The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an international organization that was founded with the purpose of developing and promoting harmonized guidelines and standards for the pharmaceutical industry worldwide. One of its key guidelines is the ICH E6, also known as Good Clinical Practice (GCP). First published in 1996, ICH-GCP has become an internationally recognized ethical and scientific standard for designing, conducting, recording, and reporting clinical trials involving human subjects. Since its initial publication over two decades ago, the guideline has been periodically revised to adapt to the growing intricacy and complexity of clinical trials. Its forthcoming revision, R3, is now in its public consultation phase, and seeks to address these challenges by incorporating supplementary considerations for non-traditional settings. One of its key focuses is to tackle concerns related to the integration of Real-World Data (RWD) sources into the clinical trial design.
So we can support our Life Sciences customers in an effective and compliant manner with their preparations to the new guideline, BC Platforms took the opportunity to participate in a multi-stakeholder workshop organized by the European Agency of Medicament (EMA) to collect the views of patients, healthcare professionals and clinical researchers on clinical trials and applying GCP. In this blog, we will explore the key principles of the ICH E6 guidelines and provide an overview of the most consequential measures that were under discussion for R3.
ICH E6 guidelines are based on 5 key principles:
Protection of subjects – the ICH E6 guidelines prioritize the rights, safety, and well-being of trial subjects. Subjects must be fully informed about the trial, enabling them to make an educated decision about participation. Additionally, participants must have the freedom to withdraw from the trial at any time without facing any penalties.
Scientific soundness – clinical trials must be scientifically robust and designed to address the research question effectively. The methods employed in the trial should be thoroughly described and justified, and the trial must adhere to the specified protocol.
Trial conduct – the ICH E6 guidelines emphasize conducting trials in accordance with GCP and local regulatory requirements. Adequate monitoring of the trial is necessary to ensure ethical and scientifically sound practices, and data must be accurately recorded and analyzed to maintain integrity.
Independent ethics committee – before commencing a clinical trial, an independent ethics committee reviews and approves the protocol. The committee possesses the authority to halt the trial if it identifies any unethical or scientifically unsound practices during the trial.
Confidentiality – protection of subjects’ personal information is a vital aspect of clinical trials. Confidentiality must be maintained, and access to data should be restricted to authorized personnel. Robust data security measures are essential to safeguard the privacy of trial participants.
IC E6(R3) is a response to advances in technology, regulatory requirements and ethical standards:
The updated ICH E6(R3) introduces new considerations and recommendations to address emerging challenges in clinical research while promoting best practices. It also emphasizes a risk-based approach to trial design, monitoring, and quality management, factoring in complexity of the trial, potential impact on patient safety, and data integrity. As importantly, it highlights the importance of considering patient perspectives, diversity, and inclusion in clinical trial design and execution. These updates include:
Quality management: ICH E6(R3) introduces a new section on quality management, focusing on aspects such as risk management, data integrity, and training. This ensures that trials maintain a high standard of quality throughout their execution.
Innovative trial designs: The revised guideline offers additional guidance on the use of innovative trial designs, including adaptive trials and trials employing electronic data capture (EDC). This enables researchers to employ advanced methodologies while maintaining ethical and scientific integrity. The changes aim to incorporate learnings from innovative clinical trial designs and public health emergencies and encourage fit-for-purpose approaches.
Diversity of data sources: Recognizing the increasing use of diverse data sources such as electronic health records (EHRs) and wearable devices in clinical trials, ICH E6(R3) provides guidance on ensuring the quality and reliability of data derived from these sources. Much of the guidance in this area will be introduced as part of a new Annex (Annex 2) expected for release in 2024. The level of granularity around RWD/RWE guidance remains to be seen.
International harmonization: ICH E6(R3) aligns with other ICH guidelines, such as ICH E8(R1) on General Considerations for Clinical Studies. This alignment promotes the acceptance of clinical trial data across different regulatory jurisdictions, streamlining global research efforts.
At BC Platforms not only do we remain committed to stay updated on different iterations of guidelines, we also aim to support our customers in preparing for its practical implementation. When adopted, CH E6(R3) guidelines will provide a flexible, modern, and clear Good Clinical Practice for conducting ethical and scientifically sound clinical trials. R3 was designed to be media-neutral to enable the use of different technologies, encourage innovative clinical trial designs and technologies, and facilitate the inclusion of diverse patient populations.
Sources:
ICH HARMONISED GUIDELINE GOOD CLINICAL PRACTICE (GCP) E6(R3) Draft version for public consultation (2023). Available online here:https://database.ich.org/sites/default/files/ICH_E6%28R3%29_DraftGuideline_2023_0519.pdf; Last accessed: 12.Jul.2023
Final Concept Paper ICH E6(R3): Guideline for Good Clinical Practice (2019). Available online here: https://database.ich.org/sites/default/files/E6-R3_FinalConceptPaper_2019_1117.pdf Last accessed: 12.Jul.2023