Key Findings from the ICH E6 (R3) Final Guideline

The ICH E6(R3) Final Guideline is a major step forward in modernising Good Clinical Practice (GCP) to keep pace with evolving trial designs, methodologies, and technologies. The finalised guideline was released in January 2025 and covers a wide range of topics. In this blog I will look at a selection of key updates and their implications for clinical trials.  

Quality by Design and Risk-Proportionate Approaches 

A big takeaway from ICH E6(R3) is its emphasis on quality by design (QbD) and adjusting trial oversight based on risk. The idea is simple: figure out what’s most important early on and focus your efforts there. This approach helps sponsors and investigators design trials that are simpler and more efficient, without cutting corners on participant safety or data quality. This move really does encourage trials to balance innovation with practicality, ensuring efforts are directed where they matter most. 

Decentralised Trials and Real-World Data 

Within the finalised guidelines there is a new focus on decentralised trials (DCTs) and the use of real-world data (RWD), which is a real game-changer within clinical research. Whether collecting data from electronic health records (EHRs), claims databases, or wearables, the guideline highlights the importance of ensuring data privacy, validation, and integrity. It is also worth pointing out that this type of data falls within the scope of long-term data retention requirements. More details can be found in our ICH E6 (R3) Annex 2 Blog 

Identifying Essential Records 

In ICH E6 (R2), the term “essential records” wasn’t mentioned at all but in R3, it appears throughout, reflecting a broader scope of what must be retained. The finalised guidelines now outline 54 categories of essential records (you can find more details in our ebook ). 

So, what exactly qualifies as an essential record in clinical trials? Think of them as the foundation of your trial, covering everything from source data and audit trails to metadata in any format. These records tell the full story of your study, capturing everything from routine trial management to major decisions that could impact outcomes. 

Why does this matter? These comprehensive records provide concrete evidence that sponsors and investigators have followed Good Clinical Practice (GCP) and met all regulatory requirements.  

Data Integrity and Long-Term Retention  

Another key highlight of the guidelines is centred around data integrity and long-term retention.  essential records, whether they’re from automated instruments, wearables, or digital health technologies (DHT’s), need to be accessible, readable, and secure for both internal audits and regulatory review. Ignoring regulations like Appendix C2.6 and EC 536/2014 Article 58 can lead to non-compliance issues. ICH E6 (R3) places the responsibility for data retention on sponsors and investigators, however it is clear that the sponsor, must oversee how the data is managed. 

Data integrity and long-term retention go hand in hand, and the key to maintaining both is simple: plan ahead. Sponsors should start thinking about data preservation from the v

ery beginning, addressing potential challenges like proprietary formats, vendor lock-in, and system dependencies. This reduces risk and ensures the data stays usable and accessible for as long as it is needed. 

Consolidating Data 

With the growth of technology, clinical trials have become very complex, it’s not unusual to see multiple systems being used throughout a single trial. Now, according to ICH E6(R3) Section C.2.4, sponsors and investigators need to keep track of where all their essential documents are stored. They also need to make sure their storage systems can properly identify documents, track version histories, and allow for quick searches and retrieval. 

But here’s the real challenge: as more and more live systems are used in trials, and data gets migrated between them, keeping accurate inventories becomes difficult. That’s why it makes more sense to consolidate data in a long-term archive for completed trials. It makes document management so much simpler and helps ensure you’re staying compliant with regulations. 

Computerised Systems 

In the finalised version of the guidelines, we can see a whole section (4.3) dedicated to computerised systems, which shows that the guidelines are evolving with the big shift to digital records. This section covers a range of topics from training to technical support.  

When we look specifically at digital archiving it is not a case of selecting any system. The guidelines are clear: your systems need to be fit for purpose, and you need to think carefully about the strengths and weaknesses. Potential vendors need to understand exactly how their system will be used and what regulations they need to follow. Arkivum published a blog in July last year titled Understanding Validated Archiving Systems in Pharma and Life Sciences this provides more considerations when selecting an archiving system.   

If you would like further information, there is also a recent blog which explains the different types of archiving systems and how they differ.  

Arkivum 101 Series: Preservation Versus | Arkivum 

Summary 

The ICH E6(R3) guideline reflects the evolution of clinical trials, from integrating RWD to designing decentralised studies. It strikes a balance between innovation and compliance, providing a flexible framework that supports modern trial methodologies while safeguarding participant rights and ensuring reliable data. 

You could argue that it is also a call to action for sponsors and investigators to adapt, plan thoughtfully, and embed quality at every stage of the trial process.  

If you would like to read more about the finalised ICH E6 (R3) guidelines, our eBook can be found here