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.     

Inference and optimal design of multiple constant-stress testing for generalized half-normal distribution under type-II progressive censoring

The generalized half-normal (GHN) distribution and progressive type-II censoring are considered in this article for studying some statistical inferences of constant-stress accelerated life testing. The EM algorithm is considered to calculate the maximum likelihood estimates. Fisher information matrix is formed depending on the missing information law and it is utilized for structuring the asymptomatic confidence intervals. Further, interval estimation is discussed through bootstrap intervals. The Tierney and Kadane method, importance sampling procedure and Metropolis-Hastings algorithm are utilized to compute Bayesian estimates. Furthermore, predictive estimates for censored data and the related prediction intervals are obtained. We consider three optimality criteria to find out the optimal stress level. A real data set is used to illustrate the importance of GHN distribution as an alternative lifetime model for well-known distributions. Finally, a simulation study is provided with discussion.     

Random effects regression mixtures for analyzing infant habituation

Random effects regression mixture models are a way to classify longitudinal data (or trajectories) having possibly varying lengths. The mixture structure of the traditional random effects regression mixture model arises through the distribution of the random regression coefficients, which is assumed to be a mixture of multivariate normals. An extension of this standard model is presented that accounts for various levels of heterogeneity among the trajectories, depending on their assumed error structure. A standard likelihood ratio test is presented for testing this error structure assumption. Full details of an expectation-conditional maximization algorithm for maximum likelihood estimation are also presented. This model is used to analyze data from an infant habituation experiment, where it is desirable to assess whether infants comprise different populations in terms of their habituation time.     

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.     

基于TMS320C40的FFT算法改进及应用

讨论了充分利用C4 0的硬件并行结构进行实数FFT的并行算法 ,并在地震勘探信号处理中得以应用     

Non-ignorable missing covariate data in survival analysis: a case-study of an International Breast Cancer Study Group trial

Summary.  Non-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.     

基于RSA的电子商务信息加密技术研究

21世纪是网络信息时代,电子商务的迅猛发展和普及打破了人们传统的经营和消费理念,网上消费已成为一种新的消费形式,但随之而来的便是电子商务赖以生存和发展的安全问题。文章主要通过对电子商务安全隐患的分析,论证了数据加密技术在电子商务安全中的作用,重点探讨了RSA公钥加密算法,并通过实例对其加密原理、计算复杂性等安全性问题作了详尽的分析和阐述。     

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。     

A semi-parametric approach to robust parameter design

Parameter design or robust parameter design (RPD) is an engineering methodology intended as a cost-effective approach for improving the quality of products and processes. The goal of parameter design is to choose the levels of the control variables that optimize a defined quality characteristic. An essential component of RPD involves the assumption of well estimated models for the process mean and variance. Traditionally, the modeling of the mean and variance has been done parametrically. It is often the case, particularly when modeling the variance, that nonparametric techniques are more appropriate due to the nature of the curvature in the underlying function. Most response surface experiments involve sparse data. In sparse data situations with unusual curvature in the underlying function, nonparametric techniques often result in estimates with problematic variation whereas their parametric counterparts may result in estimates with problematic bias. We propose the use of semi-parametric modeling within the robust design setting, combining parametric and nonparametric functions to improve the quality of both mean and variance model estimation. The proposed method will be illustrated with an example and simulations.     

Estimating household structure in ancient China by using historical data: a latent class analysis of partially missing patterns

Summary.  Social data often contain missing information. The problem is inevitably severe when analysing historical data. Conventionally, researchers analyse complete records only. Listwise deletion not only reduces the effective sample size but also may result in biased estimation, depending on the missingness mechanism. We analyse household types by using population registers from ancient China (618–907 AD) by comparing a simple classification, a latent class model of the complete data and a latent class model of the complete and partially missing data assuming four types of ignorable and non-ignorable missingness mechanisms. The findings show that either a frequency classification or a latent class analysis using the complete records only yielded biased estimates and incorrect conclusions in the presence of partially missing data of a non-ignorable mechanism. Although simply assuming ignorable or non-ignorable missing data produced consistently similarly higher estimates of the proportion of complex households, a specification of the relationship between the latent variable and the degree of missingness by a row effect uniform association model helped to capture the missingness mechanism better and improved the model fit.