Estimates of subgroup treatment effects in overall nonsignificant trials: To what extent should we believe in them?

In drug development, it sometimes occurs that a new drug does not demonstrate effectiveness for the full study population but appears to be beneficial in a relevant subgroup. In case the subgroup of interest was not part of a confirmatory testing strategy, the inflation of the overall type I error is substantial and therefore such a subgroup analysis finding can only be seen as exploratory at best. To support such exploratory findings, an appropriate replication of the subgroup finding should be undertaken in a new trial. We should, however, be reasonably confident in the observed treatment effect size to be able to use this estimate in a replication trial in the subpopulation of interest. We were therefore interested in evaluating the bias of the estimate of the subgroup treatment effect, after selection based on significance for the subgroup in an overall “failed” trial. Different scenarios, involving continuous as well as dichotomous outcomes, were investigated via simulation studies. It is shown that the bias associated with subgroup findings in overall nonsignificant clinical trials is on average large and varies substantially across plausible scenarios. This renders the subgroup treatment estimate from the original trial of limited value to design the replication trial. An empirical Bayesian shrinkage method is suggested to minimize this overestimation. The proposed estimator appears to offer either a good or a conservative correction to the observed subgroup treatment effect hence provides a more reliable subgroup treatment effect estimate for adequate planning of future studies.     

篇章具象纽带的翻译

本文就篇章具象纽带的翻译问题展开讨论。认为翻译中应考虑具象的完整性,语法的随意性和标点的缺失性三个特点。     

浅谈增强支部凝聚力的几条途径

增强支部凝聚力、战斗力 ,必须搞好“一班人”的团结。为此 ,要有大局意识 ,一切工作要以党的事业和全局利益为重 ;要搞好五湖四海 ,不搞小圈子 ;要眼界宽阔 ,胸襟宽阔 ;要处理好敏感问题 ,保持良好的同志关系 ;要开展批评和自我批评 ,及时解决不团结问题     

Methods for exploring treatment effect heterogeneity in subgroup analysis: an application to global clinical trials

Multi‐country randomised clinical trials (MRCTs) are common in the medical literature, and their interpretation has been the subject of extensive recent discussion. In many MRCTs, an evaluation of treatment effect homogeneity across countries or regions is conducted. Subgroup analysis principles require a significant test of interaction in order to claim heterogeneity of treatment effect across subgroups, such as countries in an MRCT. As clinical trials are typically underpowered for tests of interaction, overly optimistic expectations of treatment effect homogeneity can lead researchers, regulators and other stakeholders to over‐interpret apparent differences between subgroups even when heterogeneity tests are insignificant. In this paper, we consider some exploratory analysis tools to address this issue. We present three measures derived using the theory of order statistics, which can be used to understand the magnitude and the nature of the variation in treatment effects that can arise merely as an artefact of chance. These measures are not intended to replace a formal test of interaction but instead provide non‐inferential visual aids, which allow comparison of the observed and expected differences between regions or other subgroups and are a useful supplement to a formal test of interaction. We discuss how our methodology differs from recently published methods addressing the same issue. A case study of our approach is presented using data from the Study of Platelet Inhibition and Patient Outcomes (PLATO), which was a large cardiovascular MRCT that has been the subject of controversy in the literature. An R package is available that implements the proposed methods. Copyright © 2014 John Wiley & Sons, Ltd.     

两个有限群子群指数之集相等的几个充分条件

讨论了子群指数之集的性质以及给出了两个有限群子群指数之集相等的充分条件.     

"中国信心":当代中华民族凝聚力的现实解读

"中国信心"不仅仅是一个新闻词汇或政治口号,而是引领当代中国社会发展的民族精神和时代精神的精华.在内涵上,"中国信心"是民族性与时代性的辩证统一,是中国特色社会主义理论体系的重要内容;在本质上,"中国信心"是成就感与使命感的高度结合,是社会主义精神文明建设的时代展示;在功能定位上,"中国信心"是当代中华民族凝聚力增强的鲜明亮点,对提升国家文化软实力具有重要意义.     

英语语篇衔接手段与理解

正确理解单词或短语的含义及句子与句子之间的关系是语篇解读的重要前提,而任何英语学习者在语篇解读时都会不可避免地碰到以上的问题。探讨了英语语篇中几个主要的衔接手段在语篇解读时所起的重要作用。     

给定西洛子群的正规化子与有限群的结构

探讨了群G的Sylowp-子群和Sylowq-子群的正规化子是超可解群(幂零群),且研究了在G中的指数是素数的幂的{p,q}-可解群G的结构.     

“连接手段”在英语写作中的作用

“连接”并非专指连词的运用 ,代词和副词也常用来衔接上下文 ;恰当地使用过渡词语以及重复关键词也常常能取得连接的效果。连接手段主要是通过三种形式来体现 :表明逻辑关系的连接手段 ;表明句子语法关系的连接手段 :用词汇本身意义来表达的连接手段。     

培养集体荣誉感 增强班集体凝聚力

班集体的凝聚力是一个巨大的教育力量，对学生工作有关键性的影响。我校学生对集体主义和凝聚力的认识状况不理想。要以“班级为核心，宿舍为重点”作为学生工作方针和指导思想，从“班干部队伍建设”、“集体观念的培养”、“有效地沟通”三个方面着力增强班集体凝聚力，使之成为巨大的教育力量。