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.     

Development of Parenting Skills in Individuals with an Intellectual Impairment: an epigenetic explanation

Current changes in legislation in the United States support the rights of individuals with an intellectual impairment to marry and have children. Current societal views, however, are heavily influenced by our history of viewing these individuals as inadequate parents. This historical view is based upon the assumption that those with intellectual impairments are genetically inferior. Changing views of development, however, suggest that the issue of how individuals with intellectual impairments develop is somewhat more complex. The epigenetic model is one that proposes that development is the result of the complex transaction between the individual and the environment. This paper applies this model to persons with an intellectual impairment to better understand the parenting skills they display. It is argued that by intervening and changing developmental pathways, the development of parenting skills of those with intellectual impairments can be facilitated.     

GENDER AND RACE PATTERNS IN THE PATHWAYS FROM SPORTS PARTICIPATION TO SELF-ESTEEM

Athletics is the most prominent extracurricular activity in U.S. secondary schools in terms of student participation and school budgets. The latter is often justified on the grounds that healthy bodies produce healthy minds, that school sports boost school spirit, and that participation in school-based sports increases students' self-esteem. In this article we examine the interrelationships among participation in a school-based sport and the benefits assumed to be associated with it. Specifically, we test a model that postulates that school spirit, operationalized as attachment to school, and healthy bodies, operationalized as a sense of physical well-being, mediate the relationship between school sports and self-esteem. Data from the National Longitudinal Study of Adolescent Health on Caucasian and African American girls and boys were employed to test the model. School attachment and physical well-being absorbed the statistical effect of participating in a sport for all four gender-by-race groups. Among Caucasian girls a negative residual effect of sports participation was observed, which suggests that sports participation encapsulates multiple effects with contradictory influences. For African American girls school attachment by itself was not a significant mediator of the effect of sports participation on self-esteem. For all groups a sense of physical well-being was the more powerful mediator.     

Peer Crowd Affiliation and Internalizing Distress in Childhood and Adolescence: A Longitudinal Follow‐Back Study

Concurrent and longitudinal associations between peer crowd affiliation and internalized distress were examined in a sample of 246 youth (148 girls, 98 boys). Children completed measures of depression, social anxiety, loneliness, and self‐esteem when they were in grades 4 to 6 (Time 1), and again 6 years later during adolescence (grades 10 – 12; Time 2). At Time 2, adolescents also reported their self‐concept and their identification with reputation‐based peer crowds, including Populars, Jocks, Brains, Burnouts, Non‐Conformists, and None/Average crowds. Results indicated that adolescents' report of peer crowd affiliation was concurrently associated with self‐concept and levels of internalizing distress. Follow‐back analyses of internalizing trajectories revealed that Populars/Jocks had experienced significant declines in internalizing distress across development, whereas Brains exhibited some increases in internalizing distress between childhood and adolescence.     

THE EAST END, THE WEST END, AND KING'S CROSS: ON CLUSTERING IN THE FOUR-PLAYER HOTELLING GAME

We study experimentally a standard four-player Hotelling location game with a uniform density of consumers and inelastic demand. The pure strategy Nash equilibrium configuration consists of two firms located at one quarter of the "linear city," and the other two at three quarters. We do not observe convergence to such an equilibrium. In our experimental data we find three clusters. Besides the direct proximity of the two equilibrium locations, this concerns the focal midpoint. Moreover, we observe that whereas this midpoint appears to become more notable over time, other focal points fade away. We explain how these observations are related to best-response dynamics, and to the fact that the players rely on best-responses in particular when they are close to the equilibrium configuration.     

Media Publicity and the Voluntary Sector: The Case of Nonprofit Organizations in New York City

Media publicity is an important resource for contemporary voluntary associations, but very little is actually known about the resources and organizational characteristics that are most important for getting media attention. To address this question, we collected and analyzed data on the organizational attributes and news publicity of 739 nonprofit organizations in New York City. We find that an organization's income, paid staff, membership size, and library resources are significantly related to getting media publicity, whereas the number of chapter affiliations is inversely related to publicity. Association type is also a significant factor that influences an organization's ability to get publicity. We discuss the implications that these findings have for current debates about advocacy and civic engagement in the nonprofit sector.     

Rehabilitating the Criminality of Immigrants Under Section 19 of the Canadian Immigration Act1

Immigration has historically been associated with moral entrepreneurship and xenophobia. In periods of high unemployment and global dislocation, immigrants easily become the targets of political commentators who complain of their criminality, morals, demand on public services, and competition for scarce employment. In this exercise, looking at the recidivism of immigrants who come to Canada with a previous, foreign criminal history, quite a different picture emerges. Among this random sample (N=204), 97.5 percent of immigrants granted a rehabilitation waiver under the provisions of the Canadian Immigration Act were not re‐arrested in Canada within a period of about 3.5 years after their landing was approved by the Minister. Of those who were arrested, most of the delinquency was manageable and, in fact, resulted in either an acquittal, diversion or lower‐range sanctions. This is not the kind of imagery complained of by the tabloids or critics in the body politic. It behooves us, then, to exercise care in discussing crime and immigration, as it is a subject easily prone to the creation of “moral panics” and resulting repressive legislation against persons of color.