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.     

Becoming Custodial Dads: Exploring Parenting Among Low‐Income and Working‐Class African American Fathers

The authors use an ecological framework and grounded theoretical analysis to explore the circumstances in which working‐class and low‐income custodial African American fathers gain custody of their children, their transition from part‐time to full‐time parents, and the role of support networks in enhancing or inhibiting these men's parenting. Twenty‐four men from an impoverished Midwestern urban area participated in the study. The findings suggest that these men, and perhaps others sharing their demographic profiles, generally become parents by default and are often reluctant to take on a full‐time, single parenting role. Adaptation to the role seems to be enhanced by these men's use of extended kin support networks and shared living arrangements. However, low wages, a lack of sufficient assistance from public assistance programs, and informal custody arrangements often inhibit their fathering.     

高性能可重构DSP处理器的数据通路设计

介绍了高性能定点可重构DSP处理器的数据通路设计。该数据通路以功能强大的16位定点计算单元为基础,搭建起高速16位数据处理平台;并能以单指令流多数据流的方式灵活支持多维向量运算;通过重构的方法有效地支持了32位数据处理。     

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。     

《孟子》中的单音节形容词研究

文章主要从量的角度对《孟子》中的单音节形容词的句法功能进行研究,通过与现代汉语形容词的特征比较,结果发现单音节形容词作谓语(不带宾语),单音节形容词作宾语,单音节形容词带宾语以及单音节形容词作定语是《孟子》中的单音节形容词的重要特征。     

Determinants of housing quality: A comparison of white,African-American,and Hispanic single-parent women

This study examines housing quality among three groups of single-parent women: white, African-American, and Hispanic. Three indicators of housing quality—crowding, affordability, and satisfaction—are used to discover the extent to which these groups experience housing problems. This study also explores differences and similarities in the factors that precipitate problems in housing quality for these three groups of single parents. Findings suggest important differences and similarities in the nature of housing quality problems among white, African-American, and Hispanic single-parent women. The specified variables explained about 20% of the variance in crowding, housing affordability, and housing satisfaction. On measures of objective and subjective housing quality, white single mothers are better housed than their African-American or Hispanic counterparts. Hispanic single mothers have the largest housing cost burden and average more persons per household than the other groups. African-Americans are twice as likely as either group to live in low-quality housing and reported the lowest average satisfaction with their housing. Her research interests include housing and neighborhood assessment and women and public policy issues. She has recently published articles inUrban Affairs Quarterly andHousing and Society on housing and neighborhood assessment criteria among black urban households and the housing cost burden of various groups of female-headed households. She received her Ph.D. from Ohio State University. Her research interests include the housing adjustment behavior of women and public policy. She has recently completed her thesis on the role of noncustodial parents in determining the quality of life of their children. She is also the recipient of the Tessie Agan Award for research excellence from the American Association of Housing Educators for a paper titled “Unterstanding Constraints and Residential Satisfaction among Low-Income Single-Parent Families.”     

论拉伦茨氏裁判方法的实质

使用传统的判案理论系统分析了拉伦茨氏的方法论体系。指出，拉伦茨氏方法论的基础是欧洲传统“名判”逻辑，其设定目标乃个案公决。拉伦茨氏强调了法官“续造法”的权力。所续造的“法”不是条法，而是曾经自主运用诸条法的模式，它理应有“现行法”的拘束力。“条法库”的缺漏由审判员以法律运用技术补足。诸准则之不谐或与宪法条法的不谐需赖“法益衡量”调谐。分析结论是，拉伦茨氏片面突出法官的自主地位，其方法论在本质上是现代法治社会一种尚需调制的折衷系统。     

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.     

维吾尔语主位结构与句子主语关系研究

以韩礼德和汤普森关于主位结构的理论为依据,分析维语各种语气结构中的主语和单项主位的关系,发现维语主语在多数情况下充当无标记性主位,主语和主位的重合在陈述句中最为明显。但是,维语主语有时也可以充当无标记性述位。     

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.