PubPredict: Prediction of progression and survival in oncology leveraging publications and early efficacy data

In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.     

Quantification of follow-up time in oncology clinical trials with a time-to-event endpoint: Asking the right questions

For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow-up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow-up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time-to-event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow-up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time-to-event endpoint in one group, but also for comparisons. We find that different thinking about some of the relevant scientific questions around follow-up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, for example, delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations.     

The Probabilistic Final Standing Calculator: a fair stochastic tool to handle abruptly stopped football seasons

AStA Advances in Statistical Analysis - The COVID-19 pandemic has left its marks in the sports world, forcing the full stop of all sports-related activities in the first half of 2020. Football...     

Process matters – How strategic decision-making process characteristics impact capital allocation efficiency

We employ strategic decision-making process theory to study the internal capital markets of firms and argue that varying allocation efficiency can result from the configuration of the capital allocation decision-making process. Learning from earlier research on firms' portfolio allocations, we also develop assumptions on interaction effects with firm-level unrelated diversification and environmental dynamics. We test our hypotheses with structural equation modeling on an international sample of large multi-business firms. Our results suggest that process formalization and analytical comprehensiveness have a positive influence on the efficiency of allocation decisions. Another key result is that unrelated diversified portfolios positively moderate the influence of analytical comprehensiveness and formalization, while dynamic environments negatively impact the influence of formal processes but reward managerial involvement.     

‘I Just Don't Agree’: A Voice-Oriented Analysis of An IFPS Case of Alleged Child Maltreatment

In contrast to the many outcome studies of Intensive Family Preservation Services (IFPS), little is known about the underlying personal and relational dynamics of family crisis interventions. This article focuses on the core evolving dynamics of the changing self-presentations of a parent involved in an intensive home-based family preservation case of alleged child maltreatment. Three key family intervention sessions were videotaped and transcribed including both verbal and nonverbal behavior. The Listening Guide Method – a theoretically flexible, qualitative, relationally oriented method of in-depth interpretative analysis – served as our guide for this case analysis. In the processes of change toward a jointly constructed meaningful narrative on responsibility and self-care, two key elements emerged as playing a pivotal role: (1) the momentum of a potential referral of children to out-of-home care that precedes the start of an IFPS intervention and (2) the rhizomatic or root-like intertwinement of the voices of both parent and therapist with respect to the rationale for any involvement of society in the family. We argue that discourses on imminent placement in the context of family preservation deserve a genuine and valuable position in the initial discourse of a family therapist when entering a family in the context of crisis intervention. Both in understanding and driving any processes of change, we may need to reconsider our own willingness to step into the blending interplay of discourse and counter-discourse with our clients on the subject of our often drastic intervention. Consequently, we may read this narrative analysis as an invitation to reflect on the conceptualization of ‘client readiness’ in psychotherapy and to shift our thinking on preconditions for therapy from a client's readiness toward a therapist's attentiveness to listen.     

The allocation and value of time assigned to housework and child-care: An analysis for Switzerland

In this paper, data from the 1997 Swiss Labour Force Survey are used to analyse the allocation and value of time assigned to housework and child-care. It is shown that men's allocation of time to housework and child-care is largely invariant to changes in socio-economic factors. Women's allocation of time to housework and child-care, on the other hand, is shown to depend on several social, economic, and demographic factors. The value of time assigned to housework and child-care is calculated with two market replacement cost methods and three opportunity cost methods. The results show that the value of time assigned to housework and child-care ranges from 27% to 39% and from 5% to 8% of GDP (in 1997), respectively. The value of time assigned to housework and child-care is also calculated for different household structures. Received: 15 April 1999/Accepted: 5 May 2000     

Turkish Immigrants in Sweden: Are They Integrated?

Many in Europe believe that large numbers of Turkish immigrants have failed to integrate into their host communities. How is this situation in Sweden? We found that most of the Turkish immigrants felt themselves to be Turkish and Sweden was accepted as a foreign country. Turkish‐originated media was followed frequently and strong ties with relatives in Turkey were maintained. Marriage and friendship with native Swedes were not well accepted. We concluded that despite the multicultural aspects of Swedish integration policies, Turkish immigrants in Sweden were not well integrated and they prefer to live within the boundaries of their segregated, closed, small communities.