替代指标在临床试验中的应用与局限性

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (10): 1194-1197.

替代指标在临床试验中的应用与局限性

徐小国, 蒋萌

南京中医药大学附属医院临床药理科, 南京 210029, 江苏

收稿日期:2006-06-12 修回日期:2006-09-10 出版日期:2006-10-26 发布日期:2020-11-05
作者简介:徐小国, 男, 硕士研究生, 研究方向:临床药理。Tel:13913870831 E-mail:xuxiaoguo1981@sohu.com

Use and limitation of surrogate outcomes in clinical trials

XU Xiao-guo, JIANG Meng

Clinical Pharmaological Section of Hospital Attached to Nanjiang University of Traditional Chinese Medicine, Nanjing 210029 , Jiangsu, China

Received:2006-06-12 Revised:2006-09-10 Online:2006-10-26 Published:2020-11-05

摘要/Abstract

摘要： 本文依据国内外临床试验中结局指标选择的现状, 论述了替代指标与终点指标的概念及其关系,以及在临床试验中结局指标选择基本方法及其当前存在的问题。强调只有对患者有直接影响的终点指标才能够证实干预措施的真正疗效, 而以实验室为主的生物学指标和患者的临床症状或体征等替代指标, 只有被证实与真正临床结局具有因果关系且能客观反映临床措施对临床结局净效应的情况下, 才能够作为代替终点指标的评价指标使用。

关键词: 替代指标, 终点指标, 临床试验, 应用, 局限性

Abstract: According to the status quo of choosing outcome indexes in Chinese and other countries'clinical trials, propose the concepts of surrogate outcomes and end points and correlation between them, discuss the general methods and present problems of choosing true endpoints.It is emphasized that only the primary outcomes which affect the patients directly can prove the real effectiveness of the interventions.Only when the surrogate ones, such as biological indexes from laboratory and the patients'symptoms or signs, which are proved to have a correlate of the true clinical outcome and fully capture the net effect of treatment on the clinical outcome, can the latter be the substitute for the former.

Key words: surrogate outcomes, end points, clinical trials, use and limitation

中图分类号:

R969

徐小国, 蒋萌. 替代指标在临床试验中的应用与局限性[J]. 中国临床药理学与治疗学, 2006, 11(10): 1194-1197.

XU Xiao-guo, JIANG Meng. Use and limitation of surrogate outcomes in clinical trials[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1194-1197.

参考文献

1 赖世隆.中医药临床疗效的评价[J].中国中医药信息杂志, 2000;7:88-9
2 Word Health Organization Report.Consultation meeting on traditional and modern medicine:harmonizing the two approaches[ C].Beijing, China, 1996:16
3 Jay H.The use of surrogate endpoints in clinical trials [J].Statistics inMedicine, 1989;8:403
4 胡大一, 项志敏.临床医学模式转变-从经验医学到循证医学[J].中国实用内科学杂志, 1998;18:668
5 魏华凤, 郑培永, 季光.中医临床疗效评价的思路与方法[J].中西医结合学报, 2005;3:184-90
6 Temple RJ.A regular authoritys opinion about surrogate endpoints[A].Nimmo WS, Tucker GT, eds Clinical measurement in durg evaluation[M].New York:John Wiley &Sons Ltd,1995;3-22
7 Prentice RL.Surrogate endpoints in clinical trials:definition and operational criteria[J].Stat Med, 1989;8:431-40
8 Fleming TR, DeMets DL.Surrogate endpoints in clinical trials:are we being misled[J] ? Ann Intern Med, 1996;125:605-13
9 郭新峰, 赖世隆, 梁伟雄.中医药疗效评价中结局指标的选择与应用[J].广州中医药大学学报, 2002;19:251-5
10 Levin JS, Glass TA, Kushi LH, Schuck JR, Steele L, Jonas WB.Quantitation methods in research on comphementary and alternative medicine.A methodological manifesto [J].Med Cave, 1997;35:1079
11 郭新峰, 朱泉, 赖世隆.替代指标和中间指标及其在中医药疗效评价研究中应用价值的思考[J].中国中西医结合杂志, 2005;25:585-90
12 Bucher HC, Guyatt GH, Cook DJ, Holbrook A, McAlister FA.Users'guides to the medical literatrue:XIX.Applying clinical trial results.A.How to use an article measuring the effect of an intervention on surrogate end points[J].JAMA, 2000;19:192-7
13 Stuart G.Baker.Surrogate Endpoints:Wishful Thinking or Reality[J] ? J Natl Cancer Inst, 2006;98:502-3
14 方向华.替代终点在心血管病临床试验中的运用及其局限性[J].循证医学, 2005;5:364-6
15 宋军, 陈可冀.中医药临床疗效评价若干问题思考[J].中国中西医结合杂志, 2003;23:564-5
16 Susan S.Ellenberg surrogate endpoints:the debate goes on[J].Pharmacoepidemiol Drug Safety, 2001;10:493-6
17 王树堂, 周岱翰.对于目前恶性肿瘤临床疗效评价标准的评价[J].天津中医药, 2004;21:227-80
18 Tseng LN, SheuWH, Ho ES, Lan HH, Hu CC, Kao CH.Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women[J].Metab Clin Exp, 2006;55:741-7
19 Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, et al.Blood pressure, stroke,coronary heart disease.Part 2, Short-term reductions in blood pressure:overview of randomized drug trials in their epidemiological context[J].Lancet, 1990;335:827-38 Chin J Clin Pharmacol Ther 2006 Oct;11(10)
20 SHEPCooperative Research Group.Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension:final results of the systolic hypertension in the elderly program (SHEP) [J].JAMA, 1991;265:3255-64
21 Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS, Lemaitre R, Smith NL, et al.The risk of incident myocardial infarction associated with anti-hypertensive drug therapies [J].Circulation,1996;91:925
22 Ettinger b, San Martin J, Crans G, Pavo I.Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate[J].J Bone Mine Res, 2004;19:745-51
23 Riggs BL, Hodgson SF, O'Fallon WM, Chao EY, Wahner HW, Muhs JM, et al.Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis[J].N Engl J Med, 1990;322:802-9
24 Riggs BL, Seeman E, Hodgson SF, Taves DR, O'Fallon WM.Effect of the fluoride calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis.Comparison with conventional therapy[J].N Engl JMed, 1982;306:446-50

[1]	王安婧, 王亚亚, 梁轩, 闫雅婕, 苏静, 李彩东. 基于PPAR治疗胆汁淤积性肝病的机制与药物研究进展[J]. 中国临床药理学与治疗学, 2023, 28(7): 796-808.
[2]	戴加惠, 孙思嘉, 解雪峰. 医疗器械临床试验质量管理及指标体系研究[J]. 中国临床药理学与治疗学, 2023, 28(1): 51-58.
[3]	邵明坤, 刘蓉, 孙品, 关水, 廖炳灿, 李莎, 丛滔, 梁凯, 马辉, 孙长凯. 褪黑素人体网络机制及其临床应用[J]. 中国临床药理学与治疗学, 2022, 27(9): 1031-1040.
[4]	陈建芳, 娄冬华. 基于CDASH标准的肿瘤临床试验病例报告表设计[J]. 中国临床药理学与治疗学, 2022, 27(7): 762-767.
[5]	刘星, 卢晓然, 吴影, 于海涛, 王晓敏. 人工智能应用于临床试验的伦理问题分析及对策[J]. 中国临床药理学与治疗学, 2022, 27(3): 322-327.
[6]	朱丽丽, 朱秀秀, 王文俊, 张海邻, 林立. 国内儿科人群吸入制剂药物临床试验现状分析[J]. 中国临床药理学与治疗学, 2022, 27(2): 178-183.
[7]	李珊珊, 顾静文, 张菁, 杨海静, 刘薇, 喻一奇, 张文宏. 新冠病毒疫苗与单克隆中和抗体各期临床试验设计及评价概述[J]. 中国临床药理学与治疗学, 2022, 27(2): 190-197.
[8]	邓锟红, 刘亚昕, 孙媛媛, 陈文静, 杨楠, 胡展晴, 陈凯锋, 黄洁, 项玉霞, 阳国平. 2009－2020年药物首次人体试验设计及结果文献分析[J]. 中国临床药理学与治疗学, 2022, 27(1): 77-85.
[9]	郑莹, 张玲, 姚丽, 王乾合, 朱克祥. 聚腺苷二磷酸-核糖聚合酶抑制剂在胰腺癌中的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(1): 108-115.
[10]	佘志华, 陈舟, 梁松岳. 基于云架构的药物临床试验伦理审查信息化体系建设[J]. 中国临床药理学与治疗学, 2021, 26(9): 1023-1030.
[11]	宋岩, 高琳艳, 张艳平, 李想, 张兰. 医疗失效模式与效应分析在I期临床试验血液样本管理中的应用[J]. 中国临床药理学与治疗学, 2021, 26(9): 1031-1036.
[12]	欧阳晨溪, 黄洁, 项玉霞, 王晓敏. 早期临床试验的伦理问题及对策探讨[J]. 中国临床药理学与治疗学, 2021, 26(7): 802-807.
[13]	王金伙, 郭建荣. 阿芬太尼的临床药理特性及其麻醉应用进展[J]. 中国临床药理学与治疗学, 2021, 26(7): 824-829.
[14]	黄丽红, 王陵, 言方荣, 魏朝晖, 赵杨, 夏结来, 陈峰. 新视角解读临床试验中的意向性原则[J]. 中国临床药理学与治疗学, 2021, 26(4): 449-453.
[15]	张茜, 胡伟, 余斌, 秦慧玲, 陈明壮, 鲁超. 基于文献分析法的药物临床试验信息化建设[J]. 中国临床药理学与治疗学, 2021, 26(2): 182-189.