Dear Dr. Entwisle:
The Office for Human Research Protections (OHRP) conducted an on-site evaluation of the human research protections program (HRPP) at University of North Carolina (UNC) at Chapel Hill on June 2-4, 2015. The evaluation was conducted as part of our program to evaluate HRPPs of institutions that receive Department of Health and Human Services (HHS) support for research in compliance with 45 CFR Part 46.
During our visit, we met with you as the signatory official on the FWA, Institutional Review Board (IRB) chairs and vice-chairs, IRB members, researchers that conduct HHS-supported research, and the Office for Human Research Ethics (OHRE) staff. We also reviewed your records for over 50 active HHS-supported studies, IRB SOPs and IRB meeting minutes.
We observed a robust human subjects protection program at UNC. IRB leadership, chairpersons and members conveyed a sincere commitment and concern for their role in the HRPP. We acknowledge that at the time of our visit, UNC was in the process of filling the OHRE Director position that had been vacant for over a year. As such, we noted OHRE staff’s strong dedication played an essential role in successfully carrying out the daily IRB operations.
On the last day of our visit, we shared with you several observations regarding the UNC’s HRPP. Thank you for your follow-up reports (dated July 13, 2015, October 19, 2015, November 10, 2015, and March 24, 2016) in response to those observations. We make the following determinations:
1. Protocol 12-1111, titled “Microfinance and Health Intervention Trial for Young Men in Dar es Salaam, Tanzania.” This is an intervention trial to assess the effects of an intervention that combines microfinance with health promotion on reducing the incidence of sexually transmitted infections among young Tanzanian males, ages 15 years and older. According to the IRB meeting minutes, the IRB approved this study with “minor modifications.” However the meeting minutes noted that the IRB was uncertain of how the interventions would be delivered, if it was feasible or necessary for intervention groups to remain blind to the randomization scheme, or whether sexually transmitted infection (STI) testing included HIV testing.
In order to approve non-exempt human subject research, the IRB would have to make certain determinations as specified in HHS regulations at 46.111. For example, 46.111(a)(1) requires an IRB to ensure that risks to subjects are minimized: “by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk. . .” in order to approve research. This regulatory requirement cannot be met if the IRB is uncertain of how study interventions would be delivered, whether it is feasible or necessary for intervention groups to remain blind to the randomization scheme, or whether sexually transmitted infection testing in the study would include HIV testing. Since the IRB lacked the information discussed above, it did not have sufficient information to make this finding.
Protocol 14-3285, titled “Targeting Auditory Hallucinations with Alternating Current Stimulation.” This study involves transcranial current stimulation for reducing auditory hallucinations in adult psychiatric patients. According to the IRB meeting minutes, the IRB approved this study with “minor modifications.” The meeting minutes indicated that the IRB was uncertain of the rationale for: (1) studying brain-derived neurotrophic factor allele frequencies; (2) comparing alternating versus direct transcranial simulation; and (3) conducting a drug screen. Additionally, the Board sought clarification regarding the approach to be used to exclude women who become pregnant during the study and the operational definition of “impaired EEG synchronization.”
As mentioned above, in order to approve non-exempt human subject research, the IRB would have to make certain determinations as specified in HHS regulations at 46.111. This regulatory requirement cannot be met if the IRB was uncertain of the rationale for the study design, significant study procedures, or how women who become pregnant during their participation would be handled.
We determine that for the two studies above, the IRB approved research contingent upon substantive modifications or clarifications that were directly relevant to the determinations required by the IRB under HHS regulations at 45 CFR 46.111 without requiring additional review by the convened IRB. For additional information, please see the following OHRP guidance: http://www.hhs.gov/ohrp/policy/conditionalapproval2010.html. Since the IRB lacked the information discussed above, it did not have sufficient information to make the findings required by 45 CFR 46.111(a)(1).
Corrective Actions: As described in your follow-up reports, UNC has conducted extensive training of the IRB members and has revised the IRB written policies and procedures to ensure that the IRB consistently makes appropriate findings and adequately documents them.
We acknowledge and commend you on the extensive training activities implemented since our visit. Specifically, since our visit all IRB members and staff were required and have completed the PRIM&R E-ROC training module. Additionally, in October 2015, UNC provided and IRB members and OHRE staff completed a 2-day PRIM&R At Your Doorstep Workshop for IRB Chairs, members and staff with an additional half-day workshop on the second day for unaffiliated or non-scientist IRB members.
Further, we note that your HRPP’s ongoing training activities now include educational presentations at every IRB meeting, OHRE staff “field trips” to research labs and projects, monthly lunch and learn sessions for IRB coordinators, and national conference attendance for OHRE staff and IRB chairs.
We determine that the corrective actions adequately address all of the determinations and are appropriate under your FWA. 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 this conclusion.
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.
Lisa Buchanan, MAOM
Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Dr. Elizabeth Kipp, Human Protections Administrator, IRB Director
Dr. Kimberly A. Brownley, UNC IRB Co-Chair
Dr. David Weber, UNC IRB Chairperson
Dr. Ruth Humphry, UNC IRB Chairperson
Dr. J. Herbert Patterson, UNC IRB Chairperson
Dr. Doug Mann, UNC IRB Chairperson
Dr. Joanne Less, Food and Drug Administration
Dr. Sherry Rodgers, National Institutes of Health (NIH)
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, NIH
Ms. Sarah Carr, Office of Science Policy, NIH