5/25/2021
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) released draft ICH E6(R3) Principles. ICH E6 Good Clinical Practice (GCP) guideline is the blueprint for clinical trials ensuring subject safety and data quality and it specifies the processes needed for study conduct and documentation to comply with the guideline and regulatory requirements. The last revision occurred in 2016. Since then, clinical trials are increasingly complex and in electronic formats, requiring updates to the GCP guideline to ensure its agility to meet the challenges of modern clinical trials.
Summary of Draft Principles
Examples of modernization of the draft guideline includes:
focus on the need to identify critical to quality elements and to build Quality by Design (QbD) into every aspect of the clinical trial
ensuring diverse and representative study participants
focus on simplifying the comprehension of the increasingly long and complex informed consent form
emphasis on participant data protection and privacy
focus on quality and reliability of trial results
There are now 12 principles now rather than 13, and they have been expanded, reorganized, and reworded. Some of the concepts were already present throughout the GCP guideline, but there is a major focus to align with the new ICH E8(R1) expected to be final this summer. The 12 principles are:
Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practice (GCP) and applicable regulatory requirement(s). (unchanged)
Clinical trials should be designed and conducted in ways that ensure the rights, safety, and well-being of participants. (reworded, expanded with 6 subpoints)
Informed consent is an integral feature of the ethical conduct of a trial. Clinical trial participation should be voluntary and based on a consent process that ensures participants are well-informed. (reworded, expanded with 2 subpoints)
Clinical trials should be subject to objective review by an institutional review board (IRB)/independent ethics committee (IEC). (reworded, expanded with 2 subpoints)
Clinical trials should be scientifically sound for their intended purpose, and based on robust and current scientific knowledge and approaches. (reworded, expanded with 3 subpoints)
Clinical trials should be designed and conducted by qualified individuals. (reworded, expanded with 1 subpoint)
Quality should be built into the scientific and operational design and conduct of clinical trials. (significantly reworded, expanded with 4 subpoints)
Clinical trial processes, measures, and approaches should be proportionate to the risks to participants and to the reliability of trial results. (new with 4 subpoints)
Clinical trials should be described in a clear, concise, and operationally feasible protocol. (reworded, expanded with 4 subpoints)
Clinical trials should generate reliable results. (new with 8 subpoints)
Roles, tasks and responsibilities in clinical trials should be clear and documented appropriately. (new with 2 subpoints)
Investigational products used in a clinical trial should be manufactured in accordance with applicable Good Manufacturing Practice (GMP) standards and be stored, shipped, and handled in accordance with the product specifications and the trial protocol. (reworded and expanded with 6 subpoints)
ICH E6(R3) Expert Working Group continues to progress, although slower than expected due to the pandemic. Draft Annex 1 is listed for December 2021, although there is likely a delay of a few months. When it reaches Step 3 of the guideline development process, public comment will be requested.
The ICH E6(R3) and ICH E8(R1) revisions are part of the (GCP) Renovation initiative. The two guidelines interplay to support clinical trial design, conduct, and data quality. ICH is ensuring ICH E6(R3) is updated to map to these aspects of ICH E8(R1), the “master” E guideline:
Quality by Design (QbD) of clinical studies
Critical to Quality Factor focus
Risk proportionate approach
Involvement of a wide range of stakeholders in clinical trial design
Study participant engagement
Decreased burden to sites
You may be interested in our blog on the draft ICH E8(R1) HERE. As mentioned previously, the final version is expected this summer. Other E guideline updates can be expected to follow, such as E19, Safety Data Reporting.
- The Clinical Pathways Team
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