Single IRB (sIRB) Review and Reliance Agreements

Multi-site research used to mean submitting the same protocol to every institution's IRB and reconciling every board's stipulations separately. For most federally funded non-exempt multi-site studies, that model is now prohibited. Under the revised Common Rule and the NIH single IRB policy, one IRB — the "reviewing IRB" or "sIRB" — issues the determination, and every other participating site relies on that review through a reliance agreement.

This guide explains what the sIRB requirement covers, how reliance agreements work, and how to use SMART IRB to set up reliance quickly.

What the sIRB requirement covers

Two overlapping federal policies drive most sIRB decisions:

• 45 CFR 46.114(b) — the Common Rule cooperative research provision. Any US institution engaged in cooperative research covered by the Common Rule must, with limited exceptions, rely on a single IRB for the portion of the research conducted in the US.
• The NIH Single IRB Policy (NOT-OD-16-094). NIH-funded multi-site studies using the same protocol to conduct non-exempt human subjects research at more than one US site must use a single IRB of record.

When sIRB does NOT apply

• Exempt research
• Research reviewed under a different federal regulation (e.g., FDA-only trials have their own rules)
• Career development, fellowship, and training grants that do not themselves support the multi-site research
• Research where tribal law or policy requires a specific IRB
• Research where sIRB review is prohibited by federal, tribal, or state law

How reliance agreements work

A reliance agreement (sometimes called an IRB Authorization Agreement, or IAA) is a written contract between two or more institutions that designates one institution's IRB as the reviewing IRB and the others as relying IRBs. The reviewing IRB handles initial review, continuing review, amendments, and reportable events. Relying institutions remain responsible for local context — consent language that reflects state law, local recruitment practices, HIPAA authorization, and ancillary committee reviews (biosafety, radiation, conflict of interest).

Two ways to establish reliance:

1. Study-specific reliance agreement. Institutions sign a one-off agreement for a single protocol. Slow, but sometimes necessary for institutions outside a master network.
2. Master reliance agreement. Institutions sign once and opt in per study. SMART IRB is the dominant master agreement in US academic research.

SMART IRB

SMART IRB is a free, NIH-funded national master reliance agreement. More than 1,000 US institutions have joined. Once two joined institutions exist on a study, you can use the SMART IRB Online Reliance System to set reliance in place without negotiating a new contract.

Typical SMART IRB workflow:

Local context: what stays at the relying site

Reliance moves the regulatory review. It does not eliminate local responsibilities:

• State law requirements for consent (e.g., specific language around research injury)
• HIPAA authorization reviewed by the covered entity's Privacy Officer
• Institutional Biosafety Committee (IBC) review for biological agents
• Radiation Safety Committee review for ionizing radiation
• Conflict of Interest review for the local PI
• Clinical Trial Agreement or other contractual review
• Local recruitment material review, if local-specific

Budgeting time for sIRB setup

NIH expects the sIRB plan at the proposal stage. Typical timelines once funded:

• Confirming SMART IRB participation and opening reliance requests: 2–4 weeks
• Reviewing IRB initial review: 4–8 weeks (see full board review for typical timing)
• Local-context review and site activation at each relying institution: 2–6 weeks

Multi-site studies should plan for 10–18 weeks between award and first participant enrolled, even with SMART IRB in place.

Common sIRB mistakes

• Naming an sIRB that some sites cannot use. Not every commercial IRB is accepted at every academic medical center. Verify each site's HRPP will accept before committing in a grant application.
• Treating local context as optional. Missing HIPAA authorization or IBC review blocks site activation even after sIRB approval.
• Forgetting to budget sIRB fees. Commercial sIRBs charge per protocol and per site. Academic sIRBs may charge nothing to their own institution but bill external relying sites.
• Using a single consent form for all sites. Consent must reflect each state's legal language. The reviewing IRB approves the master plus site-specific addenda.

What to include in your protocol

• Explicit statement that the study will use a single IRB
• Named reviewing IRB and the reliance mechanism (SMART IRB or other)
• List of performance sites and PI at each
• Plan for collecting and transmitting local context information
• Communication plan for reportable events, amendments, and continuing review
• Budget line for sIRB fees and local ancillary reviews

If you are drafting a multi-site proposal, start here before writing the protocol — see how to write your IRB protocol for the narrative sections and consent forms for master-plus-addendum consent patterns.