IRB Reliance (Single IRB Review)

What is a single IRB review?

A review performed by one institution (IRB of Record) for multi-site research to establish the expectation that a single IRB (sIRB) of record will be used in the ethical/scientific review of non-exempt human subjects research protocols.

What it doesn't do

It does not substitute Investigator responsibilities or other institutional requirements. Investigators are still responsible for conducting research in compliance with regulations, laws, and institutional policies (local context) for the protection of human subjects in research. Should a project involve other review entities/committees such as OCTA, OCAA, PRMC, COI, etc. it is still the Investigator’s responsibility to ensure that these entities/committees have been informed of a required review, as appropriate.

What’s driving sIRB?

• NIH’s sIRB Mandate
  • In 2016, the NIH issued a policy mandate requiring the use of a sIRB for multicenter NIH-funded studies effective Jan. 25, 2018.
• Broader Common Rule Single IRB (sIRB) requirement
  • At the broader federal level, in 2017, the final changes to the Common Rule were announced, including a mandate that U.S. institutions involved in cooperative research in the U.S. (with certain exceptions) use an sIRB, effective Jan. 20, 2020.
• Groups of collaborators 
  • This is also true for collaborative groups (e.g. CTSAs and Disease-specific networks).

• Industry Sponsors

Who Can Serve as an sIRB?

• IRB of one institution – Prime awardee, or expertise in a particular field of research.
• Commercial IRB
  
  • Western Copernicus Group IRB (WCG IRB)
  • Advarra IRB
• Other central IRB
  
  • National Cancer Institute Central IRB (NCI-CIRB)
  • All of Us IRB
  • Sterling IRB

Exceptions to sIRB Mandate

• Policy-based Exceptions
  • When Federal, State, Tribal, local laws/regulations/policies require local review
  • Tribal regulations/policies given specific consideration in order to ensure that the importance of their role is recognized
  • Does not require NIH Exceptions Review Committee approval
• Time-Limited Exceptions
  • When ancillary studies are part of ongoing studies or parent studies
  • Do not require sIRB until the parent study is expected to comply with the sIRB policy
• Compelling Justification or Other Exceptions
  • When there is a compelling justification for local IRB review
  • Requires NIH Exceptions Review Committee approval

What is a Reliance Agreement (RA)?

A reliance agreement is a formal, written document that provides a mechanism for an institution engaged in research to delegate institutional review board (IRB) review to an independent IRB or an IRB of another institution. Authorization agreements may be for a specific study, a specific research, or for specific classes or categories of research. They describe the responsibilities of the relying institution and researcher as well as the responsibilities of the reviewing IRB and its institution.

Agreement Types

• IRB Authorization Agreement (IAA) 
• Individual Investigator Agreement (IIA)
• Master Reliance Agreement (Bilateral or Multi-lateral)
  • E.g. Smart IRB, WCG IRB, Advarra IRB, NCI CIRB

NOTE: Reliance agreements are executed by an authorized Signatory Official/Institutional Official (IO) or designated IRB representative. Investigators cannot sign themselves. 

Current reliance arrangements include:

• Smart IRB
• Commercial IRBs
  • Western Copernicus Group (WCG) IRB
  • Advarra IRB
• National Cancer Institute Central IRB (NCI CIRB)
• All of Us IRB

SMART IRB

The Streamlined, Multisite, Accelerated Resources for Trials IRB Reliance platform (SMART IRB), is designed to harmonize and streamline the IRB review process for multisite studies, while ensuring a high level of protection for research participants. SMART IRB is not an IRB, but a master reliance agreement with hundreds of participating institutions.  The SMART IRB master reliance agreement replaces the need to have an individual Institutional Authorization Agreement (IAA). 

Please review the list of Participating Institutions to see if your collaborator’s institution is a member of SMART IRB. Additional resources are available on the SMART IRB Learning Center webpage.

Acknowledging the use of the Smart IRB Agreement can be accomplished one of two ways:

• Executing a SMART IRB Letter of Acknowledgment (LOA) or
• Using the SMART IRB Online Reliance System (ORS)

The SMART IRB ORS allows research teams to submit an electronic request to execute reliance under the terms of the SMART IRB master reliance agreement. The request is typically initiated by the lead study team whose IRB will be serving as the IRB of Record for all sites.  Each person requiring access to the online reliance system will need to submit a separate request for access to the system. If you've requested access and haven't received confirmation within a week please contact irbrely@ucsd.edu 

Request Access: https://reliance.smartirb.org/users/sign_up

Sign In: https://reliance.smartirb.org/users/sign_in 

If you are a part of the lead study team, the next steps are required to proceed with the request in the online system:

• Basic information about the research (title of study and a brief description)
• Name of Principal Investigator
• List the engaged sites which are requesting to cede review to the IRB of Record
• Identify activities and study team personnel at each site
• Upload the research protocol and consent form templates

IREx

The IRB Reliance Exchange (IREx) is a web-based platform, supported by the Duke/Vanderbilt Trial Innovation Center (TIC), to facilitate Single IRB documentation, communication, and the exchange of information. 

 IRBs, coordinating centers, and study teams use IREx for the following features:

• Document and track reliance arrangements between FWA-holders and component sites
• Execute reliance agreements under the terms of the SMART IRB master reliance agreement
• Track participating site progress towards initial IRB approval
• Streamline and centralize the capture of participating sites’ local considerations on a study-by-study basis
• Centrally manage participating site approval documents from initial approval through study close
• Facilitate communications to participating sites when actions are required
• Automate notifications to participating sites of new approvals and upcoming continuing reviews

For more information please reference the following IREx resources:

• Using IREx as the Lead Study Team/Coordinating Center
• Using IREx as the Participating Site Study Team
• IREx Workflows

UCSD Reviewing

For single IRB studies where UCSD will be the reviewing IRB, after UCSD IRB has approved the protocol, the UCSD PI must submit an amendment for participating sites to be reviewed. For each participating site, the following documents should be include in the amendment application in the Participating Sites tab:

• Basic information regarding the sites activities for the study
• Reliance agreement
• Local context questionnaire

The following documents will require review the UCSD IRB and should be uploaded to the Supporting Information section of the project:

• Site-specific consent form (if they will be consenting subjects)
• Site-specific documents that require IRB review

Local Context Questionnaires

To allow the UCSD IRB to provide a thorough review, participating sites should complete a local context questionnaire. If a participating site PI has questions about their site policies and requirements, they should contact their IRB reliance contact for assistance.

UCSD Local Context Questionnaire

UCSD Relying

For studies where UCSD is relying on an External IRB, an administrative application to rely on an External IRB must be submitted via Kuali before any reliance agreements are signed.

The application will be reviewed by the reliance team. Please note that this review is not a duplicative review. The reliance team performs an administrative review of the application to ensure that UCSD local context will be considered as part of the reviewing IRB’s review of UCSD as a participating site and to ensure reliance agreements have been completed, as appropriate. After the application has been accepted by UCSD OIA as an External Reliance study, the research team should ensure that post approval responsibilities are followed to include submitting: Continuing Renewals, Amendments that meet our criteria for administrative review, and Reportable events where the reviewing IRB has made a determination of Unanticipated Problems/Adverse Events/Findings of Continuing or Serious non-compliance/Suspension.

Researchers should plan accordingly as there are two steps to UCSD OIA Administrative Acceptance for relying on an External IRB: 1. Clearance to submit to external IRB and 2. Administrative Acceptance

Step 1 – For Clearance Submission, upload:

    ▪  Master Protocol/Research Protocol
    ▪  Overall study approval from the reviewing institution/IRB
    ▪  Investigator's Brochure/Package Insert/Instructions for Use, as applicable to the    research
    ▪  Recruitment material template(s) from sponsor or reviewing institution/IRB, as applicable (for non-commercial IRBs only)
    ▪  Informed consent template(s) from sponsor or reviewing institution/IRB (for commercial IRBs only)
    ▪  Informed consent template with UCSD required institutional language added and tracked (for non-commercial IRBs only)
    ▪  Reliance agreement provided by the reviewing IRB (for non-commercial IRBs only)

UCSD OIA will issue the Clearance Notification via the Revisions Required comment in Kuali. After the reviewing IRB has approved UCSD as participating site, the application should be resubmitted in Kuali for acceptance.

Step 2 – Resubmit for OIA Administrative Acceptance, upload these additional documents:

    ▪  IRB approved - UCSD site specific informed consent document(s)
    ▪  IRB approved - UCSD site specific recruitment material document(s), as applicable
    ▪  IRB approval letter for UCSD as a relying site from the reviewing institution/IRB

UCSD OIA will issue an acceptance letter once we review the reviewing IRB's approval documents and verified UCSD local context has been addressed. NOTE: UCSD OIA acceptance AND required Institutional approvals must be completed before research can commence.

Consent Minimums

When relying on an External IRB, if UCSD will be consenting subjects, the IRB approved template should be updated to include our UCSD required language and requirements as outlined in the UCSD Reliance Consent Minimums document.

When submitting for Clearance to a non-commercial IRB, the research team should include the IRB approved Informed consent template with UCSD required institutional language added via track changes.

UCSD Reliance Consent Minimums

When submitting an application to UCSD OIA for Clearance to rely on a commercial IRB (Advarra/WCG), the research team should include the IRB approved template or the sponsor template. UCSD has created workflows with Advarra and WCG where they can add UCSD required language for UCSD sites. The commercial IRBs should also provide sites with a pre-review of the consent forms and may require additional input regarding UCSD required language.

If the sponsor is requesting a UCSD site-specific consent form be negotiated before submitting to the commercial IRB, the research team will be responsible for obtaining the IRB approved template from the reviewing IRB or sponsor and updating the IRB approved template to include UCSD required language and requirements as outlined in the UCSD Reliance Consent Minimums document.

UCSD Reliance Consent Minimums

UCSD Reviewing

UCSD IRB is willing serve as the IRB of Record for external sites when federally mandated, required by sponsors, or on a case-by-case basis.

How it works:

• Contact the IRB in the early stages of sIRB planning
  • Determine whether the UCSD IRB is the right choice for serving as IRB of record
  • Confirm the number of collaborating sites and if they are willing to cede IRB review
  • Determine which reliance agreement(s) to use
  • Understand the IRB fees that may be associated with the UCSD IRB's review for external sites

• Identify UCSD serving as the IRB of record for participating site(s)
• Add participating site(s)

• Submitting and approving UCSD as the lead site first
  • Additional issues may come up that could affect study documents
    • Protocol
    • Consent(s)
• After UCSD lead site approval, submit reliance documentation and site-specific documents that require IRB review from relying site(s) via an amendment submission for approval.

UCSD Relying

UCSD is willing to rely on an External IRB when federally mandated, required by sponsors, or on a case-by-case basis.

How it works:

• Contact the IRB in the early stages of sIRB planning
• Ensure it meets the criteria for external IRB review
• Provide the name of who will be serving as the IRB of Record
• Reliance agreement to be used
• Requesting approved study documentation from the reviewing IRB

• Register for Clearance (not a second IRB review) in IRB system
  • Allows the UCSD OIA to confirm that all local requirements are being met
  • Step-by-step instructions available in our KBA on Administrative Determinations

• If using a commercial IRB the UCSD team needs to submit a Site package through the respective commercial IRB system. If relying on another Institution’s IRB, the local research team at the reviewing site submits the UCSD information and documents through their local system for review and approval.

• Once the reviewing IRB has approved the addition of UCSD as a relying site, the study team is responsible for uploading copies of the approval documents in the IRB system for final acceptance.
  • Step-by-step instructions available in our KBA on Reliance Acceptance

UCSD Reviewing

Step 1 | UCSD PI Identifies UCSD Serving as the IRB of Record in the Kuali Application

• UCSD PI indicates that UCSD will be serving as the IRB of record by selecting “Yes, UCSD IRB will be IRB of record for other sites. (Please complete the Participating Site Section.)” in the General Information section of the application. Note that this can be done during an Initial submission or via an Amendment submission.
• UCSD PI adds the site(s) in the Participating Sites’ tab which appears at the top of the application.

Step 2 | UCSD IRB Approves UCSD Serving as the IRB of Record

• UCSD IRB completes the review and issues an IRB approval letter.

Step 3 | UCSD PI Forwards IRB Approved Study Documents and Reliance Documents to Site(s)

• UCSD PI forwards copies of the UCSD IRB approval letter and all approved study related documents (e.g., consent and recruitment materials) to the participating sites for local consideration.
• UCSD PI also forwards a copy of the UCSD Local Context Questionnaire (LCQ) to site(s) to complete with the help of their local IRB, as well as a copy of the reliance agreement to be executed, if one does not already exist.

Step 4 | UCSD PI Submits an Amendment in Kuali to Upload Documents from Site(s) for Review

• UCSD PI uploads copies of the completed LCQ and signed agreement (if applicable) in the Participating Sites tab for the respective participating site(s). Copies of any site-specific study documents that require stamping must be uploaded in the Supporting Information section of the application.

Step 5 | UCSD IRB Approves the Addition of Relying Site(s) and Issues Approval Letter

• UCSD IRB Analyst reviews the amendment submission and the uploaded documents pertaining to the participating site(s).
• UCSD IRB Analyst issues approval for the addition of the participating site(s), if no additional information is needed. Site-specific study documents are also stamped and released with the approval.

Step 6 | UCSD PI Forwards Site-Specific IRB Approval Documentation to Site(s)

• UCSD PI forwards the amendment approval letter and approved site-specific study document(s) to the participating site(s).

UCSD Relying

When Relying on a Non-Commercial IRB 

Step 1 | UCSD PI Submits External IRB Review Registration via Kuali

• UCSD PI creates and submits a “Request to Rely on non-UCSD IRB” Administrative Registration in Kuali. The reliance registration is an abbreviated application that is administratively reviewed by UCSD OIA to collect documentation of local requirements, and also serves the purpose of facilitating transmission of information to other UCSD offices such as OCAA, OCGA, HERC, and PRMC.
• UCSD PI uploads the following documents in the Supporting Information section of the application:

Step 2 | UCSD OIA Administrative Screening of Kuali External IRB Registration (Clearance)

• UCSD OIA screens the reliance registration submission in Kuali for completeness and to confirm the project meets the criteria for external IRB review.
• UCSD OIA provides the UCSD PI with a “Clearance Notification” attesting that UCSD has agreed to cede IRB review responsibility to the external IRB.

Step 3 | UCSD PI Provides Site-Specific Documents to the Reviewing Site

• UCSD PI provides the UCSD-specific study documents to the Lead Investigator of the reviewing site, including the “Clearance” screenshot.
• Lead Investigator at the reviewing site submits the UCSD-specific study documents to their IRB (respective IRB system) for review and approval.

NOTE: UCSD PI should communicate with UCSD ancillary committees as applicable. The OIA does not hold a submission for ancillary reviews to be completed.

Step 4 | External IRB Performs Review and Issues Approval

• External IRB performs the review of the site submission for the addition of the UCSD PI to a particular protocol.
• External IRB issues an approval notice for the addition of UCSD as a relying sites and approves any UCSD-specific study documents (stamps)

Step 5 | UCSD PI Submits External IRB Approval Notice and Approved Documents via Kuali

• Lead Investigator at the reviewing sites forwards the approval documentation to the UCSD PI.
• UCSD PI uploads the approval notice and stamped versions of the UCSD site-specific consent(s) into Kuali.

Step 6 | UCSD OIA Issues Acceptance of Commercial IRB’s Review and Approval

• UCSD OIA completes an administrative review of the approval notice and approved documents from the external IRB.
• UCSD OIA issues an “External Oversite Acceptance” letter via Kuali. This signifies completion of the UCSD OIA Administrative Review process.

When Relying on a Commercial IRB (WCG IRB & Advarra IRB)

Step 1 | UCSD PI Submits External IRB Review Registration via Kuali

• UCSD PI creates and submits a “Request to Rely on non-UCSD IRB” Administrative Registration in Kuali. The reliance registration is an abbreviated application that is administratively reviewed by UCSD OIA to collect documentation of local requirements, and also serves the purpose of facilitating transmission of information to other UCSD offices such as OCAA, OCGA, HERC, and PRMC.

Step 2 | UCSD OIA Administrative Screening of Kuali External IRB Registration (Clearance)

• UCSD OIA screens the reliance registration submission in Kuali for completeness and to confirm the project meets the criteria for Commercial IRB review.
• UCSD OIA provides the UCSD PI with a “Clearance Notification” attesting that UCSD has agreed to cede IRB review responsibility to the

Step 3 | UCSD PI Submits Site Package to the Commercial IRB

• UCSD PI submits the appropriate application, including the “Clearance” to the commercial IRB using their online system. When completing the on-line application, ensure that the submission is noted as affiliated to UCSD.
• The commercial IRB reviews the UCSD PI’s submission and will communicate directly with the UCSD PI with respect to any required revisions and/or additional information as needed.
• UCSD PI will concurrently communicate with UCSD ancillary committees as applicable.

NOTE: No need to wait for ancillary reviews to be completed before submitting to the Commercial IRB; these reviews can be conducted concurrently.

Step 4 | Commercial IRB Processing and Institutional Sign-Off

• Commercial IRB performs the review of the site package for the addition of the UCSD PI to a particular protocol.
• Commercial IRB review analysts revise the consent document(s) to meet UCSD requirements, following the UCSD-Specific Mandatory Language Document (MLD).
• Commercial IRB issues an Initial Site Review email notification to the UCSD OIA designated staff, and requests Institutional Sign-Off. The commercial IRB will place an indefinite hold on the approval docs until Institutional Sign-off.

Step 5 |  UCSD OIA Reviews Approval and Provides Institutional Sign-Off

• UCSD OIA designated staff reviews the consent document(s) to confirm UCSD Institutional requirements have been met.
• UCSD OIA provides institutional sign-off to the commercial IRB and they review the site

Step 6 | UCSD PI Submits Commercial IRB Approval Notice and Approved Documents via Kuali

• Commercial IRB approves the UCSD PI and provides approval documents.
• UCSD PI uploads the approval notice and stamped versions of the UCSD site-specific consent(s).

Step 7 | UCSD OIA Issues Acceptance of Commercial IRB’s Review and Approval

• UCSD OIA completes an administrative review of the approval notice and approved documents from the commercial IRB.
• UCSD OIA issues an “External Oversite Acceptance” letter via Kuali. This signifies completion of the UCSD OIA Administrative Review process.

UCSD Reviewing

After the UCSD IRB has approved an external site to rely on the UCSD IRB for a specific study, the UCSD PI retains certain obligations with respect to the UCSD IRB and the relying sites. These include:

• Notifying the participating sites of all UCSD IRB determinations and communications
  • This includes those for initial review, continuing review, amendments, reportable events, suspension, and termination.
• Providing access, upon request, to study records for audit by the Relying Institution, the UCSD IRB, and other regulatory or monitoring entities.
• Follow all requirements of the Relying Institution with regard to ceded review
  • For example, ensuring administrative requirements for documenting ceded review and obtaining all ancillary review approvals before study activation occurs at a Relying Institution.
• UPR, Non-compliance, & Subject Complaint Submissions
  • Provide to sites the UCSD IRB policies. This includes, but is not limited to, policies for reporting unanticipated problems, noncompliance, and subject complaints. Have a mechanism in place to obtain and collect information from Relying Site study team regarding events/incidents occurring at the relying sites that meet the UCSD IRB threshold for reporting and to submit those applicable events/incidents within the required time frames.
• Continuing Review (CR) Submissions
  • Collect CR information from all sites and report to the UCSD IRB within the required timeframe.
    • The continuing review at UCSD IRB will be conducted for all sites. Therefore, all information such as enrollment numbers, reportable events, etc., must be collected from all relying sites and included in the continuing review submission.

UCSD Relying

After the UCSD IRB has accepted to rely on an external IRB for review of a specific study, the UCSD PI retains certain obligations for submitting information within the Kuali IRB system. These are detailed in the IRB Handbook in the section "What are my obligations after IRB approval?" All of these obligations apply to PIs who are relying on an external IRB except #14 as the definitions of what is reportable and the timelines in which they must be reported vary among IRBs.

The important submissions that need to be made in Kuali IRB after the UCSD IRB has accepted to rely on an External IRB include:

• Continuing Reviews
• Amendments
  • The only types of amendments the UCSD IRB needs to see submitted through Kuali for clearance/acceptance:
    • Change in Principal Investigator* or study personnel
      • Affiliated with the institution, eligible to participate depending on their role, have completed appropriate training.
    • New or changes in COI for investigators
    • New or changes in HIPAA determination (made by UCSD)
    • New or changes in funding
    • New or additional ancillary review required (e.g., Radiation Safety Committee)
    • New to study/site consent documents*
      • For example, a new consent form for a new phase of the study or new optional element of the study.  
    • Any other changes that affect the UCSD required information in the consent document*.
  • NOTE: Items marked above with an * should be submitted to OIA for clearance before being submitted to the reviewing IRB for approval. 
• Unanticipated Problems/Continuing or Serious Non-compliance/Suspensions/Terminations
  • If the event meets the reporting requirement of the reviewing IRB, these events need to be reported to the reviewing IRB per their event reporting process. After their review is finalized and the reviewing IRB has made a determination of Unanticipated Problems, Continuing or Serious Non-compliance, Suspension, or Termination, use the Reportable Event tab in Kuali to submit the event and determination to the UCSD OIA for acknowledgment. NOTE: Terms of the agreement may specify reporting requirements.
    • Follow all determinations of the Reviewing IRB.
    • Only implement changes of protocol, including local variations, after the Reviewing IRB has approved them, except in cases where a change is required to avoid an apparent immediate hazard to participants.
• Study Closure

Special Note About Studies with a Coverage Analysis

In addition to the above, the Office of Coverage Analysis Administration (OCAA) utilizes the Kuali IRB system to keep coverage analyses up to date for study teams. If your study requires a coverage analysis, please submit an amendment any time there is a change to the protocol, investigator's brochure (IB), or informed consent form (ICF).

To ease researcher and OIA staff burden in submitting and processing these amendments, OIA has a specific question in Section A of the Kuali IRB amendment application (shown below) that asks if this submission is only for OCAA review. If your study has a coverage analysis, is reviewed by an External IRB, and the amendment doesn't contain any of the items required to be reviewed by the UCSD IRB (listed above), answer this question as "yes." This will allow you to bypass all other amendment questions to save you time in submitting for OCAA review purposes.  

If you have questions about whether OCAA review is required, please email OCAA directly at ocaa@ucsd.edu. 

Multi-site (NIH funded research): means that the same research procedures (i.e., protocol) are being conducted at one or more domestic sites and that each site is under the control of a local participating investigator. This typically involves a lead site that receives the grant or contract directly from NIH and that then establishes a subaward or subcontract to each participating site. The research could be a clinical trial, an observational study, or a basic clinical research study.

Same Research Protocol: Protocols that address the same research questions, involve the same methodologies, and evaluate the same outcomes are considered to be the “same research protocol.” Additionally, sites that are accruing research participants for studies that are identical except for variations due to local context consideration would be considered to be conducting the “same research protocol.” If a study involves a separate site for study coordination or coordination of data and statistical analyses and the site is conducting the same protocol as the other participating sites, then all sites would be expected to rely on the designated single IRB.

Collaborative Study: Human research involving more than one institution and/or site participating in the same research protocol, where each site completes a portion or portions of procedures.

Cooperative Research: Human research covered by (45 CFR 46) involving more than one institution and/or site.  When conducting cooperative research, each institution and/or site is responsible for safeguarding the rights and welfare of human participants and for complying with this provision.  Any institution and/or site located in the United States that is engaged in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States.

IRB of Record: The IRB that is responsible for the ethical review of human research on behalf of an institution and/or site or individual investigator.

Lead Site: The primary awardee of a federally funded grant who is responsible for identifying the selected sIRB for cooperative research. For non-federally funded research this role is identified as the primary institution and/or site whom develops a research protocol.

Participating Site: An institution or site engaged in multi-site research, where a local investigator is responsible for the conduct of human research at their institution or site.

Relying IRB: An IRB that has designated through an agreement to cede review to an external IRB for a particular study