Bayes shrinkage estimator for consistency assessment of treatment effects in multi-regional clinical trials

The primary objective of a multi-regional clinical trial is to investigate the overall efficacy of the drug across regions and evaluate the possibility of applying the overall trial result to some specific region. A challenge arises when there is not enough regional sample size. We focus on the problem of evaluating applicability of a drug to a specific region of interest under the criterion of preserving a certain proportion of the overall treatment effect in the region. We propose a variant of James-Stein shrinkage estimator in the empirical Bayes context for the region-specific treatment effect. The estimator has the features of accommodating the between-region variation and finiteness correction of bias. We also propose a truncated version of the proposed shrinkage estimator to further protect risk in the presence of extreme value of regional treatment effect. Based on the proposed estimator, we provide the consistency assessment criterion and sample size calculation for the region of interest. Simulations are conducted to demonstrate the performance of the proposed estimators in comparison with some existing methods. A hypothetical example is presented to illustrate the application of the proposed method.     

基于超总体模型的设计效应分解

本文基于超总体模型研究抽样调查中设计效应的计算问题。首先以随机效应模型为基础，明确了简单随机、二阶段、不等概率和分层抽样对应的超总体模型，进而通过所给模型推导出分层、类集、加权单因素设计效应的计算公式和多因素组合的设计效应计算公式并给出了对应估计量，公式表明：多因素同时存在的组合设计效应等于对应单因素设计效应的乘积。最后，对设计效应的理论值、估计值和真实值之间的关系进行了蒙特卡洛仿真，并利用相对偏倚、相对均方误进行了评价。本文的研究，对复杂抽样设计中正确计算、使用设计效应具有指导意义。     

张华“二俊”说与陆机的悲剧命运

张华推举陆机、陆云兄弟为"二俊",既是对吴郡陆氏家族文学与学术的肯定,又有着现实的政治谋虑,即试图通过延揽孙吴俊才而安抚江南人心。中朝人士拥有胜利者的优越感,对亡国吴士颇为鄙夷和嘲讽。陆机试图扭转这种偏见,因此当众称美故乡,又不肯听从顾荣、戴若思等人的规劝,执意卷入晋室纷争,试图通过匡世济难来证明吴郡陆氏的军事才能。孙吴亡国的耻辱和挽回家族声誉的努力,并试图去证明吴国灭亡非士人之过,这是陆机悲剧的心理根源。     

中国古籍竖写左行排版模式溯源

甲骨文版式的多样性使中国古籍的竖写左行模式有了选择的基础,而竹简的使用及编简者的行为习惯使竖写左行的模式成为古籍编排的必然.这种习惯一直延续到“五四新文化运动”前期,后因外来音节文字对汉语的影响而改变.     

化学/应化专业《波谱分析》课程教学方法探讨

根据《波谱分析》课程的特点和教学实践经验,运用现代化教育技术、ChemOffice软件辅助等手段对该课程的教学方法进行了一些探索.     

Modeling the Adenoma and Serrated Pathway to Colorectal CAncer (ASCCA)

Several colorectal cancer (CRC) screening models have been developed describing the progression of adenomas to CRC. Currently, there is increasing evidence that serrated lesions can also develop into CRC. It is not clear whether screening tests have the same test characteristics for serrated lesions as for adenomas, but lower sensitivities have been suggested. Models that ignore this type of colorectal lesions may provide overly optimistic predictions of the screen‐induced reduction in CRC incidence. To address this issue, we have developed the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model that includes the adenoma‐carcinoma pathway and the serrated pathway to CRC as well as characteristics of colorectal lesions. The model structure and the calibration procedure are described in detail. Calibration resulted in 19 parameter sets for the adenoma‐carcinoma pathway and 13 for the serrated pathway that match the age‐ and sex‐specific adenoma and serrated lesion prevalence in the COlonoscopy versus COlonography Screening (COCOS) trial, Dutch CRC incidence and mortality rates, and a number of other intermediate outcomes concerning characteristics of colorectal lesions. As an example, we simulated outcomes for a biennial fecal immunochemical test screening program and a hypothetical one‐time colonoscopy screening program. Inclusion of the serrated pathway influenced the predicted effectiveness of screening when serrated lesions are associated with lower screening test sensitivity or when they are not removed. To our knowledge, this is the first model that explicitly includes the serrated pathway and characteristics of colorectal lesions. It is suitable for the evaluation of the (cost)effectiveness of potential screening strategies for CRC.     

中国城镇新增住房需求规模的测算与分析

本文围绕城镇家庭户自然增长、城镇家庭户机械增长和城镇存量住房拆除三项需求来源,设计了基于人口普查等公开统计数据定量测算城镇新增住房需求规模的系统性方法,对2001—2010年和2011—2015年间全国和各省份城镇新增住房需求规模进行测算与分析。在此期间新增住房供需关系经历了从基本均衡向供过于求的变化,同时存量住房拆除引致的被动需求取代城镇家庭户自然增长和机械增长引致的主动需求,成为新增住房需求的最主要来源。东、中、西部省份在新增需求规模、新增供需比、需求结构等方面表现出明显差异。本文还进一步对2021—2030年的发展趋 势进行了定量预测。由于三项需求来源均趋于下降,2021—2025年和2026—2030年间全国年均城镇新增住房需求规模预计将较2011—2015年间分别下降33%和53%。本文设计的城镇新增住房需求规模测算方法和预测思路能够为各级政府“十四五”住房发展规划编制、房地产企业战略制定等提供参考。     

区块链技术嵌入医联体信息化建设:内在逻辑与现实挑战

信息化建设是医联体建设的重要内容和重点领域。现阶段的医联体信息化建设存在着医疗信息数据难共享、医疗隐私数据易泄露、医疗数据质量难改观等问题。文章通过梳理区块链的技术原理，发现区块链技术同医联体信息化建设有着高度的契合性并能以智能化的应对方式密切医患互动关系、保障数据高效共享、加强数据安全治理以及提升数据准确性、一致性、时效性和规整性，因此，区块链技术嵌入医联体信息化建设具有可行性。但区块链技术应用于医联体信息化建设在技术、理念、监管等方面还存在诸多挑战，未来仍需提升技术应用手段、转变医方观念体系、健全法规监管模式。     

Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.