Bayesian sample size determination for phase IIA clinical trials using historical data and semi‐parametric prior's elicitation

The Simon's two‐stage design is the most commonly applied among multi‐stage designs in phase IIA clinical trials. It combines the sample sizes at the two stages in order to minimize either the expected or the maximum sample size. When the uncertainty about pre‐trial beliefs on the expected or desired response rate is high, a Bayesian alternative should be considered since it allows to deal with the entire distribution of the parameter of interest in a more natural way. In this setting, a crucial issue is how to construct a distribution from the available summaries to use as a clinical prior in a Bayesian design. In this work, we explore the Bayesian counterparts of the Simon's two‐stage design based on the predictive version of the single threshold design. This design requires specifying two prior distributions: the analysis prior, which is used to compute the posterior probabilities, and the design prior, which is employed to obtain the prior predictive distribution. While the usual approach is to build beta priors for carrying out a conjugate analysis, we derived both the analysis and the design distributions through linear combinations of B‐splines. The motivating example is the planning of the phase IIA two‐stage trial on anti‐HER2 DNA vaccine in breast cancer, where initial beliefs formed from elicited experts' opinions and historical data showed a high level of uncertainty. In a sample size determination problem, the impact of different priors is evaluated.     

Efficient Inference for Longitudinal Data Varying‐coefficient Regression Models

Informative identification of the within‐subject correlation is essential in longitudinal studies in order to forecast the trajectory of each subject and improve the validity of inferences. In this paper, we fit this correlation structure by employing a time adaptive autoregressive error process. Such a process can automatically accommodate irregular and possibly subject‐specific observations. Based on the fitted correlation structure, we propose an efficient two‐stage estimator of the unknown coefficient functions by using a local polynomial approximation. This procedure does not involve within‐subject covariance matrices and hence circumvents the instability of calculating their inverses. The asymptotic normality of resulting estimators is established. Numerical experiments were conducted to check the finite sample performance of our method and an example of an application involving a set of medical data is also illustrated.     

中美经贸关系现状及经济发展差距的基本判断

2017年以来,中美两国之间发生了激烈的经贸摩擦,对两国宏观经济和社会福利产生一定的负面影响。中国社会科学院工业经济研究所与《中国经济学人》(China Economist)杂志从中美经贸关系现状、中美经贸摩擦影响、中美两国经济发展差距、美国总统大选等角度分析中国经济学人对中美经贸关系及经济发展差距的认知和判断。调查发现,经济学人认为虽然中美经贸摩擦短时间内难以消除,但中美两国的经济互补性仍很强,贸易增长空间较大,未来发展方向一定是合作与竞争并有。经济学人预判,今后20年中美两国的经济增速分别为4.8%和2.1%,中国将于2034年追平美国经济总量,将于2043年追平美国制造业总体技术水平,将于2072年追平美国人均GDP,实现赶超。     

Competition and Coordination in Two‐Tier Public Service Systems under Government Fiscal Policy

As a result of government budgetary limits and rapid market growth, many public service systems—such as health care—are characterized by extensive customer wait times that have become a serious problem. This problem might be solved by allowing private firms to enter these markets, which would provide customers with a choice between a free (governmental) public service provider (SP) and a fee‐charging (or “toll”) private SP. In such a two‐tier service system, the two SPs are differentiated by service quality and cost efficiency. This study focuses on the competition and coordination issues for two‐tier service systems with customers who are sensitive to both service quality and delay. The free system attempts to maximize its expected total customer utility with limited capacity, whereas the toll system attempts to maximize its profit. Neither goal is aligned with the social welfare goal of the public service. To achieve the social welfare goal, the government plays a crucial role in coordinating the two‐tier service system via the budget, the tradeoff of social members' goals, and tax‐subsidy policies. Using a mixed duopoly game, we establish Nash equilibrium strategies and identify the conditions for the existence of the two‐tier service system. We employ several interesting and counter‐intuitive managerial insights generated by the model to show that the public service can be delivered more efficiently via customer choice and SP competition. In addition, we show that a relatively low tax‐subsidy rate can almost perfectly coordinate the two SPs to achieve most of the maximum possible benefit of the two‐tier service system.     

Precise large deviations for the difference of two sums of END random variables with heavy tails

Assume that there are two types of insurance contracts in an insurance company, and the ith related claims are denoted by {X_ij, j ? 1}, i = 1, 2. In this article, the asymptotic behaviors of precise large deviations for non random difference ∑^n₁(t)_{j = 1}X_1j ? ∑^n₂(t)_{j = 1}X_2j and random difference ∑^N₁(t)_{j = 1}X_1j ? ∑^N₂(t)_{j = 1}X_2j are investigated, and under several assumptions, some corresponding asymptotic formulas are obtained.     

对明初重刑主义的再思考

在中国的历来的历史上,重刑政策做为镇压人民,维护王朝专制统治的重要手段,为古来不少封建王朝所使用,但要伦用法之严、用刑之广,杀戮之盛,首屈一指的要属明初了.但是明初的重刑并未使得社会安定,相反得是犯罪率的高频发和人民的不断反抗.所以我们要对明初重刑主义的错误进行反思,纠正我国在立法和司法实践中的重刑倾向,使得在社会中刑法的作用能真正表现出来.     

Adaptive phase I/II clinical trials for drug combination assessment in oncology using the outcomes of each cycle

Many new anticancer agents can be combined with existing drugs, as combining a number of drugs may be expected to have a better therapeutic effect than monotherapy owing to synergistic effects. Furthermore, to drive drug development and to reduce the associated cost, there has been a growing tendency to combine these as phase I/II trials. With respect to phase I/II oncology trials for the assessment of dose combinations, in the existing methodologies in which efficacy based on tumor response and safety based on toxicity are modeled as binary outcomes, it is not possible to enroll and treat the next cohort of patients unless the best overall response has been determined in the current cohort. Thus, the trial duration might be potentially extended to an unacceptable degree. In this study, we proposed a method that randomizes the next cohort of patients in the phase II part to the dose combination based on the estimated response rate using all the available observed data upon determination of the overall response in the current cohort. We compared the proposed method to the existing method using simulation studies. These demonstrated that the percentage of optimal dose combinations selected in the proposed method is not less than that in the existing method and that the trial duration in the proposed method is shortened compared to that in the existing method. The proposed method meets both ethical and financial requirements, and we believe it has the potential to contribute to expedite drug development.     

Construction of bivariate and multivariate weighted distributions via conditioning

Weighted distributions (univariate and bivariate) have received widespread attention over the last two decades because of their flexibility for analyzing skewed data. In this article, we propose an alternative method to construct a new family of bivariate and multivariate weighted distributions. For illustrative purposes, some examples of the proposed method are presented. Several structural properties of the bivariate weighted distributions including marginal distributions together with distributions of the minimum and maximum, evaluation of the reliability parameter, and verification of total positivity of order two are also presented. In addition, we provide some multivariate extensions of the proposed models. A real-life data set is used to show the applicability of these bivariate weighted distributions.     

Estimates of subgroup treatment effects in overall nonsignificant trials: To what extent should we believe in them?

In drug development, it sometimes occurs that a new drug does not demonstrate effectiveness for the full study population but appears to be beneficial in a relevant subgroup. In case the subgroup of interest was not part of a confirmatory testing strategy, the inflation of the overall type I error is substantial and therefore such a subgroup analysis finding can only be seen as exploratory at best. To support such exploratory findings, an appropriate replication of the subgroup finding should be undertaken in a new trial. We should, however, be reasonably confident in the observed treatment effect size to be able to use this estimate in a replication trial in the subpopulation of interest. We were therefore interested in evaluating the bias of the estimate of the subgroup treatment effect, after selection based on significance for the subgroup in an overall “failed” trial. Different scenarios, involving continuous as well as dichotomous outcomes, were investigated via simulation studies. It is shown that the bias associated with subgroup findings in overall nonsignificant clinical trials is on average large and varies substantially across plausible scenarios. This renders the subgroup treatment estimate from the original trial of limited value to design the replication trial. An empirical Bayesian shrinkage method is suggested to minimize this overestimation. The proposed estimator appears to offer either a good or a conservative correction to the observed subgroup treatment effect hence provides a more reliable subgroup treatment effect estimate for adequate planning of future studies.     

“一体两翼”人才培养模式下《财务管理》课程教学改革

所谓的"一体两翼","一体"是以学校培养为主体,"两翼"是以满足面向国内、国际人才需要进行培养为两翼。对于广西地方高校来说,面向国际市场主要是满足面向中国—东盟自由贸易区对人才的需要进行培养。文章初步总结了"一体两翼"人才培养模式下《财务管理》课程教学方法、教学内容以及考核方式的一些尝试,以期对改革财会人才的培养机制起到一定的作用。