Fourier–type tests involving martingale difference processes

We develop testing procedures which detect if the observed time series is a martingale difference sequence. Furthermore, tests are developed that detect change–points in the conditional expectation of the series given its past. The test statistics are formulated following the approach of Fourier–type conditional expectations first proposed by Bierens (1982 Bierens, H. J. (1982). Consistent model speci?cation tests. J. Econometr. 20:105–134.[Crossref], [Web of Science ®] , [Google Scholar]) and have the advantage of computational simplicity. The limit behavior of the test statistics is investigated under the null hypothesis as well as under alternatives. Since the asymptotic null distribution contains unknown parameters, a bootstrap procedure is proposed in order to actually perform the test. The performance of the bootstrap version of the test is compared in finite samples with other methods for the same problem. A real–data application is also included.     

Efficiency of the generalized-difference-based weighted mixed almost unbiased two-parameter estimator in partially linear model

In this paper, a generalized difference-based estimator is introduced for the vector parameter β in partially linear model when the errors are correlated. A generalized-difference-based almost unbiased two-parameter estimator is defined for the vector parameter β. Under the linear stochastic constraint r = Rβ + e, we introduce a new generalized-difference-based weighted mixed almost unbiased two-parameter estimator. The performance of this new estimator over the generalized-difference-based estimator and generalized- difference-based almost unbiased two-parameter estimator in terms of the MSEM criterion is investigated. The efficiency properties of the new estimator is illustrated by a simulation study. Finally, the performance of the new estimator is evaluated for a real dataset.     

Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

Enabling robust assessment of QTc prolongation in early phase clinical trials

Since the implementation of the International Conference on Harmonization (ICH) E14 guideline in 2005, regulators have required a “thorough QTc” (TQT) study for evaluating the effects of investigational drugs on delayed cardiac repolarization as manifested by a prolonged QTc interval. However, TQT studies have increasingly been viewed unfavorably because of their low cost effectiveness. Several researchers have noted that a robust drug concentration‐QTc (conc‐QTc) modeling assessment in early phase development should, in most cases, obviate the need for a subsequent TQT study. In December 2015, ICH released an “E14 Q&As (R3)” document supporting the use of conc‐QTc modeling for regulatory decisions. In this article, we propose a simple improvement of two popular conc‐QTc assessment methods for typical first‐in‐human crossover‐like single ascending dose clinical pharmacology trials. The improvement is achieved, in part, by leveraging routinely encountered (and expected) intrasubject correlation patterns encountered in such trials. A real example involving a single ascending dose and corresponding TQT trial, along with results from a simulation study, illustrate the strong performance of the proposed method. The improved conc‐QTc assessment will further enable highly reliable go/no‐go decisions in early phase clinical development and deliver results that support subsequent TQT study waivers by regulators.     

Testing independence based on Bernstein empirical copula and copula density

In this paper we provide three nonparametric tests of independence between continuous random variables based on the Bernstein copula distribution function and the Bernstein copula density function. The first test is constructed based on a Cramér-von Mises divergence-type functional based on the empirical Bernstein copula process. The two other tests are based on the Bernstein copula density and use Cramér-von Mises and Kullback–Leibler divergence-type functionals, respectively. Furthermore, we study the asymptotic null distribution of each of these test statistics. Finally, we consider a Monte Carlo experiment to investigate the performance of our tests. In particular we examine their size and power which we compare with those of the classical nonparametric tests that are based on the empirical distribution function.     

Model selection consistency of U-statistics with convex loss and weighted lasso penalty

In the paper we consider minimisation of U-statistics with the weighted Lasso penalty and investigate their asymptotic properties in model selection and estimation. We prove that the use of appropriate weights in the penalty leads to the procedure that behaves like the oracle that knows the true model in advance, i.e. it is model selection consistent and estimates nonzero parameters with the standard rate. For the unweighted Lasso penalty, we obtain sufficient and necessary conditions for model selection consistency of estimators. The obtained results strongly based on the convexity of the loss function that is the main assumption of the paper. Our theorems can be applied to the ranking problem as well as generalised regression models. Thus, using U-statistics we can study more complex models (better describing real problems) than usually investigated linear or generalised linear models.     

Mixture inverse Gaussian for unobserved heterogeneity in the autoregressive conditional duration model

In this paper, we assume that the duration of a process has two different intrinsic components or phases which are independent. The first is the time it takes for a trade to be initiated in the market (for example, the time during which agents obtain knowledge about the market in which they are operating and accumulate information, which is coherent with Brownian motion) and the second is the subsequent time required for the trade to develop into a complete duration. Of course, if the first time is zero then the trade is initiated immediately and no initial knowledge is required. If we assume a specific compound Bernoulli distribution for the first time and an inverse Gaussian distribution for the second, the resulting convolution model has a mixture of an inverse Gaussian distribution with its reciprocal, which allows us to specify and test the unobserved heterogeneity in the autoregressive conditional duration (ACD) model.

Our proposals make it possible not only to capture various density shapes of the durations but also easily to accommodate the behaviour of the tail of the distribution and the non monotonic hazard function. The proposed model is easy to fit and characterizes the behaviour of the conditional durations reasonably well in terms of statistical criteria based on point and density forecasts.     

Some novel results on pairwise quasi-asymptotical independence with applications to risk theory

In this article we obtain some novel results on pairwise quasi-asymptotically independent (pQAI) random variables. Concretely speaking, let X₁, …, X_n be n real-valued pQAI random variables, and W₁, …, W_n be another n non negative and arbitrarily dependent random variables, but independent of X₁, …, X_n. Under some mild conditions, we prove that W₁X₁, …, W_nX_n are still pQAI as well. Our result is in a general setting whether the primary random variables X₁, …, X_n are heavy-tailed or not. Finally, a special case of above result is applied to risk theory for investigating the finite-time ruin probability for a discrete-time risk model with a wide type of dependence structure.