Regression models for analyzing clustered binary and continuous outcomes under an assumption of exchangeability

Scientific experiments commonly result in clustered discrete and continuous data. Existing methods for analyzing such data include the use of quasi-likelihood procedures and generalized estimating equations to estimate marginal mean response parameters. In applications to areas such as developmental toxicity studies, where discrete and continuous measurements are recorded on each fetus, or clinical ophthalmologic trials, where different types of observations are made on each eye, the assumption that data within cluster are exchangeable is often very reasonable. We use this assumption to formulate fully parametric regression models for clusters of bivariate data with binary and continuous components. The regression models proposed have marginal interpretations and reproducible model structures. Tractable expressions for likelihood equations are derived and iterative schemes are given for computing efficient estimates (MLEs) of the marginal mean, correlations, variances and higher moments. We demonstrate the use the ‘exchangeable’ procedure with an application to a developmental toxicity study involving fetal weight and malformation data.     

Nonlinear regression modeling via regularized radial basis function networks

The problem of constructing nonlinear regression models is investigated to analyze data with complex structure. We introduce radial basis functions with hyperparameter that adjusts the amount of overlapping basis functions and adopts the information of the input and response variables. By using the radial basis functions, we construct nonlinear regression models with help of the technique of regularization. Crucial issues in the model building process are the choices of a hyperparameter, the number of basis functions and a smoothing parameter. We present information-theoretic criteria for evaluating statistical models under model misspecification both for distributional and structural assumptions. We use real data examples and Monte Carlo simulations to investigate the properties of the proposed nonlinear regression modeling techniques. The simulation results show that our nonlinear modeling performs well in various situations, and clear improvements are obtained for the use of the hyperparameter in the basis functions.     

A Jackknife Method for Estimation of Variance Components

This paper concerns a method of estimation of variance components in a random effect linear model. It is mainly a resampling method and relies on the Jackknife principle. The derived estimators are presented as least squares estimators in an appropriate linear model, and one of them appears as a MINQUE (Minimum Norm Quadratic Unbiased Estimation) estimator. Our resampling method is illustrated by an example given by C. R. Rao [7] and some optimal properties of our estimator are derived for this example. In the last part, this method is used to derive an estimation of variance components in a random effect linear model when one of the components is assumed to be known.     

Confidence intervals on intraclass correlation coefficients in a balanced two-factor random design

A modified large-sample (MLS) approach and a generalized confidence interval (GCI) approach are proposed for constructing confidence intervals for intraclass correlation coefficients. Two particular intraclass correlation coefficients are considered in a reliability study. Both subjects and raters are assumed to be random effects in a balanced two-factor design, which includes subject-by-rater interaction. Computer simulation is used to compare the coverage probabilities of the proposed MLS approach (GiTTCH) and GCI approaches with the Leiva and Graybill [1986. Confidence intervals for variance components in the balanced two-way model with interaction. Comm. Statist. Simulation Comput. 15, 301–322] method. The competing approaches are illustrated with data from a gauge repeatability and reproducibility study. The GiTTCH method maintains at least the stated confidence level for interrater reliability. For intrarater reliability, the coverage is accurate in several circumstances but can be liberal in some circumstances. The GCI approach provides reasonable coverage for lower confidence bounds on interrater reliability, but its corresponding upper bounds are too liberal. Regarding intrarater reliability, the GCI approach is not recommended because the lower bound coverage is liberal. Comparing the overall performance of the three methods across a wide array of scenarios, the proposed modified large-sample approach (GiTTCH) provides the most accurate coverage for both interrater and intrarater reliability.     

Inferences on the intraclass correlation coefficients in the unbalanced two-way random effects model with interaction

In this paper, the hypothesis testing and interval estimation for the intraclass correlation coefficients are considered in a two-way random effects model with interaction. Two particular intraclass correlation coefficients are described in a reliability study. The tests and confidence intervals for the intraclass correlation coefficients are developed when the data are unbalanced. One approach is based on the generalized p-value and generalized confidence interval, the other is based on the modified large-sample idea. These two approaches simplify to the ones in Gilder et al. [2007. Confidence intervals on intraclass correlation coefficients in a balanced two-factor random design. J. Statist. Plann. Inference 137, 1199–1212] when the data are balanced. Furthermore, some statistical properties of the generalized confidence intervals are investigated. Finally, some simulation results to compare the performance of the modified large-sample approach with that of the generalized approach are reported. The simulation results indicate that the modified large-sample approach performs better than the generalized approach in the coverage probability and expected length of the confidence interval.     

Testing Hypotheses for Variance Components in Mixed Linear Models

In the paper the problem of testing hypotheses for variance components in mixed linear models is considered. It is assumed that covariance matrices commute after using the usual invariance procedure with respect to the group of translations. The test for vanishing of single variance component is based on the locally best quadratic unbiased estimator of this component and rejects hypothesis if the ratio of positive and negative part of this estimator is sufficiently large. The power of this test with powers of other four tests for two-way classification models corresponding to block design is compared.     

Optimal designs in random coefficient cubic regression models

In this article we investigate the problem of ascertaining A- and D-optimal designs in a cubic regression model with random coefficients. Our interest lies in estimation of all the parameters or in only those except the intercept term. Assuming the variance ratios to be known, we tabulate D-optimal designs for various combinations of the variance ratios. A-optimality does not pose any new problem in the random coefficients situation.     

Burden of bioinformatics in medical research: Statistical perspectives and controversies

The ongoing evolution of genomics and bioinformatics has an overwhelming impact on medical and clinical research, albeit this development is often marked by genuine controversies as well as lack of scientific clarities and acumen. The search for disease genes and the gene–environment interaction has drawn considerable interdisciplinary scientific attention: environmental health, clinical and medical sciences, biological as well as computational and statistical sciences are most noteworthy. Statistical reasoning (quantitative modeling and analysis perspectives) has a focal stand in this respect while data mining resolutions are far from being statistically fully understood or interpretable. The use of human subjects, though unavoidable, under various extraneous restraints, medical ethics perspectives, and human rights undercurrents, has raised concern all over the world, especially in the developing countries. In the genomics context, clinical trials may be designed on chips and yet there are greater challenges due to the curse of dimensionality perspectives. Some of these challenging statistical issues in medical and clinical research (with emphasis on clinical trials) are appraised in the light of existing statistical tools, which are available for less complex clinical research problems.     

A graphical summary of disparities in health care and related summary measures

In order to assess the effectiveness of government programs designed to reduce disparities in the health care minority groups receive relative to the majority white population, a proper statistical measure should be used. This article proposes a measure of and its accompanying graph, which is readily interpretable and is not affected by the number of minority subgroups examined.     

Variance estimation in the central limit theorem for Markov chains

This article concerns the variance estimation in the central limit theorem for finite recurrent Markov chains. The associated variance is calculated in terms of the transition matrix of the Markov chain. We prove the equivalence of different matrix forms representing this variance. The maximum likelihood estimator for this variance is constructed and it is proved that it is strongly consistent and asymptotically normal. The main part of our analysis consists in presenting closed matrix forms for this new variance. Additionally, we prove the asymptotic equivalence between the empirical and the maximum likelihood estimation (MLE) for the stationary distribution.     

Considerations on group-wise identical designs for linear mixed models

We consider a general class of mixed models, where the individual parameter vector is composed of a linear function of the population parameter vector plus an individual random effects vector. The linear function can vary for the different individuals. We show that the search for optimal designs for the estimation of the population parameter vector can be restricted to the class of group-wise identical designs, i.e., for each of the groups defined by the different linear functions only one individual elementary design has to be optimized. A way to apply the result to non-linear mixed models is described.     

Pairwise comparisons for proportions estimated by pooled testing

When estimating the prevalence of a rare trait, pooled testing can confer substantial benefits when compared to individual testing. In addition to screening experiments for infectious diseases in humans, pooled testing has also been exploited in other applications such as drug testing, epidemiological studies involving animal disease, plant disease assessment, and screening for rare genetic mutations. Within a pooled-testing context, we consider situations wherein different strata or treatments are to be compared with the goals of assessing significant and practical differences between strata and ranking strata in terms of prevalence. To achieve these goals, we first present two simultaneous pairwise interval estimation procedures for use with pooled data. Our procedures rely on asymptotic results, so we investigate small-sample behavior and compare the two procedures in terms of simultaneous coverage probability and mean interval length. We then present a unified approach to determine pool sizes which deliver desired coverage properties while taking testing costs and interval precision into account. We illustrate our methods using data from an observational HIV study involving heterosexual males who use intravenous drugs.     

On multivariate nonlinear regression models with stationary correlated errors

In this paper we consider the statistical analysis of multivariate multiple nonlinear regression models with correlated errors, using Finite Fourier Transforms. Consistency and asymptotic normality of the weighted least squares estimates are established under various conditions on the regressor variables. These conditions involve different types of scalings, and the scaling factors are obtained explicitly for various types of nonlinear regression models including an interesting model which requires the estimation of unknown frequencies. The estimation of frequencies is a classical problem occurring in many areas like signal processing, environmental time series, astronomy and other areas of physical sciences. We illustrate our methodology using two real data sets taken from geophysics and environmental sciences. The data we consider from geophysics are polar motion (which is now widely known as “Chandlers Wobble”), where one has to estimate the drift parameters, the offset parameters and the two periodicities associated with elliptical motion. The data were first analyzed by Arato, Kolmogorov and Sinai who treat it as a bivariate time series satisfying a finite order time series model. They estimate the periodicities using the coefficients of the fitted models. Our analysis shows that the two dominant frequencies are 12 h and 410 days. The second example, we consider is the minimum/maximum monthly temperatures observed at the Antarctic Peninsula (Faraday/Vernadsky station). It is now widely believed that over the past 50 years there is a steady warming in this region, and if this is true, the warming has serious consequences on ecology, marine life, etc. as it can result in melting of ice shelves and glaciers. Our objective here is to estimate any existing temperature trend in the data, and we use the nonlinear regression methodology developed here to achieve that goal.     

A sequential design for a clinical trial with a linear prognostic factor

We study a randomized adaptive design to assign one of the L$L$ treatments to patients who arrive sequentially by means of an urn model. At each stage n$n$, a reward is distributed between treatments. The treatment applied is rewarded according to its response, 0?_Yn?1$0?Y_n?1$, and 1-_Yn$1-Y_n$ is distributed among the other treatments according to their performance until stage n-1$n-1$. Patients can be classified in K+1$K+1$ levels and we assume that the effect of this level in the response to the treatments is linear. We study the asymptotic behavior of the design when the ordinary least square estimators are used as a measure of performance until stage n-1$n-1$.     

Wilcoxon–Mann–Whitney test for stratified samples and Efron's paradox dice

Two-treatment multi-center clinical trials are the most common type of clinical trials in practice. The aim of this paper is to discuss a curious property of certain standard nonparametric procedures used in the analysis of such clinical trials. Different analyses of a simulated data example are presented, which lead to contrasting and surprising results. The source of the potentially misleading outcome is then explored while relating the simulated data with the concept of Efron's paradox dice and the notion of nontransitivity. With the root of the problem established, an alternate nonparametric method from the literature is shown to address the problem. Finally, pointing out an interpretational concern of using the alternate procedure, a modification to this procedure is also suggested and corresponding theoretical results are presented.     

Union–intersection principle and constrained statistical inference

Most statistical models arising in real life applications as well as in interdisciplinary research are complex in their designs, sampling plans, and associated probability laws, which in turn are often constrained by inequality, order, functional, shape or other restraints. Optimality of conventional likelihood ratio based statistical inference may not be tenable here, although the use of restricted or quasi-likelihood has spurred in such environments. S.N. Roy's ingenious union–intersection principle provides an alternative avenue, often having some computational advantages, increased scope of adaptability, and flexibility beyond conventional likelihood paradigms. This scenario is appraised here with some illustrative examples, and with some interesting problems of inference on stochastic ordering (dominance) in parametric as well as beyond parametric setups.     

Collapsibility of regression coefficients and its extensions

Collapsibility with respect to a measure of association implies that the measure of association can be obtained from the marginal model. We first discuss model collapsibility and collapsibility with respect to regression coefficients for linear regression models. For parallel regression models, we give simple and different proofs of some of the known results and obtain also certain new results. For random coefficient regression models, we define (average) A$A$-collapsibility and obtain conditions under which it holds. We consider Poisson regression and logistic regression models also, and derive conditions for collapsibility and A$A$-collapsibility, respectively. These results generalize some of the results available in the literature. Some suitable examples are also discussed.     

Variance Reduction Using Nonlinear Controls and Transformations

Nonlinear regression-adjusted control variables are investigated for improving variance reduction in statistical and system simulations. To this end, simple control variables are piecewise sectioned and then transformed using linear and nonlinear transformations. Optimal parameters of these transformations are selected using linear or nonlinear least-squares regression algorithms. As an example, piecewise power-transformed variables are used in the estimation of the mean for the twovariable Anderson-Darling goodness-of-fit statistic W ₂ ². Substantial variance reduction over straightforward controls is obtained. These parametric transformations are compared against optimal, additive nonparametric transformations obtained by using the ACE algorithm and are shown, in comparison to the results from ACE, to be nearly optimal.