Leveraging historical data into oncology development programs: Two case studies of phase 2 Bayesian augmented control trial designs

Leveraging historical data into the design and analysis of phase 2 randomized controlled trials can improve efficiency of drug development programs. Such approaches can reduce sample size without loss of power. Potential issues arise when the current control arm is inconsistent with historical data, which may lead to biased estimates of treatment efficacy, loss of power, or inflated type 1 error. Consideration as to how to borrow historical information is important, and in particular, adjustment for prognostic factors should be considered. This paper will illustrate two motivating case studies of oncology Bayesian augmented control (BAC) trials. In the first example, a glioblastoma study, an informative prior was used for the control arm hazard rate. Sample size savings were 15% to 20% by using a BAC design. In the second example, a pancreatic cancer study, a hierarchical model borrowing method was used, which enabled the extent of borrowing to be determined by consistency of observed study data with historical studies. Supporting Bayesian analyses also adjusted for prognostic factors. Incorporating historical data via Bayesian trial design can provide sample size savings, reduce study duration, and enable a more scientific approach to development of novel therapies by avoiding excess recruitment to a control arm. Various sensitivity analyses are necessary to interpret results. Current industry efforts for data transparency have meaningful implications for access to patient‐level historical data, which, while not critical, is helpful to adjust for potential imbalances in prognostic factors.     

‘Our young people are worse’: family backgrounds,educational progression and placement options in public care systems

Introducing continental European approaches to UK child welfare practice raises a problem of comparison: to what extent are the problems and issues similar to or different from one country compared to another. Social pedagogues trained in continental Europe and working in English residential care services often encountered the phrase ‘our young people are worse’ from their English colleagues, with the implication that the social pedagogic approach was not suitable for the client group. This paper examines two propositions: (1) that in the context of introducing the continental European approach of social pedagogy into children's residential care services in England, young people are ‘different’ in England compared to other European countries and (2) that the placement options and practices for young people living away from their birth parents in continental European countries differ from those in England. Using data from a five nation study of young people from public care backgrounds, the paper argues that while family backgrounds are remarkably similar there are marked differences in the child welfare systems that might account for the perception that young people in care are ‘worse’ in England.     

Inference Tests for Gini-Based Tax Progressivity Indexes

Distribution-free statistical inference procedures for changes in Lorenz- and Gini-based indexes of tax progressivity are developed and applied. Related but distinct tests for the Reynolds–Smolensky index of residual progression and the Kakwani index of liability progression are provided. The inference procedures are illustrated by applying them to Luxembourg Income Study microdata for Sweden, the United Kingdom, and the United States before and after periods of tax reform. In each country a finding of significant change depends on the choice among progressivity indexes. No single index exhibits a consistent pattern of significant change in all countries across time.     

Playing the Recording Once or Twice: Effects on Listening Test Performances

Much debate surrounds the issue of whether allowing candidates to listen to recordings twice is more desirable in language tests than offering just one opportunity. Using regression models, this study investigates, analyses and interconnects both item difficulty and stimulus length in relation to the frequency of stimulus presentation and its effect on test results. The study involved 1,266 eighth-grade learners with perceived A2/B1 level in English as a first foreign language. The final discussion seeks to offer explanations for the results that clearly indicate the advantages of listening once; likewise, potential implications for listening tests and classroom practice are raised.     

EXCLUSION AND REINTEGRATION IN A SOCIAL DILEMMA

Using a social dilemma game, we study the cooperative behavior of individuals who reintegrate their group after being excluded by their peers. We manipulate the length of exclusion and whether this length is imposed exogenously or results from a vote. We show that people are willing to exclude the least cooperators and they punish more, and more severely, chronic defections. In return, a longer exclusion has a higher disciplining effect on cooperation after reintegration, but only when the length of exclusion is not chosen by group members. Its relative disciplining effect on cooperation after reintegration is smaller when the length of exclusion results from a vote. In this environment, a quicker reintegration also limits retaliation. The difference in the impact of long versus short exclusion on retaliation is larger when the length of exclusion is chosen by group members than when it is exogenous. Post-reintegration cooperation and forgiveness depend not only on the length of exclusion but also on the perceived intentions of others when they punish. (JEL C92, H41, D23)     

Theoretical Beacons: Maturana's Theory in Clinical Practice

This paper introduces several theoretical constructs drawn from the work of Humberto Maturana that can be applied to a diverse range of clinical contexts, including supervision. These constructs are: love as a fundamental need of human beings; pathways of explanation: (Objectivity), Objectivity; Emotioning; Structural Coupling; Plasticity; Domains of Operational Coherences. These constructs assist in choosing a point of entry for specific clinical situations and form a foundation on which one's preferred model of practice can be built.