IRB Reliance: Single IRB Review

What is IRB Reliance?

Reliance agreements are often needed when a Northeastern project also involves non-Northeastern collaborators. These agreements extend Northeastern’s Federal Wide Assurance (FWA) to cover study team members who are not Northeastern employees. Please use the Northeastern University Reliance Flowchart to help you determine which reliance pathway you might want to use. If you have any questions, please reach out to [email protected].

Please see below for an overview of when each process applies and how to request a reliance agreement using that process.

Note that most federally funded multi-site research is subject to the Single IRB Mandate that requires reliance agreements unless an exemption applies. Please see below for details about exemptions to the sIRB mandate and exemptions.

Review Processes by Agreement Type

There are four basic types of reliance processes at Northeastern.

For non-exempt research, NU will serve as the IRB of record for US based institutions which have a FWA on file. For non-NU collaborators who are not affiliated with a US based institution or are affiliated with an institution without a FWA, please see the Individual Investigator Agreements (IIA) process.

Relying sites can be added either during the initial review or by submitting a modification to an existing NU IRB approved study. If submitting a modification, be sure to complete the modification form. See https://research.northeastern.edu/hsrp/forms/ for forms/templates used in the initial review and modification process.

To add a relying site, there are two processes that need to converge:

1. Submission of intake materials. This includes:

  • A completed NU IRB of Record Intake Form for each site that will be relying on us.
  • A completed Reliance Plan Form listing all sites (including sites that will not rely on us for any reason).
  • A protocol document that describes the activities non-NU collaborators will conduct / that is consistent with their involvement. If any other study documents should reflect non-NU collaborators, ensure these are consistent as well. A relying site can be added during initial review. However, if the process to add a relying site is occurring after approval, a modification will need to be submitted via a Modification form along with all modified and new documents needed.

2. Execution of the reliance agreement. A formal agreement will need to be executed between all institutions involved in the reliance agreement. This can be done either via the online SMART IRB platform or via a document called an IAA. Please see “Should I use SMART IRB or an IAA” in the FAQ. Note that you will want to work with each non-NU collaborating IRB to meet any requirements they might have. Most institutions have an intake process that must be collected before they are willing to execute a reliance agreement.

 

SMART IRB

The study team (either NU or external) will need to create the request in SMART IRB. Please see the Reliance Walkthrough Video here for more information about the SMART IRB process: https://smartirb.org/reliance/ . Each institution will sign off using the SMART platform and the investigator will receive an email when the agreement is executed.

IAA

Please submit a completed IAA Template: NU IRB of Record that is signed by the relying institution. When the study or amendment is ready for approval, the NU IO will countersign and NU HRPP will return the executed agreement with the approval packet. If the relying institution requests that NU sign first, please explain so when submitting.

Find forms/templates used at the bottom right of this page.

For non-exempt research, NU is willing to enter into a reliance agreement to defer review to an IRB of record at a US based institution which has a FWA on file. The NU IRB will only enter into reliance agreements for studies that are already approved by the reviewing IRB unless there are unique circumstances that require consideration. Please email [email protected] to discuss any such circumstances.

To request that NU defer review to an external sIRB:

1. NU Local Context Forms and Study Materials: Submit the following materials, via email, to [email protected]

  • A completed NU Relying – Reliance Intake Form
  • A completed NU Relying – Reliance Research Team Form (be sure to list the NU PI on this form)
  • Copies of the sIRB approval letter, the approved protocol, approved consent forms, and copies of any other documents reviewed and approved by the sIRB.
  • If the reviewing IRB requires copies of any forms to be completed by the NU IRB, please submit those as well.

2. Execution of the reliance agreement. A formal agreement will need to be executed between all institutions involved in the reliance agreement. This can be done either via the online SMART IRB platform or via a document called an IAA. Please see “Should I use SMART IRB or an IAA” in the FAQ. Note that you will want to work with each non-NU collaborating IRB to meet any requirements they might have.

SMART IRB

If the reviewing IRB will use the SMART online platform, the study team (either NU or external) will need to create the request in SMART IRB. Please see the Reliance Walkthrough Video here for more information about the SMART IRB process: smartirb.org/reliance/ . Each institution will sign off using the SMART platform and the investigator will receive an email when the agreement is executed.

If the reviewing IRB will use a SMART Letter of Authorization instead of the SMART online platform, please send that letter along with your intake materials. For more information, please see Letter of Acknowledgement, Template under smartirb.org/resources/.

IAA or other “Paper” agreement

Please submit a completed IAA form that is signed by the sIRB. When the study or amendment is ready for approval, the NU IO will countersign and NU HRPP will return the executed agreement with the approval packet. If the sIRB requests that NU sign first, please explain so when submitting.

Please note that if the reviewing sIRB requires any agreements with unusual terms or addendums to the standard or typical terms of reliance, the agreement may require additional review by NU OGC.

Find forms/templates used at the bottom right of this page.

Individual Investigator Agreements (IIAs) are used when collaborators are engaged in research on their own behalf (i.e. as an independent investigator) or when the collaborator is not affiliated with a US based institution with a FWA on file (i.e. they do not have their own IRB). IIAs are often used when a project includes collaborators from local clinics or schools that do not have an IRB or non-academic community member collaborators.

Collaborators can be added either during the initial review or by submitting a modification to an existing NU IRB approved study. See https://research.northeastern.edu/hsrp/forms/ for forms/templates used in the initial review and modification process.

To add an investigator via an IIA, submit:

  1. A completed Research Team Form listing each non-NU collaborator.
  2. A protocol document that describes the activities non-NU collaborators will conduct / that is consistent with their involvement. If any other study documents should reflect non-NU collaborators, ensure these are consistent as well.
  3. Submit a completed Individual Investigator Agreement form signed by each non-NU collaborator. Please reach out to your assigned reviewer for a copy of this.
  4. Ensure each non-NU collaborator has current IRB CITI training. Note that non-NU investigators can register at citiprogram.org as a NU affiliate. Please review the guide on how to do so.

Once submitted, the study will be reviewed using our normal review processes. Once the study materials are ready for approval, the IIA will be sent (internally) to an institutional official for signature and, once the IIA is signed, the study will be approved and a signed copy of the IIA will be sent to the PI and Lead Student alongside with the IRB approval packet.

For more information about IIA, please see https://www.hhs.gov/ohrp/register-irbs-and-obtain-fwas/forms/individual-investigator-agreement/index.html

The NU IRB does not enter into reliance agreements or establish IIAs for exempt research, except when unique circumstances prompt for an exception. Barring an exception, the NU IRB will not extend IRB review and oversight to non-NU investigators on Exempt research. Non-NU collaborators are expected to adhere to any non-NU requirements that pertain to their participation in the project. In most cases, this means the non-NU collaborator will submit an independent submission to their own IRB.

For NU investigators collaborating on non-NU exempt research, please submit for an exemption determination. Note that the protocol should reflect only the NU researchers’ scope of work – activities conducted by non-NU researchers can be included for context, but we are not reviewing and providing approval for those activities. Include any non-NU IRB approvals, consent forms, etc, for context when you submit.

FAQs

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, WIRB, or WCG IRB. 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. In general, we strongly recommend you reach out to us to discuss if it is unclear whether Northeastern is or is not engaged. 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

For studies where NU will only analyze secondary data or materials, please see the NIH flowchart Research Involving Private Information or Biospecimens: https://grants.nih.gov/grants/policy/hs/private-information-biospecimens-flowchart.pdf

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.

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.

Other Information

Definitions:

Collaborative or Cooperative Study: Research where multiple institutions or sites conduct the same research protocol, each completing specific procedures.

Engaged: In general, an institution is considered engaged in a human subjects research projects when its employees or agents: collect data about research subjects through interaction or intervention; access identifiable private information about the research subjects; secure informed consent from human subjects for the research. Please note that there are many specific exceptions to this. Please see DHHS Engagement Guidance for a more detailed overview of when institutions do and do not need to be considered engaged in human subjects research.

FWA (Federalwide Assurance): An assurance of compliance with the U.S. federal regulations for the protection of human subjects in research. A FWA is generally mandatory for institutions receiving federal funding for human subjects research and is approved by the Office for Human Research Protections (OHRP). More information is available for OHRP.

To search FWAs, please see: https://ohrp.cit.nih.gov/search/search.aspx

IAA (Institutional Review Board (IRB) Authorization Agreement): Agreement outlining the roles and responsibilities between institutions which enables IRB reliance.

IIA (Individual Investigator Agreement): Agreement defining the roles and responsibilities when an individual investigator relies on an external IRB.

IRB of Record or sIRB: The IRB that is responsible for the review of the human subjects research on behalf of another institution or individual investigator.

Lead Site: The primary recipient of a federal grant OR the institution developing the protocol for non-funded research.

Multi-site research: means that the same research procedures or protocol are being conducted at one or more institutions. This typically involves a lead site that receives the grant or contract directly and then establishes subawards to other sites.

Relying IRB: An IRB that cedes review to another IRB.

Same Protocol: Protocols addressing the same research questions and employing the same or similar methodologies to explore the same outcomes. Even if all sites are not conducting all study activities or if there are variations in procedures to adapt to local context, the activities are often still considered to be the “same protocol”.

SMARTIRB: An online platform which harmonizes and streamlines the reliance process for multi-site research. The SMART IRB platform eliminates the need for signed reliance agreements. For more information, please see https://smartirb.org/reliance/  

Multi-site Research and Reliance Forms