The Research Compliance Office (RCO) will be closed during Stanford’s Winter Closure from Monday, December 23, 2024, through Friday, January 3, 2025, and will resume operations on Monday, January 6, 2025.

Stanford
Research Compliance Office

Getting Started with Single IRB

What is Single IRB (sIRB) Review Process?

One IRB of record (or Reviewing IRB), selected on a study-by-study basis, provides the regulatory and ethical review for all sites participating in a specific multi-site or cooperative study. Please refer to the Single IRB SOP for other related definitions.

I am requesting to rely on an External IRB

Stanford's IRB may agree to rely on an external IRB for multisite or cooperative research. The reliance terms are outlined in an IRB Authorization Agreement (IAA). Stanford has signed on to SMART IRB Agreement, which supports IRB reliance agreements nationwide. The external Reviewing IRB is responsible for reviews required by federal regulations at 45 CFR 46, and 21 CFR 50 and 56 (initial review, continuing review, modifications, reportable events). When Stanford’s IRB relies on an external IRB, Stanford retains responsibility to:

  • ensure investigator compliance with the protocol
  • confirm the Reviewing IRB’s determinations
  • ensure applicable federal and state regulations and Stanford policies are followed

Stanford's IRB also maintains responsibility for the local conduct of sIRB studies. This includes review of noncompliance and unanticipated problems, confirming investigator training, study monitoring, and ensuring local institutional reviews are completed (such as COI and radiation safety).

Please see the sIRB SOP for more detailed information. See the Relying Investigator Responsibilities here.

When will Stanford agree to rely on an external IRB?

  • Stanford will rely on external IRB for review when required per NIH Single IRB policy or Common Rule cooperative research provision.
  • Stanford may consider reliance when the lead PI or the research consortium is mandating use of single IRB.
  • Industry sponsored, research supported by other funding sources and unfunded research may be reviewed on case-by-case basis if reliance is required.

Reliance on an external IRB is considered on a case-by-case basis for high-risk studies when not mandated by NIH Single IRB policy or required by the Revised Common Rule's Cooperative Research Provision (45 CFR 46.114). Some examples for when reliance might not be appropriate include first-in-human drug or device studies, certain biological agents or Recombinant DNA Vector studies, and studies that involve stem cells.  Stanford’s IRB will not rely on an external IRB when Stanford is the sole site.  

What is needed for Stanford to rely on an external IRB?

The Stanford Investigator should submit an sIRB application in eProtocol to request reliance on an external IRB. The following should be included in the sIRB application submission:

  • IRB approved Study Protocol
  • IRB approved Consent form (any template can be used with Stanford required elements included)
  • IRB Reliance document (check with Reviewing IRB)
  • Federal Grant (when Stanford is the prime awardee)
  • Investigator Brochure and/or FDA documentation (if applicable)
  • Model consent template (if provided by Reviewing IRB)
  • Initial IRB approval letter from the Reviewing IRB. (This is the initial approval for the overall study typically does not include approval to add Stanford as a site.)
  • Local Context document (when requested by Reviewing IRB)

What are the Protocol Director’s responsibilities when relying on an external IRB or serving as the lead PI on a collaborative study?

The Stanford Investigator has additional responsibilities when relying on an external IRB as outlined at SMART IRB’s website.

When the Stanford Investigator is serving as the lead PI (whether the study is reviewed by an external IRB or the Stanford IRB) additional responsibilities should be followed as outlined at SMART IRB’s website.

Will the Reviewing IRB that is identified in the NIH application/proposal be evaluated during peer review? (NIH FAQs)

No. The proposed Reviewing 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. Per NIH's Single IRB and Exception Process Webinar (October 18, 2017) the Reviewing IRB does not have to be the IRB of the parent award.

What to consider when Stanford is the Prime Awardee for a federally supported project?

When Stanford is the Prime Awardee or the lead site for a federally supported project that is a multi-site or cooperative study requiring the use of sIRB, researchers will need to consider the following reviewing IRBs to include in their proposal submitted to the Federal Department or Agency (e.g, NIH, NSF, DoD, VA, ED, DOE) for the use of sIRB:

It is important to contact the Stanford IRB when writing your federal grant proposal to discuss which IRB will be used and to include a budget for sIRB review fees. sIRB review fees should be included as a direct line item in the grant budget prior to submission. Failure to obtain and include an sIRB budget may lead to delays in study start up or have significant financial impacts on the grant once awarded.

I am requesting the Stanford IRB to be the IRB of record

The Stanford IRB may agree to act as the Reviewing IRB for some multi-site or cooperative research. Submit the Stanford Reviewing IRB Request Form to determine if a reliance on the Stanford IRB is appropriate for a particular study. The decision for Stanford to act as Reviewing IRB is made on a case-by-case basis.  Several factors are considered in this decision, including but not limited to:

  • Whether Single IRB review is mandated under federal regulations
  • What activities will occur at the relying sites
  • The number of sites requesting to rely on the Stanford IRB

When should I consider submitting a Reliance Request Form to request Stanford to be Reviewing IRB?

The Stanford IRB may consider acting as Reviewing IRB for some minimal risk research that is required to use Single IRB under the federal regulations.  In most cases, Stanford should be the prime recipient of a federal award and/or the primary research site.

What are the Protocol Director’s responsibilities when serving as the lead PI on a collaborative study?

When the Stanford Investigator is serving as the lead PI (whether the study is reviewed by an external IRB or the Stanford IRB) additional responsibilities should be followed as outlined at SMART IRB’s website.

Single IRB Review Fees

Coming soon.

Reliance Agreements

What is a Reliance Agreement?

A reliance agreement, also called an IRB Authorization Agreement (IAA), is a document signed by two or more institutions engaged in human subjects research that permit one or more institutions to cede review to another IRB. There are multiple types of reliance agreements and generally the Reviewing IRB selects the agreement type.

Who signs the Reliance Agreement?

Stanford IRB has designated a signatory official that works with the IRB office on signing the reliance agreement. The sIRB Team facilitates obtaining the Stanford signatory official’s signature on behalf of the study team. The reliance agreement is signed after Stanford receives and completes its review of the sIRB application in eProtocol.

What is the SMART IRB Agreement?

The SMART IRB (the Streamlined, Multisite, and Accelerated Resources for Trials IRB Reliance platform) Agreement is a Master IRB Reliance Agreement designed to harmonize and streamline the IRB review process for multisite and cooperative studies and supports IRB reliance across the nation. The SMART IRB Agreement is not an IRB that reviews and approves research.

The SMART agreement can be implemented in two different ways, typically determined by the reviewing IRB:

1) The use of a SMART Letter of Acknowledgement (LOA) that signatory officials affiliated with both the Reviewing IRB and the Relying IRB sign.

2) The use of an online portal to document reliance using the SMART Agreement (i.e., SMART Online Reliance System (ORS) or the IRB Reliance Exchange (IREx) ). When a portal is used, the Stanford sIRB Team executes reliance digitally in the portal without the need for the signatory official to be involved.

Single IRB Mandates

NIH Funded Research

NIH policy on the Use of a Single Institutional Review Board for Multi-Site Research (effective January 25, 2018), applies to all NIH funded multi-site studies conducting the same research at each site.

  • All sites participating in multi-site studies involving non-exempt human subjects research funded by the NIH must use a single IRB (sIRB).  Applicants must include a plan for the use of a sIRB in their applications/proposals submitted to the NIH on or after January 25, 2018.
  • Costs associated with the sIRB review may be included as direct costs in the application budget.  Work with your Research Process Manager prior to submitting your proposal to NIH. NIH FAQs on sIRB costs. 
  • Guidance on Exceptions to the NIH Single IRB Policy (NOT-OD-18-003)
  • Guidance of Implementation of the NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research (NOT-OD-18-004)
  • 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 (NOT-OD-16-109)
  • Per NIH's Single IRB and Exception Process Webinar (October 18, 2017), the Reviewing IRB does not have to be the IRB of the parent award.

Common Rule - Cooperative Research

Cooperative Research funded under a Common Rule department or agency must be reviewed in compliance with 45 CFR 46.114 (b)   (Final rule effective January 20, 2020). Policy applies to federally supported, cooperative research – i.e., studies that involve more than one institution.

  • The revised Common Rule (i.e., the 2018 Requirements) requires at 45 CFR 46.114 (b) (cooperative research) that all institutions located in the United States that are engaged in non-exempt cooperative research conducted or supported by a Common Rule department or agency rely upon approval by a single IRB for the portion of the research that is conducted in the United States. Unlike the NIH mandate, that only applies to multi-site studies where all sites are conducting the same research procedures, the Common Rule mandate also applies to cooperative research where sites are conducting different research activities.
  • When requested by the funding agency, the Single IRB plan should be identified and included by the applicant within the grant application or the contract proposal.
  • The proposed budget in the grant application/contract proposal should reflect all necessary Single IRB costs without an approved “other exception”. Applicants should not assume that an exception will be granted when considering what Single IRB costs to include in the budget. Contact the Stanford Single IRB team at singleirb@stanford.edu when writing your federal grant proposal to ensure accurate sIRB review costs have been included in the grant budget.

Cooperative Research - Supporting Docs

NCI CIRB Initiative

Protocols Qualifying for CIRB Review 

The Adult and Pediatric CIRBs are the IRBs of record for certain adult and pediatric national multi-center cooperative oncology group cancer treatment trials.

More information on NCI CIRB

Still have questions about Single IRB Review?

For questions about Single IRB please contact the Stanford sIRB Team at singleirb@stanford.edu or 650-736-9024.

The sIRB Team holds weekly office hours on Tuesdays from 12pm – 1pm on Zoom to assist with sIRB questions or inquiries. Join Zoom conference HERE. No registration is needed.

Resources