SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials

Asbjørn Hróbjartsson^{1

2}, Isabelle Boutron^{3

4}, Sally Hopewell⁵, David Moher⁶, Kenneth F Schulz⁷, Gary S Collins⁸, Ruth Tunn⁵, Rakesh Aggarwal⁹, Michael Berkwits¹⁰, Jesse A Berlin^{11

12}, Nita Bhandari¹³, Nancy J Butcher^{14

15}, Marion K Campbell¹⁶, Runcie C W Chidebe^{17

18}, Diana R Elbourne¹⁹, Andrew J Farmer²⁰, Dean A Fergusson²¹, Robert M Golub²², Steven N Goodman²³, Tammy C Hoffmann²⁴, John P A Ioannidis²⁵, Brennan C Kahan²⁶, Rachel L Knowles²⁷, Sarah E Lamb²⁸, Steff Lewis²⁹, Elizabeth Loder^{30

31}, Martin Offringa¹⁴, Philippe Ravaud³², Dawn P Richards³³, Frank W Rockhold³⁴, David L Schriger³⁵, Nandi L Siegfried³⁶, Sophie Staniszewska³⁷, Rod S Taylor³⁸, Lehana Thabane^{39

40}, David J Torgerson⁴¹, Sunita Vohra⁴², Ian R White²⁵, An-Wen Chan⁴³

Affiliations

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

PMID: 40294956
PMCID: PMC12128891
DOI: 10.1136/bmj-2024-081660

Comment

SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials

Asbjørn Hróbjartsson et al. BMJ. 2025.

. 2025 Apr 28:389:e081660.

doi: 10.1136/bmj-2024-081660.

Authors

Affiliations

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

PMID: 40294956
PMCID: PMC12128891
DOI: 10.1136/bmj-2024-081660

Abstract

High quality protocols facilitate proper planning, conduct, reporting, and external review of randomised trials, yet their completeness varies and key elements are often not considered. To strengthen good reporting of trial protocols, the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 statement has been updated to incorporate new evidence and emerging perspectives. This SPIRIT 2025 explanation and elaboration document provides users with exemplars of reporting in contemporary trial protocols, contextual elaboration, more detailed guidance on reporting, references to key empirical studies, an expanded checklist, and a link to a website for further information. The document is intended to be used in conjunction with the SPIRIT 2025 statement and serves as a resource for researchers planning a trial and for others interested in trial protocols.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Medical Research Council-National Institute for Health and Care Research (MRC-NIHR) for the submitted work. AH, A-WC, SH, IB, KFS, and DM, are members of the SPIRIT-CONSORT Executive Group. AH, AWC, SH, IB, KFS, GSC, DM, MKC, NJB, MO, RST, and SV are involved in the development, update, implementation, and dissemination of several reporting guidelines. GSC is the director of the UK EQUATOR Centre and statistics editor for The BMJ. DM is the director of the Canadian EQUATOR Centre and a member of The BMJ’s regional advisory board for North America. IB is deputy director and PR is director of the French EQUATOR Centre. TCH is director of the Australasian EQUATOR Centre. JPAI is director of the US EQUATOR Centre. RA is president of the World Association of Medical Editors. MKC is chair of the MRC-NIHR: Better Methods Better Research funding panel. RCWC is executive director of Project PINK-BLUE, which receives funding from Roche-Product. AF is director of the UK NIHR Technology Assessment Programme. DPR is a full time employee of Five02 Laboratories, which under contract to Clinical Trials Ontario 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. DLS is associate editor of the Journal of the American Medical Association and receives editing stipends from JAMA and Annals of Emergency Medicine. IRW was supported by the MRC programmes MCUU00004/07 and MCUU00004/09.

Figures

**Fig 1**
Schedule of enrolment, interventions, and assessments for SPIRIT 2025 statement. Recommended content can be displayed using various schematic formats. *List target time points and acceptable time windows (eg, 30±3 days) in this row. †Arrow indicates continuous delivery of intervention (eg, drug). ‡Example illustrates delivery of intervention or comparator at discrete time points (eg, psychotherapy). The brackets indicate placeholder text that should be replaced with the actual text for a specific trial. SPIRIT=Standard Protocol Items: Recommendations for Interventional Trials

**Fig 2**
Participant schedule of enrolment, interventions, and assessments for a randomised trial of lumbar microdiscectomy and postoperative activity restrictions. Adapted from Daly et al

See this image and copyright information in PMC

Comment on

SPIRIT 2025 statement: updated guideline for protocols of randomised trials.
Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne DR, Farmer AJ, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson DJ, Vohra S, White IR, Hróbjartsson A. Chan AW, et al. BMJ. 2025 Apr 28;389:e081477. doi: 10.1136/bmj-2024-081477. BMJ. 2025. PMID: 40294953 Free PMC article.

References

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SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials

Affiliations

SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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