Good Clinical Practices – ICH E6(R3): Updates to Support the Evolution of Clinical Research

Clinical research is evolving rapidly, driven by new approaches, emerging technologies, and more flexible trial models. Revision 3 of the Good Clinical Practices (GCP) – ICH E6 fully aligns with this transformation. It provides a modernized, quality‑focused framework that supports more efficient trials while upholding the fundamental priorities: participant protection and data reliability. This revision will come into effect on April 1, 2026.

A Modernization Driven by Flexibility and Quality

Revision 3 of ICH E6 marks an important shift toward a risk‑based quality approach. This orientation enables research to focus on what truly matters and reduce efforts on non‑critical aspects—without ever compromising safety or scientific integrity.

Several elements reinforce this vision:

• Validation of computerized systems.
• Qualification and oversight of subcontractors/service providers.
• Increased attention to data governance.

Although several changes specifically affect sponsors, sponsor‑investigators and research teams will see impacts on their day‑to‑day practices. Integrating new technologies, adapting to a risk‑based approach, and revising long‑established processes involve cultural, organizational, and training considerations for sites.

Finally, some elements of the guideline are not entirely new, but their importance has been clarified and further emphasized.

A New Guideline Structure

The guideline is now organized as follows:

• Introduction.
• The 11 GCP principles, with details developed in the annexes.
• Annex 1, covering the responsibilities of the ethics committee, investigator, and sponsor, as well as a new section on data governance.
• Annex 2, still under development, which will address trials incorporating decentralized elements, pragmatic aspects, or real‑world data.
• Three appendices, including the Investigator’s Brochure, the protocol, and essential documents.
• Glossary.

Key Changes for Investigators and Their Teams

The revision reflects the evolution of technologies and trial models, including:

• Trials incorporating decentralized elements (consent, monitoring, remote auditing, home‑care nurses).
• Greater ease of involving health‑care personnel and other health professionals.
• Engagement in the risk assessment approach.
• The need to assess and oversee potential subcontractors.

Additional improvements affect key processes:

• Enhanced consent process, now including electronic consent.
• Modernized study records management.
• Increased flexibility in the management of essential documents (now addressed in Appendix 3).
• Expanded content supporting the management of critical activities such as randomization, blinding, and participant retention, with reference to ICH E8(R1) for additional guidance.
• More flexible requirements for the expedited reporting of all SUSARs to investigators and IRB/IEC, with new alternative provisions for safety reporting to regulatory authorities.
• References to public involvement and participant diversity, including the obligation for sponsors to clearly justify the exclusion of certain participant groups.

Major Changes for Sponsors and Sponsor‑Investigators

Some of the most significant adjustments include:

• Proportionality becomes a core GCP principle. The focus is on a “fit‑for‑purpose” approach, recognizing that data need not be entirely error‑free if they support conclusions equivalent to those drawn from error‑free data. This approach aims to reduce protocol complexity.
• Introduction of Quality by Design, including the identification of critical‑to‑quality factors to prevent errors that could compromise participant safety, data reliability, or decision‑making.
• Expanded requirements for data governance, with new sections for sponsors addressing data and records (section 6) and a dedicated section on data governance (section 4).
• Stronger emphasis on the selection and oversight of subcontractors/service providers.
• Importance of computerized system validation.
• Modified requirements for SUSAR reporting.
• Numerous clarifications on the management of both paper and electronic data.

 To Learn More

• Discover more details about the changes to Good Clinical Practices: https://catalisquebec.com/GCP-Changes
• Consult the full Good Clinical Practice guideline: https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf