Guidelines for the reporting of randomized controlled trial protocols: interpretation of SPIRIT 2025_Chinese Journal of Evidence-Based Medicine

Authors：

ZHAO Wenshuo ^1,2 , LIU Ming ^3,4 , GE Long ^5,6 , LI Lun ^7,8 , SHI Jiyuan ⁹ , YANG Fengwen ^10,11 , TIAN Jinhui ^3,4 , XUE Fuzhong ^1,2 ,  GAO Ya ^1,2

1. Department of Medical Data, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250003, P. R. China;
2. National Institute of Health Data Science of China, Jinan 250003, P. R. China;
3. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P. R. China;
4. Key Laboratory of Evidence-Based Medicine of Gansu Province, Lanzhou 730000, P. R. China;
5. Department of Health Policy and Management, School of Public Health, Lanzhou University, Lanzhou 730000, P. R. China;
6. Key Laboratory of Evidence Based Medicine of Gansu Province, Lanzhou 730000, P. R. China;
7. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, P. R. China;
8. Clinical Research Center of Hunan Province, Changsha 410011, P. R. China;
9. School of Nursing, Beijing University of Traditional Chinese Medicine, Beijing 100029, P. R. China;
10. Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. China;
11. Key Laboratory of Evidence-Based Evaluation of Traditional Chinese Medicine, National Medical Products Administration, Tianjin 301617, P. R. China;

Corresponding author：

GAO Ya, Email: gaoy2021@163.com

Keywords：

Randomized controlled trial; SPIRIT 2025; Protocol; Reporting guideline; Interpretation

DOI：

10.7507/1672-2531.202505101

Video：

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Since its initial publication in 2013, the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines have received widespread international attention. The guidelines aim to enhance the standardization and transparency of clinical trial protocol reporting. With continuous advancements in clinical trial methodologies, the SPIRIT group released an updated version, SPIRIT 2025, in 2025. The SPIRIT 2025 reporting guideline comprises 34 items; compared to the 2013 version, 2 items were added, 5 were revised, 2 were merged, and 3 were deleted. Its core updates are reflected in: The addition of an "open science" section, which emphasizes trial registration, accessibility of the trial protocol and statistical analysis plan, a data sharing statement, and a dissemination policy for research findings; The addition of a "patient and public involvement" item, which requires the protocol to describe the participation of patients or the public in the trial's design, conduct, and reporting phases; Structural optimization, which reorganizes the original items into five major sections for clearer logic and strongly recommends the use of a schedule diagram to present the trial timeline. This article provides an illustrative interpretation of the items contained in the SPIRIT 2025 statement using a randomized controlled trial protocol, aiming to offer guidance and convenience for domestic researchers utilizing this tool.

1.	Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ, 2010, 340: c332.
2.	Chan AW, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ, 2013, 346: e7586.
3.	Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med, 2013, 158(3): 200-207.
4.	Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica, 2015, 38(6): 506-514.
5.	Calvert M, Kyte D, Mercieca-Bebber R, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA, 2018, 319(5): 483-494.
6.	Butcher NJ, Monsour A, Mew EJ, et al. Guidelines for reporting outcomes in trial protocols: the SPIRIT-Outcomes 2022 extension. JAMA, 2022, 328(23): 2345-2356.
7.	CONSORT-AI and SPIRIT-AI Steering Group. Reporting guidelines for clinical trials evaluating artificial intelligence interventions are needed. Nat Med, 2019, 25(10): 1467-1468.
8.	Rivera SC, Liu X, Chan AW, et al. Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension. BMJ, 2020, 370: m3210.
9.	刘明, 高亚, 史纪元, 等. 人工智能干预临床试验研究方案报告规范指南: SPIRIT-AI扩展版(2020)解读. 中国医药导刊, 2020, 22(10): 692-697.
10.	赵晶晶, 龙泳, 刘学东. 2013临床试验方案规范指南(SPIRIT)及其解读. 中国循证儿科杂志, 2014, 9(5): 381-388.
11.	陈嘉慧, 王子怡, 李洁韵, 等. 随机对照试验中替代终点的报告规范SPIRIT-Surrogate与CONSORT-Surrogate解读. 中国循证医学杂志, 2025, 25(2): 214-224.
12.	United Nations Educational Scientific Cultural Organization. UNESCO recommendation on open science. 2021.
13.	Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. The Lancet, 2025.
14.	Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med, 2025, 31(6): 1784-1792.
15.	Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. JAMA, 2025.
16.	Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: Updated guideline for protocols of randomised trials. PLoS Med, 2025, 22(4): e1004589.
17.	Hróbjartsson A, Boutron I, Hopewell S, et al. SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials. BMJ, 2025, 389: e081660.
18.	Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. BMJ, 2025, 389: e081477.
19.	Østengaard L, Barrientos A, Boutron I, et al. Development of a topic-specific bibliographic database supporting the updates of SPIRIT 2013 and CONSORT 2010. Cochrane Evid Synth Methods, 2024, 2(5): e12057.
20.	Moher D, Schulz KF, Simera I, et al. Guidance for developers of health research reporting guidelines. PLoS Med, 2010, 7(2): e1000217.
21.	Edelmann F, Wachter R, Duvinage A, et al. Combined endurance and resistance exercise training in heart failure with preserved ejection fraction: a randomized controlled trial. Nat Med, 2025, 31(1): 306-314.
22.	World Health Organization. WHO trial registration data set (Version 1.3. 1). 2017.
23.	National Institutes of Health, Department of Health and Human Services. Clinical trials registration and results information submission. Final rule. Fed Regist, 2016, 81(183): 64981-65157.
24.	Laine C, Horton R, DeAngelis CD, et al. Clinical trial registration. BMJ, 2007, 334(7605): 1177-1178.
25.	European Commission. Clinical trials - Regulation EU No 536/2014. 2022.
26.	Lundh A, Lexchin J, Mintzes B, et al. Industry sponsorship and research outcome. Cochrane Database Syst Rev, 2017, (2): MR000033.
27.	Rasmussen K, Bero L, Redberg R, et al. Collaboration between academics and industry in clinical trials: cross sectional study of publications and survey of lead academic authors. BMJ, 2018, 363: k3654.
28.	Chou R, Baker WL, Bañez LL, et al. Agency for Healthcare Research and Quality Evidence-based Practice Center methods provide guidance on prioritization and selection of harms in systematic reviews. J Clin Epidemiol, 2018, 98: 98-104.
29.	Forsythe LP, Carman KL, Szydlowski V, et al. Patient engagement in research: early findings from the patient-centered outcomes research institute. Health Aff (Millwood), 2019, 38(3): 359-367.
30.	Vanderhout S, Nicholls S, Monfaredi Z, et al. Facilitating and supporting the engagement of patients, families and caregivers in research: the "Ottawa model" for patient engagement in research. Res Involv Engagem, 2022, 8(1): 25.
31.	Staniszewska S, Brett J, Simera I, et al. GRIPP2 reporting checklists: tools to improve reporting of patient and public involvement in research. BMJ, 2017, 358: j3453.
32.	Rothwell PM. Commentary: external validity of results of randomized trials: disentangling a complex concept. Int J Epidemiol, 2010, 39(1): 94-96.
33.	Rivera SC, Liu X, Chan AW, et al. Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI Extension. BMJ, 2020, 370: m3210.
34.	Gryaznov D, von Niederhäusern B, Speich B, et al. Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE). BMJ Open, 2022, 12(5): e053417.
35.	Chen D, He E, Pace K, et al. Concordance with SPIRIT-AI guidelines in reporting of randomized controlled trial protocols investigating artificial intelligence in oncology: a systematic review. Oncologist, 2025, 30(5): oyaf112.

1. Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ, 2010, 340: c332.
2. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ, 2013, 346: e7586.
3. Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med, 2013, 158(3): 200-207.
4. Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica, 2015, 38(6): 506-514.
5. Calvert M, Kyte D, Mercieca-Bebber R, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA, 2018, 319(5): 483-494.
6. Butcher NJ, Monsour A, Mew EJ, et al. Guidelines for reporting outcomes in trial protocols: the SPIRIT-Outcomes 2022 extension. JAMA, 2022, 328(23): 2345-2356.
7. CONSORT-AI and SPIRIT-AI Steering Group. Reporting guidelines for clinical trials evaluating artificial intelligence interventions are needed. Nat Med, 2019, 25(10): 1467-1468.
8. Rivera SC, Liu X, Chan AW, et al. Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension. BMJ, 2020, 370: m3210.
9. 刘明, 高亚, 史纪元, 等. 人工智能干预临床试验研究方案报告规范指南: SPIRIT-AI扩展版(2020)解读. 中国医药导刊, 2020, 22(10): 692-697.
10. 赵晶晶, 龙泳, 刘学东. 2013临床试验方案规范指南(SPIRIT)及其解读. 中国循证儿科杂志, 2014, 9(5): 381-388.
11. 陈嘉慧, 王子怡, 李洁韵, 等. 随机对照试验中替代终点的报告规范SPIRIT-Surrogate与CONSORT-Surrogate解读. 中国循证医学杂志, 2025, 25(2): 214-224.
12. United Nations Educational Scientific Cultural Organization. UNESCO recommendation on open science. 2021.
13. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. The Lancet, 2025.
14. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med, 2025, 31(6): 1784-1792.
15. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. JAMA, 2025.
16. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: Updated guideline for protocols of randomised trials. PLoS Med, 2025, 22(4): e1004589.
17. Hróbjartsson A, Boutron I, Hopewell S, et al. SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials. BMJ, 2025, 389: e081660.
18. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. BMJ, 2025, 389: e081477.
19. Østengaard L, Barrientos A, Boutron I, et al. Development of a topic-specific bibliographic database supporting the updates of SPIRIT 2013 and CONSORT 2010. Cochrane Evid Synth Methods, 2024, 2(5): e12057.
20. Moher D, Schulz KF, Simera I, et al. Guidance for developers of health research reporting guidelines. PLoS Med, 2010, 7(2): e1000217.
21. Edelmann F, Wachter R, Duvinage A, et al. Combined endurance and resistance exercise training in heart failure with preserved ejection fraction: a randomized controlled trial. Nat Med, 2025, 31(1): 306-314.
22. World Health Organization. WHO trial registration data set (Version 1.3. 1). 2017.
23. National Institutes of Health, Department of Health and Human Services. Clinical trials registration and results information submission. Final rule. Fed Regist, 2016, 81(183): 64981-65157.
24. Laine C, Horton R, DeAngelis CD, et al. Clinical trial registration. BMJ, 2007, 334(7605): 1177-1178.
25. European Commission. Clinical trials - Regulation EU No 536/2014. 2022.
26. Lundh A, Lexchin J, Mintzes B, et al. Industry sponsorship and research outcome. Cochrane Database Syst Rev, 2017, (2): MR000033.
27. Rasmussen K, Bero L, Redberg R, et al. Collaboration between academics and industry in clinical trials: cross sectional study of publications and survey of lead academic authors. BMJ, 2018, 363: k3654.
28. Chou R, Baker WL, Bañez LL, et al. Agency for Healthcare Research and Quality Evidence-based Practice Center methods provide guidance on prioritization and selection of harms in systematic reviews. J Clin Epidemiol, 2018, 98: 98-104.
29. Forsythe LP, Carman KL, Szydlowski V, et al. Patient engagement in research: early findings from the patient-centered outcomes research institute. Health Aff (Millwood), 2019, 38(3): 359-367.
30. Vanderhout S, Nicholls S, Monfaredi Z, et al. Facilitating and supporting the engagement of patients, families and caregivers in research: the "Ottawa model" for patient engagement in research. Res Involv Engagem, 2022, 8(1): 25.
31. Staniszewska S, Brett J, Simera I, et al. GRIPP2 reporting checklists: tools to improve reporting of patient and public involvement in research. BMJ, 2017, 358: j3453.
32. Rothwell PM. Commentary: external validity of results of randomized trials: disentangling a complex concept. Int J Epidemiol, 2010, 39(1): 94-96.
33. Rivera SC, Liu X, Chan AW, et al. Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI Extension. BMJ, 2020, 370: m3210.
34. Gryaznov D, von Niederhäusern B, Speich B, et al. Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE). BMJ Open, 2022, 12(5): e053417.
35. Chen D, He E, Pace K, et al. Concordance with SPIRIT-AI guidelines in reporting of randomized controlled trial protocols investigating artificial intelligence in oncology: a systematic review. Oncologist, 2025, 30(5): oyaf112.

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