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.     

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.     

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。     

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.     

Asymptotic expansions for sequential confidence levels in inverse linear regression

Non-linear renewal theory is used to derive second order asymptotic expansions for the coverage probability of a fixed-width sequential confidence interval for an unknown parameter xin the inverse linear regression model. These expansions are obtained for a two-stage sequential procedure, proposed by Perng and Tong (1974) for the construction of a confidence interval for x.     

Sequential estimation problems for negative exponential populations

The literature on sequential estimation problems for negative exponential populations has been reviewed here, We attempt to bring in all the published and unpublished materials known to us in a fairly coherent fashion. Both the concepts and theoretical findings are discussed.     

Group sequential monitoring based on the weighted log‐rank test statistic with the Fleming–Harrington class of weights in cancer vaccine studies

In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log‐rank tests with the Fleming–Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming–Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long‐term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log‐rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.