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.     

自杀和生命的意义——来自脑科学研究的解读

生命本身是一个随机事件，并不具有高尚的意义。进化的结果使人类可通过工作、家庭和人际关系等给予自己的生命以意义感。当我们的生活方式使脑内奖赏系统获得刺激，就会带来生命具有意义的感受，这种感受给人带来更好的生存机会。生存的欲望是一切生物体最具特征的属性，一些精神疾病患者缺乏这种欲望。自杀主要发生于精神疾病患者，它并非是基于自由意志的行为。抗精神病治疗和适当的社会交往可以预防自杀。由于不同个体有着不同的大脑，人们的生活方式就应该去适应各自大脑的特征。只要人们的生活方式不对他人造成过多的伤害，政府就应该允许和保护人们自由地按照各自的方式生活。     

Book Review: Restless Nation: Starting Over in America. By James M. Jasper. Chicago: University of Chicago Press, 2000. 296 pages,hardcover, ISBN: 0-226-39478-6

Qualitative Sociology -     

Cohabitation and commitment: partnership plans of young men and women

Popular commentators on marriage and the family often interpret the increase in heterosexual couples living together without marrying as reduced willingness to create and honour life‐long partnerships. Survey and in‐depth interviews with samples of 20–29 year olds living in an urban area of Scotland finds little support for the postulated link between growing cohabitation and a weakened sense of commitment to long‐term arrangements. Most of the cohabiting couples strongly stressed their ‘commitment’. Socially acceptable vocabularies of motive undoubtedly influenced answers but interviews helped to explore deeper meanings. Many respondents’ views were consistent with previous research predictions of a weakening sense of any added value of marriage. At the same time, some respondents continued to stress the social significance of the distinction between marriage and cohabitation, consistent with research interpreting cohabitation as a ‘try and see’ strategy part‐way to the perceived full commitment of marriage. The notion that ‘marriage is better for children’ continued to have support among respondents. While, on average, cohabiting couples had lower incomes and poorer employment situations than married couples, only very extreme adverse circumstances were presented as making marriage ‘too risky’. Pregnancy‐provoked cohabitation was not always in this category. Cohabitation was maintained because marriage would ‘make no difference’ or because they ‘had not yet got round to’ marriage. Most respondents were more wary of attempting to schedule or plan in their personal life than in other domains and cohabitees’ attitudes to partnership, including their generally ‘committed’ approach, do not explain the known greater vulnerability of this group to dissolution.     

Measures of Multigroup Segregation

In this paper we derive and evaluate measures of multigroup segregation. After describing four ways to conceptualize the measurement of multigroup segregation—as the disproportionality in group (e.g., race) proportions across organizational units (e.g., schools or census tracts), as the strength of association between nominal variables indexing group and organizational unit membership, as the ratio of between–unit diversity to total diversity, and as the weighted average of two–group segregation indices—we derive six multigroup segregation indices: a dissimilarity index (D), a Gini index (G), an information theory index (H), a squared coefficient of variation index (C), a relative diversity index (R), and a normalized exposure index (P). We evaluate these six indices against a set of seven desirable properties of segregation indices. We conclude that the information theory index H is the most conceptually and mathematically satisfactory index, since it alone obeys the principle of transfers in the multigroup case. Moreover, H is the only multigroup index that can be decomposed into a sum of between– and within–group components.     

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.     

Fire and restoration of the largest urban forest of the world in Rio de Janeiro City,Brazil

National Park of Tijuca in Rio de Janeiro (Brazil) is about 3,300 ha and considered the largest urban forest in the world. Its floristic composition is typical of Atlantic Rain Forest. The reserve is being altered because of fire occurrences and urban expansion. This study identified locations and causes of forest fires, and makes management recommendations to restore damaged areas. From 1991 to 2000, forest firefighters recorded an average of 75-fire occurrences/year. Identified causes included hot air balloons (24%), intentional (24%), rubbish burning (21%) and religious practices (17%). Primary fuels included invasive grasses and ferns. Although hot air balloons destroyed larger areas of forest in each occurrence, a greater number of fires started in the invasive vegetation along roads that bisect the forest. In response to recurrent forests, invasive vegetation has spread gradually into the forest increasing forest degradation. To decrease fire damage, sites with high fire frequencies and density of invasive vegetation were planted with less flammable species. Results indicate that fire frequency decreased and density of invasive vegetation declined. This approach appears to prevent fire incidence, reduce the need for fire fighting, and preserve existing biodiversity.     

Führung durch Selbstführung

This paper outlines the conceptual bases, strategies, and psychological attributes of leadership by self-leadership. In addition, relations to other theories of leadership are drawn. Dimensions and correlates of self-leadership competence are described and discussed. Various approaches for developing self-leadership competence are discussed as well.     

Bayesian modelling of catch in a north-west Atlantic fishery

Summary. We model daily catches of fishing boats in the Grand Bank fishing grounds. We use data on catches per species for a number of vessels collected by the European Union in the context of the Northwest Atlantic Fisheries Organization. Many variables can be thought to influence the amount caught: a number of ship characteristics (such as the size of the ship, the fishing technique used and the mesh size of the nets) are obvious candidates, but one can also consider the season or the actual location of the catch. Our database leads to 28 possible regressors (arising from six continuous variables and four categorical variables, whose 22 levels are treated separately), resulting in a set of 177 million possible linear regression models for the log-catch. Zero observations are modelled separately through a probit model. Inference is based on Bayesian model averaging, using a Markov chain Monte Carlo approach. Particular attention is paid to the prediction of catches for single and aggregated ships.