Interpretation and Examples: Key Updates in SPIRIT 2025 Statement

DAI Zelei, ZHAO Renjie, LI Kefan, ZHANG Yonggang, LI Nian, YANG Wenjie, LIU Lei, CHEN Lingmin

Abstract

A high-quality clinical trial protocol is the cornerstone for ensuring the scientific integrity and ethical compliance of a study. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) has become the international benchmark for developing clinical trial protocols since its release in 2013. To adapt to the developing trends of open science and patient-centered principles, the SPIRIT group completed a comprehensive update in 2025. While retaining its core structure, this updated guideline introduces a new open science module and incorporates several new elements, including patient and public involvement, trial monitoring, and data sharing, alongside substantial revisions of five pre-existing items. In this article, we critically examine the core revisions in SPIRIT 2025 and, through analysis of representative case studies, illustrate the practical application of the new reporting guideline in drafting trial protocols. Our goal is to to provide Chinese researchers with a valuable reference for understanding and implementing this new reporting guideline, thereby enhancing the quality and rigor of clinical trial protocols developed in the country.

 

Keywords: SPIRIT 2025, Clinical trial protocol, Reporting guidelines, Interpretation

 

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References


Strengthening the credibility of clinical research. Lancet, 2010, 375(9722): 1225. doi: 10.1016/S0140-6736(10)60523-5.

LI T, BOUTRON I, Al-SHAHI SALMAN R, et al. Review and publication of protocol submissions to Trials - what have we learned in 10 years?Trials, 2016, 18(1): 34. doi: 10.1186/s13063-016-1743-0.

KRLEZA-JERIĆ K, CHAN A W, DICKERSIN K, et al. Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1). BMJ, 2005, 330(7497): 956-958. doi: 10.1136/bmj.330.7497.956. LASSERE M, JOHNSON K. The power of the protocol. Lancet, 2002, 360(9346): 1620-1622. doi: 10.1016/S0140-6736(02)11652-7.

CHAN A W, HRÓBJARTSSON A. Promoting public access to clinical trial protocols: challenges and recommendations. Trials, 2018, 19(1): 116. doi: 10.1186/s13063-018-2510-1.

CHAN A W, TETZLAFF J M, ALTMAN D G, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med, 2013, 158(3): 200-207. doi: 10.7326/0003-4819-158-3-201302050-00583.

ALTMAN D G. Better reporting of randomised controlled trials: the CONSORT statement. BMJ, 1996, 313(7057): 570-571. doi: 10.1136/bmj. 313.7057.570.

CHAN A W, TETZLAFF J M, GØTZSCHE P C, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ, 2013, 346: e7586. doi: 10.1136/bmj.e7586.

ZARIN D A, FAIN K M, DOBBINS H D, et al. 10-year update on study results submitted to ClinicalTrials.gov. N Engl J Med, 2019, 381(20): 1966-1974. doi: 10.1056/NEJMsr1907644.

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. doi: 10. 1136/bmjopen-2021-053417.

SPEICH B, ODUTAYO A, PECKHAM N, et al. A longitudinal assessment of trial protocols approved by research ethics committees: the Adherance to SPIrit REcommendations in the UK (ASPIRE-UK) study. Trials, 2022, 23(1): 601. doi: 10.1186/s13063-022-06516-1.

NEJSTGAARD C H, BOUTRON I, CHAN A W, et al. A scoping review identifies multiple comments suggesting modifications to SPIRIT 2013 and CONSORT 2010. J Clin Epidemiol, 2023, 155: 48-63. doi: 10.1016/j. jclinepi.2023.01.003.

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. doi: 10.1002/cesm.12057.

CHAN A W, BOUTRON I, HOPEWELL S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med, 2025, 31(6): 1784-1792. doi: 10.1038/s41591-025-03668-w.

HRÓBJARTSSON A, BOUTRON I, HOPEWELL S, et al. SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials. BMJ, 2025, 389: e081660. doi: 10.1136/bmj-2024-081660.

PUTOT A, MANCKOUNDIA P, KSIAZEK E, et al. ASPirin for Acute Pneumonia in the elderlY (ASPAPY): protocol of a multicentre randomised double-blind placebo-controlled trial. BMJ Open, 2025, 15(5): e102768. doi: 10.1136/bmjopen-2025-102768.

HILL K D, KANNANKERIL P J, JACOBS J P, et al. Methylprednisolone for heart surgery in infants--a randomized, controlled trial. N Engl J Med, 2022, 387(23): 2138-2149. doi: 10.1056/NEJMoa2212667.

SAKZEWSKI L, REEDMAN S E, ELLIOTT C, et al. Participate CP 2: optimising participation in physically active leisure for children with cerebral palsy--protocol for a phase Ⅲ randomised controlled trial. BMJ Open, 2023, 13(10): e075570. doi: 10.1136/bmjopen-2023-075570.

BAIS T, MEIJER E, KRAMERS B J, et al. HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial. Trials, 2024, 25(1): 120. doi: 10. 1186/s13063-024-07952-x.

MANGLA M, BEDAIR H, CHANG Y, et al. Protocol for a randomised trial evaluating the comparative effectiveness of strategies to promote shared decision making for hip and knee osteoarthritis (DECIDE-OA study). BMJ Open, 2019, 9(2): e024906. doi: 10.1136/bmjopen-2018-024906.

RADAVELLI-BAGATINI S, BONDONNO C P, SIM M, et al. Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol. BMJ Open, 2020, 10(11): e036366. doi: 10.1136/bmjopen-2019-036366.

KER K, ROBERTS I, CHAUDHRI R, et al. Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial. Trials, 2018, 19(1): 712. doi: 10.1186/s13063-018-3081-x.

DENHOLM J T, VENKATESH B, DAVIS J, et al. ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial. Trials, 2022, 23(1): 1014. doi: 10.1186/s13063-022-06929-y.

PITTET L F, MESSINA N L, ORSINI F, et al. Randomized trial of BCG vaccine to protect against Covid-19 in health care workers. N Engl J Med, 2023, 388(17): 1582-1596. doi: 10.1056/NEJMoa2212616.

DAI Z L, ZHAO R J, LI K F, et al. Interpretation and examples: Key updates in CONSORT 2025. J Sichuan Univ (Med Sci), 2025, 56(3): 678-685. doi: 10.12182/20250560504.


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