Corrective and Preventive Action Plans

Introduction

Despite a study team’s best efforts, errors in the conduct of research may occur. Errors may include deviations from the IRB approved study plan or noncompliance with applicable research regulations or policies. Whether the result of human oversight, process deficiencies, or technology failures, such errors should be identified and when appropriate, the steps taken to resolve them, and to ensure they do not happen again, should be well documented in the research records. This important documentation is known as a Corrective and Preventive Action (CAPA) Plan.

What is a CAPA Plan

A CAPA Plan is a collective process, or series of measures, to correct the immediate problem, to determine the cause or causes of the problem, and to develop and implement a plan to prevent the problem from recurring. Developing an effective CAPA Plan requires analysis and problem-solving skills and should represent a collaborative effort by the members of the study team. CAPA Plans should be followed through completion and should be monitored by the study team for their success in preventing recurrence of the problem. The entire process should be documented, and this documentation should be maintained as part of the research record.

How to develop and document a CAPA Plan

The IU HRPP Quality Improvement Office (QIO) has developed a CAPA Plan Template to assist study teams with this activity. This template is designed to incorporate the steps described below but should be modified as needed to capture additional steps taken by the study team and/or specific departmental processes. Examples of how to use the CAPA Plan Template, as well as additional information on the Root Cause Analysis (RCA) methods described below, may be requested by emailing Ashley Meyers at ashlmeye@iu.edu.

The following activities should be included in the CAPA Plan:

1. Describe the identified problem and how it was discovered.
2. Determine whether the problem should be promptly reported to the IRB.
3. Conduct a Root Cause Analysis.
   • RCA is a process of inquiry that is necessary to identify the source of a problem so that it can be effectively resolved and prevented. There may be multiple causes that contribute to a problem and multiple methods to resolve each cause. The “root cause” is the most basic cause of a problem that may trigger a chain of additional causes.
   • The RCA process is most effective when conducted with a team of people to help with brainstorming. It is important to talk to all people involved in the initial problem and to ask objective, open-ended questions in order to eliminate assumptions and pull together only facts about why a problem occurred.
   • There are multiple methods by which Root Cause Analysis (RCA) can be conducted, including the following commonly used models:
     • Gilbert’s Behavior Engineering Model (BEM) – a performance measurement tool to evaluate six key areas of potential deficiencies or contributors to a root cause. Potential contributors are categorized as organizational/environmental factors (subclassified as expectations and feedback, tools and resources, and consequences or incentives) and personal/individual factors (subclassified as knowledge and skills, staff capacity and qualification, and motives or preferences).
     • The 5 W’s – an approach to clearly identify what happened in relation to additional details including where, when, and why the event happened, along with who was involved in the event’s occurrence in an effort to pinpoint the root cause.
     • The 5 Why’s – an iterative or progressive method of “digging deeper” into an event by repeating the question “Why?” after each possible cause to ensure the ultimate root cause is identified. The answer to each “Why?” forms the basis of the next question. Of note, the question may need to be repeated more or less than 5 times, or may need to be replaced with “Why did the process fail?” in order to successfully identify the root cause. When the last answer ultimately identifies a broken process or a process that does not exist, you may have reached the root-cause level.  
     • Fishbone Diagram (Cause and Effect Method) – a graphic technique to help visually identify and display potential causes of a problem and their relationship to each other. Potential causes may be grouped under the classic model categories of Materials, Methods, Equipment, Environment, and People, or the RCA participant group may come up with their own major categories as a starting point.   
   • Document the RCA process (including maintaining the group’s notes taken during the process) and record the ultimate root cause.

4. Determine what corrective actions should be taken to correct the immediate problem.
   • Depending on the identified problem, corrective actions might include consultation with and/or reporting to the study sponsor, PI, or IRB, specific actions with a study participant (e.g., reconsent or other notification, additional follow-up or monitoring, or discontinuation/withdrawal), or correction of erroneous data. 
     • Data corrections should be made in accordance with IU HRPP Policy, and Notes to File in the Participant’s Study File should be used to explain why such actions were taken.
   • Record the planned corrective actions including who will complete them, and when they will be completed.
   • As the corrective actions are completed, evidence of their completion should be maintained with the CAPA Plan. Examples might include items such as copies of email correspondence with the study sponsor, copies of corrected study documentation, copies of IRB submissions, and/or explanatory Notes to File.

5. Determine what preventive actions should be taken to prevent the issue from occurring again.
   • Depending on the identified problem, preventive actions might include training on research policies or related topics, development of checklists or other tools, development of new processes, revision of study materials, or sequestering of outdated materials (e.g., from active folders into archive folders).
   • If study materials need to be revised, refer to HRPP Policy to determine what changes require IRB review.
   • Also, consider the magnitude of the problem identified from the RCA.
     
     • How will you prevent the problem from affecting all subjects in the study?
     • How will you prevent the problem from affecting other studies conducted by the PI or within a department?
     • What processes and procedures will prevent this problem from recurring?
   • Record the planned preventive actions including who will complete them, and when they will be completed.
   • As the preventive actions are completed, evidence of their completion should be maintained with the CAPA Plan.
     • Examples might include copies of new checklists or SOPs, training materials and/or training logs, copies of IRB submissions, or copies of email communication sent amongst the study team to notify them of the changes.

6. Determine and record who is responsible for implementing, assessing, and closing the CAPA Plan.
7. Implement the CAPA Plan and monitor its progress.
   • Record any changes to the plan that occur prior to implementation.
   • Record when actions were completed and who completed them.

8. Assess whether the CAPA Plan worked and make changes, if needed.
   • Complete a self-assessment, self-audit, or evaluation, to identify potential recurrences of the problem.
   • If the CAPA Plan did not prevent recurrence, revisit the RCA documentation to determine if the true root cause was ever identified. Often, when a CAPA Plan is ineffective, it is because the true root cause of the problem was not identified.
   • Document the assessment process and the outcomes of the assessment.

9. Close-out the CAPA Plan.
   • Confirm the completion of the CAPA Plan and document the CAPA Plan as complete or closed.
   • Document the process and any discussions that took place to come to this determination.

FDA Guidance: E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) – Guidance for Industry

FDA Guidance: Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects – Guidance for Industry

FDA Center for Devices and Radiological Health (CDRH) presentation: Corrective and Preventive Action Basics

FDA: Center for Drug Evaluation and Research (CDER) Bioresearch Monitoring (BIMO) GCP Compliance and Enforcement Webcast

FDA: Corrective and Preventive Actions (CAPA)