SPIRIT 2025 statement: updated guideline for protocols of randomized trials

An-Wen Chan¹, Isabelle Boutron^{2

3}, Sally Hopewell⁴, David Moher⁵, Kenneth F Schulz⁶, Gary S Collins⁷, Ruth Tunn⁴, Rakesh Aggarwal⁸, Michael Berkwits⁹, Jesse A Berlin^{10

11}, Nita Bhandari¹², Nancy J Butcher^{13

14}, Marion K Campbell¹⁵, Runcie C W Chidebe^{16

17}, Diana R Elbourne¹⁸, Andrew J Farmer¹⁹, Dean A Fergusson²⁰, Robert M Golub²¹, Steven N Goodman²², Tammy C Hoffmann²³, John P A Ioannidis²⁴, Brennan C Kahan²⁵, Rachel L Knowles²⁶, Sarah E Lamb²⁷, Steff Lewis²⁸, Elizabeth Loder^{29

30}, Martin Offringa¹³, Philippe Ravaud³¹, Dawn P Richards³², Frank W Rockhold³³, David L Schriger³⁴, Nandi L Siegfried³⁵, Sophie Staniszewska³⁶, Rod S Taylor³⁷, Lehana Thabane^{38

39}, David J Torgerson⁴⁰, Sunita Vohra⁴¹, Ian R White²⁵, Asbjørn Hróbjartsson^{42

43}

Affiliations

¹ Department of Medicine, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada. anwen.chan@utoronto.ca.
² Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Centre for Research in Epidemiology and Statistics (CRESS), Paris, France.
³ Centre d'Epidémiologie Clinique, Hôpital Hôtel Dieu, AP-HP, Paris, France.
⁴ Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
⁵ Centre for Journalology, Clinical Epidemiology Programme, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁶ Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ UK EQUATOR Centre, Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
⁸ Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
⁹ Office of Science Dissemination, Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹⁰ Department of Biostatistics and Epidemiology, School of Public Health, Center for Pharmacoepidemiology and Treatment Science, Rutgers University, New Brunswick, NJ, USA.
¹¹ JAMA Network Open, Chicago, IL, USA.
¹² Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
¹³ Child Health Evaluation Services, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
¹⁴ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Aberdeen Centre for Evaluation, University of Aberdeen, Aberdeen, UK.
¹⁶ Project PINK BLUE - Health & Psychological Trust Centre, Utako, Abuja, Nigeria.
¹⁷ Department of Sociology and Gerontology, Miami University, Oxford, OH, USA.
¹⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
¹⁹ Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
²⁰ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²¹ Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
²² Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.
²³ Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland, Australia.
²⁴ Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.
²⁵ MRC Clinical Trials Unit at University College London, London, UK.
²⁶ University College London, UCL Great Ormond Street Institute of Child Health, London, UK.
²⁷ NIHR Exeter Biomedical Research Centre, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
²⁸ Edinburgh Clinical Trials Unit, Usher Institute-University of Edinburgh, Edinburgh, UK.
²⁹ The BMJ, BMA House, London, UK.
³⁰ Harvard Medical School, Boston, MA, USA.
³¹ Université Paris Cité, Inserm, INRAE, Centre de Recherche Epidémiologie et Statistiques, Université Paris Cité, Paris, France.
³² Clinical Trials Ontario, MaRS Centre, Toronto, Ontario, Canada.
³³ Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
³⁴ Department of Emergency Medicine, University of California, Los Angeles, CA, USA.
³⁵ South African Medical Research Council, Cape Town, South Africa.
³⁶ Warwick Applied Health, Warwick Medical School, University of Warwick, Coventry, UK.
³⁷ MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
³⁸ Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
³⁹ St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
⁴⁰ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁴¹ Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
⁴² Centre for Evidence-Based Medicine Odense and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁴³ Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark.

PMID: 40295741
DOI: 10.1038/s41591-025-03668-w

Review

SPIRIT 2025 statement: updated guideline for protocols of randomized trials

An-Wen Chan et al. Nat Med. 2025 Jun.

. 2025 Jun;31(6):1784-1792.

doi: 10.1038/s41591-025-03668-w. Epub 2025 Apr 29.

Authors

Affiliations

¹ Department of Medicine, Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada. anwen.chan@utoronto.ca.
² Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Centre for Research in Epidemiology and Statistics (CRESS), Paris, France.
³ Centre d'Epidémiologie Clinique, Hôpital Hôtel Dieu, AP-HP, Paris, France.
⁴ Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
⁵ Centre for Journalology, Clinical Epidemiology Programme, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁶ Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ UK EQUATOR Centre, Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
⁸ Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
⁹ Office of Science Dissemination, Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹⁰ Department of Biostatistics and Epidemiology, School of Public Health, Center for Pharmacoepidemiology and Treatment Science, Rutgers University, New Brunswick, NJ, USA.
¹¹ JAMA Network Open, Chicago, IL, USA.
¹² Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
¹³ Child Health Evaluation Services, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
¹⁴ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Aberdeen Centre for Evaluation, University of Aberdeen, Aberdeen, UK.
¹⁶ Project PINK BLUE - Health & Psychological Trust Centre, Utako, Abuja, Nigeria.
¹⁷ Department of Sociology and Gerontology, Miami University, Oxford, OH, USA.
¹⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
¹⁹ Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
²⁰ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²¹ Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
²² Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.
²³ Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland, Australia.
²⁴ Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.
²⁵ MRC Clinical Trials Unit at University College London, London, UK.
²⁶ University College London, UCL Great Ormond Street Institute of Child Health, London, UK.
²⁷ NIHR Exeter Biomedical Research Centre, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
²⁸ Edinburgh Clinical Trials Unit, Usher Institute-University of Edinburgh, Edinburgh, UK.
²⁹ The BMJ, BMA House, London, UK.
³⁰ Harvard Medical School, Boston, MA, USA.
³¹ Université Paris Cité, Inserm, INRAE, Centre de Recherche Epidémiologie et Statistiques, Université Paris Cité, Paris, France.
³² Clinical Trials Ontario, MaRS Centre, Toronto, Ontario, Canada.
³³ Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
³⁴ Department of Emergency Medicine, University of California, Los Angeles, CA, USA.
³⁵ South African Medical Research Council, Cape Town, South Africa.
³⁶ Warwick Applied Health, Warwick Medical School, University of Warwick, Coventry, UK.
³⁷ MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
³⁸ Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
³⁹ St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
⁴⁰ York Trials Unit, Department of Health Sciences, University of York, York, UK.
⁴¹ Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
⁴² Centre for Evidence-Based Medicine Odense and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁴³ Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark.

PMID: 40295741
DOI: 10.1038/s41591-025-03668-w

Abstract

The protocol of a randomized 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 (Standard Protocol Items: Recommendations for Interventional Trials) 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. Here, we aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. 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 (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. 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 enrollment, 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. 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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare the following: support from MRC-NIHR for the submitted work; S.H., I.B., A.-W.C., A.H., K.F.S. and D.M. are members of the SPIRIT-CONSORT executive group. S.H., I.B., A.-W.C., A.H., K.F.S., G.S.C., D.M., M.K.C., N.J.B., M.O., R.S.T. and S.V. are involved in the development, update, implementation and dissemination of several reporting guidelines. G.S.C. is the director of the UK EQUATOR Centre and a statistical editor for The BMJ; D.M. is the director of the Canadian EQUATOR Centre and a member of The BMJ’s regional advisory board for North America; I.B. is deputy director and P.R. is director of the French EQUATOR Centre; T.C.H. is director of the Australasian EQUATOR Centre; J.P.A.I. is director of the US EQUATOR Centre; R.A. is president of the World Association of Medical Editors. M.K.C. is chair of the MRC-NIHR: Better Methods Better Research funding panel. R.C.W.C. is executive director of Project PINK-BLUE, which receives funding from Roche-Product. A.F. is director of the UK National Institute for Health and Care Research Health Technology Assessment Programme. D.P.R. is a full-time employee of Five02 Laboratories (which under contract to Clinical Trials Ontario and provides services related to patient and public engagement) and is the volunteer vice president of the Canadian Arthritis Patient Alliance (which receives funding through independent grants from pharmaceutical companies). D.L.S. is the JAMA associate editor and receives editing stipends from JAMA and Annals of Emergency Medicine. I.R.W. was supported by the MRC Programmes MCUU00004/07 and MCUU00004/09.

References

1. Altman, D. G. Better reporting of randomised controlled trials: the CONSORT statement. BMJ 313, 570–571 (1996). - PubMed - PMC
1. Strengthening the credibility of clinical research. Lancet 375, 1225 (2010).
1. Jones, G. & Abbasi, K. Trial protocols at the BMJ. BMJ 329, 1360 (2004). - PubMed - PMC
1. Li, T. et al. Review and publication of protocol submissions to trials - what have we learned in 10 years? Trials 18, 34 (2016). - PubMed - PMC
1. Krleza-Jerić, K. et al. Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1). BMJ 330, 956–958 (2005). - PubMed - PMC

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SPIRIT 2025 statement: updated guideline for protocols of randomized trials

Affiliations

SPIRIT 2025 statement: updated guideline for protocols of randomized trials

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources