Good Clinical Practice and ICH E6(R3)

Part of Clinical Research Coordinator (CRC) Training: The Regulatory Framework.

About 6 minutes. Free, in your language, no account needed.

Why this matters

Good Clinical Practice is the standard your work will be judged against. It is also the area where old training does the most damage, because a great deal of material still in circulation describes a version of the guideline that has been superseded.

Learn the current one. Learn it well enough to notice when a colleague is quoting the old one.

What Good Clinical Practice is

Good Clinical Practice, usually shortened to GCP, is an international standard for designing, conducting, recording and reporting clinical trials involving people. It has two purposes, and it states them in that order: protecting the rights, safety and wellbeing of participants, and making the trial results reliable.

The standard is written by the International Council for Harmonisation, or ICH. The guideline is called E6.

Note the word "Council". ICH was founded in April 1990 as the International Conference on Harmonization. In 2015 it became a legal entity under Swiss law and was renamed the International Council for Harmonization. Training material that still says "Conference" is at least a decade out of date.

ICH E6(R3) is the current revision

• The original ICH E6 guideline reached Step 4, meaning adoption as a harmonized guideline, on 1 May 1996.
• E6(R2) was adopted on 9 November 2016. It added risk-based quality management as an addendum to the 1996 text. E6(R2) is historical.
• ICH E6(R3), consisting of the Principles and Annex 1, was adopted at Step 4 on 6 January 2025. It became legally effective in the European Union on 23 July 2025.
• E6(R3) Annex 2, which addresses decentralized elements, pragmatic elements and real-world data, was adopted at Step 4 on 3 June 2026 and becomes legally effective in the European Union on 15 January 2027.

E6(R3) is the operative revision. Reference E6(R2) only when you are describing history.

What changed, and why it affects you

R2 was a single flat document with numbered sections. R3 has a different shape: a set of overarching Principles, followed by Annexes that apply those principles to particular kinds of trial. Annex 1 covers interventional trials and is the one your work sits under.

The principles are organized into eleven categories. Learn all of them and what each requires. Do not memorize or quote a count of the individual sub-points beneath them; different sources count them differently and the number proves nothing.

Three changes matter directly at site level.

Data governance is now explicit. R3 contains a substantial treatment of how trial data are generated, recorded, protected and retained, shared between investigator and sponsor. Module 8 of this course is built on it.

"Essential documents" became "essential records". The change is not cosmetic. Records now expressly include data and relevant metadata, such as the audit trail in an electronic system, not only signed pieces of paper.

Contract research organizations are treated as service providers. A sponsor may transfer duties to a service provider, but the sponsor retains responsibility for the quality and integrity of the trial data.

Two things GCP does not say

These corrections matter because the wrong versions are widely taught.

ICH E6(R3) does not use the acronym ALCOA. It states the data attributes directly, in words. Module 8, Lesson 1 gives the list the guideline actually uses. You may use ALCOA or ALCOA+ as a memory aid, but never write "as required by ICH E6(R3)" beside the acronym.

ICH E6(R3) states no retention period in years, and no number of hours for reporting a serious adverse event. For retention, section 3.16.3 defers to applicable regulatory requirements and requires the sponsor to tell the site in writing what those requirements are. For serious adverse events, section 2.7.2(b) says they should be reported to the sponsor immediately after the investigator reasonably becomes aware. The familiar "24 hours" is a protocol or sponsor convention, and figures such as 7 or 15 days are regional regulation.

What GCP asks of you personally

Reduced to daily practice, GCP asks the site to be able to answer four questions at any moment.

1. Did this person agree, on the current approved form, before anything study-specific happened?
2. Did what the protocol required actually happen, and can you show it from your records?
3. If something changed in a participant's health, was it recorded and reported?
4. Is the person who performed each task trained and delegated to perform it?

If you can answer all four from your records, without relying on memory, you are working to GCP.

In practice

Nadia joins Northside Clinic and finds GCP training certificates in the staff files dated 2019. They describe "the 13 principles of ICH GCP".

She is right to question them. Thirteen flat principles is an E6(R2) description. E6(R3) organizes its principles into eleven categories and has a different structure entirely.

The certificates are not fraudulent. They record training that genuinely happened, on the revision that was current at the time. Nadia does not destroy them; they are evidence of what the staff were trained on then. She files them, records the gap, and arranges E6(R3) training for everyone on the delegation log before the site initiation visit.

Old certificates are not lies. They are just not evidence of current training.

Key takeaways

• Good Clinical Practice protects participants first and data reliability second, and is written by the International Council for Harmonisation, renamed from "Conference" in 2015.
• ICH E6(R3) Principles and Annex 1 were adopted on 6 January 2025 and are the operative revision; E6(R2), adopted 9 November 2016, is historical.
• E6(R3) is structured as Principles plus Annexes, with the principles organized into eleven categories, and Annex 1 applying to interventional trials.
• R3 renamed "essential documents" to "essential records" so that data and relevant metadata, including audit trails, are expressly covered.
• E6(R3) never uses the acronym ALCOA, states no retention period in years, and gives no number of hours for serious adverse event reporting — those figures come from regional law, the protocol, or industry convention.