December 23, 2015 - Oregon Health and Science University

Daniel Dorsa, Ph.D.
Senior Vice President for Research
Oregon Health and Science University
3181 SW Sam Jackson Park Road
Portland, OR 97239

Human Research Subject Protections under Federalwide Assurance (FWA)-0161

Dear Dr. Dorsa:

The Office for Human Research Protections (OHRP) conducted an on-site evaluation of the Human Research Protection Program (HRPP) at Oregon Health and Science University (OHSU) in Portland, Oregon on September 1-3, 2015.  The site visit to OHSU is part of our program to routinely evaluate human subjects protection programs of institutions that receive Department of Health and Human Services (HHS) support for research to assess compliance with 45 CFR part 46.

This site evaluation included interviews with you as the OHSU Institutional Official, senior Human Research Protection Program (HRPP) officials, the institutional review board (IRB) Chair and vice-chairs, IRB members, IRB staff, and investigators who conduct HHS-supported research.  The site-visit team reviewed IRB files for over 48 HHS-supported research studies, IRB meeting minutes for the past six months, IRB written standard operating procedures, and attended one of your IRB meetings.

We are pleased to note that we observed a good human research protection program.  Based on our observations, OHSU officials, IRB chairpersons, staff, and members conveyed a sincere commitment to and concern for the protection of human research subjects.  We would like to highlight the essential role your IRB analysts play in successfully carrying out the daily operations of your program.  Your IRB analysts seem to be a very cohesive, collegial, and capable team.  

We also note that the OHSU HRPP under Dr. Kathryn G. Schuff as the Human Protections Administrator (HPA) and IRB Chair has gone through considerable changes in leadership, staff, policies and procedures, in addition to the implementation of a new IRB electronic protocol submission, review, and approval system.  These fundamental changes have had a positive impact on the OHSU HRPP daily operations.  However, we did identify three issues that were discussed with you during the exit interview on September 3, 2015.  We make the following determination of noncompliance based on our review.

Determinations regarding your institution’s system for protecting human subjects:

HHS regulations at 45 CFR 46.111 list certain basic requirements for an IRB to approve research which include, but are not limited to, determining that “risks to subjects are minimized: . . . by using procedures which are consistent with sound research design and which do not unnecessarily exposure subjects to risk…”.  45 CFR 46.111(a)(1)(i).  OHRP notes that (a) when the convened IRB requests substantive clarifications or modifications regarding the protocol or informed consent documents that are directly relevant to the determinations required by the IRB under 45 CFR 46.111, IRB approval of the proposed research must be deferred, pending subsequent review by the convened IRB of responsive material; and (b) only when the convened IRB stipulates specific revisions requiring simple concurrence by the investigator may the IRB Chair or another IRB member designated by the Chair subsequently approve the revised research protocol on behalf of the IRB under an expedited review procedure.

Based on our review of the OHSU IRB meeting minutes and stipulation letters, we determine  that when the convened IRB requested substantive clarifications in protocol #00011083, the IRB approved the research with conditions in the absence of information that the IRB needed in order to approve the research at 45 CFR 46.111.  One condition stated, “it is unclear what the outcomes are – it is confusing what is really happening in the study.  Please include a hypothesis.”  The IRB would have needed this information in order to make the determinations at 45 CFR 46.111(a)(1)(i) 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.”  The Center for Disease Control and Prevention (CDC) was the funding HHS agency for protocol #00011083 titled “Spina Bifida Urological Protocol”.

Corrective Action:  We acknowledge that you informed us on September 28, 2015 that OHSU is implementing a corrective action plan to “improve the accuracy of the Boards’ determinations”.  This will be accomplished by retraining the IRB Chair, IRB- Vice-Chairs, IRB Manager, and IRB Specialists on their Human Research Protections Standard Operating Procedure “HRP 106 SOP – Committee Review Conduct”, particularly item “Conditionally Approve” and OHRP’s “Guidance on IRB Approval of Research with Conditions” of November 10, 2010.  This training will include a newly developed OHSU IRB Help sheet “Approval of Research: Approve with Conditions, Defer” with particular emphasis on the restriction that the Board may grant approval with conditions.  These conditions are: a) there are specified required changes to documents, or b) the investigator is asked to confirm specific assumptions or understandings on the part of the IRB regarding how the research will be conducted, such that, based on the assumption that the condition is satisfied, the IRB is able to make all of the determinations required for approval under the regulations at 45 CFR 46.111 and subparts B, C and D, as applicable.  Finally, OHSU will add the definition of “conditionally approve” and “deferral” to the IRB’s meeting approval guide, which currently contains the criteria for approval of research and subpart D determinations and is used during Board meetings as a reference sheet by IRB Board Members, IRB Specialists and IRB Chairs and Vice-Chairs.  This corrective action plan adequately addresses the determination.

Resolved Concerns:

The following concerns were shared with you at our site visit exit meeting on September 3, 2015.  These concerns have been adequately addressed by OHSU and we also note that these are not violations of the HHS regulations at 45 CFR part 46.

1. HHS regulations at 45 CFR 46.108(b) state that initial and continuing review of research must be conducted by the IRB at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas (i.e., a quorum), except where expedited review is appropriate under 45 CFR 46.110(b)(1).  Approval of research is by a majority vote of this quorum.  Should the quorum fail during a meeting (e.g., loss of a majority through recusal of members with conflicting interests or early departures, or absence of a nonscientist member), the IRB may not take further actions or votes unless the quorum can be restored.

We noted that the prisoner representative was treated as an alternate IRB member during OHSU IRB meetings, yet was listed on the OHSU IRB roster submitted to OHRP as a voting member without clarification that the prisoner representative would only count towards quorum when he or she reviewed studies covered by subpart C and attended.  In the absence of this comment, the roster gave the appearance that quorum required six members.  In numerous approved protocols during IRB meetings, the quorum was annotated as being met by the presence of five voting members.  That is, the number of voting members present to meet IRB quorum was not the same number of voting members expected based on the IRB roster submitted to OHRP.  We expressed our concern as to whether or not these facts were consistent with the regulatory requirements at 45 CFR 46.1108(b) that approval of research by the IRB is by a majority vote of this quorum.

Institution’s Action:  We acknowledge that OHSU submitted to OHRP on September 8, 2015 a change to the IRB (#00000471) registration to reflect that the prisoner representative is an alternate voting member when the IRB reviews protocols with prisoner populations.  This change eliminates any ambiguity about the quorum, making it clearer that the number of voting members is nine (when non-prisoner research is reviewed) and the quorum number is five, which adequately addresses the concern.

2. HHS regulations at 45 CFR part 46, subpart D, outline additional protections for children involved as subjects in research.  The regulations state that an IRB shall review research covered by this subpart and approve only research that satisfies the conditions of all applicable sections of subpart D. 45 CFR 46.403.  Currently, OHRP does not require any formal documentation of this process, but it is a best and common practice for IRBs to document this subpart D review process in their files.  Note that the Food and Drug Administration does require that the findings required under 21 CFR 50.51-54 be documented.

In protocols #00009034 and #00009182 that involved children and were approved in early 2013 through expedited review, there appeared to be no evidence in the files that the IRB had considered subpart D criteria for approval.  At the exit meeting, we expressed our concern as to whether or not these facts were consistent with the regulatory requirements at 45 CFR 46 Subpart D that outline additional protections for children involved as subjects in research.  

Institution’s Action:  During post visit communications, you provided clarification and evidence that the OHSU IRB had considered the additional regulatory requirements under subpart D.  Additionally, OHSU has updated its policy to require formal documentation of subpart D approval through a “checklist”.

We determine that the corrective actions by OHSU as described in this letter adequately address our determination and concerns.  At this time, there should be no need for further involvement by our office in this matter.  We appreciate your institution’s continued commitment to the protection of human research subjects


Alfredo R. Sancho, Ph.D., MPH
Commander, U.S. PHS
Division of Compliance Oversight

1101 Wootton Parkway, Suite 200
Rockville, Maryland  20852
Telephone: 240-453-8132
FAX:    240-453-6909
E-mail: [email protected]


Dr. Kathryn G. Schuff, HPA and IRB Chair
David Holmgren, MS, IRB Manager
Ms. Merlin Williams, CDC
Ms. Tiffany Neal, CDC
Ms. Daryl Barksdale, CDC

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