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.     

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.     

Editorial

Ohne Zusammenfassung

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Editorial

     

The Young and the Realigning: A Test of the Socialization Theory of Realignment

Recent research has demonstrated that Democrats and Republicansare divided along religious lines–98) confirm that thelink between religiosity and Republican Party identificationis stronger among younger than older voters.     

Volume 30

Theory and Society -     

Book Review: A Generation Divided: The New Left,The New Right,and the 1960s. By Rebecca E. Klatch. Berkeley: University of California Press, 1999. 386 pages,paperback, ISBN: 0-520-21714-4

Qualitative Sociology -     

Challenges to Connecting Sociology and Service Learning

Service-learning programs are not free from challenges brought about by lack of financial support, lack of widespread commitment from professors, community agencies, and recipients of service, and lack of knowledge and insight in students directly involved in such programs. While service-learning initiatives and programs serve positive functions for organizations and individuals, rhetorical accolades for service learning can distort or omit the realities of program implementation and sustained delivery. This paper specifically explores the following challenges connected to service-learning programs: (1) pedagogical difficulties; (2) student limitations; (3) time constraints; and (4) community cooperation.     

Multiparameter evidence synthesis in epidemiology and medical decision-making: current approaches

Summary.  Alongside the development of meta-analysis as a tool for summarizing research literature, there is renewed interest in broader forms of quantitative synthesis that are aimed at combining evidence from different study designs or evidence on multiple parameters. These have been proposed under various headings: the confidence profile method, cross-design synthesis, hierarchical models and generalized evidence synthesis. Models that are used in health technology assessment are also referred to as representing a synthesis of evidence in a mathematical structure. Here we review alternative approaches to statistical evidence synthesis, and their implications for epidemiology and medical decision-making. The methods include hierarchical models, models informed by evidence on different functions of several parameters and models incorporating both of these features. The need to check for consistency of evidence when using these powerful methods is emphasized. We develop a rationale for evidence synthesis that is based on Bayesian decision modelling and expected value of information theory, which stresses not only the need for a lack of bias in estimates of treatment effects but also a lack of bias in assessments of uncertainty. The increasing reliance of governmental bodies like the UK National Institute for Clinical Excellence on complex evidence synthesis in decision modelling is discussed.