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.     

‘I'm a good mother really!’ gendered parenting roles and responses to the disclosure of incest

The disclosure of incestuous abuse of a child constitutes such a departure from normative expectations of mothering that it necessitates a complete reappraisal and reconstruction of the mother's identity. This article draws on interview material with women in this situation in order to demonstrate how very traditional gendered parenting models were employed in repairing damaged identities. The ways in which such reliance on the protective and selfless aspects of mothering could contribute to the failure to recognise the abuse of their child are also discussed. In conclusion, motherhood as a source of power for women within the family is critically examined. Copyright © 2002 John Wiley & Sons, Ltd.     

The Dialectic of Technology: Commentary on Warner and England1

Abstract Warner and England (1995) make a welcome argument for a technological science perspective for sociology based on a theory of humans as technological agents and an epistemology that includes ethical values. As with any sociological perspective, however, Warner and England's comments help to focus on and understand some aspects of social life and not others. This commentary provides a complementary focus by emphasizing the dialectical relationship between human agency and technological agency. Furthermore, I argue that a dialectical view is necessary for grounding Warner and England's theoretical argument and for acting on their ethical argument. Implications of a dialectical perspective for the meaning and politics of technology are explored. The paper concludes with a discussion of the suitability of “science” as a metaphor for sociology.     

Assessing accuracy of a continuous screening test in the presence of verification bias

Summary.  In studies to assess the accuracy of a screening test, often definitive disease assessment is too invasive or expensive to be ascertained on all the study subjects. Although it may be more ethical or cost effective to ascertain the true disease status with a higher rate in study subjects where the screening test or additional information is suggestive of disease, estimates of accuracy can be biased in a study with such a design. This bias is known as verification bias. Verification bias correction methods that accommodate screening tests with binary or ordinal responses have been developed; however, no verification bias correction methods exist for tests with continuous results. We propose and compare imputation and reweighting bias-corrected estimators of true and false positive rates, receiver operating characteristic curves and area under the receiver operating characteristic curve for continuous tests. Distribution theory and simulation studies are used to compare the proposed estimators with respect to bias, relative efficiency and robustness to model misspecification. The bias correction estimators proposed are applied to data from a study of screening tests for neonatal hearing loss.