SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context
Summary: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate tha...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537024005674 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591749587927040 |
|---|---|
| author | Moreno Ursino Guillermo Villacampa Jan Rekowski Munyaradzi Dimairo Olga Solovyeva Deborah Ashby Jordan Berlin Oliver Boix Melanie Calvert An-Wen Chan Courtney H. Coschi Thomas R. Jeffry Evans Elizabeth Garrett-Mayer Robert M. Golub Christina Guo Kathryn S. Hayward Sally Hopewell John D. Isaacs S. Percy Ivy Thomas Jaki Olga Kholmanskikh Andrew Kightley Shing Lee Rong Liu Adrian Mander Lynley V. Marshall James Matcham Dhrusti Patel Richard Peck Khadija Rerhou Rantell Dawn P. Richards Mahtab Rouhifard Lesley Seymour Yoshiya Tanaka Christopher J. Weir Johann de Bono Christina Yap |
| author_facet | Moreno Ursino Guillermo Villacampa Jan Rekowski Munyaradzi Dimairo Olga Solovyeva Deborah Ashby Jordan Berlin Oliver Boix Melanie Calvert An-Wen Chan Courtney H. Coschi Thomas R. Jeffry Evans Elizabeth Garrett-Mayer Robert M. Golub Christina Guo Kathryn S. Hayward Sally Hopewell John D. Isaacs S. Percy Ivy Thomas Jaki Olga Kholmanskikh Andrew Kightley Shing Lee Rong Liu Adrian Mander Lynley V. Marshall James Matcham Dhrusti Patel Richard Peck Khadija Rerhou Rantell Dawn P. Richards Mahtab Rouhifard Lesley Seymour Yoshiya Tanaka Christopher J. Weir Johann de Bono Christina Yap |
| author_sort | Moreno Ursino |
| collection | DOAJ |
| description | Summary: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity. To address this gap, the international consensus-driven SPIRIT-DEFINE checklist was developed through a robust methodological framework for guideline development, with the aim to improve completeness and clarity in EPDF trial protocols. The checklist builds on the SPIRIT statement, adding 17 new items and modifying 15 existing ones.The SPIRIT-DEFINE explanation and elaboration (E&E) document provides comprehensive information to enhance understanding and usability of the SPIRIT-DEFINE checklist when writing an EPDF trial protocol. Each new or modified checklist item is accompanied by a detailed description, its rationale with supportive evidence, and examples of good reporting curated from EPDF trial protocols covering a range of therapeutic areas and interventions. We recommend utilising this paper alongside the SPIRIT statement, and any relevant extensions, to enhance the development and review of EPDF trial protocols.By facilitating adoption of the SPIRIT-DEFINE statement for EPDF trials, this E&E document can promote enhancement of methodological rigour, patient safety, transparency, and facilitate the generation of high-quality, reproducible evidence that will strengthen the foundation of early phase research and ultimately improve patient outcomes. Funding: This work is a further extension of the SPIRIT-DEFINE study, which obtained no external funding. The principal investigator (CY) used internal staff resources, together with additional resources from external partners, to conduct this study. The SPIRIT-DEFINE study is a component of the DEFINE project, which also developed the MRC/NIHR funded CONSORT-DEFINE guidance. ICR-CTSU receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec22/100004), which has contributed to accelerating the advancement and successful completion of this work. |
| format | Article |
| id | doaj-art-16dd34d979024228b814394d19daa037 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-16dd34d979024228b814394d19daa0372025-01-22T05:43:23ZengElsevierEClinicalMedicine2589-53702025-01-0179102988SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in contextMoreno Ursino0Guillermo Villacampa1Jan Rekowski2Munyaradzi Dimairo3Olga Solovyeva4Deborah Ashby5Jordan Berlin6Oliver Boix7Melanie Calvert8An-Wen Chan9Courtney H. Coschi10Thomas R. Jeffry Evans11Elizabeth Garrett-Mayer12Robert M. Golub13Christina Guo14Kathryn S. Hayward15Sally Hopewell16John D. Isaacs17S. Percy Ivy18Thomas Jaki19Olga Kholmanskikh20Andrew Kightley21Shing Lee22Rong Liu23Adrian Mander24Lynley V. Marshall25James Matcham26Dhrusti Patel27Richard Peck28Khadija Rerhou Rantell29Dawn P. Richards30Mahtab Rouhifard31Lesley Seymour32Yoshiya Tanaka33Christopher J. Weir34Johann de Bono35Christina Yap36ReCAP/F CRIN, INSERM, 5400, Nancy, France; Unit of Clinical Epidemiology, University Hospital Centre Robert Debré, Université Paris Cité, Paris, France; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France; HeKA Team, Centre Inria, Paris, FranceClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UK; Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; SOLTI Breast Cancer Research Group, Barcelona, SpainClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UKDivision of Population Health, Sheffield Centre for Health and Related Research, University of Sheffield, Sheffield, UKClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UKSchool of Public Health, Imperial College London, St Mary's Hospital, London, UKVanderbilt-Ingram Cancer Center, Nashville, TN, USABayer, Berlin, GermanyCentre for Patient Reported Outcomes Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK; Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK; National Institute for Health and Care Research Applied Research Collaboration West Midlands, University of Birmingham, Birmingham, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Precision Transplant and Cellular Therapeutics, University of Birmingham, Birmingham, UK; National Institute for Health and Care Research Birmingham Biomedical Research Centre, NIHR Birmingham Biomedical Research Centre, Institute of Translational Medicine, University Hospital NHS Foundation Trust, Birmingham, UKDepartment of Medicine, Women's College Research Institute, University of Toronto, Toronto, CanadaCanadian Cancer Trials Group, Kingston, ON, CanadaInstitute of Cancer Sciences, CR-UK Beatson Institute, University of Glasgow, Glasgow, UKCenter for Research and Analytics, American Society of Clinical Oncology, Alexandria, VA, USADepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAThe Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UKDepartments of Physiotherapy and Medicine, University of Melbourne, VIC, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, AustraliaOxford Clinical Research Unit, NDORMS, University of Oxford, Oxford, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UKInvestigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Institute of Health, Bethesda, MD, USAMRC Biostatistics Unit, Cambridge University, Cambridge, UK; Computational Statistics Group, University of Regensburg, Regensburg, GermanyFederal Agency for Medicines and Health Products, Brussels, BelgiumPatient and Public Involvement and Engagement (PPIE) Lead, Lichfield, UKColumbia University Mailman School of Public Health, New York, NY, USARegeneron, New York, NY, USACentre for Trials Research, Cardiff University, Cardiff, UKThe Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UKStrategic Consulting, Cytel (Australia), Perth, WA, AustraliaClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UKDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK; Hoffmann-La Roche, Basel, SwitzerlandMedicines and Healthcare Products Regulatory Agency, London, UKClinical Trials Ontario, MaRS Centre, Toronto, ON, CanadaClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UKCanadian Cancer Trials Group, Kingston, ON, CanadaFirst Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, JapanEdinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UKThe Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UKClinical Trials and Statistics Unit at The Institute of Cancer Research, London, UK; Corresponding author. Clinical Trials and Statistics Unit, The Institute of Cancer Research, London SM2 5NG, UK.Summary: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity. To address this gap, the international consensus-driven SPIRIT-DEFINE checklist was developed through a robust methodological framework for guideline development, with the aim to improve completeness and clarity in EPDF trial protocols. The checklist builds on the SPIRIT statement, adding 17 new items and modifying 15 existing ones.The SPIRIT-DEFINE explanation and elaboration (E&E) document provides comprehensive information to enhance understanding and usability of the SPIRIT-DEFINE checklist when writing an EPDF trial protocol. Each new or modified checklist item is accompanied by a detailed description, its rationale with supportive evidence, and examples of good reporting curated from EPDF trial protocols covering a range of therapeutic areas and interventions. We recommend utilising this paper alongside the SPIRIT statement, and any relevant extensions, to enhance the development and review of EPDF trial protocols.By facilitating adoption of the SPIRIT-DEFINE statement for EPDF trials, this E&E document can promote enhancement of methodological rigour, patient safety, transparency, and facilitate the generation of high-quality, reproducible evidence that will strengthen the foundation of early phase research and ultimately improve patient outcomes. Funding: This work is a further extension of the SPIRIT-DEFINE study, which obtained no external funding. The principal investigator (CY) used internal staff resources, together with additional resources from external partners, to conduct this study. The SPIRIT-DEFINE study is a component of the DEFINE project, which also developed the MRC/NIHR funded CONSORT-DEFINE guidance. ICR-CTSU receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec22/100004), which has contributed to accelerating the advancement and successful completion of this work.http://www.sciencedirect.com/science/article/pii/S2589537024005674Early phase trialsPhase IDose-findingDose escalation/de-escalationProtocol guidanceSPIRIT-DEFINE |
| spellingShingle | Moreno Ursino Guillermo Villacampa Jan Rekowski Munyaradzi Dimairo Olga Solovyeva Deborah Ashby Jordan Berlin Oliver Boix Melanie Calvert An-Wen Chan Courtney H. Coschi Thomas R. Jeffry Evans Elizabeth Garrett-Mayer Robert M. Golub Christina Guo Kathryn S. Hayward Sally Hopewell John D. Isaacs S. Percy Ivy Thomas Jaki Olga Kholmanskikh Andrew Kightley Shing Lee Rong Liu Adrian Mander Lynley V. Marshall James Matcham Dhrusti Patel Richard Peck Khadija Rerhou Rantell Dawn P. Richards Mahtab Rouhifard Lesley Seymour Yoshiya Tanaka Christopher J. Weir Johann de Bono Christina Yap SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context EClinicalMedicine Early phase trials Phase I Dose-finding Dose escalation/de-escalation Protocol guidance SPIRIT-DEFINE |
| title | SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context |
| title_full | SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context |
| title_fullStr | SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context |
| title_full_unstemmed | SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context |
| title_short | SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocolsResearch in context |
| title_sort | spirit define explanation and elaboration recommendations for enhancing quality and impact of early phase dose finding clinical trials protocolsresearch in context |
| topic | Early phase trials Phase I Dose-finding Dose escalation/de-escalation Protocol guidance SPIRIT-DEFINE |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024005674 |
| work_keys_str_mv | AT morenoursino spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT guillermovillacampa spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT janrekowski spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT munyaradzidimairo spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT olgasolovyeva spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT deborahashby spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT jordanberlin spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT oliverboix spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT melaniecalvert spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT anwenchan spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT courtneyhcoschi spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT thomasrjeffryevans spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT elizabethgarrettmayer spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT robertmgolub spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT christinaguo spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT kathrynshayward spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT sallyhopewell spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT johndisaacs spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT spercyivy spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT thomasjaki spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT olgakholmanskikh spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT andrewkightley spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT shinglee spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT rongliu spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT adrianmander spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT lynleyvmarshall spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT jamesmatcham spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT dhrustipatel spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT richardpeck spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT khadijarerhourantell spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT dawnprichards spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT mahtabrouhifard spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT lesleyseymour spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT yoshiyatanaka spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT christopherjweir spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT johanndebono spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext AT christinayap spiritdefineexplanationandelaborationrecommendationsforenhancingqualityandimpactofearlyphasedosefindingclinicaltrialsprotocolsresearchincontext |