ICH E6(R3)

The original guideline was modified in 2016 to “encourage implementation of improved and more efficient

approaches to clinical trial design, conduct, oversight, recording and reporting, while continuing to ensure

human subject protection and reliability of trial results.” The revised guideline – E6(R2) – also took into

account some modernisations in the way that clinical trials were being conducted. However, the changes did

not go far enough. There has been a huge growth in the use of data acquisition tools, different trial designs are

now utilised and recent years have seen a move towards risk-proportionate approaches in trial conduct. It was

therefore deemed necessary to renovate the guideline completely.

Some excellent work has been undertaken by the ICH E6(R3) EWG, and in particularly difficult

circumstances caused by the global pandemic. The plan is for the guideline to comprise three parts:

overarching principles, Annex 1 and Annex 2.

In April 2021 a preview was made available of the updated principles, when the ICH Management

Committee shared a draft work-in-progress version from the EWG. In May 2023 the Step 2b version of the

E6(R3) guideline was released, comprising the updated principles and Annex 1.

A notable change from E6(R2) is the addition of a new section on data governance. This topic is also well

covered in recent finalised guidance published by the European Medicines Agency, and a new draft questions

and answers document issued by the FDA. Although it seems like unnecessary duplication, ICH guidelines are

global and in the absence of more rigorous local or regional requirements the ICH guideline can be applied. A

welcome change in the draft E6(R3) Guideline is the use of the term ‘participant’ rather than ‘subject’.

In this special issue of Advisor we review the content of this document. There is, of course, a great deal

of information in the guideline, and we do not claim to have covered everything. Instead, we have tried to

identify the key requirements as well as some of the important differences between E6(R3) and E6(R2).