effects.     

Conditional mix-GEE models for longitudinal data with unspecified random-effects distributions

In the longitudinal studies, the mixture generalized estimation equation (mix-GEE) was proposed to improve the efficiency of the fixed-effects estimator for addressing the working correlation structure misspecification. When the subject-specific effect is one of interests, mixed-effects models were widely used to analyze longitudinal data. However, most of the existing approaches assume a normal distribution for the random effects, and this could affect the efficiency of the fixed-effects estimator. In this article, a conditional mixture generalized estimating equation (cmix-GEE) approach based on the advantage of mix-GEE and conditional quadratic inference function (CQIF) method is developed. The advantage of our new approach is that it does not require the normality assumption for random effects and can accommodate the serial correlation between observations within the same cluster. The feature of our proposed approach is that the estimators of the regression parameters are more efficient than CQIF even if the working correlation structure is not correctly specified. In addition, according to the estimates of some mixture proportions, the true working correlation matrix can be identified. We establish the asymptotic results for the fixed-effects parameter estimators. Simulation studies were conducted to evaluate our proposed method.