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.     

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.     

Spatial Variations in Church Burnings: The Social Ecology of Victimized Communities in the South*

Abstract In recent years, church burnings in the South have attracted a great deal of attention. Many commentators have charged that they are a product of strained race relations throughout the South, and particularly of severe racial tensions in Southern rural areas. In this study we evaluate these claims. We begin by mapping the spatial coordinates of recorded church burnings from 1990 to 1997, and find that church arsons indeed are concentrated in the South. Church burnings, however, are a more urban phenomenon than popular media accounts would suggest. Our analysis then explores the influence of contextual factors (population and locale, racial composition and inequality, so‐cioeconomic conditions, local religious ecology, and patterns of reported crime) on church burnings in counties located in the study region. Logistic regression models confirm that church arsons are most likely to occur in small metropolitan statistical areas (MSAs) and non‐MSA counties containing a city of at least 10,000 residents. Church burnings also are especially likely in counties with a higher percentage of black residents, a larger number of churches relative to the rest of the state, and a higher arson rate. We conclude by discussing the implications of these findings for future research and public policy.     

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.     

The European Democratic Deficit,the Market and the Public Space: A Classical Liberal Critique

This article argues that attempts to utilize a Habermasian conception of the public space as a remedy for the democratic deficit deemed to be inherent within the political institutions of the European Union (EU) are unlikely to prove successful. It is argued that the instrumental goal demanded of the public space is contrary to the communicative rationality intrinsic to the Habermasian model. Moreover, the Habermasian conception of the public space as an arena independent of both the market and the state is non-operational because a public space independent of the market is inconceivable. An alternative conceptualization of the public space, focusing on the role of the market as a communicative process, and an alternative remedy for the European democratic deficit, focusing on liberal representative democracy, are proposed.     

Can social systems be autopoietic? Assessing Luhmann's social theory

The theory of autopoiesis, that is systems that are self‐producing or self‐constructing, was originally developed to explain the particular nature of living as opposed to non‐living entities. It was subsequently enlarged to encompass cognition and language leading to what is known as second‐order cybernetics. However, as with earlier biological theories, many authors have tried to extend the domain of the theory to encompass social systems, the most notable being Luhmann. The purpose of this article is to consider critically the extent to which the theory of autopoiesis, as originally defined, can be applied to social systems ‐ that is, whether social systems are autopoietic. And, if it cannot, whether some weaker version might be appropriate.     

The Existential Side of Kohut's Tragic Man

This article explores the way in which Kohut's concept of Tragic Man functions as a response to criticisms of self psychology as proffering a partial, utopian, strife-denying theory of human development. After citing several representative critiques in this respect, I review the concept of Tragic Man as defined by Kohut, and then seek to deepen the clinical usefulness of this concept through a discussion of affects, empathy, and free association. A clinical vignette concludes the paper, through which some of these ideas find illustration.     

Adolescents' and Mothers' Understanding of Children's Rights in the Home

Adolescents' and mothers' understanding of children's self‐determination and nurturance rights was examined in the context of the home. In individual interviews, 141 sixth, eighth, and tenth graders and their mothers responded to hypothetical vignettes in which a child story character wished to exercise a right that conflicted with parental practices. For each vignette, participants were asked to judge whether the story character should have the right in question and to provide a justification for their decision. Generally, eighth and tenth graders were more likely than their mothers to endorse requests for self‐determination and less likely than their mothers to support requests for nurturance. Mothers of tenth graders were more likely to support requests for self‐determination and less likely to favor adolescents' request for nurturance in the home than were mothers of sixth and eighth graders. In terms of reasoning, adolescents and mothers were more likely to consider the individuals' rights when discussing self‐determination situations, whereas nurturance situations elicited responses pertaining to participants' understanding of familial roles and relationships. Furthermore, mothers' reasoning about childrenà s rights reflected sensitivity to the developmental level of their children. The findings are discussed in terms of previous research on the development of children's understanding of rights and adolescent autonomy.