The purpose of this document is to outline steps that research teams should take throughout the life cycle of the study to prevent noncompliance. Achieving compliance can be difficult for even diligent study teams due to the highly technical nature of research and the involvement of research participants with complex medical or life situations. One of the most common findings of study audits is that the research team altered or did not adhere to the IRB-approved study protocol; protocol changes are not permitted under the federal regulations prior to IRB approval except when necessary to eliminate apparent immediate hazards to human subjects.
If research teams follow the steps outlined below, the likelihood of noncompliance with the study protocol (aka research plan) should be significantly reduced. For the purposes of this document, the research plan includes the formal protocol, the consent document(s), the IRB application, data collection forms and other study instruments, instructions (e.g., standard operating procedures, manual of procedures) and any corresponding grants/contracts.
- Assess research plan feasibility: Prior to IRB approval and periodically during the course of the study, determine whether the research plan can be carried out as written, including whether participants will be/are able to complete the study procedures. An effective research plan is clear, consistent and allows for variation (e.g., visit/procedure windows) wherever possible. If the research plan includes confusing or overly narrow language or discrepancies between documents (e.g., consent form and protocol), work with the IRB responsible for oversight of the study and sponsor/funding agency (if applicable) to clarify the language and ensure that the research plan can be implemented. Note that if the research plan must be altered to reduce likelihood of deviations after initial IRB approval, obtain IRB approval of a protocol amendment that addresses the problem.
- Create data collection forms and checklists: These documents can increase compliance with the research plan by reminding study team members what the research plan requires at each point in the study. These documents should be thoroughly reviewed to ensure consistency with the research plan prior to being used. For example, a checklist could be used to document the consent process and all its components (e.g., that a subject received a copy and was able to ask questions). A checklist could also be used to document each study visit and the different procedures to be performed at the visit.
- Create Standard Operating Procedures (SOPs): SOPs are beneficial and recommended for all study teams conducting research, especially clinical research. A list of SOPs and templates can be found on the Clinical Research Toolkit. Key SOPs should address processes such as:
- roles, responsibilities, training and delegation;
- informed consent procedures;
- adverse event management.
- Resource availability: Ensure that training materials, the research plan, checklists and other documentation along with the supplies necessary to conduct the research are accessible to study team members and updated promptly as needed. Study team members should also know where to go to when questions about study implementation arise.
- Training: Train study team members on the IRB-approved research plan prior to their involvement in the research as well as when any changes to the IRB-approved materials are made or when new staff join the team. Staff need to be aware of the tasks that they are assigned to perform and principal investigators (PIs) need to ensure that staff are properly qualified and trained to perform the tasks assigned.
- Document: Complete data collection forms and checklists in a timely manner. If a deviation occurs this documentation will tell the story of what happened and drive your quality assurance efforts.
- Reporting: When deviations from the IRB-approved research plan occur, the investigator must act quickly to ensure subject safety as well as report to sponsor and/or IRB when necessary.
- Implement an internal quality assurance (QA) program: An internal QA program includes mechanisms to review previous study conduct with the goal of finding errors and implementing improvements and efficiencies promptly. See Developing an Internal Quality Assurance (QA) Program Guidance for additional information.
- Developing an Internal Quality Assurance (QA) Program Guidance
- Investigating the Cause of Noncompliance and Implementing Corrective and Preventive Action (CAPA) Plans Guidance
*External IRBs have different noncompliance requirements. If your study was reviewed by another IRB, please follow their noncompliance requirements.