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.     

精神脱贫:内涵阐释与路径探索

贫困是一个多维概念,物质脱贫之后,还有精神脱贫问题.所谓精神脱贫,是指个体或者群体的精神水平和观念素质不落后于社会物质生产方式和社会整体精神与观念素质平均水平的生存状态.精神脱贫的内涵具有动态变化性,新发展阶段精神脱贫主要由互相关联的四方面构成:主体意识是基础,积极进取的人生态度、主动参与精神是核心,科学的思维方式是表现.四方面密不可分,相辅相成,共同构成新发展阶段精神脱贫的丰富内涵.新发展阶段推进精神脱贫:一是要精准识别,摸清精神扶贫对象,这是必要前提;二是加强教育,培养主体意识,这是重要基础;三是积极开展文化活动,以文化人,这是关键措施;四是巧用典型,提振精气神,这是有益补充.     

Ethical Numbers: Ethics Training in U.S. Graduate Statistics Programs, 2013–2014

As important members of research teams, statisticians bear an ethical responsibility to analyze, interpret, and report data honestly and objectively. One way of reinforcing ethical responsibilities is through required courses covering a variety of ethics-related topics at the graduate level. We assessed ethics requirements for graduate-level statistics training programs in the United States for the 2013–2014 academic year using the websites of 88 universities, examining 103 biostatistics programs, and 136 statistics degree programs. We categorized programs’ ethics training requirements as required or not required. Thirty-one (35.1%) universities required an ethics course for at least some degree students. Sixty-two (25.5%) degree programs required an ethics course for at least some students. The majority (77.4%) of required courses were worth 0 or 1 credit. Of the 177 programs without an ethics requirement, 19 (10.7%) listed an ethics elective. Although a single ethics course is insufficient for instilling an ethical approach to science, degree programs that model expectations through coursework point to the value of ethics in science. More training programs should prepare statisticians to consider the ethical dimensions of their work through required coursework. Supplementary materials for this article are available online.     

Foreign-born and native-born migration in the U.S.: evidence from linked IRS administrative and census survey records

Journal of Population Research - This paper details efforts to link administrative records from the Internal Revenue Service (IRS) to American Community Survey (ACS) and 2010 Census microdata for...     

奥古斯特·倍倍尔的社会主义思想及其对马克思主义的丰富和发展

奥古斯特·倍倍尔(1840-1913)是德国社会民主党的主要领袖和创始人之一,也是德国工人运动和国际工人运动著名的政治家和活动家.他的社会主义思想,大多是从革命实践中形成的,对德国工人运动和社会主义运动具有实际的指导作用.他的社会主义思想,既是对马克思主义基本理论的继承,又是对马克思主义思想的丰富和发展.在继承了马克思主义基本原理的基础上,倍倍尔在无产阶级政党建设的具体问题、无产阶级政党的具体斗争方式与斗争策略问题、以及妇女解放事业与实现社会主义的关系问题上,进一步丰富和发展了马克思主义.     

论电子商务对税收的冲击

针对迅速崛起的电子商务的特点深入分析电子商务对税收各个方面的冲击和影响 ,提出加大对电子商务征税力度的有关建议 ,对完善电子商务征税有积极意义。     

产业经济系统与产业分类的(f,θ,D)相对性准则

产业经济系统是由各个不同的产业和它们之间的经济关系共同构成的有机整体。在此基础上提出了产业分类的一般方法 :(f,θ,D)相对性准则。这里 f为原始经济关系 ,θ为分类准则 ,一般为半等价关系 (相似关系 ) ,D为关系 f的权重水平。分类相对性准则指出 f,θ,D这三者中任何一个发生变化 ,都会导致不同的产业划分。传统产业分类方法都是 (f,θ,D)相对性准则的特殊情况     

Measuring agreement between two statistics with applications to age standardization

Summary.  We detail a general method for measuring agreement between two statistics. An application is two ratios of directly standardized rates which differ only by the choice of the standard. If the statistics have a high value for the coefficient of agreement then the expected squared difference between the statistics is small relative to the variance of the average of the two statistics, and inferences vary little by changing statistics. The estimation of a coefficient of agreement between two statistics is not straightforward because there is only one pair of observed values, each statistic calculated from the data. We introduce estimators of the coefficient of agreement for two statistics and discuss their use, especially as applied to functions of standardized rates.     

价值新概念与资源配置和利用

经济运行从开始到达稳定状态一般经过七个阶段。传统劳动价值论认为 ,商品价值由物质生产部门的劳动者在社会生产的第二阶段实际耗费的劳动者支出量加上生产资料转移的价值决定。新价值论认为 ,现代产品价值由产品基本价值、生产资料价值和自然资源价值三部分构成 ,产品基本价值由社会各部门应该耗费的社会必要劳动能力量在生产的前提阶段内在地决定并在第七阶段成为现实。由此决定了传统的价值概念不能包含资源配置和利用。新价值概念本身就蕴涵着资源配置和利用。     

Bayesian analysis of mixture modelling using the multivariate t distribution

A finite mixture model using the multivariate t distribution has been shown as a robust extension of normal mixtures. In this paper, we present a Bayesian approach for inference about parameters of t-mixture models. The specifications of prior distributions are weakly informative to avoid causing nonintegrable posterior distributions. We present two efficient EM-type algorithms for computing the joint posterior mode with the observed data and an incomplete future vector as the sample. Markov chain Monte Carlo sampling schemes are also developed to obtain the target posterior distribution of parameters. The advantages of Bayesian approach over the maximum likelihood method are demonstrated via a set of real data.