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。     

农村互助型社会养老:中国特色与发展路径

农村互助型社会养老是具有中国特色的社会养老的发展形式，是对农村传统家庭养老的重要补充。它扎根于农村传统的亲邻互助网络，其本质在于经济互助，表现为有组织地发动邻里、志愿等社会力量，充分利用以老年人为主的各类人力资源的闲置时间、资源低成本地相互帮助和服务。社会各界应将其作为重要实施方略，纳入积极应对人口老龄化战略和乡村振兴战略之中。其发展路径可以概括为：以资金互助为基础，以组织动员为抓手，以服务互助为重点，以社区居家养老为主要阵地，创新各类互助养老模式，着力形成稳定多元的资金来源，培育互助队伍，增加互助内容，从无偿到无偿、低偿相结合，探索建立标准规范的服务管理评估制度，机构养老与社区居家养老互联互通，最终尝试建立圈层化、整合化、网络化、制度化的农村互助型社会养老体系。     

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。     

影子银行、地方政府债务及金融发展动态关系研究——基于省级面板VAR模型

基于2004—2017年中国省级面板数据,运用面板向量自回归(PVAR)模型,使用系统GMM估计、脉冲响应函数、方差分解以及格兰杰因果关系检验等方法分析了影子银行、地方政府债务及金融发展之间的动态关系.结果表明:影子银行、地方政府债务与金融发展水平三者之间存在动态耦合关系.在地方政府融资能力受到约束的情况下,影子银行为地方政府提供了多元的融资方式,在增加政府融资能力的同时提升了政府债务水平;而地方政府债务需求显著推动了影子银行规模的快速发展.同时,影子银行过度扩张危害了金融市场的健康发展,降低金融发展水平,继而使地方政府的融资渠道受到约束.但金融发展并不能有效约束影子银行规模,原因在于,政府融资需求是影子银行的主要动力,若不能控制地方政府的借贷行为则无法从源头解决问题.监管机构在去杠杆的过程中,应该综合考虑影子银行与地方政府债务、金融发展之间的动态关系,如此才能够实现预期的政策效果.     

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。     

Does a universal non-contributory social pension make sense for rural China?

China’s pension reform during the past three decades has allowed a majority of China’s population to be covered by a pension scheme. Of particular note has been the New Rural Pension Scheme (NRPS), a voluntary programme introduced starting in 2009. One goal of our analysis is to assess that pension scheme, using a variety of sources of information including data drawn from recent (2013 and 2015) nationwide China Health and Retirement Longitudinal Surveys (CHARLS). Our analysis involves an exploration of differences between the generosity and structure of the NRPS and other pension schemes currently in place. We also explore the feasibility of reforming the current “quasi-social pension” component of the NRPS by substituting a universal non-contributory social pension pillar. In connection with our assessment of the NRPS, we note the unusually low benefit levels for rural China.