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.     

中外合作办学的现状及问题分析

文章就中外合作办学的质量、合作者的水平和资质、合作办学的监管等问题进行了分析,并提出了相应的几点对策建议。     

现实化&#183;个性化&#183;多元化——试论中国当代文学农村干部形象的嬗变

中国当代农村题材的长篇小说,基本是与中国农村的社会变革同步.作为党和农民之间的桥梁,农村变革的带头人,农村干部是农村中最具时代特色的一个群体,他们是中国当代文学人物画廊中不可或缺的重要组成部分,把握住他们的精神特质、性格特征及其嬗变的轨迹,就能大体把握住新中国农村社会生活发展演变的历史,从中吸取教训和得到启迪.     

谈作文评分的误区

教师忽略学生学习的现状,对作文求高求大求全,是影响学生作文的消极因素之一。宜根据实际客观地评分,并 适当运用激励方法,激发学生的写作兴趣,提高作文水平。     

绝望者的寓言--从《变形记》和《现实一种》看卡夫卡对余华的影响

本文从影响研究的角度,以《变形记》和《现实一种》为例,分析奥地利作家卡夫卡对中国先锋派作家余华的影响。 余华不仅在叙述风格上,而且在小说意义的处理方式上和情绪浸染方面,均与现代文学鼻祖卡夫卡遥相呼应。     

A modified random-effect procedure for combining risk difference in sets of 2×2 tables from clinical trials

Summary Meta-analyses of sets of clinical trials often combine risk differences from several 2×2 tables according to a random-effects model. The DerSimonian-Laird random-effects procedure, widely used for estimating the populaton mean risk difference, weights the risk difference from each primary study inversely proportional to an estimate of its variance (the sum of the between-study variance and the conditional within-study variance). Because those weights are not independent of the risk differences, however, the procedure sometimes exhibits bias and unnatural behavior. The present paper proposes a modified weighting scheme that uses the unconditional within-study variance to avoid this source of bias. The modified procedure has variance closer to that available from weighting by ideal weights when such weights are known. We studied the modified procedure in extensive simulation experiments using situations whose parameters resemble those of actual studies in medical research. For comparison we also included two unbiased procedures, the unweighted mean and a sample-size-weighted mean; their relative variability depends on the extent of heterogeneity among the primary studies. An example illustrates the application of the procedures to actual data and the differences among the results. This research was supported by Grant HS 05936 from the Agency for Health Care Policy and Research to Harvard University.     

大学英语与专业英语的融合——基于江西农业大学的个案分析

大学英语与专业英语的教学都是大学英语课程体系的有机组成部分,以江西农业大学专业英语教学现状作为个案调查对象,分析了当前专业英语教学中存在的问题和面临的困境。     

我国网络经济发展研究

阐述了网络经济的特点及其我国网络经济的现状和发展的必要性 ,提出建立适于网络经济发展的大环境、更新观念、注重人才培养、完善金融体系、建立虚拟企业和发展电子商务等几个方面的发展途径 ,并对利用网络经济的后发优势实现经济的跨跃式发展进行了探讨。     

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.     

颜面论

颜面是由多元素多层项内容组成的多向度文化精神综合概念。故从个人、家庭、企业到国家都存在颜面问题。其礼义廉耻、自尊、个性、权利等成分若加以正确规范引导有其积极意义与价值 ;若表面化视为一种虚荣的名誉身份地位表现则易转为无形无味腐蚀剂。中国人最讲也最爱面子 ,是人情大如天、人际与人生哲学的发祥地和信奉者。它在表面人情味下往往成为各种腐败现象之温床 ,故无论个人、家庭、公司企业和国家只有育成科学合理正确的颜面观 ,才能抑丑恶扬美善 ,为自己和国家体面地生存发展争得颜面和荣誉。