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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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.

Citation： TAN Jing, WANG Wen, LI Ling, LIU Qingsong, MEI Fan, WANG Zichen, CHEN Chen, QIN Xuan, DING Ling, WANG Liqun, LIU Jiali, LUO Xiaochao, LIU Xuehong, HE Yifei, WANG Wenling, REN Yan, LAI Qinhuai, XIONG Yiquan, YAO Minghong, XU Jiayue, YAO Yuqin, CHEN Sujun, JIANG Jingwen, CHEN Chu, GAO Jie, JIN Zhao, SUN Xin. Systems evidence-based medicine (sysEBM): a new model toward the studies on effects of traditional Chinese medicine interventions. Chinese Journal of Evidence-Based Medicine, 2025, 25(2): 125-133. doi: 10.7507/1672-2531.202412110 Copy

1.	張倩, 韓星星, 毛春芹, 等. 中藥復方制劑開發的機遇與挑戰: 古代經典名方研究開發的問題分析. 中國中藥雜志, 2019, 44(19): 4300-4308.
2.	王停, 周剛, 趙保勝, 等. 中藥新藥研發策略分析. 中國新藥雜志, 2017, 26(8): 865-871.
3.	肖培根, 肖小河. 21世紀與中藥現代化. 中國中藥雜志, 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, 王豫騫, 等. 機器學習方法在中醫藥研究中的應用進展. 藥物評價研究, 2024, 47(8): 1906-1913.
6.	王露露, 李冰, 王圳伊, 等. 基于“整體觀”系統生物學技術在中藥研究中的應用進展. 中草藥, 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, 楊忠奇, 凌燕, 等. 中藥人用經驗研究的質量要求. 中國中藥雜志, 2023, 48(17): 4825-4828.
9.	張曉雨, 田思超, 尤良震, 等. 大數據時代中醫癥狀療效評價存在的問題與解決對策. 中醫雜志, 2024, 65(8): 792-795.
10.	李多靜, 邢永發, 吳哲穎, 等. 中醫藥臨床療效評價的研究進展與思考. 天津中醫藥, 2024, 41(9): 1200-1205.
11.	梁宏偉, 曾科, 張辰宇. 用復雜系統科學的“涌現”原理研究中醫藥學. 中國科學基金, 2024, 38(3): 426-433.
12.	中華中醫藥學會. 2023年度中醫藥重大科學問題、工程技術難題和產業技術問題. 中醫雜志, 2023, 64(14): 1405-1421.
13.	薛公佑. 中醫基礎理論的核心是關系哲學. 醫學與哲學, 2021, 42(3): 21-23, 64.
14.	屈婷婷, 孟慶剛. 從“天人相應”觀談中醫臨證思維的系統復雜性. 中華中醫藥學刊, 2013, 31(5): 1004-1006.
15.	徐安龍. 試從中西醫學的發展思考"陰陽"的哲學與科學內涵—解碼"陰陽"是打開中華文明寶庫的鑰匙. 北京中醫藥大學學報, 2022, 45(2): 109-115.
16.	張晨, 牛素珍, 張穎. 中國哲學與中醫哲學的源流關系探討. 哈爾濱學院學報, 2024, 45(1): 21-25.
17.	王階, 郭麗麗, 王永炎. 中藥方劑有效成(組)分配伍研究. 中國中藥雜志, 2006, (1): 5-9.
18.	宋瑋, 潘穎營, 饒響書, 等. 中醫方劑配伍方法探析. 中國中醫基礎醫學雜志, 2022, 28(9): 1416-1418, 1465.
19.	吳志生, 喬延江, 肖偉, 等. 論中藥制造測量學之4個關鍵工程技術難題. 中國中藥雜志, 2023, 48(11): 2841-2855.
20.	劉鴻達, 孫暉, 閆廣利, 等. 中醫理論視域下創新中藥發現策略和實踐. 中國科學基金, 2024, 38(3): 483-491.
21.	李梢, 肖偉. 網絡藥理學應用于中藥新藥研發專家共識總論. 中國中藥雜志, 2024, 49(18): 5055-5068.
22.	李梢. 網絡靶標: 中藥方劑網絡藥理學研究的一個切入點. 中國中藥雜志, 2011, 36(15): 2017-2020.
23.	劉昌孝, 陳士林, 肖小河, 等. 中藥質量標志物(Q-Marker): 中藥產品質量控制的新概念. 中草藥, 2016, 47(9): 1443-1457.
24.	王鳳穎, 高雪蓮, 段紅莉, 等. 基于體外化學成分-體內移行成分-功效靶點探究三葉糖脂清片治療2型糖尿病、動脈粥硬化、高脂血癥“異病同治”物質基礎及質量標志物預測. 中草藥, 2024, 55(23): 7939-7949.
25.	孫晨耀. 中西醫思維哲學方法比較研究. 北京: 北京中醫藥大學, 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, 羅燁, 趙旭, 等. 中藥有效性評價新策略、新方法: 整合證據鏈法. 中國中藥雜志, 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. 張倩, 韓星星, 毛春芹, 等. 中藥復方制劑開發的機遇與挑戰: 古代經典名方研究開發的問題分析. 中國中藥雜志, 2019, 44(19): 4300-4308.
2. 王停, 周剛, 趙保勝, 等. 中藥新藥研發策略分析. 中國新藥雜志, 2017, 26(8): 865-871.
3. 肖培根, 肖小河. 21世紀與中藥現代化. 中國中藥雜志, 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, 王豫騫, 等. 機器學習方法在中醫藥研究中的應用進展. 藥物評價研究, 2024, 47(8): 1906-1913.
6. 王露露, 李冰, 王圳伊, 等. 基于“整體觀”系統生物學技術在中藥研究中的應用進展. 中草藥, 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, 楊忠奇, 凌燕, 等. 中藥人用經驗研究的質量要求. 中國中藥雜志, 2023, 48(17): 4825-4828.
9. 張曉雨, 田思超, 尤良震, 等. 大數據時代中醫癥狀療效評價存在的問題與解決對策. 中醫雜志, 2024, 65(8): 792-795.
10. 李多靜, 邢永發, 吳哲穎, 等. 中醫藥臨床療效評價的研究進展與思考. 天津中醫藥, 2024, 41(9): 1200-1205.
11. 梁宏偉, 曾科, 張辰宇. 用復雜系統科學的“涌現”原理研究中醫藥學. 中國科學基金, 2024, 38(3): 426-433.
12. 中華中醫藥學會. 2023年度中醫藥重大科學問題、工程技術難題和產業技術問題. 中醫雜志, 2023, 64(14): 1405-1421.
13. 薛公佑. 中醫基礎理論的核心是關系哲學. 醫學與哲學, 2021, 42(3): 21-23, 64.
14. 屈婷婷, 孟慶剛. 從“天人相應”觀談中醫臨證思維的系統復雜性. 中華中醫藥學刊, 2013, 31(5): 1004-1006.
15. 徐安龍. 試從中西醫學的發展思考"陰陽"的哲學與科學內涵—解碼"陰陽"是打開中華文明寶庫的鑰匙. 北京中醫藥大學學報, 2022, 45(2): 109-115.
16. 張晨, 牛素珍, 張穎. 中國哲學與中醫哲學的源流關系探討. 哈爾濱學院學報, 2024, 45(1): 21-25.
17. 王階, 郭麗麗, 王永炎. 中藥方劑有效成(組)分配伍研究. 中國中藥雜志, 2006, (1): 5-9.
18. 宋瑋, 潘穎營, 饒響書, 等. 中醫方劑配伍方法探析. 中國中醫基礎醫學雜志, 2022, 28(9): 1416-1418, 1465.
19. 吳志生, 喬延江, 肖偉, 等. 論中藥制造測量學之4個關鍵工程技術難題. 中國中藥雜志, 2023, 48(11): 2841-2855.
20. 劉鴻達, 孫暉, 閆廣利, 等. 中醫理論視域下創新中藥發現策略和實踐. 中國科學基金, 2024, 38(3): 483-491.
21. 李梢, 肖偉. 網絡藥理學應用于中藥新藥研發專家共識總論. 中國中藥雜志, 2024, 49(18): 5055-5068.
22. 李梢. 網絡靶標: 中藥方劑網絡藥理學研究的一個切入點. 中國中藥雜志, 2011, 36(15): 2017-2020.
23. 劉昌孝, 陳士林, 肖小河, 等. 中藥質量標志物(Q-Marker): 中藥產品質量控制的新概念. 中草藥, 2016, 47(9): 1443-1457.
24. 王鳳穎, 高雪蓮, 段紅莉, 等. 基于體外化學成分-體內移行成分-功效靶點探究三葉糖脂清片治療2型糖尿病、動脈粥硬化、高脂血癥“異病同治”物質基礎及質量標志物預測. 中草藥, 2024, 55(23): 7939-7949.
25. 孫晨耀. 中西醫思維哲學方法比較研究. 北京: 北京中醫藥大學, 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, 羅燁, 趙旭, 等. 中藥有效性評價新策略、新方法: 整合證據鏈法. 中國中藥雜志, 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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Evidence-based construction of evaluation items for selecting priority clinical questions of traditional Chinese medicine guidelines

Chinese Journal of Evidence-Based Medicine

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

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