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.     

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.     

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.     

Detection and correction of artificial shifts in climate series

Summary.  Many long instrumental climate records are available and might provide useful information in climate research. These series are usually affected by artificial shifts, due to changes in the conditions of measurement and various kinds of spurious data. A comparison with surrounding weather-stations by means of a suitable two-factor model allows us to check the reliability of the series. An adapted penalized log-likelihood procedure is used to detect an unknown number of breaks and outliers. An example concerning temperature series from France confirms that a systematic comparison of the series together is valuable and allows us to correct the data even when no reliable series can be taken as a reference.     

A note on interval‐censored lifetime data and the constant‐sum condition of oiler,gómez & calle (2004)

Oiler, Gomez & Calle (2004) give a constant sum condition for processes that generate interval‐censored lifetime data. They show that in models satisfying this condition, it is possible to estimate non‐parametrically the lifetime distribution based on a well‐known simplified likelihood. The author shows that this constant‐sum condition is equivalent to the existence of an observation process that is independent of lifetimes and which gives the same probability distribution for the observed data as the underlying true process.     

Temporal pattern in number of staff on sick leave: the effect of downsizing

Summary.  The pattern of absenteeism in the downsizing process of companies is a topic in focus in economics and social science. A general question is whether employees who are frequently absent are more likely to be selected to be laid off or in contrast whether employees to be dismissed are more likely to be absent for the remaining time of their working contract. We pursue an empirical and microeconomic investigation of these theses. We analyse longitudinal data that were collected in a German company over several years. We fit a semiparametric transition model based on a mixture Poisson distribution for the days of absenteeism per month. Prediction intervals are considered and the primary focus is on the period of downsizing. The data reveal clear evidence for the hypothesis that employees who are to be laid off are more frequently absent before leaving the company. Interestingly, though, no clear evidence is seen that employees being selected to leave the company are those with a bad absenteeism profile.     

连续时延神经网络的Hopf分岔现象研究

讨论了带连续时延神经网络的Hopf分岔现象。对于强核和弱核的情况,利用平均时延作为分岔参数,证明了模型经历了Hopf分岔过程。在带弱核的神经网络模型中,得到了分岔周期解稳定性准则。给出了一些数值例子,通过计算机仿真验证了所得结论的正确性。     

高校财会人员继续教育问题

通过论述知识经济时代、经济全球化时代高校财会人员应不断地更新知识,接受继续教育的必要性和迫切性,分析当前高校财会人员继续教育中存在的主要问题,提出了加强高校财务人员继续教育问题的对策.     

Influence diagnostics and outlier tests for semiparametric mixed models

Summary. Semiparametric mixed models are useful in biometric and econometric applications, especially for longitudinal data. Maximum penalized likelihood estimators (MPLEs) have been shown to work well by Zhang and co-workers for both linear coefficients and nonparametric functions. This paper considers the role of influence diagnostics in the MPLE by extending the case deletion and subject deletion analysis of linear models to accommodate the inclusion of a nonparametric component. We focus on influence measures for the fixed effects and provide formulae that are analogous to those for simpler models and readily computable with the MPLE algorithm. We also establish an equivalence between the case or subject deletion model and a mean shift outlier model from which we derive tests for outliers. The influence diagnostics proposed are illustrated through a longitudinal hormone study on progesterone and a simulated example.     

Model diagnostics for smoothing spline ANOVA models

The author proposes some simple diagnostics for assessing the necessity of selected terms in smoothing spline ANOVA models. The elimination of practically insignificant terms generally enhances the interpretability of the estimates and sometimes may also have inferential implications. The diagnostics are derived from Kullback‐Leibler geometry and are illustrated in the settings of regression, probability density estimation, and hazard rate estimation.