Applications of Bayesian statistical methodology to clinical trial design: A case study of a phase 2 trial with an interim futility assessment in patients with knee osteoarthritis

Development of new pharmacological treatments for osteoarthritis that address unmet medical needs in a competitive market place is challenging. Bayesian approaches to trial design offer advantages in defining treatment benefits by addressing clinically relevant magnitude of effects relative to comparators and in optimizing efficiency in analysis. Such advantages are illustrated by a motivating case study, a proof of concept, and dose finding study in patients with osteoarthritis. Patients with osteoarthritis were randomized to receive placebo, celecoxib, or 1 of 4 doses of galcanezumab. Primary outcome measure was change from baseline WOMAC pain after 8 weeks of treatment. Literature review of clinical trials with targeted comparator therapies quantified treatment effects versus placebo. Two success criteria were defined: one to address superiority to placebo with adequate precision and another to ensure a clinically relevant treatment effect. Trial simulations used a Bayesian dose response and longitudinal model. An interim analysis for futility was incorporated. Simulations indicated the study had ≥85% power to detect a 14‐mm improvement and ≤1% risk for a placebo‐like drug to pass. The addition of the second success criterion substantially reduced the risk of an inadequate, weakly efficacious drug proceeding to future development. The study was terminated at the interim analysis due to inadequate analgesic efficacy. A Bayesian approach using probabilistic statements enables clear understanding of success criteria, leading to informed decisions for study conduct. Incorporating an interim analysis can effectively reduce sample size, save resources, and minimize exposure of patients to an inadequate treatment.     

The Influence of Feelings While Driving Regular Cars on the Perception and Acceptance of Self‐Driving Cars

Self‐driving vehicles will affect the future of transportation, but factors that underlie perception and acceptance of self‐driving cars are yet unclear. Research on feelings as information and the affect heuristic has suggested that feelings are an important source of information, especially in situations of complexity and uncertainty. In this study (N = 1,484), we investigated how feelings related to traditional driving affect risk perception, benefit perception, and trust related to self‐driving cars as well as people's acceptance of the technology. Due to limited experiences with and knowledge of self‐driving cars, we expected that feelings related to a similar experience, namely, driving regular cars, would influence judgments of self‐driving cars. Our results support this assumption. While positive feelings of enjoyment predicted higher benefit perception and trust, negative affect predicted higher risk and higher benefit perception of self‐driving cars. Feelings of control were inversely related to risk and benefit perception, which is in line with research on the affect heuristic. Furthermore, negative affect was an important source of information for judgments of use and acceptance. Interest in using a self‐driving car was also predicted by lower risk perception, higher benefit perception, and higher levels of trust in the technology. Although people's individual experiences with advanced vehicle technologies and knowledge were associated with perceptions and acceptance, many simply have never been exposed to the technology and know little about it. In the absence of this experience or knowledge, all that is left is the knowledge, experience, and feelings they have related to regular driving.     

Sex‐differentiated associations among negative parenting,emotion‐related brain function,and adolescent substance use and psychopathology symptoms

Parenting is a critical factor in adolescent social–emotional development, with maladaptive parenting leading to risk for the development of psychopathology. However, the emotion‐related brain mechanisms underlying the influence of parenting on psychopathology symptoms are unknown. The present study utilized functional magnetic resonance imaging and laboratory measures to examine sex‐differentiated associations among parenting, adolescent emotion‐related brain function, and substance use and psychopathology symptoms in 66 12–14‐year olds. Maternal parenting behaviors (warmth, negative parenting) were observed in a laboratory task. Adolescent brain responses to negative emotional stimuli were assessed in emotion processing regions of interest (left [L] and right [R] amygdala, anterior insula, and anterior cingulate cortex [ACC]). Adolescents reported on substance use and depressive, anxiety, and externalizing symptoms. Maternal negative parenting predicted adolescent brain activation differently by sex. For girls, negative parenting predicted heightened R ACC activation to negative emotional stimuli. For boys, negative parenting predicted blunted L and R anterior insula and L ACC activation. Furthermore, for girls, but not boys, heightened L anterior insula and heightened L and R ACC activation were associated with substance use and depressive symptoms, respectively. Findings suggest neural response to negative emotion as a possible sex‐specific pathway from negative parenting to psychopathology.     

The AART of Ethnography: A Critical Realist Explanatory Research Model

Critical realism is a philosophy of science, which has made significant contributions to epistemic debates within sociology. And yet, its contributions to ethnographic explanation have yet to be fully elaborated. Drawing on ethnographic data on the health‐seeking behavior of HIV‐infected South Africans, the paper compares and contrasts critical realism with grounded theory, extended case method and the pragmatist method of abduction. In so doing, it argues that critical realism makes a significant contribution to causal explanation in ethnographic research in three ways: 1) by linking structure to agency; 2) by accounting for the contingent, conjunctural nature of causality; and 3) by using surprising empirical findings to generate new theory. The paper develops the AART (abduction, abstraction, retroduction, testing) research schema and illustrates its strengths by employing a Bourdieusian field analysis as a model for morphogenetic explanation.     

Getting Under the Skin: Children’s Health Disparities as Embodiment of Social Class

Social class gradients in children’s health and development are ubiquitous across time and geography. The authors develop a conceptual framework relating three actions of class—material allocation, salient group identity, and inter-group conflict—to the reproduction of class-based disparities in child health. A core proposition is that the actions of class stratification create variation in children’s mesosystems and microsystems in distinct locations in the ecology of everyday life. Variation in mesosystems (e.g., health care, neighborhoods) and microsystems (e.g., family structure, housing) become manifest in a wide variety of specific experiences and environments that produce the behavioral and biological antecedents to health and disease among children. The framework is explored via a review of theoretical and empirical contributions from multiple disciplines, and high-priority areas for future research are highlighted.     

Working mothers’ emotional exhaustion from work and care: The role of core self-evaluations,mental health,and control

This research examined the direct and indirect relationships between core self-evaluations (via mental health) and emotional exhaustion originating from both the work and caregiving domains. The extent to which these relationships were moderated by control over work and care also was examined. Data came from 142 employed mothers in Australia who completed surveys at three measurement points each separated by four weeks. Results showed that core self-evaluations related positively to mental health which, in turn, related negatively to emotional exhaustion originating from work, but only when work control was high. Moreover, core self-evaluations related negatively to emotional exhaustion originating from care through improvements in mental health, but care control did not moderate this relationship. Overall, these findings contribute to a better understanding of how working mothers’ personal and work resources mitigate emotional exhaustion.     

Promoting quality parent–child visits: the power of the parent–foster parent relationship

Parent–child visits for children in foster care are often fraught with tension, particularly between foster parents and parents. Qualitative interviews with 42 social workers, foster parents and parents revealed more positive relations when foster parents recognized parent fears and shared power over parenting decisions with them. Social workers can support the process by clarifying visiting expectations and encouraging foster parents to reach out to parents.     

Casual Sexual Relationships and Mental Health in Adolescence and Emerging Adulthood

Casual sexual relationships are relatively common in emerging adulthood. Yet the mental health implications of engaging in these relationships are unclear; past research has found negative associations, positive associations, or no association with mental health. In addition, little research has accounted for mental health status prior to entering casual sexual relationships. Using data from the National Longitudinal Study of Adolescent Health (N = 12,401), we measured mental health prior to engaging in casual sexual relationships and subsequent mental health after engaging in these relationships. We found that suicidal ideation and depressive symptoms in adolescence were associated with entrance into casual sexual relationships in emerging adulthood. Furthermore, casual sexual relationships were associated with an increased likelihood of reporting suicidal ideation in emerging adulthood.