Blinded continuous monitoring in clinical trials with recurrent event endpoints

In studies with recurrent event endpoints, misspecified assumptions of event rates or dispersion can lead to underpowered trials or overexposure of patients. Specification of overdispersion is often a particular problem as it is usually not reported in clinical trial publications. Changing event rates over the years have been described for some diseases, adding to the uncertainty in planning. To mitigate the risks of inadequate sample sizes, internal pilot study designs have been proposed with a preference for blinded sample size reestimation procedures, as they generally do not affect the type I error rate and maintain trial integrity. Blinded sample size reestimation procedures are available for trials with recurrent events as endpoints. However, the variance in the reestimated sample size can be considerable in particular with early sample size reviews. Motivated by a randomized controlled trial in paediatric multiple sclerosis, a rare neurological condition in children, we apply the concept of blinded continuous monitoring of information, which is known to reduce the variance in the resulting sample size. Assuming negative binomial distributions for the counts of recurrent relapses, we derive information criteria and propose blinded continuous monitoring procedures. The operating characteristics of these are assessed in Monte Carlo trial simulations demonstrating favourable properties with regard to type I error rate, power, and stopping time, ie, sample size.     

The Impact of Neighboring on Changes in Sense of Community Over Time: A Latent Transition Analysis

Sense of community (SOC) is associated with the quality of community life and the building of social capital. While its linkage to informal social behavior, such as neighboring, is inherent in discussions regarding theory, empirical evidence remains scarce. Moreover, the degree to which neighboring behavior influences SOC over time is largely unknown. Using a latent transition analysis, the effect of neighboring on SOC was investigated over a 5-year span from 2006 to 2011 among a sample of adults (n?=?165) in Arizona. Initially, a latent class analysis identified two SOC subgroups: Low SOC and High SOC. The likelihood of shifts in SOC class membership over 5 years was generally stable, with most individuals staying in the same group (82.3% Low SOC; 92.4% High SOC). Neighboring behavior and socio-demographic covariates impacted the likelihood that individuals changed classes, with 25.3% of Low SOC individuals transitioning to High SOC in 2011 and 55.4% of High SOC individuals moving to Low SOC in 2011. Specifically, having an income greater than $60,000 and visiting with neighbors lessened the likelihood of being in the Low SOC class in 2006; and length of residence and exchanging favors with neighbors lessened the likelihood of being in the Low SOC class in 2011. These findings have implications for both community design and community development practice. Design and development interventions that promote greater social interaction may help build and sustain SOC over time.

     

Young people,social media and connective action: from organisational maintenance to everyday political talk

Social media is pervasive in the lives of young people, and this paper critically analyses how politically engaged young people integrate social media use into their existing organisations and political communications. This qualitative research project studied how young people from a broad range of existing political and civic groups use social media for sharing information, mobilisation and, increasingly, as a means to redefine political action and political spaces. Twelve in-person focus groups were conducted in Australia, the USA and the UK with matched affinity groups based on university campuses. The groups were of four types: party political group, issue-based group, identity-based group and social group. Our focus group findings suggest that this in-depth approach to understanding young people's political engagement reveals important group-based differences emerging in young people's citizenship norms: between the dutiful allegiance to formal politics and a more personalised, self-actualising preference for online, discursive forms of political engagement and organising. The ways in which political information is broadcast, shared and talked about on social media by engaged young people demonstrate the importance of communicative forms of action for the future of political engagement and connective action.     

Behavioral responses of rural and urban greater white-toothed shrews (Crocidura russula) to sound disturbance

Urban Ecosystems - The development of urban areas imposes challenges that wildlife must adapt to in order to persist in these new habitats. One of the greatest changes brought by urbanization has...     

Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

The Eurasian Economic Union: Development Prospects and Possible Obstacles

This article analyzes the development prospects and problems for the Eurasian Economic Union (EAEU). It examines issues of integration within the EAEU, as well as interactions with other countries, both CIS (Commonwealth of Independent States) and non-CIS. The main problem of integration within the EAEU is the dominance of redistributive motives over productive ones. This article assesses the extent of Russian oil and gas transfers to EAEU partners and the impact of tax maneuvers on their size. It shows that the creation of mechanisms for redistributing profits within the EAEU will allow a positive economic effect to materialize from free trade agreements with non-CIS countries. The article assesses the risks for the EAEU related to Russia’s introduction of a unilateral ban on food imports from countries on the sanctions list and to the possible establishment of tariffs on trade with Ukraine.     

Unterstützung dualer Karrieren im Spitzensport

The longstanding focus of elite athletes on top sports entails disadvantages hampering their later entry to the world of work. In order to successfully contribute their outstanding personality traits to a later job, athletes are thus particularly required to care for their employability. Contributing to this, the author carried out a competency balancing with top athletes. This coaching method significantly decreased the athletes’ need for self-information. Evaluation further showed indications of increased clarity and certainty of occupational goals as well as work satisfaction.     

Predicting the Risk of Biological Invasions Using Environmental Similarity and Transport Network Connectedness

Understanding the risk of biological invasions associated with particular transport pathways and source regions is critical for implementing effective biosecurity management. This may require both a model for physical connectedness between regions, and a measure of environmental similarity, so as to quantify the potential for a species to be transported from a given region and to survive at a destination region. We present an analysis of integrated biosecurity risk into Australia, based on flights and shipping data from each global geopolitical region, and an adaptation of the “range bagging” method to determine environmental matching between regions. Here, we describe global patterns of environmental matching and highlight those regions with many physical connections. We classify patterns of global invasion risk (high to low) into Australian states and territories. We validate our analysis by comparison with global presence data for 844 phytophagous insect pest species, and produce a list of high‐risk species not previously known to be present in Australia. We determined that, of the insect pest species used for validation, the species most likely to be present in Australia were those also present in geopolitical regions with high transport connectivity to Australia, and those regions that were geographically close, and had similar environments.