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.     

A Bayesian adaptive design for biosimilar trials with time-to-event endpoint

A biosimilar drug is a biological product that is highly similar to and at the same time has no clinically meaningful difference from licensed product in terms of safety, purity, and potency. Biosimilar study design is essential to demonstrate the equivalence between biosimilar drug and reference product. However, existing designs and assessment methods are primarily based on binary and continuous endpoints. We propose a Bayesian adaptive design for biosimilarity trials with time-to-event endpoint. The features of the proposed design are twofold. First, we employ the calibrated power prior to precisely borrow relevant information from historical data for the reference drug. Second, we propose a two-stage procedure using the Bayesian biosimilarity index (BBI) to allow early stop and improve the efficiency. Extensive simulations are conducted to demonstrate the operating characteristics of the proposed method in contrast with some naive method. Sensitivity analysis and extension with respect to the assumptions are presented.     

Bayesian MARS

A Bayesian approach to multivariate adaptive regression spline (MARS) fitting (Friedman, 1991) is proposed. This takes the form of a probability distribution over the space of possible MARS models which is explored using reversible jump Markov chain Monte Carlo methods (Green, 1995). The generated sample of MARS models produced is shown to have good predictive power when averaged and allows easy interpretation of the relative importance of predictors to the overall fit.     

城市废弃物资源化共生网络脆弱性影响机制——基于SCP与CAS融合的分析视角

在内外因素的交互干扰下,城市废弃物资源化共生网络表现得格外脆弱,探寻其脆弱性的理论内涵、影响因素及其作用机制是开展脆弱性治理的前提。借鉴复杂系统脆弱性理论,从能力和绩效两个角度解析其理论内涵,指出系统脆弱性在能力上可以用敏感性、适应性和恢复力予以刻画,在绩效上表现为增值性不强、共享性不足和生态性不佳。通过梳理国内外研究文献,从共生单元、网络结构、共生机制、网络氛围和环境不确定性5个维度提炼出脆弱性影响因素;以网络动态能力为结合点,将SCP（Structure Conduct Performance）和CAS（Complexity Adaptive System）两种理论有机融合,构建一个以共生单元素质、网络结构特征、共生机制属性、政策有效性为外因变量,以网络动态能力为中介变量,以网络脆弱性为结果变量,以网络氛围和环境不确定性为调节变量的理论框架。未来可利用大样本调查方法对该理论框架进行实证检验,探讨城市废弃物资源化共生网络脆弱性的形成机理。     

Adaptive designs for IVPT data with mixed scaled average bioequivalence

In vitro permeation tests (IVPT) offer accurate and cost-effective development pathways for locally acting drugs, such as topical dermatological products. For assessment of bioequivalence, the FDA draft guidance on generic acyclovir 5% cream introduces a new experimental design, namely the single-dose, multiple-replicate per treatment group design, as IVPT pivotal study design. We examine the statistical properties of its hypothesis testing method—namely the mixed scaled average bioequivalence (MSABE). Meanwhile, some adaptive design features in clinical trials can help researchers make a decision earlier with fewer subjects or boost power, saving resources, while controlling the impact on family-wise error rate. Therefore, we incorporate MSABE in an adaptive design combining the group sequential design and sample size re-estimation. Simulation studies are conducted to study the passing rates of the proposed methods—both within and outside the average bioequivalence limits. We further consider modifications to the adaptive designs applied for IVPT BE trials, such as Bonferroni's adjustment and conditional power function. Finally, a case study with real data demonstrates the advantages of such adaptive methods.     

基于自适应迭代更新的函数型数据聚类方法研究

函数型数据的稀疏性和无穷维特性使得传统聚类分析失效。针对此问题,本文在界定函数型数据概念与内涵的基础上提出了一种自适应迭代更新聚类分析。首先,基于数据参数信息实现无穷维函数空间向有限维多元空间的过渡;在此基础上,依据变量信息含量的差异构建了自适应赋权聚类统计量,并依此为函数型数据的相似性测度进行初始类别划分;进一步地,在给定阈值限制下,对所有函数的初始类别归属进行自适应迭代更新,将收敛的优化结果作为最终的类别划分。随机模拟和实证检验表明,与现有的同类函数型聚类分析相比,文中方法的分类正确率显著提高,体现了新方法的相对优良性和实际问题应用中的有效性。     

Detection of multiple undocumented change-points using adaptive Lasso

The problem of detecting multiple undocumented change-points in a historical temperature sequence with simple linear trend is formulated by a linear model. We apply adaptive least absolute shrinkage and selection operator (Lasso) to estimate the number and locations of change-points. Model selection criteria are used to choose the Lasso smoothing parameter. As adaptive Lasso may overestimate the number of change-points, we perform post-selection on change-points detected by adaptive Lasso using multivariate t simultaneous confidence intervals. Our method is demonstrated on the annual temperature data (year: 1902–2000) from Tuscaloosa, Alabama.     

Cycles of Adaptive Strategies Over the Life Course

An increasing number of Australia’s ageing population are aging with long-term physical impairments. This study explored the life experiences of this group using a qualitative approach. In-depth interviews were conducted with 10 disabled Victorians, aged between 51 and 84 years, and an inductive thematic analysis undertaken. A relationship was found between the adaptive strategies that participants developed as they moved through life phases and the impairment stages. The implications of the emergence of a cyclical process of adaptation across the life course. and particularly in respect of aging, delivery of aged-care services and social workers in this sector are discussed.     

侠气与民情：19世纪中叶地方军事化演变中的社会转型

太平天国运动对晚清帝国的冲击不仅体现在财政税收、人口、土地关系等社会结构要素上,更重要的是人心与世风之变以及由此形成的新的社会民情基础。这一世风丕变特别体现在：地方为应对太平军冲击而进行的军事化运动中伴生的失范型暴力,是以“任侠之气”的精神伦理作为军事动员的内在组织原则而导致的后果。“侠气”这一精神伦理以“力”的无限扩张为法则,与传统帝国政治结构中的宗法、乡礼、师道以及凝结在地权上的依附关系形成巨大张力,由此造成军事化组织与国家政治的背离。“力”的无限扩张法则打碎了帝国政治所依赖的身份与等级结构,导致了夷平化的社会形态出现,从而对传统政治治理构成挑战,并最终召唤了用现代革命的方式推进政治和社会变迁的时代的到来。     

城乡公共服务均等化建设中公共投资及其作用领域探析

针对地区经济发展不平衡,国家对城乡公共服务均等化建设的主要支持方式仍以税收优惠和财政补贴为主,但实践表明这种方式效果有限。国内外经验证明在财力有限的情况下,公共投资在促进城乡公共服务均等化建设中具有明显优势,因此我国必须重视公共投资在城乡公共服务均等化建设中的作用,明确公共投资在城乡公共服务建设中的投资领域,以促进城乡统筹发展。