Sample size calculation for recurrent events data in one‐arm studies

In some exceptional circumstances, as in very rare diseases, nonrandomized one‐arm trials are the sole source of evidence to demonstrate efficacy and safety of a new treatment. The design of such studies needs a sound methodological approach in order to provide reliable information, and the determination of the appropriate sample size still represents a critical step of this planning process. As, to our knowledge, no method exists for sample size calculation in one‐arm trials with a recurrent event endpoint, we propose here a closed sample size formula. It is derived assuming a mixed Poisson process, and it is based on the asymptotic distribution of the one‐sample robust nonparametric test recently developed for the analysis of recurrent events data. The validity of this formula in managing a situation with heterogeneity of event rates, both in time and between patients, and time‐varying treatment effect was demonstrated with exhaustive simulation studies. Moreover, although the method requires the specification of a process for events generation, it seems to be robust under erroneous definition of this process, provided that the number of events at the end of the study is similar to the one assumed in the planning phase. The motivating clinical context is represented by a nonrandomized one‐arm study on gene therapy in a very rare immunodeficiency in children (ADA‐SCID), where a major endpoint is the recurrence of severe infections. Copyright © 2012 John Wiley & Sons, Ltd.     

Handling of missing data in long‐term clinical trials: a case study

Missing data in clinical trials is a well‐known problem, and the classical statistical methods used can be overly simple. This case study shows how well‐established missing data theory can be applied to efficacy data collected in a long‐term open‐label trial with a discontinuation rate of almost 50%. Satisfaction with treatment in chronically constipated patients was the efficacy measure assessed at baseline and every 3 months postbaseline. The improvement in treatment satisfaction from baseline was originally analyzed with a paired t‐test ignoring missing data and discarding the correlation structure of the longitudinal data. As the original analysis started from missing completely at random assumptions regarding the missing data process, the satisfaction data were re‐examined, and several missing at random (MAR) and missing not at random (MNAR) techniques resulted in adjusted estimate for the improvement in satisfaction over 12 months. Throughout the different sensitivity analyses, the effect sizes remained significant and clinically relevant. Thus, even for an open‐label trial design, sensitivity analysis, with different assumptions for the nature of dropouts (MAR or MNAR) and with different classes of models (selection, pattern‐mixture, or multiple imputation models), has been found useful and provides evidence towards the robustness of the original analyses; additional sensitivity analyses could be undertaken to further qualify robustness. Copyright © 2012 John Wiley & Sons, Ltd.     

A generalisation of T‐optimality for discriminating between competing models with an application to pharmacokinetic studies

The T‐optimality criterion is used in optimal design to derive designs for model selection. To set up the method, it is required that one of the models is considered to be true. We term this local T‐optimality. In this work, we propose a generalisation of T‐optimality (termed robust T‐optimality) that relaxes the requirement that one of the candidate models is set as true. We then show an application to a nonlinear mixed effects model with two candidate non‐nested models and combine robust T‐optimality with robust D‐optimality. Optimal design under local T‐optimality was found to provide adequate power when the a priori assumed true model was the true model but poor power if the a priori assumed true model was not the true model. The robust T‐optimality method provided adequate power irrespective of which model was true. The robust T‐optimality method appears to have useful properties for nonlinear models, where both the parameter values and model structure are required to be known a priori, and the most likely model that would be applied to any new experiment is not known with certainty. Copyright © 2012 John Wiley & Sons, Ltd.     

Austérité budgétaire et flexibilisation du marché du travail: une association risquée

Les auteurs évaluent les effets de l'association entre politiques d'austérité budgétaire et de réduction du coût du travail, et apportent ainsi quelque éclairage sur les débats en cours. Ils s'attaquent au problème de l'agrégation dans une perspective mondiale au moyen d'un macromodèle mettant en évidence la dynamique de la répartition. La flexibilisation réduit la part salariale et entraîne des rétroactions qui s'enchaînent dans une spirale descendante avec une contraction de l'activité, même dans les économies tirées par les exportations. Les gains initiaux de compétitivité se révèlent éphémères. Sur le long terme, les salaires sont les premiers moteurs de l'économie mondiale, qui réagit positivement aux stimuli keynésiens coordonnés.     

Cross‐Cultural Comparison of the Effects of Optimism,Intrinsic Motivation,and Family Relations on Vocational Identity

This study explored the effects of optimism, intrinsic motivation, and family relations on vocational identity in college students in the United States and South Korea. The results yielded support for the hypothesized multivariate model. Across both cultures, optimism was an important contributing factor to vocational identity, and intrinsic motivation partially mediated the link from optimism to vocational identity. In addition, family relations moderated the mediation effect of intrinsic motivation with American students but not Korean students. With Korean students, family relations moderated the direct link from optimism to vocational identity. These results have significant implications for counseling to promote vocational identity development for diverse college students.     

Engineering Identity: Gender and Professional Identity Negotiation among Women Engineers

This article considers how women in a gendered profession, engineering, construct their professional identity in response to workplace interpersonal interactions that marginalize it. Using data from interviews with women engineers, it also explores how these interactions influence the engineers' sense of self and belonging in engineering. The interpersonal interactions place professional identity on the periphery and can overly validate gender identity. I discuss two types of identity construction strategies employed by the participants in response to these marginalizing interactions: impression management tactics and coping strategies. Although the data demonstrate that participants may be left feeling devalued or ambivalent towards their identity or fit in engineering, some interactions are more validating and offer a sense of belonging. This article also reflects on how the engineers' actions may, in fact, represent forces for change in the gendered culture of engineering.     

Fragmented Sisters? The Implications of Flexible Working Policies for Professional Women's Workplace Relationships

Much is being done by governments and organizations to help workers reconcile their family and employment responsibilities. One such measure has been the introduction of flexible working policies. While academic and policy debates focus on the barriers to flexible working, less consideration is paid to those who work alongside flexible workers. Through a gendered lens, this article focuses on professional women and explores the implications of UK flexible working policies for women's workplace relations in organizations that have traditionally been based on male models of working. Drawing on interviews conducted in three English organizations, it was found that the women's interests did not always coincide and that their social relationships, with respect to flexible working, involved both support and resentment. In particular, the women's interests were affected by organizational and job‐related factors and their stage in the life course. These findings illuminate the ways in which policies are negotiated at the level of daily workplace life and show that co‐workers are a pivotal part of the wider picture of flexible working.     

Gendering the Organization of Home‐based Work in Turkey: Classical versus Familial Patriarchy

This article examines the link between industrial homework and family dynamics in Turkey by asking how and why varied patterns emerge in the organization of industrial homework. I develop a framework for the analysis of gendered organization of industrial homework by comparing labour practices in extended family and nuclear family households. In extended family households, subcontracts are made between industrial enterprises and male family members. Women carry out piece‐rated work at home under the supervision of male family members and have very little contact with people outside their family. In nuclear family households, subcontracts are made between women homeworkers and industrial enterprises or middle persons. Women work at residential streets and neighbourhood homework stores, as well as at home. They have control over their income as well as their working hours. To explain the divergent practices of industrial homework, I show that enterprises incorporate distinct patterns of patriarchy into the subcontracting arrangements through gendered organization of industrial homework.     

The Last Stitch in the Quilt

The patterns of our working lives are fluid and often unpredictable. They are linked to the process of identity forming that we understand as a recognizable, but continuously changing pattern of actions and developments within our lifespan, which includes our career choices. This interpretation allows us to identify the multiple temporal trajectories within a working life and to see how an analysis of temporalities can help us to understand the gendered nature of our careers. By using a number of retrospective narratives of older women about their working lives, we ascertain how an externally imposed and chronologically organized linear (life‐) career story breaks down into a number of a‐chronological trajectories, each of which is personally marked by the identity of the narrator. The theme of self‐care emerges and turns into a binding notion for working women from different generations.