Treatment allocation strategies for umbrella trials in the presence of multiple biomarkers: A comparison of methods

Umbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers – equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker-guided umbrella trial. We define the pairings representing the pre-trial expectations on efficacy as linked pairs, and the other biomarker-treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment-biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre-specified treatment-biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre-specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.     

Coverage Bias in Traditional Telephone Surveys of Low-Income and Young Adults

The proportion of adults with only wireless telephones is growingrapidly. Using 2006 data from the National Center for HealthStatistics’ National Health Interview Survey, this articleis among the first to reveal that noncoverage of this populationcan result in nonnegligible bias for traditional random-digit-diallandline telephone surveys that do not call wireless telephonenumbers. In 2006 in the United States, 17 percent of low-incomeadults with household income below 200 percent of the federalpoverty thresholds, 25 percent of young adults aged 18–29years, and 32 percent of low-income young adults lived in householdswith only wireless telephones. Within each of these three subgroups,we compared wireless-only adults and adults with landline telephoneson demographic characteristics and 13 key indicators of healthstatus, health behaviors, health care service use, and healthcare access. Even after statistical adjustments that accountfor demographic differences between adults living in householdswith and without landlines, telephone surveys of landlines willunderestimate the prevalence of health behaviors, such as bingedrinking, smoking, and HIV testing. Obesity may be overestimatedand physical activity may be underestimated for low-income youngadults. No significant bias is predicted for other measuresof health status and health insurance coverage. Sample weightingprocedures that incorporate adjustments for multiple demographiccharacteristics are necessary to help attenuate coverage biasin traditional telephone surveys, but may not be sufficientfor behavioral risk factor surveys of low-income and young adults.     

Impact of Acts of Discrimination on Quality of Life Among Injecting Drug Users in Delhi, India

The study examines the association between quality of life (QOL) and discrimination perpetrated against a vulnerable population like injecting drug users (IDU). Given that QOL affects self efficacy which in turn affects behavior, it is relevant to examine QOL among IDUs in the context of HIV prevention, and to study whether discriminations and human rights abuses impact QOL in this population. A cross sectional study was conducted in two research sites in Delhi, India among 343 IDUs recruited through a respondent driven sampling. A Hindi version of the WHOQOL Bref survey along with a survey questionnaire of discrimination were used to interview participants. After controlling for demographic characteristics, experiencing physical and verbal abuse (OR: 0.46, CI 0.27–0.79),arrests and imprisonment for carrying needles and/or using drugs (OR: 0.53, CI 0.31–0.90) and lacking health information (OR: 0.49, CI 0.29–0.85)was associated with lower social QOL, while being denied health care services was associated with lower psychological QOL. The more discrimination experienced, the lower was the quality of life in the social and psychological domains. Participants’ perceived well being in the four domains was related to their living conditions, discriminatory acts and to perceptions of social support. Discriminatory acts and abuses appeared to have a greater toll on their psychological well being and social relationships, thus indicating the need for human rights advocacy in order to influence law enforcement practices and to reduce stigma, while expanding social support through an extended comprehensive IDU programme.     

外商直接投资及其影响因素——来自中国地域的面板因果关系分析

 利用中国1993-2005年29个省的面板数据,本文建立了一个系统动态的因果关系模型,检验了外商直接投资（FDI）与其他影响变量的关系,在所有影响FDI的变量中,我们重点检验了GDP、FDI、国内投资和基础设施的因果关系。结果显示短期内GDP可以吸引FDI的流入,而FDI对国内投资增长是有效的,FDI对GDP的作用是通过对国内投资影响而实现的。长期内,FDI对国内投资和经济增长有促进作用,而与基础设施没有直接的关系。     

Evidencing the harms of hate speech

The ways in which targeted communities experience hate speech is an important, but often neglected, component of the debate over the legitimacy of hate speech laws. This article reports on data drawn from interviews conducted with 101 members of Indigenous and minority ethnic communities in Australia regarding their experiences of hate speech. We give voice to targets’ experiences of face-to-face and more widely broadcast hate speech, and outline the constitutive and consequential harms they claim to have suffered. We assess these against the alleged harms of hate speech in the literature, finding a close correlation between targets’ reports and the literature.     

Care networks in play: Understanding death of a parent as a contributing factor to homelessness

Offering an understanding of specialized service needs of those becoming homeless because of the death of a parent or parental figure, this project is set in Detroit’s urban context, where residents face economic hardship and intergenerational poverty. In this study, we analyze the voices of practitioners (n = 5) and men (n = 5) who have experienced parental death as a contributing factor to homelessness in Detroit, Michigan. Findings include the following: (1) the impact of death and dying experiences on these men and (2) the role of care networks in these men’s lives, particularly when these men have and lack “default” caregivers after death of a parent. This community-based research project was a result of a partnership between a local agency serving persons experiencing homelessness, where the practitioner initiated the project with the researcher. The paper concludes with implications for social work practice.     

Improving research about us,with us: a draft framework for inclusive autism research

It is both epistemologically as well as ethically problematic if the autistic voice is not heard in relation to social scientific research seeking to further develop knowledge of autism. Ever since autism first emerged, it has remained medicalised and almost exclusively the preserve of non-autistic researchers. More recently, autistic individuals have begun to contribute to autism research. However, the vast majority of research in autism is still undertaken on autistic people, rather than with them, and is often not concerned with improving the day-to-day lives of people with autism. We discuss the concepts of participatory research and emancipatory research before presenting a draft framework for what we regard as truly inclusive research in autism. Our proposals are firmly based on ideas developed by the members of a university-based group of autistic adults (the Asperger’s Consultation Group) as well as the knowledge and experience of the other contributors.     

Eating together and eating alone: meal arrangements in British households

Sociology traditionally accounts for eating in terms of the social organization of meals, their provision and consumption. A recurrent public concern is that the meal is being subverted. This paper examines meal arrangements in British households in 2012, drawing on an online survey in the format of a food diary administered to 2784 members of a supermarket consumer panel. It charts the organization of contemporary eating occasions, paying attention to socio‐demographic variation in practice. Especially, it explores companionless meals, putting them in contexts of food provisioning and temporal rhythms. Findings show that eating alone is associated with simpler, quicker meals, and that it takes place most commonly in the morning and midday. Those living alone eat alone more often, but at similar meal times, and they take longer over their lone meals. Comparison with a similar study in 1955–6 suggests some fragmentation or relaxation in collective schedules. The implications are not straightforward, and the causes probably lie more in institutional shifts than personal preferences. Declining levels of commensality are, however, associated with a reduction in household size and, especially in households with children, difficulties of coordinating family members’ schedules.