Response‐adaptive designs for binary responses: How to offer patient benefit while being robust to time trends?

Response‐adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates. There is considerable interest in using RAR designs in drug development for rare diseases, where traditional designs are not either feasible or ethically questionable. In this paper, we discuss and address a major criticism levelled at RAR: namely, type I error inflation due to an unknown time trend over the course of the trial. The most common cause of this phenomenon is changes in the characteristics of recruited patients—referred to as patient drift. This is a realistic concern for clinical trials in rare diseases due to their lengthly accrual rate. We compute the type I error inflation as a function of the time trend magnitude to determine in which contexts the problem is most exacerbated. We then assess the ability of different correction methods to preserve type I error in these contexts and their performance in terms of other operating characteristics, including patient benefit and power. We make recommendations as to which correction methods are most suitable in the rare disease context for several RAR rules, differentiating between the 2‐armed and the multi‐armed case. We further propose a RAR design for multi‐armed clinical trials, which is computationally efficient and robust to several time trends considered.     

An algorithmic approach to construct D-optimal saturated designs for logistic model

In this paper, locally D-optimal saturated designs for a logistic model with one and two continuous input variables have been constructed by modifying the famous Fedorov exchange algorithm. A saturated design not only ensures the minimum number of runs in the design but also simplifies the row exchange computation. The basic idea is to exchange a design point with a point from the design space. The algorithm performs the best row exchange between design points and points form a candidate set representing the design space. Naturally, the resultant designs depend on the candidate set. For gain in precision, intuitively a candidate set with a larger number of points and the low discrepancy is desirable, but it increases the computational cost. Apart from the modification in row exchange computation, we propose implementing the algorithm in two stages. Initially, construct a design with a candidate set of affordable size and then later generate a new candidate set around the points of design searched in the former stage. In order to validate the optimality of constructed designs, we have used the general equivalence theorem. Algorithms for the construction of optimal designs have been implemented by developing suitable codes in R.     

The competing risks analysis for parallel and series systems using Type-II progressive censoring

Abstract

Recently, the study of the lifetime of systems in reliability and survival analysis in the presence of several causes of failure (competing risks) has attracted attention in the literature. In this paper, series and parallel systems with exponential lifetime for each item of the system are considered. Several causes of failure independently affect lifetime distributions and observations of failure times of the systems are considered under progressive Type-II censored scheme. For series systems, the maximum likelihood estimates of parameters are computed and confidence intervals for parameters of the model are obtained using Fisher information matrix. For parallel systems, the generalized EM algorithm which uses the Newton-Raphson algorithm inside the EM algorithm is used to compute the maximum likelihood estimates of parameters. Also, the standard errors of the maximum likelihood estimates are computed by using the supplemented EM algorithm. The simulation study confirms the good performance of the introduced approach.     

考虑异质性行为的灾后应急物资动态调度优化

在以人道主义为本的应急救援活动中，不可忽视被救灾民和施救决策者们异质性行为的影响。一方面，将各灾民因救援物资需求未被及时满足而呈现的差异化心理痛苦度量成经济损失，并纳入应急救援调度的社会成本这一决策目标中；另一方面，在灾后物资调度决策中，关注具有异质性偏好的各应急决策者所展现出的不同救援态度。结合面向联合机会约束规划的动态供需平衡限制，最终构建一个考虑灾民和决策者们异质性行为的多阶段灾后救援物资分配和应急路径优化模型。采用2008年汶川地震为案例背景，应用遗传算法对模型求解和参数分析，将仿真结果与不考虑异质性行为的传统救援调度方案进行比较，得出一些结论为构建高效的应急救援体系提供有益参考。     

Multi-objective optimization in partitioning the healthcare system of Parana State in Brazil

Motivated by a proposal of the local authority for improving the existing healthcare system in the Parana State in Brazil, this article presents an optimization-based model for developing a better system for patients by aggregating various health services offered in the municipalities of Parana into some microregions. The problem is formulated as a multi-objective partitioning of the nodes of an undirected graph (or network) with the municipalities as the nodes and the roads connecting them as the edges of the graph. Maximizing the population homogeneity in the microregions, maximizing the variety of medical procedures offered in the microregions, and minimizing the inter-microregion distances to be traveled by patients are considered as three objective functions of the problem. An integer-coded multi-objective genetic algorithm is adopted as the optimization tool, which yields a significant improvement to the existing healthcare system map of the Parana State. The results obtained may have a strong impact on the healthcare system management in Parana. The model proposed here could be a useful tool to aid the decision-making in health management, as well as for better organization of any healthcare system, including those of other Brazilian States.     

Estimation and Properties of a Time-Varying EGARCH(1,1) in Mean Model

Time-varying GARCH-M models are commonly employed in econometrics and financial economics. Yet the recursive nature of the conditional variance makes likelihood analysis of these models computationally infeasible. This article outlines the issues and suggests to employ a Markov chain Monte Carlo algorithm which allows the calculation of a classical estimator via the simulated EM algorithm or a simulated Bayesian solution in only O(T) computational operations, where T is the sample size. Furthermore, the theoretical dynamic properties of a time-varying-parameter EGARCH(1,1)-M are derived. We discuss them and apply the suggested Bayesian estimation to three major stock markets.     

Mixtures of regression models with incomplete and noisy data

The estimation of the mixtures of regression models is usually based on the normal assumption of components and maximum likelihood estimation of the normal components is sensitive to noise, outliers, or high-leverage points. Missing values are inevitable in many situations and parameter estimates could be biased if the missing values are not handled properly. In this article, we propose the mixtures of regression models for contaminated incomplete heterogeneous data. The proposed models provide robust estimates of regression coefficients varying across latent subgroups even under the presence of missing values. The methodology is illustrated through simulation studies and a real data analysis.     

Mixtures of Gaussian copula factor analyzers for clustering high dimensional data

Mixtures of factor analyzers is a useful model-based clustering method which can avoid the curse of dimensionality in high-dimensional clustering. However, this approach is sensitive to both diverse non-normalities of marginal variables and outliers, which are commonly observed in multivariate experiments. We propose mixtures of Gaussian copula factor analyzers (MGCFA) for clustering high-dimensional clustering. This model has two advantages; (1) it allows different marginal distributions to facilitate fitting flexibility of the mixture model, (2) it can avoid the curse of dimensionality by embedding the factor-analytic structure in the component-correlation matrices of the mixture distribution.An EM algorithm is developed for the fitting of MGCFA. The proposed method is free of the curse of dimensionality and allows any parametric marginal distribution which fits best to the data. It is applied to both synthetic data and a microarray gene expression data for clustering and shows its better performance over several existing methods.     

舆论危机的异化极化效应研究

随着Web2.0时代的到来,网络媒体逐渐成为舆论生成、传播和交锋的主阵地,舆论危机的形成及其异化也成为日益突出的社会风险问题.本文以舆论的异化演化机理为研究对象,通过梳理典型事件舆论话题的异化过程,对其基本内涵、表现形式和演化模式等进行系统总结.随后,研究以舆论超网络模型为基础,借鉴社会影响理论的基本原则,提出舆论异化机理的极化算法,并对其具体流程进行解析和实现.最后,本文以“7·23甬温动车事故”为例,对舆论危机的异化极化过程和影响因素进行系统仿真和实证分析.     

基于蚁群算法参数的最优选择问题研究

蚁群算法是受现实蚂蚁群体行为启发而得出的一类仿生算法。通过对蚁群算法中影响算法性能的参数进行分析和研究,并对蚁群算法中参数的最优选择问题进行实验分析,从而给出算法参数的最佳取值范围,以利于算法在实际问题中的应用和推广.