Frequently Asked Questions - Quality Assurance

A Quality Review is a one time snap shot look at the conduct of a Clinical Trial. RQA conducts Quality Reviews consistent with ICH-GCP definition of audits. Please see next question

An audit is a systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

A Quality Review takes a one-time snapshot look at a trial; whereas monitoring oversees the progress of a clinical trial from start to finish.

RQA creates an annual Quality Review Plan that lists the studies selected for routine Quality Reviews during the coming year.

Routine Quality Reviews: are reviews of study activities and study documentation that are performed on-site as a service to investigators, with feedback provided regarding practices associated with the conduct of the study. Studies for Routine Quality Reviews are selected by RQA using a risk-based approach based on the following criteria, which include, but are not limited to:

• Investigators who are holding an IND or IDE
• Expected level of risk to subjects/vulnerable populations
• Studies with a complex study design/protocol
• Federally-funded studies
• Investigators who are first time Principal Investigators

Directed "for-cause" Quality Reviews are conducted by RQA upon request by any of the following: IRB committee, Associate Vice Provost for Human Subject Research, Vice Provost for Research, Office of Research and Research Education, Audit Advisory Services, etc. A directed Quality Review is generally based on identified concerns, a complaint, or an allegation about human subject safety and rights, regulatory compliance, or data integrity.

Directed Quality Reviews may also result from complaints reported in person directly to RQA or via "CaneWatch."

• There can also be (routine or directed) Focused Quality Reviews, which examine a particular aspect of a clinical trial, such as the informed consent process.

No, the PI does not need to be present for the duration of the Quality Review. However, we do require the PI to attend the initial meeting at the beginning of the Quality Review, so that the auditors can explain the scope of the Quality Review; the general review process, and also to discuss the protocol with the PI and study team. If the PI is unavailable, the auditors may begin the Quality Review if a study team member can provide the study records for review; a meeting with the PI is then scheduled as soon as it is feasible. A short debrief meeting will be held on the last day of the on-site review to inform the PI and study team of the main observations noted. The PI and study team will receive a Draft Quality Review Report and will have the opportunity to review it with the auditors at the exit meeting prior to receiving the Final Quality Review Report.

RQA is always willing to work with the PI on timing. The goal is to get the Qualtiy Review done as soon as possible with the least amount of disruption to the site's operations.

No, we will not ask you to cancel any clinical activities. We want to conduct our Quality Reviews with as little disruption as possible.

The duration of a Quality Review may be affected by several variables such as the type of Quality Review, the complexity of the study, the number of subjects enrolled, number of protocol procedures, etc. On average, a full Quality Review typically takes 3 days at a study site. Focused Quality Reviews are usually completed in less than a day.

University leadership requested these notifications so that the leaders responsible (Dept. Chairs, etc.) are able to keep abreast of research compliance in their respective areas. This communication promotes accountability and awareness and allows leaders to be proactive.

No. We review studies only against the standards and regulations that apply. All Human Subjects Research at UM must comply with the policies outlined in the UM Investigator Manual. All Human Subjects Research except Social/Behavioral Research is also subject to International Conference on Harmonization (ICH) Guidelines for Good Clinical Practice (GCP). Additionally, FDA and OHRP (Office of Human Research Protection) regulations may apply depending on the type of study you are conducting and whether it is supported by the PHS (Public Health Service). Please call RQA for any questions you may have.

These categories are defined in every Quality Review report. In general, an observation is classified as "Immediate Action Required" if it appears to pose a significant risk to subject rights, safety, or to data integrity, or to represent a major deviation from applicable regulations, policies or procedures. "Action Required" observations are deviations or deficiencies in adhering to regulations, policies, procedures, or data standards, which if not corrected may lead to serious issues.

The Quality Review report is issued to the PI and it is the PI's responsibility to write the response (CAPA Plan). While it makes sense that the study team is involved in the response, it is very important that the PI responds to his/her own Quality Review report so that he/she is fully aware of all proposed corrective and preventive actions and is able to carry them out. RQA's CAPA Manager will work closely with the PI and study team by providing feedback and recommendations on how to write a good response that is specific and measurable.

Yes. RQA will issue a separate report to the IRB detailing the observation. The IRB has to provide RQA and the Vice Provost for Research with a written response to their observation. These IRB responses are evaluated using the same criteria as for the PI responses, which means that they must specify both corrective actions and preventive actions. RQA's CAPA Manager will work closely with the IRB to assist them in developing a good response that is specific and measurable.

• At the conclusion of the on-site Quality Review, the auditor will review the main observations with the PI and study team at an audit debriefing meeting
• A Draft Quality Review Report will be issued to the PI and main study team members
• The auditor will schedule an exit meeting with the PI and study team, to review the draft report for accuracy and to clarify any issues. The purpose of the exit meeting is for the auditors and the PI to have a common understanding of the observations and significance of the specific examples listed in the draft report
• A Final Quality Review Report is issued to the PI
• The PI will be given 10 business days to provide responses to the audit observations using the PI Quality Review CAPA Form provided by the auditor
• The PI and study team will be contacted by the RQA CAPA Manager to assist with the development of corrective and preventive actions (CAPA) intended to address the observations noted in the Final Audit Report
• The Final Quality Review Report and the PI's CAPA Plan are provided to the IRB/HSRO
• The relevant IRB Board determines if the PI CAPA Plan is appropriate and sufficient or whether additional actions are needed. The IRB may also ask for a follow-up Quality Review. The IRB's determination and/or further actions will be described in an IRB determination letter

Internal Quality Review Reports are confidential and must not be shared with any 3rd parties, including, but not limited to, study Sponsors. However, a specific Sponsor-related observation can be shared with your study Sponsor. Please check with RQA if you are unsure what can be shared.

Internal Quality Reviews are part of an internal quality assurance program that is designed to encourage candor and collaboration between Investigators and the various components of UM’s Human Subject Research Protection Program (RQA, IRB, etc.). For this reason, it is RQA’s practice not to provide internal Quality Review reports to the FDA (or other regulatory bodies). While the University wants to demonstrate full cooperation with Federal agencies, the risks, and benefits of full disclosure are considered on a case-by-case basis. In rare instances, UM has had to cooperate with federal agency requests for internal audit reports in order to avoid an escalation in regulatory action or the prolongation of a federal audit.

Yes, A PI may request any of the following types of reviews.

• Study Start up Review
• Study Review
• Mock FDA Audit