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- Global Clinical Trial Guidelines Modernised with ICH GCP E6(R3)
- Quality by Design (QbD): Proportional and Fit-for-Purpose Approaches
- Stronger Emphasis on Patient Centricity
- Data Governance
- Enhanced Transparency and Ethical Oversight
- Clarified Roles and Responsibilities
- Rigorous Training and Qualification Standards
Global Clinical Trial Guidelines Modernised with ICH GCP E6(R3)
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has officially released the long-awaited revision to its Good Clinical Practice (GCP) guidelines: ICH GCP E6(R3). This update towards a modernised, flexible and patient-focused approach to clinical research marks the most significant transformation in global clinical trial standards since the E6(R2) amendment in 2016.
The content of ICH E6(R3) has been revised and reorganised. It now includes:
- An introduction and 11 core GCP principles.
- Annex 1: Roles and responsibilities of the Institutional Review Board/Ethics Committee, Investigators, Sponsors, and guidance on Data Governance.
- Appendix A: Investigator’s Brochure.
- Appendix B: Clinical trial protocol and protocol amendments.
- Appendix C: Essential records for trial conduct.
- Annex 2 is currently under development and will outline further considerations for clinical trials that incorporate decentralised, pragmatic or real-world elements.
Quality by Design (QbD): Proportional and Fit-for-Purpose Approaches
Quality is now expected to be embedded from the outset of clinical trial planning. The ‘Quality by Design’ concept includes identification of factors critical to quality and implementing risk mitigation strategies proportionate to the importance of the collected data and risks to the participants’ safety and data reliability. Systems and processes used for data capture and the quality and amount of information generated in the trial should be fit for purpose. E6(R3) clarifies that the trial risks are those beyond the standard of care.
The new guidelines advocate for:
- Proactive quality measures integrated throughout the trial lifecycle.
- Data-driven risk identification and mitigation strategies that evolve dynamically.
- Study designs that yield reliable and actionable data, improving overall trial efficiency and reliability.
Stronger Emphasis on Patient Centricity
E6(R3) underscores the importance of prioritising patient needs and experiences, beyond just trial outcomes. It emphasises minimising unnecessary burdens and encourages input from patients and their communities, patient advocacy groups, healthcare professionals because “their input can help to reduce unnecessary complexity, improve feasibility and increase the likelihood of meaningful trial outcomes”.
Sponsors are encouraged to:
- Design inclusive studies with diverse, representative populations.
- Consider patient convenience and preferences to boost engagement.
- Enhance the generalisability of results through better participant representation.
Data Governance
A new Data Governance section has been added to the ICH E6(R3). This section includes comprehensive guidance on data integrity, traceability, security, and computer systems. It is applicable to sponsors and investigators.
- Embracing Technological Advancements
In recognition of the rapid growth of digital health, ICH GCP E6(R3) facilitates the integration of:
- Computerised systems, wearable technology, electronic data capture tools, and other digital health innovations.
- Novel trial designs, e.g. Decentralised Clinical Trial (DCT) models that enhance accessibility for participants.
- Flexibility to adopt emerging technologies while ensuring participant safety and data integrity.
Enhanced Transparency and Ethical Oversight
Transparency continues to be a fundamental principle in ethical clinical research, and the updated ICH GCP E6(R3) strengthens this commitment by mandating:
- Timely registration of clinical trials and public disclosure of study results, including the provision of layperson summaries.
- Enhanced ethical review procedures and more rigorous requirements for informed consent. Additional language has been introduced to reinforce the importance of public accessibility to trial outcomes.
Alignment with the EU Clinical Trial Regulation (CTR): R3 confirms that ethics committee and regulatory authority assessments can be conducted jointly to streamline the review process. Under the EU CTR, clinical trials must receive ethics committee approval prior to initiation.
- Clear and consistent communication of study objectives, risks, and benefits to participants throughout the research process.
Clarified Roles and Responsibilities
To enhance accountability and operational clarity, in the E6(R3) a new principle was added which provides:
- Clearer delineation of roles and responsibilities for sponsors, investigators.
- Explanation that investigators and sponsor can delegate the activities to other persons/parties and such delegation should be appropriately documented. E6(R3) emphasizes that investigators/sponsor retain the overall responsibility for these activities and should maintain appropriate oversight.
- Defined expectations for oversight, decision-making, and documentation across the trial continuum.
Rigorous Training and Qualification Standards
Ensuring that all personnel involved in clinical trials are appropriately trained and qualified is a core component of the revised framework. The new guidelines:
- Set stronger standards for staff competency and continuing education.
- Broadens the range of examples of qualified personnel needed for trials.
- Support consistent trial conduct and data quality across diverse global research settings.