Response‐adaptive designs for binary responses: How to offer patient benefit while being robust to time trends?

Response‐adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates. There is considerable interest in using RAR designs in drug development for rare diseases, where traditional designs are not either feasible or ethically questionable. In this paper, we discuss and address a major criticism levelled at RAR: namely, type I error inflation due to an unknown time trend over the course of the trial. The most common cause of this phenomenon is changes in the characteristics of recruited patients—referred to as patient drift. This is a realistic concern for clinical trials in rare diseases due to their lengthly accrual rate. We compute the type I error inflation as a function of the time trend magnitude to determine in which contexts the problem is most exacerbated. We then assess the ability of different correction methods to preserve type I error in these contexts and their performance in terms of other operating characteristics, including patient benefit and power. We make recommendations as to which correction methods are most suitable in the rare disease context for several RAR rules, differentiating between the 2‐armed and the multi‐armed case. We further propose a RAR design for multi‐armed clinical trials, which is computationally efficient and robust to several time trends considered.     

Conditional covariance penalties for mixed models

The prediction error for mixed models can have a conditional or a marginal perspective depending on the research focus. We introduce a novel conditional version of the optimism theorem for mixed models linking the conditional prediction error to covariance penalties for mixed models. Different possibilities for estimating these conditional covariance penalties are introduced. These are bootstrap methods, cross-validation, and a direct approach called Steinian. The behavior of the different estimation techniques is assessed in a simulation study for the binomial-, the t-, and the gamma distribution and for different kinds of prediction error. Furthermore, the impact of the estimation techniques on the prediction error is discussed based on an application to undernutrition in Zambia.     

Multivariate normal mean–variance mixture distribution based on Birnbaum–Saunders distribution

A multivariate normal mean–variance mixture based on a Birnbaum–Saunders (NMVMBS) distribution is introduced and several properties of this new distribution are discussed. A new robust non-Gaussian ARCH-type model is proposed in which there exists a relation between the variance of the observations, and the marginal distributions are NMVMBS. A simple EM-based maximum likelihood estimation procedure to estimate the parameters of this normal mean–variance mixture distribution is given. A simulation study and some real data are used to demonstrate the modelling strength of this new model.     

Simultaneous edit-imputation and disclosure limitation for business establishment data

Business establishment microdata typically are required to satisfy agency-specified edit rules, such as balance equations and linear inequalities. Inevitably some establishments' reported data violate the edit rules. Statistical agencies correct faulty values using a process known as edit-imputation. Business establishment data also must be heavily redacted before being shared with the public; indeed, confidentiality concerns lead many agencies not to share establishment microdata as unrestricted access files. When microdata must be heavily redacted, one approach is to create synthetic data, as done in the U.S. Longitudinal Business Database and the German IAB Establishment Panel. This article presents the first implementation of a fully integrated approach to edit-imputation and data synthesis. We illustrate the approach on data from the U.S. Census of Manufactures and present a variety of evaluations of the utility of the synthetic data. The paper also presents assessments of disclosure risks for several intruder attacks. We find that the synthetic data preserve important distributional features from the post-editing confidential microdata, and have low risks for the various attacks.     

The beta generalized linear exponential distribution

In this paper, a new five-parameter lifetime distribution called beta generalized linear exponential distribution (BGLED) is introduced. It includes at least 17 popular sub-models as special cases such as the beta linear exponential, the beta generalized exponential, and the exponentiated generalized linear distributions. Mathematical and statistical properties of the proposed distribution are discussed in details. In particular, explicit expression for the density function, moments, asymptotics distributions for sample extreme statistics, and other statistical measures are obtained. The estimation of the parameters by the method of maximum-likelihood is discussed and the finite sample properties of the maximum-likelihood estimators (MLEs) are investigated numerically. A real data set is used to demonstrate its superior performance fit over several existing popular lifetime models.     

Quasi-minimax estimation in the partial linear model

This article discusses the minimax estimator in partial linear model y = Zβ + f + ε under ellipsoidal restrictions on the parameter space and quadratic loss function. The superiority of the minimax estimator over the two-step estimator is studied in the mean squared error matrix criterion.     

Why do we observe misclassification errors smaller than the Bayes error?

In simulation studies for discriminant analysis, misclassification errors are often computed using the Monte Carlo method, by testing a classifier on large samples generated from known populations. Although large samples are expected to behave closely to the underlying distributions, they may not do so in a small interval or region, and thus may lead to unexpected results. We demonstrate with an example that the LDA misclassification error computed via the Monte Carlo method may often be smaller than the Bayes error. We give a rigorous explanation and recommend a method to properly compute misclassification errors.     

Generalised K-S confidence regions: some exact results

One-sided confidence regions for continuous cumulative distribution function are constructed using empirical cumulative distribution functions and the generalized Kolmogorov-Smirnov distance. The band width of such regions becomes narrower in the right or left tail of the distribution. Significance levels necessary for implementation are given. Some other K-S type distances useful in constructing a confidence region with nonconstant width are also included.     

Double shrinkage estimators for large sparse covariance matrices

Covariance matrices play an important role in many multivariate techniques and hence a good covariance estimation is crucial in this kind of analysis. In many applications a sparse covariance matrix is expected due to the nature of the data or for simple interpretation. Hard thresholding, soft thresholding, and generalized thresholding were therefore developed to this end. However, these estimators do not always yield well-conditioned covariance estimates. To have sparse and well-conditioned estimates, we propose doubly shrinkage estimators: shrinking small covariances towards zero and then shrinking covariance matrix towards a diagonal matrix. Additionally, a richness index is defined to evaluate how rich a covariance matrix is. According to our simulations, the richness index serves as a good indicator to choose relevant covariance estimator.