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.     

Secondary analysis of dangerousness among death sentenced capital murderers

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.     

The Role of Family Income in the Intergenerational Association of AFDC Receipt

Daughters from low‐income families who did not receive Aid to Families with Dependent Children (AFDC) are compared to daughters from low‐income families who did receive assistance to better account for family income in the intergenerational association of AFDC. The research models the timing of a daughter's first birth and, for those who become mothers, the number of years a daughter receives any AFDC. Women whose families received AFDC during their childhood are more likely to receive AFDC as adults relative to those women whose families did not receive AFDC. Controlling for family income in a more careful and comprehensive way than past research explains part but not all of the effects of childhood AFDC receipt. Among daughters from chronically poor families, however, parental AFDC use is not associated with additional years of AFDC participation. Although the present research cannot confirm or deny a causal role for parental welfare use, the intergenerational transmission of financial resources does explain part of the intergenerational association of welfare use.     

The Conversation of Scholarship

Abstract

At its core, scholarship is a long, threaded, multiparticipant conversation. Scholars, students, librarians, and publishers all are engaged. There are side conversations addressing specific fields and larger conversations asking probing questions about the nature of scholarship as a whole. Librarians’ contributions to the broader conversation have not always accounted for our side conversations, among ourselves or with other participants. Our choices in acquisitions, our choices in services, even our choices in library job titles and responsibilities signal and shape the scholarly conversation in ways that are often opaque. It is imperative that we openly acknowledge the influence and impact of our side conversations to ensure our full participation in the conversation of scholarship.     

Family structure and income inequality in families with children, 1976 to 2000

Using 24 years of data from the March supplements to the Current Population Survey and detailed categories of family structure, including cohabiting unions, I assess the contribution of changes in family structure to the dramatic rise in family income inequality. Between 1976 and 2000, family structure shifts explain 41% of the increase in inequality, but the influence of family structure change is not uniform within this period or across racial-ethnic groups. In general, the estimated role of family structure change is inversely related to the magnitude of the changes in inequality. Furthermore, by including cohabitation, I find lower levels of total inequality and a weaker role for demographic shifts in family structure for trends in income inequality.     

A reflected feature space for CART

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.     

The risks and incentives of disciplinary neoliberal feminism: the case of microfinance

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.     

Adolescent Deliberate Self‐Harm: Linkages to Emotion Regulation and Family Emotional Climate

Parents' responses to their children's emotional expressivity have been shown to significantly influence children's subsequent psychosocial functioning. This study hypothesized that adolescents' deliberate self‐harm (DSH) may be an outcome associated with poor emotion regulation as well as an invalidating family environment. The mediational role of specific emotion processes (i.e., poor awareness of emotion, difficulties expressing emotions) between family emotional environment and the frequency of DSH was examined with 131 psychiatrically hospitalized adolescents (M age=14.84 years, SD=1.75 years). Results indicated that adolescents who self‐injured reported that this behavior reduced their negative emotional states. Structural equation modeling provided support for the proposed model that family climate influences frequency of DSH through emotion regulation skills but the model held for girls only. A direct model effect was not supported. Emotion regulation partially mediated the relationship between family climate and DSH, and direct effects were also observed.