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.     

锌表面Mo(W)-S-Zn簇合物膜的XPS和AES研究

在锌表面获得了多种不同颜色且具有金属光泽的不溶性Mo(W)-S-Zn簇合物转化膜,所获膜层具有良好的耐蚀性能和装饰效果,加热处理后颜色将发生变化,加速腐蚀试验结果表明,金黄色膜耐蚀性最佳。FT-IR、FT-Raman、XPS和AES分析表明,该膜层厚度约为60nm。钼在膜表面的价态为+6价,而在膜内则以+6、+4价共存。从AES深度分布曲线可知,其组成为32.5％Zn,19.3％Mo,39.4％S,8.5％O。膜为多分子层组成的复杂体系,其颜色是各组分统计分布的结果。     

我国民事审级制度的改革与完善——比较法学视角下的分析

比较分析中国、日本、德国、美国、法国及我国台湾地区的民事审级制度可以看出我国审级制度中存在的弊端。实际上 ,实行有条件的三审终审制更具合理性。为此 ,我国原有的两审终审制必须加以改革 ,那就是实行以两审终审为原则、以三审终审为例外的民事审级制度。     

工业企业经济效益综合评价与分析

利用SPSS软件,对我国31个省、直辖市的大中型工业企业的总资产贡献率、成本费用利润率、资本保值增值率、流动资产周转次数、全员劳动生产率、产品销售率、资产负债率、总资产周转率、净资产收益率、销售利润率等十个经济效益指标进行了因子分析,并将这十个指标归结为盈利、销售、运营、发展等多个因子。最后,根据每个因子得分情况将所有地区归为六类,进而做出综合评价。     

A general inverse sampling scheme and its application to adaptive cluster sampling

Not having a variance estimator is a seriously weak point of a sampling design from a practical perspective. This paper provides unbiased variance estimators for several sampling designs based on inverse sampling, both with and without an adaptive component. It proposes a new design, which is called the general inverse sampling design, that avoids sampling an infeasibly large number of units. The paper provide estimators for this design as well as its adaptive modification. A simple artificial example is used to demonstrate the computations. The adaptive and non‐adaptive designs are compared using simulations based on real data sets. The results indicate that, for appropriate populations, the adaptive version can have a substantial variance reduction compared with the non‐adaptive version. Also, adaptive general inverse sampling with a limitation on the initial sample size has a greater variance reduction than without the limitation.     

哈尔滨市发展绿色食品产业集群的基本条件与优势

产业集群对集群内企业在竞争力提升上有重要作用。哈尔滨市发展绿色食品产业集群,具有得天独厚的地理环境和资源优势,具有大企业集团集中、高校和科研院所较多的优势,及在国内外市场上的品牌和信誉优势。通过绿色食品产业集群的发展壮大,必将提高产品与企业的市场竞争力,推动绿色食品产业的持续发展。     

Asymptotic bias in the linear mixed effects model under non-ignorable missing data mechanisms

Summary.  In longitudinal studies, missingness of data is often an unavoidable problem. Estimators from the linear mixed effects model assume that missing data are missing at random. However, estimators are biased when this assumption is not met. In the paper, theoretical results for the asymptotic bias are established under non-ignorable drop-out, drop-in and other missing data patterns. The asymptotic bias is large when the drop-out subjects have only one or no observation, especially for slope-related parameters of the linear mixed effects model. In the drop-in case, intercept-related parameter estimators show substantial asymptotic bias when subjects enter late in the study. Eight other missing data patterns are considered and these produce asymptotic biases of a variety of magnitudes.     

追求自我解放 寻觅自由人生--劳伦斯笔下的理想女性厄秀拉

劳伦斯笔下的叛逆女性厄秀拉是劳伦斯塑造的最理想的人物.她为人正直,追求真理与不合理的社会进行奋力抗争,虽屡遭失败,仍不放弃追求,最后在大自然和周游世界中获得了自由.厄秀拉的这种追求是作家拯救西方人摆脱精神危机的有价值的尝试.     

重庆市培育金融核心区：布局、路径与对策

金融核心区的培育是提升重庆金融集聚力和辐射力以及构建长江上游地区金融中心的关键因素.在审视金融核心区的概念、内涵和重庆市培育金融核心区的必要性、可能性基础上,运用大系统分析方法的原理,提出重庆金融核心区的规划布局和总体思路;基于产业集群理论探讨重庆金融核心区的培育路径与对策.研究认为,培育重庆金融核心区,要在运筹高端金融商务发展体系、夯实现代金融业发展平台、拓展金融业发展空间等三个方面合理布局金融产业,促进形成金融业产业集群,并优化金融生态环境和金融主体结构、强化金融资源共享和政府公共服务职能.     

从部门本位回归到基本理性——对检察机关职权配置的思考

目前,我国法学界对检察机关职权配置问题存在着激烈的争论。争论的主要问题有三个。其中,检察机关是否有侦查权是个伪问题,其本质是检察机关行使侦查权时由谁来监督;检察官不是“中立及超然”的司法人员,不应当有对强制措施的批准权;检察官不应当以居高临下的“法律监督者”的身份监督审判程序,而是应当通过程序动议权和上诉权监督审判程序。目前主张维持检察机关职权现状的学者,有严重的部门本位主义,检察权改革应当摒弃部门本位主义。