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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.  相似文献   
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The theory of incapacitation involves reducing an offender's ability or capacity to commit further crimes. Capital punishment accomplishes this goal. An executed murderer never murders again. However, we do not execute all murderers, only capital murderers. This policy produces several research questions. Do capital murderers present a special risk to society? Are capital murderers more likely to murder or commit other violent crimes again than other murderers or the average citizen? To answer these questions, many states require a prediction of future dangerousness of a newly convicted murderer. To what extent has the judgment of future dangerousness matched actuarial data of subsequent murders and serious crimes? Using a secondary analysis, this investigation attempted to assemble available data of postconviction dangerousness of death sentenced capital murderers to create a more comprehensive actuarial account of subsequent dangerousness and to present the data in a common format used by the Federal Bureau of Investigation and the Bureau of Justice Statistics. Across 14 studies identified with relevant data, there were 13 instances of subsequent murder and 462 serious crime or prison rule violations.  相似文献   
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Functional Capacity Evaluations (FCE's) are part of practice in work injury prevention and rehabilitation, and are designed to define an individual's functional abilities or limitations in the context of safe, productive work tasks. Qualitative research methodology was used to investigate the attitudes and behaviours of health professionals in relation to FCE use. The study aimed to identify why health professionals chose a particular FCE, and to identify what factors influence health professionals' clinical judgements when providing results and recommendations for the individual being assessed. Five health professionals from the Hunter Region of New South Wales, Australia, participated in semi-structured, individual interviews using a phenomenological approach. Following inductive analysis of the data, four themes reflecting participants' attitudes and behaviours of FCE use emerged: i) referrals and expectations, including why and when the assessment is completed ii) outcomes, -- what the results aim to provide iii) workplace/practice/usage issues and iv) skills of the assessor. The results indicate the need for further research on the clinical utility of FCE's. A large scale quantitative study would allow results to be generalised to a wider community of FCE users.  相似文献   
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This article develops an analysis of the concept of disciplinary neo-liberal feminism through a focus on gendered poverty alleviation strategies and illustrates the value of this through a discussion of microfinance. By locating this study within an analysis of the expansion of global capital accumulation, the article argues that the liberal frameworks of female empowerment and entrepreneurialism that are central to these programs and to feminism in this form, mask their underlying political, social and economic objectives. In contrast, a Marxist Feminist approach more adequately explains the interplay of class and gender that underpins poverty alleviation strategies. This article argues that in the context of financial crisis and reduced social provision, women living in poverty in the Global South were identified as targets for the expansion of global finance. Their integration into global financial networks via microfinance and other pro-poor strategies has facilitated the expansion of markets for credit while at the same time disciplining market participation through the twin forces of risk and incentive. Disciplinary neo-liberal feminism has underpinned this incorporation of women into global capital accumulation creating profound effects for households and families, with microfinance programs representing important sites of contestation for the politics of class and gender.  相似文献   
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We present an algorithm for learning oblique decision trees, called HHCART(G). Our decision tree combines learning concepts from two classification trees, HHCART and Geometric Decision Tree (GDT). HHCART(G) is a simplified HHCART algorithm that uses linear structure in the training examples, captured by a modified GDT angle bisector, to define splitting directions. At each node, we reflect the training examples with respect to the modified angle bisector to align this linear structure with the coordinate axes. Searching axis parallel splits in this reflected feature space provides an efficient and effective way of finding oblique splits in the original feature space. Our method is much simpler than HHCART because it only considers one reflected feature space for node splitting. HHCART considers multiple reflected feature spaces for node splitting making it more computationally intensive to build. Experimental results show that HHCART(G) is an effective classifier, producing compact trees with similar or better results than several other decision trees, including GDT and HHCART trees.  相似文献   
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Estimates of pornography use in the United States range widely. We explore the reasons for the variation in such estimates among U.S. adults using data from four different recent nationally representative samples—each of which asked a different type of question about pornography use. We attribute the notable variation in estimates to differences in question wording and answer options, and assert that a survey question asking respondents about their most recent use of pornography minimizes recall bias and is better poised to assess the overall prevalence of pornography in a population than is the more common approach of asking respondents about their historical general-use pattern. When we privileged the most-recent-use approach, survey data from 2014 reveal that 46% of men and 16% of women between the ages of 18 and 39 intentionally viewed pornography in a given week. These numbers are notably higher than most previous population estimates employing different types of questions. The results have ramifications for methods of surveying sensitive self-reported behaviors and for contextualizing scholars’ claims as well as popular conversations about the reach and implications of pornography use in the United States.  相似文献   
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There is growing recognition of the experience of non-death-related loss and grief. One unexplored area of non-death-related loss and grief is associated with older people’s transition from home to residential aged care (RAC). This paper reports findings from a qualitative study that explored the experiences of people living in RAC, carer-relatives of people living in RAC and RAC staff. Using theories of loss and grief, the paper identifies features of the transition to RAC that are associated with unresolved loss and maladaptation to changed circumstances, and the types of support that would mitigate these. Using a series of focus groups with both residents and carer-relatives, as well as staff, the study found that residents and their families need more support to negotiate the multiple, often necessarily hasty decisions and bureaucratic requirements associated with transitioning to RAC, while simultaneously experiencing loss and grief. The types of support that families would welcome from service providers include facilitating shared decision making, valuing family and community carer expertise and providing practical information and assistance to fulfil administrative obligations.  相似文献   
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We examine how use of antidepressant medications is influenced by Food and Drug Administration (FDA) warnings about the increased risk of suicidality associated with pediatric antidepressant use. With individual-level data on antidepressant use from the Medical Expenditure Panel Survey, we consider whether consumer responses to FDA warnings differ among targeted (children) and non-targeted (adult) age-groups. Because the warning labels specifically mentioned new users, we examine separately the effects of the warnings on initiations of antidepressant therapy and on continued use of antidepressants. We find evidence consistent with reduced initiation of antidepressant use among the intended population of children, and that usage among children with more highly educated parents responded earlier to FDA information. However, we also find spillover effects of reduced initiation among the non-targeted population of adults. Overall, our results indicate that the FDA warning may have led consumers to perceive risks beyond those specifically mentioned.  相似文献   
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