Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

Systematic review: Predictors of students’ success in baccalaureate nursing programs

Nursing schools strive to select a diverse student population who are likely to succeed by ensuring timely student progression through the program and effective use of educational sources. The purpose of this systematic literature review is to explore the preadmission variables and selection criteria that predict student success in 4-year baccalaureate nursing programs in the U.S. Sixteen articles met the eligibility criteria, and six measures were used to define student success: (a) early academic success, particularly during the first and second year; (b) attrition; (c) timely completion of the program; (d) graduation; (e) performance in nursing courses; and (f) academic performance in other science courses. Typically, the core set of cognitive predictors used in the admission process in nursing schools were pre-nursing GPA, pre-nursing collegiate science GPA, and scores on standardized aptitude exams. This review suggests that it is challenging to isolate one single variable as the best predictor of student success; however, using a combination of variables can offer a reliable prediction method. More researchers should consider using a theoretical basis to guide their inquiry on this topic. Additionally, researchers should examine admission variables that are most relevant across programs.     

在义务兵征兵体检中应用PHI和16PF的研究

目的　探讨 PHI和 1 6PF量表在义务征兵体验中的应用。方法　用 PHI和 1 6PF量表评定参加征兵体检并初检合格的应征青年 5 44人 ,分析应用 PHI和 1 6PF量表的可靠性 ,以量表 T分作评判依据 ,比较以国内常模及组内常模进行选拔的效果。结果　PHI与 1 6PF的相关性较好 ,但在项目上具有一定的重叠 ;以国内常模筛选 PHI的检出率相当低 ,而1 6PF则检出率过高 ,筛选有效率均低 ;应用组内的均数、标准差来计算 T分 ,以此 T分进行筛选效果较好。结论　PHI与1 6PF量表可以应用于征兵体检中 ,用组内常模进行选拔效果更好 ,正式推出尚需修订     

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary antihapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg^-) B cells (centroblasts), and most of their progeny are sIg⁺ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg⁺ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg⁺ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg⁺ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg⁺ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.     

一种自动优选标准型股骨柄的方法

髋关节置换手术中采用标准型假体时,术前只能大致选取假体,术中还要预备多个假体,往往手术时间增长。为了解决这一问题,本文提出一种利用计算机优选标准型髋关节假体的方法。从X线片中获取患者股骨解剖数据。利用这些解剖数据和股骨近端截面平均数据库三维重建患者股骨近端,重建出的股骨近端模型使优选标准假体成为可能。理论分析表明,该方法切实可行。     

进展期低位直肠癌新辅助放化疗后侧方淋巴结清扫的选择和意义

侧方淋巴引流是低位直肠癌3个重要的淋巴引流方向之一。沿引流途径清扫淋巴结是直肠癌根治术基本要求,也决定淋巴结清扫范围。但侧方淋巴结是区域淋巴结还是远处淋巴结,一直存在争议。这带来新辅助放化疗和侧方淋巴结清扫、以及新辅助放化疗对侧方淋巴结转移疗效的争议。笔者综合分析国内外研究进展,对直肠癌侧方淋巴结转移规律、影响侧方淋巴结转移复发危险因素以及放化疗前后MRI检查对侧方淋巴结评估等进行深入阐述,并结合临床实践,探讨进展期低位直肠癌新辅助放化疗后侧方淋巴结清扫的选择和意义。     

浅谈药用植物良种选育的目标和常规途径

针对传统药用植物的品质退化进行品质改良，选育优良品种，是优化中草药品质的根本途径。优质、高产、稳产、熟期适应、抗性强、适应性相对较广是各种药用植物育种的共同目标，但不同药用植物品种的侧重点和具体内容各有变化。在药用植物的良种选育工作中，确定育种目标是基础。通常用以下途径进行良种繁育：1．种质资源调查和收集；2．引种驯化；3．良种选育；4．建立良种繁育基地。     

《千金要方》哮喘选穴配方特点探析

《千金要方》记载了针灸治疗哮喘共11个处方。并从处方组成，功效，适应症，手法以及疗程方面作了详尽的阐述，为探求临床治疗哮喘选穴配方的规律和思路，特对11个千金哮喘方的特点进行了归纳总结。供临床参考。     

电针治疗失眠症不同穴位组方的对照研究

目的:探讨电针治疗失眠症的最佳穴位组方.方法:将66例患者随机分为3组,第1组取四神聪、风池;第2组取百会、左神门;第3组取印堂、神庭.进行不同穴组治疗失眠症疗程与疗效的比较观察.结果:3组有效率分别为72.73%、77.27%、95.45%,第3组疗效明显优于第1、第2组(P＜0.01),第1组与第2组间疗效差异无显著性意义(P＞0.05).结论:电针印堂、神庭治疗失眠症疗效显著.     

新型农村合作医疗制度下逆向选择问题及防范

新型农村合作医疗制度象保险制度一样,也存在着逆向选择的缺陷,本文说明了合作医疗制度中逆向选择的概念与产生机理,提出了减少合作医疗中逆向选择的对策.