Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

Endless Pressure: Life on a Low Income in Austere Times

Much has been written that details the decline in living standards following the ‘credit crunch’ in the UK. It remains that we understand to a lesser degree the lived reality of poverty through the Great Recession and into the era of austerity. This article draws on testimonies of 62 participants from low income households conducted in three different areas of the UK during 2012–13 to document the pressures that this period brought to bear on these households. According to these testimonies, the experience of poverty intensified in key respects: first, participants reported feeling, more than ever before, that they were ‘existing, rather than living’ due to the meagre budgets they were forced to live on; second, the precarious nature of work and social security contributed to a sense of insecurity that was all pervasive in our participants' lives; third, due to the pejorative political rhetoric and media coverage of poverty, our participants felt that their lives were placed under increased scrutiny which deleteriously impacted their wider relationships and sense of belonging. Our analysis demonstrates the profound consequences for those living on low incomes of the continued shift to residual forms of state welfare and the increased reliance on the ‘Big Society’ as a means to deal with the pressures identified in this article.     

Medicare and Amyloid PET Imaging: The Battle Over Evidence

We examine a recent dispute regarding the Centers for Medicare and Medicaid Services’ (CMS) refusal to unconditionally pay for amyloid positron emission tomography (PET) imaging for Medicare beneficiaries being assessed for Alzheimer’s disease. CMS will only pay for amyloid PET imaging when patients are enrolled in clinical trials that meet certain criteria. The dispute reflects CMS’s willingness in certain circumstances to require effectiveness evidence that differs from the Food and Drug Administration’s standard for pre-market approval of a medical intervention and reveals how stakeholders with differing perspectives about evidentiary standards have played a role in attempting to shape the Medicare program’s coverage policies.     

‘There’s a lot of places I’d like to go and things I’d like to do’: the daily living experiences of adults with mild to moderate intellectual disabilities during a time of personalised social care reform in the United Kingdom

Adult social care services in the United Kingdom have undergone a period of transformation over recent years, characterised by a drive towards personalised care. Concurrently, social care budgets have been significantly reduced. This study aimed to explore the daily living experiences of adults with mild/moderate intellectual disabilities, who are at risk of no longer meeting eligibility criteria for statutory support. Focus group discussions, which included both people with intellectual disabilities and support workers, were analysed thematically. Two broad themes are presented: independence and agency; and social capital and well-being. While some participants echoed ideas central to the personalisation narrative, a number of contextual barriers to achieving greater independence and agency were discussed. Moreover, greater independence was not a desired goal for all participants. The findings highlight the potential mismatch between personalised social care, as delivered within significant budget constraints, and the needs of adults with intellectual disabilities.     

Poking a sleeping bear: the challenge of organizational recruitment for controversial topics

ABSTRACT

Researchers often approach employers to investigate employees’ work and family experiences. Organizational willingness to grant access to employees can vary, especially when the research topic is seen as controversial or contentious for the employer. This paper explores this methodological challenge using a research example from Manitoba, Canada, which explored the use of parental leave by male employees and the impact of managerial attitudes and corporate culture on usage. Sixty large employers were recruited with only seven of those organizations agreeing to participate. In this paper, the reasons organizations gave for declining to participate and the implications of their decisions for the research are examined. Although the final sample included 905 managers and employees, participating organizations tended to be employee-focused and family-friendly employers. Organizations declined participation for a variety of reasons: avoiding raising the issue with unions, awareness that their policies unfairly benefited female leave takers, and simply not seeing the relevance of a topic relating to men’s work–family experiences. A dialogue often absent from the literature, it is important to understand how employers can limit researchers’ access to employees on controversial topics. The existence of such barriers suggests alternative avenues to recruit participants directly when topics are contentious for employers.     

Individualism and Marriage: Ideal Types for Making Sense of the Relationship between Self and Sacrifice

The question of how the individual and group relate is one that has long interested social theorists. Changes in family form and structure in the contemporary West resituate this question in a contentious public debate regarding how the prevalence of new family forms may contribute or be deleterious to the well-being of individuals and families. Sociological discourse on marriage and the family generally tends to mirror this debate by dichotomizing individualism and commitment and self and marriage, resulting in an obfuscation of our understanding of the forms and styles in marriage. In order to clarify and advance this discussion, we show how individualism and commitment are mutually required in a modern world. We follow this by outlining a logically-derived typology that, along with a committed individualist and a group conformer, includes two intermediate types: a self-regulator and a relationship negotiator. We empirically demonstrate the utility of these types by showing how they correspond with the ways that interviewees talk about marriage in six local congregations, and we suggest various social factors that may particularly impact the development of local marriage cultures. These types provide a theoretical frame for understanding how individualism and commitment are intertwined and require each other.     

Best practices for online Canadian prenatal health promotion: A public health approach

Background

Prenatal health promotion provides information regarding pregnancy risks, protective behaviours and clinical and community resources. Typically, women obtain prenatal health information from health care providers, prenatal classes, peers/family, media and increasingly, Internet sites and mobile apps. Barriers to prenatal health promotion and related services include language, rural/remote location, citizenship and disability. Online public health platforms represent the capacity to reach underserved women and can be customised to address the needs of a heterogeneous population of pregnant women.

Trajectories of Unintended Fertility

Having an unintended birth is strongly associated with the likelihood of having later unintended births. We use detailed longitudinal data from the Add Health Study (N = 8300) to investigate whether a host of measured sociodemographic, personality, and psychosocial characteristics select women into this “trajectory” of unintended childbearing. While some measured characteristics and aspects of the unfolding life course are related to unintended childbearing, explicitly modeling these effects does not greatly attenuate the association of an unintended birth with a subsequent one. Next, we statistically control for unmeasured time-invariant covariates that affect all birth intervals, and again find that the association of an unintended birth with subsequent ones remains strong. This persistent, strong association may be the direct result of experiencing an earlier unintended birth. We propose several mechanisms that might explain this strong association.