An approximate maximum likelihood procedure for parameter estimation in multivariate discrete data regression models

This paper considers an alternative to iterative procedures used to calculate maximum likelihood estimates of regression coefficients in a general class of discrete data regression models. These models can include both marginal and conditional models and also local regression models. The classical estimation procedure is generally via a Fisher-scoring algorithm and can be computationally intensive for high-dimensional problems. The alternative method proposed here is non-iterative and is likely to be more efficient in high-dimensional problems. The method is demonstrated on two different classes of regression models.     

A comparative study of tests for paired lifetime data

In this paper, we investigate different procedures for testing the equality of two mean survival times in paired lifetime studies. We consider Owen’s M-test and Q-test, a likelihood ratio test, the paired t-test, the Wilcoxon signed rank test and a permutation test based on log-transformed survival times in the comparative study. We also consider the paired t-test, the Wilcoxon signed rank test and a permutation test based on original survival times for the sake of comparison. The size and power characteristics of these tests are studied by means of Monte Carlo simulations under a frailty Weibull model. For less skewed marginal distributions, the Wilcoxon signed rank test based on original survival times is found to be desirable. Otherwise, the M-test and the likelihood ratio test are the best choices in terms of power. In general, one can choose a test procedure based on information about the correlation between the two survival times and the skewness of the marginal survival distributions.     

Bayesian analysis of multivariate survival data using Monte Carlo methods

This paper deals with the analysis of multivariate survival data from a Bayesian perspective using Markov-chain Monte Carlo methods. The Metropolis along with the Gibbs algorithm is used to calculate some of the marginal posterior distributions. A multivariate survival model is proposed, since survival times within the same group are correlated as a consequence of a frailty random block effect. The conditional proportional-hazards model of Clayton and Cuzick is used with a martingale structured prior process (Arjas and Gasbarra) for the discretized baseline hazard. Besides the calculation of the marginal posterior distributions of the parameters of interest, this paper presents some Bayesian EDA diagnostic techniques to detect model adequacy. The methodology is exemplified with kidney infection data where the times to infections within the same patients are expected to be correlated.     

A bivariate regression model for matched paired survival data: local influence and residual analysis

The use of bivariate distributions plays a fundamental role in survival and reliability studies. In this paper, we consider a location scale model for bivariate survival times based on the proposal of a copula to model the dependence of bivariate survival data. For the proposed model, we consider inferential procedures based on maximum likelihood. Gains in efficiency from bivariate models are also examined in the censored data setting. For different parameter settings, sample sizes and censoring percentages, various simulation studies are performed and compared to the performance of the bivariate regression model for matched paired survival data. Sensitivity analysis methods such as local and total influence are presented and derived under three perturbation schemes. The martingale marginal and the deviance marginal residual measures are used to check the adequacy of the model. Furthermore, we propose a new measure which we call modified deviance component residual. The methodology in the paper is illustrated on a lifetime data set for kidney patients.     

Conditional even point estimation for bivariate discrete distributions

This paper presents a simple procedure for estimating the parameters of bivariate discrete distributions. The procedure uses the marginal means and certain observed frequencies in one or more conditional distributions. The bivariate Poisson and Negative Binomial distributions are used as illustrative examples, Parameter estimators are derived and asymptotic efficiencies are examined for various parameter values.     

Report of the ASA Technical Panel on the Census Undercount

A new model is proposed for the joint distribution of paired survival times generated from clinical trials and certain reliability settings. The new model can be considered an extension to the bivariate exponential models studied in the literature. Here, a more flexible bivariate Weibull model will be derived, and two exact parametric tests for testing the equality of marginal survival distributions are developed.     

A bivariate regression model with cure fraction

The use of bivariate distributions plays a fundamental role in survival and reliability studies. In this paper, we introduce a location-scale model for bivariate survival times based on the copula to model the dependence of bivariate survival data with cure fraction. We create the correlation structure between the failure times using the Clayton family of copulas, which is assumed to have any distribution. It turns out that the model becomes very flexible with respect to the choice of the marginal distributions. For the proposed model, we consider inferential procedures based on constrained parameters under maximum likelihood. We derive the appropriate matrices for assessing local influence under different perturbation schemes and present some ways to perform global influence analysis. The relevance of the approach is illustrated using a real data set and a diagnostic analysis is performed to select an appropriate model.     

Rank Tests for Matched Survival Data

In a clinical trial with the time to an event as the outcome of interest, we may randomize a number of matched subjects, such as litters, to different treatments. The number of treatments equals the number of subjects per litter, two in the case of twins. In this case, the survival times of matched subjects could be dependent. Although the standard rank tests, such as the logrank and Wilcoxon tests, for independent samples may be used to test the equality of marginal survival distributions, their standard error should be modified to accommodate the possible dependence of survival times between matched subjects. In this paper we propose a method of calculating the standard error of the rank tests for paired two-sample survival data. The method is naturally extended to that for K-sample tests under dependence.     

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.     

A Multivariate Model for Repeated Failure Time Measurements

A parametric multivariate failure time distribution is derived from a frailty-type model with a particular frailty distribution. It covers as special cases certain distributions which have been used for multivariate survival data in recent years. Some properties of the distribution are derived: its marginal and conditional distributions lie within the parametric family, and association between the component variates can be positive or, to a limited extent, negative. The simple closed form of the survivor function is useful for right-censored data, as occur commonly in survival analysis, and for calculating uniform residuals. Also featured is the distribution of ratios of paired failure times. The model is applied to data from the literature     

Simultaneous inference in structured additive conditional copula regression models: a unifying Bayesian approach

While most regression models focus on explaining distributional aspects of one single response variable alone, interest in modern statistical applications has recently shifted towards simultaneously studying multiple response variables as well as their dependence structure. A particularly useful tool for pursuing such an analysis are copula-based regression models since they enable the separation of the marginal response distributions and the dependence structure summarised in a specific copula model. However, so far copula-based regression models have mostly been relying on two-step approaches where the marginal distributions are determined first whereas the copula structure is studied in a second step after plugging in the estimated marginal distributions. Moreover, the parameters of the copula are mostly treated as a constant not related to covariates and most regression specifications for the marginals are restricted to purely linear predictors. We therefore propose simultaneous Bayesian inference for both the marginal distributions and the copula using computationally efficient Markov chain Monte Carlo simulation techniques. In addition, we replace the commonly used linear predictor by a generic structured additive predictor comprising for example nonlinear effects of continuous covariates, spatial effects or random effects and furthermore allow to make the copula parameters covariate-dependent. To facilitate Bayesian inference, we construct proposal densities for a Metropolis–Hastings algorithm relying on quadratic approximations to the full conditionals of regression coefficients avoiding manual tuning. The performance of the resulting Bayesian estimates is evaluated in simulations comparing our approach with penalised likelihood inference, studying the choice of a specific copula model based on the deviance information criterion, and comparing a simultaneous approach with a two-step procedure. Furthermore, the flexibility of Bayesian conditional copula regression models is illustrated in two applications on childhood undernutrition and macroecology.     

Behavior of agreement measures in the presence of zero cells and biased marginal distributions

Kappa and B assess agreement between two observers independently classifying N units into k categories. We study their behavior under zero cells in the contingency table and unbalanced asymmetric marginal distributions. Zero cells arise when a cross-classification is never endorsed by both observers; biased marginal distributions occur when some categories are preferred differently between the observers. Simulations studied the distributions of the unweighted and weighted statistics for k=4, under fixed proportions of diagonal agreement and different patterns off-diagonal, with various sample sizes, and under various zero cell count scenarios. Marginal distributions were first uniform and homogeneous, and then unbalanced asymmetric distributions. Results for unweighted kappa and B statistics were comparable to work of Muñoz and Bangdiwala, even with zero cells. A slight increased variation was observed as the sample size decreased. Weighted statistics did show greater variation as the number of zero cells increased, with weighted kappa increasing substantially more than weighted B. Under biased marginal distributions, weighted kappa with Cicchetti weights were higher than with squared weights. Both statistics for observer agreement behaved well under zero cells. The weighted B was less variable than the weighted kappa under similar circumstances and different weights. In general, B's performance and graphical interpretation make it preferable to kappa under the studied scenarios.     

Maximum Penalized Likelihood Estimation in a Gamma-Frailty Model

The shared frailty models allow for unobserved heterogeneity or for statistical dependence between observed survival data. The most commonly used estimation procedure in frailty models is the EM algorithm, but this approach yields a discrete estimator of the distribution and consequently does not allow direct estimation of the hazard function. We show how maximum penalized likelihood estimation can be applied to nonparametric estimation of a continuous hazard function in a shared gamma-frailty model with right-censored and left-truncated data. We examine the problem of obtaining variance estimators for regression coefficients, the frailty parameter and baseline hazard functions. Some simulations for the proposed estimation procedure are presented. A prospective cohort (Paquid) with grouped survival data serves to illustrate the method which was used to analyze the relationship between environmental factors and the risk of dementia.     

Modelling Poisson marked point processes using bivariate mixture transition distributions

A class of bivariate continuous-discrete distributions is proposed to fit Poisson dynamic models in a single unified framework via bivariate mixture transition distributions (BMTDs). Potential advantages of this class over the current models include its ability to capture stretches, bursts and nonlinear patterns characterized by Internet network traffic, high-frequency financial data and many others. It models the inter-arrival times and the number of arrivals (marks) in a single unified model which benefits from the dependence structure of the data. The continuous marginal distributions of this class include as special cases the exponential, gamma, Weibull and Rayleigh distributions (for the inter-arrival times), whereas the discrete marginal distributions are geometric and negative binomial. The conditional distributions are Poisson and Erlang. Maximum-likelihood estimation is discussed and parameter estimates are obtained using an expectation–maximization algorithm, while the standard errors are estimated using the missing information principle. It is shown via real data examples that the proposed BMTD models appear to capture data features better than other competing models.     

Rank correlation plots for use with correlated input variables

A method for inducing a desired rank correlation matrix on multivariate input vectors for simulation studies has recently been developed by Iman and Conover (1982). The primary intention of this procedure is to produce correlated input variables for use with computer models. Since this procedure is distribution free and allows the exact marginal distributions to remain intact it can be used with any marginal distributions for which it is reasonable to think in terms of correlation. In this paper we present a series of rank correlation plots based on this procedure when the marginal distributions are normal, lognormal, uniform and loguniform. These plots provide a convenient tool both for aiding the modeler in determining the degree of dependence among input variables (rather than guessing) and for communicating with the modeler the effect of different correlation assumptions. In addition this procedure can be used with sample multivariate data by sampling directly from the respective marginal empirical distribution functions.     

General partially linear additive transformation model with right-censored data

We propose a class of general partially linear additive transformation models (GPLATM) with right-censored survival data in this work. The class of models are flexible enough to cover many commonly used parametric and nonparametric survival analysis models as its special cases. Based on the B spline interpolation technique, we estimate the unknown regression parameters and functions by the maximum marginal likelihood estimation method. One important feature of the estimation procedure is that it does not need the baseline and censoring cumulative density distributions. Some numerical studies illustrate that this procedure can work very well for the moderate sample size.     

Weighted bivariate logarithmic series distributions

In this paper, we are interested in the weighted distributions of a bivariate three parameter logarithmic series distribution studied by Kocherlakota and Kocherlakota (1990). The weighted versions of the model are derived with weight W(x,y) = x^[r] y^[s]. Explicit expressions for the probability mass function and probability generating functions are derived in the case r = s = l. The marginal and conditional distributions are derived in the general case. The maximum likelihood estimation of the parameters, in both two parameter and three parameter cases, is studied. A procedure for computer generation of bivariate data from a discrete distribution is described. This enables us to present two examples, in order to illustrate the methods developed, for finding the maximum likelihood estimates.     

A three-state disease model with interval-censored data: Estimation and applications to AIDS and cancer

In presence of interval-censored data, we propose a general three-state disease model with covariates. Such data can arise, for example, in epidemiologic studies of infectious disease where both the times of infection and disease onset are not directly observed, or in cancer studies where the time of disease metastasis is known up to a specified interval. The proposed model allows the distributions of the transition times between states to depend on covariates and the time in the previous state. An estimation procedure for the underlying distributions and the model coefficients is suggested with the EM algorithm. The EMS algorithm (Smoothed EM algorithm) is also considered to obtain smooth estimates of the distributions. The proposed method is illustrated with data from an AIDS study and a study of patients with malignant melanoma.     

Cure rate model with bivariate interval censored data

A mixture model is proposed to analyze a bivariate interval censored data with cure rates. There exist two types of association related with bivariate failure times and bivariate cure rates, respectively. A correlation coefficient is adopted for the association of bivariate cure rates and a copula function is applied for bivariate survival times. The conditional expectation of unknown quantities attributable to interval censored data and cure rates are calculated in the E-step in ES (Expectation-Solving algorithm) and the marginal estimates and the association measures are estimated in the S-step through a two-stage procedure. A simulation study is performed to evaluate the suggested method and a real data from HIV patients is analyzed as a real data example.     

A marginal regression model for multivariate failure time data with a surviving fraction

A marginal regression approach for correlated censored survival data has become a widely used statistical method. Examples of this approach in survival analysis include from the early work by Wei et al. (J Am Stat Assoc 84:1065–1073, 1989) to more recent work by Spiekerman and Lin (J Am Stat Assoc 93:1164–1175, 1998). This approach is particularly useful if a covariate’s population average effect is of primary interest and the correlation structure is not of interest or cannot be appropriately specified due to lack of sufficient information. In this paper, we consider a semiparametric marginal proportional hazard mixture cure model for clustered survival data with a surviving or “cure” fraction. Unlike the clustered data in previous work, the latent binary cure statuses of patients in one cluster tend to be correlated in addition to the possible correlated failure times among the patients in the cluster who are not cured. The complexity of specifying appropriate correlation structures for the data becomes even worse if the potential correlation between cure statuses and the failure times in the cluster has to be considered, and thus a marginal regression approach is particularly attractive. We formulate a semiparametric marginal proportional hazards mixture cure model. Estimates are obtained using an EM algorithm and expressions for the variance–covariance are derived using sandwich estimators. Simulation studies are conducted to assess finite sample properties of the proposed model. The marginal model is applied to a multi-institutional study of local recurrences of tonsil cancer patients who received radiation therapy. It reveals new findings that are not available from previous analyses of this study that ignored the potential correlation between patients within the same institution.