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 price of a loaf of bread: some conceptions of family support*

This paper reports on a case study of one local authority, and illustrates the different definitions of the term ‘family support’ employed by the different agencies within the authority. It provides a framework to analyse the contribution of the agencies according to the assumptions they make about methods and efficacy of intervention and access to and termination of intervention. It contrasts the findings from this framework with a needs based model of ‘family support’. Social work and health services tend to operate within a narrow, historically determined range, focusing most heavily on emotional support and behavioural change; whereas users and some of the other agencies are more likely to raise matters such as income maintenance, child care, leisure and education. The findings of the case study are discussed in relation to resources for families, key issues for the implementation of family support identified during the introduction of the Children Act, 1989, and the relevance of Social Services Inspectorate inspections to these issues. Copyright © 2002 John Wiley & Sons, Ltd.     

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.     

The Relationship Between Sense of Coherence and Career Thoughts

The authors examined the impact of sense of coherence on the career thought processes of a sample of college students. A. Antonovsky (1987) defined sense of coherence as the global orientation that the world is comprehensible, manageable, and meaningful. Study participants completed the Sense of Coherence Scale (A. Antonovsky, 1987) and the Career Thoughts Inventory (CTI; J. P. Sampson, G. W. Peterson, J. G. Lenz, R. C. Reardon, & D. E. Saunders, 1996). Multivariate tests indicated a medium relationship between sense of coherence and CTI Total and subscale scores; sense of coherence accounted for 14% of the variance. Univariate tests also indicated a medium relationship between sense of coherence and each subscale.     

Binding the Generations: Household Formation Patterns among Vietnamese Refugees1

Much of the analysis of refugee and immigrant adaptation has stressed the interaction of prior experience with the requirements of life in a new country. For refugees, that interaction has often been jarring because of the after‐effects of their flight and their relative inability to prepare for a new life in a new country. Yet refugees have often done rather well in economic terms in that new country. The reasons for that relative success have been phrased in cultural terms (e.g., the predisposition toward education) and in general socioeconomic terms (e.g., refugees as educated and skilled). This article examines a set of factors that lie between these customary cultural and socioeconomic categories. Specifically, the paper examines key features of household formation among Vietnamese refugees. An examination of historical data from southern Vietnam indicates patterns in household formation that appear durable over time yet are not shared across the breadth of Vietnam and cannot thus be viewed as “cultural” in the usual sense. A comparison of the historical data with recent national survey data on refugees in the United States indicates that these patterns continue among Vietnamese refugees and are ‐ as compared to other refugees ‐ distinctive to them. These patterns of household formation provide Vietnamese refugees with important options in adaptation to a new country.     

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.