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.     

Global Responses to the COVID-19 Pandemic

Public Organization Review -     

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.     

Sample sizes for estimation in clinical research

A sample size justification should be given for all clinical investigations. However, sometimes the objective of a trial is to estimate an effect with a view to planning a later definitive study. This paper describes the calculations for designing studies where one wishes to adopt an estimation approach through using confidence intervals around the overall response. Calculations are given for data anticipated to take a Normal form. Copyright © 2004 John Wiley & Sons, Ltd.     

Time, Self, and the Curiously Abstract Concept of Agency*

The term "agency" is quite slippery and is used differently depending on the epistemological roots and goals of scholars who employ it. Distressingly, the sociological literature on the concept rarely addresses relevant social psychological research. We take a social behaviorist approach to agency by suggesting that individual temporal orientations are underutilized in conceptualizing this core sociological concept. Different temporal foci—the actor's engaged response to situational circumstances—implicate different forms of agency. This article offers a theoretical model involving four analytical types of agency ("existential,""identity,""pragmatic," and "life course") that are often conflated across treatments of the topic. Each mode of agency overlaps with established social psychological literatures, most notably about the self, enabling scholars to anchor overly abstract treatments of agency within established research literatures.     

Women's Changing Attitudes Toward Divorce, 1974–2002: Evidence for an Educational Crossover

This article examines trends in divorce attitudes of young adult women in the United States by educational attainment from 1974 to 2002. Women with 4‐year college degrees, who previously had the most permissive attitudes toward divorce, have become more restrictive in their attitudes toward divorce than high school graduates and women with some college education, whereas women with no high school diplomas have increasingly permissive attitudes toward divorce. We examine this educational crossover in divorce attitudes in the context of variables correlated with women's educational attainment, including family attitudes and religion, income and occupational prestige, and family structure. We conclude that the educational crossover in divorce attitudes is associated most strongly with work and family structure variables.     

Muted Masculinity as an Outsider Strategy: Gender Sharing in Ethnographic Work with Wives of Professional Athletes

Using findings from a study of the world of the wives of professional athletes, this article explores the complex motivations for and displays of trust, rapport, and group acceptance during ethnographic research. Episodic exchanges between a male ethnographer and female collaborators revealed subtle issues of gender and perceived relative worth. This article proposes the outsider strategy of “muted masculinity” as a means of exploring ethnographic issues in which the boundaries between insiders and outsiders are uncertain.