Beginner’s Guide to Single IRB Mandates

As the research community continues to seek clinical trial efficiencies designed to bring therapies to patients faster, more governing bodies are pushing for single institutional review board (single IRB) review as one way to streamline efforts.

To better understand what sIRB review requirements mean for sites and sponsors, it’s important to first understand what an single IRB is and how it works. This blog provides a beginner’s overview of single IRB review in the U.S.

Basics of Single IRB Overview

Before getting into specific requirements for sIRB review, it may be helpful to define sIRB. A single IRB is used to review for human subject protections at all clinical trial sites participating in a multisite study.

This centralized review eliminates multiple local IRBs reviewing a single trial, reducing the administrative burden of managing multiple IRBs’ requirements and timelines. When one IRB reviews a multisite study, this also helps keep participant protections consistent throughout the study and across all sites; for example, single IRB review ensures consistency in the information contained in the informed consent form (ICF).

Advantages to sIRB review include:

• Reduced administrative burden: Working with an sIRB allows for centralized management of initial and continuing reviews, amendments/modifications, and event reporting for sponsors, contract research organizations (CROs), and sites
• Increased efficiency: A sIRB review process enables faster study activation, quicker and more consistent amendment and modification reviews throughout the study, and frees local resources to manage more pressing local issues
• Consistent human subject protections: All sites relying on the same IRB helps ensure consistent study information is presented to all participants during the trial
  • Additionally, since only one IRB is receiving event reports, they may be better aware of potential safety issues across the entire study

Policies and Regulations Affecting Single IRB Review

Working with an sIRB remains completely voluntary in many cases. However, several mandates currently in effect require single IRB oversight for most multisite clinical trials.

National Institutes of Health (NIH) Policy

This policy establishes the expectation that as a condition of NIH funding and support, a single IRB of record will be used in the ethical review of nonexempt human subjects research protocols funded by the NIH that are carried out at more than one site in the U.S. This rule was the first sIRB mandate announced in the U.S., with compliance required beginning January 25, 2018. The policy doesn’t apply to foreign sites.

21^st Century Cures Act

Established in December 2016, this act included a requirement for the FDA to harmonize with other U.S. Health and Human Services (HHS) regulations as much as practicable, which includes sIRB requirements. It also removed the term “local” from “institutional review board” references in the regulations governing medical device research, making it clear single IRB oversight is permitted for multisite device trials.

Common Rule Single IRB Policy

The Common Rule refers to the Federal Policy for the Protection of Human Subjects outlined at 45 CFR 46 and applies to research overseen by the Department of Health and Human Services (DHHS) Office of Human Research Protections (OHRP) and other agencies.

The Common Rule’s sIRB mandate states organizations engaged in cooperative research must rely upon approval by a single IRB for that portion of the research conducted in the U.S. Cooperative research is defined as projects covered by this policy involving more than one institution. This requirement entered the regulations as part of a broader update in 2017, commonly referred to as the Revised Common Rule.

In order to be subject to the sIRB requirement, a study must be:

• Governed by the new rule and initially approved by an IRB on or after January 21, 2019
• Nonexempt human subjects research
• Meeting the definition of cooperative research
• Supported or conducted by a Common Rule department or agency

However, there are exceptions to this, including:

• The sIRB requirement only applies to research conducted in the U.S.
• Only sites engaged in nonexempt human subjects research activity need to comply
• Only sites subject to the Common Rule are subject to their sIRB requirements

Exception to the Common Rule Single IRB Mandate

HHS has released two separate exceptions to the Common Rule sIRB Mandate.

• November 2019: The Common Rule is not in effect for cooperative research conducted or supported by HHS other than NIH if the IRB approved the research before January 20, 2020
• October 2020: HHS components can issue exceptions to the Common Rule’s sIRB requirement for any research activity conducted or supported by the component taking place during the COVID-19 pandemic

Food and Drug Administration (FDA) Notices of Proposed Rulemaking (NPRM)

The FDA released two NPRMs in September 2022, proposing harmonization with the HHS Common Rule. One proposal, Institutional Review Boards; Cooperative Research, is geared toward cooperative research. This proposal is intended to require all U.S. sites involved in multisite research to use a single IRB, which would harmonize FDA regulations with NIH and HHS requirements.

The comment period for FDA’s NPRMs is open through December 28, 2022, and stakeholders are encouraged to submit their feedback on the proposals.

While FDA does not currently require single IRB oversight for multisite clinical trials, the agency has been a longtime advocate. FDA’s 2006 guidance document Using a Centralized IRB Review Process in Multicenter Clinical Trials underscores the value a single IRB review can provide.

There are many factors to consider when deciding to work with a single IRB. Understanding the mandates will help your organization determine the best course of action for your study and for your research program.

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