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.     

Der Capability-Ansatz in der Gesundheitsförderung: Ansatzpunkte für eine Neuausrichtung der Ungleichheitsforschung

Health-related well-being is a result of individual or collective agency. Understanding and influencing health-relevant behaviour, however, requires to account for physical and social contexts of agency. Accordingly, the authors suggest a focus in modern health promotion on people’s health-relevant resources and capabilities. This requires a theoretical basis onto which issues of social inequality can be linked to specific approaches of health promotion practice, namely empowerment and participation. To this purpose, the authors present Amartya Sen’s theory-based Capability Approach (CA) and complement it with insights from Pierre Bourdieu’s theory of capital interaction. Both of these theories shed light on key issues of social inequality and can fruitfully be associated with the guiding principles in health promotion stipulated by the Ottawa Charter. Together, they provide guidelines for new areas of research to analyse the complex interplay between health behaviour and social context.     

Positive quadrant dependence tests for copulas

In this paper the interest is in testing the null hypothesis of positive quadrant dependence (PQD) between two random variables. Such a testing problem is important since prior knowledge of PQD is a qualitative restriction that should be taken into account in further statistical analysis, for example, when choosing an appropriate copula function to model the dependence structure. The key methodology of the proposed testing procedures consists of evaluating a “distance” between a nonparametric estimator of a copula and the independence copula, which serves as a reference case in the whole set of copulas having the PQD property. Choices of appropriate distances and nonparametric estimators of copula are discussed, and the proposed methods are compared with testing procedures based on bootstrap and multiplier techniques. The consistency of the testing procedures is established. In a simulation study the authors investigate the finite sample size and power performances of three types of test statistics, Kolmogorov–Smirnov, Cramér–von‐Mises, and Anderson–Darling statistics, together with several nonparametric estimators of a copula, including recently developed kernel type estimators. Finally, they apply the testing procedures on some real data. The Canadian Journal of Statistics 38: 555–581; 2010 © 2010 Statistical Society of Canada     

Institutionalising a cross-sectional policy area? Ministerial competences for migrant integration in EU member states

Migrant integration is a cross-sectional policy issue and its governance involves a network of actors operating on different regional and government levels. Its emergence as a distinct policy area in many European democracies has reinvigorated the role of state actors, particularly at the national level. National governments face a growing need to coordinate formerly disparate domestic integration measures, yet they are also encouraged by increasing activities and resources that have evolved at the EU level. From an institutional perspective, this spread of both norms and resources is likely to result in the emergence of new governmental actors assigned with these tasks. Yet, little scholarly attention has so far been dedicated to the comparison of ministerial competences for migrant integration across Europe and their relation to integration policies. The paper addresses this gap in a comparative study, presenting data on the ministerial competences in 27 EU member states and Switzerland between 2010 and 2014 and linking them to data on migrant integration policies using the MIPEX dataset. The findings show no general European trend towards top-level institutionalisation and instead reveal substantial differences between Western and Eastern European democracies associated with the respective patterns of integration policies.     

Potency Factors for Risk Assessment at Libby,Montana

We reanalyzed the Libby vermiculite miners’ cohort assembled by Sullivan to estimate potency factors for lung cancer, mesothelioma, nonmalignant respiratory disease (NMRD), and all‐cause mortality associated with exposure to Libby fibers. Our principal statistical tool for analyses of lung cancer, NMRD, and total mortality in the cohort was the time‐dependent proportional hazards model. For mesothelioma, we used an extension of the Peto formula. For a cumulative exposure to Libby fiber of 100 f/mL‐yr, our estimates of relative risk (RR) are as follows: lung cancer, RR = 1.12, 95% confidence interval (CI) =[1.06, 1.17]; NMRD, RR = 1.14, 95% CI =[1.09, 1.18]; total mortality, RR = 1.06, 95% CI =[1.04, 1.08]. These estimates were virtually identical when analyses were restricted to the subcohort of workers who were employed for at least one year. For mesothelioma, our estimate of potency is K_M = 0.5 × 10^?8, 95% CI =[0.3 × 10^?8, 0.8 × 10^?8]. Finally, we estimated the mortality ratios standardized against the U.S. population for lung cancer, NMRD, and total mortality and obtained estimates that were in good agreement with those reported by Sullivan. The estimated potency factors form the basis for a quantitative risk assessment at Libby.     

Methods for Classifying Nonprofit Organizations According to their Field of Activity: A Report on Semi-automated Methods Based on Text

VOLUNTAS: International Journal of Voluntary and Nonprofit Organizations - There are various methods for classifying nonprofit organizations (NPOs) according to their field of activity. We report...     

What makes foster carers think about quitting? Recommendations for improved retention of foster carers

Ideation, or the formulation of ideas pertaining to a particular topic, is the precursor to individuals making significant life decisions. Many individuals think about foster caring long before they actually become carers, and it stands to reason that in many cases, carer discontinuation also follows a period of ideation. This being the case, it is possible that by monitoring ideation, interventions could be introduced to prevent placement disruptions occurring, particularly if the sources of dissatisfaction are known. Using a sample of 205 foster carers, a posteriori segmentation analysis identifies groups of carers dissatisfied with the same aspects of their role. One group is particularly dissatisfied with factors that are within the control of foster care agencies and also reports high levels of discontinuation ideation. Recommendations include that the individual support needs of carers be identified such that customized support can be offered, including boosting initial and ongoing training to manage expectations and ensure carers feel prepared for the role. Results also highlight the important role of caseworkers in making carers feel appreciated and taken seriously.     

With or Without You?1 Strategic Spatial Planning and Territorial Re-Scaling in Grenoble Urban Region

Spatial planning across European city regions is undergoing substantial changes. The paper draws on the framework of territorial re-scaling, strategic spatial planning and the emergence of new governance modes in order to analyse strategic planning episodes in Grenoble urban region (France). The paper aims at showing how strategic planning processes by means of new governance arenas call into question local planning cultures, especially by reshaping planning perimeters, territorial identities and actors' roles. In particular, it shows the importance of path dependency for strategic planning, the effects of power imbalances between local actors and the crucial role planners play in spatial policy-making.     

Monitoring correlation change in a sequence of random variables

We propose a monitoring procedure to test for the constancy of the correlation coefficient of a sequence of random variables. The idea of the method is that a historical sample is available and the goal is to monitor for changes in the correlation as new data become available. We introduce a detector which is based on the first hitting time of a CUSUM-type statistic over a suitably constructed threshold function. We derive the asymptotic distribution of the detector and show that the procedure detects a change with probability approaching unity as the length of the historical period increases. The method is illustrated by Monte Carlo experiments and the analysis of a real application with the log-returns of the Standard & Poor's 500 (S&P 500) and IBM stock assets.