Single IRB (sIRB) | Reliance Agreements

The following chart provides a general overview of the reliance process. More specific guidelines can be found in subsequent sections.

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When is a Reliance Agreement Needed?

Cooperative research, which involves collaborative efforts from multiple investigators from across institutions, offers a number of benefits. By leveraging the collective expertise, resources, and perspectives of multiple institutions, cooperative research can enhance research outcomes and positively impact diverse populations.

A reliance agreement is required whenever more than one domestic institution is considered engaged in either cooperative or multi-site federally funded research. Institutions may also choose to enter into reliance agreements for non-federally funded non-exempt research at the discretion of the institution. International participating sites are not required to comply with any sIRB requirements. Instead, in these cases, a local ethics committee review is completed to ensure local customs and norms are addressed.

Furthermore, the non-UNL institutions must be engaged in the research for a reliance agreement to be necessary. Please be aware, each institution may apply the “engagement” guidance differently. It is the responsibility of the relying institution to determine if their institution is engaged. Please refer to the following flowchart to determine whether an institution is engaged in research to assist in sIRB planning:

Commercial Service: For an activity to be considered a commercial service, all of the following must be true:

• The external personnel will not receive professional recognition or publication privileges for the services provided;
• The external personnel typically perform the services for non-research purposes; AND
• The external personnel will not administer any intervention being tested or evaluated under the protocol.

Interactions: These occur when investigators communicate or have interpersonal contact with research participants, for example verbally, in writing, or electronically, to obtain information about them for the research.

Interventions: On the other hand, these include both physical procedures by which investigators collect information or biospecimens and manipulate the subjects or the subjects’ environment for the purpose of the research.

If multiple institutions are involved with a research project, but only UNL is considered engaged in the human subjects research activities, no reliance agreements are necessary. Instead, please refer to our Site Permission Documentation A-Z Guidance entry to determine whether an institution is considered a recruitment or performance site for your research and what documentation may be needed.­­ For more information regarding a Materials Transfer Agreement (MTA) or a Data Use Agreement (DUA), please refer to our Secondary Information and Biospecimens: Use in Research and IRB Applicability A-Z Guidance entry. This guidance also specifies who to contact if one of these agreements is necessary.

What Types of Projects Require Agreements?

Individual Investigator Agreement

As described in UNL HRPP Policy 3.017, Individual Investigator Agreements, the IIA is an agreement between UNL and an external collaborating independent investigator or a collaborating institutional investigator that does not hold an FWA and does not regularly conduct human subjects research. In these cases, the external collaborator will sign an agreement with UNL agreeing to complete research under UNL’s Federal Wide Assurance and IRB policies. If it is determined that an IIA is necessary, RCS will work with investigators to prepare and complete the document.

Individual Investigator Agreement Information and Forms

Reliance Agreement

This is the agreement that documents respective authorities, roles, responsibilities, and communication between an institution/organization providing the ethical (IRB) review and a participating site relying on the Single-IRB (sIRB). UNL, per policy, will only complete a Reliance Agreement for non-exempt research (i.e., Expedited or Full Board review).

UNL holds blanket agreements with the University of Nebraska Medical Center as well as Boys Town National Research Hospital. The agreements allow us to meet requirements both under HHS regulations and FDA regulations.

Considerations for Investigators

When developing your project, consider whether there is a need for reliance if at all. The reliance process can be time consuming, especially when coordination is required between multiple institutions. The following are scenarios to demonstrate when reliance would and would not be necessary.

Note: If a project involving multiple institutions is federally funded AND has been reviewed as non-exempt (i.e., Expedited or Full Board), a reliance agreement is required regardless of other project specifics.

Form Submission

Investigators at all involved sites should notify their respective IRBs of their potential need for reliance as early as possible or based on the institution’s policies and standard operating procedures. The UNL Lead investigator should submit one of two forms, depending on whether they are requesting UNL serve as the reviewing or relying institution. Depending on their institutional policies, some institutions may not require the use of a reliance agreement in certain circumstances. Once all institutions have determined they are willing to enter into a reliance agreement, the IRB points of contact will work together to determine the best timelines for reliance based on project specifics and project needs.

• For projects where UNL has agreed to become the Reviewing IRB, a new project form should be submitted. This form should outline the full scope of activities in which collaborating investigators will be engaged, including recruitment, data collection, data storage, etc. This information is necessary as the Reviewing IRB is assuming responsibility for reviewing the research activities conducted at all collaborating sites. The New Project Form will become the project’s “parent protocol.”
• For projects where UNL is expected to be the Relying IRB, a determination form should be submitted with a request to cede review. This form should provide the scope of activities that UNL-affiliated individuals will be completing as part of the overall project.

Obtaining full IRB approval for a multi-site project can be a lengthier process, as relying sites may need to be provided with the full approved protocol and consent language before they formally agree to serve as a relying institution. Accordingly, the approval of the parent protocol will be followed by an onboarding process, within which collaborating sites agree to rely on the Reviewing IRB for human subjects research. As resources, timetables, and requirements can vary substantially across institutions, PIs should budget for the additional time required in receiving approval for collaborating institutions when developing projected timetables.

Once it is determined that UNL will enter into a reliance agreement as either the Reviewing or Relying IRB, investigators will need to complete additional steps as requested by either the UNL IRB or the Reviewing IRB (when UNL is a Relying site). Please be aware that no research can begin at UNL until an appropriate approval letter is in place from UNL. This includes when UNL is a Relying Site.

Local Context Review: It is important that all applicable laws, regulations, and applicable policies at each institution are considered during IRB review and site onboarding.  To obtain this information, institutions may be asked to complete a local context review. Different institutions may have different considerations or requirements. If UNL is a Relying site, UNL’s sIRB reliance coordinator will work with investigators and the Reviewing IRB as needed to provide requested information or supply authorized signatures.

Where the collaborating site has provided local context information relevant to conducting research at a collaborating site, the Reviewing site or Lead PI is responsible for ensuring that those requirements are reflected in the research procedures applicable to that site outlined in the research protocol. The Reviewing IRB will provide researchers with any local context information provided by the relying institution.

Execution of Individual Investigator Agreements: For non-exempt research, when external investigators that are not affiliated with an institution which holds a Federalwide Assurance will be integrated into the study team, individual investigator agreements will need to be executed with each of these individuals. The Reviewing Site PI is responsible for ensuring that each of these investigators provides the Reviewing IRB with the documentation required in HRPP Policy # 3.017 – Individual Investigator Agreements.

Investigator Responsibilities: To ensure a timely review, it is the responsibility of investigators to ensure that all UNL-affiliated project personnel have completed the necessary human subjects training, have completed the Conflict of Interest statement (and have a management plan in place should a conflict be identified), and obtaining any additional ancillary reviews that may be necessary (radiation safety, biosafety, etc.).

During review, investigators are responsible for ensuring that the consent language required by collaborating institutions is adequately integrated into the consent forms utilized for the project. Subsequent revision may be required to ensure that the consent language meets HRPP policy requirements while reflecting the requirements of the collaborating institution.

The Lead PI is responsible for obtaining approval for all site-specific documentation (e.g., consent, advertisements, communication with participants, etc.) and disseminating that documentation to collaborating investigators.

Once the reliance agreement is ready to be executed, the UNL HRPP will ensure that the agreement is appropriately signed (by Institutional Officials at all institutions involved, or their delegate) and will maintain a copy of the finalized agreement. The UNL HRPP or the Lead PI will facilitate communication with Relying IRBs or the Reviewing IRB as required by the executed agreement, standard operating procedures and the agreed upon sIRB communication plan.

Once parent protocol approval has been received, reliance agreements are executed per site, and applicable sites are added to the project and onboarded, the project can commence at each site, as applicable. When UNL is the Reviewing IRB, the following items must be completed as necessary:

Modifications to the Protocol: Where a modification to the research procedures at a collaborating site is required, the Reviewing Site PI is responsible for obtaining approval from the Reviewing IRB before those changes can be implemented. This is completed via a Change Request on the approved project protocol.

Maintenance of Project Personnel: In most cases, the Relying IRB is responsible for verifying, in coordination with the Reviewing IRB point of contact, that site investigators or study team personnel meet the institutional requirements for the relying institution, including education, training, and qualifications to perform the research and safeguard the rights and welfare of research subjects. The Relying IRB is also responsible for disclosing any conflict of interest related to research conducted under a reliance agreement and providing applicable management plans to the Reviewing IRB.

Reporting Protocol Deviations, Violations, Unanticipated Problems, and Adverse Events at Collaborating Sites to the Reviewing IRB: The Reviewing Site or Lead PI is responsible for communicating reportable events to the Reviewing IRB, even where those events occur at collaborating sites. Thus, the PI will need to maintain active lines of communication with their collaborating investigators to ensure that events are reported promptly to the Reviewing IRB. Where additional information is required, the Reviewing PI will need to liaise with the collaborating institution to ensure that information is provided to the Reviewing IRB in a timely manner commensurate with the reporting time requirements and seriousness of the report.

Continuing Review/Annual Update: Annual Update or Continuing Review requirements must be met yearly. These forms are submitted based on the project’s review type and Reviewing IRB institutional requirements.

Final Report/Project or Site Closeout: When the project has been completed, a Final Report must be submitted to properly close out the project.

If UNL is the Relying IRB: Updates to UNL, as a relying institution, should be submitted specific to UNL as the site applicable to the type of documentation submitted upon completion of review by the Reviewing IRB. For example, if a change that applies to UNL is approved, this should be submitted via a change request form to the UNL IRB as a means to keep the Institution updated on the status of the study. The change, however, could be implemented without the UNL approval given that this is an institutional update.

• It is important to note that SMART IRB is not another IRB, but rather an online reliance agreement tracking system and communication tool for IRB administrators.
• PI’s will need to register in order to gain access. This process takes about 2 business days to approve, so advance notice and planning will be important.
• If a partnering institution is a member of SMART IRB, UNL may require the use of this system to manage the agreement process.
• PI’s can see if collaborators are registered members by checking the SMART IRB website.

Additional Guidance and/or External Resources:

• SMART IRB website
• Request investigator access to SMART IRB
• Online Reliance Walkthrough Video
• Searchable SMART IRB Resources

UNL and UNMC, as well as UNL and Boys Town National Research Hospital, have standing master agreements to fluidly cede review to the respective institutions without having to sign study specific agreements. The decision to serve as a Relying or Reviewing IRB is made on a project-by-project basis. All projects must be submitted via the same procedures provided above. (This does not imply that Boys Town and UNMC have a master agreement between their organizations.)

Research can only begin if all other required approvals have been obtained (i.e., radiation safety, biosafety, conflict of interest, etc.). For questions related to multi-site or cooperative research agreements, please contact unlreliance@unl.edu or call (402)472-8196.

DHHS:

• 45 CFR 46.114
• 45 CFR 46.101

NIH:

• Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
• Guidance on Exceptions to the NIH Single IRB Policy
• Single IRB for Multi-Site or Cooperative Research
• Single IRB FAQs

UNL Policy:

• 3.012: IRB Approval of Multi-Site or Cooperative Research
• 3.017: Individual Investigator Agreements