Treatment effect quantification for time‐to‐event endpoints–Estimands,analysis strategies,and beyond

A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend ICH E9 grew out of the realization of a lack of alignment between the objectives of a clinical trial stated in the protocol and the accompanying quantification of the “treatment effect” reported in a regulatory submission. We embed time‐to‐event endpoints in the estimand framework and discuss how the four estimand attributes described in the addendum apply to time‐to‐event endpoints. We point out that if the proportional hazards assumption is not met, the estimand targeted by the most prevalent methods used to analyze time‐to‐event endpoints, logrank test, and Cox regression depends on the censoring distribution. We discuss for a large randomized clinical trial how the analyses for the primary and secondary endpoints as well as the sensitivity analyses actually performed in the trial can be seen in the context of the addendum. To the best of our knowledge, this is the first attempt to do so for a trial with a time‐to‐event endpoint. Questions that remain open with the addendum for time‐to‐event endpoints and beyond are formulated, and recommendations for planning of future trials are given. We hope that this will provide a contribution to developing a common framework based on the final version of the addendum that can be applied to design, protocols, statistical analysis plans, and clinical study reports in the future.     

Challenges in Counter‐disaster Measures for People with Functional Needs in Times of Disaster Following the Great East Japan Earthquake

This article describes the three major challenges that were identified and their possible solutions are proposed in counter‐disaster measures for “people with functional needs in times of disaster (PFND)” following the 2011 Great East Japan Earthquake. First, recent developments in preparedness measures for PFND in Japan have been uncritically relying on the assumption that hazard maps represent “correct” estimates of future hazardous events, which are based on the maximum probable event (MP_rE) framework. In reality, however, a maximum possible event (MP_oE) has occurred in the Tōhoku regions. This has tremendous implications for fundamentally re‐thinking the entire hazard estimation process from a MP_rE to MP_oE framework. Second, counter‐disaster measures for PFND have focused mainly on warning and neighborhood‐based evacuation assistance activities. Needs for shelters and temporary housing units that were specially designated for PFND arose following the earthquake. However, their provisions were neither systematic nor universal due to the lack of pre‐planning. More detailed guidelines for specially designated shelter and temporary housing operations need to be developed in order to address this issue. Third, people with disabilities (PWD) became invisible in shelters and communities or in the eyes of local government administrators. This was due to the fact that a majority of PWD did not ask for help in evacuation shelters because they felt general shelters were not “barrier free” and were unresponsive to their functional needs. Furthermore, many local government administrators felt hesitant to release their PFND registry to non‐governmental and self‐help organizations that were eager to check the whereabouts and current situations of PWD. This was due to the fear of breaking the Personal Information Protection Bylaw despite the fact that the bylaw provided exceptional conditions, where the onset of disaster was clearly one of these exceptional conditions. Further elaboration and education on the use of personal information of PFND during a disaster period is needed among public and local government administrators.     

Bayesian hierarchical duration model for repeated events: an application to behavioral observations

This article presents a continuous-time Bayesian model for analyzing durations of behavior displays in social interactions. Duration data of social interactions are often complex because of repeated behaviors (events) at individual or group (e.g. dyad) level, multiple behaviors (multistates), and several choices of exit from a current event (competing risks). A multilevel, multistate model is proposed to adequately characterize the behavioral processes. The model incorporates dyad-specific and transition-specific random effects to account for heterogeneity among dyads and interdependence among competing risks. The proposed method is applied to child–parent observational data derived from the School Transitions Project to assess the relation of emotional expression in child–parent interaction to risk for early and persisting child conduct problems.     

Change in the Association Between Premarital Cohabitation and Separation,Australia 1945 – 2000

We investigate change in the association between premarital cohabitation and the risk of separation. Using retrospective marriage history data from the first wave (2001) of the Household Income and Labor Dynamics in Australian survey, we examine 6,210 first marriages formed between 1945 and 2000. We find the association between premarital cohabitation and separation is changing. The increased risk of separation for cohabitors compared to noncohabitors diminishes each year for marriages before 1988. This association then reverses for marriages after 1988, where noncohabitors have an increased risk of separation. Our results indicate that, for more recent marriages, premarital cohabitation reduces the risk of separation; more research is needed to understand the underlying mechanisms for this reversal.     

财务报告质量与投资者保护——基于事件研究法的实证考察

西方国家大量的实证研究表明,财务报告具有经济后果。在中国新兴的资本市场,财务报告是否具有信息含量,进而带来市场反应,是否保护或损害投资者的利益,目前的实证研究不仅比较鲜见,而且结论尚不一致。文中以因舞弊财务报告而被中国证监会处罚的41家上市公司为样本,运用事件研究法(event study)考察了财务报告质量与投资者保护之间的经验关系。证据表明,那些因舞弊财务报告而受到证监会处罚的上市公司,其股价的超额收益率显著为负。这些公司的投资者因为公司舞弊蒙受了较大的损失,研究还发现市场存在消息提前泄漏的现象。     

Quantitative Risk Assessment of Norovirus Transmission in Food Establishments: Evaluating the Impact of Intervention Strategies and Food Employee Behavior on the Risk Associated with Norovirus in Foods

We developed a quantitative risk assessment model using a discrete event framework to quantify and study the risk associated with norovirus transmission to consumers through food contaminated by infected food employees in a retail food setting. This study focused on the impact of ill food workers experiencing symptoms of diarrhea and vomiting and potential control measures for the transmission of norovirus to foods. The model examined the behavior of food employees regarding exclusion from work while ill and after symptom resolution and preventive measures limiting food contamination during preparation. The mean numbers of infected customers estimated for 21 scenarios were compared to the estimate for a baseline scenario representing current practices. Results show that prevention strategies examined could not prevent norovirus transmission to food when a symptomatic employee was present in the food establishment. Compliance with exclusion from work of symptomatic food employees is thus critical, with an estimated range of 75–226% of the baseline mean for full to no compliance, respectively. Results also suggest that efficient handwashing, handwashing frequency associated with gloving compliance, and elimination of contact between hands, faucets, and door handles in restrooms reduced the mean number of infected customers to 58%, 62%, and 75% of the baseline, respectively. This study provides quantitative data to evaluate the relative efficacy of policy and practices at retail to reduce norovirus illnesses and provides new insights into the interactions and interplay of prevention strategies and compliance in reducing transmission of foodborne norovirus.     

盖棺难定论：对历史事件政治评价历史的历史评价——以太谷学派黄崖山事件为例

黄崖山事件的评价争论持续了百年,将其评价的历史演变过程揭示出来并加以分析,以使我们加深对这一事件的了解并提高我们的历史判断能力。     

新时期浦东群体性事件及其应对能力分析

经济社会快速发展过程中,群体性事件上升对基层政府应急管理能力提出严峻挑战。当前,浦东政府在应对群体性事件的理念、方式、体制、善后反思等方面还存在一定缺失。近年来,浦东政府不断提高应急管理能力,在树立人本观念,不断整合管理机制、多途径解决群体性事件方面下功夫,并注重学习和体制革新。浦东群体性事件化解的缓解率不断提高,其经验对我国其他地区妥善处置群体性事件具有重要的借鉴意义。     

分布式对象调试中的事件模型(英文)

针对事件的分布式程序调试过程中,需处理大量的事件消息,如果处理不当,则会影响分布式程序的执行,提出了一种分布式对象中的事件模型,采用这种模型,可以大大简化事件消息的收集和处理,解决了分布式实时计算中的不确定性等问题,并降低了分布式调试过程本身给程序执行的影响。