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.     

Punishment and pleasure: women, food and the imprisoned body1

Food assumes enormous importance in prison: for many prisoners it conditions their life in custody and, in many respects, is symbolic of the prison experience. This article explores the complex relationship between gender, food and imprisonment through an analysis of data obtained from in‐depth interviews and group discussions conducted in three women's prisons in England. The findings indicate that, in prison, where control is taken away as the prisoner and her body become the objects of external forces, food is experienced not only as part of the disciplinary machinery, but also as a powerful source of pleasure, resistance and rebellion. The implications of such findings for health promotion in the prison context are discussed. Here, the pleasures and consolations of food may well constitute a redefinition of what it is to be healthy in this context, one that challenges the dominant meaning constructed in current health promotional discourse.     

Relations Between Measures of Irritability and Contingency Detection at 6 Months

The hypothesis that irritability and contingency detection are negatively correlated was examined in thirty‐one 6‐month‐old infants. Observation and maternal report‐based assessments of irritability were correlated with both a criterion score and a continuous score of contingency detection. Results indicated that greater irritability in infants was associated with lower contingency detection scores. Discussion focuses on identifying processes by which the 2 constructs may be associated.     

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 -