Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Parent‐Adolescent Communication About Sex: Retrospective Reports by Latino College Students

Latina female (n= 97) and Latino male (n= 69) college students (M age = 21.4 years) completed self‐report surveys regarding family of origin experiences, including sexual communication with parents while growing up. Latino parents of this comparatively highly educated sample tended to use direct rather than indirect strategies for communicating about sexuality with their children. Young women reported higher levels of sexual communication with mothers while growing up than did young men, and respondents reported less communication with fathers than mothers. Among young women, sexual communication with mother was positively associated with non‐Mexican origin and negatively associated with having older brothers living at home. In contrast, maternal education was positively associated with mother‐son communication about sex. Paternal education and the absence of older brothers positively predicted communication with both sons and daughters. The analyses provide novel information regarding sexual communication in Latino families and suggest directions for future research.     

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.     

翻译理论新标准与语言学理论

语言学的发展一直在不断地影响着翻译理论的发展,只不过有时这种影响很间接,尼达的译学思想在中国翻译界一向占据着重要的地位,但这位大师最近宣布其观点已经发生根本变化,尼达学术观点的变化无疑会给目前译学建设带来一定的负面影响。本文着重从翻译理论的作用、翻译标准及语言学与翻译的关系三个角度对尼达翻译思想的转变加以分析;重新阐述理论在译学框架中的地位及作用,理论和实践的关系及翻译理论的意义。     

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.     

走向综合化的工业设计教育

为了适应现代经济发展和市场变化 ,高校工业设计教育应从其教学思想、课程结构、教学内容和教学方法等方面着手 ,建立起一套综合化的现代工业设计教学体系 ,且注重启发思维、挖掘潜力和培养学生独立创新的综合性设计能力 ,这样才能使我国的工业设计教育与时俱进、开拓创新。     

平行进口问题探析

平行进口涉及知识产权和国际贸易,其法律关系相当复杂。至今,世界范围内对此仍无统一规定,各国立法亦不尽相同。着重阐述平行进口的涵义、各国立法现状及我国在加入WTO后应如何完善等问题。     

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.     

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.     

政治课“激凝·讨论”教学模式优化选择的实践与研究

政治课教学“激疑·讨论”模式,不同于传统的讲授法单向信息传递与谈话法一对一信息交流的模式,而是由教师主动设置疑问(激疑),以引起学生兴趣并质疑,然后通过师生间的互动讨论(释疑),最后求得共识与真知(无疑),从而培养学生的求知能力与主体意识,并进行思想政治上的自我教育。