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.     

Heteroscedastic Global Tests that the Regression Parameters for Two or More Independent Groups are Identical

Simulation results are reported on methods that allow both within group and between group heteroscedasticity when testing the hypothesis that independent groups have identical regression parameters. The methods are based on a combination of extant techniques, but their finite-sample properties have not been studied. Included are results on the impact of removing all leverage points or just bad leverage points. The method used to identify leverage points can be important and can improve control over the Type I error probability. Results are illustrated using data from the Well Elderly II study.     

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.     

“WHAT DOES SHE SEE IN HIM?”: THE EFFECT OF SHARING ON THE CHOICE OF SPOUSE

All husbands and wives share in the spoils of marriage. Sharing makes each partner a residual claimant and encourages spouses to provide marital inputs. However, because each spouse is only a partial residual claimant, each may be inclined to provide a "suboptimal" level of marital inputs. The choice of spouse influences the level of distortion, and under some circumstances the efficient mating is between individuals of equal value     

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.     

How Welfare Policies Affect Adolescents' School Outcomes: A Synthesis of Evidence From Experimental Studies

Using data from 8 random assignment studies and employing meta‐analytic techniques, this article provides systematic evidence that welfare and work policies targeted at low‐income parents have small adverse effects on some school outcomes among adolescents ages 12 to 18 years at follow‐up. These adverse effects were observed mostly for school performance outcomes and occurred in programs that required mothers to work or participate in employment‐related activities and those that encouraged mothers to work voluntarily. The most pronounced negative effects on school outcomes occurred for the group of adolescents who had a younger sibling, possibly because of the increased home and sibling care responsibilities they assumed as their mothers increased their employment.     

The Market Provision of Management Services, Information Asymmetries and Service Quality—Some Market Solutions: an Empirical Example

This article examines the problems of information asymmetry associated with the market provision of managerial services. Such problems are heightened by those characteristics which differentiate services from goods. Two unique, and central, characteristics of services, are intangibility and perishability. These create special problems for the market provision of services. In particular they make for difficulties in assessing quality; whereas the producer may know product quality, the buyer often does not. The asymmetry between sellers and buyers is of two types: Adverse selection and moral hazard. Adverse selection occurs when the buyer cannot observe the relevant characteristics of the seller or the conditions under which they work. The problem of moral hazard is the buyer's inability to observe the action taken by the sellers. If these difficulties are not overcome, the market could collapse as companies withdraw and internalize service provision. However, each market has a number of in-built mechanisms which remedy the harmful effects associated with information-related problems. The institutional arrangements which predominate in particular markets are dependent upon the trust-producing mechanisms within those markets. Consequently, market responses to information asymmetries are far from uniform. The argument is illustrated using the example of the executive recruitment industry. In this respect the paper is a highly focused study of those mechanisms which overcome information asymmetries in one service market.