The NIH single IRB policy applies to the domestic sites of NIH-funded multi-site studies where each site will conduct the same protocol involving non-exempt human subjects research, whether supported through grants, cooperative agreements, contracts, or the NIH Intramural Research Program.
The NIH single IRB policy does not apply to studies conducted under career development, research training or fellowship awards. Under the policy, “multi-site” is defined as two or more sites. Foreign sites participating in NIH- funded, multi-site studies will not be expected to follow this policy. The policy recognizes that it may not always be possible to use a single IRB, and it provides for exceptions (see Exceptions FAQ’s below).
An NIH award recipient has several possible options for complying with the NIH single IRB policy including having the IRB at one of the participating sites agree to serve as the single IRB, using an independent IRB, including the IRB of a non-participating site, or using the IRB as required in the Funding Opportunity Announcement (FOA) or Request for Proposal (RFP) (for example, certain cancer clinical trials funded by the National Cancer Institute (NCI) are required to use the NCI Central IRB (CIRB)). As required in the federal Protection of Human Subjects regulations (45 CFR 46 Part E), the IRB must be registered with the Office for Human Research Protections (OHRP) and must have the appropriate membership, including the professional competence necessary to review the proposed research. See also NIH guidance on Scenarios to Illustrate the Use of Direct and Indirect Costs for Single IRB Review under the NIH Policy on the Use of a Single IRB for Multi-site Research.
The policy was published in the NIH Guide to Grants and Contracts (NOT-OD-16-094) and the Federal Register (81 FR40325) on June 21, 2016. More information about this policy may be found on the Office of Science Policy (OSP)website (https://osp.od.nih.gov/clinical-research/irb-review/). NIH will continue to provide additional resources and guidance to this policy prior to the implementation date. Additionally, questions about the NH single IRB policy may be sent to SingleIRBPolicy@mail.nih.gov.
The single IRB policy is effective for grant applications received for due dates on or after January 25, 2018. For contracts, the policy applies to all solicitations issued on or after January 25, 2018 Please note that this date is eight months later than the effective date that appears in the published single IRB policy. NIH decided to extend the effective date to provide additional time for implementation.
For the NIH single IRB policy, “NIH-funded multi-site studies” mean that the same protocol involving non-exempt human subjects research is being conducted at more than one site and is being wholly or partially funded by NIH.
Protocols that address the same research questions, involve the same methodologies, and evaluate the same outcomes are considered to be the “same research protocol.” Additionally, sites that are accruing research participants for studies that are identical except for variations due to local context consideration would be considered to be conducting the “same research protocol.”
Investigators who have questions about whether specific research protocols fall under the policy should discuss them with the Program Official listed on the FOA.
A Privacy Board is a review body that may be established to act upon requests for a waiver or an alteration of the Authorization requirement under the Privacy Rule for uses and disclosures of protected health information (PHI) for a research study. A Privacy Board may waive or alter all or part of the Authorization requirements for a specified research project or protocol. A covered entity may use and disclose PHI, without an Authorization, or with an altered Authorization, if it receives the proper documentation of approval of such alteration or waiver from a Privacy Board. If a multi-site project also requires a privacy review under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), it may be appropriate for the single IRB to serve as the Privacy Board. For more information, see: https://privacyruleandresearch.nih.gov/privacy_boards_hipaa_privacy_rule.asp.
The NIH single IRB policy only applies to multi-site studies that use the same research protocol. In this example, each site is using a different protocol, thus the investigators would not be expected to use a single IRB of record.
Alternatively, if the study was designed such that one protocol included all procedures from all sites of the study, the investigators would be expected to use a single IRB of record.
The NIH single IRB policy applies to multi-site human subjects research regardless of the funding mechanism (e.g., grants, cooperative agreements, contracts or other mechanisms such as Cooperative Research and Development Agreements (CRADAs), and Interagency Agreements (IAA)). The policy applies whether the sites are subawards to a primary award recipient or separate awards are made for participating sites.
The NIH Single IRB policy does not apply to Other Transaction Agreements (OTAs).
Yes. The policy applies to NIH-funded collaborative research protocols where all sites for a particular study are conducting the same protocol, regardless of the number of NIH awards funding that study protocol.
If an award involves both domestic and foreign sites, the domestic sites would be expected to use a single IRB and the foreign sites could use their own IRBs or Ethics Boards. An award that involves only foreign sites would not be expected to use a single IRB under the NIH single IRB policy. Similarly, an award that involves one domestic site and multiple foreign sites would not be expected to use a single IRB.
No. Because these types of awards are generally focused on providing training/career development opportunities and primarily provide support primarily for living expenses and education with minimal support for research, these awards are not subject to the NIH single IRB policy.
The NIH single IRB policy applies to all competing grant applications (new, renewal, revision, or resubmission) with receipt dates on or after the policy effective date. Ongoing, non-competing awards will not be expected to follow the policy until the grantee submits a competing renewal application after the policy is in effect. For contracts, the policy applies to all solicitations issued on or after the effective date.
The NIH single IRB policy applies to delayed onset awards proposed in applications received after the effective date. The information that must be submitted to the funding NIH institute or Center prior to starting delayed onset research must also include the single IRB plan per the Terms of the Award.
The NIH single IRB policy applies to all competing grant applications (new, renewal, revision, or resubmission) with receipt dates on or after the policy effective date. Ongoing, non-competing awards, such as the one described here, are not expected to follow this policy until the grantee submits a competing renewal application regardless of when the multi-site protocols begin.
The NIH sIRB policy applies to non-exempt human subjects research. Multi-site studies which require limited IRB review (for exemptions at 45 CFR 16(d)(2)(iii), d(3)(C), (d)(7), and (d)(8)) are not required to comply with the NIH sIRB policy.
In the NIH application/proposal for research funding, the applicant/offeror is expected to submit a plan describing the use of a single IRB that would be selected to serve as the IRB of record for all study sites. Where possible, the plan would identify the IRB that will serve as the single IRB. For delayed-onset research, where the IRB cannot be identified, applications/proposals should include a statement indicating that award recipients will follow the NIH single IRB policy and will provide a single IRB plan to the funding NIH Institute or Center prior to initiating a multi-site protocol.
NIH’s National Center for Advancing Translational Sciences (NCATS) Streamlined, Multi-site, Accelerated Resource for Trials (SMART) IRB Reliance Platform, has FAQs with tips for selecting a reviewing IRB.
In selecting a single IRB, applicants/offerors should consider the history and experience of the IRB, as well as its capacity to serve as the IRB of record for the particular protocol. The IRB must be registered with OHRP and must have the expertise necessary to review the proposed research.
No. Any of the participating sites may serve as the single IRB or an independent IRB, or another qualified IRB may be proposed. If possible, the plan to implement the NIH single IRB policy should be described in the application/proposal.
For delayed onset human subjects research, where the research cannot be described in the application or proposal but is likely to involve multiple sites, the delayed onset justification attachment must include information regarding how the study will comply with the single IRB policy and state that the award recipient will provide a single IRB plan prior to initiating the study.
Yes. As currently required for grant applications, participating sites should be listed in the application in the Project/Performance Site Locations section to the extent possible. For contract proposals, offerors should follow the instructions in the RFP.
Sites should agree to a single IRB arrangement prior to the submission of an application or proposal. The applicant should indicate the participating sites’ willingness to rely on the selected single IRB in the single IRB plan.
No. The proposed single IRB will not be evaluated as part of the peer review process and will not affect the overall assigned score of an application/proposal or the overall rating of the acceptability of the Protection of Human Subjects section. Peer reviewers may note if the plan to comply with the NIH single IRB policy is not included in the application/proposal but this will not impact the score.
If your study does not fall under the NIH single IRB policy for any reason you should answer “No” to question 3.2. This includes studies that involve multiple sites that are conducting different protocols. There is no need to provide a justification for your answer. Response to the Single IRB question is not a review criteria. If there are questions they will be addressed after peer review.
NIH’s National Center for Advancing Translational Sciences (NCATS) has developed detailed resources, including the Reliance Agreement that will be used by the Clinical and Translational Science Awards: the Streamlined, Multi-site, Accelerated Resource for Trials (SMART) IRB Reliance Platform, https://ncats.nih.gov/expertise/clinical/smartirb.
NIH requests certification of IRB approval as part of the Just-in-Time process. However, NIH recognizes that, for some studies, obtaining signed Reliance Agreements among sites may take longer to complete. In such cases, an acceptable timeframe for establishing the single IRB and obtaining IRB approval must be agreed upon by the NIH funding Institute or Center and the award recipient(s). Awards will not be made without certification of IRB approval; however, in extenuating circumstances the grant award will be made without certification of IRB approval but will include terms and conditions restricting all human subjects activities. Once the Reliance Agreements are signed and IRB approval is obtained, the NIH Institute or Center will lift the restrictions by revising the Notice of Award and the award recipient may then start the proposed multi-site human subjects research. A Reliance Agreement must be in place at a participating site before that site engages in human subjects research for the project.
No. Signed reliance agreements from participating sites will not be required to be in place prior to funding a multi-site study but must be in place prior to starting the proposed multi-site human subjects research. A Reliance Agreement must be in place at a participating site before that site engages in human subjects research for the project.
In general, a reliance agreement should describe the responsibilities of all parties, and how communication between parties will occur, for example, notification of the outcome of regulatory review, how protocol changes will be handled and who will responsible for reporting of unanticipated problems and non-compliance. (See National Center for Advancing Translational Sciences (NCATS) the Streamlined, Multi-site, Accelerated Resource for Trials (SMART) IRB Reliance Platform, https://ncats.nih.gov/expertise/clinical/smartirb for resources on IRB reliance agreements.)
Assuming both institution A and Institution B are engaged in the research there are 3 options for one institution to sign for the other:
• If the two institutions (A and B) agree that those conducting the research are acting as agents of only one of the institutions, then only one institution would be engaged and thus only one reliance agreement would be necessary for that engaged institution to rely on an external IRB and sign for both institutions. Note the revised Common Rule provides flexibility in how an institution and an external IRB can document the institution’s reliance on the external IRB for IRB oversight. §__.103(e) requires the institution and the organization that operates the external IRB to document the institution’s reliance on the IRB for oversight of the research and the responsibilities that each entity will undertake to ensure compliance with the Common Rule requirements (e.g. in a written agreement between the institution and the IRB, by implementation of an institution-wide policy directive providing the allocation of responsibilities between the institution and an IRB that is not affiliated with the institution, or as set forth in a research protocol).
• One of the engaged institutions (e.g., institution A) could defer IRB oversight to the other engaged institution (e.g., institution B) through a reliance agreement between the two institutions (A and B), and institution B could defer IRB oversight to an external IRB. The reliance agreement between institution B and the external IRB, as well as the IRB reliance agreement between institution A and institution B would need to reflect such reliance.
• If both engaged institutions (institution A and institution B) have their own FWAs, but operate under an “umbrella” institution, a single IRB reliance agreement with an external IRB can cover both institutions provided that the individual who signs the reliance agreement possesses the legal authority to bind both FWA-holding institutions.
Participating sites need to inform the single IRB about relevant local context issues (e.g., state laws). A communication plan should be developed as part of the Reliance Agreement and should describe how such communication will be handled.
These responsibilities should be defined in the Reliance Agreement. In general, the single IRB will refer instances of serious or continuing non-compliance to OHRP and/or the FDA, the participating sites’ IRBs and the funding NIH Institute or Center as required.
Sites should refer questions/concerns to the designated single IRB administrator. The communication plan, which will be developed as part of the Reliance Agreement should describe if, when, and how determinations or considerations of concerns about single IRB review will be handled. Disagreements should be handled as specified in Standard Operating Procedures for communication between relying institutions and the single IRB.
Except for the required regulatory IRB review, the HRPP at participating sites will be responsible for meeting all of its current related responsibilities described in the HHS regulations (45 CFR 46). These may include: reviewing conflicts of interest and radiation safety; ensuring that site investigators obtain informed consent from prospective research participants; ensuring that site investigators meet local training requirements; overseeing the implementation of the approved protocol; and reporting local unanticipated problems involving risks to subjects or others, and study progress to the single IRB. Participating sites must communicate information necessary for the single IRB to consider local context issues and state/local regulatory requirements. Other responsibilities may be specified in the Reliance Agreement.
The single IRB is the IRB of record for a study. No other IRB may make changes to documents previously approved by the single IRB. A communication plan should be developed that describes how relying sites will provide information, e.g. about local context to the single IRB.
NIH expects all participating domestic sites to rely on the single IRB. While exceptions can be requested, these will only be considered if there is a compelling ethical justification or need for local IRB review. Applicants/offerors that are proposing multi-site studies should inform the sites about NIH’s single IRB requirement and obtain their agreement prior to submitting the application/proposal. It is important to note that the cost of conducting a duplicate IRB review is unallowable and may not be charged to an NIH grant.
NIH Guidance on Reporting Adverse Events to Institutional Review Boards for NIH-Supported Multicenter Clinical Trials sets the expectation that multi-site studies with a Data Safety Monitoring Board (DSMB) report summary reports of adverse events to each IRB involved in the study. Multi-site studies using a single IRB of record shouldensure that summary reports of adverse events are transmitted to the single IRB of record, and in accordance with the reliance or authorization agreement. Transmitting the summary report in no way reduces the responsibility of each site to report individual adverse events in compliance with applicable reporting requirements and regulations.
The answer depends on whether the NIH funded site is a domestic site or a foreign site. NIH funded domestic sites in a multi-site study may NOT rely on a foreign IRB as the single IRB of record. However, please note that foreign sites in an NIH-funded multi-site study may rely on another foreign IRB as the single IRB of record.
If a single IRB plan is not provided in the application, or if the plan provided is incomplete or unacceptable, the funding NIH Institute or Center may ask the applicant to provide an acceptable single IRB plan prior to award.
The funding NIH Institute or Center will either accept the single IRB proposed in an application/proposal or will work with the award recipient to select an appropriate single IRB at the time of award or prior to the start of the multi-site study.
In general for delayed onset research, if it is not possible to certify IRB approval prior to award, terms and conditions restricting human subjects research will be placed on the award. Prior to the involvement of human subjects in research, the recipient is expected to submit to the funding NIH Institute or Center a complete Protection of Human Subjects section and the single IRB plan. Once the funding NIH Institute or Center has approved the protections for human subjects and the single IRB plan and received certification of approval from the IRB, the Notice of Award will be revised to remove the restriction on the award.
The NIH single IRB policy allows exceptions for domestic sites when review by a single IRB would be prohibited by a federal, tribal, or state law, regulation, or policy.
NIH will consider requests for other exceptions to the policy and will determine if there is adequate justification to approve an exception. Most exceptions are expected to be site-specific, that is, the exception to single IRB review will be made for a particular site, but all other sites conducting the same protocol will rely on the single IRB.
Exceptions to the NIH single IRB policy are automatic when local IRB review is required by federal, tribal, or state law/regulation/policy. However, the specific law/regulation/policy should be cited in the grant application/contract proposal’s single IRB plan. Exceptions will only be made for the site(s) affected by the state law/regulation/policy; other sites not affected by the state law/regulation/policy will be expected to rely on the single IRB.
No. Research involving Tribal Nations has an automatic exception, but this should be noted in the grant application/contract proposal’s single IRB plan. However, if a Tribal Nation wishes to use the designated single IRB, they may do so.
No. An exception for foreign sites is not needed because the single IRB policy applies to only domestic sites. Any foreign site of a multi-site study to which the single IRB policy applies is not subject to the single IRB policy, and it need not use the single IRB.
Certain types of exceptions, such as those based on federal, state, or tribal law, regulation or policy which would prohibit the use of a single IRB, or time limited exceptions for ancillary studies to other ongoing studies or parent studies, are considered automatic because they do not require review and approval by the NIH sIRB exceptions review committee (ERC). When these exceptions are appropriately identified in the sIRB plan, they will be automatically granted.
No. NIH will not consider requests for entire networks involving multiple protocols conducted at domestic sites. Exception requests must be submitted for each research protocol. The exception request must include a compelling justification for each protocol and include adequate information as to why each site cannot rely on the single IRB of record.
The cost principles are described in regulation at 45 CFR 75 Subpart E, and are implemented by reference in the NIH Grants Policy Statement (<a href="http://grants.nih.gov/grants/policy/nihgps/HTML5/section_7/7.2_the_cost_principles.htm">Section 7.2</a>). They establish standards for the allowability of costs, provide detailed guidance on the cost accounting treatment of costs as direct or indirect (F&A) costs, and set forth allowability and allocability principles for selected items of cost.
Direct charges for the salaries of administrative and clerical staff are allowable, but only if all of the following conditions are met: (1) administrative or clerical services are integral to a project or activity; (2) individuals involved can be specifically identified with the project or activity; (2) such costs are explicitly included in the budget; and (4) the costs are not also recovered as indirect costs. Such charges must also meet the criteria for allowable costs described in 45 CFR 75.403. Under the NIH Standard Terms of Award, these costs do not require NIH prior approval as long as the above conditions and criteria are met, and the recipient has appropriate supporting documentation. Please see the <a href="https://grants.nih.gov/grants/policy/nihgps/HTML5/section_8/8.1_changes_in_project_and_budget.htm#NIH">NIH Grants Policy Statement Section 126.96.36.199</a>.
Yes. Independent IRBs, which are <strong><u>not</u></strong> affiliated with a research institution, are neither included under another institution’s F&A rate agreement nor do they have Federally-negotiated indirect cost rate agreements of their own. Therefore, the fees charged by independent IRBs may be charged as a direct cost when they are serving as the single IRB. Please refer to <a href="http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-109.html">NOT-OD-16-109</a> for further guidance on single IRB cost allocation.
NIH has not established a prescribed ceiling or formula for single IRB costs. It is the recipient’s institutional responsibility to determine and calculate single IRB costs. As with all charges to NIH grants, costs must be reasonable and necessary, allocable, consistently treated, and conform to the limitations and exclusions as contained in the terms and conditions of award. Please see the <a href="http://grants.nih.gov/grants/policy/nihgps/HTML5/section_7/7.2_the_cost_principles.htm">NIH Grants Policy Statement Section 7.2</a> and 45 CFR 75.403 for more information on allowable costs.
Yes. Incremental or increased costs above what is included in an organization’s indirect cost pool, such as the single IRB’s review of site-specific considerations, may be charged as direct costs. However, the organization must ensure that such costs are not also recovered as indirect costs. Please refer to <a href="http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-109.html">NOT-OD-16-109</a> for guidance on single IRB cost allocation.
Recipient institutions have the flexibility to develop their own fee structures for single IRB costs in the manner that is most appropriate for their institutional systems and procedures, including a service center, fixed fee, or other appropriate methods. NIH will not dictate how recipients implement these structures, except to apply cost principles and administrative requirements.
Some fee structure arrangements may meet the criteria for a specialized service facility. Requirements for specialized service facilities are found at 45 CFR 75.468. NIH encourages recipients to identify an appropriate fee structure that supports the recipient’s requirements and audit structure.
Yes, institutions may choose to remove all IRB costs from their indirect cost pool thereby charging all IRB costs, including single IRB costs, as direct costs. However, institutions considering making this change should consult with their cognizant Federal agency for indirect costs so that the potential impact on the institution’s indirect cost rates can be assessed.
Applicants may include the various costs associated with single IRB review under any detailed budget category that is appropriate for the cost being requested (e.g., salary & fringe for individuals listed under Personnel, or fees listed under Other Costs), in accordance with the recipient’s method of charging single IRB costs
Yes. The cost principles have always afforded applicants the ability to include any costs meeting the direct cost criteria (i.e., applicable cost principles, the NIH Grants Policy Statement, and their institutional policies) in the application budget.
Institutions should refer to their Federally-negotiated indirect cost rate agreement for guidance on how indirect costs must be calculated, including identifying any exclusions. Institutions should consider the impact of costs such as single IRB when negotiating indirect cost rate agreements.
The cost principles have always allowed for recipients to charge IRB costs as direct charges. Recipients must ensure that costs are not recovered as both direct and indirect costs. We encourage institutions that are considering changes to their cost allocations to consult with their cognizant Federal agency for indirect costs so that the potential impact on the institution’s indirect cost rates can be assessed. It is not necessary to wait until the next F&A rate negotiation to consult with your cognizant Federal agency. Recipients may determine if and when to approach their cognizant Federal agency for indirect costs.
As always, NIH IC staff will engage the applicant in pre-award evaluation and negotiation of the award to ensure that the budget is appropriate to the work proposed. If it is necessary to revise the budget based on the selection of the single IRB, revised budget information may be requested prior to award.