Robustness of the shrinkage estimator for the relative potency in the combination of multivariate bioassays

ABSTRACT

This article investigates the robustness of the shrinkage Bayesian estimator for the relative potency parameter in the combinations of multivariate bioassays proposed in Chen et al. (1999 Chen, D.G., Carter, E.M., Hubert, J.J., Kim, P.T. (1999). Empirical Bayesian estimation for combinations of multivariate bioassays. Biometrics 55(4):1035–1043. [Google Scholar]), which incorporated prior information on the model parameters based on Jeffreys’ rules. This investigation is carried out for the families of t-distribution and Cauchy-distribution based on the characteristics of bioassay theory since the t-distribution approaches the normal distribution which is the most commonly used distribution in the applications of bioassay as the degrees of freedom increases and the t-distribution approaches the Cauchy-distribution as the degrees of freedom approaches 1 which is also an important distribution in bioassay. A real data is used to illustrate the application of this investigation. This analysis further supports the application of the shrinkage Bayesian estimator to the theory of bioassay along with the empirical Bayesian estimator.     

Incomplete block designs for asymmetric parallel line assays

Abstract

A method of construction of A-optimal binary block designs for asymmetrical parallel line assays, i.e., the assays in which the number doses for standard and test preparation are unequal has been considered. The method is illustrated with examples. Two cases of this method have been considered. In the first case, designs obtained are of equal replications of the doses. In the second case, designs with unequal replications are obtained.     

Estimation of multivariate conditional-tail-expectation using Kendall's process

This paper deals with the problem of estimating the multivariate version of the Conditional-Tail-Expectation, proposed by Di Bernardino et al. [(2013), ‘Plug-in Estimation of Level Sets in a Non-Compact Setting with Applications in Multivariable Risk Theory’, ESAIM: Probability and Statistics, (17), 236–256]. We propose a new nonparametric estimator for this multivariate risk-measure, which is essentially based on Kendall's process [Genest and Rivest, (1993), ‘Statistical Inference Procedures for Bivariate Archimedean Copulas’, Journal of American Statistical Association, 88(423), 1034–1043]. Using the central limit theorem for Kendall's process, proved by Barbe et al. [(1996), ‘On Kendall's Process’, Journal of Multivariate Analysis, 58(2), 197–229], we provide a functional central limit theorem for our estimator. We illustrate the practical properties of our nonparametric estimator on simulations and on two real test cases. We also propose a comparison study with the level sets-based estimator introduced in Di Bernardino et al. [(2013), ‘Plug-In Estimation of Level Sets in A Non-Compact Setting with Applications in Multivariable Risk Theory’, ESAIM: Probability and Statistics, (17), 236–256] and with (semi-)parametric approaches.     

A comparison of statistical methods for combining relative bioactivities from parallel line bioassays

This paper compares the ordinary unweighted average, weighted average, and maximum likelihood methods for estimating a common bioactivity from multiple parallel line bioassays. Some of these or similar methods are also used in meta‐analysis. Based on a simulation study, these methods are assessed by comparing coverage probabilities of the true relative bioactivity and the length of the confidence intervals computed for these methods. The ordinary unweighted average method outperforms all statistical methods by consistently giving the best coverage probability but with somewhat wider confidence intervals. The weighted average methods give good coverage and smaller confidence intervals when combining homogeneous bioactivities. For heterogeneous bioactivities, these methods work well when a liberal significance level for testing homogeneity of bioactivities is used. The maximum likelihood methods gave good coverage when homogeneous bioactivities were considered. Overall, the preferred methods are the ordinary unweighted average and two weighted average methods that were specifically developed for bioassays. Copyright © 2013 John Wiley & Sons, Ltd.     

A randomized Baumgartner statistic for multivariate two-sample testing hypothesis

In this paper, multivariate two-sample testing problems were examined based on the Jure?ková–Kalina's ranks of distances. The multivariate two-sample rank test based on the modified Baumgartner statistic for the two-sided alternative was proposed. The proposed statistic was a randomized statistic. Simulations were used to investigate the power of the suggested statistic for various population distributions.     

Properties of two tests for outliers in multivariate data

Mardia's multivariate kurtosis and the generalized distance have desirable properties as multivariate outlier tests. However, extensive critical values have not been published heretofore. A published approximation formula for critical values of the kurtosis is shown to inadequately control the type I error rate, with observed error rates often differing from their intended values by a factor of two or more. Critical values derived from simulations for both tests for up to 25 dimensions and 500 observations are presented. The power curves of both tests are discussed. The generalized distance is the more powerful test when exactly one outlier is present and the contaminant is substantially mean-shifted. However, as the number of outliers increases, the kurtosis becomes the more powerful test. The two tests are compared with respect to power and vulnerability to masking. Recommendations for the use of these tests and interpretation of results are given.     

Integration of classification algorithms and control chart techniques for monitoring multivariate processes

We propose new multivariate control charts that can effectively deal with massive amounts of complex data through their integration with classification algorithms. We call the proposed control chart the ‘Probability of Class (PoC) chart’ because the values of PoC, obtained from classification algorithms, are used as monitoring statistics. The control limits of PoC charts are established and adjusted by the bootstrap method. Experimental results with simulated and real data showed that PoC charts outperform Hotelling's T ² control charts. Further, a simulation study revealed that a small proportion of out-of-control observations are sufficient for PoC charts to achieve the desired performance.     

A note on the inequalities for tail probability of the multivariate normal distribution

In this paper inequalities given by Harkness Godambe (1976) for the rail probabilities of the multivariate normal distribution in the equicorrelated case are improved by using the properties of the characteristic roots of a matrix and of the convex function.     

Combining Multivariate Bioassays: Accurate Inference Using Small Sample Asymptotics

For several independent multivariate bioassays performed at different laboratories or locations, the problem of testing the homogeneity of the relative potencies is addressed, assuming the usual slope‐ratio or parallel line assay model. When the homogeneity hypothesis holds, interval estimation of the common relative potency is also addressed. These problems have been investigated in the literature using likelihood‐based methods, under the assumption of a common covariance matrix across the different studies. This assumption is relaxed in this investigation. Numerical results show that the usual likelihood‐based procedures are inaccurate for both of the above problems, in terms of providing inflated type I error probabilities for the homogeneity test, and providing coverage probabilities below the nominal level for the interval estimation of the common relative potency, unless the sample sizes are large, as expected. Correction based on small sample asymptotics is investigated in this article, and this provides significantly more accurate results in the small sample scenario. The results are also illustrated with examples.     

Asymptotic Comparison of Two Discriminants Used in Normal Covariate Classification

In this paper, we examine the performance of Anderson's classification statistic with covariate adjustment in comparison with the usual Anderson's classification statistic without covariate adjustment in a two-population normal covariate classification problem. The same problem has been investigated using different methods of comparison by some authors. See the bibliography. The aim of this paper is to give a direct comparison based upon the asymptotic probabilities of misclassification. It is shown that for large equal sample size of a training sample from each population, Anderson's classification statistic with covariate adjustment and cut-off point equal to zero, has better performance.     

Estimation of a multivariate normal covariance matrix under a certain structure

We consider the estimation of Σ of the p-dimensional normal distribution N_p (0, Σ) when Σ?=?θ₀ I_p ?+?θ₁ aa′, where a is an unknown p-dimensional normalized vector and θ₀?>?0, θ₁?≥?0 are also unknown. First, we derive the restricted maximum likelihood (REML) estimator. Second, we propose a new estimator, which dominates the REML estimator with respect to Stein's loss function. Finally, we carry out Monte Carlo simulation to investigate the magnitude of the new estimator's superiority.     

Proportion estimation in mixtures with covariates

Linear maps of a single unclassified observation are used to estimate the mixing proportion in a mixture of two populations with homogeneous variances in the presence of covariates. with complete knowledge of the parameters of the individual populations, the linear map for which the estimator is unbiased and has minimum variance amongst all similar estimators can be determined. Plug-in estimator based on independent training samples from the component populations can be constructed and is asymptotically equivalent to Cochran's classification statistic V* for covariate classification; see Memon and Okamoto (1970). Under normality assumptions, asymptotic expansion of the distribution of the plug-in estimator is available. In the absence of covariates, our estimator reduces to that suggested by Walker (1980) who has investigated the problem based on information on large unclassified samples from a mixture of two populations with heterogeneous variances. In contrast, distribution of Walker's estimator seems intractable in moderate sample sizes even with normality assumption.     

A new multivariate CUSUM chart using principal components with a revision of Crosier's chart

In this article, we introduce a new multivariate cumulative sum chart, where the target mean shift is assumed to be a weighted sum of principal directions of the population covariance matrix. This chart provides an attractive performance in terms of average run length (ARL) for large-dimensional data and it also compares favorably to existing multivariate charts including Crosier's benchmark chart with updated values of the upper control limit and the associated ARL function. In addition, Monte Carlo simulations are conducted to assess the accuracy of the well-known Siegmund's approximation of the average ARL function when observations are normal distributed. As a byproduct of the article, we provide updated values of upper control limits and the associated ARL function for Crosier's multivariate CUSUM chart.     

Comparing several experimental groups with a control in the multivariate case

This paper presents a multivariate extension of Dunnett's test for comparing simultaneously k treatment group means with a single control group mean. A test based on Hotelling T²statistics is presented and approximate critical values are evaluated for the case of equal numbers of observations in each group, for the .05 and .01 levels of significance, for 1 to 5 variates, for 1 to 10 treatment groups, and for varying degrees of freedom. The accuracy of the procedure for generating approximate critical values is assessed via simulation studies conducted for selected cases and an example is presented using real data.     

Hayter and Tsui's test with double sampling for the vector mean of multivariate normal population

Abstract

In this paper, we introduce a version of Hayter and Tsui's statistical test with double sampling for the vector mean of a population under multivariate normal assumption. A study showed that this new test was more or as efficient than the well-known Hotelling's T² with double sampling. Some nice features of Hayter and Tsui's test are its simplicity of implementation and its capability of identifying the errant variables when the null hypothesis is rejected. Taking that into consideration, a new control chart called HTDS is also introduced as a tool to monitor multivariate process vector mean when using double sampling.     

Estimation of a common mean vector in bivariate meta-analysis under the FGM copula

We propose a bivariate Farlie–Gumbel–Morgenstern (FGM) copula model for bivariate meta-analysis, and develop a maximum likelihood estimator for the common mean vector. With the aid of novel mathematical identities for the FGM copula, we derive the expression of the Fisher information matrix. We also derive an approximation formula for the Fisher information matrix, which is accurate and easy to compute. Based on the theory of independent but not identically distributed (i.n.i.d.) samples, we examine the asymptotic properties of the estimator. Simulation studies are given to demonstrate the performance of the proposed method, and a real data analysis is provided to illustrate the method.     

Application of numerical interval analysis to obtain self-validating results for multivariate probabilities in a massively parallel environment

Conventional computations use real numbers as input and produce real numbers as results without any indication of the accuracy. Interval analysis, instead, uses interval elements throughout the computation and produces intervals as output with the guarantee that the true results are contained in them. One major use for interval analysis in statistics is to get results of high-dimensional multivariate probabilities. With the efforts to decrease the length of the intervals that contain the theoretically true answers, we can obtain results to any arbitrary accuracy, which is demonstrated by multivariate normal and multivariate t integrations. This is an advantage over the approximation methods that are currently in use. Since interval analysis is more computationally intensive than traditional computing, a MasPar parallel computer is used in this research to improve performance.     

Analysis of binary data in the randomized complete block design

The technique proposed by Shah and Claypool (1984) is extended here for the randomized complete block design with one binary observation per cell. In addition, it provides an al- ternative derivation of the distribution of Cochran's Q sta- tistic which is straightforward.