IRB Reliance

Many institutions are working to reduce duplicative effort and the administrative burden associated with carrying out human participant studies by relying on one Institutional Review Board (IRB) to review and approve studies when multiple sites are engaged.  This is called the single IRB (sIRB) approach and is required by for federally sponsored research.  ETSU also applies this approach more widely for non-federal projects when ETSU and collaborating institutions agree that one IRB review is sufficient to approve the study and protect the rights and welfare of human participants.

IRB Reliance

IRB reliance is when an institution agrees to rely on the IRB review and approval of another institution's IRB. Both OHRP and the FDA permit an IRB the option to rely on the review of another IRB. When this is the intention, the two institutions enter into a reliance agreement. These agreements are executed between a Reviewing IRB's institution and one or more Relying Institutions and delineate the roles and responsibilities of the involved parties. The agreements can be for a single research study or for multiple studies (e.g., a Master Reliance Agreement). Reliance agreements must be signed by an authorized institutional official because the agreement is between institutions and not between investigators.

• Reliance agreements may be put in place when:

  • ETSU has agreed to be a Reviewing IRB (or IRB of Record) for one or more other institutions/organizations
  • ETSU has agreed to rely on the IRB of another institution or an independent IRB
• ETSU may agree that reliance is appropriate when:

  • ETSU and at least one other institution are engaged in collaborative research
  • The ETSU principal investigator (PI) has adequate resources to support the compliant conduct of a multi-site study
  • The collaborating institution has a Federal Wide Assurance (FWA) in good standing with the Office of Human Research Protections and has the policies and procedures in place to oversee and take responsibility for oversight of the research
  • The study is permitted under the ETSU Human Research Protection Program
  • The study undergoes either expedited or full board review (sIRB is not used for exempt studies)
• Reliance Agreements can be the following:

  • ETSU IRB serves as IRB of record for a study
  • ETSU relying on another IRB for a study
  • Reciprocal IRB agreement: ETSU either relying on or reviewing for partner IRBs for multiple studies

Understanding Responsibilities under Reliance

Reliance may change the number of IRBs that are involved in the IRB review process for a single study, but it doesn't change the amount of work required to obtain IRB approval for a protocol or a specific site. Instead, that work is simply shifted from the relying institutions to the site responsible for IRB review. The Reviewing IRB still requires all of the information necessary to approve a research study, and the submission to the Reviewing IRB must include sufficient details about each relying site's research procedures. Additionally, sites have varying requirements and considerations that must be communicated to the Reviewing IRB for consideration during the approval process.

• Lead Study Team Responsibilities

  Collecting all the required information about multiple sites can be time- and resource-intensive, and IRB offices generally aren’t in a good position to handle this task. Under the NIH’s proposed business model for sIRB, a lead site (usually the awardee institution) is responsible for communications between the research sites (i.e. relying institutions) and the reviewing IRB (e.g. collecting the required information from sites and compiling it for the reviewing IRB, making IRB submissions on behalf of sites, and communicating IRB decisions and approved documents back to sites).

  Most study teams aren’t prepared to handle this level of coordination and communication, so studies involving reliance represent a major change in responsibilities. Some larger research networks may have resources available to lead sites through these tasks. However, in many cases, lead sites will need to be ready to handle this additional work themselves and may need to consider budgeting for additional study staff. 

  The lead ETSU investigator is responsible for communication among the ETSU IRB and the relying sites’ IRB and research study teams. The lead ETSU investigator is responsible for all submissions to the ETSU IRB on behalf of the relying sites and must distribute all IRB approvals/study documentation to each site.

• Relying Institution Study Team Responsibilities

  Reliance is unlikely to result in less work, even for those sites which aren’t designated as lead. Most institutions (including ETSU) require a submission to the local IRB office describing the protocol and requests that an external reviewing IRB be allowed to provide review for the site’s participation. These submissions are generally much shorter than a full IRB application, but are required before the reviewing IRB’s review can be accepted. In addition, the reviewing IRB often has additional forms that must be completed by each site and may even need local IRB input.

  All sites must be prepared to follow the policies and procedures of the reviewing IRB. There is no standard set of IRB policies and procedures, although many IRBs may have similar requirements. Each investigator is responsible for understanding the policies and procedures of the reviewing IRB and conducting the research accordingly. Specifically, it is important for sites to understand the reviewing IRB’s expectations for reporting adverse events, deviations, noncompliance, and other problems to the reviewing IRB, as well as expectations for updating personnel and enrollment status, submitting amendments, and tracking subject enrollment and status, among other things. The lead site should provide this information to the sites and help study sites comply with reviewing IRB requirements.

  The ETSU relying investigator is responsible for initiating the reliance request by submitting the appropriate forms and documents to ETSU IRB for consideration. The ETSU relying investigator is also responsible for communicating with the lead study team to obtain appropriate documentation and information needed by the ETSU Human Research Protection Program.

• Reviewing IRB Responsibilities

  The IRB chosen to provide review – the reviewing IRB – has to fulfill the same responsibilities as any other IRB. In fact, those same responsibilities become harder to carry out since the information that could previously be gathered from one site must now be gathered from multiple sites. The reviewing IRB has to make the same determinations without the benefit of knowing the investigators, how they conduct research, or the resources available to them.

  To provide appropriate IRB review for all sites, the reviewing IRB reviews basic information about the protocol (e.g. procedures, risks, benefits, data safety monitoring, template consent language) to determine whether the protocol meets the federally mandated criteria for approval. Then the reviewing IRB considers each site individually and how each site will implement the protocol locally, collecting information about investigator qualifications and local context information, and incorporating site-specific language into template consent and authorization documents.

  The reviewing IRB also has to ensure that any institutional requirements applied by the participating sites have been completed (e.g. human subjects training, conflict of interest disclosure, scientific review, radiation safety review). These activities are often tracked on a local level using site-specific electronic systems that aren’t available to the reviewing IRB. Therefore, that information also has to be collected and considered for all sites.

• Institutional Responsibilities

  Each institution engaged in research maintains responsibility for safeguarding the rights and welfare of human subjects and complying with their federalwide assurance and applicable regulations in the conduct of cooperative research. The respective roles and responsibilities of each institution (relying and reviewing) must be formalized in a written agreement. The written agreement must be approved and signed by the signatory official (Vice Provost for Research) at ETSU and by the correlative officials of each of the other cooperating institutions. 

Submission Process

The IRB submission process differs depending on if you are requesting ETSU IRB serve as Reviewing IRB for external sites or if you are requesting to rely on an external IRB for review. You are strongly encouraged to contact the IRB office to schedule a consultation to determine ETSU's willingness to enter into a reliance agreement. Once you have determined that ETSU is willing to proceed with reliance, you can follow the instructions below for submission. Reliance agreements can take several weeks to complete due to the complexity and institutional officials involved.

• When ETSU serves as the Reviewing IRB for other sites

  Step 1: If ETSU is being asked to serve as the single IRB for a multi-site, collaborative research study, you must seek a consultation prior to submission to ensure that ETSU willing and able to take on this role. 

  Step 2: Work with the collaborating investigator(s) to contact their institutional IRB(s) to ascertain their willingness to rely on ETSU to provide IRB oversight for the study. Note the IRB contact person(s).

  Step 3:  Requests for ETSU to serve as IRB of Record are integrated into the IRB application xForm in IRBManager.  The xform asks whether your project involves collaboration with researchers at other institutions.  A “Yes” response triggers subsequent questions about IRB approval plans, including a request for oversight by the ETSU IRB. 

  NOTE: ETSU strongly recommends that you add non-affiliated research personnel and external sites via a stand-alone amendment (i.e. the only change is the addition of the non-affiliated research personnel or sites) after initial approval, not with the new study submission. Usually, the Reviewing IRB must grant approval of the protocol before another institution will agree to cede oversight. Completion of the required agreements can take several weeks and may delay initial approvals or approvals of amendments that include additional changes/multiple sites. If sites are included in the initial review submission, approval and agreements for all sites must be finalized before ETSU IRB can grant final approval for the study.

  ---

  Relying sites must provide the following to the ETSU PI:

  • Local context information (i.e., site-specific regulations, laws, customs, or policies that will impact how the site carries out the research at their site)
  • Any study documents that have been customized for the site (i.e., informed consent document)

  The ETSU PI should be prepared to provide the following information to the IRB for each site:

  • Name of the external institution engaged in the research
  • Name and email of the primary contact of the external institution’s IRB
  • Name and email of the PI of the external institution
  • Role of external investigators in the study
  • Local Context information from the external institution
  • Study site-specific documents (i.e., informed consent document, recruitment materials)

  After the IRB receives the submission with the external site information, the IRB office will work with the ETSU PI and external site IRB contact to establish the reliance agreement while the IRB review is taking place. The ETSU PI must have both the executed reliance agreement and final IRB approval letter before allowing the Relying Site(s) to conduct research associated with the collaborative project. 

• When ETSU is relying on an External IRB for review

  Step 1: Contact the researchers at the other institution to determine whether they are willing to assume responsibility for obtaining IRB approval for the ETSU research team’s involvement in the project.

  Step 2: Consult with the ETSU IRB office to make sure ETSU is willing to rely on the proposed Reviewing IRB. Review the FAQs below for information about limitations on reliance agreements.

  Step 3: Work with the collaborating investigator to contact the proposed IRB of record to ascertain their willingness to serve as IRB of record for the study.  Note the contact person from the proposed IRB of record.

  Step 4: Obtain External IRB approval following their established processes.

  NOTE: The sIRB may require local context information specific to ETSU, such as contact information for the ETSU IRB, ETSU required informed consent language, ETSU-specific policies such as child-abuse reporting, etc. To obtain this information, please email IRB@etsu.edu.

  Step 5: Complete the Request to Rely on an External IRB xForm in IRBManager. Once you have External IRB approval and have registered the project with ETSU, be sure to carry out the research as approved by the IRB and applicable ETSU policy.

  ---

  When you submit a reliance request, be ready to provide the following:

  • Name and contact information for the Reviewing IRB, Lead PI, and the institution's signatory official
  • Documentation that the protocol has been reviewed and approved by the external IRB, unless reliance on a commercial/independent IRB is requested
  • IRB-approved protocol, informed consent(s), and other study specific documents
  • 
    
    
    
    Documents provided by the external IRB for completion by the ETSU IRB or HRPP (e.g. local context sheet, reliance agreement template, determination form, etc.)
  • List of ETSU study staff engaged in the research
  • Information about conflicts of interest for the ETSU study staff
  • Funding/sponsor information for the project, including relevant sub-awards, contracts, or other agreements

  After the IRB office receives the request to rely, the IRB office will work with the ETSU PI and external site IRB contact to establish the reliance agreement. The ETSU PI must have both the executed reliance agreement and ETSU Registration Letter before conducting research associated with the collaborative project. 

  Once the HRPP has granted your request for reliance and the external IRB has approved your study, you are still required to continue to submit some items to the ETSU HRPP including:

  • Any ETSU study staff changes
  • Copies of all external IRB approvals for the duration of the study (i.e., modifications, continuing reviews)
  • Reports of any adverse events, noncompliance, safety information, or unanticipated problems
  • Updated information for any changes to funding agreements or conflicts of interest

  Once you have External IRB approval and have registered the project with ETSU, be sure to carry out the research as approved by the External IRB and applicable ETSU policy.

FAQs

• When will ETSU consider serving as the IRB of record for external sites?

  The Human Research Protection Program (HRPP) Director and Vice Provost for Research determines whether serving as IRB of record is appropriate on a case-by-case basis. The HRPP Director may seek consultation from the IRB Chair(s), University Administration, University Counsel, or others, when needed to make this determination. In general, however, the ETSU IRB will consider serving as IRB of record for most collaborative, minimal-risk research where the ETSU IRB has the appropriate disciplinary expertise to review the project.
• When will ETSU not serve as IRB of record?

  The ETSU IRB will not typically consider serving as IRB of record in certain situations, including the following:

  • An ETSU employee or student is not involved in the research.
  • The external site does not have a Federalwide Assurance for the Protection of Human Subjects.
    
    
  • The study qualifies for exemption.
  • The ETSU IRB does not have sufficient expertise regarding the study procedures or knowledge of the local context at the external site(s) (as required by federal guidelines).
  • The protocol is a clinical trial that requires single IRB per federal sponsor requirements.
  • The ETSU IRB feels it or the ETSU PI cannot adequately oversee the external site or personnel in manner that will ensure the protection of human subjects.
  • Studies for which administrative or campus policies otherwise prohibit or limit options for serving as IRB of record.
    
    

   

• If the ETSU IRB agrees to serve as IRB of record for external collaborators, do the external collaborators need to complete ETSU human subjects training?

  Generally, no, external collaborators do not need to complete ETSU human subject protection training. The ETSU IRB does not normally assume responsibility for the compliance of external personnel who are affiliated with an external institution and prefer the terms of the reliance agreement to require external collaborators to verify their own researchers' training. External personnel should contact their institution and follow their institution’s policies for training, credentialing, conflict of interest disclosure and other applicable compliance requirements, unless ETSU communicates to the ETSU PI that the terms of the reliance require otherwise.

• What is an external reliance? 

  An external reliance is when ETSU chooses to accept the review and approval of an IRB from an external organization.
• When will ETSU rely on an external IRB? 

  Here are the factors to consider:

  • The external organization must have an accredited human subject protection program. In the absence of accreditation, ETSU may rely on an external IRB that meets ETSU human research protection standards.
  • The external IRB must have a current FWA and be registered with OHRP (and FDA if applicable).
  • Local laws, institutional policies and constraints, professional and community standards, and population differences are examples of pertinent local factors that can influence the setting of research.  In studies where these may be an issue, and at the discretion of the HRPP Director and Vice Provost for Research (VPR), review by one of the ETSU IRBs may be required.
  • VA studies require ETSU/VA IRB review and may not use an external reliance unless the external IRB is listed on the VA FWA. 
• When will ETSU not rely on an external IRB?

  Here are the factors to consider:

  • The proposed IRB of record does not have an established or current Federalwide Assurance.
  • The proposed IRB of record does not have sufficient knowledge of local context (as required by federal guidelines) to assume IRB oversight for sites that fall under ETSU purview.
  • The project does not include an ETSU  principal investigator.
  • The proposed IRB of record's human research protection program is not accredited and the study is greater than minimal risk.
  • The study qualifies for exemption.
  • The institutions cannot agree to the terms and responsibilities outlined in the formal reliance agreement.
• How do I submit the required reports for studies approved by an External IRB? 

  All reports are submitted electronically in IRBManager and must be signed by the PI. To submit the results of a continuing review from the external IRB, submit an “External Continuing Registration” xform. To submit any other report, including amendments, protocol deviations/violations, UPIRTSOs, monitoring reports, submit an “External Events” xform. The HRPP Director and VPR evaluate the post approval reports and confirm that reliance continue to be appropriate. 
• What kind of agreement is required for collaborative research relying on a single IRB?

  A formal IRB reliance agreement is required per federal regulations for cooperative research involving multiple sites. This is called an IRB Authorization Agreement (IAA), and it must be agreed to and signed by institutional officials at both institutions.

  ETSU is a participating member of the SMARTIRB consortium and prefers to utilize that reciprocal agreement but will negotiate an individual IAA with sites as needed to facilitate reliance.

• How long does it take to establish the agreements?

  Timeframes for finalizing these agreements depends on several factors, including the responsiveness of the sites' IRB offices and their experience with reliance agreements, the complexity of the research project, as well as whether language in the IAA requires negotiation. In some cases, advice from legal counsel at both institutions is required. Study teams are advised to keep this in mind when considering requesting that ETSU serve as IRB of Record.

• Who approves ETSU IRB reliances?

  The Institutional Official (IO) is vested with the authority to make the decision whether or not to review for or rely on another IRB. At ETSU the IO is the Vice Provost for Research. The IO is authorized to execute IRB reliance agreements on ETSU’s behalf and may delegate this signatory authority.

• Does the agreement need to be finalized before the research can begin?

  When ETSU agrees to serve as IRB of Record, all human subjects research activities conducted by ETSU researchers and researchers at the collaborating institution(s) must have approval from the ETSU IRB before they can begin. The IAA agreement is only one step—IRB review and approval is still necessary. However, the IAA agreement must be finalized before the activities of external researchers are considered to be “covered” by the ETSU IRB.

• What should I do if my grant proposal requires a plan for Single IRB Review, or I am asked to collaborate on a grant that will propose Single IRB Review?

  It is important to verify with the ETSU IRB any plans for use of a single IRB before a grant proposal is submitted. While most federal agencies do not require the single IRB plan to be submitted with the proposal, there must be a plan to comply with the requirement for single IRB. 

  IRBs may charge for the review of external site submissions, even on federally funded projects. Thus, it is important to consider potential IRB charges in grant budgets. 

  There is no requirement for IRBs to agree to serve as the single IRB for other sites, and each institution has its own policies and limitations for when it will take on the role of single IRB. Confirming the single IRB plan with the sites prior to proposal submission can reduce later hurdles and administrative burden.

• What if I have other questions about this process? 

  There are additional guidance documents and educational resources available on the ETSU IRB website. The HRPP Director is the primary contact for all reliance related questions and can be reached at 423-439-6054.