Blinded continuous monitoring in clinical trials with recurrent event endpoints

In studies with recurrent event endpoints, misspecified assumptions of event rates or dispersion can lead to underpowered trials or overexposure of patients. Specification of overdispersion is often a particular problem as it is usually not reported in clinical trial publications. Changing event rates over the years have been described for some diseases, adding to the uncertainty in planning. To mitigate the risks of inadequate sample sizes, internal pilot study designs have been proposed with a preference for blinded sample size reestimation procedures, as they generally do not affect the type I error rate and maintain trial integrity. Blinded sample size reestimation procedures are available for trials with recurrent events as endpoints. However, the variance in the reestimated sample size can be considerable in particular with early sample size reviews. Motivated by a randomized controlled trial in paediatric multiple sclerosis, a rare neurological condition in children, we apply the concept of blinded continuous monitoring of information, which is known to reduce the variance in the resulting sample size. Assuming negative binomial distributions for the counts of recurrent relapses, we derive information criteria and propose blinded continuous monitoring procedures. The operating characteristics of these are assessed in Monte Carlo trial simulations demonstrating favourable properties with regard to type I error rate, power, and stopping time, ie, sample size.     

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.     

为合法经营活动而侵犯公民个人信息的刑法规制

最高人民法院、最高人民检察院《关于办理侵犯公民个人信息刑事案件适用法律若干问题的解释》第六条对为合法经营活动而侵犯公民个人信息行为进行独立规制,是新型犯罪罪状表述抽象化与罪状解释具体化、信息时代信息价值多元化与危害行为多样化、现代社会犯罪治理精细化与刑法评价精准化的内在要求.为合法经营活动而侵犯公民个人信息行为相关规范要素中的“为合法经营活动”应理解为主观超过要素,“获利五万元”应作严格解释,“曾因侵犯公民个人信息”应作广义解释,“其他情节严重”应包括信息数量标准.     

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.     

Price bias and common practice in option pricing

Generally, the semiclosed-form option pricing formula for complex financial models depends on unobservable factors such as stochastic volatility and jump intensity. A popular practice is to use an estimate of these latent factors to compute the option price. However, in many situations this plug-and-play approximation does not yield the appropriate price. This article examines this bias and quantifies its impacts. We decompose the bias into terms that are related to the bias on the unobservable factors and to the precision of their point estimators. The approximated price is found to be highly biased when only the history of the stock price is used to recover the latent states. This bias is corrected when option prices are added to the sample used to recover the states' best estimate. We also show numerically that such a bias is propagated on calibrated parameters, leading to erroneous values. The Canadian Journal of Statistics 48: 8–35; 2020 © 2019 Statistical Society of Canada     

Hierarchical Bayesian Modeling of Post-Earthquake Ignition Probabilities Considering Inter-Earthquake Heterogeneity

Post-earthquake fires are high-consequence events with extensive damage potential. They are also low-frequency events, so their nature remains underinvestigated. One difficulty in modeling post-earthquake ignition probabilities is reducing the model uncertainty attributed to the scarce source data. The data scarcity problem has been resolved by pooling the data indiscriminately collected from multiple earthquakes. However, this approach neglects the inter-earthquake heterogeneity in the regional and seasonal characteristics, which is indispensable for risk assessment of future post-earthquake fires. Thus, the present study analyzes the post-earthquake ignition probabilities of five major earthquakes in Japan from 1995 to 2016 (1995 Kobe, 2003 Tokachi-oki, 2004 Niigata–Chuetsu, 2011 Tohoku, and 2016 Kumamoto earthquakes) by a hierarchical Bayesian approach. As the ignition causes of earthquakes share a certain commonality, common prior distributions were assigned to the parameters, and samples were drawn from the target posterior distribution of the parameters by a Markov chain Monte Carlo simulation. The results of the hierarchical model were comparatively analyzed with those of pooled and independent models. Although the pooled and hierarchical models were both robust in comparison with the independent model, the pooled model underestimated the ignition probabilities of earthquakes with few data samples. Among the tested models, the hierarchical model was least affected by the source-to-source variability in the data. The heterogeneity of post-earthquake ignitions with different regional and seasonal characteristics has long been desired in the modeling of post-earthquake ignition probabilities but has not been properly considered in the existing approaches. The presented hierarchical Bayesian approach provides a systematic and rational framework to effectively cope with this problem, which consequently enhances the statistical reliability and stability of estimating post-earthquake ignition probabilities.     

集中优势发展重庆电子信息产业

在分析重庆市电子信息设备制造业现状、发展的有利与不利因素以及国内外发展态势的基础上对重庆(?)子信息产业的发展提出了九条对策建议。     

试论近中国茶馆的社会功能

在近代中国 ,茶馆与民众生活紧密相连 ,并承担着广泛而又复杂的社会功能。茶馆与民众的经济生活相关联 ,也是民间纠纷调解的重要场所。同时 ,作为一个公众活动的场所 ,茶馆也是民间社会信息传播的集散地 ;民众在茶馆中表达自己的见解 ,也使得茶馆成为一种控制舆论的力量。茶馆的这些功能是近代民间社会内在运作逻辑的体现。     

时装画与服装文化

时装画是为了服装的设计、制作和推介而创作的具有审美价值的绘画样式。时装画对于服装文化的发展具有推动作用 ,探讨和研究时装画产生、发展的历史和现状 ,对于发展中国的服装文化 ,具有重要的意义。     

数字时代的挑战与教育情报的对策

分析了数字时代的信息特点以及给教育情报领域带来的挑战 ,提出了教育情报面对现实应采取的对策。旨在从某个侧面强化教育信息资源建设的整合度。