Choice of the primary analysis in longitudinal clinical trials

Missing data, and the bias they can cause, are an almost ever‐present concern in clinical trials. The last observation carried forward (LOCF) approach has been frequently utilized to handle missing data in clinical trials, and is often specified in conjunction with analysis of variance (LOCF ANOVA) for the primary analysis. Considerable advances in statistical methodology, and in our ability to implement these methods, have been made in recent years. Likelihood‐based, mixed‐effects model approaches implemented under the missing at random (MAR) framework are now easy to implement, and are commonly used to analyse clinical trial data. Furthermore, such approaches are more robust to the biases from missing data, and provide better control of Type I and Type II errors than LOCF ANOVA. Empirical research and analytic proof have demonstrated that the behaviour of LOCF is uncertain, and in many situations it has not been conservative. Using LOCF as a composite measure of safety, tolerability and efficacy can lead to erroneous conclusions regarding the effectiveness of a drug. This approach also violates the fundamental basis of statistics as it involves testing an outcome that is not a physical parameter of the population, but rather a quantity that can be influenced by investigator behaviour, trial design, etc. Practice should shift away from using LOCF ANOVA as the primary analysis and focus on likelihood‐based, mixed‐effects model approaches developed under the MAR framework, with missing not at random methods used to assess robustness of the primary analysis. Copyright © 2004 John Wiley & Sons, Ltd.     

“两个必然”和“两个决不会”的内在统一

对于马克思主义“两个必然”和“两个决不会”的关系存在着“补充论”、“修正论”、“取代论”的不同观点。“两个必然”和“两个决不会”的科学论断都是社会基本矛盾运动规律的体现,二者是内在的高度统一的理论。就资本主义社会发展趋势而言,“两个决不会”具有相对性,是“两个必然”的内在要求,“两个必然”理论中包含着“两个决不会”思想,是“两个决不会”运动的最终结果。     

Marginal and association regression models for longitudinal binary data with drop‐outs: A likelihood‐based approach

Longitudinal data often contain missing observations, and it is in general difficult to justify particular missing data mechanisms, whether random or not, that may be hard to distinguish. The authors describe a likelihood‐based approach to estimating both the mean response and association parameters for longitudinal binary data with drop‐outs. They specify marginal and dependence structures as regression models which link the responses to the covariates. They illustrate their approach using a data set from the Waterloo Smoking Prevention Project They also report the results of simulation studies carried out to assess the performance of their technique under various circumstances.     

Potential exposures and risks from beryllium-containing products.

Beryllium is the strongest of the lightweight metals. Used primarily in military applications prior to the end of the Cold War, beryllium is finding new applications in many commercial products, including computers, telecommunication equipment, and consumer and automotive electronics. The use of beryllium in nondefense consumer applications is of concern because beryllium is toxic. Inhalation of beryllium dust or vapor causes a chronic lung disease in some individuals at concentrations as low as 0.01 microg/m3 in air. As beryllium enters wider commerce, it is prudent to ask what risks this might present to the general public and to workers downstream of the beryllium materials industry. We address this question by evaluating the potential for beryllium exposure from the manufacturing, use, recycle, and disposal of beryllium-containing products. Combining a market study with a qualitative exposure analysis, we determine which beryllium applications and life cycle phases have the largest exposure potential. Our analysis suggests that use and maintenance of the most common types of beryllium-containing products do not result in any obvious exposures of concern, and that maintenance activities result in greater exposures than product use. Product disposal has potential to present significant individual risks, but uncertainties concerning current and future routes of product disposal make it difficult to be definitive. Overall, additional exposure and dose-response data are needed to evaluate both the health significance of many exposure scenarios, and the adequacy of existing regulations to protect workers and the public. Although public exposures to beryllium and public awareness and concern regarding beryllium risks are currently low, beryllium risks have psychometric qualities that may lead to rapidly heightened public concern.     

Costs and Rewards of Children: The Effects of Becoming a Parent on Adults' Lives

How do new parents differ from their childless counterparts in social and psychological resources, daily strains, and psychological well‐being? Using a nationally representative panel of 1,933 adults who were childless at the first interview, we compare 6 indicators of adults' lives for those who became parents and those remaining childless several years later, controlling for earlier states. Becoming a parent is both detrimental and rewarding. With the exception of social integration, which is greater for all groups of new parents compared with their childless counterparts, the effects of parental status on adults' lives vary markedly by gender and marital status. Unmarried parents report lower self‐efficacy and higher depression than their childless counterparts. Married mothers' lives are marked by more housework and more marital conflict but less depression than their childless counterparts. Parental status has little influence on the lives of married men.     

Valuation of childhood risk reduction: the importance of age, risk preferences, and perspective.

This article explores two problems analysts face in determining how to estimate values for children's health and safety risk reductions. The first addresses the question: Do willingness‐to‐pay estimates for health risk changes differ across children and adults and, if so, how? To answer this question, the article first examines the potential effects of age and risk preferences on willingness to pay. A summary of the literature reporting empirical evidence of differences between willingness to pay for adult health and safety risk reductions and willingness to pay for health and safety risk reductions in children is also provided. The second dimension of the problem is a more fundamental issue: Whose perspective is relevant when valuing children's health effects—society's, children's, adults‐as‐children, or parents'? Each perspective is considered, followed ultimately by the conclusion that adopting a parental perspective through an intrahousehold allocation model seems closest to meeting the needs of the estimation problem at hand. A policy example in which the choice of perspective affects the outcome of a regulatory benefit‐cost analysis rounds out the article and emphasizes the importance of perspective.     

股票股利变化市场反应的实证研究

对公司分配方案中股票股利发生变化时股票收益率的研究,显示证券市场对股票股利分配方案发生变化时有一定反应,但与国外成熟资本市场的反应并不一致,说明我国证券市场距离国外成熟资本市场还有一定差距,证券市场信息披露制度尚不规范。     

中国股票市场效率的实证研究

处于二元转型期的中国股票市场,功能定位不完全合理,结构性矛盾突出。行政导向性强,是一个不完全市场。市 场仍处于非弱效率状态。利用1999-2000年中国股票市场的时间序列数据进行的自相关系数检验和游程检验.证实了中国 股票市场非弱有效性的判断。     

近二十年中国汉民族起源、形成研究综述(二)

汉民族是我国乃至世界上最大的民族 ,而关于汉民族的研究 ,长期以来却被国内学术界所忽视 ,汉民族史常被淹没在通史和断代史研究之中。十一届三中全会后 ,汉民族研究如雨后春笋 ,一直在不断地兴旺勃发。特别是近二十年来 ,汉民族研究取得了蔚为壮观的成绩 ,为世人瞩目。     

关于改进我国天然气管输定价方式的探讨

探索了我国现行天然气管输运价形成机制严重背离天然气市场发育的弊端，进而提出与国际接轨的建议，即通过分别确定管输企业年度应收服务费和按两部制设计用户运价率来制定管输价格。