Modifications of sequential designs in bioequivalence trials

Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/ . Copyright © 2015 John Wiley & Sons, Ltd.     

腔内电光调制激光系统的混沌模拟

采用数值模拟的方法讨论了带反馈的腔內电光调制激光系统功率输出的分叉和混沌行为,得到了输出功率随控制参数变化的分叉图,和一些定量结果。     

A general inverse sampling scheme and its application to adaptive cluster sampling

Not having a variance estimator is a seriously weak point of a sampling design from a practical perspective. This paper provides unbiased variance estimators for several sampling designs based on inverse sampling, both with and without an adaptive component. It proposes a new design, which is called the general inverse sampling design, that avoids sampling an infeasibly large number of units. The paper provide estimators for this design as well as its adaptive modification. A simple artificial example is used to demonstrate the computations. The adaptive and non‐adaptive designs are compared using simulations based on real data sets. The results indicate that, for appropriate populations, the adaptive version can have a substantial variance reduction compared with the non‐adaptive version. Also, adaptive general inverse sampling with a limitation on the initial sample size has a greater variance reduction than without the limitation.     

连续时延神经网络的Hopf分岔现象研究

讨论了带连续时延神经网络的Hopf分岔现象。对于强核和弱核的情况,利用平均时延作为分岔参数,证明了模型经历了Hopf分岔过程。在带弱核的神经网络模型中,得到了分岔周期解稳定性准则。给出了一些数值例子,通过计算机仿真验证了所得结论的正确性。     

Sampling from spatial databases

This paper deals with techniques for obtaining random point samples from spatial databases. We seek random points from a continuous domain (usually ²) which satisfy a spatial predicate that is represented in the database as a collection of polygons. Several applications of spatial sampling (e.g. environmental monitoring, agronomy, forestry, etc) are described. Sampling problems are characterized in terms of two key parameters: coverage (selectivity), and expected stabbing number (overlap). We discuss two fundamental approaches to sampling with spatial predicates, depending on whether we sample first or evaluate the predicate first. The approaches are described in the context of both quadtrees and R-trees, detailing the sample first, acceptance/rejection tree, and partial area tree algorithms. A sequential algorithm, the one-pass spatial reservoir algorithm is also described. The relative performance of the various sampling algorithms is compared and choice of preferred algorithms is suggested. We conclude with a short discussion of possible extensions.     

非对称情况下的多物品拍卖

本文讨论当投标人之间存在不同的预算约束时两物品的序贯增价拍卖,对于物品之间不同的关系(互补、替代或者不相干的关系),物品价值大小的不同及与预算大小之间的关系,在一个简单的完全信息模型下,我们分不同情况讨论投标人的均衡出价策略,并发现对卖方来说,先拍卖价值高的物品是弱占优的策略。     

延迟决策对一类产出系统演化的影响研究

企业作为有限理性的经济主体,在做下阶段的生产决策时可能不仅考虑本期而是要综合考虑以往连续多期的边际利润情况。研究表明,加入时滞以后,系统纳什平衡点的稳定域明显扩大,从而为在混沌经济系统中实现倍周期分岔控制提供了现实途径,同时,还会使系统在纳什平衡点出现hopf分岔等新的动力学演化行为。而且,以累积利润为指标的系统表现可以得到改善。首先引入延迟决策的企业将获得更大的相对竞争优势。而在两家企业都引入延迟决策的情况下,伴随第二家企业产量调整速度的增加,它们将交替获得竞争优势。     

Robust block bootstrap panel predictability tests*

This article develops two block bootstrap-based panel predictability test procedures that are valid under very general conditions. Some of the allowable features include cross-sectional dependence, heterogeneous predictive slopes, persistent predictors, and complex error dynamics, including cross-unit endogeneity. While the first test procedure tests if there is any predictability at all, the second procedure determines the units for which predictability holds in case of a rejection by the first. A weak unit root framework is adopted to allow persistent predictors, and a novel theory is developed to establish asymptotic validity of the proposed bootstrap. Simulations are used to evaluate the performance of our tests in small samples, and their implementation is illustrated through an empirical application to stock returns.     

Sequential Hypothesis Tests for Identifying the Minimum Dose with a Threshold Effect

We propose a procedure to identify a lowest dose having greater effect than a threshold dose under the assumption of monotonicity of dose mean response in dose response test. So, we use statistics based on contrasts among sample means and apply a group sequential procedure to our procedure to identify effectively the dose. If we can identify the dose at an early step in the sequential test, since we can terminate the procedure with a few observations, the procedure is useful from an economical point of view. In a simulation studies, we compare the superiority among these procedures based on three contrasts.     

Bayesian blinded sample size re-estimation

Information before unblinding regarding the success of confirmatory clinical trials is highly uncertain. Current techniques using point estimates of auxiliary parameters for estimating expected blinded sample size: (i) fail to describe the range of likely sample sizes obtained after the anticipated data are observed, and (ii) fail to adjust to the changing patient population. Sequential MCMC-based algorithms are implemented for purposes of sample size adjustments. The uncertainty arising from clinical trials is characterized by filtering later auxiliary parameters through their earlier counterparts and employing posterior distributions to estimate sample size and power. The use of approximate expected power estimates to determine the required additional sample size are closely related to techniques employing Simple Adjustments or the EM algorithm. By contrast with these, our proposed methodology provides intervals for the expected sample size using the posterior distribution of auxiliary parameters. Future decisions about additional subjects are better informed due to our ability to account for subject response heterogeneity over time. We apply the proposed methodologies to a depression trial. Our proposed blinded procedures should be considered for most studies due to ease of implementation.