The latest ICH E6 (R3) guidelines could transform how clinical studies are built and operated.
The updated ICH E6 (R3) guidelines introduce a range of critical changes aimed at modernizing clinical trials. These updates refine the way trials are designed and executed, with a focus on the increasingly vital role that technology plays in ensuring compliance, data integrity, and patient-centric outcomes.
The updates to guidelines were reorganized into a principles and objectives section, with Annex 1 (interventional trials) coming into legal effect on July 23 2025 and Annex 2 (guidance on decentralized trials and real-world data) expected to be finalized later in the year.
“What the updated guidelines are really trying to do is put more encouragement around adopting risk-based practices,” explains Isaac Erickson, vice-president of consulting services at Zelta. “For eCOA and ePRO, they’ve made some pretty major changes to data privacy – and also some changes to how we’re expected to collect data remotely.”
Here’s what CROs and sponsors need to know about these updated guidelines for their clinical trials.
What are the key updates in ICH E6 (R3)?
Central to the updated guidelines is Quality by Design (QbD), ensuring that quality is proactively embedded into the clinical trial’s architecture from the beginning to significantly improve efficiency and reduce costly reworks.
Another cornerstone of the ICH E6 (R3) update is patient-centricity. Enhanced participant engagement is now being explicitly encouraged through technologies such as wearables and virtual healthcare tools.
Previously, risk-based quality monitoring (RBQM) was adopted inconsistently across the industry. The updated ICH E6 guidelines mandate a systematic approach to risk management, providing explicit strategies to identify, evaluate, and mitigate potential risks proactively. According to ACRO’s 2025 RBQM survey, 96% of trials now include at least one RBQM component (vs just 53% in 2019), with centralized monitoring and remote oversight becoming standard practice1. The survey also found that while Source Data Verification (SDV) is being significantly reduced, Source Data Review (SDR) remains prevalent, often serving as a comfort layer when centralized monitoring is in place2.
Despite this progress, a surprising number of trials still rely on 100% SDV and SDR, highlighting room for further optimization.
The updates also elevate the role of data governance and integrity, requiring robust compliance mechanisms and confidentiality protections. Detailed audit trails are now essential, requiring complete traceability of every data point and action taken within trial systems.
“Technology can outpace governance very, very quickly,” adds Erickson. “So, I think this was a needed update.”
The role of CDMS platforms in ICH E6 (R3) compliance
Clinical data management software is critical to complying with these updated standards, with integrated CDMS platforms now providing comprehensive solutions supporting QbD, RBQM, and patient-centric objectives.
By integrating eConsent, patient-reported outcomes, risk-based monitoring, and audit trails into a single unified platform, these capabilities can significantly simplify trial management.
Integrated CDMS solutions also facilitate smoother communication and coordination between stakeholders, enabling faster, data-driven decision-making – all increasingly crucial for maintaining oversight and regulatory compliance.
For sponsors and CROs, the updated ICH E6 guidelines mean greater operational efficiency, reduced costs, and better data-driven decision-making.
“When systems work together from the start, trials run more smoothly. It’s not just about efficiency, it’s about creating space for better decisions and better outcomes,” says Walker Bradham, senior director of product management and design at Zelta.
Participants also see significant benefits from these platforms, with digital engagement tools reducing participation barriers, enhancing accessibility, and improving the overall trial experience. With fewer site visits required and more efficient remote data collection, participants experience reduced inconvenience and greater satisfaction.
“Technology like wearables and ePRO makes trials more humane, it meets people where they are,” Bradham notes. “And with AI and real-time data, we’re not just reacting to problems, we’re staying ahead of them.”
The updates also support trial sites by simplifying data collection and reducing administrative burdens, enabling clinical staff to focus more directly on participant care and data analysis. Consequently, stakeholders at all levels – including participants, trial sponsors, CROs, and sites – can experience a more cohesive and efficient clinical trial environment.
Zelta’s alignment with ICH E6 (R3)
Clinical data management platforms such as Zelta exemplify the ICH E6 (R3) vision of proactive quality integration, enabling sponsors and CROs to seamlessly incorporate quality into the trial design from the beginning.
“Platforms like Zelta allow organizations to build trials around the tools from the outset, streamlining complex trial builds with flexibility, reusability, and ease of use,” adds Erickson.
Zelta is a cloud-based eClinical platform that boosts engagement and retention in clinical trials by offering flexible purpose-built tools, ensuring sites and participants stay informed and involved through the trial. Its built-in eConsent and ePRO capabilities support more accessible and transparent participation. Real-time support features such as instant chat quickly address participant and site questions, enhancing confidence and trust. And regular feedback loops help participants feel valued.
Zelta’s real-time reporting and analytics align closely with the ICH E6 (R3) emphasis on proactive, risk-based monitoring. By identifying issues as they arise, the platform supports faster, more informed responses, ensuring that trials remain compliant, efficient, and aligned with regulatory expectations.
Furthermore, Zelta’s data governance system provides a unified experience across CDMS, ePRO/eCOA, and RTMS to significantly simplify clinical data management. Having all clinical data consolidated in one system doesn’t just reduce trial complexity, it also enhances ICH E6 compliance.
Beyond just meeting the requirements of today’s ICH E6 guidelines, the Zelta platform’s capabilities are designed to anticipate future trends in clinical trial design.
“The next five years will see greater adoption of hybrid and decentralized trials, enhanced by real-time monitoring and refined patient-centric designs,” predicts Bradham. “And these are all factors we take into consideration with each update made to our platform.”
For sponsors and CROs aiming to stay competitive, embracing a CDMS platform like Zelta’s that is ahead of the game on both these capabilities and ICH E6 guidance is essential for achieving supporting regulatory compliance, risk management, and optimal trial outcomes.
To explore how Zelta can support your organization’s clinical data management needs, download the document below.
References:
- https://www.acrohealth.org/rbqm-summary-report/
- https://www.acrohealth.org/wp-content/uploads/2025/06/ACRO_2025-RBQM-Report_Final-062425.pdf
