Statistical model and inference for pharmacokinetic data

In this paper, we consider a statistical model for the drug concentration–time profiles that are obtained in a pharmacokinetic (PK) study when the drug is orally administered. In the proposed statistical PK model, the subject-specific concentration–time curve is described by the one-compartment PK model with first-order absorption and elimination. Moreover, a multivariate generalized gamma distribution is developed for the joint distribution of the drug concentrations that are repeatedly measured from the same subject. We then construct confidence intervals for the subject–exposure parameters which provide a further insight into the individual exposure of the drug under study. The proposed statistical PK model and the associated inference are then applied to illustrate a real data set. A simulation study is also implemented to investigate the performances of the coverage probability and expected length of the proposed confidence intervals. Finally, we give conclusions and discussions on the application of the proposed procedures.     

Modified likelihood ratio tests in heteroskedastic multivariate regression models with measurement error

In this paper, we develop modified versions of the likelihood ratio test for multivariate heteroskedastic errors-in-variables regression models. The error terms are allowed to follow a multivariate distribution in the elliptical class of distributions, which has the normal distribution as a special case. We derive the Skovgaard-adjusted likelihood ratio statistics, which follow a chi-squared distribution with a high degree of accuracy. We conduct a simulation study and show that the proposed tests display superior finite sample behaviour as compared to the standard likelihood ratio test. We illustrate the usefulness of our results in applied settings using a data set from the WHO MONICA Project on cardiovascular disease.     

Multivariate Birnbaum–Saunders regression model

In this paper, we propose a multivariate log-linear Birnbaum–Saunders regression model. We discuss maximum-likelihood estimation of the model parameters and provide closed-form expressions for the score function and for Fisher's information matrix. Hypothesis testing is performed using approximations obtained from the asymptotic normality of the maximum-likelihood estimator. Some influence methods, such as the local influence and generalized leverage are discussed and the normal curvatures for studying local influence are derived under some perturbation schemes. Further, a test for the homogeneity of the shape parameter of the multivariate regression model is investigated. A real data set is presented for illustrative purposes.     

Multivariate tail conditional expectation for scale mixtures of skew-normal distribution

In practice, a financial or actuarial data set may be a skewed or heavy-tailed and this motivates us to study a class of distribution functions in risk management theory that provide more information about these characteristics resulting in a more accurate risk analysis. In this paper, we consider a multivariate tail conditional expectation (MTCE) for multivariate scale mixtures of skew-normal (SMSN) distributions. This class of distributions contains skewed distributions and some members of this class can be used to analyse heavy-tailed data sets. We also provide a closed form for TCE in a univariate skew-normal distribution framework. Numerical examples are also provided for illustration.     

Bayesian validation assessment of multivariate computational models

Multivariate model validation is a complex decision-making problem involving comparison of multiple correlated quantities, based upon the available information and prior knowledge. This paper presents a Bayesian risk-based decision method for validation assessment of multivariate predictive models under uncertainty. A generalized likelihood ratio is derived as a quantitative validation metric based on Bayes’ theorem and Gaussian distribution assumption of errors between validation data and model prediction. The multivariate model is then assessed based on the comparison of the likelihood ratio with a Bayesian decision threshold, a function of the decision costs and prior of each hypothesis. The probability density function of the likelihood ratio is constructed using the statistics of multiple response quantities and Monte Carlo simulation. The proposed methodology is implemented in the validation of a transient heat conduction model, using a multivariate data set from experiments. The Bayesian methodology provides a quantitative approach to facilitate rational decisions in multivariate model assessment under uncertainty.     

A covariance-based test for shared frailty in multivariate lifetime data

We decompose the score statistic for testing for shared finite variance frailty in multivariate lifetime data into marginal and covariance-based terms. The null properties of the covariance-based statistic are derived in the context of parametric lifetime models. Its non-null properties are estimated using simulation and compared with those of the score test and two likelihood ratio tests when the underlying lifetime distribution is Weibull. Some examples are used to illustrate the covariance-based test. A case is made for using the covariance-based statistic as a simple diagnostic procedure for shared frailty in a parametric exploratory analysis of multivariate lifetime data and a link to the bivariate Clayton–Oakes copula model is shown.     

A new family of multivariate slash distributions

In this article, a new form of multivariate slash distribution is introduced and some statistical properties are derived. In order to illustrate the advantage of this distribution over the existing generalized multivariate slash distribution in the literature, it is applied to a real data set.     

Joint distribution of simultaneous exposures to several carcinogens in a case–control study: sample size determination

Consider a population of individuals who are free of a disease under study, and who are exposed simultaneously at random exposure levels, say X,Y,Z,… to several risk factors which are suspected to cause the disease in the populationm. At any specified levels X=x, Y=y, Z=z, …, the incidence rate of the disease in the population ot risk is given by the exposure–response relationship r(x,y,z,…) = P(disease|x,y,z,…). The present paper examines the relationship between the joint distribution of the exposure variables X,Y,Z, … in the population at risk and the joint distribution of the exposure variables U,V,W,… among cases under the linear and the exponential risk models. It is proven that under the exponential risk model, these two joint distributions belong to the same family of multivariate probability distributions, possibly with different parameters values. For example, if the exposure variables in the population at risk have jointly a multivariate normal distribution, so do the exposure variables among cases; if the former variables have jointly a multinomial distribution, so do the latter. More generally, it is demonstrated that if the joint distribution of the exposure variables in the population at risk belongs to the exponential family of multivariate probability distributions, so does the joint distribution of exposure variables among cases. If the epidemiologist can specify the differnce among the mean exposure levels in the case and control groups which are considered to be clinically or etiologically important in the study, the results of the present paper may be used to make sample size determinations for the case–control study, corresponding to specified protection levels, i.e., size α and 1–β of a statistical test. The multivariate normal, the multinomial, the negative multinomial and Fisher's multivariate logarithmic series exposure distributions are used to illustrate our results.     

Multivariate Birnbaum–Saunders distribution: properties and associated inference

The univariate fatigue life distribution proposed by Birnbaum and Saunders [A new family of life distributions. J Appl Probab. 1969;6:319–327] has been used quite effectively to model times to failure for materials subject to fatigue and for modelling lifetime data and reliability problems. In this article, we introduce a Birnbaum–Saunders (BS) distribution in the multivariate setting. The new multivariate model arises in the context of conditionally specified distributions. The proposed multivariate model is an absolutely continuous distribution whose marginals are univariate BS distributions. General properties of the multivariate BS distribution are derived and the estimation of the unknown parameters by maximum likelihood is discussed. Further, the Fisher's information matrix is determined. Applications to real data of the proposed multivariate distribution are provided for illustrative purposes.     

Modeling with a large class of unimodal multivariate distributions

In this paper we introduce a new class of multivariate unimodal distributions, motivated by Khintchine's representation for unimodal densities on the real line. We start by introducing a new class of unimodal distributions which can then be naturally extended to higher dimensions, using the multivariate Gaussian copula. Under both univariate and multivariate settings, we provide MCMC algorithms to perform inference about the model parameters and predictive densities. The methodology is illustrated with univariate and bivariate examples, and with variables taken from a real data set.     

Power of the Neyman Smooth Test for Evaluating Multivariate Forecast Densities

We compare and investigate Neyman's smooth test, its components, and the Kolmogorov-Smirnov (KS) goodness-of-fit test for testing the uniformity of multivariate forecast densities. Simulations indicate that the KS test lacks power when the forecast distributions are misspecified, especially for correlated sequences of random variables. Neyman's smooth test and its components work well in samples of size typically available, although there sometimes are size distortions. The components provide directed diagnosis regarding the kind of departure from the null. For illustration, the tests are applied to forecast densities obtained from a bivariate threshold model fitted to high-frequency financial data.     

Multivariate Life Testing in Variably Scaled Environments

This paper examines modeling and inference questions for experiments in which different subsets of a set of k possibly dependent components are tested in r different environments. In each environment, the failure times of the set of components on test is assumed to be governed by a particular type of multivariate exponential (MVE) distribution. For any given component tested in several environments, it is assumed that its marginal failure rate varies from one environment to another via a change of scale between the environments, resulting in a joint MVE model which links in a natural way the applicable MVE distributions describing component behavior in each fixed environment. This study thus extends the work of Proschan and Sullo (1976) to multiple environments and the work of Kvam and Samaniego (1993) to dependent data. The problem of estimating model parameters via the method of maximum likelihood is examined in detail. First, necessary and sufficient conditions for the identifiability of model parameters are established. We then treat the derivation of the MLE via a numerically-augmented application of the EM algorithm. The feasibility of the estimation method is demonstrated in an example in which the likelihood ratio test of the hypothesis of equal component failure rates within any given environment is carried out.     

On prediction from the location-scale model with a compound error distribution

The prediction distribution of future response(s) given a set of data from a location-scale model with a compound error distribution has been derived by utilizing the structural relations of the model. The compound error distribution has been specialized to cover the case of multivariate t-distribution.     

On optimal testing for the equality of equicorrelation: An example of loss in power

Sen Gupta (1988) considered a locally most powerful (LMP) test for testing nonzero values of the equicorrelation coefficient of a standard symmetric multivariate normal distribution. This paper constructs analogous tests for the symmetric multivariate normal distribution. It shows that the new test is uniformly most powerful invariant even in the presence of a nuisance parameter, σ². Further applications of LMP invariant tests to several equicorrelated populations have been considered and an extension to panel data modeling has been suggested.     

Consistent Bayesian information criterion based on a mixture prior for possibly high-dimensional multivariate linear regression models

In the problem of selecting variables in a multivariate linear regression model, we derive new Bayesian information criteria based on a prior mixing a smooth distribution and a delta distribution. Each of them can be interpreted as a fusion of the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). Inheriting their asymptotic properties, our information criteria are consistent in variable selection in both the large-sample and the high-dimensional asymptotic frameworks. In numerical simulations, variable selection methods based on our information criteria choose the true set of variables with high probability in most cases.     

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     

The multivariate component zero-inflated Poisson model for correlated count data analysis

Multivariate zero-inflated Poisson (ZIP) distributions are important tools for modelling and analysing correlated count data with extra zeros. Unfortunately, existing multivariate ZIP distributions consider only the overall zero-inflation while the component zero-inflation is not well addressed. This paper proposes a flexible multivariate ZIP distribution, called the multivariate component ZIP distribution, in which both the overall and component zero-inflations are taken into account. Likelihood-based inference procedures including the calculation of maximum likelihood estimates of parameters in the model without and with covariates are provided. Simulation studies indicate that the performance of the proposed methods on the multivariate component ZIP model is satisfactory. The Australia health care utilisation data set is analysed to demonstrate that the new distribution is more appropriate than the existing multivariate ZIP distributions.     

Multivariate extension of chi-squared univariate normality test

We propose a multivariate extension of the univariate chi-squared normality test. Using a known result for the distribution of quadratic forms in normal variables, we show that the proposed test statistic has an approximated chi-squared distribution under the null hypothesis of multivariate normality. As in the univariate case, the new test statistic is based on a comparison of observed and expected frequencies for specified events in sample space. In the univariate case, these events are the standard class intervals, but in the multivariate extension we propose these become hyper-ellipsoidal annuli in multivariate sample space. We assess the performance of the new test using Monte Carlo simulation. Keeping the type I error rate fixed, we show that the new test has power that compares favourably with other standard normality tests, though no uniformly most powerful test has been found. We recommend the new test due to its competitive advantages.     

Robust multivariate mixture regression models with incomplete data

Multivariate mixture regression models can be used to investigate the relationships between two or more response variables and a set of predictor variables by taking into consideration unobserved population heterogeneity. It is common to take multivariate normal distributions as mixing components, but this mixing model is sensitive to heavy-tailed errors and outliers. Although normal mixture models can approximate any distribution in principle, the number of components needed to account for heavy-tailed distributions can be very large. Mixture regression models based on the multivariate t distributions can be considered as a robust alternative approach. Missing data are inevitable in many situations and parameter estimates could be biased if the missing values are not handled properly. In this paper, we propose a multivariate t mixture regression model with missing information to model heterogeneity in regression function in the presence of outliers and missing values. Along with the robust parameter estimation, our proposed method can be used for (i) visualization of the partial correlation between response variables across latent classes and heterogeneous regressions, and (ii) outlier detection and robust clustering even under the presence of missing values. We also propose a multivariate t mixture regression model using MM-estimation with missing information that is robust to high-leverage outliers. The proposed methodologies are illustrated through simulation studies and real data analysis.     

Prediction distribution for a linear regression model with multivariate student-t error distribution

The distribution(s) of future response(s) given a set of data from an informative experiment is known as prediction distribution. The paper derives the prediction distribution(s) from a linear regression model with a multivari-ate Student-t error distribution using the structural relations of the model. We observe that the prediction distribution(s) are multivariate t-variate(s) with degrees of freedom which do not depend on the degrees of freedom of the error distribution.