Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study

BMC Medicine

Research Article

Dawn Richards¹  Munyaradzi Dimairo²  Shing Lee³  An-Wen Chan⁴  Christopher J. Weir⁵  Adrian Mander⁶  Moreno Ursino⁷  Thomas Jaki⁸  Khadija Rerhou Rantell⁹  Lesley Roberts^1,10  Richard Stephens^1,10  Sally Hopewell^1,11  Andrew Kightley^1,12  John Kirkpatrick^1,13  Alun Bedding^1,13  Olga Solovyeva^1,14  Christina Yap^1,14  Aude Espinasse^1,14  Dhrusti Patel^1,14  Johann de Bono^1,15  Siew Wan Hee^1,16  Sarah Hughes^1,17  Thomas R. Jeffry Evans^1,18 

[1] Clinical Trials Ontario, Toronto, Canada;Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK;Columbia University, Mailman School of Public Health, New York, USA;Department of Medicine, Women’s College Research Institute, University of Toronto, Toronto, Canada;Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK;GSK, Brentford, UK;Inserm, Centre de Recherche Des Cordeliers, Sorbonne UniversitéUniversité Paris Cité, 75006, Paris, France;HeKA, Inria Paris, 75015, Paris, France;Unit of Clinical Epidemiology, AP-HP, CHU Robert Debré, CIC-EC 1426, Paris, France;RECaP/F-CRIN, Inserm, 5400, Nancy, France;MRC Biostatistics Unit, University of Cambridge, Cambridge, UK;University of Regensburg, Regensburg, Germany;Medicines and Healthcare Products Regulatory Agency, London, UK;NCRI, London, UK;Oxford Clinical Trials Research Unit, University of Oxford, Oxford, UK;Patient and Public Involvement and Engagement (PPIE) Lead, Lichfield, UK;Roche Products Ltd, Welwyn Garden City, UK;The Institute of Cancer Research, London, UK;The Institute of Cancer Research, London, UK;The Royal Marsden NHS Foundation Trust, London, UK;University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK;University of Warwick, Coventry, UK;University of Birmingham, Birmingham, UK;University of Glasgow, Glasgow, UK;

关键词: early phase;    clinical trials;    SPIRIT guideline;    CONSORT guideline;    dose finding;   

DOI  :  10.1186/s12916-023-02937-0

 received in 2023-04-04, accepted in 2023-06-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEarly phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE).MethodsThe initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants’ feedback.ResultsThe Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar.ConclusionsBy detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility.Trial registrationSPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network (https://www.equator-network.org/).

【 授权许可】

CC BY   
© The Author(s) 2023

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