Estimates of subgroup treatment effects in overall nonsignificant trials: To what extent should we believe in them?

In drug development, it sometimes occurs that a new drug does not demonstrate effectiveness for the full study population but appears to be beneficial in a relevant subgroup. In case the subgroup of interest was not part of a confirmatory testing strategy, the inflation of the overall type I error is substantial and therefore such a subgroup analysis finding can only be seen as exploratory at best. To support such exploratory findings, an appropriate replication of the subgroup finding should be undertaken in a new trial. We should, however, be reasonably confident in the observed treatment effect size to be able to use this estimate in a replication trial in the subpopulation of interest. We were therefore interested in evaluating the bias of the estimate of the subgroup treatment effect, after selection based on significance for the subgroup in an overall “failed” trial. Different scenarios, involving continuous as well as dichotomous outcomes, were investigated via simulation studies. It is shown that the bias associated with subgroup findings in overall nonsignificant clinical trials is on average large and varies substantially across plausible scenarios. This renders the subgroup treatment estimate from the original trial of limited value to design the replication trial. An empirical Bayesian shrinkage method is suggested to minimize this overestimation. The proposed estimator appears to offer either a good or a conservative correction to the observed subgroup treatment effect hence provides a more reliable subgroup treatment effect estimate for adequate planning of future studies.     

Adaptive phase I/II clinical trials for drug combination assessment in oncology using the outcomes of each cycle

Many new anticancer agents can be combined with existing drugs, as combining a number of drugs may be expected to have a better therapeutic effect than monotherapy owing to synergistic effects. Furthermore, to drive drug development and to reduce the associated cost, there has been a growing tendency to combine these as phase I/II trials. With respect to phase I/II oncology trials for the assessment of dose combinations, in the existing methodologies in which efficacy based on tumor response and safety based on toxicity are modeled as binary outcomes, it is not possible to enroll and treat the next cohort of patients unless the best overall response has been determined in the current cohort. Thus, the trial duration might be potentially extended to an unacceptable degree. In this study, we proposed a method that randomizes the next cohort of patients in the phase II part to the dose combination based on the estimated response rate using all the available observed data upon determination of the overall response in the current cohort. We compared the proposed method to the existing method using simulation studies. These demonstrated that the percentage of optimal dose combinations selected in the proposed method is not less than that in the existing method and that the trial duration in the proposed method is shortened compared to that in the existing method. The proposed method meets both ethical and financial requirements, and we believe it has the potential to contribute to expedite drug development.     

Effects of Social Supports on the Career Choice Consideration of Chinese Farmers: A Social Cognitive Perspective

Drawing from social cognitive career theory ( Lent, Brown, & Hackett, 1994 ), this study explored social supports’ influence on the career choice consideration of farmers during China's current process of urbanization. A questionnaire was designed based on interviews with 140 people and a pretest with a sample of 419 participants. A total of 628 participants were involved in the formal questionnaire survey. Results indicated that social supports had a dual effect: Positive supports were indirectly related to career choice consideration through the mediation of career self‐efficacy, whereas negative supports were related to career choice consideration directly. Implications for future research and the development of a career guidance and social support system for Chinese farmers are discussed.     

古镇旅游资源开发的总体设计思路——以胜芳古镇旅游资源开发为例

以胜芳古镇旅游资源开发为例,通过对古镇旅游资源的分析评价、SWOT分析、古镇旅游发展目标与战略等问题的分析,扼要阐释了古镇旅游资源开发的总体设计思路。     

马克思主义关于人的全面发展理论及对研究生思想政治教育的启示

马克思主义关于人的全面发展理论包括人的需要满足、人的能力提高、人的主体性发展和人的社会关系丰富等方面。当前,研究生教育存在重视专业学习而忽视思想政治教育的现象,其思想政治教育也存在着主体性欠缺、方式单一的弊端。以马克思主义关于人的全面发展理论为指导,加强对研究生思想政治教育,促进其全面发展;坚持以人为本,提高亲和力;尊重教育对象的个性,增强针对性;立足人的社会性,为和谐社会建设添砖加瓦。     

新政府会计制度下重构水利部门整体支出绩效评价体系

2014年新修订的《预算法》实施和2018年中央出台的《关于全面实施预算绩效管理的意见》意味着我国政府非常重视预算绩效管理,财政部门还专门出台了项目支出、部门整体支出、财政预算等绩效评价共性指标体系框架。但2019年开始实施“双报告”的新会计制度,使得原来的绩效评价指标体系已经不适应新制度的要求,需要重新设计。文章以某市水利部门为例,在梳理国内外有关绩效评价的研究文献和实地调研的基础上,针对其实施现状和存在的问题,重新构建了部门整体支出绩效评价体系,以提升单位预算管理能力。     

高校后勤社会化若干实践问题的思考

根据本校后勤的实际情况 ,就高校后勤社会化改革对如下问题进行探讨 :(1)观念 ;(2 )目标实现 ;(3)内驱动力 ;(4)产权 ;(5 )人的安顿 ;(6 )基本利益 ;(7)价格 ;(8)市场 ;(9)策略     

试论以人为本与高校青年教师师德建设

“以人为本”，加强师德建设提高师德素养，是强化高校青年教师整体素质的核心，是高校德育工作的治本之策。     

马克思主义中国化研究述评

马克思主义中国化的研究经过了多年的发展取得了一系列喜人的理论建树,特别是研究的重点不断拓宽,在基本内容、内在关系等方面颇为深入,呈现出了全方位、多层次、宽领域的特点.同时研究焦点的视角不断衍伸, 但仍在诸多方面存在着盲点,而这正是必须深入耕犁的领域,我们也试图从思想下乡、范式建构、信仰研究等方面突破盲点,以期为马克思主义中国化的新发展尽绵薄之力.     

水力发电企业整体效益评价及实例

针对水力发电企业的整体经济效益难以进行评价的问题,提出了以灰色关联度技术为支撑,选择数量模型评价方法,应用层次分析法的有关技术和思想,建立起具有可操作性的评价模型及评价体系。