临床适应性设计与药物评价的考虑

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (1): 1-5.

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临床适应性设计与药物评价的考虑

赵超

国家食品药品监督管理局药品审评中心, 北京 100038

收稿日期:2007-12-24 修回日期:2008-01-05 出版日期:2008-01-26 发布日期:2020-10-13
作者简介:赵超, 理学博士, 副研究员, 国家食品药品监督管理局药品审评中心的项目负责人, 一直负责生物制品心肾、内分泌品种的综合审评和技术评价, 特别在溶栓药、糖尿病药物、骨质疏松和自身免疫性疾病的生物制品评价方面, 始终较关注国际前沿研究动态, 并在审评的具体技术尺度把握上, 注意将临床药理学的基础认识与临床试验和药品生产的保障相联系, 使药品上市前的利弊评价更赋前瞻性。在生物大分子的结构与作用机制的关系上, 多年来结合新生物制品的审评经验, 取得了部分研究成果。E-mail: zhaoch@cde.org.cn

General considerations on adaptive designs for clinical trail and drug evaluation

ZHAO Chao

Center for Drug Evaluation, State Food and Drug Administration of China(SFDA), Beijing 100038, China

Received:2007-12-24 Revised:2008-01-05 Online:2008-01-26 Published:2020-10-13

摘要/Abstract

摘要： 本文从药品评价的角度, 对目前国际十分倡导的适应性设计阐述个人的认识, 以及对一些问题的看法。合理地运用适应性设计不仅可以节省临床试验的研发时间和资金投入, 而且也能为受试者带来利益。但是, 如何保障适应性设计是在科学的基础上得到贯彻, 取决于一系列的保障措施。目前形势下, 应该是选择有代表性的品种,摸索和总结我国开展适应性设计的经验。适应性设计并不是新东西, 而是我们对待临床设计变更的思想更新了。

关键词: 适应性设计, 中期分析, 独立的数据管理委员会, 临床生物统计

Abstract: Adaptive design is a trial design that allows modifications to some aspects of the trial after its initiation without undermining the validity and integrity of the trial. Adaptive design makes it possible to discover and rectify inappropriate assumptions in trial designs, reduce development costs and the time to market. It has been very attractive to the pharmaceutical industries. In this paper, it is not focused on adaptive designs for clinical trials with multiple endpoints studied using computer simulations, but is to clarify our evolution, which is taken into consideration in a trial adaptive design at present, if need modifications.

Key words: KEYWOEDS adaptive designs, interim analysis, independent data monitoring committee, clinical biostatistics

赵超. 临床适应性设计与药物评价的考虑[J]. 中国临床药理学与治疗学, 2008, 13(1): 1-5.

ZHAO Chao. General considerations on adaptive designs for clinical trail and drug evaluation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(1): 1-5.

参考文献

[1] Exp Design Studio Manual. Lexington, MA, USA. 2005, www. CTriSoft. net.
[2] Bauer P, Kohne K. Evaluation of experiments with adaptive interim analyses[J]. Biometrics, 1994, 50(4): 1029-1041.
[3] Lan KKG, Demets DL. Discrete sequential boundaries for clinical trials[J]. Biometriku, 1988, 70(3): 659-663.
[4] Lin DY, Tao Q, Ying Z. A General theory on stochastic curtailment for censored survival data[J]. JASA, 1999, 94(446): 510-521.
[5] 国家食品药品监督管理局. 《药品注册管理办法》[S]. 2007.
[6] Docket No. 2004 -N-0181 Comments from Novartis[S]. www. fda. gov.
[7] Critical Path Initiative [Docket No. 2004N -0181, 69 Federal Register, 21839-21840, April 22, 2004]. www. fda. gov.
[8] Mark Chang. Adaptive Design for Clinical Trials[C]. International Symposium on Applied Stochastic Models and Data Analysis, France, 2005: 1251 -1261(Mark. Chang @Statisticians. org)
[9] Food and Drug Administration. Deputy Commissioner for Medical and Scientific Affairs[C]. Washington, DC, 2006.
[10] FDA. Critical path opportunities list[S]. HHS, US. 2006.
[11] Reflection paper on methodological issues in confirmatory clinical trials with flexible design and analysis plan[S]. Doc Ref. CHMP EWP2459 02 London, 23March 2006. www. emea. europa. eu
[12] Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design[S]. Doc Ref. CHMP EWP2459 02 London, 18 October 2007. www. emea. europa. eu
[13] 周海钧, 主译. 药品注册的国际技术要求(临床部分) ICH E9[M]. 2版. 北京:人民卫生出版社, 2007: 867.
[14] 《化学药物和生物制品临床试验的生物统计学技术指导原则》课题研究组. 《化学药物和生物制品临床试验的生物统计学技术指导原则》[S]. 2005.
[15] Babb JS, Rogatko A. Bayesian methods for cancer phase I clinical trials, Advances in Clinical Trial Biostatistics[M]. Nancy L. Geller (ed.), Marcel Dekker, Inc,2004.
[16] Proschan MA, Hunsberger SA. Design extension of studies based on conditional power[J]. Biometrics, 1995, 51(4): 1315-1324.
[17] Cui L, Hung HMJ, Wang SJ. Modification of sample size in group sequential clinical trials[J]. Biometrics, 1999,55(3): 853-857.
[18] Rosenberger WF, Lachin JM. Randomization in Clinical Trials[M]. New York: JohnWiley &Sons, Inc. , 2002.
[19] O'Quigley J, Pepe M, Fisher L. Continual reassessment method: A practical design for phase I clinical trial in cancer[J]. Biometrics, 1990, 46(1): 33-48.

临床适应性设计与药物评价的考虑

General considerations on adaptive designs for clinical trail and drug evaluation

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