January 11, 2024 - Vanderbilt University Medical Center

Dear Dr. Rice,

Thank you for cooperation with requests made by the Office for Human Research Protections (OHRP) between 2019 and 2023. OHRP conducted a not-for-cause onsite evaluation of the human research protections program (HRPP) at the Vanderbilt University Medical Center (VUMC) from June 18th to 20th, 2019. We regret the amount of time it has taken us to complete this assessment. The evaluation was conducted as part of OHRP’s program to review HRPPs of institutions that receive Department of Health and Human Services (HHS) support for compliance with 45 CFR part 46.

The evaluation, conducted by a team of seven OHRP staff, included interviews with senior HRPP officials, institutional review board (IRB) chairs, IRB members, HRPP staff and principal investigators who conduct HHS-supported human subjects research. In addition, OHRP staff were able to observe two VUMC IRB meetings. The team was also able to review IRB files for over 40 HHS-supported research studies, the associated IRB meeting minutes, and VUMC’s IRB written policies and procedures.

OHRP noted VUMC’s implementation of and transition to the revised subpart A, 46 CFR part 46, referred to as the “2018 Requirements.” This included the required changes to the HRPP’s structure, manuals, and electronic institutional review board (eIRB) system that facilitated the implementation of the 2018 requirements. During the visit, the OHRP team found the IRB and eIRB records to be well organized. OHRP concluded that the eIRB system contained all pertinent information about a research study, and the system assisted IRB member and principal investigator navigation of documents for the IRB approval process. OHRP documented that the IRB members and HRPP staff had access to and participated in human research protections training including online training, national conferences, and onsite training. Additionally, OHRP learned of multiple outreach efforts provided by IRB directors and staff to researchers, such as one-on-one training, walk-in hours for questions and HRPP workshops.

On January 28, 2022, OHRP requested current copies of the VUMC HRPP’s organizational chart along with their written procedures, templates, and tools. On February 8, 2022, VUMC sent OHRP the requested information. OHRP requested additional documents and scheduled a meeting with VUMC to clarify certain points. During the March 6, 2023 meeting, VUMC satisfactorily addressed the concerns raised by OHRP. As part of that meeting, VUMC officials agreed to make certain changes and clarified many points. VUMC documented what transpired at that meeting in a letter to OHRP dated March 28, 2023. Clarifications and plans for changes include the following:

1. The definition of “noncompliance” will be made consistent in VUMC written procedures and will state: “Failure to comply with Federal regulations, HRPP Policy, or the determinations or requirements of the IRB.”
2. The definition of “serious noncompliance” will state: “An action or omission taken by an investigator that shows serious disregard or violation of federal regulations or institutional policies applicable to human subject research that demonstrably increases risks to human subjects, adversely affects the rights and welfare of human participants, or compromises the integrity/validity of the research.”
3. VUMC officials explained that when VUMC relies on an external IRB, the Vanderbilt HRPP Investigator Handbook informs VUMC researchers that the IRB of record may have different IRB reporting timelines and requirements. The IRB of record is responsible for ensuring that relying-site investigators understand what written procedures will be used for the research. A link to the IRB of record’s policies and procedures is typically provided with the reliance documentation.
4. VUMC officials explained that IRB meetings are now held virtually via Zoom and that votes of members are recorded through a clear visual or verbal process.
5. VUMC officials explained that their “informed consent” template is not intended to cover every possible scenario within a study, such as when their IRBs reviews studies with pregnant women as subjects. VUMC provides additional language to be used for various processes, interventions, and populations that investigators avail themselves of when creating informed consent submissions. https://www.vumc.org/irb/template-language-and-general-guidance
6. VUMC officials noted that, in addition to HRPP written procedures and consent templates, they have other resources mentioned that are part of their education and compliance program. These include:
   1. An Investigator’s Handbook: https://www.vumc.org/irb/tool-kit
   2. Regularly offered courses (both instructor-led and on-demand): https://www.vumc.org/irb/education-and-training-0
   3. A pre review process completed by staff analysts described in Procedure I.D.1 and many others: https://www.vumc.org/irb/policies-and-procedures
   4. Analyst’s checklists used for processing submissions: (not available publicly)
   5. Notification to investigators of policy/procedure changes via VUMC’s Research Staff Council newsletter (monthly), Twitter feed, website announcements, and “pop-up’s” on Discovr-e (VUMC’s electronic platform for submissions).
   6. Regular/ongoing post approval monitoring of > 100 studies annually. This not for cause monitoring is conducted by VUMC’s Compliance Team and includes a thorough assessment of study adherence to regulatory and institutional policies.

The information provided by VUMC to OHRP adequately addresses OHRP’s concerns. Based on information obtained during the 2019 site visit, and review of additional documents, OHRP found no evidence of systemic noncompliance with HHS regulations. When changes referenced in your March 28, 2023 letter are finalized, please send us a copy of those revised written procedures.

Currently, there is no need for further involvement by our office in this matter. We appreciate your institution’s continued commitment to the protection of human subjects. Please contact me if you have any questions.

Sincerely,

Lisa Buchanan, MAOM
Director
Division of Compliance Oversight

cc:
Mr. Kyle Rybczyk, Human Protections Administrator, VUMC
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (FDA)
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, National Institutes of Health (NIH)
Dr. Pamela Kearney, Director, Division of Human Subjects Research, Office of Extramural Research, NIH
Dr. Adam Berger, Director, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Ms. Lydia Kline, Team Lead, Clinical Research Policy, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Center for Devices and Radiological Health (CDRH) IRB: BIMO-CDRH@fda.hhs.gov
Center for Biologics Evaluation and Research (CBER): CBERBIMONotification@fda.hhs.gov 
Office of Regulatory Affairs (ORA): orabimoinspectionpoc@fda.hhs.gov
Center for Drug Evaluation and Research (CDER): BIMO-CDEROSI@fda.hhs.gov