15 August 2025
Revised ICH E6(R3) GCP Guideline
Risk-based, practical, future-oriented: The key changes in the Good Clinical Practice guideline
As of August 15, 2025, the revised Good Clinical Practice guideline, ICH E6(R3), also applies in Switzerland. Introduced at the beginning of the year by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the update addresses the growing complexity of clinical trials. Its goal is to sustainably ensure efficiency, scientific quality, and—above all—the protection of study participants in clinical research, even under changing conditions.
From 13 to 11, but more comprehensive: Changes to the GCP principles
With E6(R3), the GCP core principles have been restructured: The updated version no longer contains 13, but rather 11 core principles. These are now elaborated in greater detail with subpoints and formulated in a more practical manner. Two new core principles have been introduced: the principle of risk proportionality and the principle of roles and responsibilities.
The principle of risk proportionality stipulates that study processes should be aligned with the actual risk and complexity of the respective study design. In practice, this means that study teams should not implement additional measures as a matter of course, but rather ask themselves: What is absolutely essential in this specific study for the safety of the participants and the quality of the data?
The principle of responsibilities clarifies the distribution of roles and responsibilities, particularly for the sponsor. This includes requirements for delegation, monitoring, and quality assurance. Here, too, practical solutions are to be promoted that meet both regulatory requirements and operational realities.
Quality by Design as a core element
E6(R3) explicitly reaffirms the Quality by Design (QbD) concept introduced in ICH E8(R1), translating it into concrete requirements for sponsors and investigators. QbD means integrating quality aspects from the outset—not as an afterthought. Quality is not about ticking compliance boxes; it is a mindset where the study team proactively prioritizes participant protection and data integrity. Critical quality factors (such as primary endpoint measurement and key safety assessments) are identified early and addressed with risk-appropriate measures.
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What does R3 mean for researchers?
The revised GCP guideline places purposeful, risk-based, and proactive planning and conduct of clinical studies at the forefront (see also table). It acknowledges that individual studies require tailored solutions. Aspects such as patient involvement, transparency, and the integration of decentralized and digital methods are gaining significance. For researchers, this means more personal responsibility, but also more room for manoeuvre and greater flexibility.
The most important new features of E6(R3) at a glance
Structure | Reorganisation into 11 principles, Annex 1 with explanations on interventional clinical studies, glossary and appendices as well as Annex 2 on non-traditional interventional clinical studies. Annex 2 will enter into force in 2026 at the earliest. |
Quality by Design (QbD) and risk proportionality | Quality in the sense of QbD goes beyond the mere fulfillment of compliance checklists. It describes an approach in which the study team consistently prioritises the protection of participants and data integrity right from the planning phase. This acknowledges that studies vary and that quality efforts should focus on the most important risks – a principle of risk proportionality. Appropriate quality aspects are proactively integrated into protocols and planning from the outset, rather than being added retrospectively. |
Data governance | A newly created, separate chapter deals with data integrity and traceability throughout the entire data lifecycle: from collection, via audit trails to archiving and deletion. Continuous validation of computerised systems, strict user and role management and measures to ensure blinding are required. |
Study design and technological progress | Innovative study designs such as adaptive studies, platform studies, decentralized elements, etc. as well as technological innovations are taken into account. For example, the use of electronic consent (eConsent) and remote monitoring are expressly supported. |
Roles and responsibilities | The duties of the sponsor, investigator and representatives of service providers are described in more detail and clearly delineated. In principle, delegation is permitted, but the overall responsibility remains with the delegating person. |
Patient orientation | There is a call for stronger patient focus through reduced burden, consideration of underrepresented groups, and openness to decentralized and adaptive study designs. |
Transparency | The demand for transparency and traceability throughout the entire study process is emphasised. This includes not only the obligation to register studies, report on results and disclose relevant study data, but also transparent and timely communication with all parties involved, in particular with study participants in language that is understandable to laypersons. |
Glossary | A comprehensive glossary contains revised terms such as "trial participant" instead of "subject" as well as new definitions of data sources, documents and system validation. |