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.     

Exact Bayesian modeling for bivariate Poisson data and extensions

Bivariate count data arise in several different disciplines (epidemiology, marketing, sports statistics just to name a few) and the bivariate Poisson distribution being a generalization of the Poisson distribution plays an important role in modelling such data. In the present paper we present a Bayesian estimation approach for the parameters of the bivariate Poisson model and provide the posterior distributions in closed forms. It is shown that the joint posterior distributions are finite mixtures of conditionally independent gamma distributions for which their full form can be easily deduced by a recursively updating scheme. Thus, the need of applying computationally demanding MCMC schemes for Bayesian inference in such models will be removed, since direct sampling from the posterior will become available, even in cases where the posterior distribution of functions of the parameters is not available in closed form. In addition, we define a class of prior distributions that possess an interesting conjugacy property which extends the typical notion of conjugacy, in the sense that both prior and posteriors belong to the same family of finite mixture models but with different number of components. Extension to certain other models including multivariate models or models with other marginal distributions are discussed.     

Step Down Procedures for Comparison With a Control

“Step down” or “sequentially rejective” procedures for comparisons with a control are considered for both one sided and two sided comparisons. Confidence bounds (in terms of the control) are derived for those (location) parameters not in a selected set. Special results are derived for the normal distribution with unknown variance where the sample numbers are (possibly) unequal.     

Variance Estimation and Asymptotic Confidence Bands for the Mean Estimator of Sampled Functional Data with High Entropy Unequal Probability Sampling Designs

For fixed size sampling designs with high entropy, it is well known that the variance of the Horvitz–Thompson estimator can be approximated by the Hájek formula. The interest of this asymptotic variance approximation is that it only involves the first order inclusion probabilities of the statistical units. We extend this variance formula when the variable under study is functional, and we prove, under general conditions on the regularity of the individual trajectories and the sampling design, that we can get a uniformly convergent estimator of the variance function of the Horvitz–Thompson estimator of the mean function. Rates of convergence to the true variance function are given for the rejective sampling. We deduce, under conditions on the entropy of the sampling design, that it is possible to build confidence bands whose coverage is asymptotically the desired one via simulation of Gaussian processes with variance function given by the Hájek formula. Finally, the accuracy of the proposed variance estimator is evaluated on samples of electricity consumption data measured every half an hour over a period of 1 week.     

Comparison of treatment regimes with adjustment for auxiliary variables

Treatment regimes are algorithms for assigning treatments to patients with complex diseases, where treatment consists of more than one episode of therapy, potentially with different dosages of the same agent or different agents. Sequentially randomized clinical trials are usually designed to evaluate and compare the effect of different treatment regimes. In such designs, eligible patients are first randomly assigned to receive one of the initial treatments. Patients meeting some criteria (e.g. no progressive disease) are then randomized to receive one of the maintenance treatments. Usually, the procedure continues until all treatment options are exhausted. Such multistage treatment assignment results in treatment regimes consisting of initial treatments, intermediate responses and second-stage treatments. However, methods for efficient analysis of sequentially randomized trials have only been developed very recently. As a result, earlier clinical trials reported results based only on the comparison of stage-specific treatments. In this article, we propose a model that applies to comparisons of any combination of any number of treatment regimes regardless of the number of stages of treatment adjusted for auxiliary variables. Contrasts of treatment regimes are tested using the Wald chi-square method. Both the model and Wald chi-square tests of contrasts are illustrated through a simulation study and an application to a high-risk neuroblastoma study to complement the earlier results reported on this study.     

Empirical Processes in Survey Sampling with (Conditional) Poisson Designs

It is the main purpose of this paper to study the asymptotics of certain variants of the empirical process in the context of survey data. Precisely, Functional Central Limit Theorems are established under usual conditions when the sample is drawn from a Poisson or a rejective sampling design. The framework we develop encompasses sampling designs with non‐uniform first order inclusion probabilities, which can be chosen so as to optimize estimation accuracy. Applications to Hadamard differentiable functionals are considered.     

Comparison to control in logistic regression

We are interested in comparing logistic regressions for several test treatments or populations with a logistic regression for a standard treatment or population. The research was motivated by some real life problems, which are discussed as data examples. We propose a step-down likelihood ratio method for declaring differences between the test treatments or populations and the standard treatment or population. Competitors based on the sequentially rejective Bonferroni Wald statistic, sequentially rejective exact Wald statistic and Reiers?l's statistic are also discussed. It is shown that the proposed method asymptotically controls the probability of type I error. A Monte Carlo simulation shows that the proposed method performs well for relatively small sample sizes, outperforming its competitors.     

Optimum properties of latin square designs and a matrix inequality

The paper deals with uniform and D-optimality of designs in the two-way elimination of heterogeneities. It is shown that designs which are optimum for the hypothesis that all treatment effects are equal are optimum for some other hypotheses, too. The Proof is based on a new matrix- and determinantal inequality.