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 minimum wage and poverty among full-time workers

V. Conclusions The empirical evidence is strong that minimum wages have had little or no effect on poverty in the U.S. Indeed, the evidence is stronger that minimum wages occasionally increase poverty. It also suggests that the minimum wage does not even lower poverty for the one group that, almost by definition, one would expect to be helped: full-time, year-round workers. While the empirical results suggest minimum wages do not achieve what is ostensibly their primary goal — relieving poverty among the working poor — minimum wages do seem to impose a real cost on society in terms of lost income and output. The empirical evidence on work hours suggests that a $1 increase in the minimum wage, far from being almost costless, could conceivably impose income losses to American workers in the $12-15 billion range per year — an amount equal to the “income deficit” of millions of persons counted as poor by the U.S. Bureau of the Census.     

Career Self‐Efficacy and Perceptions of Parent Support in Adolescent Career Development

The authors examined the relative contributions of both proximal and distal supports to the career interests and vocational self‐efficacy in a multiethnic sample (N = 139) of middle school adolescents. Consistent with Social Cognitive Career Theory, it was found that (a) vocational self‐efficacy and career planning/exploration efficacy consistently predicted young adolescents' career interests across Holland (J. L. Holland, D. R. Whitney, N. S. Cole, & J. M. Richards, 1969) themes; (b) gender and career gender‐typing predicted interests in Realistic, Investigative, and Social careers; and (c) perceived parent support accounted for 29% to 43% of the total unique variance in vocational self‐efficacy for all Holland theme careers.     

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.     

Effects of Marriage and Children on Financial Risk Tolerance: A Synthesis of Family Development and Prospect Theory

Family development and prospect theory were used as a framework to predict variability in individuals' subjective financial risk tolerance within distinct family structures. Gender, age, and income were expected to interact with the main effects of family structure (marital status and children). Theory-generated hypotheses were examined in Study 1 (data from university housing respondents, n = 76) and Study 2 (the 1998 Survey of Consumer Finances, n = 4,305). One family structure main effect (child presence) was significant for investment risk tolerance in both studies. Family structure interactions (marital status × age and child × income) were significant for employment risk (Study 1), and child × age was significant for investment risk in Study 2.     

Secondary analysis of dangerousness among death sentenced capital murderers

The theory of incapacitation involves reducing an offender's ability or capacity to commit further crimes. Capital punishment accomplishes this goal. An executed murderer never murders again. However, we do not execute all murderers, only capital murderers. This policy produces several research questions. Do capital murderers present a special risk to society? Are capital murderers more likely to murder or commit other violent crimes again than other murderers or the average citizen? To answer these questions, many states require a prediction of future dangerousness of a newly convicted murderer. To what extent has the judgment of future dangerousness matched actuarial data of subsequent murders and serious crimes? Using a secondary analysis, this investigation attempted to assemble available data of postconviction dangerousness of death sentenced capital murderers to create a more comprehensive actuarial account of subsequent dangerousness and to present the data in a common format used by the Federal Bureau of Investigation and the Bureau of Justice Statistics. Across 14 studies identified with relevant data, there were 13 instances of subsequent murder and 462 serious crime or prison rule violations.