#6 ICH-GCP will be updated (again) in 2024 – are you prepared?

If you’ve ever applied for a Clinical Research Associate position, you’ve likely encountered the Holy Grail of interview questions: “What is ICH-GCP?” It’s the one topic that shows up in every onboarding session, every certification exam, and every interview. If you’re in the clinical research field, you can’t escape it—and frankly, you shouldn’t want to. ICH-GCP – spelled out International Council for Harmonisation Good Clinical Practice – is the bedrock of clinical trials, ensuring they are conducted ethically, safely, and with scientifically sound practices.

Now, just when you thought you had ICH-GCP down pat, along come two updates that shake things up—E6(R2) in 2016 and the upcoming E6(R3), expected in 2024. Why were these updates needed? Because clinical trials have evolved, and the guidelines must keep pace with technological advancements. In my view, for any clinical research professional, staying familiar with these updates isn’t just important—it’s essential for navigating the modern landscape of trials. I am often shocked by how many of my fellow clinical research professionals are not familiar with this. Therefore I decided to write this article summarizing the 2 major updates, that will help you to shine in your next job interview or drop it casually at your lunch table with your colleagues.

And speaking of the future, it’s fun to speculate: What will the third update bring? Maybe something like AI-based trial monitoring or virtual reality site inspections. Who knows? But one thing’s for sure—the guidelines will keep evolving as fast as the technology does.

Lastly, I want to give you heads up, as it’s gonna be a long post, and if you only want a summary, go straight to the FAQ section at the bottom, but I encourage you to read all. Let’s dive in!

First Major Update: ICH-GCP E6(R2)

In 2016, the ICH-GCP E6(R2) update marked the first major revision to the Good Clinical Practice guidelines since their inception over two decades earlier. This update was implemented to address the evolving nature of clinical trials, which had grown significantly in complexity since the original guidelines were drafted. Here are the main reasons for the E6(R2) Update:

1. Risk-based approach: One of the most important features of the E6(R2) update was the introduction of a risk-based approach to trial design and conduct. This approach allowed clinical researchers to focus their resources on managing the most critical risks to trial participants and data integrity. Instead of applying the same level of oversight across all aspects of a clinical trial, E6(R2) enabled a more flexible and efficient approach, allowing trial managers to prioritize areas that posed the greatest potential risks. This had also huge impact on moving to targeted SDV, instead of the earlier 100% SDV method.
2. Increasing trial complexity: Clinical trials had become far more complex than they were two decades earlier. Trials now involved larger participant groups, multiple study sites, and a greater variety of study designs. The guidelines needed to adapt to ensure the continued ethical management of these increasingly intricate trials. E6(R2) provided updated processes to manage these complexities effectively, ensuring that the safety of participants and the quality of the data were not compromised.
3. Technological advancements: The 2016 update also reflected the rapid integration of new technologies in clinical research. Electronic data capture, remote monitoring, and other digital tools had become commonplace in trials, yet the original ICH-GCP guidelines did not fully account for their use. E6(R2) incorporated these advancements, providing clearer guidance on how to manage technology in clinical trials, such as handling electronic records and signatures while maintaining compliance with ethical standards.

What was the impact of E6(R2) update? The risk-based approach enabled researchers to streamline trial processes, reduce unnecessary burdens, and focus on the most important aspects of trial safety and data integrity. The update also improved the handling of trial complexity by providing clearer guidelines for multi-site trials and adaptive study designs. Researchers could now better manage large-scale, intricate studies while ensuring that ethical and scientific standards were upheld. Finally, the recognition of technological advancements in E6(R2) allowed clinical trials to integrate electronic systems more seamlessly. The update ensured that digital tools, such as electronic data capture and remote monitoring, could be used efficiently while maintaining the same high standards of data accuracy and participant protection that the original guidelines demanded.

Second Major Update: ICH-GCP E6(R3)

The second major update to the ICH-GCP guidelines, known as E6(R3), is currently in progress and expected to be implemented in 2024. This update builds on the revisions made in E6(R2) and is designed to reflect the continued evolution of clinical trials, incorporating the latest innovations in trial design and technology. The goal of E6(R3) is to further strengthen the guidelines to ensure that Good Clinical Practice remains relevant, effective, and adaptable to the future needs of clinical research. Here are the main reasons for the E6(R3) Update

1. Non-traditional trials: The rise of non-traditional trial designs, such as decentralized trials that use remote technologies, has driven the need for updated guidelines that accommodate these approaches. E6(R3) includes provisions for non-traditional trials, ensuring that these innovative models can be conducted ethically and in compliance with Good Clinical Practice.
2. Enhancing transparency: Transparency in clinical research has become increasingly important, and E6(R3) emphasizes this aspect by encouraging the public registration of clinical trials and the publication of results. This increased transparency promotes greater accountability and helps build public trust in clinical research.
3. Strengthening the risk-based approach: Building on the introduction of a risk-based approach in E6(R2), the E6(R3) update aims to further advance this concept. By refining and enhancing the risk-based framework, E6(R3) encourages even more efficient trial oversight, allowing researchers and regulators to focus on the most critical aspects of clinical trials while reducing unnecessary burdens on lower-risk areas.
4. Expanding applicability: While previous versions of ICH-GCP primarily focused on drug research, the E6(R3) update expands its applicability to other types of clinical research, including device trials, behavioral studies, and other non-drug clinical investigations. This expansion makes the guidelines more flexible and relevant across a wider range of clinical research fields.
5. Improving efficiency and data integrity: A key focus of the E6(R3) update is improving the efficiency of clinical trial processes, particularly in record management and data integrity. By streamlining these areas, the guidelines aim to reduce operational burdens while ensuring that the data collected during trials remains accurate, reliable, and secure.
6. Clarifying roles and responsibilities: The E6(R3) update also seeks to provide greater clarity regarding the roles and responsibilities of sponsors, investigators, and other stakeholders involved in clinical trials. By clearly defining these responsibilities, the guidelines aim to improve collaboration and ensure that all parties are accountable for maintaining Good Clinical Practice standards.

One of the key changes in E6(R3) is the restructuring of the guidelines into three distinct parts to ensure better organization and flexibility:

Principles: This section outlines the core principles of Good Clinical Practice that apply to all clinical research, regardless of the type of trial being conducted.

Annex I (for drug research): This annex provides specific guidance tailored to clinical trials involving drugs and biological products, ensuring that the guidelines address the unique aspects of drug development.

Annex II (for other types of clinical research): This annex offers guidance for clinical research that falls outside traditional drug research, such as device trials and behavioral studies. It allows the ICH-GCP guidelines to be applied across a broader range of clinical investigations.

By addressing new methodologies, technologies, and ethical considerations, E6(R3) aims to support the continued innovation and safety of clinical trials.

Conclusion

The two major updates to the ICH-GCP guidelines, E6(R2) and E6(R3), were driven by the need to keep pace with the evolving methodologies in clinical trials, technological advancements, and the growing demand for flexible and transparent guidelines. The introduction of a risk-based approach, the increasing complexity of trials, and the integration of new digital tools necessitated the E6(R2) update in 2016. This laid the groundwork for a more efficient and targeted approach to trial design and oversight.

Building on that foundation, the E6(R3) update, expected to be implemented in 2024, further expands the scope of the guidelines to encompass a broader range of clinical research, including non-traditional trial designs and decentralized trials. It also enhances data integrity, promotes public transparency, and clarifies roles and responsibilities within the trial process.

These updates reflect the ICH’s commitment to ensuring that Good Clinical Practice guidelines remain relevant and adaptable to the changing landscape of clinical research. By addressing new challenges and incorporating lessons learned from previous versions, E6(R2) and E6(R3) aim to improve the quality, safety, and efficiency of clinical trials on a global scale. As clinical research continues to evolve, these updates ensure that trials are conducted ethically, efficiently, and with the utmost consideration for participant safety and data integrity.

What do you think the third update will focus on? Personally, I suspect it will address emerging AI technologies in clinical research. What’s your prediction?

FAQ Section

1. What is ICH-GCP, and why is it important for clinical research?

ICH-GCP is a set of ethical and scientific guidelines for designing, conducting, and reporting clinical trials involving human participants. It ensures that trials are conducted in a way that protects participant safety and ensures the integrity of the data. Every clinical research professional needs to be familiar with ICH-GCP to maintain compliance with global standards.

2. Why was ICH-GCP updated with E6(R2) in 2016?

The E6(R2) update was introduced in 2016 to address the growing complexity of clinical trials, incorporate a risk-based approach to trial design, and account for technological advancements like electronic data capture and remote monitoring. This update helped modernize the guidelines for more efficient and effective clinical trials.

3. What are the main reasons behind the E6(R3) update?

The E6(R3) update, expected in 2024, aims to further refine the risk-based approach, expand the guidelines to cover a wider range of research (including non-drug and decentralized trials), and improve data integrity and transparency. It also introduces provisions for handling novel trial methods and clarifies the roles and responsibilities of sponsors and investigators.

4. How will E6(R3) impact clinical research professionals?

E6(R3) will require clinical research professionals to adapt to new methods for ensuring data integrity, managing risk, and handling decentralized or non-traditional trial designs. Familiarity with these changes is crucial for staying compliant with Good Clinical Practice standards and maintaining the quality and safety of clinical trials.

Sources used to write this blog post

1. https://gcpcentral.com/updates-law-regulations/implementation-of-ich-e6-r3
2. https://gcpcentral.com/updates-law-regulations/ich-gcp-r3-what-should-we-expect-part-1
3. https://arithmostech.com/the-new-ich-e6-r3-guidelines-impact-on-clinical-trials
4. https://www.linkedin.com/pulse/understanding-revised-ich-gcp-e6r3-update-comprehensive-r-uhppc
5. https://database.ich.org/sites/default/files/ICH_E6(R3)_DraftGuideline_2023_0519.pdf
6. https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice-scientific-guideline