Adapting by calibration the sample size of a phase III trial on the basis of phase II data

The problem of estimating the sample size for a phase III trial on the basis of existing phase II data is considered, where data from phase II cannot be combined with those of the new phase III trial. Focus is on the test for comparing the means of two independent samples. A launching criterion is adopted in order to evaluate the relevance of phase II results: phase III is run if the effect size estimate is higher than a threshold of clinical importance. The variability in sample size estimation is taken into consideration. Then, the frequentist conservative strategies with a fixed amount of conservativeness and Bayesian strategies are compared. A new conservative strategy is introduced and is based on the calibration of the optimal amount of conservativeness – calibrated optimal strategy (COS). To evaluate the results we compute the Overall Power (OP) of the different strategies, as well as the mean and the MSE of sample size estimators. Bayesian strategies have poor characteristics since they show a very high mean and/or MSE of sample size estimators. COS clearly performs better than the other conservative strategies. Indeed, the OP of COS is, on average, the closest to the desired level; it is also the highest. COS sample size is also the closest to the ideal phase III sample size M_I, showing averages and MSEs lower than those of the other strategies. Costs and experimental times are therefore considerably reduced and standardized. However, if the ideal sample size M_I is to be estimated the phase II sample size n should be around the ideal phase III sample size, i.e. n?2M_I/3. Copyright © 2010 John Wiley & Sons, Ltd.     

论中国航天保险法律制度的完善

航天保险法律制度是航天发射业健康发展的重要保障。航天保险法律制度有国际法和国内法两种渊源，其主要内容包括航天保险的类型、航天保险合同制度及航天保险监管制度。中国航天保险立法存在基本法缺位、航天保险定性模糊及配套法律规定不足等缺陷，故亟需完善。     

Warning Systems and Defense Policy: A Reliability Model for the Command and Control of U.S. Nuclear Forces

The U.S. Command, Control, Communication and Intelligence System (C³I) includes sensors (e.g., satellites and radars), communication links, and computer systems that allow gathering and processing of information that a missile attack on the continental United States may be on the way. The choice of a policy of response to such an attack depends in part on the reliability of the information coming from the C³I. We consider in this study four possible response policies: (1) launch on impact, (2) launch on attack assessment, (3) launch under attack, and (4) launch on warning. We propose a method to compute, for each policy, the probability of accidental nuclear strike and the probability of being unable to respond due to a malfunction of the C³I or to partial destruction of the response forces. We include in our system the launch authorization steps (permissive action links) and a very crude analysis of the survivability of second strike forces. We examine the variations of probabilities of Type I and Type II errors and the tradeoffs involved when shifting from a policy of launch on impact to another launch policy. We conclude that this simple but powerful method allows one to gain a good grasp on some of the complex issues involved.     

航天发射行为对第三人损害之危险责任研究

航天发射活动中航天器相关零部件或碎片坠落可能导致一国领土、领水及领海范围内第三人的人身、财产权利或利益遭到损害。此类侵权行为应属于民事侵权,遭受损害的第三人是受害人,参与航天器发射的各方是侵权关系中的责任人。航天发射活动致人损害应适用高度危险责任,其归责原则应为严格责任。     

Commercialization of Platform Technologies: Launch Timing and Versioning Strategy

Many emerging entrepreneurial applications and services connect two or more groups of users over Internet‐based information technologies. Commercial success of such technology products requires astute business practices related to product line design, price discrimination, and launch timing. We examine these issues for a platform firm that serves two markets—labeled as user and developer markets—such that the size of each market positively impacts participation in the other. In addition, our model allows for sequential unfolding of consumer and developer participation, and for uncertainty regarding developer participation. We demonstrate that product versioning is an especially attractive strategy for platform firms, that is, the trade‐off between market size and margins is tilted in the direction of more versions. However, when expanding the product line carries substantial fixed costs (e.g., marketing cost, cost of additional plant, increased distribution cost), then the uncertainty in developer participation adversely impacts the firm's ability to offer multiple versions. We show that for established firms with lower uncertainty about developer participation, the choice is essentially between an expanded or minimal product line. Startups and firms that are entering a new product category are more likely to benefit from a “wait and see” deferred expansion strategy.     

农村义务教育"以县为主"管理体制现状及多元化发展模式初探

农村义务教育实施"以县为主"的管理体制意义重大,是农村教育由人民办转向由政府办的里程碑."税费改革"背景下的"以县为主"管理体制遇到了一些发展中的新问题,对农村教育出现的新问题简单地按照三类地区划分方法去解决不能奏效,应该真正体现县与县之间的差别,采取多元化的发展模式才能得到解决.     

毛泽东为什么要发动反右派运动

认真研读进入社会主义时期后的毛泽东一系列重要文稿,便不难发现,在观察和思考国内社会的阶级关系、少数人闹事原因、民主党派和知识分子队伍状况以及国内思想动向等诸多社会问题时,毛泽东偏重于运用阶级斗争的观点,从而导致将国内形势看得过于严重。这就使得毛泽东对整风鸣放阶段中出现的激烈批评言论不仅不能正确对待,反而作出发动反右派运动的决策。可以说,决策发动反右派运动是毛泽东思想深处中存在的"以阶级斗争为纲"的"左"的指导思想在1957年6月这一特定历史条件下的运用与实践。     

创业氛围:不同地区企业创生行为差异新解

创业环境理论解释了"创业者到哪里创业"以及"为什么"等有关创业的客体问题,但不能很好地解释"创业者从何处来"以及"为何来自此处而非别处"等有关创业的主体问题。优越的创业环境在吸引外来投资的同时并不一定能够激发本地居民投身创业的热情。特定地区内的居民是否崇尚创业并采取创业行为,与创业氛围高度相关。而创业氛围的形成和传导,内生于区域内个体行为与参考群体的互动,取决于创业成功率与创业收益率,与企业密度正相关。     

Discounting phase 2 results when planning phase 3 clinical trials

Sample size planning is an important design consideration for a phase 3 trial. In this paper, we consider how to improve this planning when using data from phase 2 trials. We use an approach based on the concept of assurance. We consider adjusting phase 2 results because of two possible sources of bias. The first source arises from selecting compounds with pre‐specified favourable phase 2 results and using these favourable results as the basis of treatment effect for phase 3 sample size planning. The next source arises from projecting phase 2 treatment effect to the phase 3 population when this projection is optimistic because of a generally more heterogeneous patient population at the confirmatory stage. In an attempt to reduce the impact of these two sources of bias, we adjust (discount) the phase 2 estimate of treatment effect. We consider multiplicative and additive adjustment. Following a previously proposed concept, we consider the properties of several criteria, termed launch criteria, for deciding whether or not to progress development to phase 3. We use simulations to investigate launch criteria with or without bias adjustment for the sample size calculation under various scenarios. The simulation results are supplemented with empirical evidence to support the need to discount phase 2 results when the latter are used in phase 3 planning. Finally, we offer some recommendations based on both the simulations and the empirical investigations. Copyright © 2012 John Wiley & Sons, Ltd.