Enhancing quality and impact of early phase dose-finding clinical trial protocols: SPIRIT Dose-finding Extension (SPIRIT-DEFINE) guidance

Abstract

SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance for clinical trial protocol writing. However, neither the original guidance nor its extensions adequately cover the features of early phase dose-finding trials. The SPIRIT Dose-finding Extension (DEFINE) statement is a new guideline that provides recommendations for essential items that should be provided in the protocols of these trials. It details extensions to the SPIRIT 2013 guidance, incorporating 17 new items and modifying 15 existing items. The purpose of this guideline is to promote transparency, completeness, reproducibility of methods, and interpretation of early phase dose-finding trial protocols. It is envisioned that the resulting improvements in the design and conduct of early phase clinical trials will ultimately reduce research inefficiencies and inconsistencies, driving transformational advances in clinical care.

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance

“…We also developed a dose-finding extension for SPIRIT 2013, 46 SPIRIT-DEFINE, which has been reported elsewhere. 45 CONSORT-DEFINE and SPIRIT-DEFINE together form an interconnected continuum designed to facilitate the writing of the trial protocol and report, as well as assess the adherence of the final report to the protocol. 58 …”

“…Informed consent was obtained from both the Delphi survey and consensus meeting participants. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-DEFINE (protocol guidance for EPDF trials) 45 was developed in parallel with CONSORT-DEFINE.…”

Ensuring Transparency and Quality of Clinical Trial Reporting in Clinical Pharmacology & Therapeutics: Prospective Trial Registration and Compliance with Reporting Guidelines Are Required for all Clinical Trials

“…15 A similar, new guideline (SPIRIT-DEFINE) has also been developed for the publication of trial protocols. 16 CONSORT-DEFINE was developed using a modified Delphi process involving clinical investigators, trial methodologists, clinical pharmacologists, and patient representatives from academia, the pharmaceutical industry, medical charities, and regulatory authorities in North America, Europe, Asia, and Australasia. Forty items were identified for inclusion in the final checklist, 19 of which were modifications of existing CONSORT items with the rest being new items.…”

Let’s make poor reporting of early phase dose finding clinical trials a thing of the past

“…The development of these checklists published in The BMJ is just the beginning;34 their consideration and thoughtful implementation is now urgently required. Early phase dose finding trials play a vital role in establishing the foundation for future clinical development.…”