A two-stage estimation in the Clayton–Oakes model with marginal linear transformation models for multivariate failure time data

This paper considers the analysis of multivariate survival data where the marginal distributions are specified by semiparametric transformation models, a general class including the Cox model and the proportional odds model as special cases. First, consideration is given to the situation where the joint distribution of all failure times within the same cluster is specified by the Clayton–Oakes model (Clayton, Biometrika 65:141–151, l978; Oakes, J R Stat Soc B 44:412–422, 1982). A two-stage estimation procedure is adopted by first estimating the marginal parameters under the independence working assumption, and then the association parameter is estimated from the maximization of the full likelihood function with the estimators of the marginal parameters plugged in. The asymptotic properties of all estimators in the semiparametric model are derived. For the second situation, the third and higher order dependency structures are left unspecified, and interest focuses on the pairwise correlation between any two failure times. Thus, the pairwise association estimate can be obtained in the second stage by maximizing the pairwise likelihood function. Large sample properties for the pairwise association are also derived. Simulation studies show that the proposed approach is appropriate for practical use. To illustrate, a subset of the data from the Diabetic Retinopathy Study is used.     

Efficiency improvement in a class of survival models through model-free covariate incorporation

In randomized clinical trials, we are often concerned with comparing two-sample survival data. Although the log-rank test is usually suitable for this purpose, it may result in substantial power loss when the two groups have nonproportional hazards. In a more general class of survival models of Yang and Prentice (Biometrika 92:1–17, 2005), which includes the log-rank test as a special case, we improve model efficiency by incorporating auxiliary covariates that are correlated with the survival times. In a model-free form, we augment the estimating equation with auxiliary covariates, and establish the efficiency improvement using the semiparametric theories in Zhang et al. (Biometrics 64:707–715, 2008) and Lu and Tsiatis (Biometrics, 95:674–679, 2008). Under minimal assumptions, our approach produces an unbiased, asymptotically normal estimator with additional efficiency gain. Simulation studies and an application to a leukemia study show the satisfactory performance of the proposed method.     

Automatic Bayesian quantile regression curve fitting

Quantile regression, including median regression, as a more completed statistical model than mean regression, is now well known with its wide spread applications. Bayesian inference on quantile regression or Bayesian quantile regression has attracted much interest recently. Most of the existing researches in Bayesian quantile regression focus on parametric quantile regression, though there are discussions on different ways of modeling the model error by a parametric distribution named asymmetric Laplace distribution or by a nonparametric alternative named scale mixture asymmetric Laplace distribution. This paper discusses Bayesian inference for nonparametric quantile regression. This general approach fits quantile regression curves using piecewise polynomial functions with an unknown number of knots at unknown locations, all treated as parameters to be inferred through reversible jump Markov chain Monte Carlo (RJMCMC) of Green (Biometrika 82:711–732, 1995). Instead of drawing samples from the posterior, we use regression quantiles to create Markov chains for the estimation of the quantile curves. We also use approximate Bayesian factor in the inference. This method extends the work in automatic Bayesian mean curve fitting to quantile regression. Numerical results show that this Bayesian quantile smoothing technique is competitive with quantile regression/smoothing splines of He and Ng (Comput. Stat. 14:315–337, 1999) and P-splines (penalized splines) of Eilers and de Menezes (Bioinformatics 21(7):1146–1153, 2005).     

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.     

Bayesian inference for the Birnbaum–Saunders nonlinear regression model

We develop a Bayesian analysis for the class of Birnbaum–Saunders nonlinear regression models introduced by Lemonte and Cordeiro (Comput Stat Data Anal 53:4441–4452, 2009). This regression model, which is based on the Birnbaum–Saunders distribution (Birnbaum and Saunders in J Appl Probab 6:319–327, 1969a), has been used successfully to model fatigue failure times. We have considered a Bayesian analysis under a normal-gamma prior. Due to the complexity of the model, Markov chain Monte Carlo methods are used to develop a Bayesian procedure for the considered model. We describe tools for model determination, which include the conditional predictive ordinate, the logarithm of the pseudo-marginal likelihood and the pseudo-Bayes factor. Additionally, case deletion influence diagnostics is developed for the joint posterior distribution based on the Kullback–Leibler divergence. Two empirical applications are considered in order to illustrate the developed procedures.     

Test of hypotheses in panel data models when the regressor and disturbances are possibly non-stationary

This paper considers the problem of hypothesis testing in a simple panel data regression model with random individual effects and serially correlated disturbances. Following Baltagi et al. (Econom. J. 11:554–572, 2008), we allow for the possibility of non-stationarity in the regressor and/or the disturbance term. While Baltagi et al. (Econom. J. 11:554–572, 2008) focus on the asymptotic properties and distributions of the standard panel data estimators, this paper focuses on testing of hypotheses in this setting. One important finding is that unlike the time-series case, one does not necessarily need to rely on the “super-efficient” type AR estimator by Perron and Yabu (J. Econom. 151:56–69, 2009) to make an inference in the panel data. In fact, we show that the simple t-ratio always converges to the standard normal distribution, regardless of whether the disturbances and/or the regressor are stationary.     

Slice sampling mixture models

We propose a more efficient version of the slice sampler for Dirichlet process mixture models described by Walker (Commun. Stat., Simul. Comput. 36:45–54, 2007). This new sampler allows for the fitting of infinite mixture models with a wide-range of prior specifications. To illustrate this flexibility we consider priors defined through infinite sequences of independent positive random variables. Two applications are considered: density estimation using mixture models and hazard function estimation. In each case we show how the slice efficient sampler can be applied to make inference in the models. In the mixture case, two submodels are studied in detail. The first one assumes that the positive random variables are Gamma distributed and the second assumes that they are inverse-Gaussian distributed. Both priors have two hyperparameters and we consider their effect on the prior distribution of the number of occupied clusters in a sample. Extensive computational comparisons with alternative “conditional” simulation techniques for mixture models using the standard Dirichlet process prior and our new priors are made. The properties of the new priors are illustrated on a density estimation problem.     

Sine-skewed circular distributions

In this paper, we consider skew-symmetric circular distributions generated by perturbation of a symmetric circular distribution. The main focus of the paper, the sine-skewed family of distributions, is a special case of the construction due to Umbach and Jammalamadaka (Stat Probab Lett 79:659–663, 2009). Very general results are provided for the properties of any such distribution, and the sine-skewed Jones–Pewsey distribution is introduced as a particularly flexible model of this type. We study its properties as well as those of three of its special cases. General results are also provided for maximum likelihood estimation of the parameters of any sine-skewed distribution. The developed models and methods of inference are applied in analyses of three circular data sets. Two of them shed new light on previously published analyses.     

Generating data from improper distributions: application to Cox proportional hazards models with cure

Cure rate models are survival models characterized by improper survivor distributions which occur when the cumulative distribution function, say F, of the survival times does not sum up to 1 (i.e. F(+∞)<1). The first objective of this paper is to provide a general approach to generate data from any improper distribution. An application to times to event data randomly drawn from improper distributions with proportional hazards is investigated using the semi-parametric proportional hazards model with cure obtained as a special case of the nonlinear transformation models in [Tsodikov, Semiparametric models: A generalized self-consistency approach, J. R. Stat. Soc. Ser. B 65 (2003), pp. 759–774]. The second objective of this paper is to show by simulations that the bias, the standard error and the mean square error of the maximum partial likelihood (PL) estimator of the hazard ratio as well as the statistical power based on the PL estimator strongly depend on the proportion of subjects in the whole population who will never experience the event of interest.     

Feasible estimation in generalized structured models

This article introduces a feasible estimation method for a large class of semi and nonparametric models. We present the family of generalized structured models which we wish to estimate. After highlighting the main idea of the theoretical smooth backfitting estimators, we introduce a general estimation procedure. We consider modifications and practical issues, and discuss inference, cross validation, and asymptotic theory applying the theoretical framework of Mammen and Nielsen (Biometrika 90: 551–566, 2003). An extensive simulation study shows excellent performance of our method. Furthermore, real data applications from environmetrics and biometrics demonstrate its usefulness.     

Flexible competing risks regression modeling and goodness-of-fit

In this paper we consider different approaches for estimation and assessment of covariate effects for the cumulative incidence curve in the competing risks model. The classic approach is to model all cause-specific hazards and then estimate the cumulative incidence curve based on these cause-specific hazards. Another recent approach is to directly model the cumulative incidence by a proportional model (Fine and Gray, J Am Stat Assoc 94:496–509, 1999), and then obtain direct estimates of how covariates influences the cumulative incidence curve. We consider a simple and flexible class of regression models that is easy to fit and contains the Fine–Gray model as a special case. One advantage of this approach is that our regression modeling allows for non-proportional hazards. This leads to a new simple goodness-of-fit procedure for the proportional subdistribution hazards assumption that is very easy to use. The test is constructive in the sense that it shows exactly where non-proportionality is present. We illustrate our methods to a bone marrow transplant data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Through this data example we demonstrate the use of the flexible regression models to analyze competing risks data when non-proportionality is present in the data.     

A partially adaptive estimator for the censored regression model based on a mixture of normal distributions

The goal of this paper is to introduce a partially adaptive estimator for the censored regression model based on an error structure described by a mixture of two normal distributions. The model we introduce is easily estimated by maximum likelihood using an EM algorithm adapted from the work of Bartolucci and Scaccia (Comput Stat Data Anal 48:821–834, 2005). A Monte Carlo study is conducted to compare the small sample properties of this estimator to the performance of some common alternative estimators of censored regression models including the usual tobit model, the CLAD estimator of Powell (J Econom 25:303–325, 1984), and the STLS estimator of Powell (Econometrica 54:1435–1460, 1986). In terms of RMSE, our partially adaptive estimator performed well. The partially adaptive estimator is applied to data on wife’s hours worked from Mroz (1987). In this application we find support for the partially adaptive estimator over the usual tobit model.     

Dynamic Random Effects Models for Times Between Repeated Events

We consider recurrent event data when the duration or gap times between successive event occurrences are of intrinsic interest. Subject heterogeneity not attributed to observed covariates is usually handled by random effects which result in an exchangeable correlation structure for the gap times of a subject. Recently, efforts have been put into relaxing this restriction to allow non-exchangeable correlation. Here we consider dynamic models where random effects can vary stochastically over the gap times. We extend the traditional Gaussian variance components models and evaluate a previously proposed proportional hazards model through a simulation study and some examples. Besides, semiparametric estimation of the proportional hazards models is considered. Both models are easily used. The Gaussian models are easily interpreted in terms of the variance structure. On the other hand, the proportional hazards models would be more appropriate in the context of survival analysis, particularly in the interpretation of the regression parameters. They can be sensitive to the choice of model for random effects but not to the choice of the baseline hazard function.     

Estimation of extreme survival probabilities with cox model

We propose an extension of the regular Cox's proportional hazards model which allows the estimation of the probabilities of rare events. It is known that when the data are heavily censored, the estimation of the tail of the survival distribution is not reliable. To improve the estimate of the baseline survival function in the range of the largest observed data and to extend it outside, we adjust the tail of the baseline distribution beyond some threshold by an extreme value model under appropriate assumptions. The survival distributions conditioned to the covariates are easily computed from the baseline. A procedure allowing an automatic choice of the threshold and an aggregated estimate of the survival probabilities are also proposed. The performance is studied by simulations and an application on two data sets is given.     

Robust Poisson likelihood estimation for frailty Cox models: A simulation study

Frailty models can be fit as mixed-effects Poisson models after transforming time-to-event data to the Poisson model framework. We assess, through simulations, the robustness of Poisson likelihood estimation for Cox proportional hazards models with log-normal frailties under misspecified frailty distribution. The log-gamma and Laplace distributions were used as true distributions for frailties on a natural log scale. Factors such as the magnitude of heterogeneity, censoring rate, number and sizes of groups were explored. In the simulations, the Poisson modeling approach that assumes log-normally distributed frailties provided accurate estimates of within- and between-group fixed effects even under a misspecified frailty distribution. Non-robust estimation of variance components was observed in the situations of substantial heterogeneity, large event rates, or high data dimensions.     

Classification using distance nearest neighbours

This paper proposes a new probabilistic classification algorithm using a Markov random field approach. The joint distribution of class labels is explicitly modelled using the distances between feature vectors. Intuitively, a class label should depend more on class labels which are closer in the feature space, than those which are further away. Our approach builds on previous work by Holmes and Adams (J. R. Stat. Soc. Ser. B 64:295–306, 2002; Biometrika 90:99–112, 2003) and Cucala et al. (J. Am. Stat. Assoc. 104:263–273, 2009). Our work shares many of the advantages of these approaches in providing a probabilistic basis for the statistical inference. In comparison to previous work, we present a more efficient computational algorithm to overcome the intractability of the Markov random field model. The results of our algorithm are encouraging in comparison to the k-nearest neighbour algorithm.     

Orthogonal decomposition of point-symmetry for multiway tables

For multiway contingency tables, Wall and Lienert (Biom. J. 18:259–264, 1976) considered the point-symmetry model. For square contingency tables, Tomizawa (Biom. J. 27:895–905, 1985) gave a theorem that the point-symmetry model holds if and only if both the quasi point-symmetry and the marginal point-symmetry models hold. This paper proposes some quasi point-symmetry models and marginal point-symmetry models for multiway tables, and extends Tomizawa’s (Biom. J. 27:895–905, 1985) theorem into multiway tables. We also show that for multiway tables the likelihood ratio statistic for testing goodness of fit of the point-symmetry model is asymptotically equivalent to the sum of those for testing the quasi point-symmetry model with some order and the marginal point-symmetry model with the corresponding order. An example is given.     

Conditional and marginal estimates in case-control family data – extensions and sensitivity analyses

This work considers two specific estimation techniques for the family-specific proportional hazards model and for the population-averaged proportional hazards model. So far, these two estimation procedures were presented and studied under the gamma frailty distribution mainly because of its simple interpretation and mathematical tractability. Modifications of both procedures for other frailty distributions, such as the inverse Gaussian, positive stable and a specific case of discrete distribution, are presented. By extensive simulations, it is shown that under the family-specific proportional hazards model, the gamma frailty model appears to be robust to frailty distribution mis-specification in both bias and efficiency loss in the marginal parameters. The population-averaged proportional hazards model, is found to be robust under the gamma frailty model mis-specification only under moderate or weak dependency within cluster members.     

Predictive comparison of joint longitudinal-survival modeling: a case study illustrating competing approaches

The joint modeling of longitudinal and survival data has received extraordinary attention in the statistics literature recently, with models and methods becoming increasingly more complex. Most of these approaches pair a proportional hazards survival with longitudinal trajectory modeling through parametric or nonparametric specifications. In this paper we closely examine one data set previously analyzed using a two parameter parametric model for Mediterranean fruit fly (medfly) egg-laying trajectories paired with accelerated failure time and proportional hazards survival models. We consider parametric and nonparametric versions of these two models, as well as a proportional odds rate model paired with a wide variety of longitudinal trajectory assumptions reflecting the types of analyses seen in the literature. In addition to developing novel nonparametric Bayesian methods for joint models, we emphasize the importance of model selection from among joint and non joint models. The default in the literature is to omit at the outset non joint models from consideration. For the medfly data, a predictive diagnostic criterion suggests that both the choice of survival model and longitudinal assumptions can grossly affect model adequacy and prediction. Specifically for these data, the simple joint model used in by Tseng et al. (Biometrika 92:587–603, 2005) and models with much more flexibility in their longitudinal components are predictively outperformed by simpler analyses. This case study underscores the need for data analysts to compare on the basis of predictive performance different joint models and to include non joint models in the pool of candidates under consideration.