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.     

Megachurch involvement at the local level: Examining conditions for church action in economic development

The roles of small congregations and their social impacts are well known, but few theoretical studies investigate megachurch congregations. These mammoth organizations have the potential for advancing social good, but minimal research specifically focuses on the activities of these congregations in economic development (ED). This study addresses this dearth of information by answering the following research questions: (a) In what ways are megachurches involved in ED activities? (b) Who benefits from these programs and how are the programs offered? and (c) What factors influence megachurches to offer ED activities? We frame our investigation using both demand‐ and supply‐side arguments from Frumkin's (2002) model of nonprofit and voluntary action. Online survey data and follow‐up interviews with 42 megachurch leaders in the Dallas/Fort Worth and greater Houston areas show that megachurches are implementing ED activities in alignment with demand‐side explanations, especially when advancing opportunities for the unemployed and underemployed. However, supply‐side arguments provide more explanatory power, indicating that volunteer engagement with ED activities plays a significant role in the provision of ED services through megachurches. Our study offers a better understanding of why megachurches carry out ED activities with considerable attention devoted to how megachurches partner with other congregations, nonprofits, and government entities to encourage economic growth and improve the economic well‐being of community members.     

Adverse childhood experiences,post-traumatic stress disorder symptoms,and self-reported stress among traditional and nontraditional college students

Abstract

Objective: To investigate the relationships between adverse childhood experiences (ACEs), post-traumatic stress disorder symptoms (PTSD-S), and self-reported stress among college students. Participants: A total of 236 undergraduate students enrolled in nursing courses participated. Method: Using a correlational design, participants completed questionnaires online. To examine PTSD moderation between ACE and self-reported stress, multiple regression was employed. Stress outcomes were examined using a 4-group variable. Mean differences in stress response between these four groups were examined. Differences in ACE, PTSD-S, and stress response between traditional and nontraditional students were also examined. Results: PTSD-S moderated the relationship between ACEs, and self-reported stress. This indicates that students who report PTSD-S following childhood adversity perceive higher levels of stress. Nontraditional and traditional students differed in their responses to the ICLRE scale. Conclusion: Individuals who report PTSD-S following childhood adversity perceive higher levels of stress later in life. Stress reduction programs may be beneficial for students.     

Combined multiple testing of multivariate survival times by censored empirical likelihood

In each study testing the survival experience of one or more populations, one must not only choose an appropriate class of tests, but further an appropriate weight function. As the optimal choice depends on the true shape of the hazard ratio, one is often not capable of getting the best results with respect to a specific dataset. For the univariate case several methods were proposed to conquer this problem. However, most of the interesting datasets contain multivariate observations nowadays. In this work we propose a multivariate version of a method based on multiple constrained censored empirical likelihood where the constraints are formulated as linear functionals of the cumulative hazard functions. By considering the conditional hazards, we take the correlation between the components into account with the goal of obtaining a test that exhibits a high power irrespective of the shape of the hazard ratio under the alternative hypothesis.     

Beyond Neighborhoods and Crime: Expanding the Scope of Social Disorganization to Explain Occupational Deviance

This article proposes a structural explanation for the occupational deviance dimension of white collar crime. The systemic model of social disorganization theory is used as a framework for understanding organizational conditions that produce high rates of occupational deviance. The model of workplace disorganization proposed here posits parallel mechanisms can be found in communities as well as organizations. Marginalized workplaces, employee turnover, and employee heterogeneity are antecedent factors that discourage employee network formation and collective action against deviance. By refocusing on organizational factors, we offer a broader understanding of occupational deviance, one that can predict and explain the workplace conditions under which counterproductive behaviors occur.     

Ethical Numbers: Ethics Training in U.S. Graduate Statistics Programs, 2013–2014

As important members of research teams, statisticians bear an ethical responsibility to analyze, interpret, and report data honestly and objectively. One way of reinforcing ethical responsibilities is through required courses covering a variety of ethics-related topics at the graduate level. We assessed ethics requirements for graduate-level statistics training programs in the United States for the 2013–2014 academic year using the websites of 88 universities, examining 103 biostatistics programs, and 136 statistics degree programs. We categorized programs’ ethics training requirements as required or not required. Thirty-one (35.1%) universities required an ethics course for at least some degree students. Sixty-two (25.5%) degree programs required an ethics course for at least some students. The majority (77.4%) of required courses were worth 0 or 1 credit. Of the 177 programs without an ethics requirement, 19 (10.7%) listed an ethics elective. Although a single ethics course is insufficient for instilling an ethical approach to science, degree programs that model expectations through coursework point to the value of ethics in science. More training programs should prepare statisticians to consider the ethical dimensions of their work through required coursework. Supplementary materials for this article are available online.     

The demographic characteristics of populations living near oil and gas wells in the USA

Population and Environment - This study documents the prevalence of historically marginalized populations (across age, income, education, race-ethnicity, and language) living near active oil and...     

Wider Perspectives in Family Mediation: An Ecosystemic Approach

All mediation processes are constrained by their theoretical frameworks. A wider ecosystemic framework extends perspectives and can open new windows on family systems, interdisciplinary connections, and links between past, present, and future that shape decisions. While showing some similarities to family therapy, ecosystemic family mediation is a discrete process with clearly defined principles and boundaries. In practice, it needs to be tailored to the needs of the particular family, with special attention to the importance of listening and talking with children who are experiencing parental separation and major changes in their lives. Family mediators help family members to manage change. Mediators need to look for change within themselves too, remaining open to new ideas and the development of their thinking and practice.     

Open Dialogue: Frequently Asked Questions

Open Dialogue is an approach to working with people and their families experiencing psychosocial distress. Interest in Open Dialogue in Australia has been growing recently, raising questions about its adaption and implementation to local contexts. This article is an attempt to answer some of the frequently asked questions we have encountered in training and discussions about Open Dialogue. We attempt to provide responses to questions of how Open Dialogue is different to what is done already, how it fits with current approaches, how you know if you are doing it, whether it is passive or just about doing reflections, issues about including the social network, and concerns about the evidence base. This article aims to present a variety of viewpoints in relation to these questions and to hopefully further discussions on how Open Dialogue can be implemented and adapted to Australian health care and social care contexts.