February 23, 2016 - University of Texas at San Antonio

Dear Dr. Agrawal:

Thank you for your June 23, 2014 report in response to our May 22, 2014 questions and concerns regarding the University of Texas at San Antonio’s (UTSA) evaluation of allegations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46).  Based on our review of your response, we make the following determinations:

A. Determinations regarding the above-referenced research

1) In our May 22, 2014 letter, we expressed concern that the IRB frequently approves research contingent upon substantive modifications or clarifications that are 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.  We note the following:
a. The responses to the committee stipulations for the study Ml CASA (Mujeres lnteresadas en Cambios por la Salud) by Zenong Yin, Ph.D. (IRB# 10-133) were not reviewed by the convened IRB when the board requested either substantive information or information necessary to make the required determinations for approval. Dr. Yin was asked to describe the randomization procedure, to more fully describe study recruitment procedures, and to simplify the language in the consent document, information the board needed to help ensure that informed consent was adequately obtained and documented. The IRB would have needed this information in order to make the determinations for approval under HHS regulations at 45 CFR 46.111, but approved the study before receiving this information.

b. The responses to the committee stipulations for the study Alcohol and Women's Health Risk Reduction: An Innovative Experimental Approach by Tina Zawacki, Ph.D. (IRB# 09-096) were not reviewed by the convened IRB when the board requested either substantive information or information necessary to make the required determinations for approval. Dr. Zawacki was asked to provide a copy of the recruitment flyer, to describe the screening procedures, to more fully describe study procedures (alcohol level vs. timing of post-survey) and to provide a plan regarding medical services in case they are needed, information the board needed to help ensure that risks to subjects were minimized and reasonable in relation to benefits, and that informed consent was adequately obtained and documented.  The IRB would have needed this information in order to make the determinations for approval under HHS regulations at 45 CFR 46.111, but approved the study before receiving this information.

We have determined that the IRB approved the above-referenced research contingent upon substantive modifications or clarifications that are 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 and that this violated 45 CFR 46.111.

Corrective Action:  

In the course of this investigation, UTSA determined that procedures in this area could and should be improved. To foster improvements, the Senior Associate Vice President for Research Administration issued a letter to Dr. Grant, IRB Director, and Dr. Silveria, chair of the IRB, clarifying and detailing some actions they are to take to implement OHRP’s Guidance more fully. We note that such actions are intended to ensure compliance with the regulatory requirements. You have also directed the IRB to pay particular attention to ensuring that conditional approvals are only used when appropriate. We find these corrective actions adequately address the noncompliance and are appropriate under your FWA.  However, we note the following regarding your written procedures in this area, related to when IRB approval occurs:

The document STANDARD OPERATING PROCEDURE: Initial Review of Research Requiring Full Board Review states the following (section 12):
When the IRB specifies modifications in order to secure approval of a study, the IRB will determine the level of review required in order to approve the responses to those stipulated modifications. When the modifications are minor and easily verifiable, the IRB may determine that the responses can be reviewed by the Chair of the IRB or the designee of the Chair. When the modifications are more than minor, and when the modifications are needed for the Board to be able to make any determination required for approval, the modifications will be reviewed by the Board at a convened meeting. 

We also note that OHRP guidance on IRB Approval of Research with Conditions states that when conducting an initial or continuing review of a research study, or a review of proposed changes to a previously approved research study, an IRB can take any of the following actions:

1. If the IRB is able to make all of the determinations required for approval under the HHS regulations at 45 CFR 46.111 and, if applicable, subparts B, C, or D of 45 CFR part 46, the IRB may approve the research study or proposed changes either (a) as submitted without any conditions, or (b) with conditions (sometimes referred to as IRB approval with conditions).  OHRP’s guidance explains that an IRB may approve research with conditions if, given the scope and nature of the conditions, the IRB is able, based on the assumption that the conditions are satisfied, to make all of the determinations required for approval under 45 CFR 46.111 and, if applicable, subparts B, C or D.  

2. Require modifications to secure approval and defer or table the research study or proposed changes for further review at a future date after the required modifications are submitted by the investigator if the IRB requires additional information to make all of the determinations required for approval under the HHS regulations at 45 CFR 46.111 and, if applicable, subparts B, C, or D of 45 CFR part 46.

3.Disapprove the research study or proposed changes.
With regard to an IRB’s ability to approve research with conditions (1. above), UTSA’s Standard Operating Procedures for initial review of research are unclear about when UTSA believes IRB approval is occurring in the circumstance when the IRB is able to make all of the determinations required for approval under 45 CFR 46.111, based on the assumption that the IRB’s specified modifications are satisfied. The institution’s Standard Operating Procedure does not distinguish between the two situations of an IRB approving research with conditions and having those conditions verified in some way other than by the convened IRB, and tabling research due to required modifications and having the modified research come back to the convened IRB for review and approval.  

For example, we note that meeting minutes we reviewed for the February 18, 2009, April 21, 2010, and April 20, 2011 IRB meetings state “The Board determined that the responses to stipulations to secure approval may be reviewed by the Chair or his designee, and that continuing review will occur annually. After discussion, a motion was made and seconded to specify the above noted stipulations in order to secure approval.”  Based upon our review of the minutes, it appears that the IRB is actually approving the study in such a circumstance, since the minutes reflect that the IRB did make all of the required findings under 45 CFR 46.111, and is not requiring a response from the investigator to secure approval.  In such cases, we recommend that the minutes of IRB meetings indicate that the IRB approved the study at a convened meeting with conditions or stipulations, and whether or not the response to such conditions or stipulations would need to be reviewed by the convened IRB or could be verified by the IRB chairperson (and/or other individual(s) designated by the IRB).  We also recommend that UTSA’s Standard Operating Procedures be modified to clarify this scenario. See OHRP guidance at http://www.hhs.gov/ohrp/policy/conditionalapproval2010.html.

2) In our May 22, 2014 letter, we expressed concern that the institutional review board (IRB) made a determination of serious noncompliance in the study Error Detection and Performance Self-Evaluation, but the noncompliance was not reported to OHRP, as required by HHS regulations at 45 CFR 46.103(a) & (b)(5).  We note that after the UTSA IRB office received a complaint from a student, Dr. Davis reported that she had gathered data on musical ear training using her students at the time. While at UTSA, she continued the study that she had begun at her previous institution and was not aware that she needed to work with the UTSA IRB office to either submit a new application to the UTSA IRB, or pursue an IRB Authorization Agreement for UTSA to rely on her former institution’s IRB.  Dr. Grant, representing the IRB, requested that Dr. Davis complete an IRB violation report for conducting research without prior IRB review and approval, which she did. In response to the IRB violation report, the convened IRB reviewed the violation report and determined that Dr. Davis had engaged in noncompliance and that it was serious but not continuing.  However, because the UTSA IRB Office was operating under the mistaken assumption that its Assurance required them to report serious or continuing noncompliance only when the research was supported by federal funding, UTSA did not report its findings to OHRP. This was in error because at the time the institution’s assurance applied to all research regardless of support, and therefore the incident was required to be reported.

We have determined that Dr. Stacey Davis conducted the study Error Detection and Performance Self-Evaluation without institutional review board review and approval and that this serious noncompliance was not reported to OHRP as required by HHS regulations at 45 CFR 46.103(b) (5).

Corrective Action: 
UTSA submitted an incident report to OHRP on June 18, 2014 for serious noncompliance related to this project. Understanding that this discovery could mean that reporting requirements under 45 CFR 46.103(b)(5) may not have been met in the past, UTSA has volunteered to initiate a review of all applicable findings in the past five years and will promptly report them to OHRP.  UTSA will provide training regarding the requirement to transfer IRB approvals to UTSA or apply for new IRB approval when serving as an agent of the university employing the following mechanisms: a reminder in the Vice President for Research's monthly newsletter, addition of a section to UTSA's investigator guidance for human subjects research, and the addition of this topic as an FAQ discussed during educational sessions for investigators.  We recommend that this training be specifically directed toward incoming investigators. These corrective actions adequately address this determination.

B. Determinations regarding your institution’s system for protecting human subjects

The complainant alleged that the IRB does not adhere to the recordkeeping requirements of 45 CFR 46.115(a)(1) in that written reviews created by primary reviewers are typically not maintained, and  of 45 CFR 46.115(a)(4) in that communications between investigators and the IRB are selectively maintained. Based on the documentation provided in your correspondence, we have determined that the allegations of noncompliance are unproven.  No evidence was presented to us indicating that primary reviewers submit formal written reviews that must be maintained by the IRB or that communications between the IRB and investigators are not adequately maintained.

The corrective actions adequately address all of the above determinations.  Further, the remaining concerns expressed in our May 22, 2014 letter are adequately addressed by your responses and corrective actions.  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 determination.

We appreciate your institution’s continued commitment to the protection of human research subjects.  

Sincerely,

Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland  20852
Telephone: 240-453-8132
FAX:    240-453-6909
E-mail: Kristina.Borror@hhs.gov

cc:   
Dr. Judith Grant, Director, Institutional Review Board, University of Texas at San Antonio
Dr. David Silvera, PhD, Chairperson, IRB #1, University of Texas at San Antonio
Dr. Stacey Davis, investigator, UTSA
Dr. Zenong Yin, UTSA
Dr. Tina Zawacki, UTSA

Dr. Joanne Less, FDA
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, NIH
Ms. Sarah Carr, Office Science Policy, NIH