Reliance Agreements and Single IRB
INFORMATION ON RELIANCE AGREEMENTS
The U.S. regulations governing human subject research permit reliance agreements through which a research organization may defer its IRB oversight responsibilities to an external organization’s IRB. The external organization may be another research organization with a Federal Wide Assurance (FWA) and an IRB registered with the Office of Human Research Protections (OHRP), or it may be a commercial IRB that itself is not a research organization, but which has one or more IRBs that are registered with the Office of Human Research Protection (OHRP).
Effective January 20, 2020, the U.S. regulations governing human subjects research extended the NIH Single IRB requirement to all government agencies signed on to the Common Rule, and to include HHS - conducted or supported cooperative agreements. International sites and tribal sites are not included in this mandate.
This page provides information on how the BSPH handles different arrangements with external (non-JHU) IRBs. The BSPH IRB will assume IRB oversight responsibilities for external institutions in very few situations. It will defer its review responsibilities to external IRBs when required by government policy or requested by the Sponsor of a study, and in some other specific situations. The BSPH PI must submit a PHIRST Reliance application (answering “yes” to Question 13 on the first page, “Do you want the BSPH IRB to rely on a non-Hopkins external sIRB?”) as part of the process, and review the following materials prior to requesting that BSPH enter into a reliance agreement with an external institution.
FAQS ON RELIANCE AGREEMENTS AND SINGLE IRB (sIRB) AT JHU FOR BSPH INVESTIGATORS
What is a sIRB?
A Single IRB arrangement under NIH sIRB policy requires “that a single IRB (sIRB) of record will be used in the ethical review of non-exempt human subjects research protocols funded by the NIH that are carried out at more than one site in the United States.” https://grants.nih.gov/policy/humansubjects/single-irb-policy-multi-site-research.htm “sIRB” refers to the use of one IRB as lead reviewer for a U.S. based, HHS-funded, multi-site or cooperative agreement research. IRBs will either serve as the lead sIRB or deferring IRBs. All participating institutions must sign a reliance agreement with the lead site deferring IRB review responsibilities to the sIRB.
What sponsors require the use of sIRBs?
Under the Final Rule effective January 20, 2020, all non-exempt, HHS-funded, human subject research studies (with some narrow exceptions) will require sIRB review. Some other sponsors may also require sIRB review.
To what kind of grants does the sIRB requirement apply?
The sIRB requirement applies to all competing grant applications, including new, renewal, revision or resubmission, and all cooperative agreements funded by federal funding agencies signed on to the Common Rule.
Will the BSPH IRB serve as a sIRB?
The BSPH IRB is not equipped to serve as a single IRB for multi-site studies or cooperative agreements, thus if BSPH is identified as the sIRB site, the PI must contact the School of Medicine (SOM) IRB to discuss the sIRB request for sIRB services. The SOM IRB serves as JHU’s sIRB for all Divisions. If JHU serves as the sIRB for a BSPH study, and the Sponsor requires that a commercial IRB serve as the sIRB, the BSPH IRB will accommodate that request.
What happens when the BSPH relies on an External sIRB?
When an external (non-JHU) institution serves as the sIRB for a non-exempt study, the BSPH IRB must defer its review to that external IRB via a Reliance Agreement. The BSPH, as a “participating site” (or pSite) is responsible for conducting a “local context review” for that study to ensure compliance with state and local requirements and institutional policy. The BSPH PI must submit a “Reliance” application in the PHIRST system. The BSPH IRB will review the PI’s PHIRST application to determine whether the research activity is non-exempt human subject research requiring IRB review. If it is, then the IRB will complete its “local context review” and if all’s well, will execute the Reliance Agreement and provide a Letter of Support. IMPORTANT: NO RESEARCH ACTIVITIES MAY BEGIN UNTIL THE RELIANCE AGREEMENT IS SIGNED BY BOTH THE REVIEWING AND DEFERRING INSTITUTIONS; OTHERWISE, THE ACTIVITIES HAVE NO IRB APPROVAL, IN VIOLATION OF FEDERAL AND STATE LAW AND JHU POLICIES.
What is a “Letter of Support”?
A Letter of Support is provided by the BSPH IRB to the BSPH PI confirming the BSPH willingness to rely on the identified external IRB. NIH may require a Letter of Support at the grant proposal stage or after the study is funded. If funded, the BSPH IRB will complete its local context review, execute a Reliance Agreement, and release the Letter of Support to allow the study to begin. In both situations, a PHIRST application is needed to initiate the process. If the BSPH PI submits a PHIRST application and explains that the submission is at the grant proposal stage, the BSPH IRB will not perform a “local context review” at that point because approved documents from the external sIRB are not yet available. If the study is funded later, the study materials may be added by Amendment.
What happens if my study meets Exempt criteria?
Exempt studies are not subject to the sIRB mandate. The BSPH IRB may review Exempt studies itself or, if an external U.S. IRB generates an Exempt determination, the BSPH IRB may accept that external IRB’s determination if it determines that the research meets Exempt criteria. The BSPH IRB relies on the materials submitted in the PHIRST application to make these decisions.
How is Hopkins handling requests to have JHU serve as the lead sIRB?
The School of Medicine IRB (SOM IRB) will serve as the sIRB for all JHU divisions when Hopkins agrees to serve as the lead IRB. It will review all requests to have Hopkins serve as the sIRB, and will provide letters of support for those that it approves. If a Sponsor requires the use of a commercial IRB, the BSPH IRB will consider relying on those organizations.
What should a BSPH Investigator do when seeking reliance on an external IRB?
BSPH investigators who want BSPH IRB to rely on another institution's IRB should check the Guidance on How to Request BSPH Reliance on an External IRB. The BSPH PI should submit a PHIRST application, answering “yes” to Question 13 on the first page. The IRB needs to know what stage the proposal is in (grant proposal stage, or under review by the external IRB), what the BPSH investigator role in the study will be, and what activities will cause BSPH employees or agents to be “engaged" in non-exempt human subjects research. If the study has been funded, the application prompts uploading of the Reliance Request and Local Context Submission Form and an Investigator Assurance Form, in addition to study materials approved by the external IRB. No reliance agreements will be signed for Exempt research.
How can I submit a reliance request to have Hopkins serve as the sIRB for my grant proposal or study?
Contact the SOM IRB before you do so to make sure the SOM IRB can serve in that capacity. The SOM IRB provides information about serving as the sIRB here: https://www.hopkinsmedicine.org/institutional_review_board/about/agreements/jhmirb_serving_as_the_sirb.html.
What are my responsibilities as PI if BSPH agrees to rely on an external sIRB?
If the BSPH IRB agrees to the reliance arrangement and provides a Letter of Support, you as PI will need to make sure that all the responsibilities in the Investigator Assurance Form are carried out. You must ensure that study personnel receive appropriate training and are qualified to perform their duties, and that the study is conducted in accordance with the approved protocol and BSPH policies. You must notify the BSPH IRB of any changes to the study that could influence site specific requirements, such as, conflict of interest, study personnel, funding stream, clinical procedures (could affect PRA analysis), modifying the study drug (affecting local Pharmacy & Therapeutics review), etc.
Does relying on an External sIRB mean there is no BSPH IRB review?
Not completely. The sIRB is responsible for conducting the ethical review and overseeing the non-exempt study at all sites, but each relying institution’s IRB must ensure compliance with site specific state and local law, and institutional policy. That means that the BSPH IRB will conduct a “site specific” review to ensure that it is comfortable agreeing to rely on the sIRB, and that the study meets site specific requirements. In addition, the BSPH IRB must review any information about the study reported by the BSPH PI. So the BSPH PI will have to meet sIRB requirements as well as site specific requirements imposed by the BSPH IRB.
When may BSPH research activities begin if deferring to an external IRB?
BSPH research activities cannot begin until the reliance agreement is signed and the letter of support is uploaded into PHIRST. If human subject research activities begin before the reliance agreement is signed by both parties, the reliance agreement is ineffective, and the PI will be conducting research without IRB approval in violation of federal and state law and JHU policy.