Audits

There are two types of audits, routine audits and for-cause audits.

Routine audits are often performed by the sponsor, IRB, FDA or internal quality assurance department. The goal of an audit is to review, inspect and verify the ethical conduct of human subject research, integrity of previously reported data, adherence to the study protocol and applicable institutional, state and federal regulations and guidances. Most audits involve the review and inspection of informed consent forms, documentation of the consent process, reported data, regulatory records, source documents to ensure protocol compliance and drug accountability records. The auditors may also request to review the site’s internal standard operating procedures (SOPs) for conducting human subjects research and copies of the research team’s credentials and documentation of training to ensure appropriate delegation of specific research tasks.

For-cause audits may be conducted if during the monitoring process a sponsor has continual documented accounts of possible noncompliance, data discrepancies or concerns over the ethical conduct of the study by the investigator. The sponsor may contact the FDA and report these concerns which could result in a for cause FDA audit.  Study participants could also contact the FDA to report suspected wrong-doing that may lead to a for-cause audit. The IRB and sponsor can also perform a for cause-audit. The items reviewed in a for-cause audit are similar to those reviewed in a routine audit.

• HRPP Policy on Noncompliance  
• ICH E6 Good Clinical Practices  
• FDA 21 CFR 50 Protection of Human Subjects  
• HHS 45 CFR 46 Protection of Human Subjects   

Sponsor Audits

A pre-audit is often performed by sponsors in preparation for a potential FDA audit. Sponsors may also conduct audits to ensure the monitors assigned to the projects are performing to their expectations. Some sponsor auditors will not provide the site with a written report of their findings but the monitor will follow-up with the site on any of the issues noted.

IRB Audits

The Human Research Protection Program has an institutional quality improvement team that evaluates Ohio State research studies to ensure the ethical conduct of human subjects research and adherence to applicable institutional policies, state and federal guidances and regulations. Through these reviews, additional training and education is provided to the research team to help improve the quality of the research conducted at Ohio State.

• HRPP Quality Improvement Program  
• HRPP Quality Improvement (QI) Program FAQ  
• HRPP Policy on Quality Improvement Activities 

The Western IRB (WIRB) is used as the IRB for industry sponsored trials at Ohio State.  WIRB may conduct a site audit and often focuses on subject safety and protocol compliance. 

• WIRB: A Guide for Researchers  
• HRPP WIRB  
• HHS 45 CFR 46.109 IRB Review of Research 

FDA Audits

FDA inspections are conducted to ensure the quality and integrity of data submitted to the FDA for a new drug application (NDA). Sponsors, Monitors and Investigators of any clinical trial submitted with an NDA or studies submitted under an IND or IDE may be audited.  Studies audited are usually pivotal trials that are instrumental in the attempt to prove the safety and efficacy of a product for FDA approval. These audits are not for-cause. Often the site will be contacted by the FDA inspector with minimal notice of the audit. However, the FDA may conduct an unexpected audit at anytime.

FDA findings are failures to maintain adequate and accurate case histories, protocol noncompliance, failure to appropriately obtain informed consent, untimely reporting of SAEs to sponsors and IRBs, enrolling ineligible subjects, inappropriate delegation of research tasks to under-qualified research staff and failure to list all sub-investigators on the 1572. The audit findings will be discussed with the research team at the conclusion of the audit visit. The FDA inspector will then send the audit findings to headquarters and an official letter will be sent to the clinical investigator. The official letter will have detailed information as to whether a response from the investigator is warranted or if any other action will be required.

• ORRP Investigator/Staff Guidance for FDA Inspections 
• FDA Compliance Program Manual  

Preparations for an Audit

The research team should always be prepared for a potential audit.  It is essential that there are written, approved, and enforceable department policies and SOPs for how the study team should conduct human subject research. All staff should have adequate and documented training on key policies and processes. The research team should also be aware of proper audit etiquette and present themselves in a calm and professional manner at all times.

To prepare for an upcoming audit, it is helpful to review all research charts, consents, regulatory documents and source documents for accuracy and completeness. This will allow the team to be prepared for any deviations that the auditors may note during their review. A room should be reserved in advance for the auditors that is appropriately equipped with computers, internet access, fax machine and telephone. Please note that many auditors are not permitted to accept meals, so you must know in advance whether policies will allow you to provide the auditors with food. 

All necessary research charts, medical records, access to electronic medical records and regulatory documents should be requested and available upon the day of the audit for inspection. All records and charts should be organized in a similar manner to allow for easy review. It is helpful to develop a flagging mechanism so that all pertinent documents are identified and easy for the auditors to find. It is in the research team’s best interest to have everything as organized as possible.

The date of the audit, location and tentative schedule for the day should be communicated in writing to all key members of the research team, ORRP and department administrators. When the auditors arrive, they should be escorted to the audit area and oriented to the location and organization of all pertinent documents and files. The research team should request the FDA form 482, Notice of Inspection and ID of the inspectors. Key study staff should be available to answer question or address any concerns at the time of the visit and be available for the close out meeting at the conclusion of the audit. During this meeting, the auditor will typically review all major audit findings.