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.     

三国时期西部农业开发述论

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湖南省与周边区域经济发展比较及对策研究

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汪辟疆及其近代诗系的建构

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On Optimality of Bayesian Wavelet Estimators

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A Bayesian method for classification and discrimination

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Deconvolution with supersmooth distributions

Nonparametric deconvolution problems require one to recover an unknown density when the data are contaminated with errors. Optimal global rates of convergence are found under the weighted L_p-loss (1 ≤ p ≤ ∞). It appears that the optimal rates of convergence are extremely low for supersmooth error distributions. To resolve this difficulty, we examine how high the noise level can be for deconvolution to be feasible, and for the deconvolution estimate to be as good as the ordinary density estimate. It is shown that if the noise level is not too high, nonparametric Gaussian deconvolution can still be practical. Several simulation studies are also presented.     

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加快西部地区农村土地流转的对策

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对约束民族地区乡村非农产业发展诸因素的历史考察

非农产业的发展,是乡村经济结构现代转型的关键之一。然而有许多制约民族地区乡村非农经济发展的因素,如何针对这些约束因素,寻找解决的办法,在民族地区全面建设小康社会。该文指出必须进行广泛深入的调查研究,才能提供有效可行的战略性对策及付诸实施。