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.     

上证30指数股市盈率实证分析

通过对2000年上证30指数股市盈率水平及其影响因素进行实证分析,可以发现,其中股息支付率、每股收益增长率、行业平均市盈率对股票P/E值起主要的解释作用,而股本规模因素,解释力却有限,除每股收益增长率外,各变量的相关性与理论分析基本一致.     

促性腺激素、V_(D_3)、V_E亚硒酸钠对母兔繁殖力的影响

选择成年、健康、未孕母兔 32只 ,随机分成 8组 ,分别给予促性腺激素 (Ⅰ组 )、VD3(Ⅱ组 )、VE 亚硒酸钠 (Ⅲ组 ) ,促性腺激素 +VD3(Ⅳ组 )、VD3+VE 亚硒酸钠 (Ⅴ组 )、促性腺激素 +VE 亚硒酸钠(Ⅵ组 )、促性腺激 +VD3+VE 亚硒酸钠 (Ⅶ组 ) ,空白对照 8种处理。试验结果表明 ,母兔经药物处理后 ,其繁殖性能 (发情状况、排卵数、正常受精卵数 )都比对照组显著地提高 ,但Ⅰ、Ⅳ、Ⅵ组有畸形卵子存在 ,以处理Ⅶ组效果最好 ,其排卵数达 4 7± 2 0 .3个 ,正常受精卵 35个 ,分别比对照组多 36 .5个、30个。     

论电子商务对税收的冲击

针对迅速崛起的电子商务的特点深入分析电子商务对税收各个方面的冲击和影响 ,提出加大对电子商务征税力度的有关建议 ,对完善电子商务征税有积极意义。     

制约学校体育实施健康教育的诸因素分析

本文主要对影响学校体育实施健康教育的因素进行了分类研究 ,为学校体育实施健康教育提供科学的参考依据。     

论彼得·圣吉的管理哲学

彼得·圣吉是美国著名的管理学家。他的管理哲学从管理理论与管理实践、管理主体与管理客体、管理手段与管理目的、管理组织系统与管理环境之间的关系等四个维度全面揭示了管理科学的发展取向 ,深邃而富有内涵 ,值得我们研究和探讨     

高校体育教育专业人才培养模式的现状与对策

文章对高校体育教育专业人才培养模式现状进行了分析,通过对修订培养目标、拓宽培养途径、优化课程设置、改革教学方法、提高师资力量等方面的研讨,进一步明确了高校体育教育专业人才培养模式改革的基本思路,以促进高校体育教育专业教学质量和人才质量的提高。     

Lower bounds on expectations of positive L-statistics from without-replacement models

We consider samples drawn without replacement from finite populations. We establish optimal lower non-negative and upper non-positive bounds on the expectations of linear combinations of order statistics centered about the population mean in units generated by the population central absolute moments of various orders. We also specify the general results for important examples of sample extremes, Gini mean differences and sample range. The paper completes the results of Papadatos and Rychlik [2004. Bounds on expectations of L-statistics from without replacement samples. J. Statist. Plann. Inference 124, 317–336], where sharp negative lower and positive upper bounds on the expectations of the combinations were presented for the without-replacement samples.     

Bias Correction in the Dynamic Panel Data Model with a Nonscalar Disturbance Covariance Matrix

Approximation formulae are developed for the bias of ordinary and generalized Least Squares Dummy Variable (LSDV) estimators in dynamic panel data models. Results from Kiviet [Kiviet, J. F. (1995), on bias, inconsistency, and efficiency of various estimators in dynamic panel data models, J. Econometrics68:53-78; Kiviet, J. F. (1999), Expectations of expansions for estimators in a dynamic panel data model: some results for weakly exogenous regressors, In: Hsiao, C., Lahiri, K., Lee, L-F., Pesaran, M. H., eds., Analysis of Panels and Limited Dependent Variables, Cambridge: Cambridge University Press, pp. 199-225] are extended to higher-order dynamic panel data models with general covariance structure. The focus is on estimation of both short- and long-run coefficients. The results show that proper modelling of the disturbance covariance structure is indispensable. The bias approximations are used to construct bias corrected estimators which are then applied to quarterly data from 14 European Union countries. Money demand functions for M1, M2 and M3 are estimated for the EU area as a whole for the period 1991: I-1995: IV. Significant spillovers between countries are found reflecting the dependence of domestic money demand on foreign developments. The empirical results show that in general plausible long-run effects are obtained by the bias corrected estimators. Moreover, finite sample bias, although of moderate magnitude, is present underlining the importance of more refined estimation techniques. Also the efficiency gains by exploiting the heteroscedasticity and cross-correlation patterns between countries are sometimes considerable.     

浅谈电子商务涉及的法律问题

近年来,电子商务发展迅速,对社会生活产生了很大影响,并逐渐形成了一种新型的社会关系。与此同时,电子商务领域中也出现了涉及商法、刑法、民法、知识产权和国际法等许多亟待解决的法律问题。因此,分析电子商务活动中诸多涉及法律的问题及产生的原因,在遵循国际示范法的标准并借鉴国外的先进经验的同时,结合我国的国情制定出适合我国的电子商务法律,对促进我国电子商务的健康、有序、规范发展是非常必要的。