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.     

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。     

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.     

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。     

从《了凡四训》到《训儿俗说》——关于袁了凡及其家风家训的思想史考察

袁了凡（袁黄）以其《了凡四训》闻名于世，该书亦被当作训子家书。其实，了凡所作家训并非《了凡四训》，而是《训儿俗说》。作为王龙溪（王畿）的及门弟子，了凡在思想上是阳明后学的一分子，其人生轨迹属于典型的儒家士大夫，其日常修持及著述呈现三教汇通的思想特色。了凡家风淳朴，家学深厚，以儒为宗，兼收并蓄，强调道德主义，注重积德行善，具有出世情怀，对其人格产生深刻影响。     

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I–I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I–I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term “essential entities” includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state‐space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS.     

朱熹和孟子解读舜之“怨慕”的不同逻辑

对于舜之“怨慕”,朱熹作出了不同于孟子的解读。这是基于心学、理学内在逻辑的不同。孟子作为私学之儒,和孔子一样,是主张士君子的阳刚人格的,并且从性向善的人性论出发,协调义与利、公与私的关系,而以君臣父子关系都属对待关系;依此,将舜之“怨慕”解读为舜对父母的既怨又慕。朱熹则作为官学之儒,以所谓“气质之性”协调理学先驱荀子的性向恶论,以二歧化思维把天地之性、天理绝对化,以公去私,视君臣父子关系则为下对上的绝对服从关系;依此解读,舜之“怨”只能是自怨。     

需求率受推广努力水平影响的新能源汽车租赁系统协调契约

考虑由新能源汽车租赁企业和政府组成的二级系统，在需求率为随机且与推广努力水平相关的市场环境下，建立了新能源汽车租赁企业和政府之间的博弈模型，探讨了分散决策、集中决策、收益共享与成本共担契约下的最优车队配置和推广努力水平，并对三种情形下的最优决策进行了比较和分析。研究结果表明：在分散决策情况下无法实现系统协调，通过引入成本共担与收益共享组合契约，当契约参数满足一定条件时，该组合契约模型不仅可以实现系统协调而且可以使系统成员达到帕累托改进。最后通过算例分析，验证了模型了可靠性和有效性。     

Humor and satire in politics: Introducing cultural sociology to the field

The landscape of political humor and satire is changing rapidly, and it is becoming an increasingly relevant aspect of our culture. Although scholars have been actively trying to capture this change, majority of the existing frameworks for understanding humor and satire in politics still reduce these phenomena to mere genres or rhetoric tools. In addition, they provide insufficient accounts concerning the reception of humor and satire, and neglect to interpret and explain what they communicate. In the article, a general understanding of humor and satire outside of a political context, followed by an overview of studies discussing humor and satire in politics through their applications in social movements, as leadership tools, and through their manifestations in mass media has been presented. Lastly, a cultural sociological perspective to the field has been introduced. It has been argued that approaching humor and satire in politics through a structural hermeneutic method of the Strong Program will enable us to recognize and treat political humor and satire as autonomous and complex cultural systems which carry an internal power to move people.     

城市综合体建设面临的一系列问题探讨--以南通市为例

随着房地产调控和城市化进程的加快，商业地产越来越受到开发商的青睐。城市综合体作为商业地产的典型代表以其多结构多层级的功能组合迅速提升区域价值而拥有了“城中之城”的美誉，在东部地区二三线城市大量涌现。但城市综合体带动城市发展的同时，也引发了一系列风险亟待关注。