Guide, published
ICH E6(R3): what changes for research sites
The revised Good Clinical Practice guideline is written to be risk-proportionate and technology-neutral. Here is what it means for investigators and site staff.
In this guide
Where E6(R3) stands
ICH E6 is the international standard for Good Clinical Practice. The third revision, E6(R3), reached Step 4 of the ICH process, final adoption, on 6 January 2025 (ICH E6(R3) Step 4). Regulators then implement it on their own timelines. FDA publishes E6(R3) as guidance on its website (FDA: E6(R3) Good Clinical Practice); check that page for its current status in the US.
E6(R3) is organized as overarching principles, Annex 1 covering traditional interventional trials, and a planned Annex 2 with additional considerations for trials using decentralized elements, pragmatic designs and real-world data. Check the ICH website for the status of Annex 2.
This article summarizes themes from the guideline that affect sites. It is not legal or regulatory advice; your sponsor, IRB and local regulations decide what applies to each study.
1. Quality by design and risk proportionality
The guideline puts more weight on identifying the factors that are critical to the quality of a trial, the things that matter most for participant safety and reliable results, and focusing effort on them. Processes should be proportionate to the risks to participants and to the reliability of results.
For sites, this usually shows up as sponsors explaining which data points and procedures are critical, and monitoring plans that focus on those rather than checking everything equally. It is a good prompt to ask sponsors which assessments are critical-to-quality for each study.
2. Investigator oversight of delegated work
The investigator remains responsible for trial-related activities at the site, including those delegated to staff or to service providers. E6(R3) describes oversight that is proportionate: the investigator should make sure delegated people and providers are qualified and that their work is adequately supervised.
In practice: keep the delegation log current, make sure training is documented before a task is delegated, and keep records of how you oversee vendors the site engages. A delegation log template is a simple place to start.
3. Informed consent
E6(R3) keeps the core requirements of informed consent and acknowledges that information can be provided and consent obtained using different methods, including electronic ones, where appropriate and permitted. The emphasis is on participants understanding the information, not on the format.
Sites using eConsent should be able to show which version each participant signed, when, and how re-consent was handled after amendments. See how Kyros Trials eConsent tracks versions.
4. Data governance and computerized systems
The guideline adds a dedicated section on data governance. It covers the full data life cycle: capture, changes, audit trails, review, retention and access. It also sets expectations for computerized systems used in trials, such as being fit for their intended purpose, having appropriate access controls and keeping audit trails of changes to data.
Sites should know which systems hold source data, who can change it and how changes are recorded. In the US, requirements for electronic records and signatures in 21 CFR Part 11 continue to apply alongside GCP (FDA Part 11 guidance).
5. Essential records
E6(R3) refers to essential records and describes them in terms of what is needed to reconstruct and evaluate the trial, rather than only as a fixed list. Sites still need to keep the records that let a monitor or inspector follow what happened, and to retain them as required.
An organized eRegulatory binder with versioning and expiry alerts makes it easier to show the record is in order.
What to do at your site this quarter
- Read the principles section of the final guideline with your investigators. It is short.
- Review your delegation log and training records for every active study.
- List the computerized systems that hold source data or essential records, and who has access to each.
- Check your consent process documents for version tracking and re-consent steps.
- Ask each sponsor which data and procedures they consider critical-to-quality.
- Update SOPs where they quote E6(R2) wording that has changed.