Defining estimands for efficacy assessment in single arm phase 1b or phase 2 clinical trials in oncology early development

The addendum of the ICH E9 guideline on the statistical principles for clinical trials introduced the estimand framework. The framework is designed to strengthen the dialog between different stakeholders, to introduce greater clarity in the clinical trial objectives and to provide alignment between the estimand and statistical analysis. Estimand framework related publications thus far have mainly focused on randomized clinical trials. The intention of the Early Development Estimand Nexus (EDEN), a task force of the cross-industry Oncology Estimand Working Group ( www.oncoestimand.org ), is to apply it to single arms Phase 1b or Phase 2 trials designed to detect a treatment-related efficacy signal, typically measured by objective response rate. Key recommendations regarding the estimand attributes include that in a single arm early clinical trial, the treatment attribute should start when the first dose is received by the participant. Focusing on the estimation of an absolute effect, the population-level summary measure should reflect only the property used for the estimation. Another major component introduced in the ICH E9 addendum is the definition of intercurrent events and the associated possible ways to handle them. Different strategies reflect different clinical questions of interest that can be answered based on the journeys an individual subject can take during a trial. We provide detailed strategy recommendations for intercurrent events typically seen in early-stage oncology. We highlight where implicit assumptions should be made transparent as whenever follow-up is suspended, a while-on-treatment strategy is implied.     

Intermediaries in the relevance-gap debate: A systematic review of consulting roles

A highly contested issue in management science is its relevance to practice. Despite third parties’ potentially significant role in changing the interaction between divided parties, the long-standing literature on the relevance gap has paid third parties little systematic attention. Drawing on a boundary-spanning perspective, and the concept of brokerage in particular, we review how the consultant role is discussed as an intermediary third party between management science and management practice. Based on a systematic literature review of 133 articles, we identify different intermediary consultant roles linking management science to management practice. Our findings detail how the practices associated with intermediary consultant roles performed by academics or practitioners relate to several key relevance criteria, how management knowledge flows when including intermediaries and how intermediaries in different roles relate to different audiences. Based on the findings, we develop a third-party model of intermediary consultant roles and knowledge flows. The model indicates the theoretical significance of third parties in shaping the interaction and knowledge flows between management science and management practice and has theoretical implications for understanding the persistence of the relevance gap. Regarding practical implications, we suggest how management scientists could target third parties as new key practitioner audiences. Considering third parties, and thus moving away from a two-party view, opens up promising directions for further research on the roles and role shifts of various intermediary actors and on how different intermediary audiences may appreciate different types of academic knowledge.     

Robust optimal estimation of location from discretely sampled functional data

Estimating location is a central problem in functional data analysis, yet most current estimation procedures either unrealistically assume completely observed trajectories or lack robustness with respect to the many kinds of anomalies one can encounter in the functional setting. To remedy these deficiencies we introduce the first class of optimal robust location estimators based on discretely sampled functional data. The proposed method is based on M-type smoothing spline estimation with repeated measurements and is suitable for both commonly and independently observed trajectories that are subject to measurement error. We show that under suitable assumptions the proposed family of estimators is minimax rate optimal both for commonly and independently observed trajectories and we illustrate its highly competitive performance and practical usefulness in a Monte-Carlo study and a real-data example involving recent Covid-19 data.     

Optimal Steiner trees under node and edge privacy conflicts

Journal of Combinatorial Optimization - In this work, we suggest concepts and solution methodologies for a series of strategic network design problems that find application in highly data-sensitive...     

Emergency risk communication and sensemaking during smoke events: A survey of practitioners

Emergency risk communication (ERC) for smoke emitted from major fires continues to challenge governments. During these events, practitioners (including scientific, communication, and emergency response government staff) are tasked with quickly making sense of the public health risks and the communication options available. Practitioners’ sensemaking—the process of creating meaning from information about an unfolding emergency—is key to effective ERC. This article identifies the factors that ERC practitioners consider the most important to their sensemaking for smoke events. A survey of practitioners (n = 86) was conducted to elicit their views on the level of importance of 22 different factors (individual, organizational, and contextual) on their sensemaking. The results indicate that the majority of the factors tested are very important to practitioners. This finding likely reflects the multidimensional nature of emergency smoke events and provides evidence as to why practitioners are challenged when trying to make sense of emergency situations. Despite multiple factors being considered very important to practitioners, the time-limited nature of emergencies means that practitioners will inevitability be forced to prioritize in their sensemaking efforts. Our results also provide insight into practitioners’ prioritization of different information sources. Specifically, practitioners prioritize their own knowledge and the knowledge of other practitioners. The two most important factors were information from other incident management stakeholders and the practitioners’ past experience. Other information, including community-based and academic knowledge, appear to be of lower priority for practitioners. Based on the study results, recommendations for practice and future research are discussed.     

The Determinants and Some Consequences of Unemployed Workers' Wage Demands

This paper studies the determinants and consequences in the early stages of the hiring process of unemployed workers' wage demands using direct data on workers' wage requests. We show that most unemployed workers want a wage close to their previous wage, and thus much more than they get in unemployment benefits. However, some groups, such as women, tend to demand lower wages. Moreover, we find that workers with high wage demands are contacted by firms less often than otherwise similar workers with lower wage demands. Thus, our results suggest that too high wage demands may contribute to high unemployment.     

Conceptualizing,Measuring, and Theorizing the Third Sector: Embedding Statistical and Methodological Developments Awaiting Broader Scholarly Take-up

VOLUNTAS: International Journal of Voluntary and Nonprofit Organizations - This article reviews and calls attention to the work underlying significant improvements in the conceptualization,...     

Communicating social value: An experimental study on credible communication and social enterprises

The management of marketing and communication strategies involves a complex mix of different requirements, particularly for social enterprises, which try to fulfill both social and business aims while operating in a resource-constrained context. Although social enterprises are a rising phenomenon, the research on how these businesses communicate their activities remains in its infancy. This study builds on the theory of planned behavior and the source credibility theory, presenting a conceptual framework that distinguishes between high, moderate, and low credibility of a social enterprise's communication, to analyze its effects on potential customers' behavioral intentions. Through an online experiment with 260 subjects, the authors demonstrate that attitude toward a social enterprise, subjective norm, perceived behavioral control, and, ultimately, the intention to support a social enterprise by purchasing its products increases with the social enterprise's message credibility. The authors also present practical implications and avenues for future research on the communication of social enterprises based on the empirical findings.     

An approximation algorithm for a general class of parametric optimization problems

Journal of Combinatorial Optimization - In a (linear) parametric optimization problem, the objective value of each feasible solution is an affine function of a real-valued parameter and one is...