A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail.     

国有控股上市公司股权激励机制研究

我国国有控股上市公司实施经营者股权激励机制有其理论基础与实践效用支持。文章通过对国有控股上市公司实施股权激励的本土环境考察,认为要实现经营者股权激励机制的预期效果,强化国有控股上市公司监督机制,制定科学的经营业绩考核指标和恰当的业绩考核标准,是股权激励机制实施的关键,同时应充分发挥中国特色社会主义优势,采取精神激励等多种辅助激励手段。     

《看得见风景的房间》中的父亲形象研究

由于自身生活经历的影响,福斯特的作品中经常缺乏父亲形象,而福斯特小说中的“父亲”问题也很少受到关注。拉康关于父亲的理论受到广泛关注,这一理论认为,父亲-母亲-孩子的三角结构是组成稳定家庭的关键因素。父亲的缺失会使这一稳定结构遭到破坏,但是,由于父亲缺失遗留下的位置会由他人或他物来填补,父亲的缺失也是象征性的。在福斯特作品《看得见风景的房间》中,父亲的缺失就是象征性的,父亲对女儿的监控作用通过其他人物得到了实现,文本中缺失的仅是父亲的形象,父亲的声音却是贯穿始终的。     

A computationally simple bivariate survival estimator for efficacy and safety

Both treatment efficacy and safety are typically the primary endpoints in Phase II, and even in some Phase III, clinical trials. Efficacy is frequently measured by time to response, death, or some other milestone event and thus is a continuous, possibly censored, outcome. Safety, however, is frequently measured on a discrete scale; in Eastern Cooperative Oncology Group clinical trial E2290, it was measured as the number of weekly rounds of chemotherapy that were tolerable to colorectal cancer patients. For the joint analysis of efficacy and safety, we propose a non-parametric, computationally simple estimator for the bivariate survival function when one time-to-event is continuous, one is discrete, and both are subject to right-censoring. The bivariate censoring times may depend on each other, but they are assumed to be independent of both event times. We derive a closed-form covariance estimator for the survivor function which allows for inference to be based on any of several possible statistics of interest. In addition, we derive its covariance with respect to calendar time of analysis, allowing for its use in sequential studies.     

非对称基坑开挖监测位移下数值对比分析

以南京市青奥轴线地下交通工程主隧道基坑非对称开挖水平位移监测数据为依据,对水平位移监测值与ABAQUS数值模拟值进行对比分析。得出结论:墙体水平位移首先是悬臂开挖的墙顶向外发生三角形分布的位移,然后随着支撑的架设,墙体发生转动,数值模拟值与实际监测值基本符合;在开挖面附近的土压力,随着墙体高度的增加而增大;在支撑以上部分,模拟值要小于计算值,而在开挖面以下部分,则模拟值大于计算值;随着悬臂段开挖深度的增加,悬臂段最大土压力值也在逐渐增加,墙底土压力值在逐渐减小。     

A Bayesian sequential design with binary outcome

Several researchers have proposed solutions to control type I error rate in sequential designs. The use of Bayesian sequential design becomes more common; however, these designs are subject to inflation of the type I error rate. We propose a Bayesian sequential design for binary outcome using an alpha‐spending function to control the overall type I error rate. Algorithms are presented for calculating critical values and power for the proposed designs. We also propose a new stopping rule for futility. Sensitivity analysis is implemented for assessing the effects of varying the parameters of the prior distribution and maximum total sample size on critical values. Alpha‐spending functions are compared using power and actual sample size through simulations. Further simulations show that, when total sample size is fixed, the proposed design has greater power than the traditional Bayesian sequential design, which sets equal stopping bounds at all interim analyses. We also find that the proposed design with the new stopping for futility rule results in greater power and can stop earlier with a smaller actual sample size, compared with the traditional stopping rule for futility when all other conditions are held constant. Finally, we apply the proposed method to a real data set and compare the results with traditional designs.     

Monitoring the parameter vector of regression models with time-to-event response in phase II processes

In most of the existing specialized literature, monitoring regression models are a special case of profile monitoring. However, not every regression model always represents appropriately a profile data structure. This is clearly the case of the Weibull regression model (WRM) with common shape parameter γ. Even though it might be thought that existing methodologies (especially likelihood-ratio (LRT)-based methods) for monitoring generalized linear profiles can also be successfully applied to monitoring regression models with time-to-event response, it will be shown in this paper that those methodologies work fairly acceptable just for data structures with 1000 observations at least approximately. It was found out that some corrections, often referred to as Bartlett's adjustments, are needed to be implemented in order to improve the accuracy of using the asymptotic distributional properties of the LRT statistic for carrying out the monitoring of WRM with relatively small and moderate dimensions of the available datasets. Simulation studies suggest that the use of the aforementioned corrections make the resulting charts work quite acceptable when available data structures contain 30 observations at least. Detection abilities of the proposed schemes improve as dataset dimension increases.     

New V control chart for the Maxwell distribution

Control charts have been popularly used as a user-friendly yet technically sophisticated tool to monitor whether a process is in statistical control or not. These charts are basically constructed under the normality assumption. But in many practical situations in real life this normality assumption may be violated. One such non-normal situation is to monitor the process variability from a skewed parent distribution where we propose the use of a Maxwell control chart. We introduce a pivotal quantity for the scale parameter of the Maxwell distribution which follows a gamma distribution. Probability limits and L-sigma limits are studied along with performance measure based on average run length and power curve. To avoid the complexity of future calculations for practitioners, factors for constructing control chart for monitoring the Maxwell parameter are given for different sample sizes and for different false alarm rate. We also provide simulated data to illustrate the Maxwell control chart. Finally, a real life example has been given to show the importance of such a control chart.