E6(R3) is here: what it means for the future of clinical trials

Abstract

The ICH E6 Good Clinical Practice (GCP) guideline provides internationally harmonized ethical and scientific standards for the conduct of clinical trials involving human participants. While the E6(R2) revision introduced risk-based monitoring and strengthened sponsor oversight, rapid advances in trial complexity, digital technologies, and patient-centric and decentralized research models necessitated further modernization. The recently revised ICH E6(R3) guideline builds on the principles of ICH E8(R1) and emphasizes quality-by-design, proportionate risk-based approaches, and identification of factors critical to trial quality. It expands guidance on data governance, innovative trial designs, use of digital tools, and inclusive participant recruitment, while clarifying stakeholder roles and responsibilities. This article reviews the evolution of ICH E6 and discusses the key changes and practical implications of E6(R3) for the conduct of efficient, ethical, and globally acceptable clinical trials.