On 3 June 2026, the Annex 2 of the ICH E6 (R3) guideline on Good Clinical Practice (GCP) was adopted. This marked the end of the second stage in the adoption process for the guideline, which began in January with the publication of the Principles and Annex 1.

The aim of Annex 2 is to address the increased use of various operational approaches, design elements and data sources in the design of clinical trials. It provides additional GCP considerations, focusing on trials that incorporate one or more of these new methodologies:

• Decentralised elements: trial-related activities conducted outside the investigator’s location. They also encompass remote interactions, such as video calls or the use of digital health technologies (DHTs) to conduct visits, perform procedures and collect data.
• Pragmatic designs: elements, such as protocols with trial processes and eligibility criteria and streamlined data collection, which reflect usual clinical practice are integrated into the design and conduct of the trial.
• Real-world data (RWD): data reflecting patient experiences, outcomes or healthcare delivery outside of a clinical trial setting. These data are collected from a variety of sources (e.g. electronic health records, registries and claims databases) and can be used, for example, as endpoint or outcome data, or as an external control.

The final version of this Annex is the result of a public consultation in which researchers from the Benzi Foundation took part: we provided inputs to cover important ethical aspects, including informed consent and assent procedure, and considerations for the secondary use of RWD in accordance with the applicable regulatory requirements, as well as special considerations for rare diseases, reflecting the Foundation’s commitment in these fields. While some of these recommendations have been implemented in the final document, not all of the proposed changes have been incorporated, particularly those relating to rare diseases.

Annex 2 is not meant to be comprehensive of all methodologies, recognising that clinical trial ecosystems may continue to evolve, and new approaches, designs and data types may emerge. It should be read in conjunction with the Principles and Annex 1; all the three have been consolidated into a single unified ICH E6(R3) guideline. ICH will temporarily make Annex 2 available as a standalone document to help stakeholders easily locate and apply the new content (it will remain available until the end of 2026).

Further details are available via the following links: ICH Official web site : ICH, ICH E6 Good clinical practice – Scientific guideline | European Medicines Agency (EMA)