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.     

自杀和生命的意义——来自脑科学研究的解读

生命本身是一个随机事件，并不具有高尚的意义。进化的结果使人类可通过工作、家庭和人际关系等给予自己的生命以意义感。当我们的生活方式使脑内奖赏系统获得刺激，就会带来生命具有意义的感受，这种感受给人带来更好的生存机会。生存的欲望是一切生物体最具特征的属性，一些精神疾病患者缺乏这种欲望。自杀主要发生于精神疾病患者，它并非是基于自由意志的行为。抗精神病治疗和适当的社会交往可以预防自杀。由于不同个体有着不同的大脑，人们的生活方式就应该去适应各自大脑的特征。只要人们的生活方式不对他人造成过多的伤害，政府就应该允许和保护人们自由地按照各自的方式生活。     

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.     

Hidden Resources and Barriers in Career Learning Assessment With Adolescents Vulnerable to Discrimination

The authors maintain that the social learning theory of career development and counseling has not been applied to diverse populations. To address this gap in the literature, the authors conducted a qualitative analysis of interviews with 21 middle school students in a low‐income, culturally diverse, inner‐city public school. Four themes emerged, reflecting the influence of discrimination on participants' career learning: contextual barriers and resources for learning, and psychological barriers and resources for learning. The authors provide a conceptual framework for assessing resources and barriers and a rationale for why these aspects often remain hidden or unexamined in career assessment with clients who are vulnerable to discrimination.     

The PALS parenting support programme: lessons learned from the evaluation of processes and outcomes

Although there has recently been a rise in parenting support programmes within the UK, only a minority of these programmes have benefited from evaluation of either outcomes or processes. This paper describes the development of the PALS programme (Parents Altogether Lending Support), reporting both on its effectiveness in improving parents' interactions with their children and on the lessons that were learned about embedding such a programme within the local community. Over the 18‐month period of the programme, a total of 17 courses were run, with 75 parents and carers (primarily mothers) participating in the programme overall. Evaluation results indicated that participants enjoyed the course and found it beneficial, particularly in terms of altering their own actions in specific ways that were able to promote better behaviour on the part of their children. Participants also valued the opportunity to share their experiences with other parents. The key lesson identified in regard to the development of parenting programmes concerned the need for the community to feel a sense of ownership for the initiative. Copyright © 2002 John Wiley & Sons, Ltd.     

Book Review: Funding Virtue: Civil Society Aid and Democracy Promotion,Marina Ottaway and Thomas Carothers (eds.), Carnegie Endowment for International Peace,Washington, DC, 2000

VOLUNTAS: International Journal of Voluntary and Nonprofit Organizations -