Resources:
- [email protected]: Use this email to let us know what you want to hear about.
Today we welcome Mélanie Pomerleau, Vice President of Quality and Compliance at Indero, who brings over 25 years of experience in the pharmaceutical and biotechnology sectors. Recognized as a leader in quality and compliance, Mélanie Pomerleau offers deep expertise in regulatory strategy, inspection readiness, and operational excellence. The discussion will center on the forthcoming ICH E6 (R3) guideline revision and its implications for stakeholders in clinical research as the implementation date approaches in July 2025.
Key Updates in R3
One of the most evident changes in the upcoming ICH E6 (R3) revision is the complete restructuring of the document. A new appendix format has been introduced, requiring adaptation from all stakeholders, including auditors, as even the reference numbers for each article have been modified. Familiarity with this new structure will be essential moving forward.
Another significant update involves the modernization of Good Clinical Practice principles. These now emphasize quality by design, fit for purpose, and proportionality. These concepts are embedded throughout the revised guideline and represent the foundation of the new approach to conducting clinical trials. Greater focus is now placed on identifying and managing critical aspects of a study rather than striving for perfection across all data points. This shift encourages thoughtful consideration of both methodology and rationale.
The revision also promotes enhanced patient centricity. Early patient engagement is encouraged not only in the planning of drug development programs but also in protocol design. This inclusion allows for valuable patient insights, particularly regarding the feasibility and burden of study participation. For example, the complexity of visit schedules and procedures can be reassessed to improve accessibility and reduce participant strain. Ethical considerations, such as the clarity and relevance of informed consent documents, also benefit from patient input.
Support for innovative study designs is another key advancement. The guideline now explicitly acknowledges adaptive designs and the integration of emerging technologies. Decentralized trial methods, such as remote consent and home nursing, which gained prominence during the pandemic, are now formally recognized. Previously, these approaches were often treated as planned protocol deviations, resulting in administrative burdens. The new framework legitimizes these methods, allowing for greater flexibility and responsiveness in trial conduct.
Finally, a major addition to the guideline is the introduction of an entirely new section dedicated to data governance. This section underscores the importance of robust data management practices in ensuring the integrity and reliability of clinical trial outcomes.
Understanding Data Governance
To put it simply, data governance refers to the implementation of appropriate controls to ensure data integrity throughout the entire data lifecycle—from creation to eventual destruction. This encompasses a wide range of considerations, including data security, privacy, quality control, archiving, and platform validation.
For example, a robust governance framework should include a clear hierarchy of authority for platform validation. It should also define how platforms are administered, particularly in terms of user access. Different user roles—such as read-only and administrators—require tailored training. These role assignations must be clearly documented and enforced.
Access management is another critical component. Regular checks should be conducted to ensure that only authorized individuals can access specific data, and that access levels are appropriate for each role. Data quality must also be maintained through systematic data cleaning, monitoring, and, where applicable, auditing SOPs.
Inspection and Audit Trends with R3
Over the past several years, inspectors in Canada and other regions have received extensive training on data integrity systems and have significantly increased collaboration efforts. As a result, many have adopted similar approaches to data governance. However, a noticeable shift has occurred more recently, particularly following the release of the draft ICH E6 (R3) guidance.
Recent inspections by Health Canada have revealed a consistent pattern of observations related to platform access. In several cases, access was either granted too early or removed too late or even given without proper delegation. Inspectors now place greater emphasis on verifying access controls and timing.
Another emerging focus involves electronic medical records (EMR). Although these systems have been in use for many years, regulators now require supporting documentation that validates the platforms—an expectation that was not previously enforced. In the past, simple confirmation of access sufficed; today, validation evidence is essential.
Audits conducted by sponsors and regulatory authorities have also evolved. Historically, sponsors concentrated on system validation and documentation. However, current audits increasingly request detailed information about platform oversight, including governance structures and documentation practices. One notable development is the growing emphasis on audit trail review. While this practice was previously more common among larger organizations, it is now explicitly addressed in the revised guideline. Failure to conduct audit trail reviews may result in formal observations during inspections.
Standout Changes in R3
The ICH E6 (R3) revision introduces numerous updates, but one particularly noteworthy aspect is the reinforcement of accountability across all stakeholders. The long-standing notion that “everything is under the responsibility of the sponsor” is no longer sufficient. While ultimate responsibility still lies with the sponsor, the revised guideline places greater emphasis on proactive issue management involving all parties, including third-party vendors and platform users.
For instance, if a platform user identifies an issue—even without being directly responsible for implementing the system—there is now an expectation to raise the concern and take appropriate action. This evolution builds upon the accountability introduced in the R2 revision and strengthens it further in R3.
Several smaller yet impactful changes have also been introduced. One example is the clarification that study-specific training may not be required for site staff performing routine tasks. This seemingly minor adjustment provides much-needed flexibility, especially given the increasing complexity of clinical trial operations. It also helps reduce unnecessary burden and allows for more efficient organization of site responsibilities.
Another significant change involves the concept of essential documentation. Previously, a clearly defined appendix listed essential documents required before, during, and after a trial. While this approach was straightforward, it no longer reflects the complexity of modern, often digital, trial environments. The revised guideline now refers to “essential records” and “potential essential records,” aligning more closely with the structure of electronic trial master files (eTMF). This shift acknowledges that essential documentation extends beyond a fixed list and encompasses the full scope of study archiving.
Additionally, the revision introduces new terminology that reflects the growing use of digital platforms. Terms such as data acquisition tool and metadata have been added, highlighting the importance of electronic systems in clinical research. Another meaningful change is the replacement of the term trial subject with trial participant. While subtle, this change underscores a more patient-centric and inclusive approach, recognizing participants as active contributors to the research process rather than passive subjects.
Impact on Sites, Sponsors and CROs
At first glance, the revised document structure may appear overwhelming due to the extent of the changes. However, these updates have been evolving over several years. For example, the COVID-19 pandemic accelerated the adoption of decentralized approaches, and the release of guidelines such as ICH E8 emphasized broader and more inclusive patient participation. These developments laid the groundwork for the current revision.
In addition, the release of the draft ICH E6 (R3) guideline provided ample opportunity for public comment and industry engagement. With proper planning and a robust quality system in place, the transition should not require a complete overhaul of existing processes. For sponsors and CROs, only minor adjustments may be necessary to align with the new expectations.
That said, investigator sites may face greater challenges, particularly in relation to computerized systems. Many sites rely heavily on vendor-provided solutions and may not be deeply involved in platform management or fully understand the implications of system use. This limited engagement can create compliance risks.
To address this, Clinical Research Associates (CRAs) will need to deepen their understanding of these systems to effectively assess site compliance and provide appropriate support. Familiarity with platform governance and validation will be essential to ensure that all parties meet the expectations outlined in the revised guideline.
Preparing for the July 2025 Implementation
Awareness of the ICH E6 (R3) revision remains surprisingly limited. A recent article highlighted survey results indicating that a significant portion of respondents were either unaware of the new guidelines or unfamiliar with its details. This lack of awareness is concerning, as understanding the changes is the essential first step toward compliance. For those listening to this discussion, this serves as a timely introduction.
The recommended starting point for organizations is to conduct a gap analysis. This standard approach involves reviewing current systems and processes to assess alignment with the revised guideline. Once gaps are identified, prioritization should follow—focusing first on the most critical areas. Not all changes require immediate implementation, and attempting to address everything simultaneously may prove overwhelming. A phased, risk-based approach is advisable.
Training is another essential component of successful implementation. Team members should receive a clear overview of the most significant changes and their implications for day-to-day responsibilities. While in-depth knowledge may not be necessary for all roles, a foundational understanding is crucial.
In addition to guideline-specific training, education on data integrity is strongly recommended. As a central theme of the revision, data integrity, particularly in the context of electronic data, is not always well understood. Comprehensive training in this area would benefit all stakeholders and support consistent, compliant practices across the organization.
What to Expect for R4?
It is likely that work on future revisions is already underway. The gap between the original ICH E6 guideline and the R2 revision spanned two decades, an interval of 20 years. The transition from R2 to R3, however, occurred within just 10 years, suggesting that the pace of updates is accelerating. A five-year interval for the next revision would not be surprising.
Looking ahead, artificial intelligence (AI) and machine learning are expected to play a significant role in future updates. These technologies are advancing rapidly and will likely influence how clinical trials are designed, conducted, and monitored. However, organizations should not wait for the next revision to begin addressing these emerging areas. Proactive engagement with AI and digital innovation is essential, as these developments are already reshaping the research landscape.
As we conclude another illuminating episode of Phase Forward, we find ourselves at the crossroads of science and progress. Remember that behind the jargon and statistics, lies stories of unwavering commitment, meticulous observation, and the pursuit of evidence that shapes our understanding of health and disease. Stay at the forefront of knowledge and innovation and follow Phase Forward on your preferred platform. My name is Valerie Coveney. Thank you for joining us. Until next time.
