Non‐Parametric Change‐Point Tests for Long‐Range Dependent Data

Abstract. We propose a non‐parametric change‐point test for long‐range dependent data, which is based on the Wilcoxon two‐sample test. We derive the asymptotic distribution of the test statistic under the null hypothesis that no change occurred. In a simulation study, we compare the power of our test with the power of a test which is based on differences of means. The results of the simulation study show that in the case of Gaussian data, our test has only slightly smaller power minus.3pt than the ‘difference‐of‐means’ test. For heavy‐tailed data, our test outperforms the ‘difference‐of‐means’ test.     

Nonparametric Two‐Sample Tests of the Marginal Mark Distribution with Censored Marks

Occasionally, investigators collect auxiliary marks at the time of failure in a clinical study. Because the failure event may be censored at the end of the follow‐up period, these marked endpoints are subject to induced censoring. We propose two new families of two‐sample tests for the null hypothesis of no difference in mark‐scale distribution that allows for arbitrary associations between mark and time. One family of proposed tests is a nonparametric extension of an existing semi‐parametric linear test of the same null hypothesis while a second family of tests is based on novel marked rank processes. Simulation studies indicate that the proposed tests have the desired size and possess adequate statistical power to reject the null hypothesis under a simple change of location in the marginal mark distribution. When the marginal mark distribution has heavy tails, the proposed rank‐based tests can be nearly twice as powerful as linear tests.     

A nonparametric test for interaction in two‐way layouts

The authors present a new nonparametric approach to test for interaction in two‐way layouts. Based on the concept of composite linear rank statistics, they combine the correlated row and column ranking information to construct the test statistic. They determine the limiting distributions of the proposed test statistic under the null hypothesis and Pitman alternatives. They also propose consistent estimators for the limiting covariance matrices associated with the test. They illustrate the application of their test in practical settings using a microarray data set.     

Sensitivity to censored‐at‐random assumption in the analysis of time‐to‐event endpoints

Over the past years, significant progress has been made in developing statistically rigorous methods to implement clinically interpretable sensitivity analyses for assumptions about the missingness mechanism in clinical trials for continuous and (to a lesser extent) for binary or categorical endpoints. Studies with time‐to‐event outcomes have received much less attention. However, such studies can be similarly challenged with respect to the robustness and integrity of primary analysis conclusions when a substantial number of subjects withdraw from treatment prematurely prior to experiencing an event of interest. We discuss how the methods that are widely used for primary analyses of time‐to‐event outcomes could be extended in a clinically meaningful and interpretable way to stress‐test the assumption of ignorable censoring. We focus on a ‘tipping point’ approach, the objective of which is to postulate sensitivity parameters with a clear clinical interpretation and to identify a setting of these parameters unfavorable enough towards the experimental treatment to nullify a conclusion that was favorable to that treatment. Robustness of primary analysis results can then be assessed based on clinical plausibility of the scenario represented by the tipping point. We study several approaches for conducting such analyses based on multiple imputation using parametric, semi‐parametric, and non‐parametric imputation models and evaluate their operating characteristics via simulation. We argue that these methods are valuable tools for sensitivity analyses of time‐to‐event data and conclude that the method based on piecewise exponential imputation model of survival has some advantages over other methods studied here. Copyright © 2016 John Wiley & Sons, Ltd.     

Space‐time cluster identification in point processes

The authors propose a new type of scan statistic to test for the presence of space‐time clusters in point processes data, when the goal is to identify and evaluate the statistical significance of localized clusters. Their method is based only on point patterns for cases; it does not require any specific knowledge of the underlying population. The authors propose to scan the three‐dimensional space with a score test statistic under the null hypothesis that the underlying point process is an inhomogeneous Poisson point process with space and time separable intensity. The alternative is that there are one or more localized space‐time clusters. Their method has been implemented in a computationally efficient way so that it can be applied routinely. They illustrate their method with space‐time crime data from Belo Horizonte, a Brazilian city, in addition to presenting a Monte Carlo study to analyze the power of their new test.     

Statistical models for DNA copy number variation detection using read‐depth data from next generation sequencing experiments

In this ‘Big Data’ era, statisticians inevitably encounter data generated from various disciplines. In particular, advances in bio‐technology have enabled scientists to produce enormous datasets in various biological experiments. In the last two decades, we have seen high‐throughput microarray data resulting from various genomic studies. Recently, next generation sequencing (NGS) technology has been playing an important role in the study of genomic features, resulting in vast amount of NGS data. One frequent application of NGS technology is in the study of DNA copy number variants (CNVs). The resulting NGS read count data are then used by researchers to formulate their various scientific approaches to accurately detect CNVs. Computational and statistical approaches to the detection of CNVs using NGS data are, however, very limited at present. In this review paper, we will focus on read‐depth analysis in CNV detection and give a brief summary of currently used statistical analysis methods in searching for CNVs using NGS data. In addition, based on the review, we discuss the challenges we face and future research directions. The ultimate goal of this review paper is to give a timely exposition of the surveyed statistical methods to researchers in related fields.     

Covariates in multipath change‐point problems: Modelling and consistency of the MLE

Although the single‐path change‐point problem has been extensively treated in the statistical literature, its multipath counterpart has largely been ignored. In the multipath change‐point setting, it is often of interest to assess the impact of covariates on the change point itself as well as on the parameters before and after the change point. This paper is concerned only with the inclusion of covariates in the change‐point distribution. This is achieved through the hazard of change. Maximum likelihood estimation is discussed and consistency of the maximum likelihood estimators established.     

Hidden Second‐order Stationary Spatial Point Processes

In the existing statistical literature, the almost default choice for inference on inhomogeneous point processes is the most well‐known model class for inhomogeneous point processes: reweighted second‐order stationary processes. In particular, the K‐function related to this type of inhomogeneity is presented as the inhomogeneous K‐function. In the present paper, we put a number of inhomogeneous model classes (including the class of reweighted second‐order stationary processes) into the common general framework of hidden second‐order stationary processes, allowing for a transfer of statistical inference procedures for second‐order stationary processes based on summary statistics to each of these model classes for inhomogeneous point processes. In particular, a general method to test the hypothesis that a given point pattern can be ascribed to a specific inhomogeneous model class is developed. Using the new theoretical framework, we reanalyse three inhomogeneous point patterns that have earlier been analysed in the statistical literature and show that the conclusions concerning an appropriate model class must be revised for some of the point patterns.     

Non‐parametric Bayesian Intensity Model: Exploring Time‐to‐Event Data on Two Time Scales

Time‐to‐event data have been extensively studied in many areas. Although multiple time scales are often observed, commonly used methods are based on a single time scale. Analysing time‐to‐event data on two time scales can offer a more extensive insight into the phenomenon. We introduce a non‐parametric Bayesian intensity model to analyse two‐dimensional point process on Lexis diagrams. After a simple discretization of the two‐dimensional process, we model the intensity by a one‐dimensional piecewise constant hazard functions parametrized by the change points and corresponding hazard levels. Our prior distribution incorporates a built‐in smoothing feature in two dimensions. We implement posterior simulation using the reversible jump Metropolis–Hastings algorithm and demonstrate the applicability of the method using both simulated and empirical survival data. Our approach outperforms commonly applied models by borrowing strength in two dimensions.     

Non‐inferiority and networks: inferring efficacy from a web of data

In the absence of placebo‐controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non‐inferiority to an active control; that is, the test treatment is not worse than the active control by a pre‐specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non‐inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta‐analysis that models the uncertainty and heterogeneity of the historical trials into the non‐inferiority trial in a data‐driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non‐inferiority testing are discussed that are analogs of the synthesis and fixed‐margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non‐inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non‐inferiority. Copyright © 2015 John Wiley & Sons, Ltd.     

A glimpse of the impact of pál erd#ous on probability and statistics

The title of this article notwithstanding, it is the author's aspiration here to provide a bit more than merely a glimpse of some of Erdõs's contributions per se to probability‐statistics. He hopes to have succeeded in providing a guided tour of, and whenever it has appeared feasible, an introduction to, a few selected areas that have been strongly influenced by the work of Erdõs. The author also hopes to have succeeded in facilitating a glimpse of the impact of these contributions by presenting them in their historical context.