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.     

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.     

Sex Related Factors in the Perception of Threatening Facial Expressions

This study replicated and extended previously reported sex differences involving both viewer and target in the recognition of threatening facial expressions. Based on the assumption that the evolved cognitive mechanisms mediating anger recognition would have been designed by natural selection to operate quickly in the interests of survival, brief tachistoscopic presentation of stimulus photographs was used. Additionally, in contrast to prior published studies, the statistical methods of signal detection research were used to control for the confounding effects of non-random guessing. The main hypothesis, that anger posed by males would be more accurately perceived than anger posed by females, was supported. A secondary hypothesis, that female-posed anger would be more accurately perceived by women than by men, received partial support. Testosterone levels, measured inferentially in terms of diurnal cycles, failed to show the hypothesized positive relationship to accuracy of anger perception.     

Politics and Scientific Expertise: Scientists, Risk Perception, and Nuclear Waste Policy

To study the homogeneity and influences on scientists'perspectives of environmental risks, we have examined similarities and differences in risk perceptions, particularly regarding nuclear wastes, and policy preferences among 1011 scientists and engineers. We found significant differences ( p 0.05)in the patterns of beliefs among scientists from different fields of research. In contrast to physicists, chemists, and engineers, life scientists tend to: (a)perceive the greatest risks from nuclear energy and nuclear waste management; (b)perceive higher levels of overall environmental risk; (c)strongly oppose imposing risks on unconsenting individuals; and (d)prefer stronger requirements for environmental management. On some issues related to priorities among public problems and calls for government action, there are significant variations among life scientists or physical scientists. We also found that–independently of field of research–perceptions of risk and its correlates are significantly associated with the type of institution in which the scientist is employed. Scientists in universities or state and local governments tend to see the risks of nuclear energy and wastes as greater than scientists who work as business consultants, for federal organizations, or for private research laboratories. Significant differences also are found in priority given to environmental risks, the perceived proximity of environmental disaster, willingness to impose risks on an unconsenting population, and the necessity of accepting risks and sacrifices.     

Suicide Attempts by Adolescent Latinas: An Exploratory Study of Individual and Family Correlates

Epidemiological data show high rates of suicide attempts among adolescent Latinas. Few studies have addressed the psychosocial, cultural and family correlates of suicide attempts among this age group of a rapidly growing population. The authors studied 31 adolescent Hispanic females who were receiving mental health services; 14 girls had attempted suicide in the previous five years and 17 had never attempted suicide. The two groups of girls did not differ significantly with respect to demographic profiles, levels of depression, family type, acculturation, or self-esteem. However, as hypothesized, the mutuality between girls and their mothers was lower among suicide attempters. Maladaptive coping skills of withdrawal and wishful thinking were more commonly used by attempters, and non-attempters used emotional regulation and problem-solving more frequently. Findings are discussed within the context of the empirical and theoretical literature and implications for practice are considered.     

Spatial Variations in Church Burnings: The Social Ecology of Victimized Communities in the South*

Abstract In recent years, church burnings in the South have attracted a great deal of attention. Many commentators have charged that they are a product of strained race relations throughout the South, and particularly of severe racial tensions in Southern rural areas. In this study we evaluate these claims. We begin by mapping the spatial coordinates of recorded church burnings from 1990 to 1997, and find that church arsons indeed are concentrated in the South. Church burnings, however, are a more urban phenomenon than popular media accounts would suggest. Our analysis then explores the influence of contextual factors (population and locale, racial composition and inequality, so‐cioeconomic conditions, local religious ecology, and patterns of reported crime) on church burnings in counties located in the study region. Logistic regression models confirm that church arsons are most likely to occur in small metropolitan statistical areas (MSAs) and non‐MSA counties containing a city of at least 10,000 residents. Church burnings also are especially likely in counties with a higher percentage of black residents, a larger number of churches relative to the rest of the state, and a higher arson rate. We conclude by discussing the implications of these findings for future research and public policy.     

Challenges to professionalism and union voting intentions: The case of pharmacists

Using data from a national survey of pharmacists who are members of the American Pharmaceutical Association, we examine the union voting intentions of employee pharmacists. We find that union instrumentality regarding professionalism is a primary predictor of union voting intent among these employees. In addition, this predictor mediates the relationship between the level of professionalism at a pharmacist’s current employment situation and his or her expected union vote. Also important to union voting intent are respondent beliefs about union instrumentality regarding pecuniary issues, prior union experience, as well as overall job satisfaction. Implications for employers, unions, and researchers are drawn. We thank Mary Graham, Jann Skelton, Paul Swiercz, Terry Thomason, and participants at the Seventh Bar-gaining Group Conference at Michigan State University for their comments on earlier versions of this paper. This research was made possible by a grant from the American Pharmaceutical Association.     

森林可持续经营的政策支持体系——亚太区域示范林项目中国临安示范林实践

运用参与性诊断(即PRRA)方法对临安示范林地区的森林经营主要政策进行了诊断分析,找出了现行政策存在的问题,如:政策环境欠佳,产权政策不到位,税费政策不合理,林业产品生产、加工和销售脱节,森林生态效益补偿政策欠规范、不合理等.同时,运用参与性设计的方法对若干主要政策进行专项设计,并在此基础上,从优化森林可持续经营的政策环境和规范政策系统运行两方面入手,提出一套科学、合理和有效的适合当地水平的森林可持续经营综合设计方案,以促进示范林网络的发展.