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.     

体验型产品消费行为的羊群效应及机理研究——基于电影行业消费行为的实证解释

互联网环境下消费者购买体验型产品时对网络信息的依赖性很大。因此，研究社交媒体影响下体验型产品的消费者决策选择行为具有现实意义。本文以电影行业的票房偏离及消费跟风现象为切入点，探究体验型产品的羊群效应并对其产生的内在机理进行解释。采集艺恩资讯的票房数据以及豆瓣的电影基本信息及影评等数据作为研究样本，从消费者"羊群行为"视角分析其对电影票房的影响。研究发现：在控制了质量等内生性影响之后，消费者羊群效应依然存在；产品特征信息对羊群效应起到了调节作用，从而形成理性跟随；采用预期差异模型可以解释消费者实现理性跟随的过程。研究结论对于电影行业宏观政策制定及对体验型产品合理进行营销推广提供了理论基础与实证依据。     

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.     

大众传播中的“国家教师”媒介形象分析

运用传播学内容分析法，以中央媒体对获得"全国教书育人楷模"和"最美教师"荣誉称号的"国家教师"相关报道为研究对象，从外在和内在两个方面对大众传播的"国家教师"媒介形象进行分析。外在形象包括教师性别、年龄、教龄、外表、场景以及任教的学校类别、区域、学科专业等方面，内在形象包括职业精神、职业知识和职业能力等方面。研究发现，大众媒体对"国家教师"形象的刻画和宣传符合社会公众认知教师职业的基本逻辑，起到了传递教师精神、端正教师形象、唤起社会尊重教师的功效，但也存在城乡教师形象传播刻板化以及教师普通人形象展现不充分等问题，可在后续的传播中对"国家教师"形象的价值倾向进行适当调整。     

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。     

精神回溯与意象精研的本质书写--林雪诗歌评论

林雪是当代汉语诗歌的重要诗人，她“在心为志，发言为诗”，诗风大气沉郁。她近期的诗歌，情怀与思辨相互倚重、酵化，介入生活与提炼心性同步发力，题材多样，手法多变，情感收放自如，气韵放达从容。她对现实的观照，对时空的架构，对存在的开掘，都呈现出一种新的气象。她自觉地从先期女性主义诗写中觉醒，到如今的清澈中隐显尘世的味蕾，对生活细节和感念触觉的精妙镂刻，以及对世道人心的专注和细致打量。     

Overcoming Old in Age-Friendliness

In this article, we explore views on an age-friendly space in the Netherlands by analysing the responses of older individuals (N = 54) in focus groups and by examining the perspectives around an age-friendly zone in the Netherlands, Parkstad Limburg. We found that a central issue in the wishes for living at a later age are adjustments to envisioned physical limitations that come with the ageing process; this includes adjustments to ensure safety, accessibility and mobility, in order to facilitate older individuals' efforts to stay engaged with the world around them. In their wishes, the older participants constructed ideal dwelling places that closely resembled a senior home, but at the same time they rejected wishing to live in a place that was identified as a senior home. We explain this paradox by the representation of such a space as being for old people, i.e. needy older individuals, which was not how the older participants wished to be identified. We conclude that the conception of age-friendly environments will have to face the difficult challenge of overcoming the association with old age, while simultaneously taking into account adjustments that signify and relate to the ageing process and that seem inescapably tied to oldness.     

Journey towards independent living: a grounded theory investigation of leaving the care of Girls & Boys Town,South Africa

The journey out of care and towards independent living is a challenge for many care-leavers. There has been little research into the social processes involved in this care-leaving journey. This paper presents the results of a grounded theory investigation into the care-leaving journeys of nine young men who had, several years previously, been in the care of Girls & Boys Town in South Africa. Working from a resilience perspective, with an ecological emphasis, four central social processes emerged that together explain the care-leaving experiences of the participants. These processes are striving for authentic belonging; networking people for goal attainment; contextualised responsiveness and building hopeful and tenacious self-confidence. These four processes are located within contextual boundaries and at the social environmental interface. The paper presents these processes in detail, drawing on selected narratives of the participants and integrated with additional theory. It is hoped that this paper may contribute to theory building concerning care-leaving processes and enhance youth care practices for youth in care and leaving care.     

关于高校中层副职干部几个基本问题的思考

高校中层副职干部具有高校干部、中层干部和副职干部的群体特征，应当具备相应的政治、思想、道德、业务、能力和身体等方面的基本素质。高校应当按照现行干部配置规制，结合内部管理体制和工作机制任用干部。高校中层副职干部的日常活动涉及到社会、学校、家庭等多个层面，必须妥善处理好各种人事关系。