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

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.