SPIRIT 2025声明：随机试验方案指南更新版

doi:10.3969/j.issn.1673-5765.2025.05.011

摘要/Abstract

摘要： 背景随机试验方案是研究计划、实施、报告和外部评审的基础。但目前的试验方案在完整性方面差异较大，并且常遗漏设计和实施的关键要素。SPIRIT 声明于2013年首次发布，旨在提高试验方案的完整性。为确保指南与时俱进，该声明需定期整合最新证据和最佳实践进行更新。
目的更新SPIRIT声明中对随机试验方案应涵盖的必备条目的建议。
方法我们通过进行范围综述并建立项目专用的实证和理论证据数据库，生成SPIRIT 2013清单可能需要修订的条目列表。该列表整合了现有SPIRIT/CONSORT扩展（不良事件、结局、非药物治疗）及其他报告指南[如干预措施描述与复制模板（template for intervention description and replication，TIDieR）]的主要作者的建议。随后，我们通过3轮德尔菲调查对涉及的修订内容进行了评级，并召开了共识会议。
结果共317人参与德尔菲调查过程，30位专家出席共识会议。SPIRIT 2025声明最终新增2个方案条目，修订5个条目，删除/合并5个条目，并整合了其他相关报告指南中的重要内容。其值得关注的变化包括新增“开放科学”板块，强调对不良事件的评估、干预措施和对照措施的描述，以及新增关于患者和公众如何参与试验设计、实施和报告的条目。更新后的SPIRIT 2025声明包含1份基于证据的试验方案必备的34项条目清单，以及1个说明试验参与者入组登记、干预和评估时间的图表。为便于实施，我们还制定了SPIRIT 2025声明清单的扩展版本及1份配套的解释和说明文件。
结论对更新后SPIRIT 2025声明的广泛认可和遵循有可能提高试验方案的透明度和完整性，从而使研究者、试验参与者、患者、资助方、研究伦理委员会、期刊、试验注册平台、政策制订者、监管机构及其他评审人员共同受益。

关键词: 随机试验; 方案; 指南

Abstract: Importance The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users.
Objective To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial.
Design We completed a scoping review and developed a project-specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines [template for intervention description and replication (TIDieR)]. The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting.
Findings Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document.
Conclusions and Relevance Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

Key words: Randomised trial; Protocol; Guideline

中图分类号:

译者：李辉, 谢雪微. SPIRIT 2025声明：随机试验方案指南更新版[J]. 中国卒中杂志, 2025, 20(5): 636-646.

Translator: LI Hui, XIE Xuewei. SPIRIT 2025 Statement: Updated Guideline for Protocols of Randomised Trials[J]. Chinese Journal of Stroke, 2025, 20(5): 636-646.

参考文献

[1] ALTMAN D G. Better reporting of randomised controlled trials：the CONSORT statement[J]. BMJ，1996，313（7057）：570-571.
[2] ANONYMOUS. Strengthening the credibility of clinical research[J/OL]. Lancet，2010，375（9722）：1225[2025-04-30]. https://doi.org/10.1016/S0140-6736 (10) 60523-5.
[3] JONES G，ABBASI K. Trial protocols at the BMJ
[J/OL]. BMJ，2004，329（7479）：1360[2025-04-30]. https://doi.org/10.1136/bmj.329.7479.1360.
[4] LI T J，BOUTRON I，AI-SHAHI SALMAN R，et al. Review and publication of protocol submissions to Trials—what have we learned in 10 years？[J/OL]. Trials，2016，18（1）：34[2025-04-30]. https://doi.org/10.1186/s13063-016-1743-0.
[5] 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）[J]. BMJ，2005，330（7497）：956-958.
[6] LASSERE M，JOHNSON K. The power of the protocol[J]. Lancet，2002，360（9346）：1620-1622.
[7] CHAN A W，HRÓBJARTSSON A. Promoting public access to clinical trial protocols：challenges and recommendations[J/OL]. Trials，2018，19（1）：116[2025-04-30]. https://doi.org/10.1186/s13063-018-2510-1.
[8] ZARIN D A，FAIN K M，DOBBINS H D，et al.
10-year update on study results submitted to ClinicalTrials.gov[J]. N Engl J Med，2019，381（20）：1966-1974.
[9] 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）[J/OL]. BMJ Open，2022，12（5）：e053417[2025-04-30]. https://doi.org/10.1136/bmjopen-2021-053417.
[10] 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[J/OL]. Trials，2022，23（1）：601[2025-04-30]. https://doi.org/10.1186/s13063-022-06516-1.
[11] KASENDA B，VON ELM E，YOU J J，et al. Agreements between industry and academia on publication rights：a retrospective study of protocols and publications of randomized clinical trials[J/OL]. PLoS Med，2016，13（6）：e1002046[2025-04-30]. https://doi.org/10.1371/journal.pmed.1002046.
[12] GETZ K，SMITH Z，BOTTO E，et al. New benchmarks on protocol amendment practices，trends and their impact on clinical trial performance[J]. Ther Innov Regul Sci，2024，58（3）：539-548.
[13] CHAN A W，TETZLAFF J M，ALTMAN D G，et al. SPIRIT 2013 statement：defining standard protocol items for clinical trials[J]. Ann Intern Med，2013，158（3）：200-207.
[14] CHAN A W，TETZLAFF J M，GØTZSCHE P C，et al. SPIRIT 2013 explanation and elaboration：guidance for protocols of clinical trials[J/OL]. BMJ，2013，346：e7586[2025-04-30]. https://doi.org/10.1136/bmj.e7586.
[15] HOPEWELL S，CHAN A W，COLLINS G S，et al. CONSORT 2025 statement：updated guideline for reporting randomised trials[J/OL]. BMJ，2025，389：e081123[2025-04-30]. https://doi.org/10.1136/bmj-2024-081123.
[16] HOPEWELL S，BOUTRON I，CHAN A W，et al. An update to SPIRIT and CONSORT reporting guidelines to enhance transparency in randomized trials[J]. Nat Med，2022，28（9）：1740-1743.
[17] TUNN R，BOUTRON I，CHAN A W，et al. Methods used to develop the SPIRIT 2024 and CONSORT 2024 statements[J/OL]. J Clin Epidemiol，2024，169：111309[2025-04-30]. https://doi.org/10.1016/j.jclinepi.2024.111309.
[18] MOHER D，SCHULZ K F，SIMERA I，et al. Guidance for developers of health research reporting guidelines[J/OL]. PLoS Med，2010，7（2）：e1000217[2025-04-30]. https://doi.org/10.1371/journal.pmed.1000217.
[19] 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/OL]. J Clin Epidemiol，2023，155：48-63[2025-04-30]. https://doi.org/10.1016/j.jclinepi.2023.01.003.
[20] ØSTENGAARD L，BARRIENTOS A，BOUTRON I，et al. Development of a topic-specific bibliographic database supporting the updates of SPIRIT 2013 and CONSORT 2010[J/OL]. Cochrane Evid Synth Methods，2024，2（5）：e12057[2025-04-30]. https://doi.org/10.1002/cesm.12057.
[21] JUNQUEIRA D R，ZORZELA L，GOLDER S，et al. CONSORT harms 2022 statement，explanation，and elaboration：updated guideline for the reporting of harms in randomized trials[J/OL]. J Clin Epidemiol，2023，158：149-165[2025-04-30]. https://doi.org/10.1016/j.jclinepi.2023.04.005.
[22] BUTCHER N J，MONSOUR A，MEW E J，et al. Guidelines for reporting outcomes in trial protocols：the SPIRIT-outcomes 2022 extension[J]. JAMA，2022，328（23）：2345-2356.
[23] BOUTRON I，ALTMAN D G，MOHER D，et al. CONSORT statement for randomized trials of nonpharmacologic treatments：a 2017 update and a CONSORT extension for nonpharmacologic trial abstracts[J]. Ann Intern Med，2017，167（1）：40-47.
[24] HOFFMANN T C，GLASZIOU P P，BOUTRON I，et al. Better reporting of interventions：template for intervention description and replication（TIDieR）checklist and guide[J/OL]. BMJ，2014，348：g1687[2025-04-30]. https://doi.org/10.1136/bmj.g1687.
[25] HRÓBJARTSSON A，BOUTRON I，HOPEWELL S，et al. SPIRIT 2025 explanation and elaboration：updated guideline for protocols of randomised trials[J/OL]. BMJ，2025，389：e081660[2025-04-30]. https://doi.org/10.1136/bmj-2024-081660.
[26] BARNES C，BOUTRON I，GIRAUDEAU B，et al. Impact of an online writing aid tool for writing a randomized trial report：the COBWEB（CONSORT-based WEB tool）randomized controlled trial[J/OL]. BMC Med，2015，13：221[2025-04-30]. https://doi.org/10.1186/s12916-015-0460-y.
[27] CHAUVIN A，RAVAUD P，MOHER D，et al. Accuracy in detecting inadequate research reporting by early career peer reviewers using an online CONSORT-based peer-review tool（COBPeer）versus the usual peer-review process：a cross-sectional diagnostic study[J/OL]. BMC Med，2019，17（1）：205[2025-04-30]. https://doi.org/10.1186/s12916-019-1436-0.
[28] PAGE M J，MCKENZIE J E，BOSSUYT P M，et al. The PRISMA 2020 statement：an updated guideline for reporting systematic reviews[J/OL]. Syst Rev，2021，10（1）：89[2025-04-30]. https://doi.org/10.1186/s13643-021-01626-4.
[29] World Medical Association. World Medical Association Declaration of Helsinki：ethical principles for medical research involving human participants[J]. JAMA，2025，333（1）：71-74.
[30] GETZ K A，STERGIOPOULOS S，SHORT M，et al. The impact of protocol amendments on clinical trial performance and cost[J]. Ther Innov Regul Sci，2016，50（4）：436-441.
[31] ORKIN A M，GILL P J，GHERSI D，et al. Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 pandemic and other extenuating circumstances：the CONSERVE 2021 statement[J]. JAMA，2021，326（3）：257-265.
[32] CHAN A W，L KARAM G，PYMENTO J，et al. Reporting summary results in clinical trial registries：updated guidance from WHO[J/OL]. Lancet Glob Health，2025，13（4）：e759-e768[2025-04-30]. https://doi.org/10.1016/S2214-109X (24) 00514-X.
[33] GAMBLE C，KRISHAN A，STOCKEN D，et al. Guidelines for the content of statistical analysis plans in clinical trials[J]. JAMA，2017，318（23）：2337-2343.
[34] CHAN A W，PELLO A，KITCHEN J，et al. Association of trial registration with reporting of primary outcomes in protocols and publications[J]. JAMA，2017，318（17）：1709-1711.
[35] KAHAN B C，HALL S S，BELLER E M，et al. Consensus statement for protocols of factorial randomized trials：extension of the SPIRIT 2013 statement[J/OL]. JAMA Netw Open，2023，6（12）：e2346121[2025-04-30]. https://doi.org/10.1001/jamanetworkopen.2023.46121.
[36] CALVERT M，KYTE D，MERCIECA-BEBBER R，et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols：the SPIRIT-PRO extension[J]. JAMA，2018，319（5）：483-494.
[37] PORCINO A J，SHAMSEER L，CHAN A W，et al. SPIRIT extension and elaboration for n-of-1 trials：SPENT 2019 checklist[J/OL]. BMJ，2020，368：m122[2025-04-30]. https://doi.org/10.1136/bmj.m122.
[38] YAP C，REKOWSKI J，URSINO M，et al. Enhancing quality and impact of early phase dose-finding clinical trial protocols：SPIRIT dose-finding extension（SPIRIT-DEFINE）guidance[J/OL]. BMJ，2023，383：e076386[2025-04-30]. https://doi.org/10.1136/bmj-2023-076386.
[39] KENDALL T J，ROBINSON M，BRIERLEY D J，et al. Guidelines for cellular and molecular pathology content in clinical trial protocols：the SPIRIT-path extension[J/OL]. Lancet Oncol，2021，22（10）：e435-e445[2025-04-30]. https://doi.org/10.1016/S1470-2045 (21) 00344-2.
[40] CRUZ RIVERA S，LIU X X，CHAN A W，et al. Guidelines for clinical trial protocols for interventions involving artificial intelligence：the SPIRIT-AI extension[J]. Nat Med，2020，26（9）：1351-1363.
[41] DAI L，CHENG C W，TIAN R，et al. Standard protocol items for clinical trials with traditional Chinese medicine 2018：recommendations，explanation and elaboration（SPIRIT-TCM extension 2018）[J]. Chin J Integr Med，2019，25（1）：71-79.
[42] MANYARA A M，DAVIES P，STEWART D，et al. Reporting of surrogate endpoints in randomised controlled trial protocols（SPIRIT-surrogate）：extension checklist with explanation and elaboration[J/OL]. BMJ，2024，386：e078525[2025-04-30]. https://doi.org/10.1136/bmj-2023-078525.
[43] BLANCO D，DONADIO M V F，CADELLANS-ARRÓNIZ A. Enhancing reporting through structure：a before and after study on the effectiveness of SPIRIT-based templates to improve the completeness of reporting of randomized controlled trial protocols[J/OL]. Res Integr Peer Rev，2024，9（1）：6[2025-04-30]. https://doi.org/10.1186/s41073-024-00147-7.
[44] TAN Z W，TAN A C，LI T，et al. Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement？A methodological study[J/OL]. BMJ Open，2020，10（8）：e038283[2025-04-30]. https://doi.org/10.1136/bmjopen-2020-038283.
[45] RUSS H，BUSTA S，JOST B，et al. Evaluation of clinical trials by Ethics Committees in Germany—results and a comparison of two surveys performed among members of the German Association of Research-Based Pharmaceutical Companies（vfa）
[J/OL]. Ger Med Sci，2015，13：Doc02[2025-04-30]. https://doi.org/10.3205/000206.
[46] TARG Meta-Research Group & Collaborators. Estimating the prevalence of discrepancies between study registrations and publications：a systematic review and meta-analyses[J/OL]. BMJ Open，2023，13（10）：e0762642[2025-04-30]. https://doi.org/10.1136/bmjopen-2023-076264.
[47] CHAN A W，HRÓBJARTSSON A，HAAHR M T，et al. Empirical evidence for selective reporting of outcomes in randomized trials：comparison of protocols to published articles[J]. JAMA，2004，291（20）：2457-2465.
[48] SCHÖNENBERGER C M，GRIESSBACH A，TAJI HERAVI A，et al. A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols[J/OL]. J Clin Epidemiol，2022，149：45-52[2025-04-30]. https://doi.org/10.1016/j.jclinepi.2022.05.014.