A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies

One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more prespecified biomarker subpopulations at an interim analysis have been proposed in this setting but practical case studies of AEDs are still relatively rare. We present the design of an AED with a binary endpoint in the highly dynamic setting of cancer immunotherapy. The trial was initiated as a conventional trial in early triple-negative breast cancer but amended to an AED based on emerging data external to the trial suggesting that PD-L1 status could be a predictive biomarker. Operating characteristics are discussed including the concept of a minimal detectable difference, that is, the smallest observed treatment effect that would lead to a statistically significant result in at least one of the target populations at the interim or the final analysis, respectively, in the setting of AED.     

Integrating phase 2 into phase 3 based on an intermediate endpoint while accounting for a cure proportion—With an application to the design of a clinical trial in acute myeloid leukemia

For a trial with primary endpoint overall survival for a molecule with curative potential, statistical methods that rely on the proportional hazards assumption may underestimate the power and the time to final analysis. We show how a cure proportion model can be used to get the necessary number of events and appropriate timing via simulation. If phase 1 results for the new drug are exceptional and/or the medical need in the target population is high, a phase 3 trial might be initiated after phase 1. Building in a futility interim analysis into such a pivotal trial may mitigate the uncertainty of moving directly to phase 3. However, if cure is possible, overall survival might not be mature enough at the interim to support a futility decision. We propose to base this decision on an intermediate endpoint that is sufficiently associated with survival. Planning for such an interim can be interpreted as making a randomized phase 2 trial a part of the pivotal trial: If stopped at the interim, the trial data would be analyzed, and a decision on a subsequent phase 3 trial would be made. If the trial continues at the interim, then the phase 3 trial is already underway. To select a futility boundary, a mechanistic simulation model that connects the intermediate endpoint and survival is proposed. We illustrate how this approach was used to design a pivotal randomized trial in acute myeloid leukemia and discuss historical data that informed the simulation model and operational challenges when implementing it.     

Was heißt kommunikative Kompetenz im Spannungsfeld von Ost nach West?

What does communicative competence mean concerning the tension between East and West Germans? Although East and West Germany have been formaly reunified and ten years have passed the existence of different cultures cannot be denied. Trompenaars dimensions offer the possibility to make an intercultural comparison of the two cultures. I have chosen firm-cultures, individualism versus collectivism and specific versus diffuse culture. I also compare my experience as a West German lawyer in an East German administration with the results. The awareness and identification of these differences are important for more genuine recognition and acceptance of East and West Germans.     

Evidence for the use of an algorithm in resolving inconsistent and missing Indigenous status in administrative data collections

Measures of the gap in living standards, life expectancy, education, health and employment between Indigenous and non‐Indigenous Australians are primarily derived from administrative data sources. However, Indigenous identification in these data sources is affected by administrative practices, missing data, inconsistency, and error. As these factors have changed over time, assessing whether the gap between Indigenous and non‐Indigenous Australians has changed over time, based on data unadjusted for these sources of error can potentially lead to misguided conclusions. Combining administrative data on the same individuals collected from different sources provides a method by which a more consistent derived Indigenous status can be applied across all records for an individual within a linked data environment. We used the Western Australian Data Linkage system to produce derived Indigenous statuses for individuals using a range of algorithms. We found that these algorithms reduced the amount of missing data and improved within‐individual consistency. Based on these findings, we recommend our Multi‐Stage Median algorithm be used as the standard indicator of Indigenous status for any reporting based on administrative datasets when multiple datasets are available for linkage, and that algorithmic approaches also be considered for improving the quality of other demographic variables from administrative data sources.     

Immigrant students and their teachers – exploring various constellations of acculturation orientations and their impact on school adjustment

ABSTRACT

The present study examined what impact various constellations of acculturation orientations of immigrant students and their teachers have on the students’ school adjustment. For this purpose, the study analysed the acculturation orientations of 1106 5th graders and their class teachers in Switzerland. Using multiple regression analysis, we found that immigrant students were more satisfied at school if their teachers had similar attitudes about cultural assimilation and cultural diversity and could, thus, be said to have congruent acculturation orientations. With respect to students’ academic self-concept, immigrant students with a minority orientation whose teachers value cultural diversity including the heritage culture of their students showed a lower academic self-concept despite matching acculturation orientations. We interpret this result as a dilemma of teachers between the endeavour to develop culturally sensitive attitudes and behaviours and the risk to create stereotype threat and its negative effects through addressing cultural differences. Furthermore, a mismatch between the students’ (bi-)national identification at school and the teacher’s perception of the student as an immigrant or a native-born student could be shown to have adverse effects on the academic self-concept in the group of students with older teachers (50+ years).     

Coaching von Führungskräften aus Expertenorganisationen

In this text, the particularities of the situation of executives in expert organizations are discussed. Then four cases are described, in which (1) the problems that bring leaders from expert organizations into coaching are illustrated, (2) the respective coaching interventions are described and (3) the key concepts that were in the coaching helpful are summarized. Finally, some thoughts what is in executive coaching from expert organizations useful are discussed.     

Zur Gestaltung des Verhältnisses von Erwerbsarbeit und Privatleben in den ‚Creative Industries‘

The “creative industries” are considered to be a model of the future world of work and “pioneers” of new forms of earning and new forms of “work and life”. On the basis of an empirical study of the creative industries sub-sector (architecture, advertising, design, film, IT services and multimedia etc.), the contribution is concerned with the effects of changed demands of employment on the relationship between work and life. The focus is on the temporal de-limitation of employment conditions in the form of flexibilisation of the place and length of working hours as well as on the spatial de-limitation in the form of changing places of work and increasing demands for mobility. We raise the question of whether workers in this field are just coping with the changes in work or whether they are developing their own, active strategies to redefine the boundaries of work and to find a new work-life balance.