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[Preprint]. 2025 Oct 21:2025.09.03.25334905.

doi: 10.1101/2025.09.03.25334905.

INSPECT-SR: a tool for assessing trustworthiness of randomised controlled trials

Jack Wilkinson¹, Calvin Heal¹, Ella Flemyng², Georgios A Antoniou^{3

4}, Tony Aburrow², Zarko Alfirevic⁵, Alison Avenell⁶, Virginia Barbour⁷, Vincenzo Berghella⁸, Dorothy V M Bishop⁹, Esmée M Bordewijk¹⁰, Nicholas J L Brown¹¹, Jana Christopher¹², Mike Clarke¹³, Darren Dahly¹⁴, Jane Dennis¹⁵, Patrick Dicker¹⁶, Jo Dumville¹⁷, Helen Frankish¹⁸, Andrew Grey¹⁹, Steph Grohmann²⁰, Lyle C Gurrin²¹, Jill A Hayden^{22

23}, James A J Heathers²⁴, Kylie E Hunter²⁵, Ian Hussey²⁶, Lukas Jung²⁷, Emily Lam²⁸, Toby J Lasserson², Sarah Lensen²⁹, Tianjing Li³⁰, Wentao Li³¹, Jianping Liu³², Elizabeth Loder^{33

34}, Andreas Lundh^{35

36

37}, Gideon Meyerowitz-Katz³⁸, Ben W Mol³⁹, Florian Naudet^{40

41}, Anna Noel-Storr², Neil E O'Connell⁴², Lisa Parker⁴³, Rita F Redberg⁴⁴, Barbara K Redman⁴⁵, Rachel Richardson², Anna Lene Seidler⁴⁶, Kyle Sheldrick⁴⁷, Emma Sydenham⁴⁸, Madelon van Wely⁴⁹, Colby J Vorland⁵⁰, Rui Wang²⁵, Stephanie Weibel⁵¹, Matthias Wjst⁵², Lisa Bero⁵³, Jamie J Kirkham¹

Affiliations

¹ Centre for Biostatistics, Manchester Academic Health Science Centre, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK.
² Cochrane Central Executive, London, UK.
³ Manchester Vascular Centre, Manchester University NHS Foundation Trust, Manchester, UK.
⁴ Division of Cardiovascular Sciences, School of Medical Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
⁵ University of Liverpool, UK.
⁶ Aberdeen Centre for Evaluation, University of Aberdeen, UK.
⁷ Medical Journal of Australia and Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸ Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, USA.
⁹ Department of Experimental Psychology, University of Oxford, UK.
¹⁰ Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹¹ Department of Psychology, Linnaeus University, Sweden.
¹² FEBS Press, Heidelberg, Germany.
¹³ Centre for Public Health, Queen's University Belfast, Belfast, UK.
¹⁴ HRB Clinical Research Facility, School of Public Health, University College Cork, Cork, Ireland.
¹⁵ University of Bristol, UK.
¹⁶ Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland, Ireland.
¹⁷ School of Health Sciences, University of Manchester, Manchester, UK.
¹⁸ The Lancet, London, UK.
¹⁹ University of Auckland, Auckland, New Zealand.
²⁰ Research Integrity Editor, Cochrane, London, UK.
²¹ School of Population and Global Health, The University of Melbourne.
²² Department of Community Health & Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
²³ Novia Scotia Health, Halifax, Nova Scotia, Canada.
²⁴ Medical Evidence Project, Center for Scientific Integrity, NY, USA.
²⁵ NHMRC Clinical Trials Centre, University of Sydney, Australia.
²⁶ Institute of Psychology, University of Bern, Switzerland.
²⁷ Independent researcher, Heidelberg, Germany.
²⁸ Independent Lay Member, Unaffiliated, Cheshire, UK.
²⁹ Department of Obstetrics, Gynaecology and Newborn Health, Royal Women's Hospital, University of Melbourne, Australia.
³⁰ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, USA.
³¹ National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health and School of Clinical Medicine, The University of New South Wales, Sydney, Australia.
³² Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
³³ The BMJ, UK.
³⁴ Harvard Medical School, Boston, MA, USA.
³⁵ Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁶ Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark .
³⁷ Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
³⁸ University of Woolongong, NSW, Australia.
³⁹ Department of Obstetrics Gynaecology, Monash University, Melbourne, Australia.
⁴⁰ Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S, Rennes, France.
⁴¹ Institut Universitaire de France (IUF), Paris, France.
⁴² Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University of London, United Kingdom.
⁴³ Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia.
⁴⁴ Department of Medicine, UCSF Philip Lee Institute for Health Policy Studies, USA.
⁴⁵ New York University Grossman School of Medicine, New York, USA.
⁴⁶ Department of Child and Adolescent Psychiatry, University Medical Centre Rostock, Rostock, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Greifswald/Rostock, Rostock, Germany.
⁴⁷ Spine Labs, Faculty of Clinical Medicine, University of New South Wales.
⁴⁸ Cochrane Central Editorial Service, London, UK.
⁴⁹ Centre for Reproductive Medicine, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
⁵⁰ Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, USA.
⁵¹ University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany.
⁵² Institut für KI und Informatik in der Medizin, Lehrstuhl für Medizinische Informatik, Klinikum rechts der Isar, Grillparzerstr. 18, D-81675 München, Germany.
⁵³ Center for Bioethics, and Humanities, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

PMID: 40950444
PMCID: PMC12424918
DOI: 10.1101/2025.09.03.25334905

INSPECT-SR: a tool for assessing trustworthiness of randomised controlled trials

Jack Wilkinson et al. medRxiv. 2025.

[Preprint]. 2025 Oct 21:2025.09.03.25334905.

doi: 10.1101/2025.09.03.25334905.

Authors

Affiliations

¹ Centre for Biostatistics, Manchester Academic Health Science Centre, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK.
² Cochrane Central Executive, London, UK.
³ Manchester Vascular Centre, Manchester University NHS Foundation Trust, Manchester, UK.
⁴ Division of Cardiovascular Sciences, School of Medical Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
⁵ University of Liverpool, UK.
⁶ Aberdeen Centre for Evaluation, University of Aberdeen, UK.
⁷ Medical Journal of Australia and Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁸ Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, USA.
⁹ Department of Experimental Psychology, University of Oxford, UK.
¹⁰ Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹¹ Department of Psychology, Linnaeus University, Sweden.
¹² FEBS Press, Heidelberg, Germany.
¹³ Centre for Public Health, Queen's University Belfast, Belfast, UK.
¹⁴ HRB Clinical Research Facility, School of Public Health, University College Cork, Cork, Ireland.
¹⁵ University of Bristol, UK.
¹⁶ Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland, Ireland.
¹⁷ School of Health Sciences, University of Manchester, Manchester, UK.
¹⁸ The Lancet, London, UK.
¹⁹ University of Auckland, Auckland, New Zealand.
²⁰ Research Integrity Editor, Cochrane, London, UK.
²¹ School of Population and Global Health, The University of Melbourne.
²² Department of Community Health & Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
²³ Novia Scotia Health, Halifax, Nova Scotia, Canada.
²⁴ Medical Evidence Project, Center for Scientific Integrity, NY, USA.
²⁵ NHMRC Clinical Trials Centre, University of Sydney, Australia.
²⁶ Institute of Psychology, University of Bern, Switzerland.
²⁷ Independent researcher, Heidelberg, Germany.
²⁸ Independent Lay Member, Unaffiliated, Cheshire, UK.
²⁹ Department of Obstetrics, Gynaecology and Newborn Health, Royal Women's Hospital, University of Melbourne, Australia.
³⁰ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, USA.
³¹ National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health and School of Clinical Medicine, The University of New South Wales, Sydney, Australia.
³² Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
³³ The BMJ, UK.
³⁴ Harvard Medical School, Boston, MA, USA.
³⁵ Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁶ Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark .
³⁷ Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
³⁸ University of Woolongong, NSW, Australia.
³⁹ Department of Obstetrics Gynaecology, Monash University, Melbourne, Australia.
⁴⁰ Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S, Rennes, France.
⁴¹ Institut Universitaire de France (IUF), Paris, France.
⁴² Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University of London, United Kingdom.
⁴³ Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia.
⁴⁴ Department of Medicine, UCSF Philip Lee Institute for Health Policy Studies, USA.
⁴⁵ New York University Grossman School of Medicine, New York, USA.
⁴⁶ Department of Child and Adolescent Psychiatry, University Medical Centre Rostock, Rostock, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Greifswald/Rostock, Rostock, Germany.
⁴⁷ Spine Labs, Faculty of Clinical Medicine, University of New South Wales.
⁴⁸ Cochrane Central Editorial Service, London, UK.
⁴⁹ Centre for Reproductive Medicine, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
⁵⁰ Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, USA.
⁵¹ University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany.
⁵² Institut für KI und Informatik in der Medizin, Lehrstuhl für Medizinische Informatik, Klinikum rechts der Isar, Grillparzerstr. 18, D-81675 München, Germany.
⁵³ Center for Bioethics, and Humanities, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

PMID: 40950444
PMCID: PMC12424918
DOI: 10.1101/2025.09.03.25334905

Abstract

The integrity of evidence synthesis is threatened by problematic randomised controlled trials (RCTs). These are RCTs where there are serious concerns about the trustworthiness of the data or findings. This could be due to research misconduct, including fraud, or due to honest critical errors. If these RCTs are not detected, they may be inadvertently included in systematic reviews and guidelines, potentially distorting their results. To address this problem, the INSPECT-SR (INveStigating ProblEmatic Clinical Trials in Systematic Reviews) tool has been developed to assess the trustworthiness of RCTs. This will allow problematic RCTs to be identified and excluded from systematic reviews. This paper describes the development of INSPECT-SR. The tool and an associated guidance document are presented.

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Conflict of interest statement

Declarations JW, CH, GAA, LB, JJK declare funding from NIHR (NIHR203568) in relation to the current project. JW additionally declares Stats or Methodological Editor roles for BJOG, Fertility and Sterility, Reproduction and Fertility, Journal of Hypertension, and for Cochrane Gynaecology and Fertility. AL is on the editorial board of BMC Medical Ethics. TLi declares funding from the National Eye Institute, National Institutes of Health (UG1 EY020522). TLi serves as a methodological editor for Annals of Internal Medicine, the review editor for JAMA Ophthalmology, a Co-Editor-in-Chief for Trials, and is on the editorial board for Journal of Clinical Epidemiology. WL declares funding from the Australian National Health and Medical Research Council, Medical Research Future Fund, and Ramaciotti Foundations. WL serves as an associate editor for Human Reproduction and methodological reviewer for Fertility & Sterility and F&S Reviews. SL declares funding from the University of Melbourne, Norman Beischer Medical Research Foundation, and National Health and Medical Research Council. SL is co-ordinating editor of Cochrane Gynaecology and Fertility and an editor for Human Reproduction Open, Fertility and Sterility, and Trials. FN received funding from the French National Research Agency, the French ministry of health and the French ministry of research. He is a work package leader in the OSIRIS project (Open Science to Increase Reproducibility in Science, funded by the European Union’s Horizon Europe research and innovation programme under grant agreement No. 101094725). FN is also work package leader for the doctoral network MSCA-DN SHARE-CTD (HORIZON-MSCA-2022-DN-01 101120360), funded by the European Union. TJL is an employee of The Cochrane Collaboration and interim Editor in Chief of the Cochrane Library. TA is an employee of The Cochrane Collaboration. EF is an employee of the Cochrane Collaboration and editorial board member of Cochrane Evidence Synthesis and Methods. RR is an employee of The Cochrane Collaboration and editor of Cochrane Evidence Synthesis and Methods. AA and CJV declares funding from the UKRI Metascience Unit (ESRC and Open Philanthropy) for the INSPECT-AI project. UKRI1083: Evaluating the Development and Impact of AI-Assisted Integrity Assessment of Randomised Trials in Evidence Syntheses. ES is a Senior Editor of the Cochrane Database of Systematic Reviews. LP is on the editorial board for Journal of Clinical Epidemiology. SG is an employee of the Cochrane Collaboration. SW is editor for Cochrane Anesthesia and involved in development of the Research Integrity Assessment (RIA) tool for RCTs included in evidence synthesis. ALS is on the Editorial Board for Cochrane Evidence Synthesis Methods, Statistical Editor for Cochrane Neonatal and Co-Convenor for the Cochrane Prospective Meta-Analysis Methods Group. KEH is Associate Convenor for the Cochrane Prospective Meta-Analysis Methods Group. BWM reports consultancy, travel support and research funding from Merck and consultancy for Ferring, Organon, UNILAB and Norgine. RW declares funding from the Australian National Health and Medical Research Council. RW is a Deputy Editor of Human Reproduction Update, an Editorial Board Member of BJOG and Cochrane Gynaecology and Fertility Group, and a former Deputy Editor of Human Reproduction. NOC Between 2020 and 2023 NOC was Coordinating Editor of the Cochrane Pain, Palliative and Supportive Care group, whose activities were funded by The UK National Institute of Health and Care Research (NIHR). He is the Chair of the International Association for the Study of Pain (IASP) Methodology, Evidence Synthesis and Implementation Special Interest Group and has held a grant from the ERA-NET Neuron Co-Fund. LJ is the creator of the scrutiny package in R. VB is the Editor in Chief of the Medical Journal of Australia and on the Editorial Board of Research Integrity and Peer Review. MC declares Coordinating Editor or Editor in Chief roles for James Lind Library, Cochrane Methodology Review Group and Journal of Evidence-Based Medicine, and many years of funded research using randomised trials and systematic reviews. ZA declares membership of the Cochrane Library Editorial Board, and PI on a grant from Children Investment Foundation Fund to University of Liverpool to investigate research integrity of clinical trials related to nutritional supplements in pregnancy. JDe is a member of the Cochrane Emergency and Acute Care Thematic Group. MvW is sign-off Editor for Cochrane, Senior Editor of Cochrane Gynaecology and Fertility and Cochrane Sexually Transmitted Infections, and Editor in Chief of Human Reproduction Update. JAJH declares funding from Open Philanthropy and consultancy for the Gates Foundation and Helena Foundation. HF declares an editorial role at The Lancet. All other authors declare no conflict of interest.

Figures

**Figure 1:**
Summary of the development of INSPECT-SR

**Figure 2:**
Structure of the INSPECT-SR tool

See this image and copyright information in PMC

References

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This is a preprint.

INSPECT-SR: a tool for assessing trustworthiness of randomised controlled trials

Affiliations

INSPECT-SR: a tool for assessing trustworthiness of randomised controlled trials

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials