This document provides guidance for study teams regarding how to develop a Corrective and Preventive Action (CAPA) plan. A CAPA plan is written to describe and address a deviation/noncompliance event (event) discovered during the conduct of a human subjects research study.

When a deviation/noncompliance event is discovered, study teams should take immediate measures (also referred to as Corrections) to correct the issue; mitigate risk; and protect the rights, safety and welfare of the participant(s). Depending on the nature of the event, follow-up with the participant or other tests and procedures may be needed to ensure the participant’s safety. For minor deviations, corrections such as a Note to File, submission of a Change of Protocol, or changes to internal workflows may resolve the event. However, corrections alone may not effectively resolve more significant or systemic noncompliance, which generally requires a more thorough CAPA plan. CAPA plans are implemented to prevent the occurrence and recurrence of an event. The following steps can be taken to develop and implement a CAPA plan.

CAPA Plan Development Steps

1. State the problem, event, or issue identified

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

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

Begin by collecting data: Analyze the situation fully before you move on to look at the 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 and how many subjects were affected
  • Whether this event occurred in one or multiple studies under this Principal Investigator’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

Once you’ve collected data, the next step is to 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. One method for identifying root causes is the “5 Whys.” The 5 Whys is an iterative process for identifying underlying causes of a problem. For this technique, the question “why” is repeated five times, each time in response to the last why’s answer. This often results in identifying a process that is not working as intended or identifying that a needed process is missing.

You may also try using the following questions to complete your analysis:

  • 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)

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

Now that the root cause has been identified, 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?

4. 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 plan be periodically assessed for effectiveness and modified as needed. Modifying an ineffective CAPA plan may require reexamining the causes of the initial event and restarting the root cause analysis process.

When monitoring a CAPA plan, consider at least the following:

  • How will the CAPA plan be monitored (i.e. how will problems with the CAPA plan 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?

Assistance with CAPA Plan 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 Oversight Programs are also available to provide consultation at any point during the CAPA plan development process.

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.

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