Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.     

Conceptualizing reflection in experience-based workplace learning

This paper seeks to understand key dimensions of reflection in experience-based workplace learning for research being collaboratively undertaken by scholars in Dutch and US research institutions. We systematically explore and compare Tara Fenwick’s analysis of five perspectives on cognition to distinguish among constructivist, psychoanalytic, situative, critical-cultural, and enactivist perspectives on reflection. Our aim is to examine how to conceptualize reflection so that one or more perspectives can complement our understanding of learning through experience at work. We position reflection not only from a practical but also from a theoretical perspective that moves beyond the individual focus of the constructivist perspective. Fenwick’s five perspectives are described in terms of whether and how reflection is utilized, key activities in the process of reflection, relative focus on the individual and/or the context, triggers for reflection, role of power and positionality, role of emotions, and reflection outcomes. We conclude that adding other lenses to the dominant constructivist perspective helps expand our understanding of reflection as well as identify and attend to other tools, people, and factors in the work situation that influence reflection processes and learning outcomes. The paper closes with a discussion of promising new approaches that have emerged since Fenwick’s analysis.     

Mobility and Professional Networks in Academia: An Exploration of the Obligations of Presence

This article explores the obligations of presence behind work-related mobility for academics in internationalizing higher education systems. By further developing John Urry’s concept of ‘meetingness’, the article reveals how academics depend on corporeal and virtual mobility to create and maintain a networked professional life outside their own institution, which is crucial in the context of changing work conditions. Our insights are drawn from original qualitative research (42 interviews) in a Flemish and Danish context. The data reveal obligations of presence associated with an interrelated mix of functionality, and the construction of dense and sparse social networks that together support career success and work at the frontiers of academic knowledge. Despite the now well-recognized costs of corporeal mobility, obligations of presence result in virtual and corporeal mobility coexisting, rather than the former substituting for the latter. Virtual mobility is mainly used when conflicting obligations of presence exist, and as a means of sustaining networks over time given the processual nature of meetingness, rather than as a means to reduce levels of corporeal mobility.     

Misestimating Betting Behavior: The Role of Negative Asymmetries in Emotional Self Prediction

This paper addresses the role of negative asymmetries in emotional self-prediction by looking at the extent to which individuals misestimate their own betting behavior in sequential gambles. In a series of three experimental studies, we demonstrate that losses lead to higher than planned bets whereas bets are on average carried over after gains. Such asymmetric deviations from the plan emerge (1) when monetary and non-monetary incentives are used, and (2) when participants face fair and unfair gambles. The asymmetry is based on people’s inability to predict how much the negative emotions generated by a bad experience (e.g. the loss) will influence them to put more effort (e.g. bet more) than planned in an attempt to re-establish a homeostatic state in the prospect of a good experience (e.g. winning).     

Mean shift and influence measures in linear measurement error models with stochastic linear restrictions

We present influence diagnostics for linear measurement error models with stochastic linear restrictions using the corrected likelihood of Nakamura in 1990. The case deletion and mean shift outlier models are developed to identify outlying and influential observations. We derive a corrected score test statistic for outlier detection based on mean shift outlier models. The analogs of Cook's distance and likelihood distance are proposed to determine influential observations based on case deletion models. A parametric bootstrap procedure is used to obtain empirical distributions of the test statistics and a simulation study has been used to evaluate the performance of the proposed estimators based on the mean squares error criterion and the score test statistic. Finally, a numerical example is given to illustrate the theoretical results.     

Children's Physiological Regulation and Sibling Conflict as Correlates of Children's Conscience Development

Children's conscience, including the ability to experience guilt and engage in rule‐compatible behavior, develops across early childhood. The current study investigated whether within‐family variation in children's baseline respiratory sinus arrhythmia (RSA) and sibling conflict behavior were associated with individual differences in children's guilt and internalized conduct. Between‐family differences across sibling dyad gender compositions were also examined. A within‐family design that included 70 families with two siblings between the ages of 2 and 5 was utilized. Children's baseline RSA was measured while sitting quietly with their family. Mothers and fathers completed questionnaires that assessed siblings’ conflict behavior, guilt, and internalized conduct. Older siblings had higher levels of guilt and internalized conduct than younger siblings. Results from actor‐partner interdependence models indicated that there were no direct effects of children's baseline RSA. The interaction effects approached significance (p's ≤ .08) suggesting that older siblings’ conflict moderated the association between older siblings’ baseline RSA and both older and younger siblings’ guilt. In contrast, older siblings’ conflict was positively associated with older and younger siblings’ internalized conduct. Guilt and internalized conduct also differed for older and younger siblings in different dyad gender compositions. The results underscore the need for greater clarity regarding the function that siblings serve in promoting children's moral development during early childhood.