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.     

Becoming Custodial Dads: Exploring Parenting Among Low‐Income and Working‐Class African American Fathers

The authors use an ecological framework and grounded theoretical analysis to explore the circumstances in which working‐class and low‐income custodial African American fathers gain custody of their children, their transition from part‐time to full‐time parents, and the role of support networks in enhancing or inhibiting these men's parenting. Twenty‐four men from an impoverished Midwestern urban area participated in the study. The findings suggest that these men, and perhaps others sharing their demographic profiles, generally become parents by default and are often reluctant to take on a full‐time, single parenting role. Adaptation to the role seems to be enhanced by these men's use of extended kin support networks and shared living arrangements. However, low wages, a lack of sufficient assistance from public assistance programs, and informal custody arrangements often inhibit their fathering.     

The Persistent Problem of Colorism: Skin Tone, Status, and Inequality

Colorism is a persistent problem for people of color in the USA. Colorism, or skin color stratification, is a process that privileges light-skinned people of color over dark in areas such as income, education, housing, and the marriage market. This essay describes the experiences of African Americans, Latinos, and Asian Americans with regard to skin color. Research demonstrates that light-skinned people have clear advantages in these areas, even when controlling for other background variables. However, dark-skinned people of color are typically regarded as more ethnically authentic or legitimate than light-skinned people. Colorism is directly related to the larger system of racism in the USA and around the world. The color complex is also exported around the globe, in part through US media images, and helps to sustain the multibillion-dollar skin bleaching and cosmetic surgery industries.     

Zusammenfassungen

Ohne Zusammenfassung German translations by Monika Lütke-Daldrup.     

Will taxpayers ever like taxes?: Responses to the U.S. Tax Reform Act of 1986

Major policy changes like the 1986 Tax Reform Act (TRA) in the United States provide natural experiments to study attitudinal and behavior responses to law. Surprisingly, public evaluations of the TRA became increasingly negative after passage, while general support for the tax system became more positive in response to the changes. To explain this puzzle, we propose a dynamic model of taxpayer attitudes that is consistent with the observed loose linkage between logically-connected concepts. We briefly review the political context, objectives and impacts of the 1986 Tax Reform Act, and present several studies testing the impact of self-interest, prior beliefs, and social discussion on changes in attitudes and behavior.Results suggest that the complexity of taxes and difficulty in knowing objective impacts weakens the role of self-interest in attitudinal changes, thereby strengthening the role of prior beliefs and discussion. Evaluations of tax laws are most responsive to more politically-oriented influences.