Risk-Based Monitoring of Clinical Investigations
This guidance provides recommendations on risk-based approaches to monitoring clinical investigations of human drug and biological products, medical devices, and combination products. It focuses on planning monitoring approaches, developing monitoring plan content, and addressing/communicating monitoring results.
Recommended Actions
- Develop and document a comprehensive risk assessment methodology
- Create a risk-based monitoring plan that includes:
- Investigation design description
- Sampling plans
- Issue escalation procedures
- Communication protocols
- Documentation requirements
- Implement centralized monitoring capabilities using electronic systems where possible
- Establish processes for:
- Early monitoring visits
- Regular risk evaluation
- Documentation of monitoring activities
- Communication of findings
- Root cause analysis of issues
- Corrective and preventive actions
- Review and update monitoring plans as new risks are identified
- Ensure adequate training of all monitoring personnel
- Set up proper documentation systems for monitoring activities and results
- Create clear communication channels for sharing monitoring findings with relevant stakeholders
Key Considerations
Clinical testing
- Monitoring should be a quality control tool to determine if investigation activities are carried out as planned
- Sponsors must provide oversight and ensure proper monitoring of investigations
- Early monitoring visits should be considered after first few participants enroll
- Processes must be in place to maintain appropriate blinding when applicable
Human Factors
- Consider adequate staffing and training of site personnel
- Consider participant locations and data collection points
- Consider experience level of investigators and staff
Software
- Electronic data capture systems should have capability to assess quality metrics in real-time
- Consider use of statistical and analytical methods for centralized monitoring
Safety
- Must ensure protection of rights, safety and welfare of participants
- System should help identify and track potential risks to participants
- Significant safety issues must be promptly evaluated and communicated
Other considerations
- Risk assessment should be documented including methodologies and conclusions
- Monitoring plans should be risk-based and revised as needed
- Both anticipated and unanticipated risks should be monitored
- Results of monitoring activities must be documented and shared appropriately
- Root cause analysis and corrective actions needed for significant issues
Relevant Guidances
- Risk-Based Monitoring in Clinical Investigations of Medical Products
- Clinical Investigation Requirements for Prostate Tissue Ablation Systems
- Design Considerations for Medical Device Pivotal Clinical Studies
- Clinical Study Design for Surgical Ablation Devices Used in Treatment of Atrial Fibrillation Under Direct Visualization
- Clinical Trial Considerations for Neurological Devices Intended to Slow, Stop, or Reverse Disease Progression
Related references and norms
- IEC 31010:2019: Risk Management — Risk Assessment Techniques
Original guidance
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