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.     

Efficient designs based on orthogonal arrays of type I and type II for experiments using units ordered over time or space

For a wide variety of applications, experiments are based on units ordered over time or space. Models for these experiments generally may include one or more of: correlations, systematic trends, carryover effects and interference effects. Since the standard optimal block designs may not be efficient in these situations, orthogonal arrays of type I and type II, which were introduced in 1961 by C.R. Rao [Combinatorial arrangements analogous to orthogonal arrays, Sankhya A 23 (1961) 283–286], have been recently used to construct optimal and efficient designs for many of these experiments. Results in this area are unified and the salient features are outlined.     

桑弘羊经济立法思想探微

西汉中期,时为掌管封建中央财政事务大臣的桑弘羊在坚持先秦法家思想的基础上,先后推行和提出了大力发展官商,打击私商,实施盐铁专卖,均输平准等一系列的经济立法措施和财政政策,它是汉王朝社会经济方式由自由放任转向国家干预控制的重要转折,其思想对加强封建中央财政管理,充实封建国家财政收入和缓解社会财政危机发挥了重要的作用,其许多首创的理论和实践被后代各封建王朝的理财大臣看作是可望不可及的成功的财政典型,且为当时世界上不少国家所推崇和采用。研究这一中国古代法制史上的重要成果,对思考我们现实社会财政经济的改革发展有宝贵的借鉴意义。     

串联稳压器基准误差放大电路的设计

针对串联型稳压器,设计了一种应用于串联型稳压器具有自建基准的新型误差放大电路。该电路具有构思巧妙,结构优化,易于集成及较高的开环增益,共模抑制比及交流特性的优点。通过验证,实测数据与仿真结果基本一致。     

言内语境--言外语境--现代西方名称指称语境观的嬗变

现代西方语言哲学家、逻辑学家在名称指称语境观方面呈现出由言内语境向言外语境转化的特征.形式语言学派大都从语言与实在同构的观念出发,在语言内部探究语词的指称方式.日常语言学派认为,指称是一种人们使用日常语言的实践活动,只有在变化多样的语言实践活动这样一个大语言背景下才能合理解释名称所指及其确定问题.指称语境观的这一重大转变标志着人们对名称指称理论的研究走向更加成熟、更加科学的阶段.     

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.     

国外教师期望效应研究进展与当代教育启示

教师期望效应是教师对学生的期望在学生的未来发展中得到证实的现象,它反映了教师对学生的态度会影响学生发展的方向和程度,开展该现象的研究对教师观念的改变和学生的健康发展均有重要意义。对教师期望效应的种类、理论模型及国外的相关研究进行了介绍,探讨了其对教育现实的一些重要启示。     

A modified random-effect procedure for combining risk difference in sets of 2×2 tables from clinical trials

Summary Meta-analyses of sets of clinical trials often combine risk differences from several 2×2 tables according to a random-effects model. The DerSimonian-Laird random-effects procedure, widely used for estimating the populaton mean risk difference, weights the risk difference from each primary study inversely proportional to an estimate of its variance (the sum of the between-study variance and the conditional within-study variance). Because those weights are not independent of the risk differences, however, the procedure sometimes exhibits bias and unnatural behavior. The present paper proposes a modified weighting scheme that uses the unconditional within-study variance to avoid this source of bias. The modified procedure has variance closer to that available from weighting by ideal weights when such weights are known. We studied the modified procedure in extensive simulation experiments using situations whose parameters resemble those of actual studies in medical research. For comparison we also included two unbiased procedures, the unweighted mean and a sample-size-weighted mean; their relative variability depends on the extent of heterogeneity among the primary studies. An example illustrates the application of the procedures to actual data and the differences among the results. This research was supported by Grant HS 05936 from the Agency for Health Care Policy and Research to Harvard University.     

The impact of sales promotions on store performance: a structural vector autoregressive approach

The present paper analyses the impact of sales promotions on store performance, in the short and long term, from the retailer's point of view. Relationships among promoted and regular sales in the hypermarkets of a large-scale retail chain of national importance, are investigated by means of a structural vector autoregressive model (SVAR). Statistically significant effects of sales promotions in the heavy household section on store sales are found in the short-run; these promotions produce additional sales and thus act as an attractive factor. Promotions in textile category, on the contrary, produce an immediate negative effect on net sales. In the long run, negative statistically significant effects on regular sales are detected when promotions are repeatedly implemented within perishables category.     

Generalized additive models for location, scale and shape

Summary.  A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y , as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.