In the course of conducting research even the most experienced and diligent research teams deviate from the approved protocol or experience unexpected events. These deviations and unexpected events must be identified, evaluated, and responded to in order to protect the rights, safety, and welfare of participants and others, and the integrity of the research data.
Immediate Corrective Actions:
If you become aware of a deviation or unexpected event, you must first take immediate corrective actions. These actions are taken without first obtaining IRB approval because they are needed to protect the rights, welfare and safety of participants and others.
They may be in the form of a phone call or an office visit with a qualified research team member. The investigator may need to order tests and other procedures to ensure the participant is safe. Document the deviation, the reason it occurred, and immediate corrections taken.
Root Cause Analysis:
It is important to identify the cause or source of a deviation or problem so that it can be resolved to prevent recurrence. There may be multiple reasons or causes that contribute to a problem. Conversely, there may be multiple methods to resolve each cause. The root cause is the initiating, most basic cause of a problem that may or may not lead to a chain of causes or other problems. Eliminating the root cause should prevent recurrence.
A root cause analysis (RCA) is the process of identifying and documenting the root cause and the downstream effect on the causal chain. RCA should focus on identifying underlying problems that contribute to error rather than focusing on mistakes made by individuals.
- Identify the problem
- Interview those impacted by the problem
- Interview those people responsible for the problem, if applicable
Questions to identify root causes:
- What happened? What is the problem?
- Why and how did the problem occur? What were the steps?
- Who was affected by the problem? Was it one subject or all subjects in the study?
- What is the magnitude of the problem? Is it in one study or does the problem exist in all studies under this PI or even in an entire clinical department?
- Keep asking “why” and “how” until you reach the root cause
Once the root cause has been identified, the next step is to develop a corrective and preventive action plan to eliminate the root cause.
Corrective and Preventive Action (CAPA) Plans:
Corrective actions are those taken to resolve a problem and preventive actions are those actions that keep the problem from recurring.
Now that you have assessed the rights, welfare, and safety of the participants and have identified the root cause, you should consider additional reporting to the sponsor and IRB. Ensure that the reports to the sponsor and IRB are accurate and thorough and that the CAPA is included. Additionally, there may be actions that should be taken to correct the problem, but that were not required to be taken before IRB review as they were not needed to protect the rights, welfare and safety of participants and others.
Preventive actions are necessary to ensure that the problem does not repeat itself. Preventive actions should be based on process. Create and document a process or standard operating procedure (SOP). Train on the process, implement the process, evaluate the process, and amend the process as necessary. Consider revising the protocol or informed consent as necessary.
CAPAs must be thorough:
Specific: Identify the actions that will be taken to address the root cause, the individual (role) responsible for taking the actions, and where documentation of the actions will be kept.
Timely: Include the date(s) when the actions will be completed
Measurable: Include a process of assessment of the action plan effectiveness and a process by which the plan will be amended if it is found to be ineffective.
CAPAs must be well documented!
Documenting the CAPA:
- Action type (corrective or preventive)
- Action description
- Responsible person
- Due date
- Plan for effectiveness check
- Effectiveness check outcomes
Root Cause: There was not a process to ensure that new hires to the research team had all required actions taken before participating in Human Subject Research.
Corrective Actions: The Research Manager reviewed the study history and IRB approved personnel log with the study team history and determined that there was only one occurrence where an unapproved member of the study team participated in research. This review is documented in a note-to-file, see attached, and will be kept in the regulatory record.
Preventive Actions: The research manager created an SOP for new hire onboarding and a supporting checklist, see attached. The new hire checklist will be utilized by the research manager and the principal investigator to ensure that new hires are appropriately onboarded before participating in the research. The final step of the onboarding process is the sign-off on the checklist by both the research manager and the principal investigator. A note-to-file was created by the research manager indicating the start date of the new SOP and checklist, see attached. The completed checklists will be kept in the regulatory record with the delegation of authority log. The research manager and the principal investigator will review the implementation of the new SOP and checklist after each of the next three new hires and will document the review in a note to file to be kept in the regulatory record. If the result of the reviews is that the SOP and checklist are working as expected, a note to file will be placed in the regulatory record indicating the plan as effective with effectiveness check moving to an annual review. If the SOP and/or checklist require revision, those revisions will be documented in a note to file kept in the regulatory record and the process for evaluating the next three new hires will start again.