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药物利用研究(DUR)是促进用药安全、有效和经济的重要手段[1]。随机对照临床试验(RCT)作为评价药物安全性、有效性的金标准,在外推至日常诊疗环境时往往面临挑战。作为RCT的重要补充,真实世界研究(RWS)考察日常诊疗环境中产生的真实世界数据(RWD),注重评价药物使用的“安全性”和“有效性”,已经成为药物利用研究的热点[2]。RWS着眼于应用到医疗实践环境中,大大缩短了试验周期、降低了成本,真实世界实效性临床研究更加易于获取全面的病例数据,使其结果更具有可靠性及可行性[3]。应当正确认识两者关系,将两者作为互补且相辅相成的研究方法和手段来为药物利用评价和监管评价等方面提供循证支持[4-7]。
随着医院管理信息系统(HIS)的高速发展以及高新传感器技术在生物医疗领域探索运用,使得逐步精准化、数字化患者的各项检查及健康诊疗数据成为现实,并进一步完善患者诊疗、实验室检查以及用药信息等全生命周期的医疗记录,且便于追溯及交互关联[2]。尽管数据库技术及大数据挖掘服务于药物安全性、有效性等方面研究成为现实,但应用于DUR尚缺乏具体的技术指导方案、自然流程等。本研究借鉴国内外RWS在药品器械上市后适应证开发及安全性评价方面的做法,梳理DUR中RWS有效技术手段和方法路径,为RWS更好的服务于DUR提供借鉴和参考。
Review of drug utilization research based on real-world data
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摘要: 近年来,医学信息技术突飞猛进,基于真实环境分析大规模的诊疗数据并挖掘其中规律,已经成为国内外药械上市评价及监管决策的重要手段。真实世界研究作为药物利用研究领域一种新的药物临床评价方法,为观察性研究在实际疗效或效果方面的评价带来了机遇和挑战。然而,作为药物利用研究领域广大学者关注的热门方法学手段,当前真实世界研究关于人群用药特征分析还存在一些局限和不足,尚未形成系统性的评估研究方法,还不能很好的生成真实世界证据。该研究旨在综述基于真实世界数据的药物利用研究的研究设计、方法路径、评价指标、混杂因素及偏倚处理等进展,以便为药物利用研究深入开展提供参考。Abstract: In recent years, the rapid development of medical information technology has made it critical to analyze large-scale diagnosis and therapeutic data and extract rules based on real medical environment. This has become an essential approach for marketing evaluation and regulatory decision-making of drugs and devices both domestically and internationally. Real world study (RWS), as a novel methodology for clinical evaluation of drugs in the field of drug utilization research (DUR), have presented opportunities and challenges for observational studies in assessing actual efficacy or effectiveness. However, despite being a popular methodological approach among scholars in the field, there are still limitations and deficiencies when analyzing population medication characteristics in RWS. Systematic evaluation research methods have not yet been established, leading to inadequate generation of real-world evidence (RWE). The research design, methodological pathways, evaluation indicators, confounding factors, and bias management involved in DUR based on real-world data (RWD) were reviewed in this artical with the intention of providing guidance for further exploration into DUR.
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[1] WETTERMARK B, ELSEVIERS M, ALMARSDÓTTIR AB, et al. Introduction to drug utilization research. In: Elseviers [M]. Chichester, UK: John Wiley & Sons, Ltd; 2016:1-12. [2] 杜春霖, 李晓松, 刘元元. 真实世界研究及国内文献综述[J]. 中国卫生信息管理杂志, 2018, 15(5):597-601. [3] 张晓雨, 陈静, 赵晨, 等. 真实世界理念下观察性与实验性临床研究协同应用[J]. 中国循证医学杂志, 2018, 18(4):284-288. doi: 10.7507/1672-2531.201710034 [4] 黄卓山, 罗艳婷, 刘金来. 真实世界研究的方法与实践[J]. 循证医学, 2014, 14(6):364-368. [5] 田磊, 岳彩宾, 管欣, 等. 真实世界研究与随机对照试验在临床实践及卫生决策中应用的比较[J]. 中国医院药学杂志, 2019, 39(3):274-277. [6] 吴一龙, 陈晓媛, 杨志敏. 真实世界研究指南[M].2018版. 北京:人民卫生出版社,2019:1-28. [7] FRANKLIN J M, SCHNEEWEISS S. When and how can real world data analyses substitute for randomized controlled trials?[J]. Clin Pharmacol Ther, 2017, 102(6):924-933. doi: 10.1002/cpt.857 [8] 方碧陶. 国家药品监督管理局印发《真实世界证据支持药物研发与审评的指导原则(试行)》[J]. 中医药管理杂志, 2020, 28(2):107. [9] OHTSU H, SHIMOMURA A, SASE K. Real-world evidence in cardio-oncology: what is it and what can it tell us?[J]. JACC CardioOncol, 2022, 4(1):95-97. doi: 10.1016/j.jaccao.2022.02.002 [10] 李雪迎, 沙若琪, 姚晨, 等. 面向真实世界数据的临床研究数据治理模式选择[J]. 中国循证医学杂志, 2020, 20(10):1150-1156. doi: 10.7507/1672-2531.202003122 [11] 孙鑫, 谭婧, 唐立, 等. 重新认识真实世界研究[J]. 中国循证医学杂志, 2017, 17(2):126-130. doi: 10.7507/1672-2531.201701088 [12] MONTILLA S, MARCHESINI G, SAMMARCO A, et al. Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry[J]. Nutr Metab Cardiovasc Dis, 2014, 24(12):1346-1353. doi: 10.1016/j.numecd.2014.07.014 [13] SHANG N, WENG C H, HRIPCSAK G. A conceptual framework for evaluating data suitability for observational studies[J]. J Am Med Inform Assoc, 2018, 25(3):248-258. doi: 10.1093/jamia/ocx095 [14] WEISKOPF N G, WENG C H. Methods and dimensions of electronic health record data quality assessment: enabling reuse for clinical research[J]. J Am Med Inform Assoc, 2013, 20(1):144-151. doi: 10.1136/amiajnl-2011-000681 [15] 国家药品监督管理局. 国家药监局药审中心关于发布《真实世界研究支持儿童药物研发与审评的技术指导原则(试行)》的通告(2020年第22号)[EB/OL]. (2020-09-01) [2024-01-01]. https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20200901104448101.html. [16] 赵亮, 张婷, 孔文妹, 等. 基于医院信息系统的真实世界研究主题分析[J]. 医药导报, 2022, 41(1):63-72. [17] 王俊月, 何泽慧, 邓浩, 等. 基于真实世界数据的芍苓方治疗寻常型银屑病的疗效与安全性分析[J]. 中药新药与临床药理, 2021, 32(5):739-743. [18] LIU F X, OU W M, DIEDE S J, et al. Real-world experience with pembrolizumab in patients with advanced melanoma: a large retrospective observational study[J]. Medicine, 2019, 98(30):e16542. doi: 10.1097/MD.0000000000016542 [19] 刁一凡. 我国新型抗肿瘤药物公共保障政策与药物可及性评估研究[D]. 北京: 北京协和医学院, 2021. DOI: 10.27648/d.cnki.gzxhu.2020.000907. [20] 贾玉龙, 姚明宏, 刘艳梅, 等. 特许医疗政策下真实世界数据治理的模式探索[J]. 中国循证医学杂志, 2021, 21(12):1373-1380. doi: 10.7507/1672-2531.202108147 [21] 周雪莹, 张策, 方丽萍, 等. 基于真实世界的3种止吐方案预防含顺铂多日化疗相关恶心呕吐的成本-效用分析[J]. 中国药房, 2021, 32(20):2509-2513. doi: 10.6039/j.issn.1001-0408.2021.20.12 [22] 张若梅, 吴斌. 3种促排卵药物在IVF-ET/ICSI中的临床疗效与经济学分析: 1项基于真实世界的回顾性分析[J]. 中国现代应用药学, 2021, 38(17):2128-2133. [23] ARMSTRONG A W, FOSTER S A, COMER B S, et al. Real-world health outcomes in adults with moderate-to-severe psoriasis in the United States: a population study using electronic health records to examine patient-perceived treatment effectiveness, medication use, and healthcare resource utilization[J]. BMC Dermatol, 2018, 18(1):4. doi: 10.1186/s12895-018-0072-2 [24] 乔佳慧, 杨浦, 董丽, 等. 真实世界研究方法在中成药上市后安全性评价中的应用[J]. 中国新药杂志, 2021, 30(9):769-772. doi: 10.3969/j.issn.1003-3734.2021.09.001 [25] 孙鑫, 张俊华, 王雯, 等. 制定中国中成药真实世界研究技术指导原则, 促进中成药临床研究向决策证据转化[J]. 中国循证医学杂志, 2020, 20(9):993-999. [26] 王明霞, 王淑梅, 刘明, 等. 真实世界中30 012例参麦注射液使用情况与安全性评价[J]. 中国循证医学杂志, 2021, 21(2):133-138. [27] 胡文, 侯政昆, 刘凤斌, 等. 关于大数据时代的中医药临床研究的思考[J]. 世界科学技术-中医药现代化, 2019, 21(8):1656-1661. [28] 邹冲, 蒋萌, 蒋卫民, 等. 构建基于临床大数据真实世界的中医药临床科研模式[J]. 中华中医药杂志, 2016, 31(10):4113-4116. [29] 陈秋平, 邵明义, 毕倩, 等. 基于叙事循证医学对中医临床疗效评价问题的解决策略[J]. 中国中药杂志, 2022, 47(2):557-561. [30] KLONOFF D C. The new FDA real-world evidence program to support development of drugs and biologics[J]. J Diabetes Sci Technol, 2020, 14(2):345-349. doi: 10.1177/1932296819832661 [31] U.S.FOOD AND DRUG ADMINISTRATION. Statement from FDA Commissioner Scott Gottlieb, M. D. , on FDA's new strategic framework to advance use of real-world evidence to support development of drugs and biologics[EB/OL]. (2018-01-01) [2024-01-01]. https://www.regulatoryaffairsnews.com/post/ ema-guidance-good-practice-guide-for-the-use-of-the-metadata- catalogue-of-real-world-data-sources. [32] EUROPEAN MEDICINES AGENCY. Good practice guide for the use of the Metadata Catalogue of Real-World Data Sources[EB/OL].(2022-09-01) [2023-12-31]. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/good-practice-guide-use-metadata-catalogue-real-world-data-sources_en.pdf. [33] 田磊, 徐赫, 孟蕊, 等. 不同类型临床证据在卫生决策中的应用进展: 以英国NICE为例[J]. 中国循证医学杂志, 2020, 20(1):112-118. [34] KRASENBAUM L J, PEDARLA V L, THOMPSON S F, et al. A real-world study of acute and preventive medication use, adherence, and persistence in patients prescribed fremanezumab in the United States[J]. J Headache Pain, 2022, 23(1):54. doi: 10.1186/s10194-022-01413-z [35] SULTANA J, TRIFIRÒ G, IENTILE V, et al. Traceability of pediatric antibiotic purchasing pathways in Italy: a nationwide real-world drug utilization analysis[J]. Front Pharmacol, 2020, 11:1232. doi: 10.3389/fphar.2020.01232 [36] POULIN Y, BEAUCHEMIN C, ROYER C, et al. Real-world experience with apremilast in the treatment of adults with moderate to severe plaque psoriasis in québec: a claims-based analysis of drug utilization and healthcare resource utilization[J]. J Cutan Med Surg, 2020, 24(6):573-587. doi: 10.1177/1203475420936652 [37] 董晓丽, 宫建. 真实世界药物评价的伦理价值与伦理问题[J]. 医药导报, 2022, 41(1):44-47. [38] 张海洪, 熊保权, 丛亚丽. 伦理审查质量: 以真实世界研究的伦理审查质量改进为例[J]. 医学与哲学, 2021, 42(21):11-14,18. doi: 10.12014/j.issn.1002-0772.2021.21.03 [39] 于茜, 王卯, 赵晓倩, 等. 真实世界研究的知情同意方式探讨[J]. 中药新药与临床药理, 2021, 32(7):1055-1058. [40] 李洪, 魏来, 郭晓蕙, 等. 真实世界研究伦理审查初探[J]. 中国循证医学杂志, 2018, 18(11):1198-1202. [41] 王思成, 刘保延, 熊宁宁, 等. 真实世界临床研究伦理问题及策略探讨[J]. 中国中西医结合杂志, 2013, 33(4):437-442. [42] HOLLINGWORTH S, KAIRUZ T. Measuring medicine use: applying ATC/DDD methodology to real-world data[J]. Pharmacy, 2021, 9(1):60. doi: 10.3390/pharmacy9010060 [43] SOLÀ-MORALES O, SIGURÐARDÓTTIR K, AKEHURST R, et al. Data governance for real-world data management: a proposal for a checklist to support decision making[J]. Value Health, 2023, 26(4S):32-42. [44] 王雯, 谭婧, 任燕, 等. 重新认识真实世界数据研究: 更新与展望[J]. 中国循证医学杂志, 2020, 20(11):1241-1246. [45] WINTZELL V, SVANSTRÖM H, PASTERNAK B. Selection of Comparator Group in Observational Drug Safety Studies: Alternatives to the Active Comparator New User Design [J]. Epidemiology, 2022, 33(5): 707-714. [46] VELENTGAS P, DREYER NA, NOURJAH P, et al. Developing a Protocol for Observational Comparative Effectiveness Research: A User’s Guide[M]. Rockville(MD): Agency for Healthcare Research and Quality(US), 2013. [47] TALBOT J, STUCKEY R, CRAWFORD L, et al. Improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment - real world outcomes[J]. J Headache Pain, 2021, 22(1):5-10. doi: 10.1186/s10194-020-01214-2 [48] PAJECKI D, KAWAMOTO F, DANTAS A C B, et al. Real-world evidence of health outcomes and medication use 24 months after bariatric surgery in the public healthcare system in Brazil: a retrospective, single-center study[J]. Clinics, 2020, 75:e1588. doi: 10.6061/clinics/2020/e1588 [49] 张学成, 刘岩, 张晶晶, 等. 急性心力衰竭患者30天再住院率: 基于真实世界研究与随机对照试验比较的Meta分析[J]. 中国循证医学杂志, 2021, 21(10):1203-1210. [50] AL-MADFAA R O, ALALAWI M A, BASUDAN L O, et al. Dual versus triple therapy for uncomplicated brucellosis: a retrospective cohort study[J]. J Infect Dev Ctries, 2020, 14(12):1380-1386. doi: 10.3855/jidc.12741 [51] TAKEUCHI Y, SANO H, ASAI Y, et al. Real-world evidence of the safety and efficacy profile of suvorexant in elderly patients with insomnia: a sub-analysis of the post-marketing drug-use results survey in Japan[J]. Curr Med Res Opin, 2020, 36(3):465-471. doi: 10.1080/03007995.2019.1700361 [52] 宣建伟, 李幼平. 真实世界研究与创新药物价值[J]. 中国循证医学杂志, 2018, 18(4):273-276. doi: 10.7507/1672-2531.201801090 [53] 刘雪丽, 韩晟, 官海静, 等. 基于真实世界数据开展药物经济学评价[J]. 中国研究型医院, 2017, 4(3):24-27. [54] HUANG J F, MENG Z, ZHENG X Q, et al. Real-world evidence in prescription medication use among U. S. adults with neck pain[J]. Pain Ther, 2020, 9(2):637-655. doi: 10.1007/s40122-020-00193-1 [55] 柏柳安宁, 夏结来, 王陵, 等. 真实世界研究中的常见偏倚及其控制[J]. 中国临床药理学与治疗学, 2020, 25(12):1422-1428. doi: 10.12092/j.issn.1009-2501.2020.12.015
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