Inferences on the Means of Two Log-Normal Distributions: A Computational Approach Test

In this article, we propose a novel approach for testing the equality of two log-normal populations using a computational approach test (CAT) that does not require explicit knowledge of the sampling distribution of the test statistic. Simulation studies demonstrate that the proposed approach can perform hypothesis testing with satisfying actual size even at small sample sizes. Overall, it is superior to other existing methods. Also, a CAT is proposed for testing about reliability of two log-normal populations when the means are the same. Simulations show that the actual size of this new approach is close to nominal level and better than the score test. At the end, the proposed methods are illustrated using two examples.     

Statistical testing strategies for assessing treatment efficacy and marker accuracy in phase III trials

When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided.     

Blinded continuous monitoring in clinical trials with recurrent event endpoints

In studies with recurrent event endpoints, misspecified assumptions of event rates or dispersion can lead to underpowered trials or overexposure of patients. Specification of overdispersion is often a particular problem as it is usually not reported in clinical trial publications. Changing event rates over the years have been described for some diseases, adding to the uncertainty in planning. To mitigate the risks of inadequate sample sizes, internal pilot study designs have been proposed with a preference for blinded sample size reestimation procedures, as they generally do not affect the type I error rate and maintain trial integrity. Blinded sample size reestimation procedures are available for trials with recurrent events as endpoints. However, the variance in the reestimated sample size can be considerable in particular with early sample size reviews. Motivated by a randomized controlled trial in paediatric multiple sclerosis, a rare neurological condition in children, we apply the concept of blinded continuous monitoring of information, which is known to reduce the variance in the resulting sample size. Assuming negative binomial distributions for the counts of recurrent relapses, we derive information criteria and propose blinded continuous monitoring procedures. The operating characteristics of these are assessed in Monte Carlo trial simulations demonstrating favourable properties with regard to type I error rate, power, and stopping time, ie, sample size.     

Modifications of sequential designs in bioequivalence trials

Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/ . Copyright © 2015 John Wiley & Sons, Ltd.     

Multivariate outlier detection in incomplete survey data: the epidemic algorithm and transformed rank correlations

Summary.  As a part of the EUREDIT project new methods to detect multivariate outliers in incomplete survey data have been developed. These methods are the first to work with sampling weights and to be able to cope with missing values. Two of these methods are presented here. The epidemic algorithm simulates the propagation of a disease through a population and uses extreme infection times to find outlying observations. Transformed rank correlations are robust estimates of the centre and the scatter of the data. They use a geometric transformation that is based on the rank correlation matrix. The estimates are used to define a Mahalanobis distance that reveals outliers. The two methods are applied to a small data set and to one of the evaluation data sets of the EUREDIT project.     

"民官比"不是影响政治体制改革的重要因素

在政治体制改革中,公务员或国家干部人数的多少并不是一个关键因素,重要的是必须把政府的社会定位(包括角色、权力和责任)划分清楚。与世界各国相比较,我国197.69∶1(或116.27∶1)的“民官比”并不高,因此,今后的政治体制改革不需要再把精力集中在“精简”上,而应按邓小平的部署,首先把党政分开和权力下放的工作做好。毕竟“小政府”是指“政府权力受限制”,而非“人数更少”;“大社会”是指“社会权利更广泛”,而非“人数更多”。     

基于移动代理的新型IDS维护更新机制设计

提出了一种基于移动代理的新型分布式入侵检测系统。该系统是针对广域网环境专门设计的,数据的处理通过各节点所设置的代理来进行分布式计算,不仅能实现全网络范围内的入侵检测功能,具有良好的可移植性;而且对网络系统和主机的资源占用较低,减少了出现网络瓶颈的可能。还建立了移动代理的新型分布式入侵检测系统的体系结构和理论分析模型,并讨论了该系统的维护更新机制。     

遗传算法在入侵检测中的应用

介绍了基于模型推理和基于模型两种入侵检测系统,提出了一种新的基于智能体技术的入侵检测系统体系结构,解决了传统集中式入侵检测系统的弊病,将任务处理和数据分布到网络各个结点上,充分利用网络资源协同完成入侵检测任务;介绍了遗传算法在该系统中的应用,因系统安全的先验知识体现在对原始数据中有价值特征属性变量集的选择上,故利用遗传算法对特征属性变量子集的选择进行优化,找到相对最优的由特征向量表示的特征属性变量集,以降低入侵检测系统的负荷。     

CCD图象检测信号的失真校正

本文从CCD图象输入系统误差引起图象检测信号失真的原因分析出发,以降低系统装校误差精度要求和增大元器件离散性的宽容度为目标,讨论朱真校正方法的原理和数学描述。最后,介绍两种失真校正方法。