Explaining the ICH GCP E6 (R3) Guidelines: Updates, Changes, and Next Steps

The International Council for Harmonisation (ICH) is standardizing drug and medicine development for greater safety and efficacy. Good Clinical Practice (GCP) guidelines for the industry date back to the 1990s, and there was an update to these in 2016. But this third revision (R3) is a real modernization of the guidelines as we know them today. There are new provisions addressing diversity in clinical trials and a greater emphasis on patient centricity. R3 also looks to address new methodological and technological advancements in clinical trials.

Fiona Maini, Principal Global Compliance and Strategy Director at Medidata, and Sharina Brewer, Director, Clinical Data Management at Quanticate—a biometric specialist global CRO—explore the latest Guidelines for Good Clinical Practice as established by the International Council for Harmonisation (ICH). They also discuss what ICH GCP E6 (R3) means for those in the clinical trial management industry and new technologies, patient safety, and data integrity. It’s essentially a renovation of the GCP guidelines, adding quality aspects to trials, risk and management measures.

Fiona: What are the main elements that jump out at you, Sharina?

Sharina: It’s important to note the greater emphasis on technological advancements—which the industry has been asking for—for a number of years. These new guidelines are essential for helping us broaden into this new technological era. The COVID-19 pandemic showed the industry the value of quick responses and reactions that don’t necessarily compromise on quality of patient outcomes.

Fiona: I agree it’s a great step forward and the differences in R3 are significant in structure and readability. R3 builds upon ICH E8(R1) the ‘General Considerations for Clinical Studies’. 

The regulators recommend reading R3 in conjunction with this and other guidelines which are related to clinical trial design and conduct, such as E2A clinical safety data management, E3 clinical study reporting, and E9 statistical principles, as they all work together to ensure comprehensive guidance across clinical research. R3 lays out eleven key principles. These principles include added emphasis around quality and risk management, and the reliability of results. There are three appendices on the roles of ethics committees, sponsors and investigators, and two annexes on data governance and patient centricity. What are your views on the latter, Sharina?

Sharina: We know the guidelines in totality are incredibly important, but the two annexes from a data perspective are what interest me the most. The first annex goes into data governance, which is key in today’s clinical trials environment—given the amount of data streams and threads we have to manage. Having a complete and robust governance structure to manage that is critical. The second annex focuses on patient centricity, which seeks to provide as much power to patients as possible. For example, reducing the administrative burden, enhancing engagement and improving the overall experience of trials for patients. It allows us to adopt and bring new technology to the forefront of clinical trials.

I believe these guidelines will give us a solid, structured framework and allow the industry to move forward, while embracing and implementing new technology.

“A greater harmonization of clinical trial partners across regions is another important outcome. The other aspect is efficiency, by leveraging technology to achieve patient centricity.”

– Fiona Maini, Principal Global Compliance and Strategy Director, Medidata

Sharina: I agree. In this industry we’ve been involved in numerous audits, and it’s not unusual to get conflicted feedback from auditors on how they expect technology to be used in trials. My hope is these guidelines can steer us all in the right direction. If we’re all working to the same standards, there will be a greater positive outcome for getting drugs to market.

Quanticate and Medidata have been working together since 2012 and one of the things we’re excited to see is the development of Medidata’s Clinical Data Studio (CDS) which allow us to aggregate data—we’re able to collate and manage health data, and that’s what we really mean when we refer to risk management.

Fiona: The new guidelines emphasize the necessity of audit trails within electronic data systems to ensure data integrity. Medidata’s CDS is designed to do this and it’s a powerful solution for optimizing audit trail reviews. It offers data management and quality tools, including AI-driven automation, to streamline workflows and ensure compliance with data integrity and regulatory standards. CDS improves the data experience for clinical researchers and it’s a key part of Medidata’s Study, Data, and Patient Experiences that center on the full ecosystem of clinical trials—from development through commercialization—providing the digital solutions to support sites and sponsors to unify clinical trial processes, reduce cost and accelerate therapy development.

Sharina: Yes, and it ties into one of the annexes concerning data governance. This is especially important given various labs have their own processes of managing and sharing data.

“Health data is only going to grow and get more complex, so having solid data structures is key to how we drive clinical trials of the future.”

– Sharina Brewer, Director, Clinical Data Management, Quanticate

Fiona: It’s important for us to monitor the regulatory environment shaping the new guidelines since it was adopted in January.

Sharina: At Quanticate, we created a taskforce to examine the draft proposals, their implications and broke down silos between our different work departments. For example, what works for our data management team is not the same as what works for our clinical operations or statistical analysis team. We had to be proactive to prepare for the new guidelines so that all of our capabilities and functions were represented.

Fiona: Do you believe there is now certainly a need for training and engagement across clinical trial organizations?

Sharina: Absolutely. Organizations need to show they have a plan to adjust to the updates that will affect the industry. We are also going to need to bring in management to support companies as they adapt to the new guidelines.

Fiona: Now the guidelines are final and adopted, there is a transition period and the guidelines take effect in the EU on July 23 this year (2025). Preparation across organizations is key.

Sharina: We’re also going to need open dialogue with our clients, such as pharmaceutical and biotech companies, to make the transition for any active clinical studies as smooth as possible. Another key area these guidelines will make us focus more on is risk and data quality management. We already know the importance of risk management, but these guidelines will provide us with a more robust quality management system, where the risks of studies can be assessed and tracked more efficiently. It will also enable us to help clients make more informed decisions regarding their data management.

Fiona: The section on data governance is an important addition, covering things from user access management and data capture to data transfer and vendor management.

Sharina: I agree, and I hope that when people adopt these guidelines, stakeholders will be more proactive and diligent with their processes and requirements at their own individual organizations, rather than passing over key processes like data capture and user access to external companies.

Fiona: There is additional emphasis on the role of ethics groups with these guidelines, with an even greater focus on the patient involved in trials and their needs which should be flexible. There is a greater push for these committees to understand newer technologies so that they can make more informed ethical decisions about patient involvement. What are your thoughts around that?

Sharina: It’s important to ensure patients actually benefit from technological innovations. That is at the heart of why we are in this industry. With the use of virtual technology and devices where patients can enter their own data, we can reduce the physical and time burdens on patients involved in trials. These guidelines will help facilitate that.

Fiona: These guidelines have been a long time coming and will be extremely positive for the industry. I am looking forward to seeing them rolled out. 

Sharina: I am looking forward to this as well—particularly as it will allow us to take more of a risk-informed approach to clinical trial design because of the emphasis on risk management. If we can aggregate data more efficiently with these guidelines, we can generate really succinct outputs of analysis, and ultimately improve patients’ experiences. I’m enthusiastic about Medidata's Clinical Data Studio to provide strong support to clinical researchers now and in the future.