Heterogeneity in treatment effects across diverse populations

Differences in patient characteristics, including age, sex, and race influence the safety and effectiveness of drugs, biologic products, and medical devices. Here we provide a summary of the topics discussed during the opening panel at the 2018 Johns Hopkins Center for Excellence in Regulatory Science and Innovation symposium on Assessing and Communicating Heterogeneity of Treatment Effects for Patient Subpopulations: Challenges and Opportunities. The goal of this session was to provide a brief overview of FDA-regulated therapeutics, including drugs, biologics and medical devices, and some of the major sources of heterogeneity of treatment effects (HTE) related to patient demographics, such as age, sex and race. The panel discussed the US Food and Drug Administration's role in reviewing and regulating drugs, devices, and biologic products and the challenges associated with ensuring that diverse patient populations benefit from these therapeutics. Ultimately, ensuring diverse demographic inclusion in clinical trials, and designing basic and clinical research studies to account for the intended patient population's age, sex, race, and genetic factors among other characteristics, will lead to better, safer therapies for diverse patient populations.     

系列性权利组合:有限责任公司股东优先购买权性质新探

股东优先购买权体现出有限责任公司人合性与资合性之间的冲突。中国对于股东优先购买权的法律规范存在缺陷,其根本原因在于缺乏一套体系性的股东优先购买权理论。股东优先购买权本质上是系列性权利组合,而非单一的权利,具体包括资格维持请求权、告知请求权、强制缔约权和优先受领权。股东于其取得股东身份时取得优先购买权,并于此时得以行使。至于优先购买权的行使期限,则不宜做过多理论上的探讨,而应当交由立法者根据本国国情加以规定。     

竞业限制条款法律适用及其完善

企业基于商业秘密之保护和维持永续竞争力,通常要求员工签订竞业限制协议或条款,其中涉及商业秘密保护权和员工劳动就业权的冲突。因我国目前相关法律规定零散而不成体系,因此应合理构建竞业限制条款的具体制度,规定一般员工的法定竞业限制义务,明确竞业限制的主体、适用范围、经济补偿、违约责任、期限等,准确理解违反竞业限制义务的责任构成及其责任形式是实现权利冲突的合理解决和劳资双方共赢的最佳途径。     

民汉双语诉讼规则之探索

我国宪法赋予了公民用自己的民族语言文字参加诉讼的权利，目的在于实现民族平等、促进民族团结、禁止民族分裂、保护中华民族语言文化的多样性，进而提高我国的文化软实力。通过调查民族语言文字诉讼司法实务，发现当前存在着少数民族语言文字诉讼程序混乱、不符合诉讼原理等问题，不利于民族语言文字诉讼权利的实现。究其原因，在于该诉讼制度缺乏程序保障。为了确保民族语言文字诉讼权利的有效实现，应设立“民汉双语诉讼规则”，以为司法机关提供统一的操作规范。民汉双语诉讼规则应该明确民汉双语诉讼的概念、类型以及民族语言文字诉讼权利的内容，并且根据不同诉讼类型有针对性地设置审判语言与诉讼语言的适用规则。     

Children's experiences with an intervention aimed to prevent further physical abuse

Although many children across cultures are victims of physical abuse, few treatment models target these children and their parents. In Sweden, Combined Parent–Child Cognitive Behavioural Therapy for families at risk for child physical abuse has been successfully used according to pretreatment and posttreatment studies. However, few studies have explored how physically abused children experience treatment. This study includes 20 physically abused children aged 9–17 who completed Combined Parent–Child Cognitive Behavioural Therapy. Children had a positive overall impression of the treatment and highlighted addressing the abuse, as well as processing their experiences as particularly essential. Children described a positive transformation in their family life as a result of treatment, including violence cessation and bonding among family members. Children experienced the intervention as inclusive and child‐friendly. The implications of the promising findings are discussed.     

Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.     

Modelling of connected processes

The problem of comparing, contrasting and combining information from different sets of data is an enduring one in many practical applications of statistics. A specific problem of combining information from different sources arose in integrating information from three different sets of data generated by three different sampling campaigns at the input stage as well as at the output stage of a grey-water treatment process. For each stage, a common process trend function needs to be estimated to describe the input and output material process behaviours. Once the common input and output process models are established, it is required to estimate the efficiency of the grey-water treatment method. A synthesized tool for modelling different sets of process data is created by assembling and organizing a number of existing techniques: (i) a mixed model of fixed and random effects, extended to allow for a nonlinear fixed effect, (ii) variogram modelling, a geostatistical technique, (iii) a weighted least squares regression embedded in an iterative maximum-likelihood technique to handle linear/nonlinear fixed and random effects and (iv) a formulation of a transfer-function model for the input and output processes together with a corresponding nonlinear maximum-likelihood method for estimation of a transfer function. The synthesized tool is demonstrated, in a new case study, to contrast and combine information from connected process models and to determine the change in one quality characteristic, namely pH, of the input and output materials of a grey-water filtering process.     

Improved communality estimation in factor analysis

The symmetric treatment of an asymmetric approach to factor analysis is shown to provide accurate communality estimates. In comparison with existing estimates including upper and lower bounds, the present approach is shown to be superior. In one example with known communalities, the present approach perfectly captures those communalities. In two empirical examples, it is shown to produce better communality estimates than any existing method.     

Healthy Barbs: Activism Confronts Mortality

Barbara Brenner, JD, was the Executive Director of Breast Cancer Action (BCA) from 1995–2010. Before that, she was a longtime activist in the anti-war movement and an attorney who, for most of her career, practiced public policy law. After she was diagnosed with breast cancer in 1993 at the age of 41, she took the helm of BCA. Under her leadership, the organization moved into a position of national advocacy—demanding research on the causes and prevention of breast cancer, including the role of industrial pollutants. Barbara started the “Think Before You Pink” campaign, encouraging people to question whether companies that display pink ribbons actually produce products that harm women's health or generate any funds to fight breast cancer. Her blog, “Healthy Barbs,” challenged readers to critique routine healthcare practices and policies. Barbara received numerous awards, including a Jefferson Award for Public Service in 2007, the Smith College Medal in 2012, and the ACLU-Northern California's Lola Hanzel Courageous Advocacy Award in 2012. Barbara had a recurrence of breast cancer in 1996. She died of complications associated with amyotrophic lateral sclerosis, ALS, on May 10, 2013.     

平等权的修辞功能研究

近年来,乙肝歧视、身高歧视和户籍歧视等主张同等对待的诉讼案件不断见诸报端。然而,深究这些案件中“平等权”的含义,不难发现,在日常生活中,“平等权”这一言辞将人们的注意焦点引向了追求“同等对待”上,而忽略了区分“同等”的正当标准。文章基于“平等”的多层次内涵,阐释“平等权”到底如何发挥对利益分配的合理化修辞功能的,进而结合案件探究解决各类歧视案件的有效途径。