Note: On July 26, 2011, the U.S. Department of Health and Human Services (HHS) and the Office of Science Technology Policy (OSTP) published an Advanced Notice of Proposed Rulemaking (ANPRM) titled, Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators. This ANPRM contains a proposal to mandate the use of a single IRB for all domestic multi-site studies. Should this proposal be incorporated into the Final Rule, institutions may need to address certain logistical issues including the establishment of reliance (authorization) agreements.
What is a reliance (authorization) agreement?
A reliance agreement is a formal, written document that provides a mechanism for an institution engaged in research to delegate institutional review board (IRB) review to an independent IRB or an IRB of another institution. Institutions may use different descriptive terms, e.g., reliance agreement, cooperative agreement, IRB authorization agreement (IAA), or memorandum of understanding (MOU). Agreements may cover single studies, categories of studies, or all human subjects research under an organization’s Federalwide Assurance (FWA). MOUs are generally used when covering an entire research program; reliance agreements are generally used to cover a designated protocol or protocols.
The type of agreement may be based on the nature of established financial, legal, or collaborative relationships between the entities. The HHS Office for Human Research Protections (OHRP) sample template uses the term “authorization agreement”; the Food and Drug Administration (FDA) uses the term “agreement.” The agreement should clearly identify the IRB of record for a protocol or program and the delineation of responsibilities.
When is a reliance (authorization) agreement used?
What are the benefits of using reliance (authorization) agreements?
Decreasing the number of IRB reviews of the same protocol reduces duplication and variation across sites. Delays in protocol activation times may be reduced, and an institution may increase its research portfolio size without increasing burden on its own IRB. The overall costs for implementing multisite studies may also be reduced. Institutions with small research portfolios may use reliance agreements instead of incurring costs to establish and maintain an IRB. Using reliance (authorization) agreements may also promote collaborative research efforts between institutions.
What are the challenges for institutions entering into reliance (authorization) agreements?
Institutions may have several concerns regarding the delegation of IRB review to an outside entity. Key concerns raised by institutions regarding delegating IRB review have included 1) ensuring quality and thoroughness of external review, as well as lack of precise metrics to measure IRB quality; 2) local context issues; 3) institutional liability; 4) complexity of shared control and accountability; and 5) costs of delegating review and/or loss of revenue for the relying institution.
Read a discussion of these and related issues in Alternative IRB Models—2006 National Conference on Alternative IRB Models report and 2005 Workshop Summary Report (Association of American Medical Colleges website).
Detailed agreements delineating roles and responsibilities of all parties are important tools to facilitate collaboration and trust in the delegation of IRB review. OHRP is considering regulatory revision to address some liability concerns; more information may be found at Request for Information and Comments on IRB Accountability (also referenced in the July 26, 2011 ANPRM) and OHRP Correspondence—Use of a Centralized Institutional Review Board (IRB) (April 30, 2010).
What is the administrative process for using an authorization (reliance) agreement?
Institutions must 1) complete a reliance (authorization) agreement document (See OHRP sample template, PDF) and 2) establish and clearly document roles and responsibilities, communication channels, etc., as part of the agreement or in a separate document. The FWA of the institution relying on another institution’s IRB or independent IRB may need to be amended to list the reviewing institution’s IRB or independent IRB. Please see OHRP's Assurance Process—FAQs and Terms of the Federalwide Assurance (FWA) for the Protection of Human Subjects (HHS website) for specific requirements on listing IRBs and other FWA requirements.
Reliance (authorization) agreement content must meet applicable OHRP and FDA regulatory requirements (see Regulations, Guidances, and Related Information). See also Tip Sheet 24: Relying on an External IRB (PDF), by the Association for the Accreditation of Human Research Protection Programs (AAHRPP).
For more information on AHHRPP standards, an IRB evaluation checklist, and related information, go to the AAHRPP website.
Institutions may also have specific internal standard operating procedures (SOPs)/policies to address requests for providing review for another organization or for delegating review. Policies may specify the phase/risk level of protocols to be considered for outside review, criteria for evaluating outside IRB qualifications if delegating, relationship to the outside organization, and/or other restrictions or requirements. Institutions entering into agreements for IRB review must each maintain the agreements on file and submit them to OHRP and/or FDA upon request.
What is an “Individual Investigator Agreement”?
An individual investigator agreement allows an institution with an FWA to extend the applicability of its FWA to cover collaborating investigators who do not work at an institution with an FWA.
Institutions may engage in research covered under an FWA with physicians in private practice, who frequently do not have an FWA but may be research collaborators. Also, in some cases, the investigator may be an employee of an institution that does not routinely engage in research and therefore does not hold an active FWA.
OHRP does place some restrictions on the use of individual investigator agreements; see Guidance on Extension of an FWA to Cover Collaborating Individual Investigators and Introduction of the Individual Investigator Agreement.
See a sample individual investigator agreement (PDF).
Who signs the reliance (authorization) agreement?
Neither FDA nor OHRP identifies a specific signatory. Institutions may designate the FWA signatory official, the director of the human research protection program, the vice president for research, or other designees as authorized entities, in accordance with internal policies.
Is it necessary for FDA or OHRP to approve these agreements?
No. However, if the agreement is in some way novel and/or deviates from regulations and guidances, consultation may be necessary.
Last Updated November 03, 2015