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.     

Assessing the Moderating Effects of Depressive Symptoms on Antisocial Behavior among Urban Youth in Public Housing

This study assesses whether the influences of attitude towards deviance, exposure to delinquent peers and parental supervision and encouragement on antisocial behavior are moderated by depressive symptoms. Two hundred and thirty eight African American adolescents ages 13–19 from three public housing developments participated in this study. Results indicate that approximately half of the youth did not engage in antisocial behaviors in the last year. Gender, depression, attitudes and peers were significant correlates of antisocial behavior. Parental supervision and encouragement, and age were not related to antisocial behavior. Interaction effects suggest that the relative influences of attitudes towards deviance and delinquent peers on antisocial behaviors depend upon gender and level of depression symptoms. Implications for social work practice and future research are discussed.     

Development and Consideration of Global Policies for Managing the Future Risks of Poliovirus Outbreaks: Insights and Lessons Learned Through Modeling

The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes.     

Redressing Inequity in Parent Care Among Siblings

When inequities occur in the division of labor among adult siblings caring for older parents, conflict may result. This paper uses equity theory as a framework for understanding the processes used by siblings to rectify imbalances in their parental responsibilities. The study is based on a sample of 40 focus group participants who described caregiving relationships among siblings. Consistent with equity theory, these participants used two approaches to redress inequities in their sibling caregiving relationships: requesting behavioral changes from siblings and making cognitive changes. The findings suggest that these two approaches can result in more perceived equity but may also lead to even greater perceived inequity and distress.     

Testing for a trend in exponential means: A two-moment approximation to the null distribution of the likelihood-ratio statistic

The likelihood-ratio test statistic for testing homogeneity of exponential means with an ordered alternative has a rather complex null distribution. Expressions for the mean and variance of its null distribution are derived, and the accuracy of a two-moment chi-squared approximation is studied. The coefficients needed to implement the approximation are tabled. The application of these results in testing for a constant versus a nondecreasing intensity in a nonhomogeneous Poisson process is also discussed.     

Generic Strategies and Business Performance: an Empirical Study of the Screw Machine Products Industry

Select businesses in industry may attempt to compete through distinct strategies. But some may be successful in adopting distinct strategic profiles while others may not prove successful. In this study it was expected that six different groups of businesses might be present in the empirical exploration – those competing successfully with the low cost strategy and those competing unsuccessfully with this strategy; those competing successfully with the differentiation strategy and those competing unsuccessfully with this strategy; and those competing successfully with low cost and differentiation strategies and those competing unsuccessfully with these strategies. The results of the investigation portray the presence of three strategic profiles. They are unsuccessful low cost businesses with the lowest performance, unsuccessful differentiated businesses with the second lowest performance, and successful businesses with combination strategies with the highest performance.     

Examining the Relationship Between Female Inmate Homosexual Behavior and Attitudes Toward Homosexuality and Homosexuals

Most sociologists and penologists tend to shy away from studying inmate attitudes toward homosexuality and homosexuals. Researchers within the corrections field who focus on prison sexuality typically conduct their research on consensual samesex sexual behavior and sexual coercion. The focus of the present study, however, was to ascertain female inmates' attitudes toward homosexuality and homosexuals while exploring the role ofseveral predictor variables on their attitudes. Specifically, the authors examine the relationship between female inmate homosexual behavior and attitudes toward homosexuality and homosexuals. Because of the number of items pertaining to attitudes toward homosexuality and homosexuals, factor analysis was conducted to examine whether the items measured similar constructs. Results ofthe factor analysis revealed two distinct factors/issues:civil/personal rights and personal deviance models. The mostsalient, and only statistically significant, variables in the civil/personal rights model were age, homosexual activity prior to incarceration, and homosexual activity during incarceration. Homosexual behavior during incarceration was the only statistically significant predictor of the personal deviance model.     

Are they lonely at the top? Social relationships and social support among Australian managers

This research tested the possibility that managers may be lonely at the top. A total of 572 Australian managers responded to a questionnaire-based survey. Results showed that social support was more frequently available from non-work relationships than from work relationships. The support available from work and non-work sources was also qualitatively different. Workplace relationships offered mainly distraction, whereas non-work sources also offered care, acceptance, and consolation. Within the workplace, co-workers were the primary source of support. Moreover, support for work stressors was received from within the workplace, or from a spouse or partner. However, support was seldom received from within the workplace for non-work stressors. Concerns about social relationships also contributed to most of the nominated stressful situations.     

Why some Conferences are Difficult: a Study of the Professionals' Experience of Some Initial Child Protection Conferences

The views of 261 professionals attending 36 initial child protection conferences with parental participation were collected by means of a questionnaire. Overall, the professionals found the involvement of parents beneficial to the consideration of risk and the decision-making process, with some provisos. The data revealed that most of the negative responses arose from one third of the conferences, and that these conferences shared particular features relating to family profile and certain conference characteristics. The nature of the difficulties is identified and explored, especially with regard to the ambiguities and the uncertainties involved in risk assessments which contributed to the professionals, negative experiences, and which seemed to be heightened by the parents' presence.