Every study should have internal QA processes and procedures in place to ensure compliance with the research plan and subject safety while efficiently collecting high quality data. For the purposes of this document, the research plan includes the protocol, the consent form(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.
Prior to implementing an internal QA program, you should follow the steps outlined in the Preventing Noncompliance.
An internal QA program provides for periodic and systematic examination of compliance with the research plan. As described below, an internal QA program should include both Self-Auditing and Continuous Improvement; see both tabs below for more information about each.
Self-Auditing
Self-auditing processes provide an additional level of confidence that all activities are being conducted in a compliant manner. Self-auditing is a mechanism to discover processes that are susceptible to error. A written self-audit plan should identify who will conduct the audits, how often they will occur, which studies will be reviewed, the focus areas, the tools that will be used, how the results will be shared, and how any findings that suggest a need for correction will be addressed.
Self-auditing should be performed by members of the study team but not necessarily those members who completed the procedures being audited. The more distant someone is from the conduct of the daily activities, the more objective review that person may be able to provide; however, the more removed a person is from the study, the more effort that may be required for that person to become familiar with the study.
When designing a self-auditing program prioritize the studies and areas that present the greatest potential risks. Focus first on those risks that could have the most significant impact on subject safety or data integrity and that are more likely to occur. Identifying these risks will allow prioritization between studies, especially for research teams with larger study portfolios. Studies that have more of the below characteristics should be given priority over studies that have fewer or none of the below characteristics:
- Procedures with risks to subject safety
- High level of complexity (study design and/or procedures)
- FDA Regulated (with UW-Madison held Investigational New Drug (IND)/Investigational Device Exemptions (IDE) studies prioritized over other FDA regulated studies including those using IDE exempt devices and externally held INDs)
- Not externally monitored
- Less experienced study team members
These same factors should inform the frequency, focus (e.g., review of regulatory files, subject records, drug accountability records) and the extent (e.g., number of subjects) of reviews for each study.
Once you have identified those studies that you will review first, you may also need to prioritize the items to review within a given study. The specific prioritization will depend on the risk level and design of the study.
Any items related to subject safety (e.g., safety related eligibility criteria or study procedures) should be given highest priority. Items related to core human subjects protection requirements (e.g., informed consent and protocol compliance) should be given second highest priority. Lower priority should be given to regulatory files and other similar items.
Self-audit tools are available through the Post-Approval Monitoring and the ICTR Clinical Research Toolkit. However, further customization or additional tools may be needed based on the nature of your study. As self-auditing is being conducted, ensure the approved IRB protocol, application, and materials are being used to compare against study records and conduct.
Continuous Improvement
The results of all self-audits and other assessments (e.g. regular conversations with study teams and subject feedback) should be used to make continuous improvements. The continuous improvement process is very similar to the process of developing a Corrective and Preventative Action Plan. Ensure any items that require reporting are reported to the IRB per Reportable Event guidelines. External IRBs have different noncompliance requirements; if your study was reviewed by another IRB, please follow their noncompliance requirements.
The first step in making continuous improvements is to organize the results of these assessments in a way that allows for the identification of trends. Assembling the results in a short written report is recommended.
The next step is creating and utilizing a process that allows individuals who can make changes in study conduct to review the report. This review process is most effective when it is collaborative and involves study team members with different perspectives on study conduct. Having regularly scheduled study team meetings focused on continuous improvement is recommended.
The goal of these study team meetings should be to identify deficiencies and/or improvements that can be made based upon the review of the results. Deficiencies should be fully analyzed and improvements developed using the process identified in the Investigating the Cause of Noncompliance and Implementing Corrective and Preventive Action (CAPA) Plans Guidance.
Finally, improvements need to be monitored to ensure that they are having their intended effect. If they are not, this process should be restarted.