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.     

Lives in limbo: Temporary Protected Status and immigrant identities

The United States formulates much of its immigration and refugee policy to match economic and political circumstances. We interpret these policy shifts as a set of graduated positions on immigration and refugee flows that attempts to discipline the lives of newcomers and, in so doing, shapes immigrant identities. In this article, we analyse the interplay between the US government and Salvadoran asylum applicants negotiating procedures that grant only temporary relief from deportation via the policy of Temporary Protected Status (TPS). We find that each policy shift results in the strategic renegotiation of asylum applicants’ identities so as to achieve the best opportunity for a successful outcome. Based on Foucault’s ideas of governmentality and Ong’s concept of flexible citizenship, we argue that what appears more superficially as a patchwork strategy of immigration laws and asylum practices may be theorized more deeply as a set of flexible responses by the state that turn on identity construction at different scales, and that aim to mediate transnational relations.     

LOG-PERIODOGRAM ESTIMATION OF LONG MEMORY VOLATILITY DEPENDENCIES WITH CONDITIONALLY HEAVY TAILED RETURNS

Many recent papers have used semiparametric methods, especially the log-periodogram regression, to detect and estimate long memory in the volatility of asset returns. In these papers, the volatility is proxied by measures such as squared, log-squared, and absolute returns. While the evidence for the existence of long memory is strong using any of these measures, the actual long memory parameter estimates can be sensitive to which measure is used. In Monte-Carlo simulations, I find that if the data is conditionally leptokurtic, the log-periodogram regression estimator using squared returns has a large downward bias, which is avoided by using other volatility measures. In United States stock return data, I find that squared returns give much lower estimates of the long memory parameter than the alternative volatility measures, which is consistent with the simulation results. I conclude that researchers should avoid using the squared returns in the semiparametric estimation of long memory volatility dependencies.     

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.     

CALGARY FAMILY INTERVENTION MODEL: ONE WAY TO THINK ABOUT CHANGE

This article defines and describes the Calgary Family Intervention Model (CFIM). CFIM is an organizing framework conceptualizing the intersect between a particular domain (i.e., cognitive, affective, or behavioral) of family functioning and a specific intervention offered by a health professional. Examples and discussion of interventions such as storying the illness experience, encouraging respite, and asking interventive questions are presented. CFIM is one way that health professionals can conceptualize about change.     

Was there a “golden past” for the introductory sociology textbook? A citation analysis of leading journals

Much debate over the years has centered around whether there was ever a “golden past” for the introductory sociology textbook, when high quality books influenced the development of scholarship and thinking. Some empirical evidence is added to this debate through an analysis of the citations to introductory sociology textbooks in all the articles and research notes appearing in theAmerican Journal of Sociology, theAmerican Sociological Review, andSocial Forces from 1960 to 1969 and from 1984 to 1993. The data show that, although seldom cited in recent journals, introductory sociology textbooks were often cited in the earlier period. The article concludes with some thoughts about why introductory sociology textbooks have had a declining influence on scholarship.