On 3 June 2026, the final version of ICH E6(R3) Annex 2 was adopted, marking another significant step in the modernisation of Good Clinical Practice (GCP). Annex 2 acknowledges this reality and provides formal GCP guidance to match it.
What is Annex 2 and Where Does It Fit?
ICH E6(R3) is the international standard for Good Clinical Practice. The Principles and Annex 1 have been in effect since July 2025, covering the core framework for trial conduct. Annex 2 builds on these by addressing the specific considerations that arise in decentralised, pragmatic and real-world data trials.
It is important to note that Annex 2 is not a standalone document. It must always be read alongside the GCP Principles and Annex 1, not as a replacement for them.
What Does It Cover?
Decentralised trial elements
For the first time, formal GCP guidance now covers trial activities conducted outside the investigator’s site. This includes home visits, local healthcare centres, mobile medical units and remote interactions. If your trial design involves any of these, Annex 2 is directly relevant to how you plan, document and oversee those activities.
A proportionate, risk-based approach
Annex 2 reinforces the principle that GCP should be applied in a way that is proportionate to the trial design and the technologies being used. This does not mean cutting corners. It means that the level of oversight and procedural rigour should be calibrated to the actual risks involved, without ever compromising participant rights, safety or data reliability.
Real-world data
One of the most forward-thinking aspects of Annex 2 is its treatment of real-world data. Electronic health records, registries and other real-world sources are increasingly being used as trial endpoints or external controls. Annex 2 provides considerations around data access, consent and fitness for purpose, giving sponsors clearer guidance on how to use RWD compliantly within a trial framework.
Room for further evolution
Perhaps most notably, the guideline is explicitly designed to anticipate further changes in trial methodology. It leaves room for emerging approaches, which is a recognition that clinical research will continue to evolve and that the regulatory framework needs to keep pace.
What Does This Mean in Practice?
If you are designing a clinical trial that incorporates any decentralised elements or plans to use real-world data, Annex 2 is now part of your compliance landscape. Sponsors will need to consider how their protocols, monitoring plans and data management processes reflect the new guidance.
For those already running trials, it is worth reviewing your current setup against Annex 2 to identify any gaps, particularly around oversight of remote activities and the handling of real-world data sources.
If you want to understand how ICH E6(R3) Annex 2 affects your specific trial design or evidence strategy, feel free to book a call and we can talk through where you stand and how to move forward. Click here
To read the document in full: https://database.ich.org/sites/default/files/ICH_E6(R3)_Annex%202_Guideline_Step%204_2026_0603_0.pdf
