The updates to ICH E6(R3) reflect the increasing complexity of clinical trials by establishing more explicit requirements for service provider management.
While sponsors and investigators have always been accountable for trial activities, the new guidelines provide clearer expectations for vendor oversight in an ecosystem increasingly dependent on specialised service providers.
Understanding these requirements is essential for compliance and also for efficient clinical trial delivery.
Below I have highlighted the my top 8 critical service provider management requirements under ICH E6(R3) and how to implement them effectively.
1. Document Transferred Activities Precisely
What: Create comprehensive agreements clearly defining all activities transferred to service providers, with explicit documentation of activities retained by the sponsor.
Why: ICH E6(R3) states that activities not specifically documented as transferred remain the sponsor’s responsibility. Clear documentation prevents accountability gaps and establishes the foundation for proper oversight.
How: Develop detailed responsibility assignment matrices (RACI) as part of vendor agreements.
Example:
a data management transfer might include specific documentation of database design ownership, edit check implementation, query resolution processes, and data validation responsibilities—with clear delineation of which tasks are transferred and which remain with the Sponsor.
2. Establish Clear Sponsor-Investigator Responsibilities
What: Document the delineation of responsibility between sponsor and investigator regarding service provider selection, oversight, and management.
Why: ICH E6(R3) emphasises that investigators retain final decision authority for providers supporting investigator activities, even when Sponsors recommend providers. This ensures appropriate site-level accountability and autonomy.
How: Create standardised information packages for investigator review of potential service providers, along with formal documentation of investigator assessment and approval.
Example:
when proposing a central lab to investigators, provide detailed capability information, but maintain a formal process for investigator review and approval before implementation.
3. Implement Risk-Based Oversight
What: Develop oversight measures tailored to trial complexity and risk, with documented rationale for the level of oversight applied to each service provider.
Why: ICH E6(R3) specifically requires that “the range and extent of oversight measures should be fit for purpose and tailored to the complexity of and risks associated with the trial.”
How: Create a risk assessment matrix for each service provider based on criticality of services, complexity, and experience.
Example:
a provider handling primary endpoint data might require monthly quality reviews and on-site audits, while a translation service might need only quarterly performance reviews and documentation checks.
4. Establish Quality Management Requirements
What: Ensure service providers implement appropriate quality management processes and incident reporting systems for events that might impact participant safety or trial results.
Why: ICH E6(R3) requires that “any service provider used to perform clinical trial activities should implement appropriate quality management and report to the sponsor incidents that might have an impact on the safety of trial participants or/and trial results.”
How: Define specific quality management expectations and incident reporting thresholds in agreements.
Example:
require an eCRF vendor to have validated change control processes and report any system performance issues affecting data entry within 24 hours, with formal impact assessments.
5. Maintain Vendor Qualification System
What: Assess and document service provider suitability before selection, including capability evaluation, and maintain essential records demonstrating qualification.
Why: ICH E6(R3) explicitly lists “documents that service providers are suitably qualified” among essential records, making qualification documentation a regulatory requirement.
How: Implement a structured qualification process with standardised documentation.
Example:
when qualifying an imaging core lab, document their experience with similar endpoints, technical capabilities, staff qualifications, quality system assessment, and the decision rationale—maintaining these as essential records.
6. Ensure Subcontractor Visibility
What: Implement oversight of activities further subcontracted by service providers, with clear documentation and monitoring requirements extending through the entire vendor chain.
Why: ICH E6(R3) requires sponsors to “ensure appropriate oversight of important trial-related activities that are transferred to service providers, including activities further subcontracted by the service provider.”
How: Include subcontractor notification and approval requirements in vendor agreements, with clear oversight expectations.
Example:
if a CRO subcontracts biomarker analysis, require formal approval, documentation of the subcontractor’s qualifications, and inclusion in oversight activities like periodic joint quality reviews.
7. Create Non-Compliance Management Processes
What: Develop clear escalation pathways for addressing persistent service provider non-compliance, including remediation steps, termination criteria, and regulatory reporting requirements.
Why: ICH E6(R3) states that Sponsors should “consider terminating the service provider’s participation in the trial” for persistent significant non-compliance, with appropriate regulatory notification.
How: Establish an escalation framework with defined compliance thresholds and actions.
Example:
create a escalation process where initial issues require a corrective action plan, continued issues prompt a formal quality review with executive involvement, and persistent issues trigger termination assessment and regulatory notification planning.
8. Implement Blinding Protection Measures
What: Establish role-based access controls for service providers to safeguard trial blinding, with documented justification for any access to unblinded information.
Why: ICH E6(R3) specifies that “Sponsor staff or service providers who are involved in operation of the trial and directly or indirectly interact with investigator site staff should not have access to unblinding information except when justified by the trial design.”
How: Create documented role definitions with clear blinding requirements for each service provider.
Example:
implement separate unblinded statistical teams with documented firewalls, physical separation, and independent oversight to maintain blinding integrity throughout the trial.
Transforming Requirements into Effective Processes
These eight critical requirements establish a comprehensive framework for service provider management under ICH E6(R3).
While the guidelines maintain that accountability cannot be delegated, they recognise the reality of modern clinical trials—collaborative ecosystems requiring well-defined responsibilities, clear documentation, and systematic oversight.
Successfully implementing these requirements demands robust processes and consistent documentation that quickly becomes unmanageable with manual approaches.
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Purpose-built software can transform these complex requirements into streamlined workflows, automate documentation, and provide real-time oversight visibility across your entire provider network.
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Contact us for a demonstration of how our vendor management platform can help you meet these ICH E6(R3) requirements while reducing administrative burden and strengthening trial delivery.
