Distribution of the two‐sample t‐test statistic following blinded sample size re‐estimation

We consider the blinded sample size re‐estimation based on the simple one‐sample variance estimator at an interim analysis. We characterize the exact distribution of the standard two‐sample t‐test statistic at the final analysis. We describe a simulation algorithm for the evaluation of the probability of rejecting the null hypothesis at given treatment effect. We compare the blinded sample size re‐estimation method with two unblinded methods with respect to the empirical type I error, the empirical power, and the empirical distribution of the standard deviation estimator and final sample size. We characterize the type I error inflation across the range of standardized non‐inferiority margin for non‐inferiority trials, and derive the adjusted significance level to ensure type I error control for given sample size of the internal pilot study. We show that the adjusted significance level increases as the sample size of the internal pilot study increases. Copyright © 2016 John Wiley & Sons, Ltd.     

论中国现代文学史起点的"向前移"问题

"'五四'新文学运动"曾被视为中国现代文学史的"起点",这样就遮蔽了"五四"前中国文学现代化的实际进程,相应也忽视了"五四"前许多文学作品已经初具的现代性.从早期启蒙者身份的重新认定,在文学作品中对科学、人权的引进时序,中国期刊的三波现代化浪潮,早期白话文的倡导和早期翻译作品的成就等方面来看,有必要将中国现代文学史的起点"向前"位移,才能将20世纪文学作为一个不可分割的整体来加以把握.     

The ABC of pharmaceutical trial design: some basic principles

This is a teaching paper intended as a quick introduction to some of the key concepts in the design of pharmaceutical trials for those new to the industry. Since the first ‘modern’ randomized clinical trial was reported in 1948 by the Medical Research Council, clinical trials have become a central component in the assessment of new therapies. The primary objective of any clinical trial is to obtain an unbiased and reliable assessment of a given regimen response independent of any known or unknown prognostic factors. The essential principals of trial design can be thought of as the ABC of allocation at random, blinding and controlled. In addition, the three Rs of endpoint selection – representative, reliability and reproducibility – are relevant in this context. This paper briefly describes the basic concepts for clinical trials and highlights possible points to consider. It draws heavily on the principles highlighted in the International Conference on Harmonisation guidelines as well as recommendations in the CONSORT statement. Copyright © 2002 John Wiley & Sons, Ltd.