When Do You Need a Single IRB for Multi-Site Research Under the Revised Common Rule?

If your research spans multiple sites, you may already know that a single IRB is now required in many cases. The rule took effect in 2020, and it still catches people off guard, especially teams used to having each site run its own IRB review. This post covers when the single IRB requirement applies, when it doesn't, and how to get one set up.

Where the single IRB mandate came from

Before 2018, multi-site studies went through IRB review at every participating institution. A five-site study meant five separate IRBs reviewing essentially the same protocol. The outcome was what you'd expect: duplicated work, inconsistent feedback across sites, and delays that compounded as everyone waited on each other.

The 2018 revised Common Rule addressed this. Under 45 CFR 46.114, cooperative research conducted or supported by a federal department or agency that has adopted the Common Rule must use a single IRB of record for the portion of the research conducted in the United States. The compliance date was January 20, 2020. The logic is simple enough: if every site is running the same protocol on the same population, one IRB doing the ethical review is both faster and more consistent than five doing it separately.

When the sIRB requirement applies

The mandate kicks in when three conditions are all true:

1. The research is cooperative, meaning more than one institution is actually conducting research activities with human subjects (not just providing data or specimens).

2. The research is conducted in the United States. The sIRB requirement covers only the domestic portion of a study.

3. The research is funded or supported by a Common Rule agency, which includes HHS, NIH, NSF, DoD, DOE, and roughly 20 other federal departments. If you're unsure which regulations apply to your study, that's a good place to start.

All three? You need a single IRB.

NIH went further with its own policy (effective January 25, 2018), requiring a single IRB for all NIH-funded multi-site research even if the sites aren't using an identical protocol. The NIH policy covers grants, cooperative agreements, contracts, and intramural research. If NIH is funding it and it's multi-site, plan on a single IRB from day one.

When it doesn't apply

The exceptions are worth knowing just as well as the rule itself:

• Research conducted entirely outside the United States is not covered. The sIRB mandate is domestic only.

• The funding agency can grant an exception if it determines a single IRB isn't appropriate for a particular study, for example where there are logistical or ethical reasons favoring local review.

• Research involving tribal communities may be excluded. Tribal nations often have their own sovereignty-based review processes, and the regulation respects that.

• FDA-regulated studies that aren't federally funded don't fall under this mandate. If your multi-site trial is governed only by 21 CFR 50 and 21 CFR 56 with no Common Rule agency money involved, you can still use a single IRB (and many sponsors do), but the regulation doesn't require it.

• Exempt research is also excluded. Studies that qualify for an exempt determination under 45 CFR 46.104 are not subject to the sIRB requirement.

How it works in practice

The idea itself is not complicated. The coordination is where people lose time.

One IRB is designated as the IRB of record for the study. That IRB reviews the protocol, consent materials, and amendments, and issues the approval that all participating sites rely on.

Each participating institution signs a reliance agreement (sometimes called an IRB Authorization Agreement) that cedes review authority to the IRB of record for that specific protocol. In plain terms, the institution is saying: "We'll defer to this IRB's review for this study."

Local context still matters, though. Participating sites are responsible for flagging things like state-specific consent age laws, institutional policies, and site-level requirements. The reviewing IRB needs that information to make a properly informed decision.

Ongoing oversight runs through the single IRB too. Continuing reviews, amendments, reportable events: they all go through the IRB of record, even though individual sites are still responsible for reporting local issues up the chain.

Why independent IRBs make good sIRB candidates

When several institutions collaborate on a study, choosing one institution's IRB to be the IRB of record can get political. Nobody loves deferring to a peer institution's board, and there can be a perception that one site's priorities are driving the review.

An independent IRB avoids that problem. It sits outside the institutional hierarchy, so there's no turf issue and no appearance of bias. Institutions are generally more comfortable deferring to a board that has no affiliation with any of the sites involved.

The other thing is speed. Academic IRBs are juggling their own institution's protocols alongside reliance requests from external studies, and the external ones tend to get deprioritized. An independent IRB is built around turnaround time. If your team is trying to get the submission right the first time, that difference in responsiveness matters a lot.

Practical tips for setting up a sIRB arrangement

Pick your IRB of record early, ideally before the grant is even funded. Reliance agreements take time to negotiate and sign, and they need to be in place before research begins. This is the single biggest thing people underestimate.

Get your reliance agreements drafted upfront. Most institutions have templates, and if you're working with an independent IRB, they'll have one ready. Don't reinvent the wheel here.

Collect local context information from each site as early as you can: state laws, institutional requirements, site-specific consent language. The reviewing IRB needs all of it, and gathering it late is one of the main reasons sIRB setups stall.

Designate one point of contact at each site. Amendments, event reports, and local issues all need a clear channel to the single IRB, and "someone on the team will handle it" is not a plan.

Budget for sIRB costs during the proposal stage. Some grants include a line item for this. If your IRB of record charges per site or per amendment, get those numbers into the budget before you submit.

How Tempus IRB can help

Tempus IRB is an independent IRB that serves as the IRB of record for multi-site studies. We handle protocol review, reliance agreements, amendments, and continuing reviews, all at flat-rate pricing. If you're putting together a sIRB arrangement and want to talk through the setup, schedule a call or email us.

This post is for informational purposes only and does not constitute legal advice.