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.     

Ethical Numbers: Ethics Training in U.S. Graduate Statistics Programs, 2013–2014

As important members of research teams, statisticians bear an ethical responsibility to analyze, interpret, and report data honestly and objectively. One way of reinforcing ethical responsibilities is through required courses covering a variety of ethics-related topics at the graduate level. We assessed ethics requirements for graduate-level statistics training programs in the United States for the 2013–2014 academic year using the websites of 88 universities, examining 103 biostatistics programs, and 136 statistics degree programs. We categorized programs’ ethics training requirements as required or not required. Thirty-one (35.1%) universities required an ethics course for at least some degree students. Sixty-two (25.5%) degree programs required an ethics course for at least some students. The majority (77.4%) of required courses were worth 0 or 1 credit. Of the 177 programs without an ethics requirement, 19 (10.7%) listed an ethics elective. Although a single ethics course is insufficient for instilling an ethical approach to science, degree programs that model expectations through coursework point to the value of ethics in science. More training programs should prepare statisticians to consider the ethical dimensions of their work through required coursework. Supplementary materials for this article are available online.     

Foreign-born and native-born migration in the U.S.: evidence from linked IRS administrative and census survey records

Journal of Population Research - This paper details efforts to link administrative records from the Internal Revenue Service (IRS) to American Community Survey (ACS) and 2010 Census microdata for...     

三国时期西部农业开发述论

三国时期 ,曹魏控制西北 ,蜀汉占据西南 ,两国主要在西部地区争战 ,粮草供给成为决定胜负的关键因素 ,为此双方都采取了恢复和发展粮食生产的措施。曹魏在西部一些适宜农业的战略要地大兴屯田 ,开发关陇、稳定河西 ,每年收获大量谷物供给军粮 ,以守为攻 ,迎战蜀军 ;蜀汉占据西南之后 ,诸葛亮注意处理好民族关系 ,发挥当地的农业资源优势 ,劝农积谷。为了解决北伐运粮的困难 ,还在汉中及渭水南岸一些地区设置少量屯田。不同的农业开发措施与双方的治乱胜败有很大关系。     

日本研讨自然辩证法的思想方法

日本是开展自然辩证法研究比较早的国家之一 ,并在研讨自然辩证法方面形成了许多富有启发性的思想方法。可将其概括为 :自由论争的思想方法、“具体化”的思想方法、发展的思想方法、联盟的思想方法     

Measuring agreement between two statistics with applications to age standardization

Summary.  We detail a general method for measuring agreement between two statistics. An application is two ratios of directly standardized rates which differ only by the choice of the standard. If the statistics have a high value for the coefficient of agreement then the expected squared difference between the statistics is small relative to the variance of the average of the two statistics, and inferences vary little by changing statistics. The estimation of a coefficient of agreement between two statistics is not straightforward because there is only one pair of observed values, each statistic calculated from the data. We introduce estimators of the coefficient of agreement for two statistics and discuss their use, especially as applied to functions of standardized rates.     

证券市场中上市公司粉饰报表的原因及治理

上市公司粉饰报表对我国经济的健康发展危害严重。上市公司粉饰报表的原因主要在于 :一是上市公司存在粉饰报表的内在动因 ,二是企业外部监督约束机制不健全。解决上市公司粉饰报表的问题 ,首先要加强会计人员的职业道德教育 ,其次要进一步完善上市公司的外部监管机制     

Empirical likelihood confidence intervals for the mean of a population containing many zero values

If a population contains many zero values and the sample size is not very large, the traditional normal approximation‐based confidence intervals for the population mean may have poor coverage probabilities. This problem is substantially reduced by constructing parametric likelihood ratio intervals when an appropriate mixture model can be found. In the context of survey sampling, however, there is a general preference for making minimal assumptions about the population under study. The authors have therefore investigated the coverage properties of nonparametric empirical likelihood confidence intervals for the population mean. They show that under a variety of hypothetical populations, these intervals often outperformed parametric likelihood intervals by having more balanced coverage rates and larger lower bounds. The authors illustrate their methodology using data from the Canadian Labour Force Survey for the year 2000.     

Bayesian analysis of mixture modelling using the multivariate t distribution

A finite mixture model using the multivariate t distribution has been shown as a robust extension of normal mixtures. In this paper, we present a Bayesian approach for inference about parameters of t-mixture models. The specifications of prior distributions are weakly informative to avoid causing nonintegrable posterior distributions. We present two efficient EM-type algorithms for computing the joint posterior mode with the observed data and an incomplete future vector as the sample. Markov chain Monte Carlo sampling schemes are also developed to obtain the target posterior distribution of parameters. The advantages of Bayesian approach over the maximum likelihood method are demonstrated via a set of real data.     

采用二阶特征窗的语音盲分离方法

利用语音信号的短时平稳特性,提出了一种二阶特征窗语音盲分离方法。该方法采用新的联合差分相关矩阵白化算法去除有色噪声影响;用长度等于语音信号基音周期的等距特征窗连续分割预白化观测数据,在每个加窗的数据帧计算不同的时滞协方差矩阵。利用联合近似对角化时滞协方差矩阵集合得到旋转参数,最终达到语音信号的盲分离。该方法消除了有色噪声的影响,只需用到二阶信息就能很好地分离语音信号。仿真实验验证了该方法的有效性。