The Food and Drug Administration released a new draft guidance, “A Risk-Based Approach to Monitoring of Clinical Investigations: Questions and Answers Guidance for Industry”. The purpose of the guidance is to provide additional clarification to the finalized Risk Based Monitoring (RBM) guidance from 2013. Questions and answers provide details about:
Planning a monitoring approach
Monitoring plan content
Follow up and communication of monitoring results
Questions from each section include:
1. Question: Why is a risk assessment important and what activities should sponsors record in their risk assessment?
A risk assessment serves to identify potential problems in collecting critical data and conducting important study procedures.
The risk assessment serves as a foundation for the development of the monitoring plan.
Sponsors should record:
The rationale for assessing risk,
Conclusions made from the risk assessment, and
How the assessment impacted decision-making for risk management.
2. Question: Should sponsors monitor only risks that are important and likely to occur?
RBM means that sponsor oversight should focus on activities that are at greater risk to quality data or subject protections.
Risks that are less likely to occur but could have a significant impact to a quality clinical trial should also be considered.
3. Question: What factors should sponsors consider when determining the timing, types, frequency, and extent of monitoring activities?
There are many factors described in the original guidance, such as complexity of the study and experience of the investigator.
In addition, it is recommended to consider these factors:
Experience and qualifications of the coordinator.
Workload at the site.
Turnover of personnel at the site.
Complexity of the data to be collected.
4. Question: How can a risk-based approach to monitoring that includes centralized monitoring help minimize missing data, protocol violations, or protocol deviations?
Real-time monitoring of data can support finding issues sooner, so the issues may be managed to minimize risks to the remainder of the clinical trial.
5. Question: Should the risk-based monitoring approach ensure that appropriate blinding is maintained?
The risk assessment should include evaluating potential risks to maintaining the blind, which is considered a critical process.
The monitoring plan should allow for tracking deviations that create risk for unintentional unblinding.
6. Question: What should be included in the monitoring plan for RBM?
The monitoring plan should include the identified risks and how the risks will be managed.
Elements from the RBM guidance should be included.
Additional elements are mentioned that would define how monitors would address risks to the study, such as:
Critical issues that would trigger escalation.
How to determine whether issues occurring at one site also occur at other sites and corrective actions.
7. Question: How should sponsors follow up on significant issues and communicate the monitoring results?
Follow-up of critical issues needs to occur promptly and at the right authority level.
Appropriate corrective and preventive actions should be taken.
Any systemic issues should be identified and remedied.
Significant issues should be documented and communicated to the appropriate entities.
8. Question: How should centralized monitoring results be documented?
In addition to elements commonly found in documentation, a description of a non-compliance, potential non-compliance, or deficiencies and any actions taken or recommended to address these issues should be included.
Documentation of centralized monitoring activities should be detailed enough to demonstrate adherence to the monitoring plan.
A key concept from RBM is that monitoring plans should address critical issues that may adversely affect subject safety, wellbeing, and rights or the integrity of the data. “The Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring” was FDA’s first step to supporting RBM. This guidance is in draft form and is likely to change, but once finalized will further facilitate sponsor’s adoption of RBM.
Visit here to comment on the draft guidance through May 14, 2019.
- The Clinical Pathways Team
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