On implementation of a test for Kronecker product covariance structure for multivariate repeated measures data

Under the assumption of multivariate normality the likelihood ratio test is derived to test a hypothesis for Kronecker product structure on a covariance matrix in the context of multivariate repeated measures data. Although the proposed hypothesis testing can be computationally performed by indirect use of Proc Mixed of SAS, the Proc Mixed algorithm often fails to converge. We provide an alternative algorithm. The algorithm is illustrated with two real data sets. A simulation study is also conducted for the purpose of sample size consideration.     

Reml estimation for repeated measures analysis

Models for repeated measures or growth curves consist of a mean response plus error and the errors are usually correlated. Both maximum likelihood and residual maximum likelihood (REML) estimators of a regression model with dependent errors are derived for cases in which the variance matrix of the error model admits a convenient Cholesky factorisation. This factorisation may be linked to methods for producing recursive estimates of the regression parameters and recursive residuals to provide a convenient computational method. The method is used to develop a general approach to repeated measures analysis.     

Influence analysis in multivariate linear general models

In this paper we obtain several influence measures for the multivariate linear general model through the approach proposed by Muñoz-Pichardo et al. (1995), which is based on the concept of conditional bias. An interesting charasteristic of this approach is that it does not require any distributional hypothesis. Appling the obtained results to the multivariate regression model, we obtain some measures proposed by other authors. Nevertheless, on the results obtained in this paper, we emphasize two aspects. First, they provide a theoretical foundation for measures proposed by other authors for the mul¬tivariate regression model. Second, they can be applied to any linear model that can be formulated as a particular case of the multivariate linear general model. In particular, we carry out an application to the multivariate analysis of covariance.     

Multivariate analysis for the two-period repeated measures crossover design with application to clinical trials

Multivariate analysis techniques are applied to the two-period repeated measures crossover design. The approach considered in this paper has the advantage over the univariate analysis approach proposed recently by Wallenstein and Fisher (1977) that the former does not require any specific structure on the variance-covariance matrix of the repeated measures factor. (It should be noted that sums and differences of observations over periods are used for all tests. Therefore, there are two matrices under consideration, one for sums and one for differences.) Tests of significance are derived using the Wilks? criterion, and the procedure is illustrated with a numerical example from the area of clinical trials.     

Recursive computation for repeated measures models with patterned variance matrices

A convenient recursive computational method for repeated measures analysis, provided by McGilchrist and Cullis (1990), has been extended by the authors to heterogeneous error structures and also to the repeated measures model with random coefficients. The approach is outlined briefly in this paper. A computing program for the approach has been written and used to obtain results for simulated data having various error structures. A summary of the results is given. The computing program together with some subroutines is available from the authors.     

Scheffés mixed model for multivariate repeated measures:a relative efficiency evaluation

Scheffé’s mixed model, generalized for application to multivariate repeated measures, is known as the multivariate mixed model (MMM). The primary advantages the MMM are (1) the minimum sample size required to conduct an analysis is smaller than for competing procedures and (2) for certain covariance structures, the MMM analysis is more powerful than its competitors. The primary disadvantage is that the MMM makes a very restrictive covariance assumption; namely multivariate sphericity. This paper shows, first, that even minor departures from multivariate sphericity inflate the size of MMM based tests. Accordingly, MMM analyses, as computed in release 4.0 of SPSS MANOVA (SPSS Inc., 1990), can not be recommended unless it is known that multivariate sphericity is satisfied. Second, it is shown that a new Box-type (Box, 1954) Δ-corrected MMM test adequately controls test size unless departure from multivariate sphericity is severe or the covariance matrix departs substantially from a multiplicative-Kronecker structure. Third, power functions of adjusted MMM tests for selected covariance and noncentrality structures are compared to those of doubly multivariate methods that do not require multivariate sphericity. Based on relative efficiency evaluations, the adjusted MMM analyses described in this paper can be recommended only when sample sizes are very small or there is reason to believe that multivariate sphericity is nearly satisfied. Neither the e-adjusted analysis suggested in the SPSS MANOVA output (release 4.0) nor the adjusted analysis suggested by Boik (1988) can be recommended at all.     

Small area estimation under a multivariate linear model for repeated measures data

In this article, small area estimation under a multivariate linear model for repeated measures data is considered. The proposed model aims to get a model which borrows strength both across small areas and over time. The model accounts for repeated surveys, grouped response units, and random effects variations. Estimation of model parameters is discussed within a likelihood based approach. Prediction of random effects, small area means across time points, and per group units are derived. A parametric bootstrap method is proposed for estimating the mean squared error of the predicted small area means. Results are supported by a simulation study.     

CASE-DELETION DIAGNOSTICS FOR TEST STATISTICS IN MULTIVARIATE REGRESSION

Influence measures in multivariate regression analysis have been widely developed, especially through use of the case-deletion approach. However, there seem to be few accounts of the influence of observations on test statistics in hypothesis testing. This paper examines four common multivariate tests, namely the Wilks' ratio, Lawley-Hotelling trace, Pillai's trace and Roy's greatest root for testing a general linear hypothesis of the regression coefficients in multivariate regression. The influence of observations is measured using the case-deletion approach. The proposed diagnostic measures, except that of Roy's greatest root, can be expressed in terms of statistics without involving the actual deletion of observations. An illustrative example is given with satisfactory results.     

Aligned rank statistics for repeated measurement models with orthonormal design, employing a Chernoff–Savage approach

In this paper, aligned rank statistics are considered for testing hypotheses regarding the location in repeated measurement designs, where the design matrix for each set of measurements is orthonormal. Such a design may, for instance, be used when testing for linearity. It turns out that the centered design matrix is not of full rank, and therefore it does not quite satisfy the usual conditions in the literature. The number of degrees of freedom of the limiting chi-square distribution of the test statistic under the null hypothesis, however, is not affected, unless rather special hypotheses are tested. An independent derivation of this limiting distribution is given, using the Chernoff–Savage approach. In passing, it is observed that independence of the choice of aligner, which in the location problem is well-known to be due to cancellation, may in scale problems occur as a result of the type of score function suitable for scale tests. A possible extension to multivariate data is briefly indicated.     

Bartlett's Test Applied to Variance Component Models

Exact methods for testing equality between variance components obtained from several cases of the same type of balanced orthogonal design are discussed. In particular, methods for successively testing equality of a number of components using Bartlett's tests are outlined for univariate and multivariate responses. Two clinical trial examples of repeated‐measures data are presented.     

Comparison of designs for multivariate generalized linear models

The purpose of this paper is to discuss response surface designs for multivariate generalized linear models (GLMs). Such models are considered whenever several response variables can be measured for each setting of a group of control variables, and the response variables are adequately represented by GLMs. The mean-squared error of prediction (MSEP) matrix is used to assess the quality of prediction associated with a given design. The MSEP incorporates both the prediction variance and the prediction bias, which results from using maximum likelihood estimates of the parameters of the fitted linear predictor. For a given design, quantiles of a scalar-valued function of the MSEP are obtained within a certain region of interest. The quantiles depend on the unknown parameters of the linear predictor. The dispersion of these quantiles over the space of the unknown parameters is determined and then depicted by the so-called quantile dispersion graphs. An application of the proposed methodology is presented using the special case of the bivariate binary distribution.     

Group sequential analysis op a clinical trial with repeated measurements

Recently some work has been done in group sequential analysis for comparing two treatments with respect to the rate of change in a repeated measures design with staggered subject entries. We relax the involved assumption of linearity for the time-response curve and propose a group sequential procedure assuming multivariate normality with an ante-dependence structure for the repeated measurements obtained at protocol scheduled visits. The exit probabilities are determined through an a-spending function proposed by Lan and DeMets. A numerical example is given to illustrate the methodology.     

Robust Small Sample Inference for Generalised Estimating Equations: An Application of the Anova‐type Test

Asymptotically, the Wald‐type test for generalised estimating equations (GEE) models can control the type I error rate at the nominal level. However in small sample studies, it may lead to inflated type I error rates. Even with currently available small sample corrections for the GEE Wald‐type test, the type I error rate inflation is still serious when the tested contrast is multidimensional. This paper extends the ANOVA‐type test for heteroscedastic factorial designs to GEE and shows that the proposed ANOVA‐type test can also control the type I error rate at the nominal level in small sample studies while still maintaining robustness with respect to mis‐specification of the working correlation matrix. Differences of inference between the Wald‐type test and the proposed test are observed in a two‐way repeated measures ANOVA model for a diet‐induced obesity study and a two‐way repeated measures logistic regression for a collagen‐induced arthritis study. Simulation studies confirm that the proposed test has better control of the type I error rate than the Wald‐type test in small sample repeated measures models. Additional simulation studies further show that the proposed test can even achieve larger power than the Wald‐type test in some cases of the large sample repeated measures ANOVA models that were investigated.     

Sample Size Calculation and Power Analysis of Changes in Mean Response Over Time

Despite tremendous effort on different designs with cross-sectional data, little research has been conducted for sample size calculation and power analyses under repeated measures design. In addition to time-averaged difference, changes in mean response over time (CIMROT) is the primary interest in repeated measures analysis. We generalized sample size calculation and power analysis equations for CIMROT to allow unequal sample size between groups for both continuous and binary measures, through simulation, evaluated the performance of proposed methods, and compared our approach to that of a two-stage model formulization. We also created a software procedure to implement the proposed methods.     

Bayesian local bandwidth selector in multivariate associated kernel estimator for joint probability mass functions

ABSTRACT

This work treats non-parametric estimation of multivariate probability mass functions, using multivariate discrete associated kernels. We propose a Bayesian local approach to select the matrix of bandwidths considering the multivariate Dirac Discrete Uniform and the product of binomial kernels, and treating the bandwidths as a diagonal matrix of parameters with some prior distribution. The performances of this approach and the cross-validation method are compared using simulations and real count data sets. The obtained results show that the Bayes local method performs better than cross-validation in terms of integrated squared error.     

Equivalence of maximum likelihood estimation and iterative two-stage estimation for seemingly unrelated regression models

The seemingly unrelated regression model is viewed in the context of repeated measures analysis. Regression parameters and the variance-covariance matrix of the seemingly unrelated regression model can be estimated by using two-stage Aitken estimation. The first stage is to obtain a consistent estimator of the variance-covariance matrix. The second stage uses this matrix to obtain the generalized least squares estimators of the regression parameters. The maximum likelihood (ML) estimators of the regression parameters can be obtained by performing the two-stage estimation iteratively. The iterative two-stage estimation procedure is shown to be equivalent to the EM algorithm (Dempster, Laird, and Rubin, 1977) proposed by Jennrich and Schluchter (1986) and Laird, Lange, and Stram (1987) for repeated measures data. The equivalence of the iterative two-stage estimator and the ML estimator has been previously demonstrated empirically in a Monte Carlo study by Kmenta and Gilbert (1968). It does not appear to be widely known that the two estimators are equivalent theoretically. This paper demonstrates this equivalence.     

Group sequential x2 statistic for testing the difference of two mean vectors in clinical trials

In this study we discuss the group sequential procedures for comparing two treatments based on multivariate observations in clinical trials. Also we suppose that a response vector on each of two treatments has a multivariate normal distribution with unknown covariance matrix. Then we propose a group sequential x² statistic in order to carry out repeated significance test for hypothesis of no difference between two population mean vectors. In order to realize the group sequential test where average sample number is reduced, we propose another modified group sequential x² statistic by extension of Jennison and Turnbull ( 1991 ). After construction of repeated confidence boundaries for making the repeated significance test, we compare two group sequential procedures based on two statistics regarding the average sample number and the power of the test in the simulations.     

A gradient approach to efficient design and analysis of multivariate EWMA control charts

Compared to the grid search approach to optimal design of control charts, the gradient-based approach is more computationally efficient as the gradient information indicates the direction to search the optimal design parameters. However, the optimal parameters of multivariate exponentially weighted moving average (MEWMA) control charts are often obtained by using grid search in the existing literature. Note that the average run length (ARL) performance of the MEWMA chart can be calculated based on a Markov chain model, making it feasible to estimate the ARL gradient from it. Motivated by this, this paper develops an ARL gradient-based approach for the optimal design and sensitivity analysis of MEWMA control charts. It is shown that the proposed method is able to provide a fast, accurate, and easy-to-implement algorithm for the design and analysis of MEWMA charts, as compared to the conventional design approach based on grid search.     

Multivariate linear regression with non-normal errors: a solution based on mixture models

In some situations, the distribution of the error terms of a multivariate linear regression model may depart from normality. This problem has been addressed, for example, by specifying a different parametric distribution family for the error terms, such as multivariate skewed and/or heavy-tailed distributions. A new solution is proposed, which is obtained by modelling the error term distribution through a finite mixture of multi-dimensional Gaussian components. The multivariate linear regression model is studied under this assumption. Identifiability conditions are proved and maximum likelihood estimation of the model parameters is performed using the EM algorithm. The number of mixture components is chosen through model selection criteria; when this number is equal to one, the proposal results in the classical approach. The performances of the proposed approach are evaluated through Monte Carlo experiments and compared to the ones of other approaches. In conclusion, the results obtained from the analysis of a real dataset are presented.     

Modeling a mixture of ordinal and continuous repeated measures

We study the correlation structure for a mixture of ordinal and continuous repeated measures using a Bayesian approach. We assume a multivariate probit model for the ordinal variables and a normal linear regression for the continuous variables, where latent normal variables underlying the ordinal data are correlated with continuous variables in the model. Due to the probit model assumption, we are required to sample a covariance matrix with some of the diagonal elements equal to one. The key computational idea is to use parameter-extended data augmentation, which involves applying the Metropolis-Hastings algorithm to get a sample from the posterior distribution of the covariance matrix incorporating the relevant restrictions. The methodology is illustrated through a simulated example and through an application to data from the UCLA Brain Injury Research Center.