New Strategies for Effective Sponsor Oversight in Clinical Trials

The 3rd Clinical Quality Oversight Conference, run by Momentum Events in May of 2024, opened with a critical presentation by Dawn Niccum, Executive Vice President of Quality Assurance & Compliance at inSeption Group. Niccum’s insightful discussion revolved around the ICH E6(R3) guidelines, emphasizing the importance of sponsor oversight in clinical trials. Her presentation highlighted the evolving responsibilities of sponsors and provided practical strategies for ensuring compliance and enhancing the quality of clinical trials.

Sponsor Responsibilities and Documentation

Niccum emphasized that while sponsors may delegate activities to service providers, they retain ultimate responsibility for the trial’s outcomes. This necessitates rigorous documentation to prove sponsor oversight and compliance. Niccum’s mantra, “If it wasn’t documented, it wasn’t done,” highlights the need for detailed records. She explained that ICH E6(R3) introduces a new section on sponsor oversight, requiring comprehensive documentation of all oversight activities, from data monitoring to managing deviations. Niccum provided examples of audits revealing gaps in documentation, such as unrecorded meetings and unreviewed trip reports, which can lead to issues during inspections.

Niccum also stressed documenting the reasons and methods behind decisions, especially those affecting participant rights, safety, and data integrity. For example, when using a Data Monitoring Committee (DMC), sponsors should document the qualifications of its members, the rationale for their selection, and the outcomes of their assessments. She emphasized the need for clear and timely escalation processes, illustrating how issues identified during monitoring should be documented and escalated to ensure prompt resolution. Niccum coined the term “inspection steady,” meaning the Trial Master File should always be prepared for regulatory scrutiny. These practices, she argued, are essential for ensuring transparency, accountability, and the success of clinical trials.

Risk Management and Quality by Design

Niccum emphasized the importance of integrating risk management principles into trial oversight, highlighting the need to identify and document “important” deviations rather than merely categorizing them as critical, major, or minor. This aligns with the quality-by-design philosophy, which focuses on critical to quality (CTQ) elements from the outset of the protocol design phase. Niccum elaborated by discussing the oversight of temperature-controlled investigational products (IPs) in decentralized clinical trials. The transport and storage of temperature-sensitive IPs, such as those used in cell and gene therapies, require precise control to maintain efficacy. Any deviation from required conditions can severely impact trial results and necessitate robust risk management plans to document how these deviations are identified, managed, and mitigated.

Niccum also highlighted the importance of anticipating risks during the trial design phase. She provided examples involving decentralized clinical trials, where components like home health visits and remote monitoring introduce additional risks. Sponsors can mitigate these by using Electronic Data Capture (EDC) systems to monitor IP conditions in real-time and promptly address and document deviations. Another example involved autologous cell and gene therapies, which require meticulous handling and monitoring due to their personalized nature; incorrect dosing or handling errors can critically impact the therapy’s effectiveness and the trial’s success.

Service Provider Oversight

Niccum emphasized the critical steps sponsors must take to ensure compliance, including verifying the qualifications and training of service provider teams, validating their systems, and maintaining thorough documentation. She shared a case study from an FDA symposium where a sponsor’s failure to oversee a service provider properly resulted in improper dosing and the enrollment of ineligible subjects, compromising the trial’s integrity. The service provider also missed scheduled visits and failed to identify site non-compliance, leading to ineffective corrective actions. This example highlights the importance of continuous monitoring and timely intervention.

Niccum recommended rigorous qualification and training verification to avoid such issues, validate systems, and maintain clear communication channels. She advised using tools like Clinical Trial Management Systems (CTMS) to efficiently track monitoring reports and issue logs. Niccum also stressed the need for direct access to essential records, such as the Trial Master File (TMF), from the beginning to enable continuous sponsor oversight. Regular audits and in-process reviews provide insights into the service provider’s performance, allowing for necessary adjustments. These practices are crucial for ensuring the success and reliability of clinical trials, ultimately protecting their integrity.

Practical Implementation Strategies

Niccum provided practical strategies for implementing the ICH E6(R3) guidelines. She advised sponsors to:

• Establish Oversight Mechanisms: Develop comprehensive oversight plans that include regular monitoring visits, data reviews, and clear escalation processes for addressing issues.
• Utilize Direct Access to Records: Ensure sponsors have direct access to TMFs, EDC systems, and Interactive Response Technology (IRT) from the outset.
• Maintain Clear Communication: Keep detailed meeting minutes and ensure all decisions and actions are well-documented and accessible.
• Adapt Training Methods: Regularly assess and update training programs to ensure all team members are adequately prepared for their roles.

Summary

In closing, Niccum emphasized that proper documentation and proactive risk management are crucial to effective sponsor oversight. She encouraged organizations to start small, prioritize critical areas, and gradually expand their oversight processes. As the industry prepares for the full implementation of ICH E6(R3) in 2025, her guidance provides a clear path for sponsors to enhance compliance and ensure the quality of their clinical trials.

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