The IRB Review Process in Multi-Site Research

Multi-site research is typically overseen by a Single IRB (sIRB), also referred to as the Reviewing IRB, which reviews and approves the research for all the sites involved in the study. This approach is taken to streamline the review process, enhance consistency, and reduce duplication of effort, rather than each site obtaining approval from their own IRB for their individual site.

Using an sIRB is intended to:

• Streamline the IRB review process for study teams, institutions, sponsors and IRBs
• Allow research to begin faster without compromising on ethical principles, human research protections, and IRB review quality
• Help identify any study-wide safety issues sooner

Since January 2018, the NIH has required a single IRB to review multi-site studies. In January 2020, the main research regulations, known as the Common Rule, also began requiring a single IRB for all Cooperative Research. These “sIRB Mandates” aim to simplify and harmonize the ethical review process across participating sites.

The mandates apply if the study has NIH or Federal funding. Even if a study is only partially funded by these sources, it may still need to follow the sIRB mandate.

Lead Principal Investigators (PIs) must establish with confidence that proposed Participating Sites (pSites) can implement the protocol and comply with applicable regulatory requirements. Dedicating time to this effort can lead to efficiencies, identify where additional resources are needed, and how best to apply them to the multi-site study.

Lead PIs should:

• Evaluate the pSite PI's research experience and capacity to participate effectively. Do they have a dedicated regulatory contact to support them?
• Confirm the pSite study team’s understanding of their own HRPP/IRB’s role and requirements when planning to use an External IRB. For example, do they need to submit a shadow protocol to their local IRB?
• Consider local context issues, such as whether what the pSite considers clinical care aligns with the standards of the Lead Team and their home institution. 
• Establish if the research protocol will be implemented across multiple locations associated with the pSite and if they all fall under the same HRPP/ IRB office or are separate entities.

Reliance Agreements enable the single IRB review process and establish the IRB review arrangement. They document that the Relying Institution will use the Reviewing IRB to provide ethical review and approval of the research activities conducted by the Participating Site Study team. This process streamlines the IRB review, reduces redundancy, and ensures consistent ethical oversight.

NIH study teams establish a Reliance Agreement by submitting a request and working with the NIH IRB office.

Conducting the IRB review of a multi-site study is a collective endeavor that involves 4 key players and, to be successful, each player must know their role and responsibilities.

Reviewing IRB: This IRB reviews and approves the research according to applicable regulations. It provides regulatory oversight and protects human subjects across all sites conducting the study. You may also refer to the Reviewing IRB as the Single IRB, IRB of Record, or Central IRB.

Lead Study Team: Typically led by the Lead Principal Investigator (PI) and based at the institution of the Reviewing IRB, this team acts as the main point of contact with the Reviewing IRB. They facilitate communication between the Reviewing IRB and the Participating Sites. They develop the protocol and consents for the multi-site study.

Relying Institution: This institution participates in the multi-site research and uses the external Reviewing IRB for human subjects research oversight.

Participating Site Study Team: This team operates at a research site involved in multi-site research and is embedded within the Relying Institution. Led by the Participating Site PI, they conduct the research at their site and comply with both their home institution's requirements and those of the Reviewing IRB.

When the NIH Study Team leads a multi-site study and submits it to the NIH IRB for review and approval, the NIH acts as the Reviewing IRB and the NIH team becomes the Lead Study Team.

Each institution that joins the multi-site study must enter a Reliance Agreement with the NIH IRB and identify itself as a Relying Institution. Researchers from the institution that carries out the study are known as the Participating Site Study Team.

When the NIH Study Team implements a study at the NIH that is led by an External PI and overseen by an External IRB, the NIH acts as the Relying Institution and the NIH study team is the Participating Site Study Team.

In this case, the External PI oversees the Lead Study Team, and the External IRB serves as the Reviewing IRB for the multi-site study.

In the initial review process of a multi-site study, Reviewing IRBs typically use the parent-child approach. They first review and approve the overall protocol and the lead study team's site. Once the Reliance Agreement is in place, they add each participating site to the protocol, considering each site's research role and local context. The Reviewing IRB will receive the pSite’s first submission either through the Lead PI’s study team or directly from the pSite; it depends on the Reviewing IRB’s eIRB system.

Local context in multi-site research refers to the specific cultural, social, regulatory, and institutional factors unique to each research site. This includes the local population's characteristics, the environment where the research is conducted, and any local laws or guidelines that must be followed. Reviewing IRB’s and study teams must understand the local context to ensure the research is ethical, relevant, and effectively addresses the needs of each specific site.