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.     

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。     

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。     

On a class exhibiting trend change in average failure rate

Abstract

Weak convergence and moment convergence issues are investigated for the New Better than Average Failure Rate (NBAFR) family (introduced by Loh (1984 Loh, W. Y. 1984. A new generalization of the class of NBU distributions. IEEE Transactions on Reliability R-33 :97–113[Crossref], [Web of Science ®] , [Google Scholar])). We explore the validity of these results in the context of a more general ageing class that we introduce. We prove some new properties of this class and derive its interrelationships with other non-monotonic ageing families. Reliability and moment bounds are obtained and an interesting characterization of exponentiality is proved. Special cases of our results lead to new theorems for the NBAFR class. Finally weak convergence and related issues are established for this class.     

美国、中国与朝鲜停战谈判中的战俘遣返问题

在1951年6月至1953年7月的朝鲜停战谈判中，战俘遣返问题是谈判双方争论最为激烈、耗时最长的议题。美国出于冷战需要，拒不同意遣返所有被俘朝中人员；而朝中方面则依据关于战俘遣返问题的日内瓦公约，要求遣返所有战俘。由于在此问题上僵持不下，致使谈判几次陷于停顿。最终，谈判双方各自做出一定让步，使得战俘遣返问题得以解决，为朝鲜停战协定的签订消除了最后也是最大的一个障碍。     

Beyond Piketty: A new perspective on poverty and inequality in India

The socio-economic literature has focused much on how overall inequality in income distribution (frequently measured by the Gini coefficient) undermines the “trickle down” effect. In other words, the higher the inequality in the income distribution, the lower is the growth elasticity of poverty. However, with the publication of Piketty’s magnum opus (2014), and a subsequent study by Chancel and Piketty (2017) of evolution of income inequality in India since 1922, the focus has shifted to the income disparity between the richest 1% (or 0.01%) and the bottom 50%. Their central argument is that the rapid growth of income at the top end of millionaires and billionaires is a by-product of growth. The present study extends this argument by linking it to poverty indices in India. Based on the India Human Development Survey 2005–12 – a nationwide panel survey-we examine the links between poverty and income inequality, especially in the upper tail relative to the bottom 50%, state affluence (measured in per capita income) and their interaction or their joint effect. Another feature of our research is that we analyse their effects on the FGT class of poverty indices. The results are similar in as much as direction of association is concerned but the elasticities vary with the poverty index. The growth elasticities are negative and significant for all poverty indices. In all three cases, the disparity between the income share of the top 1% and share of the bottom 50% is associated with greater poverty. These elasticities are much higher than the (absolute) income elasticities except in the case of the poverty gap. The largest increase occurs in the poverty gap squared – a 1% greater income disparity is associated with a 1.24% higher value of this index. Thus the consequences of even a small increase in the income disparity are alarming for the poorest.     

《1844年经济学哲学手稿》与《神圣家族》中的生活思想

《1844年经济学哲学手稿》和《神圣家族》都是马克思主义创始人早期思想的代表性著作，二者都把“生活”作为重要概念进行论述。从作为经济学哲学概念到作为社会批判概念，马克思主义创始人对“生活”的认识经历了从对物质生产活动的重视到对无产阶级普遍贫困生活的揭露，从分析“生产生活”的异化到对“非人性”生活的批判，从“生活的手段”到消灭“非人性的生活条件”的思想历程。人类的历史是人类生活发展的历史。解决人的美好生活如何实现的问题，在马克思恩格斯的生活思想中居于核心地位，这对当今中国具有重要的理论指导价值。中国特色社会主义进入新时代，从开启一种全新文明的生活形态的高度来理解新时代的美好生活，才能准确把握我国社会主要矛盾变化的深刻意义。     

冷战后的中美政治安全关系

冷战结束十年以来 ,美国的对华政策依然摇摆不定。之所以如此 ,是因为十年来美国视中国为敌还是为友 ,或者非敌非友 ,至今还未定性。而美国难于在其国际政治安全战略中给中国定性的原因 ,则与以下的三个层次密切相关 ,即美国的国内政治层次、中美关系的发展层次和全球层次。     

福建省科技资源配置的现状、问题及对策

利用翔实的统计数据和资料,从科技人力资源、财力资源、技术资源等方面分析了福建省科技资源配置的现状及存在的问题,并针对存在的问题提出了相应的对策和建议。     

Trends in the Race and Ethnicity of Eminent Americans

During the last several decades, the ethnic and racial composition of the American elite has changed to include some ethnic minorities and women. This study examines changes in the composition of one segment of the American elite: those who have obtained eminence in their occupations. Lieberson and Carter's study of the ethnic composition of eminent Americans, using Who's Who in America, is replicated with data from the 1990s (Lieberson and Carter, 1979, American Sociological Review 44:347–366). In addition, comparisons between blacks listed in Who's Who in America and blacks listed only in Who's Who among Black Americans are made. During the 20 years since Lieberson and Carter's study, Jews have made remarkable gains in eminent membership, while the rate of black representation has increased only moderately. Women are a small percentage of the eminent regardless of ethnicity, although black women are better represented than their counterparts in white ethnic groups.