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.     

Changing Frameworks in Attitudes Toward Abortion

For more than two decades, legal abortion has been the subject of heated political debate and adversarial social movement activity; however, national polls have shown little change in aggregate levels of support for abortion. This analysis examines how the determinants of abortion attitudes have changed between 1977 and 1996, using data from the General Social Surveys. While in early time periods, whites were more approving of abortion than blacks, that pattern had reversed by the late 1980s. After controlling for other factors, older people are more accepting of abortion throughout the two decades, while gender is generally unrelated to abortion views. Catholic religion weakens slightly as a predictor of abortion attitudes, while religious fundamentalism and political liberalism increase in explanatory power. The associations between attitudinal correlates and abortion approval also change over this time period. Religiosity becomes a less powerful predictor of abortion attitudes, while respondents' attitude toward sexual freedom and belief in the sanctity of human life increase in their predictive power. Support for gender inequality remains a weak but stable predictor of abortion attitudes. This pattern of results suggests that the public is influenced more by the pro-life framework of viewing abortion than by the pro-choice perspective.     

The PALS parenting support programme: lessons learned from the evaluation of processes and outcomes

Although there has recently been a rise in parenting support programmes within the UK, only a minority of these programmes have benefited from evaluation of either outcomes or processes. This paper describes the development of the PALS programme (Parents Altogether Lending Support), reporting both on its effectiveness in improving parents' interactions with their children and on the lessons that were learned about embedding such a programme within the local community. Over the 18‐month period of the programme, a total of 17 courses were run, with 75 parents and carers (primarily mothers) participating in the programme overall. Evaluation results indicated that participants enjoyed the course and found it beneficial, particularly in terms of altering their own actions in specific ways that were able to promote better behaviour on the part of their children. Participants also valued the opportunity to share their experiences with other parents. The key lesson identified in regard to the development of parenting programmes concerned the need for the community to feel a sense of ownership for the initiative. Copyright © 2002 John Wiley & Sons, Ltd.     

Book Review: Funding Virtue: Civil Society Aid and Democracy Promotion,Marina Ottaway and Thomas Carothers (eds.), Carnegie Endowment for International Peace,Washington, DC, 2000

VOLUNTAS: International Journal of Voluntary and Nonprofit Organizations -     

Becoming Custodial Dads: Exploring Parenting Among Low‐Income and Working‐Class African American Fathers

The authors use an ecological framework and grounded theoretical analysis to explore the circumstances in which working‐class and low‐income custodial African American fathers gain custody of their children, their transition from part‐time to full‐time parents, and the role of support networks in enhancing or inhibiting these men's parenting. Twenty‐four men from an impoverished Midwestern urban area participated in the study. The findings suggest that these men, and perhaps others sharing their demographic profiles, generally become parents by default and are often reluctant to take on a full‐time, single parenting role. Adaptation to the role seems to be enhanced by these men's use of extended kin support networks and shared living arrangements. However, low wages, a lack of sufficient assistance from public assistance programs, and informal custody arrangements often inhibit their fathering.     

Existence and Nash implementation of efficient sharing rules for a commonly owned technology

Suppose that a group of individuals owns collectively a technology which produces a consumption good by means of a (possibly heterogeneous) input. A sharing rule associates input contributions with a vector of consumptions that are technologically feasible. We show that the set of allocations obtained by any continuous sharing rule contains Pareto efficient allocations. We also present a mechanism that implements in Nash equilibrium the Pareto efficient allocations contained in an arbitrary sharing rule. Received: 29 June 1998/Accepted: 15 November 2000     

REVIEWS

Bailey, C. E. (Ed.) (2000). Children in therapy: Using the family as a resource. Doherty, W. J. (2001). Take back your marriage: Sticking together in a world that pulls us apart. New York: Guilford. Larson, J. H. (2000). Should we stay together? A scientically proven method for evaluating your relationship and improving its chances for long‐term success. Weiner‐Davis, M. (2001). The divorce remedy: The proven 7‐step program for saving your marriage.     

Life Experiences and Vulnerabilities of Homeless Women: A Comparison of Women Unaccompanied Versus Accompanied by Minor Children, and Correlates with Children's Emotional Distress

The histories and service needs of 2 groups of homeless women, those unaccompanied by minor children (n = 46) and those accompanied by minor children (n = 22), were compared, on the basis of their responses to a biennial survey of homeless people in a midsize city in the southeast United States. Mothers of children aged 2–10 also completed a measure of stress symptoms for their children (n = 20). Irrespective of family status group, problems such as substance abuse, history of mental illness, health problems, chronicity of homelessness, and crime victimization tended to cluster together. The findings also suggest that declining and/or inadequate levels of public benefits, Temporary Assistance to Needy Families, and Medicaid-funded health care in particular, have adversely affected the 2 groups, particularly families with children. The young children in this sample experienced elevated levels of stress, and significant associations were found between children's stress levels and certain risk factors of their mothers. Implications for service delivery are discussed.     

Frustration in Infancy: Implications for Emotion Regulation,Physiological Processes,and Temperament

A study sample of 162 six‐month‐old children was selected from a larger sample of 346 infants on the basis of parents' report of their infants' temperament and a laboratory assessment of temperament. Infants were classified as easily frustrated and less easily frustrated and compared on a number of emotion regulation, physiology, and temperament measures. Results indicated that male and female infants were equally likely to be classified as frustrated and less easily frustrated; however, male infants were less able to regulate physiologically. Easily frustrated infants used different emotion regulation strategies and were observed to be less attentive and more active than less easily frustrated infants when observed in the laboratory. These infants were also characterized by their parents as more active, less attentive, and more distressed to novelty. Infants classified as easily frustrated were more reactive physiologically and less able to regulate physiological reactivity than their less easily frustrated counterparts. It is hypothesized that this cluster of characteristics may constitute a unique temperamental type that may have implications for other types of behavioral functioning. Limitations of the study are that observations are based on a single brief assessment of the infant, modest effect sizes were found, and the study is cross‐sectional.