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.     

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.     

Fundamentals of Theory and Practice Revisited; The Mutiny and the Bounty: The Place of Milan Ideas Today

The author traces the development of the Milan approach from the beginning, through the split into two teams in 1980, and subsequent developments in theory and application. He identifies possible unrecognised or undeclared influences of Milan in other family therapy approaches.     

Scheduling Updates of Probabilistic Risk Assessments: The Arkansas Nuclear One-Unit 1 Experience

This paper presents the results of a study that identified how often a probabilistic risk assessment (PRA)should be updated to accommodate the changes that take place at nuclear power plants. Based on a 7-year analysis of design and procedural changes at one plant, we consider 5 years to be the maximum interval for updating PRAs. This conclusion is preliminary because it is based on the review of changes that occurred at a single plant, and it addresses only PRAs that involve a Level 1 analysis (i.e., a PRA including calculation of core damage frequency only). Nevertheless, this conclusion indicates that maintaining a useful PRA requires periodic updating efforts. However, the need for this periodic update stems only partly from the number of changes that can be expected to take place at nuclear power plants–changes that individually have only a moderate to minor impact on the PRA, but whose combined impact is substantial and necessitates a PRA update. Additionally, a comparison of two generations of PRAs performed about 5 years apart indicates that PRAs must be periodically updated to reflect the evolution of PRA methods. The most desirable updating interval depends on these two technical considerations as well as the cost of updating the PRA. (Cost considerations, however, were beyond the scope of this study.)     

Racial differences in urban neighboring

Despite mixed expectations generated by existing theories and evidence, this analysis documents clear racial differences in urban neighboring behavior. Using data from a survey of Nashville, Tennessee, residents, we show that blacks interact with their neighbors more often than whites do, and in a greater variety of ways. The only noteworthy similarity between the two groups is the positive impact of neighboring on feelings of community affect. Overall, our results support the view that neighbor relations — like other kinds of informal participation — have helped blacks cope with constrained social opportunities and provided them with access to resources unavailable through formal institutional channels.Revised version of a paper presented at the annual meeting of the American Sociological Association, San Francisco, August 1989.