Understanding ICH E6(R3): The Evolution of Good Clinical Practice and Its Impact on Clinical Trials
The Good Clinical Practice (GCP) guidelines, developed by the International Council for Harmonisation (ICH), serve as the international ethical and scientific standard for designing, conducting, recording, and reporting clinical trials involving human participants. These guidelines are essential for ensuring the protection of trial participants and maintaining the credibility and reliability of clinical trial data.
As the field of clinical research continues to evolve—driven by technological advances, increasing regulatory complexity, and a heightened emphasis on patient-centricity—GCP guidelines must also adapt. The upcoming revision, ICH E6(R3), reflects these developments and represents a significant update to the global framework governing clinical trials.
What’s New in ICH E6(R3): Effective 23 July 2025
Key Principles of ICH for Clinical Trials
Understanding the Role of ICH in Clinical Trials
Revision 3 (R3) of ICH E6 introduces important updates aimed at increasing flexibility, fostering innovation, and embedding a risk-based approach to clinical trial design and execution. The revised guideline is structured to be more adaptable and fit-for-purpose, accommodating the diversity of today’s clinical trial methodologies.
The new structure includes the following key components:
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Introduction
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Principles of ICH GCP (applicable to all clinical trials)
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Annex 1 and Appendices (specific to interventional clinical trials)
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Annex 2 (focused on non-traditional interventional trials)
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Glossary
One of the most notable changes is the reorganization of the original 13 GCP principles into 11 updated principles. This revision reflects the evolving priorities in clinical research. Two new principles have been introduced:
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Risk proportionality (Principle 7): Emphasizes that trial oversight, design, and conduct should be proportionate to the risks and complexity involved.
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Roles and responsibilities (Principle 10): Clearly defines expectations around the accountability of all stakeholders involved in clinical trials.
Another significant update is the shift in terminology, replacing the term “subjects” with “trial participants.” This change underscores a more respectful and inclusive approach, recognizing the active role of individuals participating in research and the growing emphasis on patient-centered trial conduct.
Promoting Fit-for-Purpose Clinical Trials
A central theme of ICH E6(R3) is the concept of “fit-for-purpose” clinical trials. Rather than applying a one-size-fits-all approach, the guideline promotes tailoring trial design and quality expectations to the specific objectives and complexity of the trial. The goal is to enhance efficiency while maintaining ethical standards and scientific integrity.
Key elements of this approach include:
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Greater flexibility in defining protocol parameters
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Adoption of risk-based strategies in trial oversight and technology use
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Integration of quality by design principles from the earliest stages of protocol development
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Embracing new technologies such as wearable devices, electronic informed consent (eIC), and remote monitoring tools
By encouraging innovation and adaptability, ICH E6(R3) supports more responsive and streamlined clinical trial processes without compromising data quality or participant safety.
Protocol Development Under ICH E6(R3)
The protocol remains the cornerstone of any clinical trial. ICH E6(R3) reinforces the importance of a well-designed protocol in ensuring the trial’s scientific validity and ethical soundness. According to the guideline, “Protocols should be designed to minimize unnecessary complexity, mitigate risk, and ensure trial participant protection and data integrity.”
A well-crafted protocol should:
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Clearly define the study’s objectives, endpoints, and methodology
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Identify and justify the target population, inclusion/exclusion criteria, and sample size
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Outline risk mitigation strategies relevant to both participant safety and data quality
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Describe procedures for collecting, managing, and reporting safety data
Protocol development should be a collaborative process. In line with ICH E6(R3), contributions from sponsors, principal investigators, and Clinical Research Organizations (CROs) are essential to producing a document that is not only scientifically robust but also operationally feasible.
At 1MED, our Medical Writing and Clinical Operations teams work together to co-develop protocols that translate complex regulatory and scientific requirements into clear, patient-friendly, and compliant study designs. This cross-functional collaboration ensures that every protocol is both actionable and aligned with evolving regulatory expectations.
Collaboration for Success
The revised ICH E6(R3) makes it clear that protocol development is not just a regulatory requirement—it is a strategic element that underpins the success of a clinical trial. By engaging relevant experts early in the process, sponsors can ensure that their protocols are designed with operational efficiency, participant protection, and data quality in mind.
A well-developed protocol serves as a critical link between scientific objectives, regulatory compliance, and practical trial conduct. It defines the scope and direction of the study while providing a framework for ethical oversight and reliable data generation. At 1MED, we view protocol development as an opportunity to build this foundation carefully, integrating risk management, innovation, and patient-centered thinking from the start.
As ICH E6(R3) comes into effect, stakeholders in clinical research will need to adjust their practices accordingly. The revision offers an opportunity to embrace modern tools and approaches, streamline operations, and strengthen participant protections. Ultimately, the new guideline reinforces the central goal of clinical research: to generate high-quality evidence through ethical, transparent, and efficient study conduct.