Unifying CRM and EWOC designs for phase I cancer clinical trials

The main goal of phase I cancer clinical trials is to determine the highest dose of a new therapy associated with an acceptable level of toxicity for the use in a subsequent phase II trial. The continual reassessment method (CRM) [O’Quigley, J., Pepe, M., Fisher, L., 1990. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 46, 33–48] and escalation with overdose control (EWOC) [Babb, J., Rogatko, A., Zacks, S., 1998. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statist. Med. 17 (10), 1103–1120] are two model-based designs used for phase I cancer clinical trials. A few modifications of the (original) CRM and EWOC have been made by many authors. In this paper, we show how CRM and EWOC can be unified and present a hybrid design. We study the characteristics of the approach of the hybrid design. The comparisons of the three designs (CRM, EWOC, and the hybrid design) are presented by convergence rates and overdose proportions. The simulation results show that the hybrid design generally has faster convergence rates than EWOC and smaller overdose proportions than CRM, especially when the true maximum tolerated dose (MTD) is above the mid-level of the dose range considered. The performance of these three designs is also evaluated in terms of sensitivity to outliers.     

Doubly adaptive biased coin designs with heterogeneous responses

Doubly adaptive biased coin design (DBCD) is an important family of response-adaptive randomization procedures for clinical trials. It uses sequentially updated estimation to skew the allocation probability to favor the treatment that has performed better thus far. An important assumption for the DBCD is the homogeneity assumption for the patient responses. However, this assumption may be violated in many sequential experiments. Here we prove the robustness of the DBCD against certain time trends in patient responses. Strong consistency and asymptotic normality of the design are obtained under some widely satisfied conditions. Also, we propose a general weighted likelihood method to reduce the bias caused by the heterogeneity in the inference after a trial. Some numerical studies are also presented to illustrate the finite sample properties of DBCD.     

乡镇统计工作机制有效运转的思考

 乡镇统计是统计工作的重要基础,同时也是目前统计工作的薄弱环节。巩固和加强乡镇统计工作,推动乡镇统计基础工作规范化建设,促进乡镇统计工作机制有效运转,本文提出了具体的设想和思考。本文重点从乡镇统计站建设、人员建设、制度建设三个方面,对乡镇统计工作机制有效发挥作用进行研究,目的在于推进乡镇统计工作机制产生有效生产力。     

宋代与中国古代取保候审制度的形成

取保候审古称责保知在,是刑事司法中普遍采用的限制人身自由的强制方法,是借助于保证人的信誉约束诉讼参加人,以配合司法活动的诉讼保障措施.在中国古代史籍中,取保候审于北齐初见使用,<唐律疏议>亦有条文记栽,两宋时期形成制度.与前代相比,宋代取保候审的规定更加具体,其适用条件的详备程度已达到当今立法水平,甚至有些规定今世未能企及.宋代取保候审制度的完善,可为宋代司法制度发达的又一力证.     

论十八世纪小农家庭的生存经济——以清中期527件服制命案为中心

本文利用527件清代刑科题本中关于服制命案的材料,尝试勾勒十八世纪小农家庭的大致轮廓,并据此提出了一些对于小农家庭经济的新解释。本文的结论是:即使在号称盛世的雍乾时期,小农家庭仍然在生存经济之中苦苦挣扎;在面对人口压力而"内卷化"的小农家庭经济中,恰亚诺夫的家庭人口周期理论的解释力是有限的;同时,江南一带童养媳现象要比华北远为普遍,可能是因为长江流域的女性在小农家庭经济中的作用更大。     

张庆五教授户籍管理学术观点述评

作为户籍管理问题专家 ,张庆五教授的研究领域涉及到户籍制度史、户籍制度改革、户口登记、户口统计、户口迁移、流动人口管理等诸多方面。在中国户籍制度史研究方面 ,他的成果为深入研究民国户籍制度史打下了良好的基础。他很好地总结了户口登记和户口统计两个制度之间的关系 ,主张应把市镇建制标准和城乡人口的划分作为两个问题分别考虑 ,主张改革人口管理统计体制。他认为我国现行户口迁移政策既有弊端 ,又有积极功能 ,认为我国现阶段通过户口迁移控制大城市人口机械增长具有必要性。他认为应该根据我国的国情 ,以现行户口登记制度的基本原则为依据来表述流动人口的概念。他估算分析了我国流动人口的规模、特点和发展趋势。他依据乡镇工业的发展状况 ,乡村城市化的要求 ,鲜明地主张以小城镇为先导改革户籍制度     

深化户籍管理制度改革 进一步适应市场经济发展

改革开放动摇了传统户籍管理制度,市场经济发展要求建立城乡一体化的劳动力市场,在传统户籍管理制度基础上的修修改改已不能满足时代要求。因此,必须建立与市场经济发展相一致的全新户籍管理制度。     

Variance estimation for the 2006 French housing survey

In the 2006 French housing survey, information is collected on many aspects of housing to describe the housing stock in France and the housing conditions of French households. The basic national sample results from a multistage sampling design. Complementary samples were selected to perform accurate estimations for socio-demographic domains. Some French regions proceeded to a regional and local extension of the national sample. The variance is estimated for a region with a regional and local extension of the basic national sample.     

基于分群体非均衡推进的新型农村社会养老保险模式创新研究——以山东临沂农村养老保险为例

通过对山东省临沂市农村社会养老保险实施情况的研究以及探讨,提出一种新的制度模式——分群体非均衡推进。该制度主要针对不同的群体现状,先以计生户和失地农民为突破口,鼓励其主动参加社会养老保险,然后逐步带动其它群体加入到社会养老保险行列,最终实现全面覆盖。     

Estimates of subgroup treatment effects in overall nonsignificant trials: To what extent should we believe in them?

In drug development, it sometimes occurs that a new drug does not demonstrate effectiveness for the full study population but appears to be beneficial in a relevant subgroup. In case the subgroup of interest was not part of a confirmatory testing strategy, the inflation of the overall type I error is substantial and therefore such a subgroup analysis finding can only be seen as exploratory at best. To support such exploratory findings, an appropriate replication of the subgroup finding should be undertaken in a new trial. We should, however, be reasonably confident in the observed treatment effect size to be able to use this estimate in a replication trial in the subpopulation of interest. We were therefore interested in evaluating the bias of the estimate of the subgroup treatment effect, after selection based on significance for the subgroup in an overall “failed” trial. Different scenarios, involving continuous as well as dichotomous outcomes, were investigated via simulation studies. It is shown that the bias associated with subgroup findings in overall nonsignificant clinical trials is on average large and varies substantially across plausible scenarios. This renders the subgroup treatment estimate from the original trial of limited value to design the replication trial. An empirical Bayesian shrinkage method is suggested to minimize this overestimation. The proposed estimator appears to offer either a good or a conservative correction to the observed subgroup treatment effect hence provides a more reliable subgroup treatment effect estimate for adequate planning of future studies.