Advarra is ready. Is your IRB?
Key takeaways:
- Now that FDA has published the ICH E6(R3) Good Clinical Practice (GCP) guidance, aligning early with these requirements can prepare organizations for the future.
- ICH E6(R3) encourages ethics review committees to more intelligently apply their resources by enhancing efficiency without compromising participant safety or data integrity particularly regarding continuing review, informed consent, decentralized logistics, and data governance.
- Sponsors partnering with Advarra can be confident that their studies remain regulation-ready on both sides of the border today and E6(R3)-ready for tomorrow.
Released on January 6, 2025, the ICH E6 (Revision 3) Good Clinical Practice guideline has now been formally incorporated into U.S. FDA regulatory guidance recently issued on September 9, 2025 (Final E6(R3) GCP Guidance). FDA has had a long history of supporting ICH, and as anticipated FDA has now formally adopted the “R3” version of ICH E6 into its formal guidance. As with past iterations of ICH E6, there remain additional regulations and standards which must be adhered to at a country level. Regulators in North America will continue to enforce the current FDA regulations (21 CFR Parts 50 and 56), GCP standards, the U.S. Common Rule, and the Canadian Tri-Council Policy Statement 2 (TCPS 2).
The European Medicines Agency (EMA) has announced that trials conducted in the European Union must comply with R3 guidelines beginning 23 July 2025.
At Advarra, we follow the E6(R3) guideline where it strengthens participant protections or operational efficiency. As an IRB, we have also always fully complied with section 3.0 of the guidelines. However, when E6(R3) conflicts with existing clinical trial regulations, Advarra complies with the more protective applicable regulatory requirements. See our Statement of Compliance for more.
Annex 1 in the E6(R3) guideline rewrites several expectations for research review committees.
Written for institutional review boards (IRBs) and research ethics boards (REBs) (collectively ethics review committees) across North America, this blog takes a close look at five changes most likely to touch these committees’ workflows. (For a broader look at how ICH E6(R3) impacts clinical trial operations, read this blog.)
Human research protection programs (HRPPs) and institutional leadership should consider these elements as they review and update local policies.
1 – Risk-Proportionate Continuing Review
ICH E6(R3) re-writes the implied “one-size-fits-all” annual review. Instead, Annex 1 Section 1.2.4 instructs ethical review committees to set renewal frequency according to real participant risk (rather than a calendar default).
This language dovetails with the 2018 revised Common Rule and TCPS 2 Article 6.14, both of which already permit flexibility by lengthening the continuing review interval or foregoing continuing review for certain minimal risk research when appropriate. U.S. FDA regulations have for years contained the idea of risk-proportionate continuing review intervals. But while the IRB may set continuing review at a frequency proportionate to the risk for FDA regulated research, the frequency must not be less than once a year (21 CFR 56.109(f)).
Practically, the E6(R3) revisions give North American ethics review committees even more credence to apply a risk based continuing review frequency as long as the frequency is in keeping with the applicable underlying regulations.
Since 2021, Advarra’s IRB approval letters now specify the exact interval of approval, rather than the legacy “valid for one year” standard language. This updated information more clearly communicates the study’s specific continuing review timelines.
2 – Expanded informed consent transparency
Annex 1 §3.15.3 adds modern transparency demands to the informed consent elements themselves.
To comply with ICH E6(R3) Good Clinical Practice, investigators must now tell participants what happens to their data if they withdraw, how long information will be stored, whether results will be communicated, and what safeguards protect secondary use.
This requirement aligns with existing North American regulations at 21 CFR 50.25, 45 CFR 46.116, and TCPS 2 Article 3.2. In the U.S., these disclosures to participants are considered in some part as additional elements of informed consent the IRB can choose to include, or not, depending on the specific trial. In Canada, these parallel the generally required consent information in TCPS 2.
Nothing in the E6(R3) guideline appears to conflict with existing U.S. or Canadian consent regulations. If anything, the disclosures discussed in ICH E6(R3) overlap with existing regulation or are additional language researchers can add to the consent without conflicting with underlying regulatory obligations.
Most North American ethics review committees will likely already have these elements incorporated into their processes. However, the E6(R3) guideline presents a good opportunity for ethics review committees to re-assess existing consent templates with an eye towards Good Clinical Practice.
Advarra’s internal IRB review templates and checklists already include confirmation that specific consent elements, including optional elements, are present in the consent as applicable.
3 – Decentralized logistics and direct-to-participant supply chains
In Annex 1 §3.15.3, the E6(R3) guideline explicitly recognizes investigational product (IP) shipped directly to a participant’s home, the use of local pharmacies, and remote data-capture devices.
Research ethics reviews adopting ICH GCP E6(R3) must now assess cold-chain integrity, tamper-evident labelling that protects privacy, and cybersecurity validation for wearables and software applications.
The COVID-19 pandemic necessitated expansion of decentralized trial (DCT) research, and many ethics review committees may already have associated review policies in place. In some cases, DCT elements have been used in research and reviewed by IRBs for years. Decentralized studies involving autonomous home-delivery methods are already taking place, so ethics review committees without such policies should consider developing them.
Advarra’s IRB already reviews the reasonably foreseeable risks associated with decentralized research, including but not limited to any elements of risk associated with the specific items called out by E6(R3). For more, read our blog The Evolution of IRB Reviews in Decentralized Clinical Trials.
4 – Data governance moves from footnote to headline
Chapter 4 of the ICH GCP E6(R3) guideline assembles an integrated data governance framework of audit trails, metadata integrity, user access controls, and end-to-end retention.
Although sponsors routinely implement these controls, ethics review committees must be able to interrogate these controls as they relate to protecting the rights and welfare of research participants. This might include steps like requiring submission of a short data security synopsis at initial review, capturing any concerns related to this proposal in the board meeting minutes, and making approval contingent on a satisfactory security plan.
At Advarra, the IRB already evaluates the reasonably foreseeable risks of data protection and confidentiality depending on the nature and context of the study. This includes, as appropriate, evaluating the sponsor’s or CRO’s data security plans as they relate to participant privacy and confidentiality risks which must be disclosed in the consent form.
5 – From subjects to participants—a linguistic shift that matters
Perhaps the most visible change for anyone reading the ICH GCP E6(R3) guideline is the wholesale replacement of the term “trial subject” with “trial participant.”
The shift mirrors the latest revision of the Declaration of Helsinki and is more than semantics. It signals an ethic of partnership and respect for research participant autonomy. Research ethics boards should consider making similar changes in their documentation.
Internally, Advarra has adopted “participant” in all reviewer forms, training materials, and board correspondence. Advarra does not require sponsors or sites to change existing templates, but stakeholders will notice the updated terminology in Advarra documentation going forward.
Advarra’s compliance position with ICH E6(R3)
Our 2024 IRB Handbook for Investigators documents Advarra’s commitment to IRB compliance with U.S. federal regulations, the Common Rule, and Health Canada requirements. It also states that ICH-GCP elements are enforced for Canadian research and applied to U.S. studies when requested by the sponsor.
Where E6(R3) goes beyond binding law (such as encouraging risk-proportionate renewal schedules or richer data governance questions), Advarra has chosen to adopt a more rigorous standard.
Where E6(R3) is silent but national regulations remain prescriptive, the stricter national rules continue to control.
Our boards therefore already meet or exceed every substantive expectation in the E6(R3) guideline without compromising IRB compliance with FDA, Common Rule, or Tri-Council directives.
Sponsors partnering with Advarra can be confident that their studies remain regulation-ready on both sides of the border today and E6(R3)-ready for tomorrow.
Final Thoughts on ICH GCP E6(R3) for Research Ethics Boards
ICH E6(R3) encourages ethics review committees to more intelligently apply their resources by enhancing efficiency without compromising participant safety or data integrity. Now that FDA has published the ICH E6(R3) Good Clinical Practice (GCP) guidance, aligning early with these requirements can prepare organizations for the future.
By calibrating oversight to proportional risk, demanding transparent data stewardship, and adopting participant-first language, ethics review committees can both protect volunteers and accelerate therapeutic innovation.
Advarra’s early adoption shows the transition can be seamless for ethics review committees when quality systems are already robust and tailored to existing regulatory standards. If you have questions about a study reviewed by Advarra or are planning a new submission to Advarra, contact our regulatory experts using the “Ask Advarra” section of our website.
