Optimizing trial design in pharmacogenetics research: comparing a fixed parallel group,group sequential,and adaptive selection design on sample size requirements

Two‐stage clinical trial designs may be efficient in pharmacogenetics research when there is some but inconclusive evidence of effect modification by a genomic marker. Two‐stage designs allow to stop early for efficacy or futility and can offer the additional opportunity to enrich the study population to a specific patient subgroup after an interim analysis. This study compared sample size requirements for fixed parallel group, group sequential, and adaptive selection designs with equal overall power and control of the family‐wise type I error rate. The designs were evaluated across scenarios that defined the effect sizes in the marker positive and marker negative subgroups and the prevalence of marker positive patients in the overall study population. Effect sizes were chosen to reflect realistic planning scenarios, where at least some effect is present in the marker negative subgroup. In addition, scenarios were considered in which the assumed ‘true’ subgroup effects (i.e., the postulated effects) differed from those hypothesized at the planning stage. As expected, both two‐stage designs generally required fewer patients than a fixed parallel group design, and the advantage increased as the difference between subgroups increased. The adaptive selection design added little further reduction in sample size, as compared with the group sequential design, when the postulated effect sizes were equal to those hypothesized at the planning stage. However, when the postulated effects deviated strongly in favor of enrichment, the comparative advantage of the adaptive selection design increased, which precisely reflects the adaptive nature of the design. Copyright © 2013 John Wiley & Sons, Ltd.     

Pseudo latent models: Goodness of fit measures, residuals, estimation, testing, and simulation

Binary response models consider pseudo-R ² measures which are not based on residuals while several concepts of residuals were developed for tests. In this paper the endogenous variable of the latent model corresponding to the binary observable model is substituted by a pseudo variable. Then goodness of fit measures and tests can be based on a joint concept of residuals as for linear models. Different kinds of residuals based on probit ML estimates are employed. The analytical investigations and the simulation results lead to the recommendation to use standardized residuals where there is no difference between observed and generalized residuals. In none of the investigated situations this estimator is far away from the best result. While in large samples all considered estimators are very similar, small sample properties speak in favour of residuals which are modifications of those suggested in the literature. An empirical application demonstrates that it is not necessary to develop new testing procedures for the observable models with dichotomous regressands. Well-know approaches for linear models with continuous endogenous variables which are implemented in usual econometric packages can be used for pseudo latent models. An erratum to this article is available at .     

On the role of data,statistics and decisions in a pandemic

AStA Advances in Statistical Analysis - A pandemic poses particular challenges to decision-making because of the need to continuously adapt decisions to rapidly changing evidence and available...     

Instabile Beschäftigung

Sociologists and economists emphasize the relevance of employment stability for labour market participants and the welfare state. Consequently, changes in the distribution of stable and unstable employment are discussed intensively and controversially. Based on the IAB Employment Subsample 1975–2001 (regional sample) and the second collection of the SFB 580-Firmpanel the paper analyses trends and determinants of employment stability. The results show: Employment becomes more unstable. Past “barriers of mobility” of the job market theory against an expansion of open job markets, like production and receipt of firm specific knowledge or readiness to perform, prove as a little stable.     

Dismissal of a Sociologist: The AAUP Report on Carl C. Taylor1

ABSTRACT The dismissal in 1931 of a distinguished sociologist, Carl C. Taylor, after 11 years as an influential faculty member, and the investigation by the American Association of University Professors which followed has received little attention in the literature on the history of sociology. Taylor did not have the security of a tenure system. Years later, he received an honorary degree from the same institution, now North Carolina State University, from which he had been dismissed. This paper makes accessible the AAUP's full report on the Taylor case and highlights his career and contributions. The AAUP report summarizes alternative explanations for the dismissal, concluding that the compelling cause was not the budgetary pressures cited by the president of the university. Our interpretation is that the university president had Taylor dismissed because of deterioration in their interpersonal relations and the cumulative effect of anti-liberal, conservative forces in the state at the time.     

Developments and new dimensions in econometrics

Summary This special issue of the Journal of the German Statistical Society presents 14 papers with surveys on the development and new topics in econometrics. The articles aim to demonstrate how German econometricians see the discipline from their specific view. They briefly describe the main strands and emphasize some recent methods.     

Work-related stress, coping resources, and heavy drinking in the restaurant business

On the basis of findings of high levels of alcohol consumption and risk of alcohol-related disease among employees of the restaurant business, the ability of the Karasek work-strain model to predict heavy drinking was investigated in a cross-sectional study of 3204 Norwegian male and female waiters and cooks. In the logistic regression analyses, no strong associations between work stress and heavy drinking were found. However, the effectiveness of individual coping resources, measured as frequency of difficulty in relaxing after work, was an important predictor of heavy drinking, as were household type, age group, and occupation. Although no strong direct associations between work stress and heavy drinking were found, the results are consistent with a model where coping resources are the mediatiing variable between work stress and heavy drinking.     

Entlassungen: Gerechtigkeitsempfinden und Folgewirkungen.

Zusammenfassung:  Entlassungen sind zu einer allt?glichen Erfahrung vieler Menschen geworden. In diesem Beitrag wird die Frage untersucht: Unter welchen Bedingungen werden Entlassungen als gerecht wahrgenommen und inwieweit rufen sie innerbetriebliche Widerst?nde hervor? Die Untersuchung stützt sich auf eine Befragung von mehr als 3 000 Personen im Alter zwischen 20 und 60 Jahren in Ost- und Westdeutschland. Die Ergebnisse zeigen: Entlassungen werden nicht als selbstverst?ndlich akzeptiert. Darauf weisen die Bewertungen hypothetischer Szenarien und eigener Erfahrungen hin. Durch die Prozessgestaltung kann jedoch die Wahrnehmung der Ma?nahmen positiv oder negativ beeinflusst werden.