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.     

Bayesian analysis of mixture modelling using the multivariate t distribution

A finite mixture model using the multivariate t distribution has been shown as a robust extension of normal mixtures. In this paper, we present a Bayesian approach for inference about parameters of t-mixture models. The specifications of prior distributions are weakly informative to avoid causing nonintegrable posterior distributions. We present two efficient EM-type algorithms for computing the joint posterior mode with the observed data and an incomplete future vector as the sample. Markov chain Monte Carlo sampling schemes are also developed to obtain the target posterior distribution of parameters. The advantages of Bayesian approach over the maximum likelihood method are demonstrated via a set of real data.     

Maintaining the connection: Parenting as a noncustodial father

The purpose of this study was to identify relevant factors associated with the noncustodial father's frequency of contact with his child following divorce. The findings of the research revealed that a combination of demographic, personal characteristics, and psychosocial factors are related to the father's frequency of contact with the child.     

The 10% Flat Tax: Tithing and the Definition of Income

Developing a fair and widely accepted income definition presents one of the greatest challenges to tax reform. To arrive at a definition separate from the federal tax code, we surveyed 1200 Latter‐day Saints about their practice of tithing. Tithing is similar to a flat tax with no deductions, where individuals voluntarily contribute 10% of self‐defined income to the church. The results of our survey indicate that most respondents operate on a cash realization basis, which excludes savings and does not allow any deductions. Respondents' income concepts generally do not coincide with current tax laws or economists' views of comprehensive income.     

ATSDR Science Panel on the Bioavailability of Mercury in Soils: Lessons Learned

On the basis of discussion and analysis during and following an ATSDR science panel on the bioavailability of mercury in soils, it is apparent that the default assumption of 100% relative bioavailability for mercury-contaminated soils is excessively conservative. However, current knowledge does not allow the development of default assumptions or guidelines for determining relative bioavailability of mercury in soils. Until such default assumptions or guidelines can be developed, site-specific assays of bioavailability, preferably using either animal bioassays or validated in vitro techniques, may provide the best approach for estimating soil-mercury bioavailability.     

What Drives Citizen Participation in Political Gatherings in Modern South Africa? A Quantitative Analysis of Self-Reported Behaviour

Social Indicators Research - Community and public gatherings are an important component of political participation in sub-Saharan Africa. Formal and informal community meetings and rallies are...     

The reification of celebrity: global newspaper coverage of the death of David Bowie*

This paper examines global English-language newspaper coverage of the death of David Bowie. Drawing upon the concept of reification, it is argued that the notion of celebrity is discursively (re)produced and configured through a ‘public face’ that is defined, maintained and shaped via media reports and public responses that aim to know and reflect upon celebrity. The findings highlight how Bowie’s reification was supported by discourses that represented him as an observable, reified form. Here, Bowie’s ‘reality’, that is, his authentic/veridical self, was obscured behind a façade of mediation, interpretation and representation that debated and decided his ‘authenticity’ as a cultural icon. Such debates, however, were engagements with a reified image, enveloped in continual (re)interpretation. As a result, Bowie’s reification was grounded in a polysemous process that allowed numerous versions of ‘himself’ to be aesthetically reimagined, reinvented and repeated.