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.     

论“莱西会议精神”对新时期全面深化农村基层党组织建设的价值和意义

农村基层党组织是党在农村的神经末梢,也是党的路线、方针、政策的"终端"推动者和实践者。现阶段农村党组织建设面临新兴组织不断涌现与党组织作用削弱的不适应,"权力和资源缺失"与服务刚性增强的不适应,村民自治进一步发展与群众政治参与欠充分的不适应,群众诉求多样化与满足渠道单一的不适应,部分党员党性不强、意识淡化与始终保持先进性的要求不适应等问题。在加强以党支部为核心的农村基层组织建设的"莱西会议精神"指导下,全面深化农村基层党组织建设:思想上高度认识是前提,加强支部建设是核心,坚持法治、完善村民自治是重点,紧扣服务、创新制度是关键,统筹协调、综合配套是保障。     

文学意义的消解与重建

在商品化和信息化的时代大潮冲击下 ,文学面临着意义的流失与消解。文学的这种现状是与整个人类文化的困境紧密相关的 ,是人类发展特殊阶段上的必然产物。中国当代文学应致力于意义的探寻与重建 ,这表现为在对现实的清醒认识的基础上对理想的重新肯定 ,对现实中的物欲的批判性把握 ,以及对人类生存意义的重新认识。     

刑事诉讼主体的法理分析--以刑事法律关系为基础

犯罪行为引起的刑事法律关系是考察刑事诉讼主体问题的真正法理基础。国家与被告人作为刑事法律关系的主体是刑事诉讼的当事人 ,被害人及其近亲属不是刑事法律关系的主体 ,故不是刑事诉讼当事人 ,只是发动、支持公法性诉讼的公民追诉人。审判权与公诉权的分立 ,本质上是国家将自身作为自己的对象 ,并在自己(裁判者 )与作为对象的自身 (当事人 )之间建立绝对区分 ,体现了作为公共权力的国家的自我反思节制。其他刑事诉讼主体均不是刑事法律关系的主体 ,按照意志关系或者是国家的代表、被告人和被害人的代理人或帮助人 ,或者是不从属于任何一方的诉讼主体。     

传统壮族文人文论的价值和意义

传统壮族文人的文论在全国影响并不大,但是否就因此而没有价值和意义?尽管受到汉族文人文论的巨大影响,并因此还具有滞后性,但传统壮族文人文论的存在仍有其价值和意义,这种价值和意义表现为:它是对传统壮族文人文学创作的总结;它是壮族民间文论的发展,是壮族人民对文学思考的进一步深化;它是对全国文论的一种丰富。在这三个方面,它有着别的文论无法替代的价值和意义。     

中国古代城市文学研究的文学史意义

研究中国古代城市文学的文学史意义在于，从空间视角重新认识和研究古代文学，充分发掘和利用长期以来被忽略的城市文学资源。有助于建构起时空并置、更加完整和系统的中国古代文学史。此外，研究中国古代城市文学还可以为当代文学史研究提供一个广阔的历史视野与意蕴深厚的历史文本。     

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。     

论老建筑再生与城市空间品质的塑造

通过老建筑再生对于城市的价值意义的研究以及对城市与老建筑关系的分析，从多个角度阐述由老建筑再生所带来的城市意象、城市肌理、场所精神、城市色彩、城市风貌等要素的变化及其促进城市空间品质的提高，并结合国内外案例对这一观点行论证。     

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。