The precision of regression-type estimator for incremental cost–effectiveness ratio

The estimation of incremental cost–effectiveness ratio (ICER) has received increasing attention recently. It is expressed in terms of the ratio of the change in costs of a therapeutic intervention to the change in the effects of the intervention. Despite the intuitive interpretation of ICER as an additional cost per additional benefit unit, it is a challenge to estimate the distribution of a ratio of two stochastically dependent distributions. A vast literature regarding the statistical methods of ICER has developed in the past two decades, but none of these methods provide an unbiased estimator. Here, to obtain the unbiased estimator of the cost–effectiveness ratio (CER), the zero intercept of the bivariate normal regression is assumed. In equal sample sizes, the Iman–Conover algorithm is applied to construct the desired variance–covariance matrix of two random bivariate samples, and the estimation then follows the same approach as CER to obtain the unbiased estimator of ICER. The bootstrapping method with the Iman–Conover algorithm is employed for unequal sample sizes. Simulation experiments are conducted to evaluate the proposed method. The regression-type estimator performs overwhelmingly better than the sample mean estimator in terms of mean squared error in all cases.     

Utilizing Bayesian predictive power in clinical trial design

The Bayesian paradigm provides an ideal platform to update uncertainties and carry them over into the future in the presence of data. Bayesian predictive power (BPP) reflects our belief in the eventual success of a clinical trial to meet its goals. In this paper we derive mathematical expressions for the most common types of outcomes, to make the BPP accessible to practitioners, facilitate fast computations in adaptive trial design simulations that use interim futility monitoring, and propose an organized BPP-based phase II-to-phase III design framework.     

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.     

Predictive Hierarchic Modeling of Operational Characteristics in Clinical Trials

An analytic methodology for patient enrollment modeling using a Poisson-gamma model is developed by Anisimov & Fedorov (2005–2007). For modeling hierarchic processes associated with enrollment, a new methodology using evolving stochastic processes is proposed. This provides rather general and unified framework to describe various operational processes associated with enrollment. The technique for calculating predictive distributions, mean, and credibility bounds for evolving processes is developed. Some applications to modeling operational characteristics in clinical trials are considered with focus to modeling events associated with incoming and follow-up patients in different settings. For these models, predictive characteristics are derived in a closed form.     

知识产权“十二五”发展规划实施的关键难题与机遇研究

知识产权＂十二五＂发展规划具有多重属性与复杂性、制定组织结构多元化、地区发展不平衡及其与环境匹配较难等特点,较薄弱的知识产权基础因素与国际发展动态影响下,使得我国知识产权＂十二五＂发展规划实施挑战与机遇并存。     

一个人的绞刑架——从苔丝看哈代的悲剧观

《德伯家的苔丝》是英国著名小说家托马斯.哈代的悲剧代表作。透过作品品读作者哈代的悲剧观,这种悲剧观不是让人痛让人哭,而是让人以一种淡淡的忧伤感受悲观,以局外人的淡定感受一种注定如此、必然这样的悲剧生成。哈代通过笔下的人物让读者看到他对待悲剧的态度,直接面对并坦然接受这种结局。     

有效提高远程学习者自主学习的策略

本文通过对远程学习者自主学习的现状分析，提出相应的策略以帮助学员更有效地开展和提高远程自主学习。     

Randomization tests in recursive response-adaptive randomization procedures

In a randomized clinical trial, response-adaptive randomization procedures use the information gathered, including the previous patients' responses, to allocate the next patient. In this setting, we consider randomization-based inference. We provide an algorithm to obtain exact p-values for statistical tests that compare two treatments with dichotomous responses. This algorithm can be applied to a family of response adaptive randomization procedures which share the following property: the distribution of the allocation rule depends only on the imbalance between treatments and on the imbalance between successes for treatments 1 and 2 in the previous step. This family includes some outstanding response adaptive randomization procedures. We study a randomization test to contrast the null hypothesis of equivalence of treatments and we show that this test has a similar performance to that of its parametric counterpart. Besides, we study the effect of a covariate in the inferential process. First, we obtain a parametric test, constructed assuming a logit model which relates responses to treatments and covariate levels, and we give conditions that guarantee its asymptotic normality. Finally, we show that the randomization test, which is free of model specification, performs as well as the parametric test that takes the covariate into account.     

电动空调涡旋压缩机型线优化

选取我国三大经济区2001—2017年的数据,运用面板数据模型分析了政府财政、金融市场及其相互作用对区域自主创新能力提升的影响,结果表明:政府财政对自主创新能力的提升作用较金融市场更为显著,但三大经济区存在差异;就全国总体而言,金融支持效率指标在是否存在政府中介的情况下均不显著,金融市场对自主创新的支持效率还很低下;误差修正模型表明区域自主创新能力提升还受自身前期自主创新能力水平影响;人力资本的投入对区域自主创新能力的提升起到至关重要的作用。     

中、韩两国大学自主招生政策的比较研究

中韩两国的历史文化以及价值观存在很大的相似性,因此,两国的大学自主招生政策在政策性质、政策价值取向、适用范围以及政策的实际效果方面存在较大的可比较性。而正是两者之间的差异性启示我们：中国的自主招生政策应该坚持统一高考以保证公正性,扩大自主招生以保证多样性;实现大学与中学“双向”联动改革,建立综合多元化的录取机制;理顺政府、高校与社会的关系,构建高校自主招生的监督机制。