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The DEFINE study: Guidance for Early-Phase Dose Finding trials

This project aims to develop extensions to the Consolidated Standards of Reporting Trials (CONSORT) and Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance for early phase dose-finding trials.

Background

The SPIRIT 2013  and CONSORT 2010  statements provide minimum guidance for writing protocol and reporting of randomised trials, and have been widely adopted. Several extensions have been developed to further refine the tool for specific types of studies (e.g. adaptive designs and cluster randomised trials).

Existing protocol and reporting guidance do not fully cover features specific to dose-finding. The DEFINE study aims to promote enhance transparency, completeness, reproducibility of methods and the interpretation of results of early phase trials, across all disease areas, and to build on the checklists outlined in the CONSORT 2010 and SPIRIT 2013 statements.

This will be achieved through a staged consensus process involving a broad range of stakeholders, before being widely disseminated for adoption by the wider scientific community.

Increasing efficiency and transparency in early phase trials will translate into a reduction of research waste and, ultimately, improve outcomes for patients.

Methodology

The DEFINE study will develop the dose-finding SPIRIT and CONSORT extensions following the EQUATOR (Enhancing the Quality and Transparency of Health Research) network’s methodological framework through a staged consensus process. It includes:

  • Conducting literature review and generating candidate items for each DEFINE extensions
  • Assessing the candidate items with international multi-stakeholders in a two to three stage Delphi survey.
  • Conducting an international consensus meeting to review the Delphi survey findings
  • Refining the draft checklist via a pilot run prior to it being finalised, as illustrated below:

DEFINE STUDY: SPIRIT AND CONSORT Extensions development steps.

Take part in the Delphi Survey

If you are interested in helping to develop the SPIRIT-DEFINE and CONSORT-DEFINE statements, please read the Participant Information Sheet and click on the link  to access the registration page for the Delphi Survey.

DEFINE Study Participant Information Sheet

DEFINE Study Delphi Survey Registration

The team

To ensure the guidance designed is as impactful and as widely adopted as possible, a multidisciplinary team of national and international experts and early phase trial stakeholders has been brought together to drive delivery of the project.

DEFINE Executive committee

Professor Christina Yap, Institute of Cancer Research (Principal Investigator)
Dr Munyaradzi Dimairo, University of Sheffield
Professor Christopher Weir, University of Edinburgh
Professor Adrian Mander, Cardiff University
Professor Thomas Jaki, Lancaster University / University of Cambridge
Professor Jeff Evans, University of Glasgow
Dr Rong Liu, Bristol-Myers Squibb
Associate Professor Shing Lee, Columbia University
Mr Andrew Kightley, Patient and Public Involvement lead
Associate Professor Sally Hopewell, University of Oxford
Professor Johann de Bono, Institute of Cancer Research
Dr Olga Solovyeva, Institute of Cancer Research
Ms Aude Espinasse, Institute of Cancer Research
Dr Alun Bedding, Roche [CONSORT-DEFINE only]
Dr John KirkPatrick, Roche [SPIRIT-DEFINE only]
Dr Siew Wan Hee, Institute of Cancer Research [SPIRIT-DEFINE only]
Professor An-Wen Chan, University of Toronto [SPIRIT-DEFINE only]

Collaborators

Dr Moreno Ursino, Université de Paris [SPIRIT-DEFINE only]

Dr Vicky Sanchez Perez, Institute of Cancer Research [SPIRIT-DEFINE only]

Advisors

Professor Stephen Hahn, Flagship Pioneering
Dr Kadhija Rantell, MHRA

Independent expert panel

Professor Deborah Ashby, Imperial College London
Professor Elizabeth Garret-Mayer, American Society of Clinical Oncology [Chair]
Professor John Issacs, Newcastle University
Professor Melanie Calvert, Birmingham University

Publications

The Dose-Finding CONSORT (CONSORT-DEFINE) and SPIRIT (SPIRIT-DEFINE) guidelines development as well as the rapid methodological (scoping) review protocols have been published and are available from the links below:

The initiation of the work on the CONSORT-DEFINE project  was announced in Nature Medicine (Yap et al. The need for reporting guidelines for early phase dose-finding trials: Dose-Finding CONSORT Extension. Nat Med. 2022 Jan;28(1):6-7. doi: 10.1038/s41591-021-01594-1. PMID: 34992264) and is accessible at the link below:

Funding

CONSORT-DEFINE is funded by MRC-NIHR Methodology Research Programme (2021 – 2023)

References

DEFINE Glossary

SPIRIT Checklist - Unchanged Items for SPIRIT-DEFINE

CONSORT Checklist - Unchanged items for CONSORT-DEFINE

DEFINE study - Feedback on Delphi Round One - 27th May 2022.pdf

Equator Network

In this section

Publications The DEFINE study: SPIRIT and CONSORT extensions Professional activities

Contact us

Contact us to find out more about the ICR.