Model averaging inconcentration–QT analyses

This article describes how a frequentist model averaging approach can be used for concentration–QT analyses in the context of thorough QTc studies. Based on simulations, we have concluded that starting from three candidate model families (linear, exponential, and Emax) the model averaging approach leads to treatment effect estimates that are quite robust with respect to the control of the type I error in nearly all simulated scenarios; in particular, with the model averaging approach, the type I error appears less sensitive to model misspecification than the widely used linear model. We noticed also few differences in terms of performance between the model averaging approach and the more classical model selection approach, but we believe that, despite both can be recommended in practice, the model averaging approach can be more appealing because of some deficiencies of model selection approach pointed out in the literature. We think that a model averaging or model selection approach should be systematically considered for conducting concentration–QT analyses. Copyright © 2016 John Wiley & Sons, Ltd.     

A Comparison of Some Methods for the Selection of a Common Eigenvector Model for the Covariance Matrices of Two Groups

Two new nonparametric common principal component model selection procedures based on bootstrap distributions of the vector correlations of all combinations of the eigenvectors from two groups are proposed. The performance of these methods is compared in a simulation study to the two parametric methods previously suggested by Flury in 1988, as well as modified versions of two nonparametric methods proposed by Klingenberg in 1996 and then by Klingenberg and McIntyre in 1998. The proposed bootstrap vector correlation distribution (BVD) method is shown to outperform all of the existing methods in most of the simulated situations considered.     

A New Quantile Function with Applications to Reliability Analysis

In this article, we propose a new class of distributions defined by a quantile function, which nests several distributions as its members. The quantile function proposed here is the sum of the quantile functions of the generalized Pareto and Weibull distributions. Various distributional properties and reliability characteristics of the class are discussed. The estimation of the parameters of the model using L-moments is studied. Finally, we apply the model to a real life dataset.     

Asymmetric Forecast Densities for U.S. Macroeconomic Variables from a Gaussian Copula Model of Cross-Sectional and Serial Dependence

Most existing reduced-form macroeconomic multivariate time series models employ elliptical disturbances, so that the forecast densities produced are symmetric. In this article, we use a copula model with asymmetric margins to produce forecast densities with the scope for severe departures from symmetry. Empirical and skew t distributions are employed for the margins, and a high-dimensional Gaussian copula is used to jointly capture cross-sectional and (multivariate) serial dependence. The copula parameter matrix is given by the correlation matrix of a latent stationary and Markov vector autoregression (VAR). We show that the likelihood can be evaluated efficiently using the unique partial correlations, and estimate the copula using Bayesian methods. We examine the forecasting performance of the model for four U.S. macroeconomic variables between 1975:Q1 and 2011:Q2 using quarterly real-time data. We find that the point and density forecasts from the copula model are competitive with those from a Bayesian VAR. During the recent recession the forecast densities exhibit substantial asymmetry, avoiding some of the pitfalls of the symmetric forecast densities from the Bayesian VAR. We show that the asymmetries in the predictive distributions of GDP growth and inflation are similar to those found in the probabilistic forecasts from the Survey of Professional Forecasters. Last, we find that unlike the linear VAR model, our fitted Gaussian copula models exhibit nonlinear dependencies between some macroeconomic variables. This article has online supplementary material.     

Finie mixures of canonical fundamenal skew $$$$-disribuions

This paper introduces a finite mixture of canonical fundamental skew \(t\) (CFUST) distributions for a model-based approach to clustering where the clusters are asymmetric and possibly long-tailed (in: Lee and McLachlan, arXiv:1401.8182 [statME], 2014b). The family of CFUST distributions includes the restricted multivariate skew \(t\) and unrestricted multivariate skew \(t\) distributions as special cases. In recent years, a few versions of the multivariate skew \(t\) (MST) mixture model have been put forward, together with various EM-type algorithms for parameter estimation. These formulations adopted either a restricted or unrestricted characterization for their MST densities. In this paper, we examine a natural generalization of these developments, employing the CFUST distribution as the parametric family for the component distributions, and point out that the restricted and unrestricted characterizations can be unified under this general formulation. We show that an exact implementation of the EM algorithm can be achieved for the CFUST distribution and mixtures of this distribution, and present some new analytical results for a conditional expectation involved in the E-step.     

Variable selection for survival data with a class of adaptive elastic net techniques

The accelerated failure time (AFT) models have proved useful in many contexts, though heavy censoring (as for example in cancer survival) and high dimensionality (as for example in microarray data) cause difficulties for model fitting and model selection. We propose new approaches to variable selection for censored data, based on AFT models optimized using regularized weighted least squares. The regularized technique uses a mixture of \(\ell _1\) and \(\ell _2\) norm penalties under two proposed elastic net type approaches. One is the adaptive elastic net and the other is weighted elastic net. The approaches extend the original approaches proposed by Ghosh (Adaptive elastic net: an improvement of elastic net to achieve oracle properties, Technical Reports 2007) and Hong and Zhang (Math Model Nat Phenom 5(3):115–133 2010), respectively. We also extend the two proposed approaches by adding censoring observations as constraints into their model optimization frameworks. The approaches are evaluated on microarray and by simulation. We compare the performance of these approaches with six other variable selection techniques-three are generally used for censored data and the other three are correlation-based greedy methods used for high-dimensional data.     

Randomization tests in recursive response-adaptive randomization procedures

In a randomized clinical trial, response-adaptive randomization procedures use the information gathered, including the previous patients' responses, to allocate the next patient. In this setting, we consider randomization-based inference. We provide an algorithm to obtain exact p-values for statistical tests that compare two treatments with dichotomous responses. This algorithm can be applied to a family of response adaptive randomization procedures which share the following property: the distribution of the allocation rule depends only on the imbalance between treatments and on the imbalance between successes for treatments 1 and 2 in the previous step. This family includes some outstanding response adaptive randomization procedures. We study a randomization test to contrast the null hypothesis of equivalence of treatments and we show that this test has a similar performance to that of its parametric counterpart. Besides, we study the effect of a covariate in the inferential process. First, we obtain a parametric test, constructed assuming a logit model which relates responses to treatments and covariate levels, and we give conditions that guarantee its asymptotic normality. Finally, we show that the randomization test, which is free of model specification, performs as well as the parametric test that takes the covariate into account.     

Power analysis for clustered non-continuous responses in multicenter trials

Power analysis for multi-center randomized control trials is quite difficult to perform for non-continuous responses when site differences are modeled by random effects using the generalized linear mixed-effects model (GLMM). First, it is not possible to construct power functions analytically, because of the extreme complexity of the sampling distribution of parameter estimates. Second, Monte Carlo (MC) simulation, a popular option for estimating power for complex models, does not work within the current context because of a lack of methods and software packages that would provide reliable estimates for fitting such GLMMs. For example, even statistical packages from software giants like SAS do not provide reliable estimates at the time of writing. Another major limitation of MC simulation is the lengthy running time, especially for complex models such as GLMM, especially when estimating power for multiple scenarios of interest. We present a new approach to address such limitations. The proposed approach defines a marginal model to approximate the GLMM and estimates power without relying on MC simulation. The approach is illustrated with both real and simulated data, with the simulation study demonstrating good performance of the method.