4. The Role of Non-University of Nevada, Reno (External) IRBs, Single IRB and Independent Investigator Agreements

Updated September 28, 2023

The University considers an external IRB to be any IRB that is not the University IRB (i.e., the local IRB) including:

• Independent IRB: a review board that is not owned or operated by the research organization for which it provides review services; an independent IRB may or may not charge for these services.
• Central IRB: an IRB that provides review services for multiple sites participating in a clinical trial.

The University strongly supports the notion that resources devoted to the evaluation and management of research – whether internally or externally reviewed – should be calibrated appropriately according to the risks posed by the research. This extends to the content, assessment, and implementation of reliance agreements, including Master Agreements or reliance agreements. Examples of when the use of specific external IRBs may be required include: (1) Use of the Central Institutional Review Board for the National Cancer Institute (NCI CIRB). (2) The funding entity requires use of an external IRB when the organization is a participating site in a multi-site research. (3) Federal regulations, state laws, or local policies require use of a specific IRB. (4) The principal investigator(s) (PI), or a research consortium is mandating use of a single IRB.

University may enter into an IRB Authorization Agreement (IAA) with other entities to delegate IRB review or to conduct the review. Reliance relationships include reliance on an external IRB for review of multiple projects meeting defined criteria, reliance on a central IRB, and review by local IRB for a single project. Federal regulations require written agreements between/among institutions when IRB review and oversight of non-exempt research is not provided by the investigator's home institution.

Research Integrity senior staff review and determine if it is appropriate to proceed with execution of a Reliance Agreement. Director or senior staff will inquire if the external IRB's policies and procedures are compliant with AAHRPP standards. The external institution must provide copies or share web access if the IRB policies/procedures are not a public resource. Research Integrity staff will verify the FWA.

The decision to enter into an agreement with another institution for reliance of both institutions on one of the IRBs is made, depending on the risks of the study, after consideration of one or more of the following:

• evaluation of the external institution’s IRB policies and procedures;
• whether regulatory compliance and University standards may be upheld through the relationship;
• analysis of whether an efficient process may be implemented to conduct the reviews;
• discussions between IRB administrators from each institution;
• the level of risk from study procedures;

Definitions

Single IRB (sIRB): One IRB of record (or Reviewing IRB), selected on a study-by-study basis, provides the ethical review for all sites participating in a specific multisite study.

Relying IRB: IRB that relies on the reviewing IRB for the regulatory reviews. The relying IRB is still responsible for institutional reviews (Conflict of Interest, Radiation, Biosafety, Privacy, and others).

Reviewing IRB: The selected IRB of record that conducts the ethical review for participating sites of the multi-site study, including initial reviews, modifications, continuing reviews, and reportable events.

Lead PI: Responsible for the communication and overall conduct of the study and regulatory compliance. The Lead PI will be submitting the regulatory IRB submissions on behalf of all the sites relying on the reviewing IRB. (Note: The Lead PI may not always be associated with the reviewing IRB, but the Lead PI’s responsibilities nevertheless remain the same).

Relying PI: Responsible for providing the Lead PI with necessary information according to the reviewing IRB’s policies and procedures so the reviewing IRB can conduct an IRB review. The relying PI must know what is also required from their local relying IRB.

Commercial IRB: Commercial or independent IRBs are contracted agencies that are not affiliated with specific institutions and are paid to conduct reviews of research with human participants.

Independent Investigator Agreements: When an investigator is not engaged with the University as an employee or student for the purpose of conducting a research project involving human participants, that project will be considered external and will require an agreement to utilize the University IRB.

External IRB: a review board that is not the University IRB.

Commercial IRB

The University has a Master Agreement with WCG IRB (formerly WIRB) to utilize regulatory review services when the research involves a multi-center, industry sponsored, non-federally funded clinical study, excluding the VA. (The VA permits use of a commercial IRB as an IRB of Record for VA facilities only if it has been specifically designated by ORD as a commercial IRB that may serve as an IRB for cooperative research.) These include pediatric, as well as adult studies and drug, device, or observational studies. The commercial IRB will review HIPAA Authorization language in consent documents. PIs planning to conduct research that is under 21 CFR 56.104 (for FDA-regulated research) at WCG IRB must complete the steps outlined below. PI will have all WCG IRB submissions in IRBNet archive.

• Create a New Project in IRBNet; go to Select Library, click on WCG IRB (formerly WIRB), Puyallup WA-documents for Researchers
• Add a Part I Cover Sheet
• Obtain PI signature electronically through IRBNet.
• Submit the project for Administrative Review.

Research Integrity staff will forward to WCG IRB. WCG IRB accepts the transmission via IRBNet as local policy review and approval.

SMART IRB Portal

The University has joined Streamlined, Multisite, and Accelerated Resources for Trials known as SMART IRB. Through a SMART IRB Master Common Reciprocal Authorization Agreement, reliance arrangements between collaborating institutions can be determined and documented, paving the way for easier collaboration and adherence to the National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board for Multi-Site Research. Access to SMART IRB allows research investigators or their designee to submit requests for IRB reliance. Typically, the SMART IRB request is initiated by the researchers who’s "Home Institution" IRB will be requested as the Reviewing IRB (the IRB accepting the reliance of other IRBs). If you have never used the SMART IRB online reliance system, you must first Request Investigator Access through SMART IRB. Please review SMART IRB's Checklist for Initiating a Request in the Online System for instructions on how to submit a request for reliance. Please review this flowchart on the SMART IRB process.

Reliance Agreements

A reliance agreement, also called an IRB Authorization Agreement (IAA), is a document signed by two or more institutions engaged in human research that permit one or more institutions to cede review to another IRB. This is generally initiated and provided by the relying IRB. If the research project is NOT using SMART IRB or another partner for which we already have an existing agreement, then a Reliance Agreement is needed. The Human Research Protection Program will route the Reliance Agreement to the appropriate person for signature when a request is submitted for review. Templates are available in the Researcher and Committee Member Libraries in IRBNet. The Research Integrity will assist the investigator in preparing IAA and obtaining the requisite signatures of the two Institutional Signatories. The University templates specify responsibilities for the participating sites (including the University) that are relevant to the protection of human participants. Therefore, the University IRB prefers investigators use its templates, but may allow use of the external site's IAA or the investigator's agreement form only on a case-by-case basis. IRB agreements may apply to one or more specific projects; to select aspects of a project; or to all projects conducted by a single investigator or overseen by a specific IRB. The agreement should specify research to which it applies.
Written agreement must describe whether the organization conducting the IRB review, or the relying organization, is responsible for the following:

• Education to researchers and research staff;
• Identifying which organization’s process is used to decide whether each incident of noncompliance is serious or continuing;
• Obtaining management plans for researcher and research staff conflicts of interest;
• Ensuring that, should termination of a reliance agreement occur, one of the parties clearly is responsible for continued oversight of active studies until closure or a mutually agreed upon transfer of the studies.

When local University serves as the Reviewing IRB

For local University principal investigator (PI) requests that the local University IRB serve as the reviewing IRB for an external research site, the PI submits a protocol for review and approval prior to or concurrent with the addition of external sites. The IRB determines on a case by-case basis whether to review the site additions as separate protocols or as modifications to the previously approved research. If a site is added through a modification, the IRB decides whether to handle such a modification using expedited review procedures or the convened IRB for review.

The relying site provides the local University IRB with general information (e.g., FWA, Point of Contact/Signatory Authority, ancillary reviews, local consent language, local laws, investigator qualifications, local resources, recruitment materials, and communication plan). When relying upon an IRB that is not AAHRPP-accredited, policies and procedures must also define: (1) The process ensuring research is being reviewed appropriately and complies with applicable law and (2) Criteria describing the extent of the review to confirm compliance with the organization’s ethical standards and with applicable laws and regulations. The extent of the review of the non-accredited IRB can vary, depending upon the level of risk to participants in the research.

The relying site must have policies and procedures that describe the roles of the reviewing IRB.

• Ensuring the structure and composition of the IRB is appropriate to the research reviewed and complies with applicable laws and is properly constituted
• Conducting review of research to determine that research is ethically justifiable, according to all applicable regulations and laws;
• Conducting review of the addition of investigative sites to previously approved protocols;
• Ensuring the IRB has the final authority to decide whether researcher or research staff conflict of interest and its management;
• Making available relevant IRB, including but not limited to minutes, approved protocols, consent documents, and other records that document the IRB’s determinations to the relying organization upon request.
• Making relevant IRB policies readily available to the relying organization, including HRPP staff, and researchers and research staff, and having a mechanism for communicating to the organization when policies are updated;
• Specifying the contact person and providing contact information for the reviewing IRB for researchers and research staff to obtain answers to questions, express concerns, and convey suggestions regarding the IRB.

The local University IRB considers this information when conducting its review. Each relying site complies with its own institution’s HIPAA policies and procedures.

Open communication between relying sites and the local University IRB is encouraged. The relying institution staff members may reach out via phone or email using the contact information provided in the reliance agreement.

When local University relies on an External IRB

The determination to defer review is made on a case-by-case basis based on criteria outlined in Request to Use an External IRB form. IRB does not sign reliance agreements for exempt activities or activities deemed to be not human subject research (exceptions may be made on a case-by-case basis for exempt activities).

The University IRB may voluntarily decide to rely on an external IRB in certain situations. Examples of voluntary reliance include:

• Using another IRB because it has expertise for reviewing the research.
• Identifying an external IRB to act as the IRB on behalf of the organization when the organization has determined due to resources, legal, organizational conflicts of interest, or other concerns that conducting its own review or serving as the IRB for a multi-site project is not feasible.

Relying upon an external IRB to facilitate collaborations among researchers and organizations.
Local University may agree to cede/defer responsibility for IRB review to an institution not accredited by AAHRPP for research that is not greater than minimal risk. The local University investigator complies with the reviewing IRB’s policies and procedures for initial and continuing review, record keeping, and reporting requirements, and ensures that all information requested by the reviewing IRB is provided in a timely manner. The relying organization’s policies and procedures must:

• Describe the roles of the organization and researchers when relying upon another organization’s IRB;
• Specify which studies are eligible for review by another organization’s IRB;
• Ensure that researchers are knowledgeable about the need to obtain any approvals from their own organization prior to seeking review by another IRB;
• Providing the reviewing IRB with requested information about local requirements or local research context issues relevant to the IRB’s determination, prior to IRB review;
• Ensure that officials of the relying organization may not approve the research subject to the reliance agreement if it has not been approved by the reviewing IRB;
• Acknowledge that researchers must cooperate in the reviewing IRB’s responsibility for initial and continuing review, record keeping, and reporting, and that all information requested by the reviewing IRB must be provided in a timely manner.
• Ensure that researchers, when responsible for enrolling participants, will obtain, document, and maintain records of consent for each participant;
• Report promptly to the reviewing IRB any unanticipated problems involving risks to participants or others;
• Ensure researchers and research staff have appropriate qualifications and expertise to conduct the research;

Research Integrity staff maintain electronic versions of all fully executed Reliance Agreements for three years after project closure. When an agreement applies to a project/package in IRBNet, Research Integrity staff add the fully executed agreement to the project/package as a Board Document.

UNR Medical Students Join A Research Study Approved by an External IRB

UNR Medical students may be asked by a Community Physician to join a research study that was reviewed and approved by an external IRB. Documentation of the approved study should be uploaded into IRBNet submission, as follows:

• Create a New Project in IRBNet
• Add a Part I Cover Sheet
• Add completed Request to use External IRB form
• Upload the Approval letter from the external IRB
• Upload the documentation to external IRB adding the UNR medical student as study personnel
• Upload the approved consent form
• Obtain PI signature electronically through IRBNet (alternatively, UNR Med Research Director, Clinical Research Programs for non-local PI)
• Submit the project for Administrative Review ceding regulatory review to external IRB

Determination that Dual or Joint Review by an External and the local University IRB Is Required

Review by both an external and the local University IRB may be required when research activities take place at both an external institution and a University/Affiliate site; University/Affiliate faculty, students, or staff will be enrolled as participants in multi-site research; the sponsor requests use of a central/independent IRB for multi-site research, but the local University IRB determines local oversight is warranted (e.g., participant risk is extreme, the research involves highly regulated or toxic substances, local context issues are significant); or limited review by the local University IRB is necessary to assess/monitor local context issues or concerns directly affecting the local community.

Submission Requirements when Research Integrity Determines Review by an External IRB Is Acceptable

After Research Integrity confirms review by an external IRB is acceptable the PI must complete the following steps:

• Determine if an existing IAA applies or if a new IAA is required (see policy for IRB agreements).
• Use the Consent Form Checklist and revise the sponsor/external IRB-prepared consent templates to include University/AAHRPP-required elements for informed consent, including local contacts for research participants’ questions or compensation for injuries, where applicable.
• Comply with University training requirements.
• Comply with University or the Affiliate institution's conflict of interest disclosure requirements.
• Comply with applicable University/Affiliate-site requirements for review by local, ancillary committees (e.g., biosafety, radiation safety, pharmacy). Documentation of ancillary committee approval should be added to the project in IRBNet.
• Create a New Project in IRBNet.
• Add Part I, Cover Sheet.
• Complete the Request for External IRB form.
• Add the proposed consent document, protocol, data collection tools, and recruitment materials.
• Obtain the PI's signature electronically through IRBNet.
• Submit the project to IRBNet for Administrative Review. (NOTE: The Research Integrity Director may determine a request to use an external IRB requires Expedited or Full Committee Review.)
• Research Integrity staff will instruct PI on obtaining an IAA or use of SMART IRB.

Submission of External IRB Approval

PI should submit the external IRB approval correspondence (including IRB correspondence requesting changes contingent on approval) and approved informed consent form (and any revised documents) within sixty days of the initial submission, Request to Use External IRB, in IRBNet.

• Open the existing project in IRBNet.
• Create a New Package for the existing project, selecting Submission Type "Other."
• Add the external IRB of Record approval letter and approved consent document (including any revised documents and IRB correspondence requesting changes)
• Obtain the PI's signature electronically through IRBNet.
• Submit the project to IRBNet for Administrative Review.

As noted previously, the preferred sequence of events is for the local University IRB to (1) confirm the proposed consent document complies with University requirements and acknowledge the external IRB as the IRB of Record BEFORE the project is submitted for review by the external IRB; and (2) after the external IRB approves the project, acknowledge the external approval, again by administrative review. If this order is reversed, the PI should attach the external IRB of Record approval letter and approved consent form when submitting the request to use an external IRB. Under these circumstances, the University IRB may require changes to consent documents approved by the external IRB if the documents do not comply with University requirements.

Requirements for Post-Approval Notifications to the local University IRB

To enable the local University IRB to ensure requirements for post-approval monitoring are met, University/Affiliate PIs conducting research reviewed by an external IRB promptly notify the local University IRB of:

• the IRB of Record's approval for continuing reviews (including the regulatory requirement to assess interim findings that may affect the research) and amendments;
• the IRB of Record's determinations of noncompliance, unanticipated problems, and suspension of termination of the IRB approval or investigators involvement in the research; and local, unexpected, and related serious adverse events (SAEs) and study closures.

Notifying the local University IRB of the External IRB's Approvals for Continuing Review

For the duration of the research, University/Affiliate PIs must promptly provide the local University IRB with documentation of each continuing review approval from the external IRB of Record.

• Open the existing project in IRBNet.
• Create a New Package for the existing project, selecting Submission Type "Other"
• Submit Continuing Review/Progress form in IRBNet or the equivalent form reviewed by IRB of Record
• Add documentation of IRB approval for each continuing review

Notifying the local University IRB of the External IRB's Approvals for Amendments

For the duration of the research, University/Affiliate PIs must promptly provide the local University IRB with documentation of each substantial change or amendment approval from the external IRB of Record. (Do not report minor changes, i.e. personnel changes, minor word changes in consent, etc.)

• Open the existing project in IRBNet.
• Create a New Package for the existing project, selecting Submission Type "Other"
• Submit Amendment form in IRBNet or the equivalent form reviewed by IRB of Record
• Add documentation of IRB approval for each amendment review

Notifying the local University IRB of the External IRB's Determinations of Noncompliance, Unanticipated Problems, or Suspension/Termination of IRB Approval or Investigator's Involvement in the Research

For the duration of the research, University/Affiliate PIs must promptly provide the University IRB with documentation of each determinations of Noncompliance, Unanticipated Problems, or Suspension/Termination of IRB Approval from the external IRB of Record.

• Open the existing project in IRBNet.
• Create a New Package for the existing project, selecting Submission Type "Other."
• Add documentation of the IRB of Record's determination (IRB of Record Reporting form and IRB correspondence).

Notifying the local University IRB of Closure of Projects Overseen by External IRB of Record

University/Affiliate PIs must promptly notify the University IRB of closures of research projects that are overseen by an external IRB of Record.

Single IRB (sIRB) Criteria

Single IRB means that the local University IRB either assumes (reviewing IRB) or gives up (relying IRB) its oversight of the research activity to another equally qualified IRB. sIRB is designed to reduce duplication and increase efficiency by designating a sIRB review when more than one site is involved in a research project. The basis for the Single IRB Model is to allow multiple institutions that are conducting the same protocol to use a single IRB for review, instead of using multiple IRBs to review the research at the sites individually. University IRB also bears responsibility for the local conduct of sIRB studies, including managing noncompliance and unanticipated problems, ensuring training, study monitoring, local ancillary requirements, managing reliance agreements, and handling study specific issues.

The University will decline to serve as the single IRB of record for greater than minimal risk research unless there are extenuating circumstances, such as University faculty being the lead PI for the multi-site study.

The University may allow for single IRB review when:

• The local University investigator is a collaborator on human research primarily conducted at another organization where: The PI of the organization will have direct oversight of the University investigator; The organization agrees to take responsibility for the University investigator;
• The other organization is AAHRPP accredited. Note: For organizations that are not AAHRPP accredited, decisions are made on a per-protocol basis to ensure that the organization can maintain equivalent standards to AAHRPP accreditation.
• When the lead PI or the research consortium is mandating use of single IRB.
• The funding entity requires use of an external IRB when the organization is a participating site in a multi-site research. For example, the Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research requires all multi-site research to use a single IRB with a few exceptions.
• Federal regulations, state laws, or local policies require use of a specific IRB. For example, the revised Common Rule released in 2017 requires review by a single IRB for any cooperative research as of January 20, 2020.

The University may not allow for single IRB review when:

• The project involves prisoners or vulnerable populations that require special considerations.
• The proposed IRB of record does not have sufficient knowledge of local context or a robust human research program (as required by federal guidelines and AAHRPP accreditation) to assume IRB oversight for sites that fall under University purview;
• A study team member has a conflict of interest that requires a management plan, and the management plan prohibits or limits activities that the individual can engage in related to human research; or
• A team member has a history of noncompliance with IRB policies or processes.
• Applies to participating research sites in the United States of America.

Documentation Required

Before a project can participate in a sIRB agreement, the University must verify that all institutional approvals are in place prior to issuing the approval to allow another IRB to review the project.

A request for sIRB submitted to IRBNet must include, but not limited to, the following approvals:

• Request to Use External IRB form
• Current sIRB approved study protocol
• Training Certificates for study team members
• Reliance Agreement
• Consent Template, protocol, data collection tools and recruitment materials
• After receiving the approved study documents from the Relying/Lead site, submit the approved consent document, approval letter from the IRB of Record (Relying/Lead IRB), and any additional supporting materials related to enrollment at the University
• Any adverse event or noncompliance with the protocol that takes place at University;

The University remains responsible for ensuring all staff listed on a protocol, even one reviewed by another IRB, are appropriately trained in human research protections. As such, a personnel change amendment should be submitted if new staff are to be added. As with other personnel changes, approval of the personnel changes must be granted before the individuals may begin work on the study. The above cited submissions requirements for Relying on External IRB apply to sIRB.

Reporting Requirements for Multi-Site Research

When a University or Affiliate investigator is involved in the conduct of a multi-center study, reporting requirements vary as follows:

• For problems that occur locally (i.e., at the investigator’s institution), the PI must inform the University IRB of complaints from participants or other local situations or events that involve possible noncompliance, and unanticipated problems involving risks to participants or others.
• PIs must inform the sponsor of complaints and local problems and adverse events as described in the clinical protocol or contract.
• The investigator must inform the University IRB and sponsor of her/his decision to suspend or terminate a research project at the local site.
• PIs are required to report sponsor assessments or notifications, or safety reports involving external adverse events that may be unanticipated problems involving risks to participants or others; and all notifications of suspension or termination of a research project.
• If a University or affiliate investigator is the lead PI or managing investigator for a multi-center study, she/he/they must inform the University IRB of external (i.e., occurring at other sites) complaints from participants or others, possible noncompliance, and unanticipated problems involving risks to participants or others. If the University or affiliate investigator is not the lead PI or managing investigator, and University of Nevada, Reno is in the position as a relying institution, she/he/they will promptly notify Overall PI, Site Investigator(s), and Relying Institution(s) of any findings of serious and/or continuing noncompliance. The Reviewing IRB will also notify the Overall PI, Site Investigator(s), and Relying Institution(s) of any suspension or termination of IRB approval and any remediation actions pertaining to findings of serious and/or continuing noncompliance at any other institution if such finding or actions relate to or may affect the conduct of the Research or the safety, rights, or welfare of human participants participating in the Research at the Relying Institution(s). The Reviewing IRB shall inform the Relying Institution of any corrective actions in connection with the audit, investigation, or resolution of any matter that are required by the Reviewing IRB but shall not prevent the Relying Institution from adopting its own more stringent additional corrective actions.

Independent Investigator Agreements

An Independent Investigator Agreement is required when an individual wish to conduct human research at or on behalf of an external entity that does not have an IRB, and she/he/they wants the University IRB to be the IRB of Record. Research Integrity Director determines on a case by-case basis whether to proceed with an Independent Investigator Agreement. Generally, the research study and/or investigator must have a direct relationship to the University.
The IRB will only conduct external reviews of proposals for which it is qualified in terms of adequate experience and subject expertise. The infrastructure that supports the IRB is funded by the indirect (F&A) return on expenditures. That cost is not captured when the funding is run outside of the University. The fees are charged to help offset the costs of such operations, including expertise-based protocol reviews, administrative support, technological infrastructure (electronic-based submission systems), educational and training requirements, and other activities of the Human Research Protection Program (HRPP).