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

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/).

Metadata

Authors/Creators:	Solovyeva, O. https://orcid.org/0000-0001-7828-4099 Dimairo, M. https://orcid.org/0000-0002-9311-6920 Weir, C.J. https://orcid.org/0000-0002-6494-4903 Hee, S.W. https://orcid.org/0000-0002-0415-263X Espinasse, A. https://orcid.org/0000-0002-1271-302X Ursino, M. https://orcid.org/0000-0002-5709-4322 Patel, D. https://orcid.org/0009-0001-4113-2726 Kightley, A. https://orcid.org/0000-0002-5228-3255 Hughes, S. Jaki, T. https://orcid.org/0000-0002-1096-188X Mander, A. https://orcid.org/0000-0002-0742-9040 Evans, T.R.J. https://orcid.org/0000-0002-4175-914X Lee, S. Hopewell, S. https://orcid.org/0000-0002-6881-6984 Rantell, K.R. https://orcid.org/0000-0002-6747-7650 Chan, A.-W. Bedding, A. Stephens, R. Richards, D. https://orcid.org/0000-0003-1151-0826 Roberts, L. Kirkpatrick, J. de Bono, J. https://orcid.org/0000-0002-2034-595X Yap, C. https://orcid.org/0000-0002-6715-2514
Copyright, Publisher and Additional Information:	© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords:	CONSORT guideline; SPIRIT guideline; clinical trials; dose finding; early phase
Dates:	Accepted: 12 June 2023 Published (online): 5 July 2023 Published: 5 July 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research
Depositing User:	Symplectic Sheffield
Date Deposited:	07 Jul 2023 10:32
Last Modified:	07 Jul 2023 10:32
Status:	Published
Publisher:	Springer Science and Business Media LLC
Identification Number:	https://doi.org/10.1186/s12916-023-02937-0
Related URLs:	PubMed URL

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

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