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.     

离退休职工养老问题探讨

离退休职工的养老问题是目前我国所面临的亟待解决的重大问题.要解决这一问题,必须充分发挥国家、家庭、社区、单位和个人的作用,建立国家、家庭、社区、单位、个人五个层次相结合的养老体系.     

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.     

Frontier spaces of vulnerability: Regional change,urbanization, drought and fire hazard in Santarém,Pará, Brazil

Fire hazard is a mounting concern in tropical rainforests of the Brazilian Amazon and has raised awareness within the science community of the links between agricultural fire use, drought and accidental fire. As a result, fire is being addressed as a crisis event with mitigation focused on those who light fires, particularly smallholder agriculturalists. Little attention is paid to the historical and ongoing ways in which Amazon landscapes and peoples have been made more susceptible to fire. Frontier regions of the Brazilian Amazon serve a variety of functions within the larger Brazilian society, including as extractive reserves for economic development, as social safety valves to reduce population pressures, and as areas to support urban regional integration. Each of these functions has impacted frontier environments in ways that create more flammable landscapes and/or shape the vulnerability of people to fire hazard. This paper uses a case study inthe Brazilian Lower Amazon to understand how vulnerability to fire hazard develops. It argues that if fire mitigation remains centered on fire as a crisis event, an understanding of what constitutes frontier spaces of vulnerability, both in landscape and in populations, will be limited.     

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.     

GENDER AND RACE PATTERNS IN THE PATHWAYS FROM SPORTS PARTICIPATION TO SELF-ESTEEM

Athletics is the most prominent extracurricular activity in U.S. secondary schools in terms of student participation and school budgets. The latter is often justified on the grounds that healthy bodies produce healthy minds, that school sports boost school spirit, and that participation in school-based sports increases students' self-esteem. In this article we examine the interrelationships among participation in a school-based sport and the benefits assumed to be associated with it. Specifically, we test a model that postulates that school spirit, operationalized as attachment to school, and healthy bodies, operationalized as a sense of physical well-being, mediate the relationship between school sports and self-esteem. Data from the National Longitudinal Study of Adolescent Health on Caucasian and African American girls and boys were employed to test the model. School attachment and physical well-being absorbed the statistical effect of participating in a sport for all four gender-by-race groups. Among Caucasian girls a negative residual effect of sports participation was observed, which suggests that sports participation encapsulates multiple effects with contradictory influences. For African American girls school attachment by itself was not a significant mediator of the effect of sports participation on self-esteem. For all groups a sense of physical well-being was the more powerful mediator.     

Peer Crowd Affiliation and Internalizing Distress in Childhood and Adolescence: A Longitudinal Follow‐Back Study

Concurrent and longitudinal associations between peer crowd affiliation and internalized distress were examined in a sample of 246 youth (148 girls, 98 boys). Children completed measures of depression, social anxiety, loneliness, and self‐esteem when they were in grades 4 to 6 (Time 1), and again 6 years later during adolescence (grades 10 – 12; Time 2). At Time 2, adolescents also reported their self‐concept and their identification with reputation‐based peer crowds, including Populars, Jocks, Brains, Burnouts, Non‐Conformists, and None/Average crowds. Results indicated that adolescents' report of peer crowd affiliation was concurrently associated with self‐concept and levels of internalizing distress. Follow‐back analyses of internalizing trajectories revealed that Populars/Jocks had experienced significant declines in internalizing distress across development, whereas Brains exhibited some increases in internalizing distress between childhood and adolescence.     

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