1.3 UNMC Serving as Central IRB for Multisite Research

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for the UNMC IRB to serve as the Central IRB (CIRB) for multisite research.

2.0 Policy

2.1. It is the policy of the Organization that the UNMC IRB may serve as the CIRB for multisite research as permitted by HHS regulations at 45 CFR 46.114 and FDA regulations at 21 CFR 56.114.

2.2. It is the policy of the Organization that the IO has the sole authority to determine whether or not to allow the UNMC IRB to serve as the Central IRB for multisite research.

2.2.1. For all non-exempt research, the Organization requires execution of a Reliance Agreement.

2.2.2. For exempt research, the Organization does not normally require execution of a Reliance Agreement.

2.3. It is the policy of the Organization that the UNMC IRB may serve as the IRB of record as permitted by HHS regulations at 45 CFR 46.114 and FDA regulations at 21 CFR 56.114 for NIH-funded research, in accordance with the NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research (NOT-OD-16-094).

2.3.1. The following requirements must be met for NIH funded research

2.3.1.1. The requirement for single IRB review applies to awardees in the United States and participating research sites in the United States.

2.3.1.2. The requirement for single IRB review does not apply to organization as outside the United States.

2.3.1.3. Awardee organizations are responsible for ensuring authorization agreement are in place, and that documentation is maintained.

2.3.1.4. The reviewing IRB is responsible for determining the additional requirements of the NIH Genomic Data Sharing Policy have been appropriately addressed.

2.3.2. Participating sites are expected to rely on the single IRB, though they may conduct their own review in accordance with NIH policy on exceptions from single IRB review.

3.0 Definitions

3.1. Ceded Review: An institution agrees to transfer IRB review and oversight authority for specified research to another institution’s IRB.

3.2. Local Context: Unique legal requirements, cultural or religious values, or other site-specific variables that exist at a site where subjects are enrolled in research.

3.3. Reliance Agreement (also known as an Authorization Agreement): An agreement between two Organizations engaged in human subject research that documents respective authorities, roles, responsibilities, and communication between an organization providing the ethical review and a participating organization relying on a reviewing IRB.

3.4. Relying Institution: A participating Institution that cedes IRB review to the IRB of record designated under a Reliance Agreement.

3.5. Site Principal Investigator (SPI): The lead investigator at each institution participating in multisite research usually responsible for the conduct of the research at the participating institution.

3.6. Study-Wide Principal Investigator (PI): The lead Principal Investigator with ultimate responsibility for the conduct and integrity of multisite research.

4.0 Responsibilities

4.1. Responsibilities of the UNMC IRB

4.1.1. Determining if the relying organization(s) apply their FWA to some or all of the research and ensuring the IRB review is consistent with the requirements of the Relying Institutions FWA (as applicable per DHHS and FDA regulations).

4.1.2. Provide the Site PIs/Relying Institutions with template informed consent form(s) which indicate areas where the Relying Institutions must add information related to local context.

4.1.3. Assume responsibility for IRB review of the research in full accordance with applicable federal and state regulations, and all relevant HRPP policies (including, but not limited to, initial review, continuing review, review of amendments, noncompliance, unanticipated problems involving risk to subject or others, deviations, adverse events, study holds, suspensions, and terminations).

4.1.3.1. The UNMC IRB is responsible for obtaining any additional approvals from DHHS when the research involves pregnancy women, fetuses, and neonates; or children; or prisoners.

4.1.3.2. The UNMC IRB is responsible for reporting all determinations of serious or continuing noncompliance, unanticipated problems involving risk to the subject or others, and suspensions or terminations to the Relying Institution, Institutional Officials and Federal Agencies HRPP policy 8.7 (Reporting Incidents to Institutional Officials and Federal Agencies)

4.1.4. Notify the Investigator and the Relying Institution (when applicable) of the IRB’s determinations.

4.1.5. Ensure HRPP policies are readily accessible to Relying Institutions through the IRB website (http://www.unmc.edu/irb) and there is a mechanism for communicating updates to the policies.

4.1.6. Provide the Relying Institution’s investigators and research staff with the Point of Contact (POC) to obtain answers to questions, express concerns, and convey suggest regarding the IRB.

4.1.7. Upon written request, provide Relying Institutions with access to relevant records related to IRB review (including, but not limited to minutes, approved protocols, consent forms, and other records that document the IRBs determinations to the Relying Institution).

4.1.8. Notify the Relying Institution within three business days, in the event that the FDA or other governmental agency issues the Organization any “Notice of Inspectional Observations”, “Warning Letters”, or other communications citing improper or inadequate research practices.

4.1.9. Maintain all research records for at least three years after completion of the research and make available for inspection or copying by the HHS Office of Human Research Protection (OHRP) and/or FDA upon request in accordance with federal regulations.

4.1.10. Ensure compliance with UNMC’s OHRP-approved FWA.

4.2. Responsibilities of the Relying Institution

4.2.1. Advise the UNMC IRB of any applicable state or local laws which govern research conducted at the site.

4.2.2. Advise the UNMC IRB of the results of additional reviews conducted at the Relying Institution, including but not limited to biosafety review, radiation safety review, recombinant DNA research review, human stem cell research review and conflict of interest.

4.2.2.1. Educate the investigators and research personnel at the Relying site of any requirements resulting from the additional reviews.

4.2.3. Advise the UNMC IRB of any circumstances when the review must take into account additional regulatory requirements.

4.2.4. Ensure that all investigators participating in the research are members of the Institution’s medical staff in good standing and are credentialed and privileged to perform the procedures outlined in the studies.

4.2.5. Ensure that all investigators participating in the research understand their responsibilities under applicable federal regulations (45 CFR 46 including subparts as applicable, 21 CFR 50, 56, 312, 812, and HIPAA Privacy Rule), state laws, institutional policies, and the protocol.

4.2.6. Ensure that all research personnel involved in the process of consent or assent are properly trained and are fully aware of their responsibilities relative to the obtainment of informed consent/assent according to institutional policies, applicable federal regulations, and state law

4.2.7. Notify the UNMC IRB within three business days of the termination, suspension, or modification of any clinical privileges of members of its Medical Staff who are participating in the studies authorized by the UNMC IRB.

4.2.8. Inform the UNMC IRB of any contact by the FDA, HHS, or any other persons or entities regarding any of the research specified above within three business days of contact. The Local Institution will also notify the UNMC IRB within three business days, in the event that the FDA or other governmental agency issues the Local Institution any “Notice of Inspectional Observations”, “Warning Letters”, or other communications citing improper or inadequate research practices with respect to the research specified above.

4.2.9. Maintain a copy of the signed informed consent document in the subject’s medical record for each subject participating in studies approved by the UNMC IRB.

4.2.10. Maintain all research records for at least three years after completion of the research and made available for inspection or copying by OHRP and/or FDA upon request in accordance with federal regulations.

4.2.11. Ensure compliance with its OHRP approved FWA (if applicable).

4.2.12. Permit the UNMC IRB, or its authorized representatives, the FDA, and OHRP to the extent permitted by law, to conduct the following:

4.2.12.1. Examine and inspect the Relying Institution facilities used for the performance of the studies, including storage and use of any investigational products.

4.2.12.2. Observe the conduct of the studies.

4.2.12.3. Inspect and copy all documents relating to the studies, including research records, patient medical records, informed consent documents, Investigational Product logs, and other study specific data.

4.2.12.4. Interview, as necessary, all necessary personnel involved in patient care for the studies.

4.2.13. Modify their FWA to designate the UNMC IRB as the IRB of record for the research.

4.3. Responsibilities of the Study-Wide PI

4.3.1. Serve as the primary contact with the UNMC IRB. The Study-Wide PI assumes primary responsibility for notifying the relying sites of all UNMC IRB actions.

4.3.2. Promptly respond to questions or request for information from Site PIs and/or study teams at relying institutions or the Relying Institution IRBs.

4.3.3. Assure the Site PIs have access to the HRPP policies.

4.3.4. Ensure all site consent forms/information sheets follow the UNMC IRB approved template and include applicable site-specific required language provided by each relying institution.

4.3.5. Provide the Site PIs and study teams with the IRB approved versions of all study documents.

4.3.6. Promptly report to all Site PI’s any unanticipated problems involving risks to subjects or others, research related subject injuries, or significant subject complaints that are related to or may affect subject’s willingness to continue participation in the study.

4.3.7. Notify Site PIs of all UNMC determinations and communications, including initial review, continuing review, Requests for Change, and reportable events.

4.3.8. Ensure Site PIs submit in a timely manner the Continuing Review Worksheet in order for the information to be included in the formal Continuing Review Application submitted to the UNMC IRB for review.

4.3.8.1. If a Site PI does not provide the Study-Wide PI with the required information in a timely manner, the Continuing Review application must report the absence of this information.

4.3.8.2. The Study-Wide PI must notify the Site PI of the lapse in IRB approval of their site and any applicable corrective action plans.

4.3.8.3. Provide access, upon request, to all study records by audit by any Relying Institution, the UNMC IRB, and other regulatory or monitoring entities.

4.3.8.4. Further description of PI responsibilities are defined in HRPP policy 1.26 (PI Qualifications and Responsibilities).

5.0 Procedures

5.1. A request that the UNMC IRB serve as the CIRB for multisite research must:

5.1.1. Identify the research network (if applicable) and the participating sites

5.1.2. Provide rationale for use of the UNMC IRB as the CIRB for the research.

5.1.3. Specify if this request applies to one, or multiple, research proposals.
Note: If the request applies to multiple research proposals specify if a UNMC PI will serve as the Lead Study Site for all research proposals or if Lead Study Site will vary according to the research.

5.1.4. Provide any relevant deadlines or funding agency requirements.

5.2. The UNMC IO must agree to allow the UNMC IRB to serve as the CIRB.

5.3. An IRB Reliance Agreement must be executed between the respective institutions. The fully executed IRB Reliance Agreement must be maintained as documentation verifying the responsibilities of each organization to ensure compliance with the requirements of the Common Rule.

Note: The Organization prefers to utilize the “SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement” platform. However, if the External Site cannot use that platform, a separate Reliance Agreement will be initiated between the Organization and the Relying Institution/IRB.

5.4. Each Relying Institution IRB must agree to cede IRB review to the UNMC IRB for each specific research proposal by completion of the Relying Institution Agreement to Cede IRB Review to the UNMC IRB. Note: All local institutional requirements regarding ceding review to the UNMC IRB must be complete before study activation at the Relying Institution.

5.5. Once the Organization has agreed to serve as the CIRB, the Study-Wide PI will complete the appropriate UNMC IRB applications throughout the life of the research through in RSS (https://net.unmc.edu/rss) in compliance with HRPP policy 2.1 (Submission of Items for Review by the IRB).
Note: Section I of the IRB application must clearly identify the external site(s) requiring UNMC IRB oversight.

5.6. The research will be reviewed by the IRB in accordance with the criteria for approval specified in HRPP policy 2.5 by either full IRB review (HRPP policy 2.2), or expedited review (HRPP policy 2.3) as applicable.
Note: All research conducted at participating sites will be subject to all relevant UNMC HRPP policies.

5.7. The UNMC-approved consent forms and information sheets will serve as the template for the relying sites. The template consent forms/information sheets to be used for the external sites will be created by the ORA/IRB Administrator.

5.8. Each Site PI must complete and submit for IRB review the CIRB Site Specific Application for the research. This application provides local context information specifically related to the research proposal. The application must include:

5.9. Verification of human subject protection training for all personnel listed on the CIRB Site Specific Application.

5.10. Information related to financial conflict of interest for personnel listed on the CIRB Site Specific Application.

5.11. Consent form(s)/information sheets(s) for that site based upon the template consent form/information sheet templates provided by the IRB Administrator.
Note: The Site Specific Application may be submitted at the time of initial submission of the protocol for IRB review, or at a later date to be reviewed as a Request for Change. The IRB has determined that addition of sites may be handled under expedited review (see HRPP policy 2.3, as applicable.

ADMINISTRATIVE APPROVAL: BRUCE G. GORDON, MD IRB EXECUTIVE CHAIR & ASSISTANT VICE CHANCELLOR FOR REGULATORY AFFAIRS CHRISTOPHER KRATOCHVIL, MD INSTITUTIONAL OFFICIAL

POLICY AMENDED:

 APRIL 4, 2016

 MARCH 27, 2018