Collaborative Accountability for Both Sponsors and Sites
In an ever-evolving clinical trial landscape, the final ICH E6(R3) guideline brings a new level of operational rigor and shared accountability for both sponsors and sites. This forward-looking framework builds on ICH E6(R2), heightening emphasis on formal documentation, risk-based oversight, and the integration of digital technologies—all while ensuring the safety and well-being of trial participants.
Below, we examine the crucial updates under ICH E6(R3) and the practical implications for site readiness. Each section is accompanied by direct references to the final guideline (adopted 06 January 2025) for ease of verification and compliance.
Investigator & Resource Readiness
Under ICH E6(R3), the principal investigator (PI) must be qualified (by education, training, and experience) and ensure delegated team members are similarly prepared and competent. Documented training and delegation records are required, creating an auditable trail of who performed which tasks.
Practical Implications
- Maintain up-to-date CVs and training logs for each individual performing trial-related tasks.
- Confirm each delegated staff member has the expertise and time to carry out their assigned responsibilities.
Resource Availability & Task Delegation
While resource allocation has always been integral, ICH E6(R3) clarifies that delegating tasks to qualified individuals is acceptable—provided every assignment is carefully documented, with the PI retaining ultimate oversight and accountability.
Practical Implications
- Keep a detailed delegation log (paper or electronic) showing who is responsible for which tasks.
- Ensure you have clearly defined SOPs for training, supervision, and ongoing oversight of staff and sub-investigators.
Enhanced Compliance & Data Integrity
ICH E6(R3) places a higher premium on robust data governance throughout the data life cycle. Sites must demonstrate version control, track changes via audit trails, and secure electronic systems to support the reliability and traceability of trial data.
Practical Implications
- Adopt or update SOPs to ensure data are captured, reviewed, and corrected in a traceable manner (audit trails).
- Validate or confirm validation of any computerized systems in accordance with Section 4.3 (Computerised Systems).
Risk-Based Oversight & Adaptive Monitoring
Under ICH E6(R3), sponsors and sites share responsibility for identifying potential risks early and adjusting oversight accordingly. While third-party support (e.g., central monitoring) is permissible, the PI and sponsor remain ultimately responsible for patient safety and data quality.
Practical Implications
- Collaborate with sponsors to develop a tailored monitoring plan.
- Focus monitoring resources on critical data and processes that have the highest impact on participant safety and overall study outcomes.
Digital Integration & IP Management
Electronic systems for data capture, eConsent, and investigational product (IP) management are now central to compliance. ICH E6(R3) allows sponsors to share IP accountability with sites, but robust version control, auditing, and user-management processes must be maintained.
Practical Implications
- If using eConsent, ensure local regulations allow it and that systems are validated (per Section 4.3).
- Set transparent processes for IP receipt, storage, dispensing, and return, with rigorous documentation at each step.
Key Takeaways for Sites & Sponsors
Stronger Focus on Formal Training
- Investigators and delegated staff must have documented qualifications and role-specific training.
- References: Sections 2.1, 2.3
Resource & Delegation Documentation
- Each task and the person executing it must be clearly logged.
- References: Sections 2.3, 3.2, 3.7
Risk-Based Compliance & Monitoring
- Sponsors and sites must tailor oversight to the protocol’s complexity and specific risk profile.
- References: Sections 3.9, 3.10, 3.11.4
Digital Integration & Data Governance
- E-consent, validated computerized systems, and thorough version control are required.
- References: Sections 2.8 (Informed Consent of Trial Participants), 4 (Data Governance)
Safety & Accountability
- Delegation of monitoring responsibilities is permitted, but the PI remains ultimately responsible.
- References: Sections 2.7 (Participant Medical Care and Safety Reporting), 2.10, 3.15
By aligning site operations with ICH E6(R3), sponsors and sites not only meet regulatory requirements but also cultivate a proactive culture of safety, risk management, and consistent data integrity.
