A response-adaptive design in crossover trial

In the present work, whenever the response variables are binary, we frame an adaptive allocation rule for a two-treatment two-period crossover design in the presence of possible carry-over effects. The proposed rule is a combination of the play-the-winner and randomized play-the-winner rules. We study various properties of the proposed rule through asymptotics and simulations. Some related inferential problems are also considered. The proposed procedure is compared with some possible competitor.     

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.     

Exact sample-size determination in testing non-inferiority under a simple crossover trial

For testing the non-inferiority (or equivalence) of an experimental treatment to a standard treatment, the odds ratio (OR) of patient response rates has been recommended to measure the relative treatment efficacy. On the basis of an exact test procedure proposed elsewhere for a simple crossover design, we develop an exact sample-size calculation procedure with respect to the OR of patient response rates for a desired power of detecting non-inferiority at a given nominal type I error. We note that the sample size calculated for a desired power based on an asymptotic test procedure can be much smaller than that based on the exact test procedure under a given situation. We further discuss the advantage and disadvantage of sample-size calculation using the exact test and the asymptotic test procedures. We employ an example by studying two inhalation devices for asthmatics to illustrate the use of sample-size calculation procedure developed here.     

Notes on estimation of the intraclass correlation under the AB/BA crossover trial

Under the AB/BA crossover trial, we focus our attention on estimation of the intraclass correlation in normal data. We develop both point and interval estimators in closed form for the intraclass correlation. We employ Monte Carlo simulation to study the performance of these estimators in a variety of situations. We note that the estimators developed here for the intraclass correlation remain valid even when there are possibly unexpected carry-over effects.     

Notes on interval estimation of the proportion ratio under a three-treatment three-period crossover trial

When comparing two experimental treatments with a placebo, we focus our attention on interval estimation of the proportion ratio (PR) of patient responses under a three-period crossover design. We propose a random effects exponential multiplicative risk model and derive asymptotic interval estimators in closed form for the PR between treatments and placebo. Using Monte Carlo simulations, we compare the performance of these interval estimators in a variety of situations. We use the data comparing two different doses of an analgesic with placebo for the relief of primary dysmenorrhea to illustrate the use of these interval estimators and the difference in estimates of the PR and odds ratio (OR) when the underlying relief rates are not small.     

Sample size determination for testing equality in Poisson frequency data under an AB/BA crossover trial

Assuming that the frequency of occurrence follows the Poisson distribution, we develop sample size calculation procedures for testing equality based on an exact test procedure and an asymptotic test procedure under an AB/BA crossover design. We employ Monte Carlo simulation to demonstrate the use of these sample size formulae and evaluate the accuracy of sample size calculation formula derived from the asymptotic test procedure with respect to power in a variety of situations. We note that when both the relative treatment effect of interest and the underlying intraclass correlation between frequencies within patients are large, the sample size calculation based on the asymptotic test procedure can lose accuracy. In this case, the sample size calculation procedure based on the exact test is recommended. On the other hand, if the relative treatment effect of interest is small, the minimum required number of patients per group will be large, and the asymptotic test procedure will be valid for use. In this case, we may consider use of the sample size calculation formula derived from the asymptotic test procedure to reduce the number of patients needed for the exact test procedure. We include an example regarding a double‐blind randomized crossover trial comparing salmeterol with a placebo in exacerbations of asthma to illustrate the practical use of these sample size formulae. Copyright © 2013 John Wiley & Sons, Ltd.     

Multivariate Control Chart Based on Multivariate Smirnov Test

Robust control charts are useful in statistical process control (SPC) when there is limited knowledge about the underlying process distribution, especially for multivariate observations. This article develops a new robust and self-starting multivariate procedure based on multivariate Smirnov test (MST), which integrates a multivariate two-sample goodness-of-fit (GOF) test based on multivariate empirical distribution function (MEDF) and the change-point model. As expected, simulation results show that our proposed control chart is robust to nonnormally distributed data, and moreover, it is efficient in detecting process shifts, especially large shifts, which is one of the main drawbacks of most robust control charts in the literature. As it avoids the need for a lengthy data-gathering step, the proposed chart is particularly useful in start-up or short-run situations. Comparison results and a real data example show that our proposed chart has great potential for application.     

Multivariate geometric distributions

Families of multivariate geometric distributions with flexible correlations can be constructed by applying inverse sampling to a sequence of multinomial trials, and counting outcomes in possibly overlapping categories. Further multivariate families can be obtained by considering other stopping rules, with the possibility of different stopping roles for different counts, A simple characterisation is given for stopping rules which produce joint distributions with marginals having the same form as that of the number of trials. The inverse sampling approach provides a unified treatment of diverse results presented by earlier authors, including Goldberg (1934), Bates and Meyman (1952), Edwards and Gurland (1961), Hawkes (1972), Paulson and Uppulori (1972) and Griffiths and Milne (1987). It also provides a basis for investigating the range of possible correlations for a given set of marginal parameters. In the case of more than two joint geometric or negative binomial variables, a convenient matrix formulation is provided.     

Multivariate quality control

This paper includes both the motivation for multivariate quality control, and a discussion of some ot rhe techniques currently available. The emphasis focuses primarily on control charts and includes the T² -chart, the use of principal components anm some recent developments, multivariate analogs of CUSUM cnarts and the use of the Andrews procedure. Some of the problems associated with multivariate acceptance sampling are presented, and the paper concludes with some recommendauons for future researcn and development.     

Multivariate order statistics

Classical order statistics are generalized to random samples from continuous multivariate distributions.     

Multivariate parabolic bioassay

A general linear model approach to quantitative parabolic bioassays with multivariate responses is proposed. The point and interval estimator of the relative potency and an associated test for validity is presented. The relationships with known univariate methods are illustrated.     

Multivariate outbreak detection

Online monitoring is needed to detect outbreaks of diseases such as influenza. Surveillance is also needed for other kinds of outbreaks, in the sense of an increasing expected value after a constant period. Information on spatial location or other variables might be available and may be utilized. We adapted a robust method for outbreak detection to a multivariate case. The relation between the times of the onsets of the outbreaks at different locations (or some other variable) was used to determine the sufficient statistic for surveillance. The derived maximum-likelihood estimator of the outbreak regression was semi-parametric in the sense that the baseline and the slope were non-parametric while the distribution belonged to the one-parameter exponential family. The estimator was used in a generalized-likelihood ratio surveillance method. The method was evaluated with respect to robustness and efficiency in a simulation study and applied to spatial data for detection of influenza outbreaks in Sweden.     

Notes on estimation of the proportion ratio in the presence of carryover effects under the AB/BA crossover trial

The authors focus discussion on estimation of the proportion ratio (PR) in the presence of residual effects under the AB/BA design. Under a random effects multiplicative risk model, we develop three point estimators and three interval estimators accounting for residual effects for the PR. Using Monte Carlo simulations, we compare the performance of these point (or interval) estimators with point (or interval) estimators assuming no residual effects with respect to the bias and mean-squared-error (or the coverage probability and average length). The authors use the data taken from an AB/BA trial comparing two new inhalation devices to illustrate the use of these estimators.     

Multivariate Three-Parameter Log-Elliptical Distributions

The three-parameter log-elliptical distribution class is developed for the general situation in which the hypothesis of independence for the elements in a sample is not assumed. The parameter estimators are theoretically showed to be invariant under all distributions in the class by considering only a change in the constant of the scale parameter estimator. An estimation procedure based on the three-parameter lognormal distribution is proposed for the parameter estimation problem in any three-parameter log-elliptical distribution. Two classical lognormal data sets are analyzed without assuming independence in the sample in order to illustrate the proposed estimation procedure.     

Multivariate tests for non-additivity

A full bivariate generalization of the Anscombe-Tukey one degree of freedom for univariate non-additivity is presented, and is compared to other proposals. Higher dimensional extensions follow directly. In general, k(k+1)/2 degrees of freedom can be allocated to assessing non-additivity in k dimensions. Hence coordinate-wise additivity is necessary but not sufficient for multivariate additivity.     

Multivariate geometric skew-normal distribution

Azzalini [A class of distributions which include the normal. Scand J Stat. 1985;12:171–178] introduced a skew-normal distribution of which normal distribution is a special case. Recently, Kundu [Geometric skew normal distribution. Sankhya Ser B. 2014;76:167–189] introduced a geometric skew-normal distribution and showed that it has certain advantages over Azzalini's skew-normal distribution. In this paper we discuss about the multivariate geometric skew-normal (MGSN) distribution. It can be used as an alternative to Azzalini's skew-normal distribution. We discuss different properties of the proposed distribution. It is observed that the joint probability density function of the MGSN distribution can take a variety of shapes. Several characterization results have been established. Generation from an MGSN distribution is quite simple, hence the simulation experiments can be performed quite easily. The maximum likelihood estimators of the unknown parameters can be obtained quite conveniently using the expectation–maximization (EM) algorithm. We perform some simulation experiments and it is observed that the performances of the proposed EM algorithm are quite satisfactory. Furthermore, the analyses of two data sets have been performed, and it is observed that the proposed methods and the model work very well.     

Testing for Multivariate Autocorrelation

This paper concerns the problem of assessing autocorrelation of multivariate (i.e. systemwise) models. It is well known that systemwise diagnostic tests for autocorrelation often suffers from poor small sample properties in the sense that the true size overstates the nominal size. The failure of keeping control of the size usually stems from the fact that the critical values (used to decide the rejection area) originate from the slowly converging asymptotic null distribution. Another drawback of existing tests is that the power may be rather low if the deviation from the null is not symmetrical over the marginal models. In this paper we consider four quite different test techniques for autocorrelation. These are (i) Pillai's trace, (ii) Roy's largest root, (iii) the maximum F-statistic and (iv) the maximum t² test. We show how to obtain control of the size of the tests, and then examine the true (small sample) size and power properties by means of Monte Carlo simulations.     

Robust Multivariate Outlier Labeling

A criterion for robust estimation of location and covariance matrix is considered, and its application in outlier labeling is discussed. This method, unlike the methods based on MVE and MCD, is applicable to large and high-dimension data sets. The method proposed here is also robust and has the same breakdown point as the MVE- and MCD-based methods. Furthermore, the computational complexity of the proposed method is significantly smaller than that of other methods.     

Multivariate Process Variability Monitoring

Understanding multivariate variability is a difficult task because there is no single measure that can be properly used. This article presents a new measure that features good properties. If this measure is simultaneously used with generalized variance, it will give a better understanding of multivariate variability. It can also efficiently be used for large data sets with high dimensions. Furthermore, when it is used for constructing a Shewhart-type chart to monitor multivariate variability, the resulting chart has a much better out-of-control ARL than the generalized variance chart. An example illustrates its advantage.