Kurinchi S Gurusamy1,2, David Moher3,4, Marilena Loizidou1, Irfan Ahmed5, Marc T Avey3,4, Carly C Barron3,4,6, Brian Davidson1, Miriam Dwek7, Christian Gluud8, Gavin Jell1, Kiran Katakam8, Joshua Montroy9, Timothy D McHugh10, Nicola J Osborne11, Merel Ritskes-Hoitinga12, Kees van Laarhoven13, Jan Vollert14,15, Manoj Lalu9. 1. Research Department of Surgical Biotechnology, University College London, London, England, UK. 2. Surgery and Interventional Trials Unit, University College London, London, England, UK. 3. Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada. 4. School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. 5. Department of Surgery, NHS Grampian, Aberdeen, Scotland, UK. 6. Department of Medicine, McMaster University, Hamilton, ON, Canada. 7. School of Life Sciences, University of Westminster, London, England, UK. 8. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copehagen, Denmark. 9. Department of Anesthesiology and Pain Medicine, Blueprint Translational Research Group, Clinical Epidemiology and Regenerative Medicine Programs, Ottawa Hospital Research Institute, Ottawa Hospital, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada. 10. UCL Centre for Clinical Microbiology, Division of Infection & Immunity, University College London, London, England, UK. 11. Responsible Research in Practice, London, England, UK. 12. SYRCLE, Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands. 13. Department of Surgery, Radboud Institute for Health Sciences, Nijmegen, Netherlands. 14. Pain Research, Department of Surgery & Cancer, Imperial College, London, England, UK. 15. Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Abstract
BACKGROUND: Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. METHODS: We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. RESULTS: This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. CONCLUSION: We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.
BACKGROUND: Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. METHODS: We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. RESULTS: This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. CONCLUSION: We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.
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