Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

医患关系现状及基于EAP视角的改进对策研究

医生的天职是治病救人，医生同患者之间彼此信任、和谐友好的关系是取得良好治疗效果的前提。但是近些年来医患之间矛盾不断，医患纠纷事件频发。这个问题已经不仅仅是牵涉到医疗方面的问题，而是已经上升至整个社会层面的问题。引起医患矛盾产生的因素有很多，对这些因素进行总结分析，并对建立和谐的医患关系的方法进行探讨和分析，能够基于EAP视角对构建和谐的医患关系提供一些参考和思路。     

医疗信息共享对患者转移数量和服务质量水平影响研究

当前我国医院间存在严重的"信息孤岛"，医院参与医疗信息共享意愿不高，患者的诊疗信息被静态碎片化储存而无法充分有效地利用。考虑到医院进行医疗信息共享将降低患者转移成本，本文构建一个多阶段双寡头动态博弈模型研究医疗信息共享对医院竞争过程中患者转移数量和服务质量水平决策的影响。首先，根据是否存在转移成本，将患者分为新患者和经验性患者，借助Hotelling模型刻画患者的效用函数，分析患者就诊决策。然后，在政府价格规制和不考虑医院利他性情景下，构建了医院累积期望收益目标函数，使用动态规划方法，求解实现医院累积期望收益最大化的服务质量水平，获得了实现患者相互转移且医院在市场中共存的马尔可夫完美均衡。最后，根据医院参与医疗信息共享后患者转移成本降为零，分析与比较信息共享前后患者转移数量和服务质量水平变化。研究发现：在不同医院间本身存在患者转移背景下，医院参与信息共享后，患者转移数量增加但存在一个上限，增加的转移量与患者在医院间的转移成本呈正相关，与初始感知效用的差值范围呈负相关；医院参与信息共享后，均衡状态下的医院服务质量水平高于信息共享前的服务质量水平。因此，在不改变当前医保支付方式下，要加快推进医疗信息共享，政府部门可以根据医院的患者数量和服务质量水平变化对其进行定期补贴，以激励医院积极参与医疗信息共享，本文给出了这个补贴的量化表达。     

A stochastically curtailed two-arm randomised phase II trial design for binary outcomes

Randomised controlled trials are considered the gold standard in trial design. However, phase II oncology trials with a binary outcome are often single-arm. Although a number of reasons exist for choosing a single-arm trial, the primary reason is that single-arm designs require fewer participants than their randomised equivalents. Therefore, the development of novel methodology that makes randomised designs more efficient is of value to the trials community. This article introduces a randomised two-arm binary outcome trial design that includes stochastic curtailment (SC), allowing for the possibility of stopping a trial before the final conclusions are known with certainty. In addition to SC, the proposed design involves the use of a randomised block design, which allows investigators to control the number of interim analyses. This approach is compared with existing designs that also use early stopping, through the use of a loss function comprised of a weighted sum of design characteristics. Comparisons are also made using an example from a real trial. The comparisons show that for many possible loss functions, the proposed design is superior to existing designs. Further, the proposed design may be more practical, by allowing a flexible number of interim analyses. One existing design produces superior design realisations when the anticipated response rate is low. However, when using this design, the probability of rejecting the null hypothesis is sensitive to misspecification of the null response rate. Therefore, when considering randomised designs in phase II, we recommend the proposed approach be preferred over other sequential designs.     

中国传统文化何以容纳患者自主

患者自主概念源于生命伦理学的自主原则,它在概念上强调对医患关系的依附和医生对患者自主权利的尊重。传统儒家的仁学在强调人与人之间的关系的同时,没有否定个人的自主,通过对“人”的肯定和对人的“情感自由”的认可来体现自主的力量。传统中国医患关系中,要求医生尊重生命、尊重患者,治病时要了解患者的心理和情感等,表明了中国传统文化能够容纳患者自主。     

Model free audit methodology for bias evaluation of tumour progression in oncology

Many oncology studies incorporate a blinded independent central review (BICR) to make an assessment of the integrity of the primary endpoint, progression free survival. Recently, it has been suggested that, in order to assess the potential for bias amongst investigators, a BICR amongst only a sample of patients could be performed; if evidence of bias is detected, according to a predefined threshold, the BICR is then assessed in all patients, otherwise, it is concluded that the sample was sufficient to rule out meaningful levels of bias. In this paper, we present an approach that adapts a method originally created for defining futility bounds in group sequential designs. The hazard ratio ratio, the ratio of the hazard ratio (HR) for the treatment effect estimated from the BICR to the corresponding HR for the investigator assessments, is used as the metric to define bias. The approach is simple to implement and ensures a high probability that a substantial true bias will be detected. In the absence of bias, there is a high probability of accepting the accuracy of local evaluations based on the sample, in which case an expensive BICR of all patients is avoided. The properties of the approach are demonstrated by retrospective application to a completed Phase III trial in colorectal cancer. The same approach could easily be adapted for other disease settings, and for test statistics other than the hazard ratio. Copyright © 2015 John Wiley & Sons, Ltd.     

Theoretical Factors Influencing Adolescent Sexual Behavior: Evidence from a Rural Sample Living in Poverty

ABSTRACT

This study of 414 adolescents who resided in rural Arkansas families receiving AFDC was designed to investigate what theoretical factors predicted frequency of sexual intercourse in the past year prior to the study and number of lifetime sexual partners among males and females. Multivariate analyses indicated that elements of bonding were important to the sexual behavior of females, but not males. On the other hand, feelings of frustration influenced male sexual behavior only. The number of sex partners was increased by associations with sexually active peers for both genders while only females made excuses. The only factor which was associated with both sexual behaviors among both genders was having sex to have a baby to love or to draw a partner closer. The family social work implications of these findings were discussed.     

东晋南朝医学知识的新发展:以医家、病者为中心的研究

本文以医家、病者为中心,结合医籍的相关叙述,来探讨东晋南朝医学知识的新发展。文中分析指出,此时期医家与病者多数都是出自社会地位较高的士大夫阶层。作为病者,他们世代内部通婚,过度优逸,嗜好饮酒,易受精神刺激,早婚多妾侍,多种因素导致了体貌柔弱,不堪劳作。显现于医学典籍,则是许多医方以体质偏虚之人为预设目标。而又作为医家的他们,传习家学,博通医术,或由信仰之故,兼修岐黄,这促使医界病源学理盛行以及佛道知识常被引入医书。综合诸历史迹象,作者认为东晋南朝医学知识有显著的贵胜特点。     

转型期中国医务社会工作服务范围与优先介入领域研究

医务社会工作是现代健康照顾体系的重要组成部分,服务范围广泛多样,覆盖疾病预防、临床医院、康复服务、社会卫生服务、公共卫生和区域卫生规划等所有服务领域。在恢复医务社会工作过程中,医务社会工作发展的优先领域、战略重点与介入策略至关重要。在医患关系日趋紧张、医疗事故频繁发生和医疗纠纷不断增多的处境下,医患关系和医患沟通是医务社会工作介入的优先领域,改善医患关系是医务社会工作战略重点和最佳介入策略。