FDA Guidance: A Risk-Based Approach to Monitoring of Clinical Investigations (Q&A)

11 April 2023: https://www.fda.gov/media/121479/download

EXECUTIVE SUMMARY

What is the purpose of the risk assessment, and should sponsors document their methodologies and activities for assessing risk?

1. Optimize study quality
2. Assess and manage risks during protocol design
3. Document risk assessment and update monitoring plans

Should sponsors monitor only risks that are important and identified during their initial risk assessment as likely to occur?

1. Monitor important and likely risks
2. Address additional risks detected during the investigation
3. Ensure comprehensive monitoring plans to identify and address unanticipated risks

What factors should sponsors consider when determining the timing, types, frequency, and extent of monitoring activities?

1. Consider investigation and site-specific risks
2. Determine types and intensity of monitoring activities
3. Evolve monitoring activities based on identified risks and issues
4. Account for clinical investigation infrastructures and experience
5. Utilize electronic data capture and centralized monitoring when suitable
6. Assess staffing adequacy and location of participant visits

How can a risk-based approach to monitoring that includes centralized monitoring help minimize missing data or protocol deviations?

1. Centralized monitoring enables systematic evaluation of study conduct
2. Allows sponsors to review and compare data for inconsistencies or omissions
3. Helps detect potential anomalies and quality issues more quickly

Should the risk-based monitoring approach include processes to ensure that appropriate blinding is maintained?

1. Ensuring blinding is maintained is a critical process in risk-based monitoring
2. Mitigate risks to blinding in advance of investigation initiation
3. Monitor deviations that could lead to unintentional unblinding during the investigation

What elements should sponsors include in monitoring plans?

1. Monitoring plans should address study-specific and site-specific risks and manage anticipated and unanticipated risks.
2. Emphasize critical risks affecting investigation quality, participant rights, safety, welfare, and collection or analysis of critical clinical data.
3. Include a description of the investigation design, blinding, and randomization procedures.
4. Detail the sampling plan for identifying specific records and data to be monitored, providing a representative picture of the overall information.
5. Describe the issue escalation process, approach to determining the presence of issues at other clinical sites, and systemic problem identification.

How should sponsors follow up on significant issues identified through monitoring, including communication of such issues?

1. Thoroughly evaluate significant issues promptly at appropriate levels.
2. Conduct root cause analysis and implement corrective and preventive actions promptly.
3. Review and revise risk assessment and monitoring plan as needed.
4. Examples of actions include improved training, halting enrollment, revising protocol, and modifying vendor service agreements.
5. Document and communicate significant issues and actions taken to appropriate parties, including sponsor management, clinical sites, institutional review boards, and regulatory agencies.

How should monitoring activities and the results of these activities be documented and shared with those involved in the investigation?

1. Document monitoring activities with details on the date, individuals involved, a summary of reviewed data, identified deficiencies, and actions are taken.
2. Include results of monitoring activities in sufficient detail to allow verification of adherence to the monitoring plan.
3. Provide reports of monitoring activities to appropriate management and inform the clinical investigator of relevant findings.