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.     

Pierre Bourdieu's Masculine Domination: A Critique*

Les auteurs montrent que la tentative de Pierre Bourdieu de résoudre le problème de la « domination masculine» est limitée par l'application inconséquente de son propre répertoire conceptuel, par l'emploi d'exemples empiriques périmés et par l'utilité douteuse du cas des relations sociales en Kabylie. Un rejet des catégories fondamentales (« homme », « femme ») et le recours à une conception plus nuancée de la domination seraient une approche plus prometteuse. An uneven application of his own conceptual repertoire, outdated empirical materials and the questionable utility of the example of relations in Kabylia limit Bourdieu's attempts to come to grips with “masculine domination.” A more useful approach would move beyond essentializing categories and engage with a more nuanced conception of domination.     

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.     

Using the lessons learned from US and English law to create a regulatory framework for charities in evolving democracies

The evolving democracies of Eastern Europe and the former USSR republics are keenly interested in establishing charities. They have little law on this issue because their former governments did not encourage the development of charities. This article compares US and English regulation of charities and proposes a regulatory framework based on what the authors believe are the best attributes of both. Although the framework is based on the common law system, it can be adapted to the civil law systems of the Eastern European nations and the former USSR republics. The article includes such issues as developing a body of law, tax relief and creating a regulatory agency.Mr Hopkins is a lawyer with Powers, Pyles & Sutter, 1275 Pennsylvania Ave., N.W., Washington, D.C. 20007, and author ofThe Law of Tax-Exempt Organizations (1992a).Ms Moore is also a lawyer, 5908 N. 35th St., Arlington, Virginia 22207.The authors would like to thank Mssrs Kersi Shroff and Stephen F. Clarke, Senior Legal Specialists, American-British Law Division, Library of Congress, and Mr. William H. Morris, an attorney at Steptoe & Johnson, Washington, D.C., for their kind assistance during the researching of this article.     

Undercover Drug-Use Evasion Tactics: Excuses and Neutralization

Although research has examined the corruptive influences of undercover drug operations on agents (Girodo 1991 b; Manning and Reddlinger 1977, 1978), it has not examined the processes by which these influences can be neutralized. In this paper, I address these neutralization processes through a typology of routine and non-routine drug-use evasion tactics. Routine tactics involve excuses based on greed, business constraints, and role obligations (occupational, legal, and interpersonal). Nonroutine tactics involve two components: reverse accusation and simulation. Discussion focuses on excuses where I provide a dramaturgical interpretation that accentuates their deceptive and fraudulent nature, unlike traditional interpretations (e.g., Scott and Lyman 1968) which highlight their role as a reparative technique and aligning action (Margolin 1990). Data were drawn from ethnographic interviews with 35 light undercover narcotics agents located in a moderate-sized midwestern municipality.