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.     

Development of Parenting Skills in Individuals with an Intellectual Impairment: an epigenetic explanation

Current changes in legislation in the United States support the rights of individuals with an intellectual impairment to marry and have children. Current societal views, however, are heavily influenced by our history of viewing these individuals as inadequate parents. This historical view is based upon the assumption that those with intellectual impairments are genetically inferior. Changing views of development, however, suggest that the issue of how individuals with intellectual impairments develop is somewhat more complex. The epigenetic model is one that proposes that development is the result of the complex transaction between the individual and the environment. This paper applies this model to persons with an intellectual impairment to better understand the parenting skills they display. It is argued that by intervening and changing developmental pathways, the development of parenting skills of those with intellectual impairments can be facilitated.     

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 -