A comparison of analysis procedures for correlated binary data in dedicated multi‐rater imaging trials

In this paper, three analysis procedures for repeated correlated binary data with no a priori ordering of the measurements are described and subsequently investigated. Examples for correlated binary data could be the binary assessments of subjects obtained by several raters in the framework of a clinical trial. This topic is especially of relevance when success criteria have to be defined for dedicated imaging trials involving several raters conducted for regulatory purposes. First, an analytical result on the expectation of the ‘Majority rater’ is presented when only the marginal distributions of the single raters are given. The paper provides a simulation study where all three analysis procedures are compared for a particular setting. It turns out that in many cases, ‘Average rater’ is associated with a gain in power. Settings were identified where ‘Majority significant’ has favorable properties. ‘Majority rater’ is in many cases difficult to interpret. Copyright © 2014 John Wiley & Sons, Ltd.     

A prior for the variance in hierarchical models

The choice of prior distributions for the variances can be important and quite difficult in Bayesian hierarchical and variance component models. For situations where little prior information is available, a ‘nonin-formative’ type prior is usually chosen. ‘Noninformative’ priors have been discussed by many authors and used in many contexts. However, care must be taken using these prior distributions as many are improper and thus, can lead to improper posterior distributions. Additionally, in small samples, these priors can be ‘informative’. In this paper, we investigate a proper ‘vague’ prior, the uniform shrinkage prior (Strawder-man 1971; Christiansen & Morris 1997). We discuss its properties and show how posterior distributions for common hierarchical models using this prior lead to proper posterior distributions. We also illustrate the attractive frequentist properties of this prior for a normal hierarchical model including testing and estimation. To conclude, we generalize this prior to the multivariate situation of a covariance matrix.     

THE BOOTSTRAP RISK OF LINEAR EMPIRICAL BAYES ESTIMATES

This paper discusses the bootstrap risk of the linear empirical Bayes estimate of the form θ=Ǎ+B̌x, where x is the current observation, and Ǎ and B̌ are generally functions of the estimates of the prior parameters. The standard error of this risk is developed and ‘computations’ of both the bootstrap risk and its standard error are made.     

The use of variance components for the assessment of outcome measures in rheumatology

There is current interest in the development of new or improved outcome measures for rheumatological diseases. In the early stages of development, attention is usually directed to how well the measure distinguishes between patients and whether different observers attach similar values of the measure to the same patient. An approach, based on variance components, to the assessment of outcome measures is presented. The need to assess different aspects of variation associated with a measure is stressed. The terms ‘observer reliability’ and ‘agreement’ are frequently used in the evaluation of measurement instruments, and are often used interchangeably. In this paper, we use the terms to refer to different concepts assessing different aspects of variation. They are likely to correspond well in heterogeneous populations, but not in homogeneous populations where reliability will generally be low but agreement may well be high. Results from a real patient exercise, designed to study a set of tools for assessing myositis outcomes, are used to illustrate the approach that examines both reliability and agreement, and the need to evaluate both is demonstrated. A new measure of agreement, based on the ratio of standard deviations, is presented and inference procedures are discussed. To facilitate the interpretation of the combination of measures of reliability and agreement, a classification system is proposed that provides a summary of the performance of the tools. The approach is demonstrated for discrete ordinal and continuous outcomes.     

Deletion residuals in the detection of heterogeneity of variances in linear regression

The heterogeneity of error variance often causes a huge interpretive problem in linear regression analysis. Before taking any remedial measures we first need to detect this problem. A large number of diagnostic plots are now available in the literature for detecting heteroscedasticity of error variances. Among them the ‘residuals’ and ‘fits’ (R–F) plot is very popular and commonly used. In the R–F plot residuals are plotted against the fitted responses, where both these components are obtained using the ordinary least squares (OLS) method. It is now evident that the OLS fits and residuals suffer a huge setback in the presence of unusual observations and hence the R–F plot may not exhibit the real scenario. The deletion residuals based on a data set free from all unusual cases should estimate the true errors in a better way than the OLS residuals. In this paper we propose ‘deletion residuals’ and the ‘deletion fits’ (DR–DF) plot for the detection of the heterogeneity of error variances in a linear regression model to get a more convincing and reliable graphical display. Examples show that this plot locates unusual observations more clearly than the R–F plot. The advantage of using deletion residuals in the detection of heteroscedasticity of error variance is investigated through Monte Carlo simulations under a variety of situations.     

Dependent radius marks of Laguerre tessellations: a case study

We study a particular marked three-dimensional point process sample that represents a Laguerre tessellation. It comes from a polycrystalline sample of aluminium alloy material. The ‘points’ are the cell generators while the ‘marks’ are radius marks that control the size and shape of the tessellation cells. Our statistical mark correlation analyses show that the marks of the sample are in clear and plausible spatial correlation: the marks of generators close together tend to be small and similar and the form of the correlation functions does not justify geostatistical marking. We show that a simplified modelling of tessellations by Laguerre tessellations with independent radius marks may lead to wrong results. When we started from the aluminium alloy data and generated random marks by random permutation we obtained tessellations with characteristics quite different from the original ones. We observed similar behaviour for simulated Laguerre tessellations. This fact, which seems to be natural for the given data type, makes fitting of models to empirical Laguerre tessellations quite difficult: the generator points and radius marks have to be modelled simultaneously. This may imply that the reconstruction methods are more efficient than point-process modelling if only samples of similar Laguerre tessellations are needed. We also found that literature recipes for bandwidth choice for estimating correlation functions should be used with care.     

Diagnosis of Multivariate Control Chart Signal Based on Dummy Variable Regression Technique

Abstract

It is common to monitor several correlated quality characteristics using the Hotelling's T ² statistic. However, T ² confounds the location shift with scale shift and consequently it is often difficult to determine the factors responsible for out of control signal in terms of the process mean vector and/or process covariance matrix. In this paper, we propose a diagnostic procedure called ‘D-technique’ to detect the nature of shift. For this purpose, two sets of regression equations, each consisting of regression of a variable on the remaining variables, are used to characterize the ‘structure’ of the ‘in control’ process and that of ‘current’ process. To determine the sources responsible for an out of control state, it is shown that it is enough to compare these two structures using the dummy variable multiple regression equation. The proposed method is operationally simpler and computationally advantageous over existing diagnostic tools. The technique is illustrated with various examples.     

A statistical testing framework for evaluating the quality of measurement processes

In this paper we address the evaluation of measurement process quality. We mainly focus on the evaluation procedure, as far as it is based on the numerical outcomes for the measurement of a single physical quantity. We challenge the approach where the ‘exact’ value of the observed quantity is compared with the error interval obtained from the measurements under test and we propose a procedure where reference measurements are used as ‘gold standard’. To this purpose, we designed a specific t-test procedure, explained here. We also describe and discuss a numerical simulation experiment demonstrating the behaviour of our procedure.     

Econometric methodology and the philosophy of science

Econometricians have generally used the term ‘methodology’ to be synonymous with ‘methods’ and, consequently, the field of econometric methodology has been dominated by the discussion of econometric techniques. The purpose of this paper is to present an alternative perspective on econometric methodology by relating it to the more general field of economic methodology, particularly through the use of concepts drawn from the philosophy of science. Definitional and conceptual issues surrounding the term ‘methodology’ are clarified. Three methodologies, representing abstractions from the actual approaches found within econometrics, are identified. First, an ‘a priorist’ methodology, which tends to accord axiomatic status to economic theory, is outlined, and the philosophical foundations of this approach are explored with reference to the interpretive strand within the philosophy of the social sciences. A second approach is an ‘instrumentalist’ one emphasising prediction as the primary goal of econometrics, and a third methodology is ‘falsificationism’, which attempts to test economic theories. These are critically evaluated by introducing relevant issues from the philosophy of science, so that the taxonomy presented here can serve as a framework for future discussions of econometric methodology.     

Statistical testing strategies for assessing treatment efficacy and marker accuracy in phase III trials

When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided.     

LOCATION OF THE OPTIMAL SAMPLING POINT FOR THE QUALITY ASSESSMENT OF CONTINUOUS STREAMS

The paper makes an appraisal of the most appropriate sampling point for situations where a single sample must be used to estimate the mean flow of a continuous stream during a set time interval. Taking ‘optimal’ to mean the point at which the estimation error variance is minimised, optimal sampling locations are obtained for constant, linear and exponential flow rates when the process variogram is assumed linear or exponential. Numerical results illustrate the significance of failing to sample at the optimal point.     

Symmetrically distributed and unbiased estimators in linear models

Let Y be distributed symmetrically about Xβ. Natural generalizations of odd location statistics, say T‘Y’, and even location-free statistics, say W‘Y’, that were used by Hogg ‘1960, 1967)’ are introduced. We show that T‘Y’ is distributed symmetrically about β and thus E[T‘Y’] = β and that each element of T‘Y’ is uncorrelated with each element of W‘Y’. Applications of this result are made to R-estiraators and the result is extended to a multivariate linear model situation.     

关于统计学的性质与发展问题

一、对统计学学科性质的基本认识　　“什么是统计学 ,怎样发展统计学”在我国统计学界是一个有争议的问题。统计学者对统计学的性质问题历来众说纷纭 ,远在 1 869年的第七次国际统计会议上 ,在讨论关于统计学的定义时 ,据说竟有 1 80余种之多。对于学科性质的理解既是学术问题 ,也有思想认识问题 ,只能通过研讨和交流来加深理解 ,以达到提高认识、促进学科健康发展的目的。笔者的基本观点是 :既不赞成统计学属于数学范畴 ,也不赞成统计学属于经济学范畴 ,更不赞成“社会经济统计学”与“数理统计学”分立的观点。我推崇“大统计”思想 ,认…     

Impact of Model Choice on LR Assessment in Case of Rare Haplotype Match (Frequentist Approach)

The likelihood ratio (LR) measures the relative weight of forensic data regarding two hypotheses. Several levels of uncertainty arise if frequentist methods are chosen for its assessment: the assumed population model only approximates the true one, and its parameters are estimated through a limited database. Moreover, it may be wise to discard part of data, especially that only indirectly related to the hypotheses. Different reductions define different LRs. Therefore, it is more sensible to talk about ‘a’ LR instead of ‘the’ LR, and the error involved in the estimation should be quantified. Two frequentist methods are proposed in the light of these points for the ‘rare type match problem’, that is, when a match between the perpetrator's and the suspect's DNA profile, never observed before in the database of reference, is to be evaluated.     

An alternative to the analysis of covariance for comparing randomized treatments

The problem of comparing mean responses for several treatments applied to a common population is considered. The analysis of co-variance ‘ANCOVA’ is frequently used to take advantage of covariate information in this setting, but in many cases ANCOVA's assumption of parallel regression functions precludes the use of ANCOVA. In this paper, an alternative method is developed which does not make this assumption     

Regular graph designs

In this survey paper, measures of optimality of experimental designs are discussed from a combinatorial viewpoint. The main vehicle for this discussion is the regular graph design. This family of designs was introduced in the hope that they would be ‘good’ designs in cases where no balanced incomplete block design can exist. Various properties of these designs are discussed.     

Relation of modified power series distributions to lagrangian probability distributions

The class of Lagrangian probability distributions ‘LPD’, given by the expansion of a probability generating function f‘t’ under the transformation u = t/g‘t’ where g ‘t’ is also a p.g.f., has been substantially widened by removing the restriction that the defining functions g ‘t’ and f‘t’ be probability generating functions. The class of modified power series distributions defined by Gupta ‘1974’ has been shown to be a sub-class of the wider class of LPDs     

The 'improved' brown and forsythe test for mean equality: some things can't be fixed

Mehrotra (1997) presented an ‘;improved’ Brown and Forsythe (1974) statistic which is designed to provide a valid test of mean equality in independent groups designs when variances are heterogeneous. In particular, the usual Brown and Fosythe procedure was modified by using a Satterthwaite approximation for numerator degrees of freedom instead of the usual value of number of groups minus one. Mehrotra then, through Monte Carlo methods, demonstrated that the ‘improved’ method resulted in a robust test of significance in cases where the usual Brown and Forsythe method did not. Accordingly, this ‘improved’ procedure was recommended. We show that under conditions likely to be encountered in applied settings, that is, conditions involving heterogeneous variances as well as nonnormal data, the ‘improved’ Brown and Forsythe procedure results in depressed or inflated rates of Type I error in unbalanced designs. Previous findings indicate, however, that one can obtain a robust test by adopting a heteroscedastic statistic with the robust estimators, rather than the usual least squares estimators, and further improvement can be expected when critical significance values are obtained through bootstrapping methods.     

ESTIMATION OF THE CONDITIONAL PROBABILITY OF TUBERCULOSIS GIVEN THE RESPONSE OF A MANTOUX TEST

For the planning of community tuberculosis, prophylaxis one must know the prevalence of tuberculosis (TB) infection as a function of response to the Mantoux intradermal tuberculin test; the standard test for indicating Mycobacterium TB infection. The skin induration size used to select individuals for prophylaxis must be chosen carefully, in view of the costs associated with carrying out and supervising such prophylaxis. The Mantoux test was used to obtain measurements on adolescents in metropolitan Victoria and on a small sample of adolescents with clinical TB. These data are employed to obtain estimates and to construct upper confidence bounds for the conditional probability of TB infection, given the level of Mantoux response. Two conservative methods are presented; one is ‘nonparametric’, the other ‘semiparametric’. The analyses indicate that for responses up to and including 13 mm, the probability of TB infection is less than.07 with ninety-five percent confidence.     

A nonparametric maximum likelihood approach for survival data with observed cured subjects,left truncation and right-censoring

We consider observational studies in pregnancy where the outcome of interest is spontaneous abortion (SAB). This at first sight is a binary ‘yes’ or ‘no’ variable, albeit there is left truncation as well as right-censoring in the data. Women who do not experience SAB by gestational week 20 are ‘cured’ from SAB by definition, that is, they are no longer at risk. Our data is different from the common cure data in the literature, where the cured subjects are always right-censored and not actually observed to be cured. We consider a commonly used cure rate model, with the likelihood function tailored specifically to our data. We develop a conditional nonparametric maximum likelihood approach. To tackle the computational challenge we adopt an EM algorithm making use of “ghost copies” of the data, and a closed form variance estimator is derived. Under suitable assumptions, we prove the consistency of the resulting estimator which involves an unbounded cumulative baseline hazard function, as well as the asymptotic normality. Simulation results are carried out to evaluate the finite sample performance. We present the analysis of the motivating SAB study to illustrate the advantages of our model addressing both occurrence and timing of SAB, as compared to existing approaches in practice.