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.     

Markov chain Monte Carlo methods for high dimensional inversion in remote sensing

Summary.  We discuss the inversion of the gas profiles (ozone, NO₃, NO₂, aerosols and neutral density) in the upper atmosphere from the spectral occultation measurements. The data are produced by the 'Global ozone monitoring of occultation of stars' instrument on board the Envisat satellite that was launched in March 2002. The instrument measures the attenuation of light spectra at various horizontal paths from about 100 km down to 10–20 km. The new feature is that these data allow the inversion of the gas concentration height profiles. A short introduction is given to the present operational data management procedure with examples of the first real data inversion. Several solution options for a more comprehensive statistical inversion are presented. A direct inversion leads to a non-linear model with hundreds of parameters to be estimated. The problem is solved with an adaptive single-step Markov chain Monte Carlo algorithm. Another approach is to divide the problem into several non-linear smaller dimensional problems, to run parallel adaptive Markov chain Monte Carlo chains for them and to solve the gas profiles in repetitive linear steps. The effect of grid size is discussed, and we present how the prior regularization takes the grid size into account in a way that effectively leads to a grid-independent inversion.     

State of the unions: Assessment by elite American labor leaders

One hundred and sixty-four elite union leaders in the United States completed a survey to assess the condition of the American labor movement and the factors affecting it. The respondents included high-level international union and state federation officers, central labor presidents, and 58 shop stewards. This study compares the responses of these labor officials and finds that they have similar, negative assessments of the condition of the American labor movement. The study also finds that these leaders agree that the most important factors affecting the labor movement are collective bargaining rights, union leadership, union member solidarity, and the NLRB.     

Fast retraction of evidence in a probabilistic expert system

We present and justify a propagation algorithm to facilitate the simultaneous calculation, for every node in a probabilistic exper system of the distribution of the associated random quantity, conditional on all the evidence obtained about the remaining nodes.     

Sexual identity in the ghetto

The more things change, the worse they get.Presented April 18, 1991, Duke University, at the Department of Psychiatry's Grand Rounds, this paper condenses, integrates and updates the author's earlier publication. Acknowledgement and thanks for funding and professional sponsorship of the four research studies this paper draws from are selectively due to the Eugene and Agnes E. Meyer Foundation, the Edgar Stern Family Fund, The National Institute for Mental Health, the Baltimore-Washington Institute for Psychoanalysis and the Department of Psychiatry, Children's Hospital National Medical Center.