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[Preprint]. 2025 Sep 5:2025.09.03.25334905.

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, Andrew Grey¹⁸, Steph Grohmann¹⁹, Lyle C Gurrin²⁰, Jill A Hayden^{21

22}, James A J Heathers²³, Kylie E Hunter²⁴, Ian Hussey²⁵, Lukas Jung²⁶, Emily Lam²⁷, Toby J Lasserson², Sarah Lensen²⁸, Tianjing Li²⁹, Wentao Li³⁰, Jianping Liu³¹, Elizabeth Loder^{32

33}, Andreas Lundh^{34

35

36}, Gideon Meyerowitz-Katz³⁷, Ben W Mol³⁸, Florian Naudet^{39

40}, Anna Noel-Storr², Neil E O'Connell⁴¹, Lisa Parker⁴², Rita F Redberg⁴³, Barbara K Redman⁴⁴, Rachel Richardson², Anna Lene Seidler⁴⁵, Kyle Sheldrick⁴⁶, Emma Sydenham⁴⁷, Madelon van Wely⁴⁸, Colby J Vorland⁴⁹, Rui Wang²⁴, Stephanie Weibel⁵⁰, Matthias Wjst⁵¹, Lisa Bero⁵², 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 University of Auckland, Auckland, New Zealand.
¹⁹ Research Integrity Editor, Cochrane, London, UK.
²⁰ School of Population and Global Health, The University of Melbourne.
²¹ Department of Community Health & Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
²² Novia Scotia Health, Halifax, Nova Scotia, Canada.
²³ Medical Evidence Project, Center for Scientific Integrity, NY, USA.
²⁴ NHMRC Clinical Trials Centre, University of Sydney, Australia.
²⁵ Institute of Psychology, University of Bern, Switzerland.
²⁶ Independent researcher, Heidelberg, Germany.
²⁷ Independent Lay Member, Unaffiliated, Cheshire, UK.
²⁸ Department of Obstetrics, Gynaecology and Newborn Health, Royal Women's Hospital, University of Melbourne, Australia.
²⁹ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, USA.
³⁰ 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.
³¹ Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
³² The BMJ, UK.
³³ Harvard Medical School, Boston, MA, USA.
³⁴ Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁵ Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
³⁶ Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
³⁷ University of Woolongong, NSW, Australia.
³⁸ Department of Obstetrics Gynaecology, Monash University, Melbourne, Australia.
³⁹ Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S, Rennes, France.
⁴⁰ Institut Universitaire de France (IUF), Paris, France.
⁴¹ Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University of London, United Kingdom.
⁴² Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia.
⁴³ Department of Medicine, UCSF Philip Lee Institute for Health Policy Studies, USA.
⁴⁴ New York University Grossman School of Medicine, New York, USA.
⁴⁵ 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.
⁴⁶ Spine Labs, Faculty of Clinical Medicine, University of New South Wales.
⁴⁷ Cochrane Central Editorial Service, London, UK.
⁴⁸ Centre for Reproductive Medicine, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
⁴⁹ Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, USA.
⁵⁰ University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany.
⁵¹ Institut für KI und Informatik in der Medizin, Lehrstuhl für Medizinische Informatik, Klinikum rechts der Isar, Grillparzerstr. 18, D-81675 München, Germany.
⁵² 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 Sep 5:2025.09.03.25334905.

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 University of Auckland, Auckland, New Zealand.
¹⁹ Research Integrity Editor, Cochrane, London, UK.
²⁰ School of Population and Global Health, The University of Melbourne.
²¹ Department of Community Health & Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
²² Novia Scotia Health, Halifax, Nova Scotia, Canada.
²³ Medical Evidence Project, Center for Scientific Integrity, NY, USA.
²⁴ NHMRC Clinical Trials Centre, University of Sydney, Australia.
²⁵ Institute of Psychology, University of Bern, Switzerland.
²⁶ Independent researcher, Heidelberg, Germany.
²⁷ Independent Lay Member, Unaffiliated, Cheshire, UK.
²⁸ Department of Obstetrics, Gynaecology and Newborn Health, Royal Women's Hospital, University of Melbourne, Australia.
²⁹ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, USA.
³⁰ 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.
³¹ Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
³² The BMJ, UK.
³³ Harvard Medical School, Boston, MA, USA.
³⁴ Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³⁵ Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
³⁶ Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
³⁷ University of Woolongong, NSW, Australia.
³⁸ Department of Obstetrics Gynaecology, Monash University, Melbourne, Australia.
³⁹ Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S, Rennes, France.
⁴⁰ Institut Universitaire de France (IUF), Paris, France.
⁴¹ Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University of London, United Kingdom.
⁴² Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia.
⁴³ Department of Medicine, UCSF Philip Lee Institute for Health Policy Studies, USA.
⁴⁴ New York University Grossman School of Medicine, New York, USA.
⁴⁵ 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.
⁴⁶ Spine Labs, Faculty of Clinical Medicine, University of New South Wales.
⁴⁷ Cochrane Central Editorial Service, London, UK.
⁴⁸ Centre for Reproductive Medicine, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
⁴⁹ Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, USA.
⁵⁰ University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg, Germany.
⁵¹ Institut für KI und Informatik in der Medizin, Lehrstuhl für Medizinische Informatik, Klinikum rechts der Isar, Grillparzerstr. 18, D-81675 München, Germany.
⁵² 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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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

1. Cochrane. Cochrane Policy for managing potentially problematic studies. Cochrane Database of Systematic Reviews: editorial policies Cochrane Library [Available from: https://www.cochranelibrary.com/cdsr/editorial-policies.
1. Hill A, Mirchandani M, Pilkington V. Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud. Open Forum Infect Dis. 2022;9(2):ofab645. - PMC - PubMed
1. Ker K, Shakur H, Roberts I. Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. BJOG. 2016;123(11):1745–52. - PubMed
1. Okesene-Gafa KA, Moore AE, Jordan V, McCowan L, Crowther CA. Probiotic treatment for women with gestational diabetes to improve maternal and infant health and well-being. Cochrane Database Syst Rev. 2020;6(6):CD012970. - PMC - PubMed
1. Carlisle JB. False individual patient data and zombie randomised controlled trials submitted to Anaesthesia. Anaesthesia. 2021;76(4):472–9. - PubMed

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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

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials