A comparison study on modeling of clustered and overdispersed count data for multiple comparisons

Data collected in various scientific fields are count data. One way to analyze such data is to compare the individual levels of the factor treatment using multiple comparisons. However, the measured individuals are often clustered – e.g. according to litter or rearing. This must be considered when estimating the parameters by a repeated measurement model. In addition, ignoring the overdispersion to which count data is prone leads to an increase of the type one error rate. We carry out simulation studies using several different data settings and compare different multiple contrast tests with parameter estimates from generalized estimation equations and generalized linear mixed models in order to observe coverage and rejection probabilities. We generate overdispersed, clustered count data in small samples as can be observed in many biological settings. We have found that the generalized estimation equations outperform generalized linear mixed models if the variance-sandwich estimator is correctly specified. Furthermore, generalized linear mixed models show problems with the convergence rate under certain data settings, but there are model implementations with lower implications exists. Finally, we use an example of genetic data to demonstrate the application of the multiple contrast test and the problems of ignoring strong overdispersion.     

Variance estimation based on blocked 3×2 cross-validation in high-dimensional linear regression

In high-dimensional linear regression, the dimension of variables is always greater than the sample size. In this situation, the traditional variance estimation technique based on ordinary least squares constantly exhibits a high bias even under sparsity assumption. One of the major reasons is the high spurious correlation between unobserved realized noise and several predictors. To alleviate this problem, a refitted cross-validation (RCV) method has been proposed in the literature. However, for a complicated model, the RCV exhibits a lower probability that the selected model includes the true model in case of finite samples. This phenomenon may easily result in a large bias of variance estimation. Thus, a model selection method based on the ranks of the frequency of occurrences in six votes from a blocked 3×2 cross-validation is proposed in this study. The proposed method has a considerably larger probability of including the true model in practice than the RCV method. The variance estimation obtained using the model selected by the proposed method also shows a lower bias and a smaller variance. Furthermore, theoretical analysis proves the asymptotic normality property of the proposed variance estimation.     

Testing for bioequivalence of highly variable drugs from TR‐RT crossover designs with heterogeneous residual variances

Traditional bioavailability studies assess average bioequivalence (ABE) between the test (T) and reference (R) products under the crossover design with TR and RT sequences. With highly variable (HV) drugs whose intrasubject coefficient of variation in pharmacokinetic measures is 30% or greater, assertion of ABE becomes difficult due to the large sample sizes needed to achieve adequate power. In 2011, the FDA adopted a more relaxed, yet complex, ABE criterion and supplied a procedure to assess this criterion exclusively under TRR‐RTR‐RRT and TRTR‐RTRT designs. However, designs with more than 2 periods are not always feasible. This present work investigates how to evaluate HV drugs under TR‐RT designs. A mixed model with heterogeneous residual variances is used to fit data from TR‐RT designs. Under the assumption of zero subject‐by‐formulation interaction, this basic model is comparable to the FDA‐recommended model for TRR‐RTR‐RRT and TRTR‐RTRT designs, suggesting the conceptual plausibility of our approach. To overcome the distributional dependency among summary statistics of model parameters, we develop statistical tests via the generalized pivotal quantity (GPQ). A real‐world data example is given to illustrate the utility of the resulting procedures. Our simulation study identifies a GPQ‐based testing procedure that evaluates HV drugs under practical TR‐RT designs with desirable type I error rate and reasonable power. In comparison to the FDA's approach, this GPQ‐based procedure gives similar performance when the product's intersubject standard deviation is low (≤0.4) and is most useful when practical considerations restrict the crossover design to 2 periods.     

Forecast mean squared error reductionin the VAR(1) process

When VAR models are used to predict future outcomes, the forecast error can be substantial. Through imposition of restrictions on the off-diagonal elements of the parameter matrix, however, the information in the process may be condensed to the marginal processes. In particular, if the cross-autocorrelations in the system are small and only a small sample is available, then such a restriction may reduce the forecast mean squared error considerably.

In this paper, we propose three different techniques to decide whether to use the restricted or unrestricted model, i.e. the full VAR(1) model or only marginal AR(1) models. In a Monte Carlo simulation study, all three proposed tests have been found to behave quite differently depending on the parameter setting. One of the proposed tests stands out, however, as the preferred one and is shown to outperform other estimators for a wide range of parameter settings.     

Conditional variance estimation in heteroscedastic regression models

First, we propose a new method for estimating the conditional variance in heteroscedasticity regression models. For heavy tailed innovations, this method is in general more efficient than either of the local linear and local likelihood estimators. Secondly, we apply a variance reduction technique to improve the inference for the conditional variance. The proposed methods are investigated through their asymptotic distributions and numerical performances.     

Quasi-minimax estimation in the general linear regression model

This paper is mainly concerned with minimax estimation in the general linear regression model y=Xβ+ε$y=X\beta +\epsilon$ under ellipsoidal restrictions on the parameter space and quadratic loss function. We confine ourselves to estimators that are linear in the response vector y  . The minimax estimators of the regression coefficient β$\beta$ are derived under homogeneous condition and heterogeneous condition, respectively. Furthermore, these obtained estimators are the ridge-type estimators and mean dispersion error (MDE) superior to the best linear unbiased estimator b=(X^′W^-1X)^-1X^′W^-1y$b=(X^{\prime }{W}^{-1}X{)}^{-1}{X}^{\prime }{W}^{-1}y$ under some conditions.     

Transformed generalized linear models

The estimation of data transformation is very useful to yield response variables satisfying closely a normal linear model. Generalized linear models enable the fitting of models to a wide range of data types. These models are based on exponential dispersion models. We propose a new class of transformed generalized linear models to extend the Box and Cox models and the generalized linear models. We use the generalized linear model framework to fit these models and discuss maximum likelihood estimation and inference. We give a simple formula to estimate the parameter that index the transformation of the response variable for a subclass of models. We also give a simple formula to estimate the r$r$th moment of the original dependent variable. We explore the possibility of using these models to time series data to extend the generalized autoregressive moving average models discussed by Benjamin et al. [Generalized autoregressive moving average models. J. Amer. Statist. Assoc. 98, 214–223]. The usefulness of these models is illustrated in a simulation study and in applications to three real data sets.     

Confidence interval estimation of the difference between paired AUCs based on combined biomarkers

In many diagnostic studies, multiple diagnostic tests are performed on each subject or multiple disease markers are available. Commonly, the information should be combined to improve the diagnostic accuracy. We consider the problem of comparing the discriminatory abilities between two groups of biomarkers. Specifically, this article focuses on confidence interval estimation of the difference between paired AUCs based on optimally combined markers under the assumption of multivariate normality. Simulation studies demonstrate that the proposed generalized variable approach provides confidence intervals with satisfying coverage probabilities at finite sample sizes. The proposed method can also easily provide P-values for hypothesis testing. Application to analysis of a subset of data from a study on coronary heart disease illustrates the utility of the method in practice.     

A note on the equality of the OLSE and the BLUE of the parametric function in the general Gauss–Markov model

In this note we consider the equality of the ordinary least squares estimator (OLSE) and the best linear unbiased estimator (BLUE) of the estimable parametric function in the general Gauss–Markov model. Especially we consider the structures of the covariance matrix V for which the OLSE equals the BLUE. Our results are based on the properties of a particular reparametrized version of the original Gauss–Markov model.