Cumulative cohort design for dose-finding

We introduce a new design for dose-finding in the context of toxicity studies for which it is assumed that toxicity increases with dose. The goal is to identify the maximum tolerated dose, which is taken to be the dose associated with a prespecified “target” toxicity rate. The decision to decrease, increase or repeat a dose for the next subject depends on how far an estimated toxicity rate at the current dose is from the target. The size of the window within which the current dose will be repeated is obtained based on the theory of Markov chains as applied to group up-and-down designs. But whereas the treatment allocation rule in Markovian group up-and-down designs is only based on information from the current cohort of subjects, the treatment allocation rule for the proposed design is based on the cumulative information at the current dose. We then consider an extension of this new design for clinical trials in which the subject's outcome is not known immediately. The new design is compared to the continual reassessment method.     

隐含期权对商业银行久期匹配策略的影响分析

随着利率市场化进程的发展,利率调整越来越频繁,利率波动的幅度也越来越大,隐含期权越来越多地嵌入在商业银行的资产负债项目中,成为利率风险管理的新难题。在识别、分解隐含期权以及理论分析隐含期权对久期模型影响的前提下,选择跳跃模型,并基于蒙特卡罗模拟方法,实证分析隐含期权对商业银行久期匹配策略的影响,得出如下结论:商业银行存贷款中无隐含期权的时候,久期匹配策略能很好的管理商业银行的利率风险;而当隐含期权存在时,使用有效久期匹配策略只能对冲久期不匹配风险,但是不能对冲由凸度缺口带来的隐含期权利率风险。     

行为金融理论的前沿发展

行为金融学就是以新的人性模式来研究不确定性环境下投资者决策行为的科学。它是对传统金融学如有效市场理论、套利定价理论等的创新,也反映了现代金融学研究的最新发展。而且行为金融理论地位的上升和理论的渐趋成熟也预示着金融理论研究范式与方法上的变革,预示现代经济学大变革的开始。本文试图对行为金融学作一点介绍,以便开拓学界的视野。     

Determinants of outcome in the pathways through care for children hearing voices

Auditory hallucination, or hearing voices, is generally associated with psychopathology. In psychiatry it is inter-preted as a symptom of an illness, with no connection to the individual's life history. Voice hallucinations in childhood occur in a variety of contexts and have variable long-term outcomes. Little is known about the course of the experience. In this study, 80 children and youngsters hearing voices were interviewed on four occasions over a period of three years about the content of the voices and their overall experience of voices, focusing on the determinants for a promising outcome in the pathways through care. The results indicate that the need for care in the context of the experience of voices is associated not only with high levels of problem behaviour and associated negative symptoms of psychosis, but also, independently, with an appraisal of the voices in terms of anxiety, depression, dissociation and frequency of occurrence. In 60 per cent of the participants the voices disappeared during the three-year research period. The relationship between the disappearance of voices and the course of mental health treatment is, however, ambiguous.     

An adaptive model switching approach for phase I dose‐finding trials

Model‐based phase I dose‐finding designs rely on a single model throughout the study for estimating the maximum tolerated dose (MTD). Thus, one major concern is about the choice of the most suitable model to be used. This is important because the dose allocation process and the MTD estimation depend on whether or not the model is reliable, or whether or not it gives a better fit to toxicity data. The aim of our work was to propose a method that would remove the need for a model choice prior to the trial onset and then allow it sequentially at each patient's inclusion. In this paper, we described model checking approach based on the posterior predictive check and model comparison approach based on the deviance information criterion, in order to identify a more reliable or better model during the course of a trial and to support clinical decision making. Further, we presented two model switching designs for a phase I cancer trial that were based on the aforementioned approaches, and performed a comparison between designs with or without model switching, through a simulation study. The results showed that the proposed designs had the advantage of decreasing certain risks, such as those of poor dose allocation and failure to find the MTD, which could occur if the model is misspecified. Copyright © 2013 John Wiley & Sons, Ltd.     

Designs foe phase i cancer clinical trials with differentiation of graded toxicity

For phase I cancer clinical trials, toxicity is a major concern. Commonly, toxicity is categorized to five levels of severity. In addition to the traditional standard dose-escaiation design, the Continual Reassessment Method (CRM) provides a promising alternative to estimate the maximum tolerated dose of a drug. However, in both standard design (STD) and CRM, the severity level of toxicity on grade 3/4 of a previous patient's response would not be a differentiated factor for the next dose level assignment. In this study, we extend the procedure incorporating the idea of unequal weights on the assessments of grade 3 and grade 4 toxicity in the dose escalation. The simulation results show that the proposed extended procedures by taking the impact of grade 4 toxicity into account, both for STD and CRM, reduce the chance of recommendation to the higher dose levels. Similar trends are observed for patient allocation to the higher levels. Additionally, for CRM which performs more accurately on the estimation of maximum tolerated dose (MTD), the proposed extended CRM maintains the same characteristic.     

Inference on the Minimum Effective Dose Using Binary Data

This article proposes a confidence interval procedure for an open question posted by Tamhane and Dunnett regarding the inference on the minimum effective dose of a drug for binary data. We use a partitioning approach in conjunction with a confidence interval procedure to provide a solution to this problem. Binary data frequently arise in medical investigations in connection with dichotomous outcomes such as the development of a disease or the efficacy of a drug. The proposed procedure not only detects the minimum effective dose of the drug, but also provides estimation information on the treatment effect of the closest ineffective dose. Such information benefits follow-up investigations in clinical trials. We prove that, when the confidence interval for the pairwise comparison has (or asymptotically controls) confidence level 1 ? α, the stepwise procedure strongly controls (or asymptotically controls) the familywise error rate at level α, which is a key criterion in dose finding. The new method is compared with other procedures in terms of power performance and coverage probability using simulations. The simulated results shed new light on the discernible features of the new procedure. An example on the investigation of acetaminophen is included.     

Some Classes of Estimators for Median Estimation in Survey Sampling

In this article, we have suggested some classes of estimators for estimating finite population median using information on an auxiliary variable. To study the properties of suggested classes of estimators under large sample approximation, a generalized class of estimators has been suggested with its properties. It has been shown that the suggested classes of estimators are more efficient than other existing estimators. The results have been illustrated through an empirical study.     

Weibull accelerated life tests when there are competing causes of failure

Accelerated life testing of a product under more severe than normal conditions is commonly used to reduce test time and costs. Data collected at such accelerated conditions are used to obtain estimates of the parameters of a stress translation function. This function is then used to make inference about the product's life under normal operating conditions. We consider the problem of accelerated life tests when the product of interest is a p component series system. Each of the components is assumed to have an independent Weibull time to failure distribution with different shape parameters and different scale parameters which are increasing functions stress. A general model i s used for the scale parameter includes the standard engineering models as special This model also has an appealing biological interpretation     

Step-Down Multiple Comparison Procedures Using Medians and Permutation Tests

Richter and McCann (2007 Richter , S. J. , McCann , M. H. ( 2007 ). Multiple comparisons using medians and permutation tests . Journal of Modern Applied Statistical Methods 6 ( 2 ): 399 – 412 . [Google Scholar]) presented a median-based multiple comparison procedure for assessing evidence of group location differences. The sampling distribution was based on the permutation distribution of the maximum median difference among all pairs, and provides strong control of the FWE. This idea is extended to develop a step-down procedure for comparing group locations. The new step-down procedure exploits logical dependencies between pairwise hypotheses and provides greater power than the single-step procedure, while still maintaining strong FWE control. The new procedure can also be a more powerful alternative to existing methods based on means, especially for heavy-tailed distributions.