At the Momentum Events’ ICH E6 R3 Clinical Trials Virtual Conference, which took place in early September 2023, industry stalwarts took center stage to demystify the differences between the new draft ICH E6 R3 guidance and the previous R2 version as well as TMF compliance. As these regulatory frameworks become more central to the world of clinical trials, the insights from such seasoned professionals are invaluable. Their discussions shed light on the pressing challenges and potential pathways forward, serving as a beacon for sponsors, CROs, and other key stakeholders.

Managing Data Outside Investigational Sites in Clinical Trials

The rapidly changing landscape of clinical trials, with more data sources emerging, poses unique challenges. Speakers stressed that data might come from various avenues such as direct eSource, home health visits, or even central readings, which aren’t always stationed at the investigational sites. Given these varied sources, how do we ensure the integrity and accuracy of this data? Speakers questioned, “How is that data outside the investigator site being fed back to the investigator?” Especially when some of this data, like PK results, might be blinded to prevent bias. The conversation highlighted the need for robust data management strategies for these diverse data streams.

Monitoring Reports: Ensuring Integrity and Timely Action

The speakers brought forth the critical nature of monitoring reports in clinical trials. She underscored the importance of including summaries of significant findings and promptly addressing unresolved issues. Speakers cited instances where monitoring reports had issues open for numerous visits, spanning months. They asked the audience, “How often have you seen unresolved issues in monitoring reports?” Highlighting the necessity for an escalation process, they emphasized the need to retrain sites and address gaps promptly, ensuring the integrity of the trials.

Service Provider Oversight

There was a discussion on the intricacies of service provider oversight, drawing insights from the ICH E6 R3 guidance. The speakers underscored the importance of meticulous documentation, from investigational product details to trial-specific computerized system validations. The role of committees, notably the Independent Data Monitoring Committee (IDMC), was highlighted, emphasizing the significance of detailed meeting minutes that capture key decisions and deviations. A key takeaway from the discussions was establishing clear quality agreements or contracts with service providers. These agreements, the speakers noted, are foundational in delineating responsibilities, ensuring compliance, and maintaining the highest standards of quality throughout the clinical trial process.

Access, Validation, and TMF Compliance Validation in the Age of Digital Trials

One topic that resonated with the audience was digital access and validation. In an age where trials are increasingly digitized, and information is stored electronically, questions arise about the accessibility and validation of these systems. For instance, can an inspector directly access a Trial Master File (TMF)? The speakers emphasized the importance of having systems that are both validated and capable of restricting access based on roles. They also discussed the challenges of providing inspectors direct access to certain systems while maintaining privacy and confidentiality to maintain TMF compliance.


The conference vividly illustrated the intricacies of clinical data management in today’s dynamic clinical trial environment and the ongoing challenges of staying compliant with changing regulations and guidances. As discussions meandered through data management challenges, the significance of timely monitoring, vendor oversight, and the nuances of digital access, it became clear that the industry is at an inflection point. With experts leading the charge, the future promises a more streamlined, efficient, and compliant landscape for clinical trials and TMF compliance.

For more information on ICH E6 R3 guidance, check out the full-day workshop at the upcoming 2nd GCP Inspection Readiness Hybrid Conference on December 4-6 in Philadelphia.  Register with discount code CVAN to save 15% AND receive complimentary access to the recorded presentations from September 7, 2023, ICH E6 R3 guidance virtual event featured in this article.