ICH E6(R3) Annex 2: Draft Version for Good Clinical Practice in Modern Clinical Trials

The International Council for Harmonisation (ICH) has released a draft of Annex 2 for the Good Clinical Practice (GCP) Guideline, ICH E6(R3). This draft, made available for public consultation on November 6, 2024, addresses the challenges and opportunities posed by modern clinical trial designs. As clinical research increasingly embraces decentralized and pragmatic elements, Annex 2 aims to provide comprehensive GCP guidance, ensuring the rights, safety, and well-being of participants while maintaining the reliability of trial results.

Key Aspects of the Draft Guideline

Here below are the key highlights that are addressed in the draft of Annex 2:

Decentralized and Pragmatic Elements

The draft focuses on trials incorporating decentralized and pragmatic elements. Decentralized elements refer to conducting trial activities outside traditional clinical settings, such as remote data collection using digital health technologies (DHTs). Pragmatic elements integrate clinical practice into trial protocols, simplifying data collection and aligning research with real-world clinical settings.

• Remote Informed Consent: The draft outlines procedures for obtaining informed consent using remote methods, ensuring participants’ identities are verified securely.
• Data Privacy and Security: There is a strong emphasis on protecting participant data, particularly when trial-related activities are conducted at home or involve DHTs.

Investigator Responsibilities

Investigators are expected to maintain oversight even when trial activities occur remotely. This includes:

• Ensuring investigational products are properly managed when dispensed to participants or administered in decentralized settings.
• Tailoring the informed consent process to match the trial’s design, ensuring participants understand how their data will be used and safeguarded.

Sponsor Obligations

The draft emphasizes the need for sponsor engagement and proactive communication:

• Sponsors should consult with stakeholders, including patient advocacy groups, to ensure that decentralized tools and methodologies are accessible and effective.
• Early regulatory engagement is encouraged to address challenges related to integrating real-world data (RWD) and using complex trial designs.

Protocol and Trial Design Considerations

The draft outlines specific adaptations for protocol development:

• Detailed descriptions of design elements, such as the integration of RWD from sources like EHRs (Electronic Healthcare Records), are required.
• Sponsors must address the potential variability and quality issues associated with RWD, ensuring it is reliable and fit for purpose.

Safety and Risk Management

Managing participant safety remains a top priority:

• The draft calls for innovative approaches to safety monitoring that accommodate remote and decentralized trial elements.
• Safety protocols must account for the multiple data sources used in these trials, ensuring investigators receive timely and actionable information.

SEE ALSO: Quality Risk Management in Pharma

Conclusion

The draft of ICH E6(R3) Annex 2 represents a significant step forward in modernizing GCP guidelines to accommodate the evolving landscape of clinical trials. It acknowledges the complexities of decentralized and pragmatic trial designs while reinforcing the importance of participant safety and data integrity. Stakeholders are invited to review and provide input on the draft, shaping the future of clinical research practices.

For access to the draft and more information, visit the link to the ICH official website.