ICH E6(R3) Finalization – An Action Plan for Clinical Compliance

Critical Impacts of ICH E6 (R3) and Business Process Updates for Clinical Trial Sponsors

The release of ICH E6 (R3) ushers in a new era of clinical trial management, focusing heavily on risk management, quality by design, and enhanced oversight. While the updated guidance emphasizes principles, its implementation requires sponsors to translate these into actionable business process updates. Below, we outline practical examples of how sponsor organizations now need to adapt their processes to align with ICH E6 (R3). 

1.  Risk-Based Quality Management Integration

Proactive Risk Identification and Assessment

• Description:  Tools and workflows must be implemented to identify critical-to-quality factors and assess risks during trial planning. This might involve establishing cross-functional risk assessment teams and leveraging centralized monitoring systems.
• Example:  A sponsor updates its trial planning process to include a “Risk Identification Workshop” during protocol design. The team evaluates trial aspects such as participant safety, investigational product risks, and data integrity.

Dynamic Risk Mitigation Strategies

• Description:  Risk management plans (RMPs) must be living documents, updated as new risks or insights emerge during the trial.
• Example:  A mid-trial safety signal triggers an update to the RMP, requiring additional monitoring for specific sites or participants.

Ongoing Training on Risk-Based Thinking

Sponsors need to train staff on risk-based thinking and integrate this mindset into existing quality management systems (QMS).  It is not enough to do this at the start of the study, but it must be an ongoing activity that evolves as the study progresses.

2. Oversight and Vendor Management 

Enhanced CRO Oversight

• Description: Sponsors must have formalized oversight processes, including routine vendor audits, performance metrics tracking, and escalation pathways.
• Example: A sponsor implements a quarterly CRO review meeting to assess adherence to trial protocols and address identified gaps.

Clear Role Allocation

• Description: All agreements with vendors must explicitly define responsibilities, ensuring tasks like data handling or safety reporting align with regulatory requirements.
• Example:  Update all contracts to include KPIs for vendors, such as adherence to data integrity processes and timelines for adverse event reporting.

Build or Refine Vendor Oversight SOPs

Sponsors need to create or refine Vendor Oversight SOPs and ensure sufficient internal resources to monitor vendor activities.

3. Quality by Design in Trial Planning 

Incorporate Quality into Protocol Design

• Description:  Quality considerations must be embedded into protocol design and execution workflows.
• Example: A sponsor mandates a “Quality by Design” checklist during protocol review to identify unnecessary complexities, such as redundant data collection points, and reducing participant burden.

More Stakeholder Engagement

• Description:  Engage with key stakeholders, including patients and healthcare providers, during trial design to ensure feasibility and meaningful outcomes.
• Example: Sponsors conduct virtual focus groups with patient advocates to evaluate the usability of remote data capture devices.

Establish Trial Planning Teams

Sponsors need to establish multidisciplinary trial planning teams, including operational, regulatory, and patient representation.

4. Data Integrity and Technology Governance 

System Validation and Compliance

• Description: Sponsors must ensure all computerized systems used in trials are validated and compliant with regulatory expectations.
• Example: A sponsor is using an IRT provided by a vendor.  The sponsor must qualify the vendor and ensure the validation of the system.  During the study, the sponsor should be performing oversight activities of data within the IRT.

Data Governance Processes

• Description:  New or updated policies for managing audit trails, data corrections, and system access.
• Example: Sponsors implement automated user access logs to ensure data access is restricted to authorized personnel.

Build or Develop a Data Governance Framework

Sponsors may need to partner with IT and compliance teams to develop and implement a robust data governance framework.

5. Risk-Proportionate Monitoring 

Hybrid Monitoring Models

• Description: Adopt hybrid monitoring approaches that balance on-site and remote monitoring based on identified risks.
• Example: Sites with historically high compliance rates are monitored remotely, while sites with higher risk profiles receive increased on-site visits.

Centralized Monitoring Systems

• Description: Leverage technology to flag trends or anomalies in real time needs to be a cornerstone of proportionate monitoring. 
• Example: A centralized dashboard highlights deviations in safety reporting timelines, prompting immediate follow-up with affected sites.

Upgrade Monitoring Technologies and Related Process

Sponsors need to invest in monitoring technologies and train staff on interpreting and acting on monitoring outputs.

6.  Participant-Centric Approaches

Simplified Informed Consent Processes

• Description: Update informed consent workflows to incorporate technology and ensure comprehension.
• Example: Sponsors adopt eConsent platforms that include multimedia components to explain trial risks and benefits in layman’s terms.

Diverse Population Inclusion

• Description: Update recruitment strategies to ensure trials reflect the real-world population intended to use the investigational product.
• Example: Recruitment teams work with community organizations to increase enrollment of underrepresented populations.

Revise Recruitment Workflows and Stakeholder Engagement in Trial Planning

These changes require sponsors to rethink recruitment workflows and engage new stakeholders in trial planning.

Conclusion

The ICH E6 (R3) guideline challenges sponsors to modernize their business processes to enhance risk management, quality, and oversight in clinical trials. While these changes may seem daunting, they also present an opportunity to drive greater efficiency and reliability in trial execution. 

At Just in Time GCP, we specialize in guiding sponsors through regulatory transitions. From updating risk management frameworks to optimizing eClinical systems, we provide the tools and expertise to help sponsors stay compliant and competitive in the evolving clinical trial landscape.  We support these transitions with a robust change management process that is critical to the success of this work.  Learn more about change management here.  

Ready to Amplify your Study’s Success by Simplifying Clinical Compliance?  Contact us to learn how Just in Time GCP can help your organization implement these essential updates and more.