The ICH E6 Good Clinical Practice Guideline is a cornerstone in today’s guidance for Good Clinical Practice (GCP). The guidance addresses an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. With the goal to provide a unified standard for all ICH regions to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions. As of March 2021, the newest revision R3 is in a draft state, so we took the opportunity to run down the important aspects of Data Integrity and Data Governance inside the first iteration of the ICH E6 GCP principles.
The Appropriate Management of Information
Before we address the aforementioned aspects, it is important to know that the basic guideline structure is going to change with the revision 3. ICH E6 R3 will be composed of an overarching principles document (which we cover here), Annex 1 (addressing interventional clinical trials), and Annex 2 (providing any needed additional considerations for non-traditional interventional clinical trials). The overarching principles document and Annex 1 will replace the current ICH E6 R2.
In 2019, the concept paper published by the ICH mentioned the application of GCP principles to the very diverse data sources of clinical trials as one central goal of the revision. The draft encourages the use of innovative digital health technologies to keep clinical trials in line with advancing technologies, which then lead to an increasing diversity of data sources. As per the usual risk-based approach, the processes involving those technologies should be proportionate to the risk and the importance of the data being collected. Therefore, many focal points are set on the assurance of reliable results and in awareness of protecting data privacy.
Although the principles document does not explicitly contain Data Integrity aspects (which were part of ICH E6 R2, Chapter 4.9), it is to assume that all this information will be found in the upcoming Annex 1.
Still, Chapter 10 is dedicated to the generation of reliable results, which in turn are supported by known Data Integrity and Data Governance fundamentals:
- The quality of the information generated should be adequate.
- Systems, tools and processes should be adequately controlled (means: validated) in order to be fit for the intended use.
- Including IT systems, the importance of IT security and user management is a prevalent aspect.
- Processes must provide controls to ensure Data Integrity, Traceability and Protection of Data
- Clinical Trial information should be secure and available for regulatory authorities throughout the retention period. It is critical to allow reconstruction of the conducted trial to ensure reliable results.
- All principles apply irrespective of the media used for documentation and information.
Interestingly, a definition about results, information and data is given that seems adopted from the widely known “Pyramid of Wisdom”, but with the term “Results” instead of “Knowledge”. The ICH E6 principles document states:
“For the purpose of this guideline, the term “information” reflects meaningful organization and processing of data and documentation and “data” reflects measurement and assessment of variable parameters relevant to specific outcomes. The “results” are a composition of organized and fit-for-purpose information.”
The 3rd revision of the ICH E6 Good Clinical Practice sets one key point on the importance of reliable results and information. Albeit being already represented in ICH E6 R2 in terms of an updated management of electronic records, an increasing focus on clinical data and information was observed, as was covered by the effort to assess data integrity in global trials, published in the joint paper of the U.S. FDA and MHRA. This includes the importance of validated systems and processes according to the EMA Sponsor Notice and their “GCP matters” questionnaire. The statement that Data Integrity is of outstanding importance during the early phases of the product lifecycle is also represented by the new U.S. FDA Pre Approval Inspection Program.
Finally, the principles guidance emphasizes the parallelism between GCP and GMP as seen in our small illustration. It clarifies that, for the production of investigational products, the same standards known for GMP have to be applied, which of course also applies all the important aspects of Data Integrity.
Since this publication is part of the overarching process of the ICH GCP Renovation initiative, we are excited about the publication of Annex 1 & 2, as well as to see the guidelines standing together in linkage with the modernized ICH E8.
Authored by Julian Oberle, Dr. Elham Abdollahi-Mirzanagh and Dr. Ulrich Koellisch