Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

行政耦合、新型关系网络及其于乡村治理的作用机制研究

作为中国特色的政府治理策略定制，“行政耦合”是指政府或政府行为通过一系列途径实现与乡村社会权力结构的有效融合，从而实现政府有效治理的政策工具。这种工具在乡村治理中表现出运作主体多元化、服务导向、协同合作的运作特征。本文以贵州省新民镇的“四在农家，美丽乡村”建设作为案例样本，分析基层政府“行政耦合”所形成的新型耦合式关系网络对乡村治理的作用机制。这种新型耦合式关系网络是政府体制吸纳与乡村社会政治参与的均衡演进的结果，二者的交互作用促进和强化乡村治理目标的实现，展现了其各自的价值。在乡村振兴战略背景下，对其在乡村治理实践中“沁润式”发展所产生的深层矛盾和风险进行反思，以期为乡村治理提供理论指引和实践参考。     

村庄非农化、社会资本与农民家庭收入

聚焦于社会资本影响农民收入的微观和宏观机制，利用中国家庭动态追踪调查数据构建“家庭—村庄”两个层次的交互模型，考察了不同生产情景下社会资本效用的差异性以及村庄非农化过程对其产生的影响。研究表明：在微观层面，家庭社会网络规模的扩张能够同时提高农业收入和非农收入，而社会网络结构异质性的提高只有利于非农收入的增长；并且随着村庄非农化程度的提高，社会网络的效应对于农业收入逐步减弱，而对于非农收入的影响则逐步增强。在宏观层面，村庄社会融合程度的提高仅有利于农民农业收入的增长，但随着非农化进程的推进，村庄集体社会资本在农业生产中所凸显的优势将会逐渐削弱。这预示着，中国农村非农经济的迅猛发展正逐步改变乡村社会资本的经济意涵。     

河北省电子认证发展现状及对策建议

电子认证是保障网络及信息安全的重要手段。通过对河北省电子认证工作现状、取得的成绩和存在问题进行深入剖析,提出创新政府监管,加强人力、物力投入,鼓励开展跨省、跨境互认,推动电子认证服务创新升级,开展跨地区、跨行业电子认证协同,共建全国性密码与密钥基础设施等发展建议。     

Bayesian inference for stable Lévy–driven stochastic differential equations with high‐frequency data

In this paper, we consider parametric Bayesian inference for stochastic differential equations driven by a pure‐jump stable Lévy process, which is observed at high frequency. In most cases of practical interest, the likelihood function is not available; hence, we use a quasi‐likelihood and place an associated prior on the unknown parameters. It is shown under regularity conditions that there is a Bernstein–von Mises theorem associated to the posterior. We then develop a Markov chain Monte Carlo algorithm for Bayesian inference, and assisted with theoretical results, we show how to scale Metropolis–Hastings proposals when the frequency of the data grows, in order to prevent the acceptance ratio from going to zero in the large data limit. Our algorithm is presented on numerical examples that help verify our theoretical findings.     

Application of a non-homogeneous Markov chain with seasonal transition probabilities to ozone data

In this work, we assume that the sequence recording whether or not an ozone exceedance of an environmental threshold has occurred in a given day is ruled by a non-homogeneous Markov chain of order one. In order to account for the possible presence of cycles in the empirical transition probabilities, a parametric form incorporating seasonal components is considered. Results show that even though some covariates (namely, relative humidity and temperature) are not included explicitly in the model, their influence is captured in the behavior of the transition probabilities. Parameters are estimated using the Bayesian point of view via Markov chain Monte Carlo algorithms. The model is applied to ozone data obtained from the monitoring network of Mexico City, Mexico. An analysis of how the methodology could be used as an aid in the decision-making is also given.     

全媒体时代主流媒体的数据化生存与发展

基于互联网连接的媒体平台，正在成为各类原生数据的源发地和汇聚中心，对大数据进行整合及应用的能力，将成为未来媒体平台运营的核心能力。建构在互联网平台之上的主流媒体必然要经历从信息总汇向数据总汇的转变，在这一过程中，媒体的业态、社会功能都将发生重大变化。伴随全媒体时代信息技术的快速发展，新闻传播呈现出新的特点和规律：传播主体大众化；传播容量海量化；传播方式交互化；传播手段多维化；传播时效全时化。在这样的背景下，主流媒体应不断进行数据化的探索和创新，基于5G网络，通过大数据技术运用，强化数据库建设，以此为基础，运用基于大数据的人工智能技术改变内容生产和分发方式，并以之作为内容监管的有力武器。未来基于大数据分析的综合业务推动自身产业结构优化。     

Inference and optimal design of multiple constant-stress testing for generalized half-normal distribution under type-II progressive censoring

The generalized half-normal (GHN) distribution and progressive type-II censoring are considered in this article for studying some statistical inferences of constant-stress accelerated life testing. The EM algorithm is considered to calculate the maximum likelihood estimates. Fisher information matrix is formed depending on the missing information law and it is utilized for structuring the asymptomatic confidence intervals. Further, interval estimation is discussed through bootstrap intervals. The Tierney and Kadane method, importance sampling procedure and Metropolis-Hastings algorithm are utilized to compute Bayesian estimates. Furthermore, predictive estimates for censored data and the related prediction intervals are obtained. We consider three optimality criteria to find out the optimal stress level. A real data set is used to illustrate the importance of GHN distribution as an alternative lifetime model for well-known distributions. Finally, a simulation study is provided with discussion.     

浙江省城市绿色技术创新效率评价及影响因素分析

基于网络DEA模型和Malmquist指数模型，利用浙江省11个地级市的2011-2020年的数据，以降维后的污染指数为非期望产出对绿色技术创新效率进行测度和分析。发现:浙江各市总体上成果转化阶段的效率优于研发阶段，城市间发展差异较大；整体TFP指数均值为1.121，其提升主要源自技术进步；城镇化水平、产业结构优化、对外开放、政府干预和研发强度对绿色技术创新效率有促进作用，但经济发展水平与绿色技术创新效率的U型关系不显著。     

Flood Risk Perceptions and Insurance Choice: Do Decisions in the Floodplain Reflect Overoptimism?

In the presence of rare disasters, risk perceptions may not always align with actual risks. These perceptions can nevertheless influence an individual's willingness to mitigate risks through activities such as purchasing flood insurance. In a survey of Maryland floodplain residents, we find that stated risk perceptions predict voluntary flood insurance take‐up, while perceptions themselves varied widely among surveyed residents, owing in large part to differences in past flood experience. We use a formal test for overoptimism in risk perceptions and find that, on aggregate, floodplain residents are overly optimistic about flood risks.