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 Ethnicity of Efficacy: Vietnamese Goddess Worship and the Encoding of Popular Histories

This article examines the reasons for the popularity of spirits of different ethnic backgrounds in the southern Vietnamese plain. The official approach is to induct the cults to these spirits into defence of the nation and its culture, a construct which privileges ethnic Kinh views of history. However, the 'Lady of the Realm', a goddess in the Mekong delta, illustrates the more complex ethnicity of this symbolism. Popular views denying her Khmer origins naturalise the Vietnamese colonisation of Cambodian lands. A preferred lineage in some quarters is to regard her as Cham, a view which disputes a more popular view of her as a Chinese belief, particularly influential in circles where ethnic Chinese business practices have become the norm. This play of interpretations indicates that conventional motifs of cultural resistance or survival are inadequate to understanding religious symbols which speak to the more complex identity of this region of the country.     

Time, Self, and the Curiously Abstract Concept of Agency*

The term "agency" is quite slippery and is used differently depending on the epistemological roots and goals of scholars who employ it. Distressingly, the sociological literature on the concept rarely addresses relevant social psychological research. We take a social behaviorist approach to agency by suggesting that individual temporal orientations are underutilized in conceptualizing this core sociological concept. Different temporal foci—the actor's engaged response to situational circumstances—implicate different forms of agency. This article offers a theoretical model involving four analytical types of agency ("existential,""identity,""pragmatic," and "life course") that are often conflated across treatments of the topic. Each mode of agency overlaps with established social psychological literatures, most notably about the self, enabling scholars to anchor overly abstract treatments of agency within established research literatures.     

Seymour Martin Lipset: The social uses of anomaly

Let me preface my remarks by saying that we are here to honor a living, breathing colleague. My great concern, and in this I am sure that I speak for my colleagues as well, is that any imputation of a postmortem be avoided. Indeed, I would like to believe that Marty will review these various contributions and make his own assessments-critical or approvingly. The fact that he is not present in this conference hall should not deter us from speaking frankly and forthrightly. Marty merits nothing less. What binds us all is the sure knowledge that the work of Lipset speaks to us in personal as well as professional ways. That he has touched so many of us in both the private and public realms is itself a testimonial of the magnitude of his contribution to the field of political sociology. So it is in that spirit of a collégial dialogue that I offer these remarks. Let us hope that a year from now a session of one person can be held, at which S. M. Lipset will provide rebuttals and responses to those of us herein gathered. His most recent work in the field is Behemoth: Main Currents in the History and Theory of Political Sociology. The two major sources for traching the written works of Seymour Lipset are contained in Reexamining Democracy: Essays in Honor of Seymour Martin Lipset, edited by Gary Marx and Martin Diamond. Newberry Park, California: Sage Publishers. 1992, especially pp. 332–355. For work done by Lipset after 1991; as embodied in his later work, see Lipset's essay on “Steady Work: An Academic Memoir,” Annual Review of Socialogy: Greenwich, CT: JAI Press, 1996, pp. 1–27. My reference to works mentioned in the narrative can be found in either of these bibliography sources.     

三螺旋创新模式的理论探讨

基于非线性网状创新模型提出的“三螺旋场”和“三螺旋循环”概念进一步推进了三螺旋创新模式的理论研究。三螺旋场概念旨在解释在大学、产业和政府三股螺旋之间存在的相对独立和彼此作用的本质，说明三螺旋的生成原理、静态表现和动态演化特征。三螺旋的生成原理在于创新过程的非线性本质和多主体特征，静态表现为“内核外场模型”，而动态演化过程则在于纵向进化和横向循环。发生在三股螺旋之间的三螺旋循环揭示了在大学、产业和政府之间以人员、信息和产品流动为特征的相互作用和运行机制。     

Social impact Analysis in Australia: Policy Issues for the 1980s

Over the last ten years in Australia the social component of Australian Environmental Impact statements has gradually increased in size as the importance of Social Impact Analysis has been recognised. This commendable trend has not been without mishap, however, and there remain many areas largely ignored in Social Impact Assessment. This paper seeks to identify these areas, identifying value questions that need to be addressed in the preparation of the social impact component.     

Children's gender- and age-based categorization in similarity and induction tasks

The present studies examined children's and adults' preferences for gender- or age-based categorization using similarity and inductive inference tasks. Four-year-olds, 6-year-olds, and adults looked at pictures of people and decided which of two was more like a target (similarity condition) or which shared a novel age- or gender-related property with the target (inference condition). Age or gender-based matches were possible. The results are consistent with previous findings that gender-based classification decreases with age. However, they also demonstrate that children use gender more for judging similarity than for making inferences about novel properties. Distinct patterns emerge from the two tasks: 6-year-olds and adults in both conditions categorize more by age than gender; 4-year-olds categorize by gender more than age in the similarity task, but by age more in the induction task. Only adults differentiated by property in the inference condition. These findings suggest that the salience of gender categories cannot entirely be attributed to their inductive potential. Gender has a salience beyond what would be predicted by its power for directing novel generalizations.     

Household debt and financial assets: evidence from Germany, Great Britain and the USA

Summary.  We explore the determinants of debt, financial assets and net worth at the household level by using survey data for Germany, Great Britain and the USA. To identify which households are potentially vulnerable to adverse changes in the economic environment, we also explore the determinants of a range of measures of financial pressure: the probability that a household has negative net worth; the debt-to-income ratio; mortgage income gearing; the saving-to-income ratio. Our empirical findings suggest that the poorest and the youngest households are the most vulnerable to adverse changes in their financial circumstances.