IRB Reliance: Single IRB Review

When conducting multi-site research, each institution typically has its own Institutional Review Board (IRB) responsible for ensuring ethical standards are met. An IRB reliance agreement is a formal agreement between two or more institutions engaged in research. The agreement allows one institution’s IRB (relying institution) to defer aspects of the IRB review to another institution’s IRB (reviewing institution). The reviewing institution’s IRB will oversee many aspects of the research protocol on behalf of the relying institution. This process is intended to streamline IRB review across all participating institutions. A reliance agreement will define institutional roles, responsibilities, and procedures for oversight.

Reliance agreements for non-federally funded projects

The NU IRB recommends establishing reliance agreements for any non-exempt collaborative research with US-based institutions who have a FWA on file.

NIH sIRB Requirements:

Effective Jan 25, 2018, the NIH established the expectation that a (sIRB) will review non-exempt human subjects research protocols funded by the NIH that are carried out at more than one site in the United States unless the study qualifies for an exception. The policy can be found here: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-094.html .

NIH also has provided guidance on when projects require sIRB and what exemptions might apply here: https://grants.nih.gov/sites/default/files/sIRB-Determination-workflow.pdf

Common Rule sIRB Requirement:

Effective Jan 20, 2020, the revised common rule requires all non-exempt cooperative research conducted or supported by a Federal department or agency rely upon a sIRB unless the research qualifies for an exception. Details  policy can be found here: https://www.hhs.gov/ohrp/regulations-and-policy/single-irb-exception-determinations/index.html

Often the lead site is responsible for selecting the sIRB for federally funded cooperative research. In non-funded research, this role often goes to the institution/site developing the research protocol. At Northeastern, there are three options for who can serve as a sIRB:

IRB of one of the institutions involved: The NU IRB can enter into reliance agreements with all US-based institutions who have a FWA on file. Northeastern does not require that an institution be AAHRPP accredited. When deciding which institution should serve as the sIRB, a number of factors that should be considered including: lead site on the award, institutional expertise, location, accreditation status, level of engagement, and cost. Since each project and institution are different, it is advisable to start an informal discussion with each engaged IRB early.

Commercial IRB: such as Advarra or WCG. Note that there are often fees associated with using a commercial IRB.

Other Central IRB: such as the All of Us IRB or the National Cancer Institute Central IRB.

There are several criteria for determining whether an institution is or is not engaged in human subjects research. Please see the Engagement Worksheet for guidance on determining whether NU is or is not engaged in human subjects research.

Relevant guidance includes:

For general activities, please see HHS engagement guidance for determining when an institution is engaged and exceptions: https://www.hhs.gov/ohrp/regulations-and-policy/guidance/guidance-on-engagement-of-institutions/index.html

Non-NU sites and investigators are responsible for determining whether they are or are not engaged in research. Please see HHS engagement guidance for determining when an institution is engaged and exceptions: https://www.hhs.gov/ohrp/regulations-and-policy/guidance/guidance-on-engagement-of-institutions/index.html

If NU is not engaged in human subjects research, no NU IRB oversight is required. Researchers will need to work with departments and ensure their activities are consistent with non-NU policies.

We encourage investigators to use SMART IRB whenever possible. The platform streamlines the reliance process for all parties. The IAA process is older and requires signatures from the Institutional Official which can add additional time to the review process.

Before deciding on a process, you should check with any non-NU IRBs to confirm that they are willing to use SMART IRB or an IAA. Some institutions do not use SMART IRB or have different processes. If the non-NU IRB requires a different process, please explain so during the NU review process. NU is flexible and able to use most reliance agreement processes as long as the agreement doesn’t not contain any terms or stipulations the university feels it is unable to agree to. For IRBs who don’t want to use SMART IRB, please reach out to those IRBs to obtain copies of any forms/agreements they would like to use to execute the reliance agreement.

4 Types of Agreements:

IRB Authorization Agreements IAAs

An IAA is a document signed by signatory officials at two institutions that establishes an agreement to defer review of one or more studies to another institution’s IRB. Typically, an IRB has its own template IAA template they prefer to use. NU can provide an IAA upon request, but prefers to use SMART IRB or the site’s template. Review by the NU OGC may be required if the IAA has contractual or legal terms. The template will be signed by one institution then sent to the second institution for the second signature/execution. Research teams are responsible for routing the documents to the appropriate signature officials.

SMART IRB

SMART IRB is an online IRB reliance platform designed to harmonize and streamline the IRB review process for multisite studies. This online reliance system allows research teams to submit requests for a reliance agreement that can replace the need for Institutional Authorization Agreements (IAAs). Research teams are responsible for submitting the initial request/responding to any revisions needed and SMART IRB uses an online workflow where the request will automatically be routed between IRBs.

SMART Letter of Acknowledgement (LOA)

A SMART IRB Letter of Acknowledgement (LOA) allows research teams to utilize a paper or e-document to execute reliance agreements under the terms of the SMART IRB master reliance agreement without using the SMART IRB online platform. This document follows a similar process as an IAA.

Memorandums of Understanding or Master Agreements

Memorandums of Understanding (MOUs), also known as Master Agreements, establish a permanent and standing arrangement between entities which can cover any number of research projects (as opposed to being limited to one or a few specific projects). These agreements are often used by large reliance networks or to establish larger institutional collaborations. Developing and finalizing MOUs is a time-intensive process, often spanning several months and a MOU will be part of a much larger process establishing the collaboration. MOUs are institution driven rather than investigator initiated.

To begin the process of establishing IRB reliance through the SMART IRB Online Reliance System, you will need to log in to the system and create and submit a reliance request. You may need to create a new account by requesting investigator access if this is your first time using this system. There are some instructional videos at https://smartirb.org/reliance/, including one describing how an investigator submits a request, which may be helpful.

In situations where a researcher is affiliated with more than one institution, it is important to delineate what roles they are conducting the research activity under. Occasionally, the nature of the research aligns with only one of these positions, while in other instances, it may be relevant to both. When it remains ambiguous whether a researcher is engaged in research as an agent of an institution, it is recommended they consult with the respective IRBs of each institution. The IRB at each institution assumes the responsibility of determining whether a researcher is conducting research as a representative of their specific institution. The NU IRB does not and cannot make these determinations on the behalf of other institutions. When submitting, be sure to clearly explain how you arrived at any determinations.

If a researcher is engaged in research as an agent of two institutions, both IRBs will need to provide oversight OR one IRB will need to defer review to the other via a reliance agreement.

The NU IRB follows DHHS engagement guidance when making these determinations.

When NU is the Prime recipient or Primary Awardee of a federal grant, where a subrecipient institution or organization will conduct only exempt human subjects, and NU will not be involved in any human subjects research activities, we ask that NU investigators provide us with the following information via email:

1. Copies of the materials from the external IRB. This includes their exemption determination letter, copies of any protocols, copies of any content materials, etc.
2. A list identifying the sponsor, grant number, and NU PI on the grant.
3. Confirm that no one at NU will be: interacting with participants, obtaining consent, contacting participants, collecting data/information from or about participants, or analyzing identifiable (or coded) data.
4. Confirm that no NU investigators will access identifiable data. OHRP considers private information or specimens to be individually identifiable as defined in 45 CFR 46.102(f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.

Once this information is received and confirmed, the DHR will review and acknowledge the external exemption determination. If 3 or 4 cannot be acknowledged, the activity may require review by the NU IRB.

This process is important as it allows us to verify proper oversight and have records of the activity as the prime on the grant. NU research teams are encouraged to save these materials (and correspondence with the DHR) for their own records as well.

Note: this process only applies to exempt research where the activity is exempt at all sites. Non-exempt sponsored research typically requires a reliance agreement due to federal engagement regulations.

Investigators should be aware that reliance arrangements frequently require additional work on the part of the local study team, including submission to the NU IRB and the external IRB, as well as managing communication between these offices.

Furthermore, the NU’s DHR must have a current record of all research team personnel associated with the protocol. An updated research team form is to be submitted anytime a Northeastern investigator is added or removed from the study.

If the reliance request was initiated after the reviewing IRB approved the study, the addition of sites and/or collaborators will need to be specifically reviewed and approved, via a modification to the existing study.

Any reliance agreement containing indemnification language will be referred to the Office of General Counsel for review and approval prior to finalizing the agreement.

The Northeastern University IRB may serve as the IRB of record for non-exempt research related to a SBIR/STTR grant in limited circumstances. These decisions are made on a case-by-case basis by leadership. If you would like Northeastern to serve as the IRB of record, please complete and submit a SBIR STTR Reviewing IRB Decision Form to [email protected].

Please note: IRB approval from Northeastern does not automatically extend to the small business without an executed reliance agreement.

Federal Wide Assurance Requirements for SBIR/STTR grants

Under federal regulations, any institution (which includes small businesses) engaged in non-exempt human subjects research must have a Federalwide Assurance (FWA) on file with HHS. According to OHRP engagement guidance:

Institutions that receive an award through a grant, contract, or cooperative agreement directly from HHS (or another federal agency under the common rule) for the non-exempt human subjects research (i.e. awardee institutions), even where all activities involving human subjects are carried out by employees or agents of another institution.

In practice, this means that the small business that is the direct recipient of a SBIR/STTR award is almost always engaged in human subjects research and is required to have and maintain its own FWA. The small business should NOT use Northeastern’s FWA.

Submitting to the Northeastern IRB

Submission of an SBIR/STTR project follows the same process as other IRB submissions. This includes:

• A complete study submission to review (see the Getting Started on the top of this page), and
• Reliance documentation required if Northeastern will serve as the reviewing IRB (see Process to Request NU Serve as Reviewing sIRB).

COI Review and Consent Disclosure Information

Study teams should consult their grant officer to determine applicable COI review requirements. In many situations, COI review will be required for collaborators from Northeastern, but not the small business. Even if COI review isn’t required for the small business collaborator, the COI still needs to be disclosed as part of the consent process to meet IRB regulatory requirements.

Per federal regulations:

“The prospective subject or the legally authorized representative must be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate”

Because of this, in nearly all cases, the consent form must include a plain-language disclosure that the research is intended to develop a commercial product and that members of the research team may have a financial interest in its outcome.

Northeastern students often work with other institutions to conduct research. This might include, for example, a co-op at another Boston area college that involves conducting research there. When this occurs, it is necessary to determine if NU IRB oversight is required. Students should work with their faculty advisors and/or mentors to determine whether or not Northeastern IRB oversight or a reliance agreement

Step 1: Are you acting as an agent of Northeastern?

When Northeastern students conduct research at another institution (e.g., in collaboration with that institution or using its facilities, participants, or data), they must disentangle if they are acting as an agent of Northeastern or if the activity is not related to their student status at Northeastern. NU students are “agents” of Northeastern when performing degree-required research or if that research is related to their employment at Northeastern. This might include a co-op that is being done to satisfy NU degree requirements.

Step 2: If you are an agent of Northeastern, is Northeastern engaged in the research?

If a NU student is acting as an agent of Northeastern, we must next determine if Northeastern is engaged. In general, NU is engaged if that student will be interacting with participants or using identifiable data. However, there are two specific carve outs that makes Northeastern not engaged:

1. Northeastern University agents:

• obtain coded private information or human biological specimens from another institution involved in the research that retains a link to individually identifying information (such as name or social security number); and
• are unable to readily ascertain the identity of the subjects to whom the coded information or specimens pertain because the institution’s employees or agents and the holder of the key enter into an agreement prohibiting the release of the key to the those employees or agents under any circumstances;

2. Northeastern University agents access or utilize individually identifiable private information only while visiting an institution that is engaged in the research, provided their research activities are overseen by the IRB of the institution that is engaged in the research.

Step 3: If Northeastern is engaged, who will review?

If NU is engaged in the research, NU IRB oversight is required. Depending on the circumstances, this may mean:

• Direct NU IRB review of the student’s research activities, or
• A reliance agreement (if the activity is non-exempt) where NU defers review to the other institution’s IRB (or vice versa).

The appropriate path depends on where the research takes place, which institution has primary responsibility, and whether reliance mechanisms (e.g., SMART IRB, IAA) are available. You should consult with your faculty mentors and the study PI on how to navigate which review pathway is most appropriate.