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.     

Secondary analysis of dangerousness among death sentenced capital murderers

The theory of incapacitation involves reducing an offender's ability or capacity to commit further crimes. Capital punishment accomplishes this goal. An executed murderer never murders again. However, we do not execute all murderers, only capital murderers. This policy produces several research questions. Do capital murderers present a special risk to society? Are capital murderers more likely to murder or commit other violent crimes again than other murderers or the average citizen? To answer these questions, many states require a prediction of future dangerousness of a newly convicted murderer. To what extent has the judgment of future dangerousness matched actuarial data of subsequent murders and serious crimes? Using a secondary analysis, this investigation attempted to assemble available data of postconviction dangerousness of death sentenced capital murderers to create a more comprehensive actuarial account of subsequent dangerousness and to present the data in a common format used by the Federal Bureau of Investigation and the Bureau of Justice Statistics. Across 14 studies identified with relevant data, there were 13 instances of subsequent murder and 462 serious crime or prison rule violations.     

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.     

Boundary Spaces

While shows like The X-Files and 24 have merged conspiracy theories with popular science (fictions), some video games have been pushing the narrative even further. Electronic Art's Majestic game was released in July 2001 and quickly generated media buzz with its unusual multi-modal gameplay. Mixing phone calls, faxes, instant messaging, real and "fake' websites, and email, the game provides a fascinating case of an attempt at new directions for gaming communities. Through story, mode of playing, and use of technology, Majestic highlights the uncertain status of knowledge, community and self in a digital age; at the same time, it allows examination of alternative ways of understanding games' role and purpose in the larger culture. Drawing on intricate storylines involving government conspiracies, techno-bio warfare, murder and global terror, players were asked to solve mysteries in the hopes of preventing a devastating future of domination. Because the game drew in both actual and Majestic-owned/-designed websites, it constantly pushed those playing the game right to borders where simulation collides with " factuality'. Given the wide variety of "legitimate' conspiracy theory, alien encounters and alternative science web pages, users often could not distinguish when they were leaving the game's pages and venturing into " real' World Wide Web sites. Its further use of AOL's instant messenger system, in which gamers spoke not only to bots but to other players, pushed users to evaluate constantly both the status of those they were talking to and the information being provided. Additionally, the game required players to occupy unfamiliar subject positions, ones where agency was attenuated, and which subsequently generated a multi-layered sense of unease among players. This mix of authentic and staged information in conjunction with technologically mediated roles highlights what are often seen as phenomenon endemic to the Internet itself; that is, the destabilization of categories of knowing, relating, and being.     

The organizational formation of atmospheric science

In this paper, the history of atmospheric science is traced, from the earliest discussions from meteorologists, and the first meetings to describe this new research area. The development of atmospheric science proceeded in three phases with each phase being marked by the attempt to organize resources, and bring into the atmospheric science network, scientists from other fields. I argue here that this construction of a science provides evidence of the social nature of science as well as the importance of organizations to the creation of a science.     

Narrating Significant Experience: Reflective Accounts and the Production of (Self) Knowledge

Notwithstanding the rise of evidence-based practice, other tendencieswithin social work scholarship are also discernible. One ofthese is the study of the everyday, routine accomplishment ofpractice, drawing on microsociological methods and techniques.In this article, I apply techniques drawn from narrative anddiscourse analysis to the study of reflective practice accounts,which hold an important place in social work education. In particular,it is relevant to examine the form that reflective accountstake and the rhetorical and narrative devices deployed withinthem to accomplish a competent professional identity. My argumentis not that such accounts of practice are untruthful, ratherI propose that we would do well to move beyond taking texts(and talk) for granted and treating language as merely the mediumfor expressing inner thoughts and feelings. Social work shouldtake seriously the need to explore its modes of representationand to cultivate a more self-conscious approach to the way professionaland client identities are produced in practice.