Joint models for multiple longitudinal processes and time-to-event outcome

ABSTRACT

Joint models are statistical tools for estimating the association between time-to-event and longitudinal outcomes. One challenge to the application of joint models is its computational complexity. Common estimation methods for joint models include a two-stage method, Bayesian and maximum-likelihood methods. In this work, we consider joint models of a time-to-event outcome and multiple longitudinal processes and develop a maximum-likelihood estimation method using the expectation–maximization algorithm. We assess the performance of the proposed method via simulations and apply the methodology to a data set to determine the association between longitudinal systolic and diastolic blood pressure measures and time to coronary artery disease.     

Simultaneous Bayesian modeling of longitudinal and survival data in breast cancer patients

Abstract

Using simultaneous Bayesian modeling, an attempt is made to analyze data on the size of lymphedema occurring in the arms of breast cancer patients after breast cancer surgery (as the longitudinal data) and the time interval for disease progression (as the time-to-event occurrence). A model based on a multivariate skew t distribution is shown to provide the best fit. This outcome was confirmed by simulation studies too.     

A stochastic variant of the EM algorithm to fit mixed (discrete and continuous) longitudinal data with nonignorable missingness

Abstract

In longitudinal studies data are collected on the same set of units for more than one occasion. In medical studies it is very common to have mixed Poisson and continuous longitudinal data. In such studies, for different reasons, some intended measurements might not be available resulting in a missing data setting. When the probability of missingness is related to the missing values, the missingness mechanism is termed nonrandom. The stochastic expectation-maximization (SEM) algorithm and the parametric fractional imputation (PFI) method are developed to handle nonrandom missingness in mixed discrete and continuous longitudinal data assuming different covariance structures for the continuous outcome. The proposed techniques are evaluated using simulation studies. Also, the proposed techniques are applied to the interstitial cystitis data base (ICDB) data.     

Estimating finite mixture of continuous trees using penalized mutual information

Abstract

In this paper we introduce continuous tree mixture model that is the mixture of undirected graphical models with tree structured graphs and is considered as multivariate analysis with a non parametric approach. We estimate its parameters, the component edge sets and mixture proportions through regularized maximum likalihood procedure. Our new algorithm, which uses expectation maximization algorithm and the modified version of Kruskal algorithm, simultaneosly estimates and prunes the mixture component trees. Simulation studies indicate this method performs better than the alternative Gaussian graphical mixture model. The proposed method is also applied to water-level data set and is compared with the results of Gaussian mixture model.     

A detection algorithm for the first jump time in sample trajectories of jump-diffusions driven by α-stable white noise

Abstract

The purpose of this paper is to develop a detection algorithm for the first jump point in sampling trajectories of jump-diffusions which are described as solutions of stochastic differential equations driven by α-stable white noise. This is done by a multivariate Lagrange interpolation approach. To this end, we utilize computer simulation algorithm in MATLAB to visualize the sampling trajectories of the jump-diffusions for various combinations of parameters arising in the modeling structure of stochastic differential equations.     

Comparing crossing hazard rate functions by joint modelling of survival and longitudinal data

Abstract

It is one of the important issues in survival analysis to compare two hazard rate functions to evaluate treatment effect. It is quite common that the two hazard rate functions cross each other at one or more unknown time points, representing temporal changes of the treatment effect. In certain applications, besides survival data, we also have related longitudinal data available regarding some time-dependent covariates. In such cases, a joint model that accommodates both types of data can allow us to infer the association between the survival and longitudinal data and to assess the treatment effect better. In this paper, we propose a modelling approach for comparing two crossing hazard rate functions by joint modelling survival and longitudinal data. Maximum likelihood estimation is used in estimating the parameters of the proposed joint model using the EM algorithm. Asymptotic properties of the maximum likelihood estimators are studied. To illustrate the virtues of the proposed method, we compare the performance of the proposed method with several existing methods in a simulation study. Our proposed method is also demonstrated using a real dataset obtained from an HIV clinical trial.     

Combined synthetic and |S| chart for monitoring process dispersion

This article proposes a multivariate control chart, the syn-|S| chart, which comprises a standard |S| subchart and a multivariate synthetic sample generalized variance |S| (synthetic |S|) subchart, for detecting shifts in the covariance matrix of a multivariate normally distributed process. A procedure for the optimal design of the syn-|S| chart by minimizing the average extra quadratic loss is provided. The syn-|S| chart has better overall performance compared to the synthetic |S| chart and the standard |S| chart, based on the zero-state and steady-state modes. An example is given to illustrate the operation of the synthetic |S| chart.     

VARIANCE ESTIMATION IN NONPARAMETRIC MULTIPLE REGRESSION

ABSTRACT

We consider the variance estimation in a general nonparametric regression model with multiple covariates. We extend difference methods to the multivariate setting by introducing an algorithm that orders the design points in higher dimensions. We also consider an adaptive difference estimator which requires much less strict assumptions on the covariate design and can significantly reduce mean squared error for small sample sizes.     

Robust multivariate diagnostics for PLSR and application on high dimensional spectrally overlapped drug systems

ABSTRACT

Statistical methods are effectively used in the evaluation of pharmaceutical formulations instead of laborious liquid chromatography. However, signal overlapping, nonlinearity, multicollinearity and presence of outliers deteriorate the performance of statistical methods. The Partial Least Squares Regression (PLSR) is a very popular method in the quantification of high dimensional spectrally overlapped drug formulations. The SIMPLS is the mostly used PLSR algorithm, but it is highly sensitive to outliers that also effect the diagnostics. In this paper, we propose new robust multivariate diagnostics to identify outliers, influential observations and points causing non-normality for a PLSR model. We study performances of the proposed diagnostics on two everyday use highly overlapping drug systems: Paracetamol–Caffeine and Doxylamine Succinate–Pyridoxine Hydrochloride.     

On the Computation and Finite Sample Behavior of the Constrained M-Estimates for Multivariate Location and Scatter

Abstract

Constrained M (CM) estimates of multivariate location and scatter [Kent, J. T., Tyler, D. E. (1996). Constrained M-estimation for multivariate location and scatter. Ann. Statist. 24:1346–1370] are defined as the global minimum of an objective function subject to a constraint. These estimates combine the good global robustness properties of the S estimates and the good local robustness properties of the redescending M estimates. The CM estimates are not explicitly defined. Numerical methods have to be used to compute the CM estimates. In this paper, we give an algorithm to compute the CM estimates. Using the algorithm, we give a small simulation study to demonstrate the capability of the algorithm finding the CM estimates, and also to explore the finite sample behavior of the CM estimates. We also use the CM estimators to estimate the location and scatter parameters of some multivariate data sets to see the performance of the CM estimates dealing with the real data sets that may contain outliers.     

Concurrent generation of multivariate mixed data with variables of dissimilar types

ABSTRACT

Data sets originating from wide range of research studies are composed of multiple variables that are correlated and of dissimilar types, primarily of count, binary/ordinal and continuous attributes. The present paper builds on the previous works on multivariate data generation and develops a framework for generating multivariate mixed data with a pre-specified correlation matrix. The generated data consist of components that are marginally count, binary, ordinal and continuous, where the count and continuous variables follow the generalized Poisson and normal distributions, respectively. The use of the generalized Poisson distribution provides a flexible mechanism which allows under- and over-dispersed count variables generally encountered in practice. A step-by-step algorithm is provided and its performance is evaluated using simulated and real-data scenarios.     

On the estimation of extreme directional multivariate quantiles

Abstract

In multivariate extreme value theory (MEVT), the focus is on analysis outside of the observable sampling zone, which implies that the region of interest is associated to high risk levels. This work provides tools to include directional notions into the MEVT, giving the opportunity to characterize the recently introduced directional multivariate quantiles (DMQ) at high levels. Then, an out-sample estimation method for these quantiles is given. A bootstrap procedure carries out the estimation of the tuning parameter in this multivariate framework and helps with the estimation of the DMQ. Asymptotic normality for the proposed estimator is provided and the methodology is illustrated with simulated data-sets. Finally, a real-life application to a financial case is also performed.     

Bayesian analysis of multivariate t linear mixed models with missing responses at random

The multivariate t linear mixed model (MtLMM) has been recently proposed as a robust tool for analysing multivariate longitudinal data with atypical observations. Missing outcomes frequently occur in longitudinal research even in well controlled situations. As a powerful alternative to the traditional expectation maximization based algorithm employing single imputation, we consider a Bayesian analysis of the MtLMM to account for the uncertainties of model parameters and missing outcomes through multiple imputation. An inverse Bayes formulas sampler coupled with Metropolis-within-Gibbs scheme is used to effectively draw the posterior distributions of latent data and model parameters. The techniques for multiple imputation of missing values, estimation of random effects, prediction of future responses, and diagnostics of potential outliers are investigated as well. The proposed methodology is illustrated through a simulation study and an application to AIDS/HIV data.     

A Bayesian wavelet approach to estimation of a change-point in a nonlinear multivariate time series

ABSTRACT

We propose a semiparametric approach to estimate the existence and location of a statistical change-point to a nonlinear multivariate time series contaminated with an additive noise component. In particular, we consider a p-dimensional stochastic process of independent multivariate normal observations where the mean function varies smoothly except at a single change-point. Our approach involves conducting a Bayesian analysis on the empirical detail coefficients of the original time series after a wavelet transform. If the mean function of our time series can be expressed as a multivariate step function, we find our Bayesian-wavelet method performs comparably with classical parametric methods such as maximum likelihood estimation. The advantage of our multivariate change-point method is seen in how it applies to a much larger class of mean functions that require only general smoothness conditions.     

Gaussian Scale Mixture Models for Robust Linear Multivariate Regression with Missing Data

We present an algorithm for multivariate robust Bayesian linear regression with missing data. The iterative algorithm computes an approximative posterior for the model parameters based on the variational Bayes (VB) method. Compared to the EM algorithm, the VB method has the advantage that the variance for the model parameters is also computed directly by the algorithm. We consider three families of Gaussian scale mixture models for the measurements, which include as special cases the multivariate t distribution, the multivariate Laplace distribution, and the contaminated normal model. The observations can contain missing values, assuming that the missing data mechanism can be ignored. A Matlab/Octave implementation of the algorithm is presented and applied to solve three reference examples from the literature.     

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.     

Optimal designs of multivariate synthetic |S| control chart based on median run length

The multivariate synthetic generalized sample variance |S| (synthetic |S|) chart is a combination of the |S| sub-chart and the conforming run length sub-chart. A procedure for optimal designs of the synthetic |S| chart, based on the median run length (MRL), for both zero and steady-state modes are provided by minimizing the out-of-control MRL. The comparative results show that the synthetic |S| chart performs better than the standard |S| chart for detecting shifts in the covariance matrix of a multivariate normally distributed process, in terms of the MRL. An example is given to illustrate the operation of the synthetic |S| chart.     

Application of trajectories from growth curve in identification of longitudinal biomarker for the multivariate survival data

In clinical studies, the researchers measure the patients' response longitudinally. In recent studies, Mixed models are used to determine effects in the individual level. In the other hand, Henderson et al. [3,4] developed a joint likelihood function which combines likelihood functions of longitudinal biomarkers and survival times. They put random effects in the longitudinal component to determine if a longitudinal biomarker is associated with time to an event. In this paper, we deal with a longitudinal biomarker as a growth curve and extend Henderson's method to determine if a longitudinal biomarker is associated with time to an event for the multivariate survival data.     

Evaluation of process capability in multivariate nonlinear profiles

ABSTRACT

Process capability indices measure the ability of a process to provide products that meet certain specifications. Few references deal with the capability of a process characterized by a functional relationship between a response variable and one or more explanatory variables, which is called profile. Specifically, there is not any reference analysing the capability of processes characterized by multivariate nonlinear profiles. In this paper, we propose a method to measure the capability of these processes, based on principal components for multivariate functional data and the concept of functional depth. A simulation study is conducted to assess the performance of the proposed method. An example from the sugar production illustrates the applicability of this approach.     

An alternative algorithm of the empirical likelihood estimation for the parameter of a linear regression model

ABSTRACT

Empirical likelihood (EL) is a nonparametric method based on observations. EL method is defined as a constrained optimization problem. The solution of this constrained optimization problem is carried on using duality approach. In this study, we propose an alternative algorithm to solve this constrained optimization problem. The new algorithm is based on a newton-type algorithm for Lagrange multipliers for the constrained optimization problem. We provide a simulation study and a real data example to compare the performance of the proposed algorithm with the classical algorithm. Simulation and the real data results show that the performance of the proposed algorithm is comparable with the performance of the existing algorithm in terms of efficiencies and cpu-times.