Systems evidence-based medicine (sysEBM): a new model toward the studies on effects of traditional Chinese medicine interventions_Chinese Journal of Evidence-Based Medicine

Authors：

TAN Jing ^1,2,3 , WANG Wen ^1,2,3 , LI Ling ^1,2,3 , LIU Qingsong ^1,2,3 , MEI Fan ^1,2,3 , WANG Zichen ^2,3,4 , CHEN Chen ^1,2,3 , QIN Xuan ^1,2,3 , DING Ling ^1,2,3 , WANG Liqun ⁴ , LIU Jiali ^1,2,3 , LUO Xiaochao ^1,2,3 , LIU Xuehong ^1,2,3 , HE Yifei ^1,2,3 , WANG Wenling ^1,2,3 , REN Yan ^1,2,3 , LAI Qinhuai ^1,2,3 , XIONG Yiquan ^1,2,3 , YAO Minghong ^1,2,3 , XU Jiayue ^1,2,3 , YAO Yuqin ⁴ , CHEN Sujun ⁴ , JIANG Jingwen ⁴ , CHEN Chu ⁵ , GAO Jie ⁶ , JIN Zhao ⁷ ,  SUN Xin ^1,2,3,4

1. Chinese Evidence-Based Medicine Center/Chinese Cochrane Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Sichuan Center for Real World Data Innovation, Chengdu 610041, P. R. China;
3. Sichuan Center for Evidence-Based Chinese Medicine, Chengdu 610041, P. R. China;
4. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, P. R. China;
5. Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, P. R. China;
6. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, P. R. China;
7. Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China;

Corresponding author：

SUN Xin, Email: sunxin@wchscu.cn

Keywords：

Traditional Chinese medicine; Complex interventions; Effect off-target; Multidisciplinary research; Systems evidence-based medicine

DOI：

10.7507/1672-2531.202412110

Video：

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Abstract Full text Figures/Tables Video References Cited by

Traditional Chinese medicine (TCM) is a treasure of the Chinese nation. Presence of clinical effects represents a fundamental issue for TCM development. Nevertheless, the complexities of TCM interventions often result in presented effects deviating from expected ones, a phenomenon so called as "effect off-target"; this issue has become a major challenge for the development and use of TCM interventions. In continuing efforts, we have proposed an innovative evidence-based medicine model for studying the effects of TCM interventions, termed "systems evidence-based medicine (sysEBM)". Essentially, the sysEBM model integrates clinical and non-clinical evaluation to develop a systematic pathway for studying effects of TCM interventions, and the methodological steps typically include the development of PICO framework for a putative effect, exploration of the effect and confirmation of the effect by using animal models, observational studies and clinical trials. As an additional step, multidisciplinary technologies including pharmaceutical, pharmacological, information and biological technologies will be used to provide multidimensional analyses of potential action networks and mechanisms of TCM interventions. Building on this concept, we have developed a sysEBM model ("6R" model) for acupuncture and marketed Chinese patent medicines by integrating real-world evidence, clinical trials, evidence syntheses, and rapid recommendation methodologies, as well as information technology and biomedical technologies. We also applied this model for developing TCM interventions for maternal health, critical care, and knee osteoarthritis.

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2.	王停, 周刚, 赵保胜, 等. 中药新药研发策略分析. 中国新药杂志, 2017, 26(8): 865-871.
3.	肖培根, 肖小河. 21世纪与中药现代化. 中国中药杂志, 2000, (2): 3-6.
4.	Wang Y, Shi X, Li L, et al. The impact of artificial intelligence on traditional Chinese medicine. Am J Chin Med, 2021, 49(6): 1297-1314.
5.	王志杰, 樊薛津, 王豫骞, 等. 机器学习方法在中医药研究中的应用进展. 药物评价研究, 2024, 47(8): 1906-1913.
6.	王露露, 李冰, 王圳伊, 等. 基于“整体观”系统生物学技术在中药研究中的应用进展. 中草药, 2020, 51(19): 5053-5064.
7.	Zhu L, Sun Y, Kang J, et al. Effect of acupuncture on neurogenic claudication among patients with degenerative lumbar spinal stenosis : a randomized clinical trial. Ann Intern Med, 2024, 177(8): 1048-1057.
8.	唐雅琴, 杨忠奇, 凌燕, 等. 中药人用经验研究的质量要求. 中国中药杂志, 2023, 48(17): 4825-4828.
9.	张晓雨, 田思超, 尤良震, 等. 大数据时代中医症状疗效评价存在的问题与解决对策. 中医杂志, 2024, 65(8): 792-795.
10.	李多静, 邢永发, 吴哲颖, 等. 中医药临床疗效评价的研究进展与思考. 天津中医药, 2024, 41(9): 1200-1205.
11.	梁宏伟, 曾科, 张辰宇. 用复杂系统科学的“涌现”原理研究中医药学. 中国科学基金, 2024, 38(3): 426-433.
12.	中华中医药学会. 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. 中医杂志, 2023, 64(14): 1405-1421.
13.	薛公佑. 中医基础理论的核心是关系哲学. 医学与哲学, 2021, 42(3): 21-23, 64.
14.	屈婷婷, 孟庆刚. 从“天人相应”观谈中医临证思维的系统复杂性. 中华中医药学刊, 2013, 31(5): 1004-1006.
15.	徐安龙. 试从中西医学的发展思考"阴阳"的哲学与科学内涵—解码"阴阳"是打开中华文明宝库的钥匙. 北京中医药大学学报, 2022, 45(2): 109-115.
16.	张晨, 牛素珍, 张颖. 中国哲学与中医哲学的源流关系探讨. 哈尔滨学院学报, 2024, 45(1): 21-25.
17.	王阶, 郭丽丽, 王永炎. 中药方剂有效成(组)分配伍研究. 中国中药杂志, 2006, (1): 5-9.
18.	宋玮, 潘颖营, 饶响书, 等. 中医方剂配伍方法探析. 中国中医基础医学杂志, 2022, 28(9): 1416-1418, 1465.
19.	吴志生, 乔延江, 肖伟, 等. 论中药制造测量学之4个关键工程技术难题. 中国中药杂志, 2023, 48(11): 2841-2855.
20.	刘鸿达, 孙晖, 闫广利, 等. 中医理论视域下创新中药发现策略和实践. 中国科学基金, 2024, 38(3): 483-491.
21.	李梢, 肖伟. 网络药理学应用于中药新药研发专家共识总论. 中国中药杂志, 2024, 49(18): 5055-5068.
22.	李梢. 网络靶标: 中药方剂网络药理学研究的一个切入点. 中国中药杂志, 2011, 36(15): 2017-2020.
23.	刘昌孝, 陈士林, 肖小河, 等. 中药质量标志物(Q-Marker): 中药产品质量控制的新概念. 中草药, 2016, 47(9): 1443-1457.
24.	王凤颖, 高雪莲, 段红莉, 等. 基于体外化学成分-体内移行成分-功效靶点探究三叶糖脂清片治疗2型糖尿病、动脉粥硬化、高脂血症“异病同治”物质基础及质量标志物预测. 中草药, 2024, 55(23): 7939-7949.
25.	孙晨耀. 中西医思维哲学方法比较研究. 北京: 北京中医药大学, 2023.
26.	Mansinho A, Boni V, Miguel M, et al. New designs in early clinical drug development. Ann Oncol, 2019, 30(9): 1460-1465.
27.	肖小河, 罗烨, 赵旭, 等. 中药有效性评价新策略、新方法: 整合证据链法. 中国中药杂志, 2024, 49(19): 5113-5124.
28.	Tan J, Xiong Y, Qi Y, et al. Data resource profile: Xiamen registry of pregnant women and offspring (REPRESENT): a population-based, long-term follow-up database linking four major healthcare data platforms. Int J Epidemiol, 2021, 50(1): 27-28.
29.	Tan J, Xiong Y, Liu C, et al. A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics. Eur J Epidemiol, 2024, 39(4): 433-445.
30.	Tan J, Liu C, Li M, et al. A methodological framework for tackling confounding by indication when assessing the treatment effects of Chinese herbal injections in the real world. J Evid Based Med, 2022, 15(1): 64-72.
31.	Li MX, Liu CR, Chen M, et al. Effects of motherwort injection versus intramuscular oxytocin for preventing postpartum hemorrhage among women who underwent cesarean section. Front Pharmacol, 2022, 13: 859495.
32.	Tan J, Qi Y, Liu C, et al. The use of rigorous methods was strongly warranted among prognostic prediction models for obstetric care. J Clin Epidemiol, 2019, 115: 98-105.
33.	Tan J, Liu C, Yang M, et al. Investigation of statistical methods used in prognostic prediction models for obstetric care: a 10 year-span cross-sectional study. Acta Obstet Gynecol Scand, 2024, 103(3): 611-620.
34.	Liu C, Xiong Y, Zhao P, et al. The suboptimal clinical applicability of prognostic prediction models for severe postpartum hemorrhage: a meta-epidemiological study. J Clin Epidemiol, 2024, 173: 111424.
35.	Xu J, Wu W, Zhang X, et al. The use of real-world evidence for regulatory decisions in China. Clin Pharmacol Ther, 2024, 116(1): 82-95.
36.	Wang W, Tan J, Wu J, et al. Use of real world data to improve drug coverage decisions in China. BMJ, 2023, 381: e068911.
37.	Wang W, Jin YH, Liu M, et al. Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD). Mil Med Res, 2024, 11(1): 52.
38.	Liu S, Fu B, Wang W, et al. Dynamic sepsis prediction for intensive care unit patients using xgboost-based model with novel time-dependent features. IEEE J Biomed Health Inform, 2022, 26(8): 4258-4269.
39.	Wang W, Zhu S, He Q, et al. Developing a registry of healthcare-associated infections at intensive care units in west china: study rationale and patient characteristics. Clin Epidemiol, 2019, 11: 1035-1045.
40.	Wang W, Zhu S, He Q, et al. Fluid balance and ventilator-associated events among patients admitted to ICUs in China: a nested case-control study. Crit Care Med, 2022, 50(2): 307-316.
41.	Wang W, He Q, Wang MQ, et al. Effects of Tanreqing injection on ICU mortality among ICU patients receiving mechanical ventilation: time-dependent Cox regression analysis of a large registry. Chin J Integr Med, 2023, 29(9): 782-790.
42.	Zhang X, Wang M, Wang W, et al. Utilization of traditional Chinese medicine in the intensive care unit. Chin Med, 2021, 16(1): 84.
43.	Wang W, He Q, Xu J, et al. Reporting, handling, and interpretation of time-varying drug treatments in observational studies using routinely collected healthcare data. J Evid Based Med, 2023, 16(4): 495-504.
44.	Xu J, He Q, Wang M, et al. Handling time-varying treatments in observational studies: a scoping review and recommendations. J Evid Based Med, 2024, 17(1): 95-105.
45.	Tang L, Jia P, Zhao L, et al. Acupuncture treatment for knee osteoarthritis with sensitive points: protocol for a multicentre randomised controlled trial. BMJ Open, 2018, 8(10): e023838.
46.	Jia P, Liu J, Li L, et al. Acupuncture for knee osteoarthritis with sensitized acupoints: results from a pilot, feasibility randomized controlled trial. Pilot Feasibility Stud, 2020, 6: 144.
47.	Liu J, Li L, Luo X, et al. Specification of interventions and selection of controls in randomized controlled trials of acupuncture: a cross-sectional survey. Acupunct Med, 2022, 40(6): 524-537.
48.	Liu J, Luo X, Yao M, et al. Use of statistical methods among acupuncture randomized controlled trials was far from satisfactory. J Clin Epidemiol, 2022, 152: 1-12.
49.	Liu J, Li Y, Li L, et al. Effects of acupuncture at acupoints with lower versus higher pain threshold for knee osteoarthritis: a multicenter randomized controlled trial. Chin Med, 2022, 17(1): 67.
50.	Li Q, Luo X, Li L, et al. Toward better translation of clinical research evidence into rapid recommendations for traditional Chinese medicine interventions: a methodological framework. Integr Med Res, 2022, 11(3): 100841.
51.	Luo X, Liu J, Li Q, et al. Acupuncture for treatment of knee osteoarthritis: a clinical practice guideline. J Evid Based Med, 2023, 16(2): 237-245.

1. 张倩, 韩星星, 毛春芹, 等. 中药复方制剂开发的机遇与挑战: 古代经典名方研究开发的问题分析. 中国中药杂志, 2019, 44(19): 4300-4308.
2. 王停, 周刚, 赵保胜, 等. 中药新药研发策略分析. 中国新药杂志, 2017, 26(8): 865-871.
3. 肖培根, 肖小河. 21世纪与中药现代化. 中国中药杂志, 2000, (2): 3-6.
4. Wang Y, Shi X, Li L, et al. The impact of artificial intelligence on traditional Chinese medicine. Am J Chin Med, 2021, 49(6): 1297-1314.
5. 王志杰, 樊薛津, 王豫骞, 等. 机器学习方法在中医药研究中的应用进展. 药物评价研究, 2024, 47(8): 1906-1913.
6. 王露露, 李冰, 王圳伊, 等. 基于“整体观”系统生物学技术在中药研究中的应用进展. 中草药, 2020, 51(19): 5053-5064.
7. Zhu L, Sun Y, Kang J, et al. Effect of acupuncture on neurogenic claudication among patients with degenerative lumbar spinal stenosis : a randomized clinical trial. Ann Intern Med, 2024, 177(8): 1048-1057.
8. 唐雅琴, 杨忠奇, 凌燕, 等. 中药人用经验研究的质量要求. 中国中药杂志, 2023, 48(17): 4825-4828.
9. 张晓雨, 田思超, 尤良震, 等. 大数据时代中医症状疗效评价存在的问题与解决对策. 中医杂志, 2024, 65(8): 792-795.
10. 李多静, 邢永发, 吴哲颖, 等. 中医药临床疗效评价的研究进展与思考. 天津中医药, 2024, 41(9): 1200-1205.
11. 梁宏伟, 曾科, 张辰宇. 用复杂系统科学的“涌现”原理研究中医药学. 中国科学基金, 2024, 38(3): 426-433.
12. 中华中医药学会. 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. 中医杂志, 2023, 64(14): 1405-1421.
13. 薛公佑. 中医基础理论的核心是关系哲学. 医学与哲学, 2021, 42(3): 21-23, 64.
14. 屈婷婷, 孟庆刚. 从“天人相应”观谈中医临证思维的系统复杂性. 中华中医药学刊, 2013, 31(5): 1004-1006.
15. 徐安龙. 试从中西医学的发展思考"阴阳"的哲学与科学内涵—解码"阴阳"是打开中华文明宝库的钥匙. 北京中医药大学学报, 2022, 45(2): 109-115.
16. 张晨, 牛素珍, 张颖. 中国哲学与中医哲学的源流关系探讨. 哈尔滨学院学报, 2024, 45(1): 21-25.
17. 王阶, 郭丽丽, 王永炎. 中药方剂有效成(组)分配伍研究. 中国中药杂志, 2006, (1): 5-9.
18. 宋玮, 潘颖营, 饶响书, 等. 中医方剂配伍方法探析. 中国中医基础医学杂志, 2022, 28(9): 1416-1418, 1465.
19. 吴志生, 乔延江, 肖伟, 等. 论中药制造测量学之4个关键工程技术难题. 中国中药杂志, 2023, 48(11): 2841-2855.
20. 刘鸿达, 孙晖, 闫广利, 等. 中医理论视域下创新中药发现策略和实践. 中国科学基金, 2024, 38(3): 483-491.
21. 李梢, 肖伟. 网络药理学应用于中药新药研发专家共识总论. 中国中药杂志, 2024, 49(18): 5055-5068.
22. 李梢. 网络靶标: 中药方剂网络药理学研究的一个切入点. 中国中药杂志, 2011, 36(15): 2017-2020.
23. 刘昌孝, 陈士林, 肖小河, 等. 中药质量标志物(Q-Marker): 中药产品质量控制的新概念. 中草药, 2016, 47(9): 1443-1457.
24. 王凤颖, 高雪莲, 段红莉, 等. 基于体外化学成分-体内移行成分-功效靶点探究三叶糖脂清片治疗2型糖尿病、动脉粥硬化、高脂血症“异病同治”物质基础及质量标志物预测. 中草药, 2024, 55(23): 7939-7949.
25. 孙晨耀. 中西医思维哲学方法比较研究. 北京: 北京中医药大学, 2023.
26. Mansinho A, Boni V, Miguel M, et al. New designs in early clinical drug development. Ann Oncol, 2019, 30(9): 1460-1465.
27. 肖小河, 罗烨, 赵旭, 等. 中药有效性评价新策略、新方法: 整合证据链法. 中国中药杂志, 2024, 49(19): 5113-5124.
28. Tan J, Xiong Y, Qi Y, et al. Data resource profile: Xiamen registry of pregnant women and offspring (REPRESENT): a population-based, long-term follow-up database linking four major healthcare data platforms. Int J Epidemiol, 2021, 50(1): 27-28.
29. Tan J, Xiong Y, Liu C, et al. A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics. Eur J Epidemiol, 2024, 39(4): 433-445.
30. Tan J, Liu C, Li M, et al. A methodological framework for tackling confounding by indication when assessing the treatment effects of Chinese herbal injections in the real world. J Evid Based Med, 2022, 15(1): 64-72.
31. Li MX, Liu CR, Chen M, et al. Effects of motherwort injection versus intramuscular oxytocin for preventing postpartum hemorrhage among women who underwent cesarean section. Front Pharmacol, 2022, 13: 859495.
32. Tan J, Qi Y, Liu C, et al. The use of rigorous methods was strongly warranted among prognostic prediction models for obstetric care. J Clin Epidemiol, 2019, 115: 98-105.
33. Tan J, Liu C, Yang M, et al. Investigation of statistical methods used in prognostic prediction models for obstetric care: a 10 year-span cross-sectional study. Acta Obstet Gynecol Scand, 2024, 103(3): 611-620.
34. Liu C, Xiong Y, Zhao P, et al. The suboptimal clinical applicability of prognostic prediction models for severe postpartum hemorrhage: a meta-epidemiological study. J Clin Epidemiol, 2024, 173: 111424.
35. Xu J, Wu W, Zhang X, et al. The use of real-world evidence for regulatory decisions in China. Clin Pharmacol Ther, 2024, 116(1): 82-95.
36. Wang W, Tan J, Wu J, et al. Use of real world data to improve drug coverage decisions in China. BMJ, 2023, 381: e068911.
37. Wang W, Jin YH, Liu M, et al. Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD). Mil Med Res, 2024, 11(1): 52.
38. Liu S, Fu B, Wang W, et al. Dynamic sepsis prediction for intensive care unit patients using xgboost-based model with novel time-dependent features. IEEE J Biomed Health Inform, 2022, 26(8): 4258-4269.
39. Wang W, Zhu S, He Q, et al. Developing a registry of healthcare-associated infections at intensive care units in west china: study rationale and patient characteristics. Clin Epidemiol, 2019, 11: 1035-1045.
40. Wang W, Zhu S, He Q, et al. Fluid balance and ventilator-associated events among patients admitted to ICUs in China: a nested case-control study. Crit Care Med, 2022, 50(2): 307-316.
41. Wang W, He Q, Wang MQ, et al. Effects of Tanreqing injection on ICU mortality among ICU patients receiving mechanical ventilation: time-dependent Cox regression analysis of a large registry. Chin J Integr Med, 2023, 29(9): 782-790.
42. Zhang X, Wang M, Wang W, et al. Utilization of traditional Chinese medicine in the intensive care unit. Chin Med, 2021, 16(1): 84.
43. Wang W, He Q, Xu J, et al. Reporting, handling, and interpretation of time-varying drug treatments in observational studies using routinely collected healthcare data. J Evid Based Med, 2023, 16(4): 495-504.
44. Xu J, He Q, Wang M, et al. Handling time-varying treatments in observational studies: a scoping review and recommendations. J Evid Based Med, 2024, 17(1): 95-105.
45. Tang L, Jia P, Zhao L, et al. Acupuncture treatment for knee osteoarthritis with sensitive points: protocol for a multicentre randomised controlled trial. BMJ Open, 2018, 8(10): e023838.
46. Jia P, Liu J, Li L, et al. Acupuncture for knee osteoarthritis with sensitized acupoints: results from a pilot, feasibility randomized controlled trial. Pilot Feasibility Stud, 2020, 6: 144.
47. Liu J, Li L, Luo X, et al. Specification of interventions and selection of controls in randomized controlled trials of acupuncture: a cross-sectional survey. Acupunct Med, 2022, 40(6): 524-537.
48. Liu J, Luo X, Yao M, et al. Use of statistical methods among acupuncture randomized controlled trials was far from satisfactory. J Clin Epidemiol, 2022, 152: 1-12.
49. Liu J, Li Y, Li L, et al. Effects of acupuncture at acupoints with lower versus higher pain threshold for knee osteoarthritis: a multicenter randomized controlled trial. Chin Med, 2022, 17(1): 67.
50. Li Q, Luo X, Li L, et al. Toward better translation of clinical research evidence into rapid recommendations for traditional Chinese medicine interventions: a methodological framework. Integr Med Res, 2022, 11(3): 100841.
51. Luo X, Liu J, Li Q, et al. Acupuncture for treatment of knee osteoarthritis: a clinical practice guideline. J Evid Based Med, 2023, 16(2): 237-245.

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Latest ArticlesSystems evidence-based medicine (sysEBM): a new model toward the studies on effects of traditional Chinese medicine interventions

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