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.     

An approximation of logarithmic functions in the regression setting

We consider a method of moments approach for dealing with censoring at zero for data expressed in levels when researchers would like to take logarithms. A Box–Cox transformation is employed. We explore this approach in the context of linear regression where both dependent and independent variables are censored. We contrast this method to two others, (1) dropping records of data containing censored values and (2) assuming normality for censored observations and the residuals in the model. Across the methods considered, where researchers are interested primarily in the slope parameter, estimation bias is consistently reduced using the method of moments approach.     

雄安新区科技企业创新能力评价研究

科技企业是实现科技创新的驱动者和科技成果转化的重要载体,也是推动研究开发的重要参与者,科学评价科技企业创新能力有助于企业自身不断发展壮大。在分析国内外新区科技企业创新驱动发展相关理论研究的基础上,从研发投入、研发基础、研发效益和现代科技四个角度,运用层次分析法构建科技企业创新能力评价系统,并通过实证分析说明评价系统的可靠性;根据评价系统测算出现阶段雄安新区科技企业创新能力,通过与成熟新区科技企业的比较,发现其短板和不足,力图为决策者科学合理评价、管理科技企业创新发展提供有益参考。     

英文影片的中国方言版字幕翻译

2012年3D 版《泰坦尼克号》的华丽上映曾掀起影迷们对它的新一轮热捧。文章就同样备受中国观众喜爱的中国方言版《泰坦尼克号》为案例，结合功能目的论来探寻中国方言版字幕翻译的目的与性质，进而分析、总结英文影片字幕的中国方言版译制活动过程。     

章公祖师佛像跨国追索诉讼国际私法问题研究

从章公祖师佛像跨国追索诉讼主体资格问题切入,分析佛像的法律性质,探讨涉案物权准据法的确定及适用问题。该案原告应由阳春村全体村民担任。涉案佛像属于文物,建议村民在荷兰法院提起原物返还之诉。受案法院应当适用物权冲突法确定准据法,即可能适用中国内地、中国香港或荷兰法律。被告在购买时应当对涉案佛像来源产生合理怀疑,因此不构成“善意”;原告应尽可能搜集证据证明《荷兰民法典》规定的20年消灭时效因起诉而中断。依据《香港货品售卖条例》和中国内地物权法理论与实践,被告均不能取得系争佛像的所有权。     

当代资本主义经济停滞问题:制度结构与治理危机——基于积累的社会结构理论的分析

关于经济停滞问题的探讨是对马克思主义经济危机理论的传承。2008年金融危机爆发十余年,资本主义经济停滞趋于常态化。积累的社会结构理论从资本积累与支撑这一积累的制度环境之间的矛盾出发,发现了主流经济学探讨资本主义经济停滞所忽略的制度性因素。积累的社会结构学派沿着"中间层次"的路径,将2008年金融危机界定为系统性的结构危机,认为新自由主义SSA的失灵是此次经济停滞持续的原因。资本主义经济停滞引发欧美发达资本主义国家的社会治理危机升级,一系列政治、社会和文化危机不断加剧。积累的社会结构理论从微观层面深刻把握了资本主义制度转型的轨迹,但并未深入探讨开展根本的制度变革。在面临百年未有之大变局的时代境遇下,中国在参与全球治理的过程中不断探索并推动世界经济政治新秩序朝着更加公正、合理的方向发展。     

Toward a sociology of global comparative placemaking

I call for a globally informed sociology of comparative placemaking that integrates historical and contemporary processes and includes the ephemeral, institutional, and personal. By placemaking, I am referring to the explicit or tacit cooperation among people to create, maintain, and give meaning to places in space through bodily occupation given differential resources and constraints. I review select place, space, and community-based literature about urban, Black, migrant, LGBTQ, and international populations to think about how we can build upon and integrate multiple theoretical, methodological, and epistemological insights to form an explicit placemaking research agenda. A US focus on neighborhoods contrasts with a comparative examination of global urban networks, social polarization, and transformation of the built environment in the interdisciplinary field of global urban studies (Ren, 2018). I argue for a placemaking research agenda that bridges insight from US Urban Sociology with Global Urban Studies to consider how various structures and actors constrain and facilitate place projects. With a globally reaching and comparatively informed sociology of placemaking, we can illuminate our multi-structured story of place and agency in context. We can answer questions about how and why we co-create and are simultaneously disciplined by the process of creation.     

Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

“动物与人”：叙事伦理、悖反性与双重困境指向——论“抉择之痛”作为功能指涉的效力边际

对初始情境中受难者“陷困”功能的探讨，是“动物叙事”叙事语法研究中不容忽视的一环，其中贯穿了一个最为基础的叙事功能指向——“抉择之痛”。强调“动物与人”两类受难者角色在身体、心理抑或情感维度陷入某种矛盾与纠结的状态，并且彼此间时常呈现出一定的矛盾悖反性。这一角色身份由动物形象与人类形象分别或共同承担，均指向一种叙事伦理层面的现代境遇的表达。在题材范畴方面，这一功能指涉涵盖了家养类与野生类“动物叙事”各自的叙事范畴。其效力边际已不仅仅局限在单纯生态视域与人性指涉的层面，而是凸显现代语境下人类所面临的共通性的伦理困境：一种挥之不去的矛盾、困惑与不安的情感和心境的写照。     

制度风险的法律维度: 突破非物质文化遗产保护的瓶颈

以风险理论审视非物质文化遗产的现行法律制度,根据风险产生根源不同,非物质文化遗产保护的制度风险会表现为制度运转失灵风险、制度功能偏差风险和公平性缺失风险。化解制度风险,形成制度风险的维度,不可基于同一个标准,而是需要在大的框架之下论及制度风险的法律管控,需要有针对性地创构"建立私权,善用公权"的多元法律控制体系,并在体系内引入技术规制,创设"非物质文化遗产权",推动民间习惯法与法律制度、公法与私法的互动式发展。