U.S. Department of Health and Human Services (HHS) regulations (45 CFR 46.114) state that nonexempt, federally funded, cooperative research involving more than one site in the U.S. must rely on one site’s institutional review board (referred to on this page as IRB, or Brown IRB for the University’s board) for study review and approval. The “single IRB” (sIRB) policy applies to sites approved on or after the effective date of January 20, 2020, with the exception of the following:

• Cooperative research for which review by more than one board is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe) 
• Cooperative research for which any federal department of agency supporting or conducting the research determines and documents that the use of a sIRB is not appropriate for the particular context
• Cooperative research conducted or supported by HHS agencies other than the National Institutes of Health (NIH), if an IRB initially approved the research before January 20, 2020
• Cooperative research conducted or supported by the NIH if either:
  • the NIH sIRB policy does not apply, and the research was initially approved by an IRB before January 20, 2020, or  
  • NIH excepted the research from its sIRB policy before January 20, 2020.

In accordance with federal regulations, any institution covered by this policy that is engaged in cooperative research must rely upon approval by a sIRB for that portion of the research that is conducted in the U.S. There are three basic ways an institution is considered to be engaged: participant interaction, access to identifiable data and if the institution is serving as prime awardee.

• Participant interaction — Researchers at the institution are involved in participant interactions, such as screening for eligibility, consenting, conducting surveys or administering interventions.
• Access to identifiable data — Researchers at the institution have access to identifiable data, including biospecimens and recordings.
• Prime awardee — The institution is the prime awardee or the affiliated investigator is named as a multiple principal investigator (MPI) on the grant. The prime awardee or MPI is considered to hold "parental rights" to all data collected for the project. Researchers at the prime awardee institution may not be interacting directly with the participants or planning to view any of the identifiers associated with the research, but as the “parent” they have intrinsic rights that allow access to the data.

HHS Engagement of Institutions in Human Subjects Research

Examples of Nonengagement

There are certain situations in which it may seem that an institution or organization is engaged in the research but they actually are not.

Commercial

Institutions or agencies that perform commercial or other services for investigators are not considered engaged provided that the services do not merit professional recognition or publication privileges, the services are typically performed for nonresearch purposes and the institution or agency doesn’t administer any study interventions.   

Submissions including a commercial entity will be reviewed by the Brown IRB to determine engagement. Determinations will be considered for each protocol on an individual basis. The following criteria must be met for a commercial entity to be considered not engaged in the research:

• The commercial entity must have established procedures for both staff training and confidentiality measures in human subjects research.
• The commercial entity does not retain research data. Any data collected on behalf of the research study will be destroyed upon transference to the investigator.
• The commercial entity must utilize research materials (i.e., informed consent documents, recruitment materials) approved by the Brown IRB for the associated protocol.

Examples that meet this condition include transcription services, survey firms or lab services (blood or urine analysis), MRI and X-ray. The use of Brown’s fMRI facility alone does not engage Brown in the research.

Routine Clinical Services

Institutions or agencies that provide clinical trial-related medical services that would typically be performed as part of routine clinical monitoring or follow-up are not considered engaged, provided that the institution or agency doesn’t recruit or consent, the institution or agency doesn’t administer any study interventions, and the study investigator retains responsibility.

These are generally health-related services that may be included in the research but are part of a participant’s routine care. Examples of this might also be blood work or a physical exam, X-rays or CT scans.

One-Time Service

Institutions or agencies that administer the study interventions limited to a one-time or short-term basis are not considered engaged, provided that it would be in the participant’s best interest, the institution or agency doesn’t recruit or consent, the study investigator retains responsibility and the overseeing IRB is informed

This scenario is designed to address emergency situations in which a participant is suddenly called out of town or is unexpectedly hospitalized. It is intended for clinical trials in which the participant’s well-being is dependent on the study procedures being administered.

Site Use or Recruitment

Institutions or agencies that permit the use of their facilities are not considered engaged.  Institutions or agencies that inform prospective participants about the research are not considered engaged.

Nonengaged institutions or agencies can:

• provide recruitment materials;
• provide consent forms;
• provide study contact information; or
• obtain permission for the study team to contact them.

Nonengaged institutions or agencies cannot:

• conduct screening for eligibility;
• obtain informed consent; or
• provide participant contact information without expressed permission for the study team to contact them.

Secondary Data

​Institutions whose employees or agents obtain coded private information must not have the means to re-identify the data to be considered nonengaged.

Also not engaged are institutions whose employees or agents release identifiable private information or identifiable biological specimens provided that the data was collected for purposes outside of the proposed research, the release of data conducted for a previous research study would not violate the informed consent and the research results will not be linked back to the original source for use in their research projects.

The institution that owns the data decides what and how they want to share. They may require a data use agreement (DUA). All DUA inquiries and requests should be directed to Brown’s Research Data Management team at dua@brown.edu.

Data Use Agreements

On-Site Individuals Covered under Overseeing IRB

People who are working at the institution, for a particular project, and not retaining any of the work or data for projects under the auspices of any other institution are not considered engaged. They only access research data and materials while on site for the project. Examples include contracted work, research assistants and study physicians.

Student Researcher Engagement

Student researchers, including medical students at The Warren Alpert Medical School, are engaged in research under the auspices of Brown University if any of the following conditions are met:

• The student researcher is receiving sponsored funding (external or internal funding of research through a formal application, competitive award or achievement/recognition award). 
• The research is fulfilling an educational requirement.
• The student researcher is utilizing Brown University resources to carry out their research activities. 
• The student will utilize study data for research under the auspices of Brown University.

Nonengaged Student Researchers

Student researchers, including medical students at The Warren Alpert Medical School, who are hired as research staff outside of the above conditions are not engaged in the research under the auspices of Brown University provided that:

• All proposed research activities are being conducted regardless of the involvement of the student researcher.
• The student researcher will not be retaining any of the data for use in Brown University research. 
• Brown University is not and will not be included in the approved protocol. 

Clinical Faculty Engagement

Clinical faculty generally submit their research to the IRB of their hospital affiliation. However, their research activities engage Brown University if any of the following conditions are met:

• The investigator is receiving sponsored funding for the research under their Brown University affiliation.
• The investigator is utilizing Brown University resources to carry out their research activities.

Clinical faculty may need to submit a PI Eligibility Form with the appropriate signatures to request approval to conduct research under the auspices of Brown University.

Request for Approval to Serve as PI

Brown Recipients of Nonfederal Parent Awards

Brown University employees or agents who receive a nonfederal parent award and provide subawards to subrecipients, internal or external to Brown, may request a nonengagement determination from the Division of Research for their involvement in the human subjects research conducted by the subrecipients. This determination may not be made by the Brown recipients themselves.

Requests for nonengagement will be considered on a case-by-case basis and guided by whether any participation by Brown researchers is so limited or marginal that considering them to be engaged would not meaningfully add to the protection of the human subjects in research.

Email irb@brown.edu for more information and a list of the required materials needed for this process.

Once it has been determined that you are conducting nonexempt, cooperative research and that your research partners are engaged, you will need to enact a reliance agreement. A reliance agreement is a written contract between two or more research partners used to document the delegation of IRB review responsibilities. 

Whether Brown is acting as the IRB of record or ceding review to another institution, all requests must be submitted in Huron for review and approval. Upon approval, Human Research Protection Program (HRPP) staff will take action to authorize the reliance agreement. After that, you will receive an official approval memo and can begin research activities

Determining the IRB of Record

There are several factors that can influence the decision on which site should maintain ethical oversight. In making this choice, consider any sponsor or budget requirements; which organization or institution is the prime awardee or home institution of the overall PI; and the location of research activities, data storage and analysis.

Brown is only able to be the IRB of record for up to three sites total, including Brown. Studies that involve more than three sites must either rely on one of the other sites or contract an independent IRB. (Sites that are not engaged in human subjects research or conducting exempt research do not count toward the total number of research sites.)

A reliance agreement with research partners can be established in several ways. The HRPP team has standard letters of agreement for all forms of reliance agreements that can be used when submitting your grant application.

When using a letter of agreement, HRPP staff will send Brown’s contract for review and signature from the partner institution’s authorized signatory once internal review is complete. When the HRPP team receives the signed document back, staff will issue an official approval memo and research activities can begin.

IRB Authorization Agreement

An IRB authorization agreement (IAA) is used when working with an established research institution or organization with its own IRB responsible for the ethical oversight of research activities. Brown may act as the IRB of record in an IAA or cede review to another institution. If you are planning to use an IAA, consult the HRPP-provided checklist to ensure all procedural requirements are met.

IAA Investigator Checklist

Organizational Authorization Agreement

An organizational authorization agreement (OAA) is used when working with a community organization that does not typically conduct human subjects research, with a PI whose qualifications meet the criteria to serve as an investigator. Brown may act as the IRB of record in an OAA, provided certain approval criteria are met. Discuss with HRPP staff to determine that the reliance is appropriate.

The organization entering an OAA must be established, meaning it has a searchable online presence corroborating that its organizational mission and values are aligned with the research activities, has an infrastructure that is able to provide the required resources and has an organizational representative or delegate who is able to serve as an authorized signatory. 

Individual Investigator Agreement 

An individual investigator agreement (IIA) is used when working with an individual investigator who is not affiliated with Brown University or any other institution with respect to this project or who is acting as an employee or agent of a non-assured institution that is not engaged in the research. Brown can act as the IRB of record in an IIA, provided certain approval criteria are met. Discuss with HRPP staff to determine that the reliance is appropriate.

If Brown Is the IRB of Record (All Agreements)

For new studies in which Brown is the IRB of record, complete a study submission in Huron that includes a site supplement for each relying site, the following templates and all accompanying documents (i.e., appendices, study materials, consent documents and recruitment materials), as well as the documented reliance agreement. Once the study is approved, you will need to submit a modification to enact the reliance agreement. This allows for timely approval of the study while accommodating the procedural demands of coordinating with the relying research partner.

The collaborating organization will have its own requirements for approving the request. For an efficient review and approval period, please communicate with your collaborator to ensure these requirements have been met.

For amendments, submit a modification in Huron with revised documents inclusive of new study sites and personnel. Be sure to reflect any changes in procedure, recruiting and consenting.

• Adding a Relying Site to Approved Studies [DOC]
• HRP-508 Template: Site Supplement [DOC]
• HRP-503 Template: Protocol [DOC]
• HRP-503a Template: SBS Protocol [DOC]

If Brown Is the IRB of Record (IIAs and OAAs)

If you are submitting an IIA or OAA with Brown as the IRB of record, you also will need to determine that any PIs meet Brown’s qualifications for an investigator, complete a Conflict of Interest Disclosure Form, provide a signed IIA or OAA and ensure all investigators complete human subjects research training in compliance with Brown policies. 

OAAs also require a Federalwide Assurance (FWA) for the term of the current submission with your submission for IRB review.

• Adding a Community Collaborator to Approved Studies [DOC]
• PI and Advisor Qualifications
• Non-Brown Investigator Conflict of Interest Disclosure Form [DOC]
• Complete Human Subjects Research Education and Training

If Brown Is the Relying Site (IAAs)

For new studies in which Brown is the relying site, complete a study submission in Huron using the Site Supplement template below. The submission must include a notice of IRB approval from the IRB of record (either the initial submission or the most recent continuing renewal), the approved protocol and any accompanying materials, including information about Brown University investigators and research activities. You also must submit the documented reliance agreement.

• Creating a Multi-Site Study to Rely on an External Site [DOC]
• HRP-508 Template: Site Supplement [DOC]

According to institutional policy, Brown is only able to be the IRB of record for up to three sites. Studies that involve more than three sites must rely on one of the collaborating organizations or engage an independent IRB. There are several independent IRBs that can be contracted. Investigators are not obligated to use a particular IRB's services. Below are some options of commercial IRBs that have collaborative experience with Brown. If you are proposing to use an IRB that is not featured below, please contact the HRPP so that we may vet their services prior to the initiation of reliance. There is no institutional funding available to cover costs associated with using a commercial IRB.

Advarra

Advarra is a commercial IRB providing comprehensive ethical oversight for all areas of research. Brown has negotiated a master reliance agreement with Advarra, which eliminates the need for an additional signed contract to rely on Advarra for IRB review. A signed cover page is required with all submissions to indicate to Advarra that Brown is aware and accepting of the pending review.

To initiate this process:

• Submit a collaborative research application to irb@brown.edu indicating your request to rely on Advarra.
• Upon initial review and acceptance, a cover page will be issued for inclusion with any submission to Advarra. 
• Once Advarra has approved the study, an approved protocol and approval letter must be submitted to Brown for processing. A Brown approval memo will be issued once the IAA has been fully executed. 

 Advarra's fee schedule is available upon request.

Advarra

SMART IRB

Brown University, many peer institutions and many sIRBs have signed the SMART IRB Agreement, a generic master reliance agreement that eliminates the need to establish a study-specific agreement. Studies and institutions making use of this existing agreement will have a streamlined startup process.

SMART IRB serves as a central, cloud-based location where all sites involved can view the procedures, access study documents and make a determination to cede or provide oversight. Brown University has joined SMART IRB by signing their joinder agreement, which delineates all of the expectations and requirements in entering into a reliance agreement. By using Smart IRB, institutions agree to comply with the established terms, eliminating the need to sign reliance agreements for each study.

The SMART IRB request is in conjunction with the actual submission to be reviewed and approved by HRPP or IRB. Investigators must submit a collaborative research application with accompanying required materials into Huron. Once approved, HRPPs staff will take action to execute the reliance on the SMART IRB portal.

The initiation of the reliance should be done by the overall PI. Investigators can delegate this role to a member of their research team (e.g., a co-investigator or study coordinator) or other staff member by having them request an account. To establish yourself as a Brown investigator, you should first request investigator access to SMART IRB. Once granted, you can begin the reliance request in the SMART IRB portal.

SMART IRB

WCG IRB

WCG IRB provides high-quality, full-service independent review for single and multi-site studies spanning all phases of research. WCG is the parent company of several integrated IRBs (New England IRB, Aspire IRB, Copernicus IRB and Midlands IRB) dedicated to improving the quality and efficiency of clinical trials. WCG IRB's fee schedule is available upon request.

WCG IRB

Researcher Responsibilities for Externally Reviewed Research

Brown University PIs are responsible for following the policies of the external IRBs and knowing the terms and conditions of your IAA. This includes submitting to the reviewing IRB using their forms and processes (or assisting the lead site with that process), following their reporting requirements for unanticipated problems and new information about the study, and complying with the stipulations of the IRB’s approval.

Brown University PIs are also responsible for:

• ensuring that any relevant financial conflicts of interest are disclosed to the reviewing IRB as required;
• obtaining any required ancillary review and approvals (e.g., biosafety, radiation safety, etc.) and providing the results of these reviews to the reviewing IRB if requested; and
• making copies of IRB approvals available for inspection.

IRB Reliance Exchange

IRB Reliance Exchange (IREx) serves as a central, cloud-based location where all sites involved can view the procedures, access study documents and make a determination to cede or provide oversight. The IREx platform includes an institutional profile that serves as a local context review and allows for the documentation of amendments and continuing reviews.

IREx does not have an internal master agreement and requires documentation of the terms and conditions of the reliance agreement through a commercial IRB or a letter of agreement.  Investigators must submit a collaborative research application indicating their request to use IREx to irb@brown.edu. Upon review and acceptance, HRPP staff will initiate the study in the IREx portal. Investigators will receive notification from IREx to log in and complete the required elements within the IREx portal.

• IRB Reliance Exchange
• Watch: IREx System Overview and Demo

Local Context Review

IRBs must consider many different regulations as part of their review, including state and local policies. A reviewing IRB may request this information in a variety of ways (e.g., worksheets, surveys, questionnaires), which generally require a signature from an authorized signatory. Some commercial IRBs, such as SMART IRB, and IREx allow for institutional profiles within their platform, eliminating the need for ancillary forms. 

Brown as the IRB of Record

For studies in which Brown serves as the reviewing IRB, HRPP staff may request the completion of the local context review form. This form can be submitted with the IAA application or HRPP staff will communicate with IRB administration at the relying organization for form completion. Not all relying organizations will be required to complete this form. Determinations are dependent on familiarity of collaboration and platform used for documentation.

Brown as the Relying Institution

When a collaborating IRB requires ancillary documentation, it should be submitted with the IAA application or directly to the IAA reviewer. The Brown HRPP team will work with the Brown PI and/or the collaborating institution to provide information about local context considerations and supply an authorized signature. PIs and study administrators are not authorized to sign reliance documents on behalf of Brown University.

If Brown is the lead research site you will need to contact the Brown IRB at least three weeks before the internal Sponsored Projects grant submission deadline, to discuss the use of sIRB review. Consider the following:

• The costs for IRB review are the responsibility of the lead site. 
• Brown is only able to be the IRB of record for up to three sites total, including Brown. In the rare instance that a fourth site is added mid-study and is engaged in human subjects research, and Brown is already serving as the sIRB, the HRPP team will evaluate to determine if Brown's IRB could continue to serve as the sIRB. 
• You must include relevant information about the sIRB plan in the grant application, including a budget and letters of support

When Brown Is the Lead Site

If Brown is the lead site (the sIRB of record), you will need to take the following steps before submitting your grant application to the appropriate authorized organizational representative — either Sponsored Projects or the BioMed Research Administration (BMRA).

When Brown Is a Participating Site

If Brown is a participating research site but not the lead site, the HRPP team can provide a letter of support indicating that Brown will rely on the chosen sIRB. Email irb@brown.edu at least one week before the internal Sponsored Projects grant submission deadline to request this letter. Your request should provide the following information:

• Name of Brown PI
• Name of lead PI and lead site
• Name of sIRB, if already selected
• Title of study/grant
• Grant deadline
• Brief description of study or link to NIH request for applications
• Any additional relevant information, such as whether a commercial IRB master reliance agreement will be used

Information to Include in the Grant Application

When using a sIRB to review your human subjects research protocol, make sure to include all necessary information with your application for grant funding.

The costs for IRB review have traditionally been included as indirect costs under an institution’s facilities and administration (F&A) rate and could not be described or direct-charged separately. The NIH sIRB policy expects that sIRBs will charge fees. Those fees are the responsibility of the lead site. NIH has provided guidance on which IRB review fees should be charged as direct vs. indirect costs under different IRB review scenarios.

Using an Independent sIRB

If you are the lead site and will use an independent, commercial board as the sIRB, you must work with the HRPP team to obtain that IRB’s fee structure. Brown has established a pre-negotiated reliance agreement with several commercial IRBs to facilitate this process.

There is no institutional funding available to cover costs associated with using a commercial IRB. The HRPP team strongly encourages collaborating research sites to determine up front which will serve as the IRB of record.

There is no mandate that a cooperative research study use an external commercial IRB. Any site engaged in a cooperative research study can serve as the IRB of record. There are several independent IRBs that can be contracted. Brown has negotiated a master reliance agreement with several commercial IRBs to facilitate a more expeditious review, but you are not obligated to use their services. In instances where all engaged research sites involved in collaborative research refuse to serve as the IRB of record, notify HRPP staff so the team can keep track of how frequently this occurs and if it occurs in instances where there is a total cost cap mandated by the sponsor.

Using another Institution’s IRB

If you are the lead site and will use the board of another institution (e.g., one of the participating sites) as the sIRB, you will find that IRB fees vary among institutions. Work directly with the sIRB to get information about their fees.

After receiving grant funding for human subjects research with sIRB review, the Brown lead PI should be prepared to take the following steps to ensure full compliance with federal regulations and Brown policies.