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

Solovyeva, O. et al. (2023) Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study. BMC Medicine, 21, 246. (doi: 10.1186/s12916-023-02937-0) (PMID:37408015) (PMCID:PMC10324137)

Abstract

Background: Early 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). Methods: The 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. Results: The 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. Conclusions: By 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 registration: SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network (https://www.equator-network.org/).

• Item Type: Articles
• Additional Information: The CONSORT-DEFINE part of this study was supported by the UKRI’s MRC-NIHR grant number MR/T044934/1. The SPIRIT-DEFINE part received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. T Jaki received funding from the UK Medical Research Council (MC_UU_00002/14). Christopher J Weir was supported in this work by NHS Lothian via Edinburgh Clinical Trials Unit. Shing Lee was funded through the National Center for Advancing Translational Sciences, National Institutes of Health (Grant Number UL1TR001873).
• Keywords: SPIRIT guideline, CONSORT guideline, dose finding, clinical trials, early phase.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Jeff
• Authors: Solovyeva, O., Dimairo, M., Weir, C. J., Hee, S. W., Espinasse, A., Ursino, M., Patel, D., Kightley, A., Hughes, S., Jaki, T., Mander, A., Evans, T. R. J., Lee, S., Hopewell, S., Rantell, K. R., Chan, A.-W., Bedding, A., Stephens, R., Richards, D., Roberts, L., Kirkpatrick, J., de Bono, J., and Yap, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BMC Medicine
• Publisher: BioMed Central
• ISSN: 1741-7015
• ISSN (Online): 1741-7015
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in BMC Medicine 21: 246
• Publisher Policy: Reproduced under a Creative Commons License