Investigating the Cause of Noncompliance and Implementing Corrective and Preventive Action (CAPA) Plans Guidance

When a deviation/noncompliance event is discovered, study teams should take immediate measures (also referred to as Corrections) to mitigate risk and protect rights, safety and welfare of the subject(s) and others should be taken. This may be in the form of a phone call or an office/clinic visit between the subject and a member of the research team, or other tests and procedures to ensure the subject's safety. Corrections alone may resolve minor deviations but they will not effectively resolve more significant or systematic noncompliance, which generally also require corrective and preventive action.

Corrective and Preventive Actions are developed and implemented for more significant or systematic noncompliance, once the root cause is known. Corrective and Preventive Actions are implemented to prevent the occurrence and recurrence of an event. To avoid the need for a CAPA, study teams should have prevention and quality assurance procedures in place to proactively avoid problems. However, if a CAPA needs to be developed, the following approach will be helpful.

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CAPA Development Steps:

State the problem, event, or issue identified

1. Briefly outline the problem, event, or issue identified. This outline should be as objective as possible and include a description of:
   • What occurred
   • Where and when the event occurred
   • What should have occurred instead
   • What the source of the information was
   • Who discovered the information/event

Examine the issue and identify the cause(s) of the event (i.e. Root Cause Analysis)

1. Collect data: Analyze the situation fully before you can move on to look at factors that contributed to the problem. To maximize the effectiveness of this step, talk to everyone with knowledge of the problem and process. You may become aware of additional information that you were not aware of at the time the event was initially discovered. Data collection should provide you with information on:
   • Whether the problem truly exists, including the evidence indicating that a problem occurred
   • What the true scope and magnitude of the problem is, including:
     • How many times the event occurred
     • How many subjects were affected
   • Whether this event occurred in one or multiple studies under this PI's purview, with similar study team members, and/or within the program
   • How long the problem has existed, including:
     • When the event first occurred and how long it continued
     • What the effect or impact of the problem is and who was affected

2. Identify Possible Causes: The goal of this step is to identify and document as many factors contributing to the problem as possible. There can be multiple reasons or causes that contribute to one single problem. This list may include human error, and/or process or equipment/space related factors. The focus should be on identifying underlying problems that contribute to error rather than on mistakes made by individuals.

   Root cause analysis tools, including many common types of charts and graphs, can be helpful during this process. A Why Chart can be particularly helpful in determining a root cause, as it helps analyze the different layers of causes.

   During the Root Cause Analysis, ask at least the following questions:

   • What sequence of events lead to the problem or allowed the problem to occur?
   • What conditions allowed the problem to occur?
   • What other problems surround the occurrence of the central problem?
   • What were the contributing factors that led to this event? (i.e. all the items in the causal chain)
   • What is the underlying, root cause of the event? (i.e. the first item in the causal chain)

Propose and Implement a Corrective and Preventive Action (CAPA) Plan

Create simple, measurable solutions that address the root cause(s). These solutions should take the form of durable corrective and preventive actions that eliminate the cause and prevent it from recurring in the future, instead of just resolving the issue at hand.

When developing a CAPA, consider at least the following:

• What are the available solutions to prevent the event from occurring or recurring?
• Are the solutions feasible?
• How will the solution(s) be implemented?
• What are the available resources (internal and external to the study team) to implement and monitor the CAPA plan?
• Who will be responsible and accountable for implementing and monitoring the CAPA Plan?
• Are the deadlines reasonable and achievable?
• Can it be monitored?

Monitor the progress and effectiveness of the CAPA Plan

Despite best efforts to identify root causes and solutions, the identified root causes may be incorrect and/or the solutions ineffective. Therefore, it is important that any CAPA be periodically assessed for effectiveness and modified as needed. Modifying an ineffective CAPA may require reexamining the causes of the initial event and restarting the root cause analysis process.

When monitoring a CAPA, consider at least the following:

• How will the CAPA plan be monitored (i.e. how will problems with the CAPA be identified and reported)?
• When will you review the progress and effectiveness of the CAPA Plan?
• At what intervals or frequency will you review the progress and effectiveness of the plan?
• When and to whom should the outcome of the CAPA Plan be reported?

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Assistance with CAPA Development: Individuals not involved in day-to-day study conduct can provide valuable objective feedback on the potential causes of and solutions to events. It may be beneficial to engage others in your department or unit/program in this process. The Post-Approval Monitoring and FDA Regulated Research Programs are also available to provide consultation at any point during the CAPA development process.

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Reporting Noncompliance: When noncompliance is discovered, submit the reportable event to the reviewing IRB as soon as possible within their required timelines as well as any other applicable oversight bodies (e.g. sponsor, FDA if the PI is sponsor-investigator). If you believe more time is necessary to conduct a full assessment of the event, contact the IRB to determine the next steps.

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UW–Madison Resources:

1. UW–Madison Noncompliance Policy¹
2. UW–Madison Health Sciences IRBs Events Requiring Reporting to the IRB
3. UW–Madison Health Sciences IRBs Protocol Exceptions and Deviations Guidance
4. UW–Madison Education/Social Behavioral Sciences IRB Guidance: Reportable Events
5. Preventing Noncompliance Guidance
6. Investigating the Cause of Noncompliance and Implementing Corrective and Preventive Action (CAPA) Plans Guidance

¹ External IRBs have different noncompliance requirements. If your study was reviewed by another IRB, please follow their noncompliance requirements.