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.     

Parent‐Adolescent Communication About Sex: Retrospective Reports by Latino College Students

Latina female (n= 97) and Latino male (n= 69) college students (M age = 21.4 years) completed self‐report surveys regarding family of origin experiences, including sexual communication with parents while growing up. Latino parents of this comparatively highly educated sample tended to use direct rather than indirect strategies for communicating about sexuality with their children. Young women reported higher levels of sexual communication with mothers while growing up than did young men, and respondents reported less communication with fathers than mothers. Among young women, sexual communication with mother was positively associated with non‐Mexican origin and negatively associated with having older brothers living at home. In contrast, maternal education was positively associated with mother‐son communication about sex. Paternal education and the absence of older brothers positively predicted communication with both sons and daughters. The analyses provide novel information regarding sexual communication in Latino families and suggest directions for future research.     

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.     

Farmers,the Practice of Farming and the Future of Agroforestry: An Application of Bourdieu's Concepts of Field and Habitus

Abstract Agroforestry, the practice of raising crops and trees together in ways that are mutually beneficial, provides farmers with an alternative to more conventional farming practices. In this paper, we apply Bourdieu's concepts of “field” and “habitus” in an attempt to better understand the practice of farming and the role that agroforestry may have in farming systems. Analysis is based on qualitative and quantitative interviews of farmers and other key informants in two regions, Fox‐Wyaconda Watershed in northeast Missouri and Scott County in southeast Missouri. Within the field of farming, farmers emphasized the importance of economic, family and rental relations. Important habitus considerations include different interpretations of what constitutes farming and what constitutes forestry. Based on Bourdieu's theoretical framework, we offer three alternative paths of social change that may lead to more widespread utilization of agroforestry.     

Modelling data from single-photon emission computerized tomography

The completely random character of radioactive disintegration provides the basis of a strong justification for a Poisson linear model for single-photon emission computed tomography data, which can be used to produce reconstructions of isotope densities, whether by maximum likelihood or Bayesian methods. However, such a model requires the construction of a matrix of weights, which represent the mean rates of arrival at each detector of photons originating from each point within the body space. Two methods of constructing these weights are discussed, and reconstructions resulting from phantom and real data are presented.     

FAMILY THERAPISTS' RESPONSE TO AIDS: AN EXAMINATION OF ATTITUDES,KNOWLEDGE, AND CONTACT*

As the number of individuals and families impacted by AIDS continue to multiply, family therapists will increasingly be asked to become engaged in the challenge of caring for those affected. To date, little has been written in family therpy journals regarding the response of family therapists to this crisis. This paper represents an initial attempt to examine the atitudes of clinical members of the American Association for Marriage and Family Therapy toward AIDS and persons with AIDS. Included in the study are data regarding the therapists' contact with persons with AIDS, gays, and lesbians, and the impact of such contact on attitudes. Implications for future research, training, and treatment of those affected by AIDS are also provided.     

Small Business Success Among Men- and Women-Owned Firms in Rural Areas1

Abstract Rural women have difficulty finding good jobs. Ownership of small businesses offers an alternative but the sales and income of women-owned firms are significantly lower than those of men-owned firms. Compared with men, women owners are more likely to operate smaller and newer businesses; however, these differences do not completely account for the gap in gross sales between men- and women-owned businesses. The strongest influences on business success are firm size, corporate status, and industrial sector. Though significant, the owner's gender is less important than these organizational characteristics. The factors influencing success of small businesses generally are the same for men- and women-owned businesses. More research on business networks and the start-up phase of small businesses is necessary for a better understanding of the sources of gender differences in success.