1.3 UNMC IRB Serving as the Single 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 Single IRB (SIRB) for multisite research.

2.0 Policy

• 2.1. It is the policy of the Organization that the UNMC IRB may serve as the SIRB 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 Single 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).
• 2.4. It is the policy of the Organization that research conducted at external organizations where UNMC is the IRB of record must comply with HRPP policies of the relying institution, except as specified in this policy and/or in the Reliance agreement.

3.0 Definitions

• 3.1. Cede Review: An institution agrees to transfer IRB review and oversight authority for specified research to another institution’s IRB (reviewing 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 the reviewing and relying IRBs.
• 3.4. Relying Institution: A participating Institution that cedes IRB review to the IRB of record (reviewing IRB) designated under a Reliance Agreement.
• 3.5. Site Principal Investigator (Site PI): The lead investigator at each institution participating in multisite research usually responsible for the conduct of the research at the participating institution.
• 3.6. Lead Principal Investigator (Lead PI): The study wide lead Principal Investigator with ultimate responsibility for the conduct and integrity of multisite research.
• 3.7 Reviewing IRB: The IRB which is responsible for conducting IRB review and approval as described in 45 CFR 46.109 for cooperative human subject research.

4.0 UNMC IRB, Relying Institution, and Lead PI Responsibilities

• 4.1. It is the responsibility of the UNMC IRB (as reviewing IRB) to:
  • 4.1.1. Conduct 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).
    • 4.1.1.1. Review any COI management plans from the relying institution to assure the plan is adequate in consideration of the nature of the conflict. The UNMC IRB as reviewing IRB may apply additional restrictions and/or limitations but may not override those required by the relying institution.
  • 4.1.2. Obtain any additional approvals from DHHS when the research involves pregnant women, fetuses, and neonates; or children; or prisoners, as required by DHHS and FDA regulations.
  • 4.1.3. Determine 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).
    • 4.1.4. Report 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
    • 4.1.5. Report to the Relying Institution:
      • 4.1.5.1. Any unanticipated problems involving risk to the subject or others associated with subjects enrolled at the institution.
      • 4.1.5.2. Any serious or continuing noncompliance.
      • 4.1.5.3. Any serious complaints which impact the rights and welfare of research subjects.
      • 4.1.5.4. The results of any external audits conducted by FDA, OHRP, sponsors, and CROs.
      • 4.1.5.5. Any reports filed with the FDA or OHRP.
      • 4.1.5.6. Any FDA Form 483 or warning letter pertaining to the study or IRB review.
      • 4.1.5.7. Any other communication from FDA or other governmental agency citing improper or inadequate research practices.
    • 4.1.6. Notify the Investigator and the Relying Institution (when applicable) of the IRB’s determinations.
    • 4.1.7. Provide the Relying Institution’s investigators and research staff with the Point of Contact (POC) to obtain answers to questions, express concerns, and convey suggestions regarding the IRB.
    • 4.1.8. 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 IRB’s determinations to the Relying Institution).
    • 4.1.9. Ensure HRPP policies are readily accessible to Relying Institutions through the IRB website and there is a mechanism for communicating updates to the policies.
      • 4.1.10. Maintain all research records for at least seven 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.
      • 4.1.11. Ensure compliance with UNMC’s OHRP-approved FWA.
• 4.2. It is the responsibility of the Relying Institution to:
  • 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 completion of all additional reviews required by the Institution, including but not limited to biosafety review, radiation safety review, recombinant DNA research review, human stem cell research review and conflict of interest, and of any requirements resulting from the additional Institutional reviews.
  • 4.2.3. Advise the UNMC IRB of any circumstances when the review must take into account additional regulatory or local HRPP 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.
    • 4.2.4.1. 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.
  • 4.2.5. Advise the UNMC IRB of any allegations of noncompliance. The UNMC IRB, in conjunction with the participating site IRB, will determine how best to handle the allegation in consideration of the need to maintain due process and protect the whistleblower.
  • 4.2.6. Advise the UNMC IRB of any complaint directly from subjects or others. The Research Subject Advocate Office will assist in the resolution of the complaint as necessary.
  • 4.2.7. Inform the UNMC IRB of any contact by the FDA, HHS, or any other persons or entities regarding any of the research within three business days of contact. The relying Institution will also notify the UNMC IRB within three business days, in the event that the FDA or other governmental agency issues the relying Institution any “Notice of Inspectional Observations”, “Warning Letters”, or other communications citing improper or inadequate research practices with respect to the research specified above.
  • 4.2.8. 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.
  • 4.2.9. 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.
  • 4.2.10. Maintain a copy of the signed informed consent document in accordance with relying institution policies, applicable HHS and FDA regulations, and ICH-GCP.
  • 4.2.11. Maintain all research records in accordance with relying institution policies, applicable HHS and FDA regulations, ICH-GCP and HIPAA Privacy rule as appropriate.
  • 4.2.12. Ensure compliance with its OHRP approved FWA (if applicable).
  • 4.2.13. Permit the UNMC IRB, or its authorized representatives, the FDA, and OHRP to the extent permitted by law, to conduct the following:
    • 4.2.13.1. Examine and inspect the Relying Institution facilities used for the performance of the studies, including storage and use of any investigational products.
    • 4.2.13.2. Observe the conduct of the studies.
    • 4.2.13.3. 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.
    • 4.2.13.4. Interview, as necessary, all necessary personnel involved in patient care for the studies.
• 4.3. It is the responsibility of the Lead (UNMC) PI to:
  • 4.3.1. Serve as the primary contact with the UNMC IRB. The Lead 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 participating sites 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 participating site (pSite) Continuing Review Application.
    • 4.3.8.1. The Lead PI must notify the Site PI of any lapse in IRB approval of their site and any applicable corrective action plans.
    • 4.3.8.2. 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 single IRB request form must be submitted for each research protocol to the UNMC IRB. The sIRB request form requests:

  • 5.1.1. The identity of the research network (if applicable) and participating sites
  • 5.1.2. Provides rationale for use of the UNMC IRB as the sIRB for the research.
  • 5.1.3. Identifies any relevant deadlines or funding agency requirements.

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

• 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” electronic platform. However, if justifiable, an alternate form of the Reliance Agreement will be initiated between the Reviewing and the Relying Institutions/IRBs.

• 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 Reliance Agreement and Implementation Checklist, or other agreed upon mechanism.

  Note: All local institutional requirements regarding ceding review to the UNMC IRB must be completed before study activation at the Relying Institution.

• 5.5. Once the Organization has agreed to serve as the sIRB, the Lead PI will complete the appropriate UNMC IRB application through in 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, such as those related to reporting adverse events, deviations, noncompliance, and compensation, as well as relevant participating site HRPP policies, such as those related to, advertisement, ethical access, recruitment, short form consent, process and documentation of consent, etc.

• 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 UNMC study team, modified with local context information by the participating site study team, and approved by the ORA/IRB Administrator. These are available in RSS.

• 5.8. Each Site PI must complete and submit to the UNMC IRB the pSite Application for the research. This application provides local context information specifically related to the research proposal. 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).

DOCUMENT HISTORY:

 Undocumented activity: 4/4/2016

 Undocumented activity: 3/27/2018

 Revised: 10/21/2021 - Major revisions in format; content revised to be consistent responsibilities described in HRPP 1.4, Notification: not documented

 Revised 8/25/2023 - Added additional responsibility for UNMC HRPP regarding review of relying institution COI management plan (section 4.1.1.1). {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}