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.     

我国深化素质教育改革的主要对策

目前我国素质教育改革的重点应是尽快启动素质教育评价体系建设国家研究项目,积极推进高校招生制度改革,促进学生身心协调健康成长,加快推进中小学实施小班化教学和加强农村师资建设。力争在较短的时间内实现高等教育质量的根本性恢复,稳步推进教育管理体制改革为素质教育改革目标的实现提供制度环境支持。     

A Bayesian Adjustment for Covariate Misclassification with Correlated Binary Outcome Data

Estimated associations between an outcome variable and misclassified covariates tend to be biased when the methods of estimation that ignore the classification error are applied. Available methods to account for misclassification often require the use of a validation sample (i.e. a gold standard). In practice, however, such a gold standard may be unavailable or impractical. We propose a Bayesian approach to adjust for misclassification in a binary covariate in the random effect logistic model when a gold standard is not available. This Markov Chain Monte Carlo (MCMC) approach uses two imperfect measures of a dichotomous exposure under the assumptions of conditional independence and non-differential misclassification. A simulated numerical example and a real clinical example are given to illustrate the proposed approach. Our results suggest that the estimated log odds of inpatient care and the corresponding standard deviation are much larger in our proposed method compared with the models ignoring misclassification. Ignoring misclassification produces downwardly biased estimates and underestimate uncertainty.     

Examples of the use of an equivalence theorem in constructing optimum experimental designs for random-effects nonlinear regression models

The problem considered is that of finding an optimum measurement schedule to estimate population parameters in a nonlinear model when the patient effects are random. The paper presents examples of the use of sensitivity functions, derived from the General Equivalence Theorem for D-optimality, in the construction of optimum population designs for such schedules. With independent observations, the theorem applies to the potential inclusion of a single observation. However, in population designs the observations are correlated and the theorem applies to the inclusion of an additional measurement schedule. In one example, three groups of patients of differing size are subject to distinct schedules. Numerical, as opposed to analytical, calculation of the sensitivity function is advocated. The required covariances of the observations are found by simulation.     

论校报独特的思想政治教育优势

高校校报在进行大学生思想政治教育方面具有独特的优势，面对日益变化的国际国内形势，高校校报要充分发挥校报自身的特点和优势，进一步推动高校思想政治教育工作的发展，需要从以下几方面努力：一是加强工作制度和工作机制建设；二是扬长避短出精品；三是与时俱进拓展功能。     

也谈"错案追究制"

错案追究制自运行以来存在着许多问题,其所具有的负面影响超过了其积极效应的一面.本文从多角度分析了错案追究制产生的影响,并对错案进行了科学的界定.在此基础上,本文倡导错案追究制应让位于全面的司法改革,并提出了具体的司法改革措施.     

浅议民事责任竞合

违约责任与侵权责任竞合是由于某种违反民事义务的行为既符合违约责任构成要件又符合侵权责任构成要件 ,从而在法律上导致多种民事责任并存和冲突所产生的现象。因此 ,采取责任聚合与自由选择诉因的措施来解决责任竟合 ,以期充分保护受害方权利 ,消灭责任重叠可能导致的不公平 ,合并不重叠部分的责任。     

Non-ignorable missing covariate data in survival analysis: a case-study of an International Breast Cancer Study Group trial

Summary.  Non-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.     

Statistical and Combinatorial Aspects of Comparative Genomics*

Abstract. This document presents a survey of the statistical and combinatorial aspects of four areas of comparative genomics: gene order based measures of evolutionary distances between species, construction of phylogenetic trees, detection of horizontal transfer of genes, and detection of ancient whole genome duplications.     

ASSESSING CONGRUENCEAMONG DISTANCE MATRICES: SINGLE-MALT SCOTCH WHISKIES REVISITED

A test of congruence among distance matrices is described. It tests the hypothesis that several matrices, containing different types of variables about the same objects, are congruent with one another, so they can be used jointly in statistical analysis. Raw data tables are turned into similarity or distance matrices prior to testing; they can then be compared to data that naturally come in the form of distance matrices. The proposed test can be seen as a generalization of the Mantel test of matrix correspondence to any number of distance matrices. This paper shows that the new test has the correct rate of Type I error and good power. Power increases as the number of objects and the number of congruent data matrices increase; power is higher when the total number of matrices in the study is smaller. To illustrate the method, the proposed test is used to test the hypothesis that matrices representing different types of organoleptic variables (colour, nose, body, palate and finish) in single‐malt Scotch whiskies are congruent.