Use and limitation of surrogate outcomes in clinical trials

Abstract

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

CLC Number:

R969

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.

References

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

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