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.     

Subjective utility with upper and lower probabilities on finite states

This article is concerned with thresholds of discrimination of preference judgments under uncertainty. We establish an axiomatic characterization for a threshold representation, where thresholds are represented by inexact measurement of subjective probabilities, i.e., upper and lower probabilities. Since upper and lower probabilities need not be additive, the representational form adopts the Choquet integration.     

明清时期长江中下游地区的土地利用

我国明清时期长江中下游地区的土地利用状况是自汉、唐以来人地关系日益尖锐的结果。文章在分析了当时土地利用方式的基础上 ,进一步对形成土地集约化经营趋势日趋明显的原因进行了论述 ,并从明清时期的土地利用得出启示 :我国土地资源的开发利用必须走可持续发展之路     

Modelling daily multivariate pollutant data at multiple sites

Summary. This paper considers the spatiotemporal modelling of four pollutants measured daily at eight monitoring sites in London over a 4-year period. Such multiple-pollutant data sets measured over time at multiple sites within a region of interest are typical. Here, the modelling was carried out to provide the exposure for a study investigating the health effects of air pollution. Alternative objectives include the design problem of the positioning of a new monitoring site, or for regulatory purposes to determine whether environmental standards are being met. In general, analyses are hampered by missing data due, for example, to a particular pollutant not being measured at a site, a monitor being inactive by design (e.g. a 6-day monitoring schedule) or because of an unreliable or faulty monitor. Data of this type are modelled here within a dynamic linear modelling framework, in which the dependences across time, space and pollutants are exploited. Throughout the approach is Bayesian, with implementation via Markov chain Monte Carlo sampling.     

公共政策的社会观基础

本文从一个新的视角──社会现的视角──审视了公共政策。因为在过去的有关公共政策的定义中，我们无法看出各个政策的重大区别，而事实上它们在是否符合人性的需求，充分考虑民意的基础并有效促进了人民的自由与福利等方面是有着重大区别的。本文将公共政策界定为是一定的权利中心在众多备选的计划、规划或可行之行动方案中作出选择并采取行动的这样一个过程。由此对选择的社会观基础进行考察，社会观影响到了人们对待集体行动的态度，进而又影响到社会秩序观。而持有不同的社会秩序观的人对公共政策有着根本不同的看法，最终得出好的公共政策的基本的制度安排。     

非统计专业统计学教育刍议

针对非统计专业统计学教育目前存在的问题,阐述了提高对统计学重要性的认识是保证统计教学效果的前提;统计学教学环节的改革是提高教学效果的重要保证;统计教师的业务素质是提高统计教学效果的关键。     

将分段函数表示为初等函数的方法

本文给出了一种化具有多个分段点，且在各区间段上的表达式为多项式函数的分段函数为初等函数的具体方法．     

Divergence-based estimation and testing with misclassified data

The well-known chi-squared goodness-of-fit test for a multinomial distribution is generally biased when the observations are subject to misclassification. In Pardo and Zografos (2000) the problem was considered using a double sampling scheme and ø-divergence test statistics. A new problem appears if the null hypothesis is not simple because it is necessary to give estimators for the unknown parameters. In this paper the minimum ø-divergence estimators are considered and some of their properties are established. The proposed ø-divergence test statistics are obtained by calculating ø-divergences between probability density functions and by replacing parameters by their minimum ø-divergence estimators in the derived expressions. Asymptotic distributions of the new test statistics are also obtained. The testing procedure is illustrated with an example.     

唐五代敦煌的宴饮坐向和座次研究

敦煌壁画中有数十幅宴饮图像 ,这些图像不仅提供了宴饮场合、“会食”状况、宴饮座制、会食人数等信息 ,而且反映了当时宴饮的方位坐向、男女、座次等尊卑观念     

几类循环图的分数染色数

通过构造几类图的最大独立集,给出了它们的分数染色数的下界;再通过构造具有该下界值的分数染色,给出了这几类循环图的分数染色数的上界,于是就确定了它们的分数染色数.