Phase II trial design with growth modulation index as the primary endpoint

Molecularly targeted, genomic‐driven, and immunotherapy‐based clinical trials continue to be advanced for the treatment of relapse or refractory cancer patients, where the growth modulation index (GMI) is often considered a primary endpoint of treatment efficacy. However, there little literature is available that considers the trial design with GMI as the primary endpoint. In this article, we derived a sample size formula for the score test under a log‐linear model of the GMI. Study designs using the derived sample size formula are illustrated under a bivariate exponential model, the Weibull frailty model, and the generalized treatment effect size. The proposed designs provide sound statistical methods for a single‐arm phase II trial with GMI as the primary endpoint.     

From waterfall plots to spaghetti plots in early oncology clinical development

Waterfall plots are used to describe changes in tumor size observed in clinical studies. They are frequently used to illustrate the overall drug response in oncology clinical trials because of its simple representation of results. Unfortunately, this visual display suffers a number of limitations including (1) potential misguidance by masking the time dynamics of tumor size, (2) ambiguous labelling of the y‐axis, and (3) low data‐to‐ink ratio. We offer some alternatives to address these shortcomings and recommend moving away from waterfall plots to the benefit of plots showing the individual time profiles of sum of lesion diameters (according to RECIST). The spider plot presents the individual changes in tumor measurements over time relative to baseline tumor burden. Baseline tumor size is a well‐known confounding factor of drug effect which has to be accounted for when analyzing data in early clinical trials. While spider plots are conveniently correct for baseline tumor size, they cannot be presented in isolation. Indeed, percentage change from baseline has suboptimal statistical properties (including skewed distribution) and can be overly optimistic in favor of drug efficacy. We argued that plots of raw data (referred to as spaghetti plots) should always accompany spider plots to provide an equipoised illustration of the drug effect on lesion diameters.     

中国失独妇女总量、结构及变动趋势计算机仿真研究

在回顾以往对独生子女死亡和失独家庭研究的基础上，文章从基本概念、分析方法和关键研究问题等方面指出以往研究中存在的问题，提出终身失独概率估计方法和失独育龄妇女再生育可能性等，指出用独生子女死亡概念近似失独妇女，其结果有可能大大高估时期失独妇女的总量。由于受计划生育政策影响，中国育龄妇女二孩生育水平和生育模式发生巨大变化，将失独育龄妇女再生育看做是1－＞2递进生育也有可能高估失独妇女的总量。通过人口普查、抽样调查数据和计算机微观人口系统仿真分析技术，估计目前35岁及以上失独妇女数量在140万左右，2050年前中国时期失独妇女总量超过600万的可能性不大，失独家庭达到或超过1000万的可能性也不大。     

The claim that China's fertility restrictions contributed to the use of prenatal sex selection: A sceptical reappraisal

Most observers assume that China's fertility restrictions contribute to the use of prenatal sex selection. I question the logic and evidence underlying that assumption. Experts often stress that China's low fertility is largely voluntary, and that fertility restrictions are an unneeded safety valve. Others claim that China's ‘1.5-child’ loophole, common throughout rural areas, reinforces son preference or intensifies prenatal sex discrimination by hardening fertility constraints. These claims defy logic upon closer examination. Moreover, almost two-thirds of the exceptional distortion of the sex ratio in 1.5-child areas results from excess underreporting of daughters and enforced sex-specific stopping. Prenatal sex selection may explain the remaining third but probably reflects the stronger rural son preference that led to the 1.5-child loophole itself. The recent surge in sex selection of first births that has perpetuated the distortions also seems unrelated to policy. Some son-preferring parents who formerly wanted two children may now genuinely want only one.     

An investigation into the two‐stage meta‐analytic copula modelling approach for evaluating time‐to‐event surrogate endpoints which comprise of one or more events of interest

Clinical trials of experimental treatments must be designed with primary endpoints that directly measure clinical benefit for patients. In many disease areas, the recognised gold standard primary endpoint can take many years to mature, leading to challenges in the conduct and quality of clinical studies. There is increasing interest in using shorter‐term surrogate endpoints as substitutes for costly long‐term clinical trial endpoints; such surrogates need to be selected according to biological plausibility, as well as the ability to reliably predict the unobserved treatment effect on the long‐term endpoint. A number of statistical methods to evaluate this prediction have been proposed; this paper uses a simulation study to explore one such method in the context of time‐to‐event surrogates for a time‐to‐event true endpoint. This two‐stage meta‐analytic copula method has been extensively studied for time‐to‐event surrogate endpoints with one event of interest, but thus far has not been explored for the assessment of surrogates which have multiple events of interest, such as those incorporating information directly from the true clinical endpoint. We assess the sensitivity of the method to various factors including strength of association between endpoints, the quantity of data available, and the effect of censoring. In particular, we consider scenarios where there exist very little data on which to assess surrogacy. Results show that the two‐stage meta‐analytic copula method performs well under certain circumstances and could be considered useful in practice, but demonstrates limitations that may prevent universal use.     

主位—述位理论对英语写作的启示——以大学英语四级作文为例

本文旨在探讨主位—述位理论对英语写作的启示,使之具有实际应用意义。     

Human resource development practice: the paradox of empowerment and individualization

The main objective of the current paper is to point to the dualistic nature of HRD practice: employee empowerment strategy juxtaposed with high levels of individualization. HRD practice contributes to a series of dualities in organizations such as flexibility vs. loyalty, commitment vs. individualization and responsibility vs. alienation. The paper will argue that current HRD strategies have an individualistic role rather than an interactive and interpersonal influence for better knowledge sharing and organizational learning. The research implies that HRD should change its interventions in terms of how the individual is conceptualized to make knowledge actionable in social contexts to create favourable conditions for knowledge sharing and organizational learning.     

中国的生育率:到底下降了多少?

1990年代以来 ,中国的生育水平持续下降 ,已经进入低生育国家的行列。 2 0 0 0年人口普查 ,中国的总和生育率为 1 2 2 ,明显存在漏报。那么中国的生育率到底下降了多少 ?本文利用亲生子女法、生育史重构法和胎次递进比方法分析了 1 990年代生育率的下降过程 ,认为 2 0 0 0年总和生育率最准确的估计应为 1 5 8。通过分解总和生育率的变化 ,认为 1 990年代生育水平的下降 ,2 /5归因于结婚年龄的推迟 ,3/5归因于婚内生育率的下降     

Brief Communications: Gender Differences in Gambling Progression

The authors compared 39 women and 38 men entering an outpatient treatment program for pathological gambling. They were diagnosed according to DSM-IV and selected by SOGS, followed by a semi-structured interview for demography and progression of the gambling behavior prior to treatment. Women were more often single (59% vs. 26%; p = .005) and started gambling significantly later than men (34.2 vs. 20.4 years; p < .001). The progression of the disorder was more than 2 times faster in women than in men. There was no difference in the age of seeking treatment (44.7 vs. 42.3 years). Findings from this study resemble gender differences in other addictions—in particular the faster progression among women—challenge pharmacodynamic hypotheses for this phenomenon, and suggest gender into account when devising treatment strategies for pathological gambling.     

论基础教育中人文精神的培养

如何使我国的基础教育适合时代发展的需要,是我国教育改革面临的重要课题。本文首先从社会历史发展的进程分析了近现代以来与科技进步相伴的不仅仅是文明的进步,以及存在的诸多社会问题的原因,提出了在我国基础教育中应加强人文精神的培养。