Final ICH E6(R3) Annex 2

The ICH E6(R3) Guidance has been updated in its latest revision to reflect new developments and modern technical solutions. Alongside the core text and Annex 1, Annex 2 has now been introduced to support international harmonisation regarding newer concepts. It provides additional GCP considerations for trials incorporating decentralised elements, pragmatic designs, and/or real-world data.

Additional GCP Considerations

Good Clinical Practice (GCP), as described in the ICH E6(R3) core document and Annex 1, applies to different study types, designs, and settings and remains relevant when various operational approaches (or methodologies), design elements, and data sources are used in a clinical trial. As clinical trial methodologies continue to evolve and technological advances must be taken into account, the application of GCP should be tailored to the study design and the technologies used. In this context, the use of a proportionate risk-based approach (as explained in the GCP Principles and Annex 1) remains relevant and supports the use of evolving study designs and technologies without compromising the rights, safety, and well-being of trial participants or the reliability of trial results. In response to the increasing use of different operational approaches, design elements, and data sources, ICH E6(R3) Annex 2 provides additional GCP considerations focusing on studies that incorporate decentralised elements, pragmatic elements, and/or real-world data (RWD):

• Decentralised elements in a clinical trial are those trial-related activities conducted outside the investigator’s location. These may include trial visits and/or protocol-related procedures conducted at the trial participant’s home, local healthcare centres or mobile medical units. 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.
• The term DHTs is used as a broad term to reflect the wide range of technologies supporting healthcare used to collect, measure, or monitor health-related data from participants or patients (e.g., mobile applications, wearables, and sensors). Depending on the context, the term may refer to those technologies used specifically in trials or those used within broader healthcare settings. Where a DHT is used to acquire participant data for a clinical trial, it is considered a data acquisition tool.

Clinical trials may include one or more of these methods. However, Annex 2 cannot cover all new methods and approaches, as it is already evident that new approaches, designs, and data types may emerge. The considerations and concepts contained in Annex 2 can be applied to these continuously evolving methods, provided they have been developed in accordance with local regulatory requirements. 

More information is available in Annex 2 of the ICH GCP Guideline E6(R3).