Human Research Protection Program (HRPP)
Process to Rely on a CIRB/SIRB↓

HRPP: Human Research Protection Program. The HRPP is usually comprised of multiple offices tasked with the ethical and compliant conduct of human subject research at an institution. The IRB is often one of the groups within the HRPP, which may also include other groups, e.g. Conflict of Interest, Radiation Safety, HIPAA Privacy Boards, Biosafety, etc.

Reliance Invitation Letter: This letter is composed and sent by the lead study team (with the assistance of the single IRB (sIRB)) to a site or institution that may need/would like to rely on an IRB other than their usual IRB of record. The reliance invitation should identify the study/studies proposed for reliance, the investigator requesting the single IRB model, the name/affiliation of the sIRB, and in most cases, a copy of the draft protocol and draft consent.

Consultations can be conducted in-person, or via video or teleconferencing. Consultations can be anywhere from five minutes long to over an hour, depending on the complexity of the study and proposed reliance relationship.

Some questions to ask during the consultation:

1. What are the characteristics of the study (design, study procedures, consent process)?
2. Which sites are engaged in research? Who will have access to identifiable data/biospecimens?
3. Which sIRB are you proposing we rely on? OR Which sites are you requesting rely on us?
4. Are there any specific institutional, community, or HRP concerns with the proposed relationship?
5. Are there any timing issues we should be aware of, e.g. pending grant funding, pending FDA determinations, protocol development, etc.?

It is advisable that the consultation also be used as an opportunity to educate the investigator about how the sIRB and HRP Review processes work. In particular, emphasis should be placed on the difference between sIRB approval, and HRP study activation (see below for more information), which are both required before the research can begin at the relying site.

Reliance Decision Letter: Sometimes referred to as the “reliance handshake letter”, the Reliance Decision Letter is the first step in a reliance relationship between two institutions. The letter is the means by which each institution documents that the HRPP is amenable to relying on the sIRB. It also assures the sIRB that it is worth devoting resources to conducting the IRB review on behalf of the relying institution, and provides the HRPP with a starting point for reliance negotiations.

The format of the Reliance Decision Letter should follow local policies, keeping in mind that due to the nature of the reliance relationship with an entity external to themselves, each institution should be flexible with regard to the format, style and verbiage of the letter itself. In some cases, a simple email from an authorized individual may be sufficient documentation, while in others, a form letter signed by a designated signatory may be appropriate. However, this letter is not intended to replace the formal Reliance Agreement that will follow this step; it is merely a simple statement of intent to initiate the process.

Reliance Agreement: A formal, written document that allows an institution, entity, or individual engaged in human subjects research to delegate Institutional Review Board (IRB) review to a specific IRB. This agreement allows one or more institution(s) to cede review to another IRB.

It is recommended that a Local Considerations Package include:

1. The Institutional/Community Profile for the relying institution
2. Any consent document language required by the relying institution, with legal citations, policy references, and/or other justifications for why the language is required at the particular institution.

Institutional/Community Profile: A detailed profile of a research site’s local community. This report is a tool to assist a reviewing IRB in understanding social, economic, and legal aspects of the research site that are relevant to protecting human subjects and should include a detailed description of applicable institutional policies, site-specific template consent language, and state laws. (e.g. circumstances that affect the age of consent, institutional policies related to record-keeping, and state-mandated public health reporting). Information included in this profile should be relatively static, should require infrequent updating, and should not be significantly affected by individual research studies.

The process by which a research site relying on a single IRB (SIRB) completes their required Human Research Protection Program (HRPP) review and communicates local concerns to the CIRB/SIRB, if needed. This process is sometimes referred to as “local review”. Every institution/relying site has different processes for collaborating with a CIRB/sIRB and ensuring the additional, non-IRB requirements are met at their site before the research begins. It is the responsibility of the site investigator in collaboration with the site HRPP Administrator to ensure local HRP review is completed according to local policies.

Non-IRB requirements include, but are not limited to the following:

• Financial conflict of interest (COI) review and management plans for any investigators or study staff at your site.
• Institutional conflict of interest management plans for your site.
• Ensuring sufficient resources, training, or compliance measures relevant to this study being conducted at your site.
• Ancillary committee reviews that are performed at your site.
• Ensuring compliance with local laws or policies.

Local sites are under no obligation to activate the study at their site, even if CIRB /sIRB approval is granted.

Note: CIRB/sIRB approval may be issued before HRP Review is completed. If sIRB approval is issued before local review is completed, the reviewing sIRB must require amended materials if a study is not compliant with a site’s local requirements.

While a relying HRPP may not be responsible for the IRB review portion of the HRP Review for a study where a reliance relationship exists with a sIRB, there are many other HRP requirements that must be completed before a study can begin at a given site. When IRB review and the rest of HRP Review are conducted altogether within an institution, the IRB approval and study activation are typically granted together. When the IRB piece of the HRP Review is delegated to an external sIRB, the study activation piece remains with the rest of the HRP Review.

It is critical that institutions educate their investigators about this part of the reliance process. Local sites are under no obligation to activate the study at their site, even if CIRB/sIRB approval is granted, which means the investigator may NOT begin research procedures until both sIRB approval AND HRPP activation have been received and documented.