留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望

卢存存 陈子佳 王志飞

卢存存, 陈子佳, 王志飞. 基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望[J]. 协和医学杂志, 2024, 15(2): 422-428. doi: 10.12290/xhyxzz.2023-0398
引用本文: 卢存存, 陈子佳, 王志飞. 基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望[J]. 协和医学杂志, 2024, 15(2): 422-428. doi: 10.12290/xhyxzz.2023-0398
LU Cuncun, CHEN Zijia, WANG Zhifei. Novel Framework (Target Trial Emulation) in Observational Causal Inference Research Based on Real-world Data and Its Application Prospects in Traditional Chinese Medicine[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(2): 422-428. doi: 10.12290/xhyxzz.2023-0398
Citation: LU Cuncun, CHEN Zijia, WANG Zhifei. Novel Framework (Target Trial Emulation) in Observational Causal Inference Research Based on Real-world Data and Its Application Prospects in Traditional Chinese Medicine[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(2): 422-428. doi: 10.12290/xhyxzz.2023-0398

基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望

doi: 10.12290/xhyxzz.2023-0398
基金项目: 

中国中医科学院科技创新工程 CI2021A00702

详细信息
    通讯作者:

    卢存存, E-mail: cuncunlu2017@163.com

    王志飞, E-mail: wzhftcm@163.com

  • 中图分类号: R181.2; R242

Novel Framework (Target Trial Emulation) in Observational Causal Inference Research Based on Real-world Data and Its Application Prospects in Traditional Chinese Medicine

Funds: 

CACMS Innovation Fund CI2021A00702

More Information
  • 摘要: “目标试验模拟”(target trial emulation)作为一种新的真实世界研究框架在近年来被正式确立,其可用于指导基于真实世界数据开展观察性因果推断研究,继而进行医疗干预有效性和安全性评价。该框架的核心思想是参照随机对照试验的原则,利用真实世界数据模拟相应的随机对照试验,进而得出干预措施与临床结局间因果关联的结论。其主要实施要点可总结为“3-7-2”,即声明因果问题、制订模拟方案和模拟目标研究3个实施步骤,纳排标准、治疗策略、干预分配、随访期、结局指标、因果比较和分析计划7个设计要素,对永恒时间偏倚和现用药者偏倚2个关键偏倚的控制。本文通过对该框架的历史与现状、实施要点、经典案例、优势与局限性及其在中医药领域中的应用前景进行概述,以期帮助中医药学者开展中医药真实世界研究,并为构建具有中医药特色的临床评价体系提供新思路。
    作者贡献:卢存存负责查阅资料、论文撰写;陈子佳负责论文修订;王志飞负责论文修订与审校。
    利益冲突:所有作者均声明不存在利益冲突
  • [1] 马忠贵, 徐晓晗, 刘雪儿. 因果推断三种分析框架及其应用综述[J]. 工程科学学报, 2022, 44(7): 1231-1243. https://www.cnki.com.cn/Article/CJFDTOTAL-BJKD202207013.htm

    Ma Z G, Xu X H, Liu X E. Three analytical frameworks of causal inference and their applications[J]. Chin J Eng, 2022, 44(7): 1231-1243. https://www.cnki.com.cn/Article/CJFDTOTAL-BJKD202207013.htm
    [2] 任国强, 王于丹, 周云波. 科学研究中因果推断的方法、应用与展望——以个体健康研究为例[J]. 人口与经济, 2022(2): 1-25. https://www.cnki.com.cn/Article/CJFDTOTAL-RKJJ202202001.htm

    Ren G Q, Wang Y D, Zhou Y B. Methods, applications and prospects of causal inference in scientific research: a study of individual health research[J]. Popul Econ, 2022(2): 1-25. https://www.cnki.com.cn/Article/CJFDTOTAL-RKJJ202202001.htm
    [3] 卢存存, 陈子佳, 张强, 等. 基于真实世界数据的目标试验模拟研究: 现状与展望[J]. 中国循证医学杂志, 2023, 23(4): 492-496. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ202304011.htm

    Lu C C, Chen Z J, Zhang Q, et al. Target trial emulation study based on real world data: status quo and prospect[J]. Chin J Evid Based Med, 2023, 23(4): 492-496. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ202304011.htm
    [4] 谢朝荣, 陶庆锋, 胡缤予, 等. 孟德尔随机化研究及其在中医药领域的应用展望[J]. 中医杂志, 2023, 64(5): 438-442. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202305002.htm

    Xie C R, Tao Q F, Hu B Y, et al. Mendelian randomization and its application in traditional Chinese medicine[J]. J Tradit Chin Med, 2023, 64(5): 438-442. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202305002.htm
    [5] Schuler M S, Rose S. Targeted maximum likelihood estima-tion for causal inference in observational studies[J]. Am J Epidemiol, 2017, 185(1): 65-73. doi:  10.1093/aje/kww165
    [6] Hernán M A, Robins J M. Causal inference: what if[M]. Boca Raton: Chapman & Hall/CRC, 2020.
    [7] Thomas L E, Li F, Pencina M J. Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial[J]. JAMA, 2020, 323(23): 2417-2418. doi:  10.1001/jama.2020.7819
    [8] Franklin J M, Glynn R J, Martin D, et al. Evaluating the use of nonrandomized real-world data analyses for regulatory decision making[J]. Clin Pharmacol Ther, 2019, 105(4): 867-877. doi:  10.1002/cpt.1351
    [9] Zhao S S, Lyu H, Solomon D H, et al. Improving rheuma-toid arthritis comparative effectiveness research through causal inference principles: systematic review using a target trial emulation framework[J]. Ann Rheum Dis, 2020, 79(7): 883-890. doi:  10.1136/annrheumdis-2020-217200
    [10] Bykov K, Patorno E, D'Andrea E, et al. Prevalence of avoidable and bias-inflicting methodological pitfalls in real-world studies of medication safety and effectiveness[J]. Clin Pharmacol Ther, 2022, 111(1): 209-217. doi:  10.1002/cpt.2364
    [11] Hansford H J, Cashin A G, Jones M D, et al. Reporting of observational studies explicitly aiming to emulate randomized trials: a systematic review[J]. JAMA Netw Open, 2023, 6(9): e2336023. doi:  10.1001/jamanetworkopen.2023.36023
    [12] Murray E J, Marshall B D L, Buchanan A L. Emulating target trials to improve causal inference from Agent-Based models[J]. Am J Epidemiol, 2021, 190(8): 1652-1658. doi:  10.1093/aje/kwab040
    [13] Hernán M A, Robins J M. Using big data to emulate a target trial when a randomized trial is not available[J]. Am J Epidemiol, 2016, 183(8): 758-764. doi:  10.1093/aje/kwv254
    [14] Fu E L. Target trial emulation to improve causal inference from observational data: what, why, and how?[J]. J Am Soc Nephrol, 2023, 34(8): 1305-1314. doi:  10.1681/ASN.0000000000000152
    [15] 赵骏, 王骏. 应用模拟目标临床试验概念设计观察性研究时的若干考虑[J]. 中国新药杂志, 2022, 31(18): 1801-1803. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202218007.htm

    Zhao J, Wang J. Considerations for designing observational studies using targeted trial emulation concept[J]. Chin J New Drug, 2022, 31(18): 1801-1803. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202218007.htm
    [16] He W L, Fang Y X, Wang H W. Real-world evidence in medical product development[M]. Cham: Springer, 2023.
    [17] 国家药监局药审中心. 国家药监局药审中心关于发布《药物真实世界研究设计与方案框架指导原则(试行)》的通告(2023年第5号)[EB/OL]. (2023-02-16)[2023-08-25]. https://www.cde.org.cn/main/news/viewInfoCommon/14aac16a4fc5b5841bc2529988a611cc.

    National Medical Products Administration Drug Approval Center. Notice of the Drug Review Center of the National Medical Products Administration on issuing the guiding principles for the design and protocol framework of real world drug research (trial) (No. 5, 2023)[EB/OL]. (2023-02-16)[2023-08-25]. https://www.cde.org.cn/main/news/viewInfoCommon/14aac16a4fc5b5841bc2529988a611cc.
    [18] 程海波, 张磊, 付勇, 等. 2023年度中医药重大科学问题、工程技术难题和产业技术问题[J]. 中医杂志, 2023, 64(14): 1405-1421. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202314001.htm

    Cheng H B, Zhang L, Fu Y, et al. 2023 Major scientific issues, engineering challenges and industrial technology problems[J]. J Tradit Chin Med, 2023, 64(14): 1405-1421. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202314001.htm
    [19] Hernán M A, Alonso A, Logan R, et al. Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease[J]. Epidemiology, 2008, 19(6): 766-779. doi:  10.1097/EDE.0b013e3181875e61
    [20] Kutcher S A, Brophy J M, Banack H R, et al. Emulating a randomised controlled trial with observational data: an introduction to the target trial framework[J]. Can J Cardiol, 2021, 37(9): 1365-1377. doi:  10.1016/j.cjca.2021.05.012
    [21] Dickerman B A, García-Albéniz X, Logan R W, et al. Avoidable flaws in observational analyses: an application to statins and cancer[J]. Nat Med, 2019, 25(10): 1601-1606. doi:  10.1038/s41591-019-0597-x
    [22] Stürmer T, Wang T S, Golightly Y M, et al. Methodological considerations when analysing and interpreting real-world data[J]. Rheumatology (Oxford), 2020, 59(1): 14-25. doi:  10.1093/rheumatology/kez320
    [23] Vail E A, Gershengorn H B, Wunsch H, et al. Attention to immortal time bias in critical care research[J]. Am J Respir Crit Care Med, 2021, 203(10): 1222-1229. doi:  10.1164/rccm.202008-3238CP
    [24] Sendor R, Stürmer T. Core concepts in pharmacoepidemiology: Confounding by indication and the role of active comparators[J]. Pharmacoepidemiol Drug Saf, 2022, 31(3): 261-269. doi:  10.1002/pds.5407
    [25] Hernán M A. How to estimate the effect of treatment duration on survival outcomes using observational data[J]. BMJ, 2018, 360: k182.
    [26] Schneeweiss S, Patorno E. Conducting real-world evidence studies on the clinical outcomes of diabetes treatments[J]. Endocr Rev, 2021, 42(5): 658-690. doi:  10.1210/endrev/bnab007
    [27] Hansford H J, Cashin A G, Jones M D, et al. Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline[J]. BMJ Open, 2023, 13(9): e074626. doi:  10.1136/bmjopen-2023-074626
    [28] Wang S V, Schneeweiss S, RCT-DUPLICATE Initiative. Emulation of randomized clinical trials with nonrandomized database analyses: results of 32 clinical trials[J]. JAMA, 2023, 329(16): 1376-1385. doi:  10.1001/jama.2023.4221
    [29] Patorno E, Schneeweiss S, Gopalakrishnan C, et al. Using real-world data to predict findings of an ongoing phase Ⅳ cardiovascular outcome trial: cardiovascular safety of linagliptin versus glimepiride[J]. Diabetes Care, 2019, 42(12): 2204-2210. doi:  10.2337/dc19-0069
    [30] Admon A J, Donnelly J P, Casey J D, et al. Emulating a novel clinical trial using existing observational data. Predicting results of the PreVent study[J]. Ann Am Thorac Soc, 2019, 16(8): 998-1007. doi:  10.1513/AnnalsATS.201903-241OC
    [31] Hernán M A, Wang W, Leaf D E. Target trial emulation: a framework for causal inference from observational data[J]. JAMA, 2022, 328(24): 2446-2447. doi:  10.1001/jama.2022.21383
    [32] 王志飞, 谢雁鸣. 中药上市后"三维四阶" 临床定位技术的构想与实践[J]. 中国中药杂志, 2021, 46(8): 1967-1972. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY202108016.htm

    Wang Z F, Xie Y M. Conception and practice of "three dimensions and four stages" clinical orientation method for post-marketing evaluation of traditional Chinese medicine[J]. Chin Mater Med, 2021, 46(8): 1967-1972. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY202108016.htm
    [33] 安娜, 韩玲, 陈平雁. "三结合" 中药注册审评证据体系下中药新药真实世界研究的思考[J]. 中国新药杂志, 2022, 31(14): 1359-1363. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202214003.htm

    An N, Han L, Chen P Y. Reflections on real world research under the evidence system of "three combinations" registration and evaluation of new traditional Chinese medicine[J]. Chin J New Drug, 2022, 31(14): 1359-1363. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202214003.htm
    [34] Moler-Zapata S, Hutchings A, O'neill S, et al. Emulating target trials with real-world data to inform health technology assessment: findings and lessons from an application to emergency surgery[J]. Value Health, 2023, 26(8): 1164-1174. doi:  10.1016/j.jval.2023.04.010
    [35] Gomes M, Latimer N, Soares M, et al. Target trial emulation for transparent and robust estimation of treatment effects for health technology assessment using real-world data: opportunities and challenges[J]. Pharmacoeconomics, 2022, 40(6): 577-586. doi:  10.1007/s40273-022-01141-x
    [36] Zhang Y Q, Lu L M, Xu N G, et al. Increasing the usefulness of acupuncture guideline recommendations[J]. BMJ, 2022, 376: e070533.
    [37] Zuo H X, Yu L, Campbell S M, et al. The implementation of target trial emulation for causal inference: a scoping review[J]. J Clin Epidemiol, 2023, 162: 29-37. doi:  10.1016/j.jclinepi.2023.08.003
    [38] Scola G, Chis Ster A, Bean D, et al. Implementation of the trial emulation approach in medical research: a scoping review[J]. BMC Med Res Methodol, 2023, 23(1): 186. doi:  10.1186/s12874-023-02000-9
    [39] 中华医学会临床流行病学和循证医学分会中医学组. 新时代中医药临床研究方法论专家共识[J]. 协和医学杂志, 2022, 13(5): 783-788. doi:  10.12290/xhyxzz.2022-0428

    Chinese Medicine Group, Clinical Epidemiology and Evidence-Based Medicine Association of Chinese Medical Association. Expert consensus on clinical research methodology of traditional Chinese medicine in the new era[J]. Med J PUMCH, 2022, 13(5): 783-788. doi:  10.12290/xhyxzz.2022-0428
    [40] 杨丰文, 季昭臣, 张明妍, 等. 中医药临床研究浪费原因及对策[J]. 中国循证医学杂志, 2018, 18(11): 1212-1215. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ201811015.htm

    Yang F W, Ji Z C, Zhang M Y, et al. Causes and countermeasures of waste in clinical research of Chinese medicine[J]. Chin J Evid Based Med, 2018, 18(11): 1212-1215. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ201811015.htm
    [41] Hoffmann J M, Bauer A, Grossmann R. The carbon footprint of clinical trials: a global survey on the status quo and current regulatory guidance[J]. BMJ Glob Health, 2023, 8(9): e012754. doi:  10.1136/bmjgh-2023-012754
  • 加载中
计量
  • 文章访问数:  193
  • HTML全文浏览量:  14
  • PDF下载量:  56
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-08-25
  • 录用日期:  2023-10-25
  • 网络出版日期:  2023-12-11
  • 刊出日期:  2024-03-30

目录

    /

    返回文章
    返回

    【温馨提醒】近日,《协和医学杂志》编辑部接到作者反映,有多名不法人员冒充期刊编辑发送见刊通知,鼓动作者添加微信,从而骗取版面费的行为。特提醒您,本刊与作者联系的方式均为邮件通知或电话,稿件进度通知邮箱为:mjpumch@126.com,编辑部电话为:010-69154261,请提高警惕,谨防上当受骗!如有任何疑问,请致电编辑部核实。谢谢!