Insight into the New ICH E6(R3) Draft Guidance on Clinical Trials

Earlier this year, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) released ICH E6(R3), the newest version of the draft Good Clinical Practices (GCP) Guideline. Stakeholders were invited to leverage comment periods set forth by their respective competent health authorities and provide feedback. The FDA received 45 sets of public comments, including those provided by Medable.

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The new draft guidance makes it clear that regulators recognize the value of modern clinical trial models, such as decentralization, and supporting technologies. They are creating principles that allow for forward-looking flexibility, and annexes and appendices that provide more detailed guidance to ensure data reliability and that the rights, safety, and well-being of trial participants are protected in clinical trials.

One of the most significant changes over the previous version is the addition of a new section on data governance—both the investigator and sponsor. Multiple commenters also requested clarification on the term “computerized systems,” a term used throughout the document and potentially subject to multiple interpretations and some unintended consequences as a result. Comments also sought clarity on the definition of “laboratories” and “principal investigator” in the context of the current range of studies being conducted.

There are also sections, such as IRB review, that have not garnered any comments yet. The ICH E6(R3) guidance recognizes that the IRB should review, “any other information to be provided to the trial participant(s), including a description of the media,” thereby recognizing that patients may receive information from digital and social media. However, there may be newer approaches, such as the use of gamification as a potential non-financial incentive, that need to be raised to make sure the final GCP guidelines meet changing approaches to participant engagement.

Decentralized elements are being increasingly considered in clinical trials, and the ICH E6(R3) includes language to address the use of related technology and non-PI providers in studies. Two new principles, in addition to the data governance section, that have implications for decentralized approaches will greatly benefit from feedback from research professionals who have experience implementing decentralized approaches in real life. The first principle (number 7 in the document) concerns clinical trial processes, measures, and approaches, and the second principle (number 10) focuses on staff roles and responsibilities.

In collaboration with the Reagan-Udall Foundation for the Food and Drug Administration, the primary independent non-profit aiming to advance the FDA's objectives, the FDA held a two-day conference focusing on decentralized and pragmatic features and considerations for clinical trials. Much of what was discussed echoes in the draft of ICH GCP E6 R(3), and future releases of the draft annexes are expected to further clarify the use of decentralized and other digital or remote elements across a variety of trial designs (i.e., decentralized elements) and data sources (i.e., real world data sources such as registries and electronic health records).

Close analysis and feedback will help the ICH working group refine language around the assessment, use, and accountability of decentralized clinical trial (DCT) models. It’s crucial for progress as DCTs have the potential to expand the number of people who can participate in, and benefit from, clinical trials while accelerating more therapies to more patients in need.

The GCP guideline will only become better, clearer, and more robust with perspectives from a diverse range of stakeholders (e.g., sponsors, investigators, patients, academia, service providers). This is our community’s opportunity to assure future prevailing principles and guidelines for decentralized approaches to research ensure data quality and reliability plus participant safety even as we continue to innovate.

About the Author

Kevin Potgieter, Vice President of Regulatory Affairs, Medable.