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.
What You Need to Know? 👇
What is the primary purpose of risk assessment in clinical trial monitoring?
The purpose is to optimize study quality by eliminating or mitigating important risks to human subject protection and data integrity. Sponsors should identify risks during protocol design, evaluate their causes, likelihood of detection, and severity of consequences to inform monitoring plans.
Should sponsors only monitor risks identified in their initial risk assessment?
No. Sponsors should monitor both initially identified important risks and additional risks detected during the investigation. They should also monitor less likely risks that could significantly impact participant safety, welfare, or investigation quality, requiring comprehensive monitoring plans.
What factors determine the timing and frequency of monitoring activities?
Key factors include clinical site infrastructure, investigator experience, electronic data capture capabilities, study stage and complexity, data criticality, adequate staffing, participant visit locations, and the benefit of early monitoring visits to identify issues promptly.
How does centralized monitoring help minimize missing data and protocol deviations?
Centralized monitoring enables systematic analytical evaluation across multiple sites, allowing real-time review of study-wide data for inconsistencies, performing data completeness checks, and identifying quality issues earlier than on-site monitoring alone, facilitating prompt corrective actions.
What essential elements should be included in monitoring plans?
Monitoring plans should include investigation design description, randomization confirmation processes, sampling plans with rationale, immediate escalation triggers, approaches for detecting systemic problems, and methods for determining if site-specific issues affect other locations.
How should sponsors handle significant issues identified through monitoring?
Significant issues require timely evaluation, root cause analysis, and appropriate corrective/preventive actions. Sponsors should review and revise risk assessments and monitoring plans, document findings, and communicate to relevant parties including management, sites, IRBs, and regulatory agencies when appropriate.
What You Need to Do 👇
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