Feature Article

BUMC IRB Quality Assurance Reviews: What to Expect

By Russell Gontar
Manager of Research Quality Assurance
Issue: February, 2006

Author has nothing to disclose with regards to commercial support.

Educational Objectives:

• Identify the agencies/organizations who are authorized to audit research
• List the three types of QA audits that the IRB conducts
• Explain the purpose of a corrective action plan
• Explain ways the investigator can help make the audit process run smoothly

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• Introduction
• Goals of a QA Review
• Types of QA Reviews
• Some Tips on Preparing for a Review
• The QA Review Process
• QA Review Findings: What Are They and What Do They Mean?
• QA Review Reports
• What is a Corrective Action Plan?
• Quiz

"Oh, no. We're being audited!!!"

If you have ever been through an audit of a research study, this may well have been your initial reaction to being notified of a forthcoming site inspection. Actually, even if you have never been audited, just the thought that it could happen might be enough to fill you with anxiety.

It is important for investigators to realize that any study can potentially be audited at any time. Site inspections or audits can be initiated on a federal level or locally. A study might be audited by the FDA (21 CFR 312.68), OHRP, the study sponsor, a contract research organization, or by the Institutional Review Board. The purpose of this article is to help you understand what is involved and to help you prepare for a BUMC IRB audit of a research protocol.

Goals of a QA Review:

The BUMC IRB conducts internal audits, which are officially referred to as “Quality Assurance Reviews”. These Quality Assurance (QA) reviews are performed by the IRB’s Manager of Research Quality Assurance (often called the “IRB Auditor”). The primary goals of these QA reviews are to:

• Help investigators protect the rights and safety of human research participants;
• Help ensure that the study is conducted in compliance with federal (21 CFR 50, and 45 CFR 46), state and Institutional regulations;
• And to help educate investigators and study staff about the regulations governing human subjects research at BUMC.

QA reviews are not conducted to simply find out if investigators are doing something wrong or to get investigators into trouble. QA reviews do not start with the assumption that something is wrong with the study. It is the IRB’s position that most investigators and their study teams are extremely devoted to conducting their research with the highest regard for research ethics and concern for the safety of their research subjects. History has shown that most deviations identified during QA audits occurred due to honest error or because the PI and the study team mistakenly thought they were doing the right thing. The QA review process is designed to help investigators identify areas of misunderstanding and provide them with the assistance they need to get back on track.

Types of QA Reviews:

Okay, so exactly what is a QA review and what does it involve? As stated in the BUMC policies and procedures “The IRB has the responsibility to oversee the conduct of research that it approves. Consistent with this responsibility, the IRB may audit research studies at BUMC or studies in which faculty and/or staff of BUMC is engaged in research outside the institution”. Situations that may warrant audit include, but are not limited to:

In general, BUMC QA audits fall into one of three categories:

• Routine or “random” reviews
• For Cause or “directed” reviews
• Investigator-Initiated reviews

Routine reviews are the most common type of audit done by the IRB. They may involve either open or closed studies. Studies are selected at random by the IRB Manager of Research Quality Assurance. For cause reviews are less common and are initiated in response to an issue or concern such as a complaint from a study subject or member of the study staff, an indication of possible investigator non-compliance, numerous reports of study deviations or a lapse in study approval.

Remarkable as it may seem, some investigators have actually requested a QA review of their research! An investigator-initiated review might be requested in anticipation of an expected external audit or just because the PI wants to be sure the study is being conducted in compliance with the regulations. This is a service that the QA program is happy to provide and it is the wise investigator who takes advantage of it!

QA reviews are either comprehensive or targeted (limited) in scope. Comprehensive reviews involve a more global inspection of the study. Typically, a comprehensive review will evaluate:

• Informed consent documentation and/or process
• Confirmation of subject eligibility
• Compliance with HIPAA regulations
• Confirmation that study safety evaluations are being performed
• Confirmation that the research intervention is being conducted per protocol (all versions of the protocol and all protocols amendments/modifications have been submitted to the IRB for approval prior to initiation)
• Data collection
• Adverse event reporting
• Regulatory documents

Some Tips on Preparing for a Review:

The most important thing for investigators to do when they find they are being audited is not to panic! The QA auditor will let the Principal Investigator (PI) know which study documents are needed for the audit and will give him/her adequate time to obtain them. Depending on whether the audit is comprehensive or targeted, the auditor may request such items as:

Obviously, it is extremely helpful to the auditor if the materials provided are organized and complete. Investigators should only provide what is requested and materials related to other studies should not be included. Investigators who are savvy in “auditor management” have learned that the best way to ensure that the audit process is as smooth (and brief) as possible is to provide the auditor with all the materials requested in as organized a manner as possible.

The QA Review Process:

The QA review process commences with the auditor reviewing the IRB study file. Written notification that the study is being audited is then sent to the PI via e-mail and BUMC interoffice mail. (If the review is of an urgent nature, the review could start immediately with an unannounced visit to the study site). Following written notice, the auditor contacts the PI to arrange a brief initial meeting and to start the review. The purpose of the initial meeting is for the auditor to explain the QA review process to the PI, as well as being an opportunity for the auditor to ask the PI questions about the protocol.

In most cases, an inspection of the study records begins immediately following the initial meeting. It is helpful if a member of the study staff is available initially to help the auditor locate and identify the required documents. It is not necessary for this person to remain with the auditor during the entire audit.

Following the completion of the record audits, a list of queries is compiled and sent to the PI for review and resolution. Assuming the list isn’t overwhelming, a response is requested within one week. If any concerning issues remain unresolved, a follow-up meeting with the PI is usually arranged.

QA Review Findings: What Are They and What Do They Mean?

The findings of a QA review are “graded” in a couple of different ways. The overall conduct of the study is graded, as is each individual category of study conduct. The ratings given are “Acceptable”, “Needs Improvement” and “Unacceptable”; and are evaluated according to the number and type of deviations found. There are two types of deviations that may be identified:

Major Deviations are considered those errors that result in an increased risk to subject safety or subject rights, significantly depart from the IRB approved protocol, or compromise the reliability of the study data. Failure to comply with federal or Institutional regulations or policies would also be considered a Major Deviation.

Minor Deviations do not impact subject safety or rights, significantly depart from the IRB approved protocol or jeopardize study data. (For more information on the definitions of Major and Minor deviations, please refer to Appendix B in the policies and procedures section of the BUMC IRB website.

Major and minor deviations are tallied by “type” in the categories in which they occurred. For example, if a PI forgot to print his/her name on a small number of consent forms, and if a subject was consented on an outdated consent form, then these deviations would be considered two types of minor deviations occurring in the category of informed consent.

QA Review Reports:

A preliminary report of the audit findings is prepared by the IRB Auditor. Recommendations for a possible corrective action plan (CAP) or Protocol Deviation reports that need to be submitted by the PI are also included in the report.

The Chair may concur with the findings and recommendations of the Auditor or may ask for additional information. The Chair might identify other areas of concern requiring further response or corrective action from the investigator. A comprehensive QA report is then submitted to the PI, who is then given 10 business days to respond to the report’s findings and to submit a CAP. If the PI strongly disagrees with the findings, he/she may include remarks or a rebuttal in his/her response to the QA report.

The investigator’s CAP, responses, and comments are included in the Final QA report reviewed by the Board. The Board can accept (or not) the Final QA report, approve (or not) the CAP, order a re-audit or take other actions as required, including suspension or termination of the study. Suspension or termination of a study must be reported by the IRB to the appropriate federal agency and to the study sponsor.

What IS a Corrective Action Plan?

The purpose of a corrective action plan is to address specific major and minor deviations identified during the audit. Not all deviations will require a CAP. The CAP should:

More Information About Audits
In conclusion, while any audit can be a stressful experience for a research team, the primary goal of the BUMC Quality Assurance program is to educate investigators and research staff and to identify opportunities for improvement. To better disseminate this information throughout BUMC, we are announcing a new addition to future issues of the CR Times called “From the Auditor’s Desk”. This column will be written by the BUMC QA Auditor and will periodically address issues of concern identified during the audits.

Click here and close window if you are a BUMC researcher
and would like to take the quiz now.