June 17, 2024 – Emory University

Dear Dr. Nobles:

The Office for Human Research Protections (OHRP) conducted an evaluation of Emory University’s (Emory) Human Research Protections Program (HRPP) on May 3 to May 18, 2023. The evaluation was conducted as part of OHRP’s program to evaluate, for compliance with 45 CFR part 46, HRPPs of institutions and institutional review boards (IRBs) that review research receiving Department of Health and Human Services (HHS) support.

This evaluation was conducted by an OHRP team and involved a review of study files for approximately 30 active HHS-funded studies, IRB written procedures and checklists, IRB meeting minutes, and reliance agreements. Three IRB meetings were observed on May 3rd, May 11th, and May 17th of 2023, and OHRP observed that each meeting was conducted efficiently. OHRP was pleased to observe that continuing education was provided during the IRB meetings. In addition, during meetings staff were very accessible and promptly responsive to the needs of the IRB members.

Multiple interviews were conducted with Emory’s IRB officials, IRB Chairs, IRB members, Quality Assurance (QA) staff and other support staff with a variety of responsibilities. Those we interviewed displayed a sincere commitment to the work of Emory’s HRPP and viewed themselves as providing a valuable service in the IRB’s process. The Signatory Official and Human Protections Administrator (HPA) were very engaged and helpful.

Based on review of your responses provided on February 23, 2024, to the questions and concerns outlined in our letter dated January 11, 2024, OHRP makes the following determination:

Determination

1. In our letter dated January 11, 2024, we expressed concern that at times the convened IRB approved the research with conditions in the absence of information that the IRB needed to approve the research at 45 CFR 46.111. Based on our review of IRB meeting minutes, we noted an example of an HHS funded study approved with conditions in which the conditions suggested the unknown information would be required to determine if the 45 CFR 46.111 approval criteria were satisfied.
   
   STUDY00005602 entitled, “RITE PrEP: A Double-Blind, Placebo-Controlled, Randomized Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Rectally Administered Tenofovir Alafenamide/Elvitegravir Inserts” was reviewed by the convened IRB on February 1, 2023 and approved with conditions. As reflected in the IRB meeting minutes and the IRB approval letter to the investigator specifying the changes required for IRB approval, the IRB requested the following information from the investigator after the IRB meeting:

The committee expressed concern about asking people to take pictures of administering the drug vaginally or rectally. Please provide rationale to explain why this is this necessary. If it is, add detail to the protocol as to how will the study team obtain this information from participants and how you will ensure confidentiality. Please add detail about this process including how confidentiality will be maintained to both the protocol and the consent form. The IRB wonders if an alternative method could be utilized, such as a study medication diary.

Please clarify whether any genetic testing be performed as part of this study? If so, this needs to be explained in the protocol and the required GINA language needs to be added to the informed consent.

Response: According to your response regarding the first condition, Emory reported it was clear to the IRB members and staff present at the meeting that the IRB was comfortable approving the study with the plan to request photographs, as long as the study team confirmed the IRB’s assumption that the rationale for the photographs was to ensure the study drug was administered correctly. In addition, the IRB members and staff are knowledgeable about the Emory-approved software solutions for handling sensitive data, which the IRB uses to assess plans to maintain confidentiality. Emory acknowledged it should have made these considerations clearer in both the minutes and the IRB approval letter to the investigator specifying the changes required to secure IRB approval.

According to your response regarding the second condition, Emory reported the condition should have documented the Board’s stated assumption that no genetic testing would be performed as part of the study and noted that a modification would be required if the study team wanted to add such procedures.

Determination: We considered Emory’s responses and the language of the clarifications that the IRB requested from the study investigator, quoted above. In our view, from the phrasing of the conditions for approval, it appears that the IRB did not have sufficient information regarding how confidentiality would be maintained or whether genetic testing would be performed as part of this study. This information is pertinent for the IRB to determine whether the regulatory approval criteria were satisfied, including the criteria at 45 CFR 46.111(a)(1), (2), and (7). We determine that the IRB, when reviewing the study, lacked sufficient information to make the determinations required for approval of research under HHS regulations at 45 CFR 46.111.

Corrective actions: Emory acknowledged that in the past, their IRB has documented conditions of IRB approval in a way that could be perceived as asking investigators open-ended clarifying questions to determine that the 45 CFR 46.111 approval criteria can be met, instead of requesting specific prescriptive revisions, although this has not been the IRB’s intent. Emory noted this is a challenging area of IRB review and conducts periodic training for their IRB analysts and IRB members about the difference between pending and deferred items (i.e., “pending” referring to studies qualifying for conditional approval vs. deferred studies referring to studies that are not yet approvable under 45 CFR 46.111 criteria). In July 2023 Emory conducted another formal training for their IRB members and staff at the start of each of that month’s IRB meetings, which was also shared with all members via email and posted on Emory’s website for future review. Emory’s IRB staff and Chairs continue to reiterate this guidance during meeting discussions when needed, to ensure that outcomes are compliant with OHRP guidance. These corrective actions adequately address the determination.

Recommendations

The following recommendation is offered for Emory’s consideration, and OHRP clarifies that no determination of noncompliance is made regarding the observation described.

We make the following recommendation regarding Emory’s human subject protection program:

1. During our observation of the three IRB meetings, OHRP noted that all conditions required to secure IRB approval may not be clear to all members prior to the vote. However, according to your response, IRB staff take notes throughout all IRB meetings to capture the discussion of all agenda items. Requested changes are documented by IRB staff throughout the discussion. Prior to the vote, the Chair summarizes the motion and general categories of pending issues and calls for a vote. We recommend that, immediately prior to a vote, the IRB recap an explicit list of any changes or clarifications required by the IRB as a condition of IRB approval, consistently across IRB panels.

Emory’s February 23, 2024 response adequately addresses OHRP’s determination. At this time, there should be no need for further involvement by our office in this matter. Please notify us if you identify new information which might alter our determination.

We appreciate the continued commitment of your institution to the protection of human research subjects. Please do not hesitate to contact me should you have any questions.

Sincerely,

Crystal M Kelly, MPH
Compliance Analyst
Division of Compliance Oversight

CC (email only):  
Rebecca Rousselle, Human Protections Administrator, Emory University  
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 
Micah Bass, Deputy Director, Office of Public Health Ethics and Regulations, Centers for Disease Control and Prevention
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