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.     

Comparing the Prevalence and Organizational Distinctiveness of Faith-Based and Secular Development NGOs in Canada

Faith-based development organizations (FBOs) have been argued to deliver more cost-efficient development projects than their secular counterparts through exclusive access to faith networks, which provide predictable decentralized funding, the recruitment of volunteers, low employee salaries, and less overhead and indirect costs. To date, however, comparative analyses of religious and secular organizations have relied on a case-by-case approach, limiting the generalizability of findings. This study addresses this methodological gap by analyzing Registered Charity Information Return filings and organizational websites of 844 Canadian development NGOs to determine the proportion of FBOs and their organizational distinctiveness. The results show that FBOs comprise 40% of the Canadian NGO sector in terms of the number of organizations and their expenditures in developing countries, and are significantly less reliant on federal funding (p?<?.1), pay employees lower salaries (p?<?.01), but do not exhibit a significant difference in their expenditures on overhead and indirect costs. Thus, Canadian FBOs participation in faith networks shapes their organizational modus operandi but does not result in a low overhead alternative to secular NGOs.

     

Volume 30

Theory and Society -     

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.     

Cognitive-behavioral-expressive interventions with aggressive and resistant youths.

Research into the nature of aggressive behavior in youths has demonstrated that these youths are often the victims of abuse, exhibit aggressive behavior in early childhood, and remain aggressive into young adulthood. The treatment approach described in this article is a modification of Monahan's [1981] model of the prediction of violent behavior and the anger-management approach of Novaco [1985], and integrates the developmental models of Piaget [1963] and Erikson [1959]. The program is a combination of cognitive, behavioral, and expressive therapies and is targeted to the reduction of dysfunctional cognitive, affective, behavioral, and problem-solving patterns of aggressive youths. As referrals of such aggressive clients are often involuntary, interventions with unwilling and resistant clients are also presented.