Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

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.     

立足高起点发展新方向培养应用型复合型人才——对我院法学专业教学的认识及建议

我院法学专业培养目标是为社会培养应用型、复合型人才 ,针对实际情况 ,作者提出应改革教学内容 ,优化课程体系 ;改革教学方法 ,完善教学手段 ;提高教师业务水平 ,加强学术梯队建设等建议。     

Simple detection of outlying short time series

Sets of relatively short time series arise in many situations. One aspect of their analysis may be the detection of outlying series. We examine the performance of standard normal outlier tests applied to the means, or to simple functions of the means, of AR(1) series, not necessarily of equal lengths. Although unequal lengths of series implies that the means have unequal variances, that are only known approximately, it is shown that nominal significance levels hold good under most circumstances. Thus a standard outlier test can usefully be applied, avoiding the complication of estimating the time series' parameters. The test's power is affected by unequal lengths, being higher when the slippage occurs in one of the longer series     

基于复杂适应系统的作战理论哲学反思

传统的作战理论与方法已经不能适应像现代信息化战争系统这类充满“活”的个体和变化因素的复杂系统，需要进行理论创新。而复杂适应系统理论是当代系统科学的一个新发展。有望成为创新作战理论的突破口。本文在分析比较作战系统的基础上，认为作战系统实质是复杂的适应系统，作战系统内的作战双方都力图以增强自身的适应性和复杂性，削弱对方的适应性和复杂性取得作战的胜利。     

孔子的富贵观及其现代价值解读

孔子的富贵观是其思想体系的重要组成部分。孔子关于世人应否追求富贵,怎样处理富贵与道义的关系,以及富裕之后还当如何等问题在《论语》中都有论述。孔子的这些论述,对当代人们创业致富,以义求利,以及坚持经济建设与精神文明建设两手抓,仍然具有启迪作用和借鉴价值。     

DBF系统的通道校正技术

描述了影响DBF系统特性的主要因素,研究了阵元间互耦对自适应方向图旁瓣和零深的影响及校正方法,讨论了在DBF阵中校正接收通道幅、相误差和I/Q支路正交误差的技术途径。计算机模拟和测试证明,按照所述方法进行校正可以得到满意的结果。另外,为了减小I/Q支路产生正交误差,建议采用中频直接采样和数字化的接收机方案。     

Some remarks on the physical models concerning two different approaches to inference in statistical process control

Summary For technological applications it can be useful to identify some simple physical mechanisms, which, on the basis of the available knowledge of the production process, may suggest the most appropriate approach to statistical control of the random quantities of interest. For this purpose the notion of rupture point is introduced firstly. A rupture point is characterized bym randomly arising out of control states, assumed to be mutually exclusive and stochastically independent. Shewhart's control charts seem to represent the natural statistical tool for controlling a rupture point; however it is shown that they are fully justified only when the hazard rates attached to the causes of failure are constant. Otherwise, typically in the presence of time increasing hazard rates, Shewhart's control charts should be completed by a preventive intervention rule (preventive maintenance). In the second place, the notion of dynamic instability point is introduced, which is specifically characterized by assuming that the random quantity of interest is ruled by a stochastic differential equation with constant coefficients. By discretization, developed according to a possibly new approach, it is shown that the former model reduces to an equation error model, which is among the simplest used in adaptive control, and thus particularly easy to deal with in regard to parameter estimation and the definition of the optimum control rule.     

Divergence-based estimation and testing with misclassified data

The well-known chi-squared goodness-of-fit test for a multinomial distribution is generally biased when the observations are subject to misclassification. In Pardo and Zografos (2000) the problem was considered using a double sampling scheme and ø-divergence test statistics. A new problem appears if the null hypothesis is not simple because it is necessary to give estimators for the unknown parameters. In this paper the minimum ø-divergence estimators are considered and some of their properties are established. The proposed ø-divergence test statistics are obtained by calculating ø-divergences between probability density functions and by replacing parameters by their minimum ø-divergence estimators in the derived expressions. Asymptotic distributions of the new test statistics are also obtained. The testing procedure is illustrated with an example.