Feature Article

An IRB Reliance Agreement — Is this an Option for Your Research?
April 2014 Issue

By Mary A. Banks, BS, BSN
BUMC IRB Director
Authors has nothing to disclose with regards to commercial support.

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• Introduction
• Reliance on a central or independent IRB
• Reliance on another institution’s IRB review
• Is a reliance agreement necessary?
• Considerations
• Standard Operating Procedures (SOPs)
• Site-specific information
• Summary
• Quiz

Introduction

Definition: verb: rely, (1) depend on with full trust or confidence. “I know I can rely on your discretion”. Depend on, count on, bank on, place reliance on, reckon on; be confident of, be sure of, believe in, have faith in, trust in; swear by.  (google.com) 

It is not unusual for investigators to inquire about available options for IRB review. In some cases, investigators want to know if their protocols can be reviewed by external (non-BUMC) IRBs; while, in other instances, investigators want to know if their non-BUMC co-investigators can be listed on their BUMC IRB protocols and can rely on BUMC’s IRB review. 

The purpose of this article is to provide an overview of the options for IRB review currently available to BUMC investigators, and to describe the steps used by the institution to determination if delegation of IRB review to an external IRB is appropriate. 

Reliance on a central or independent IRB

Instead of having IRB review conducted by one of BUMC’s four “internal” IRB panels, there is an option for some studies to be reviewed by an external independent IRB.   In order for this delegation of IRB review to be permissible, BUMC must have a formal reliance agreement in place that delegates IRB review to the external independent IRB; there must be policies in place outlining the circumstances under which IRB review can be delegated and which outline the responsibilities of each institution; and, there must be SOPs in place that explain how delegation of review is implemented. Currently, BUMC has several options for delegation of IRB review for clinical trials. These are listed below. Several additional options are currently under consideration.  

• Western IRB (WIRB): BUMC investigators who are participating in industry- sponsored multi-center clinical trials involving drugs and/or devices have the option of submitting these studies to WIRB for IRB review.  There are specific procedures that must be followed, and pre-review by the BUMC IRB is required.  Details regarding the WIRB process for BUMC clinical trials are available on the BUMC IRB website.  Currently, WIRB is the only “commercial” IRB that BUMC contracts with for external review of industry-sponsored multi-center clinical trials.

• National Cancer Institute’s Central IRB (NCI-CIRB): Submission of protocols to this external central IRB is limited to  oncology clinical trials.  Protocols must be submitted to BUMC IRB via INSPIR for pre-review.  At that time, a determination is made by the IRB as to whether IRB can be delegated to NCI-CIRB.  Contact BUMC IRB Coordinator Rosana Schomer for more information at Phone: 617-414-1320 or at roz@bu.edu.     

• Other central IRBs and review groups such as IRB Share, NeuroNEXT, Harvard Catalyst, etc.:  BUMC is reviewing the numerous options being proposed locally and nationally for centralized IRB review. At this time, no protocols are automatically sent to these external review groups. Decisions about whether to delegate IRB review is made on a case-by-case basis based on a number of factors  (see “Considerations” section later in this article for more details.)

Reliance on another institution’s IRB review

Under certain circumstances, to eliminate the need for duplicate IRB review, BUMC may agree to delegate its responsibilities for IRB review to another institution’s IRB; or allow another institution to delegate their responsibility for IRB review to the BUMC IRB. This process occurs through a formal signed agreement, called an Institutional Authorization Agreement (IAA) or a reliance agreement.  A number of considerations go into determining whether a reliance agreement is appropriate.  The key ones will be discussed below.

Is a reliance agreement necessary?

Before deciding whether BUMC will enter into a reliance agreement, the determination must be made as to whether a reliance agreement is even necessary.  A reliance agreement is only needed when BUMC and the other research site are both engaged in non-exempt human subjects research. Although some research studies may involve researchers from two or more institutions, sometimes both institutions may not actually be engaged in the research.   Also, it may be determined that the research meets the regulatory definition of NHSR (Not Human Subjects Research) or qualifies as Exempt Research.  In these cases, a reliance agreement is not required because reliance agreements are only used by two “assured institutions” for non-exempt research.

The December 2010 CR TIMES Feature article titled, “On Being Engaged”, provides an in- depth discussion of engagement in human subjects research. Provided below is a brief overview about how the engagement determination is made. Please refer to that article for more details.

From the IRB perspective, the term “engagement” relates to the OHRP guidance on Engagement of Institutions in Human Subjects Research. In general, this document states that an institution is considered engaged in a human subjects research project when its employees or agents, for the purposes of the research project, are engaged in human subjects research. The document then goes on to provide example scenarios with an explanation as to whether or not they are considered by OHRP to represent engagement in human subjects research.

• Section III.A describes scenarios where institutions/investigators would be considered to be engaged in human subjects research.

• Section III.B describes scenarios where institutions/investigators would be considered to not be engaged in human subjects research.

The following document (Scenarios related to engagement in research.doc) summarizes, in less regulatory terms, the types of research activities that are likely to be determined to constitute engagement, and those that are likely to NOT constitute engagement based on the OHRP guidance. This information may be useful to investigators to help them anticipate whether certain activities conducted by others at other institutions as part of their research might constitute engagement in the research. This engagement determination is important, especially when investigators from more than one institution or site are involved, as it drives the decision about whether more than one IRB review is necessary.

Considerations

Funding:  The funding source is a key factor.  The IRB needs to know all the sources of funding; specifically, who is the prime recipient of the award, and who are all the sub-award sites. If an institution is the prime recipient of a federal award, then that institution, by federal rule, is automatically engaged in the research and is ultimately accountable for the conduct of the research.

• If BU or BMC is the prime recipient of the award, then delegation of IRB review to one of the other sites is usually not an option.  Since BUMC is ultimately responsible for the overall conduct of the research, then the institution’s preference is for the research to be reviewed by one of the BUMC internal IRBs.  
• If BU or BMC is a sub-award site and the other institution is the prime recipient of the award, then typically BUMC will not accept delegation of IRB review. This is because the other institution is ultimately responsible for the oversight of the grant and for ensuring appropriate human subjects protections are in place for the overall grant. This does not hold true when the other institution is the Boston Public Health Commission (BPHC) or one of the Boston HealthNet Community Health Centers (BHN-CHCs), as they do not have their own IRBs, and there is an understanding in place that allows them to rely on the BUMC IRB.
• If BU or BMC is the prime recipient of an award that involves research at the Veterans Administration (VA), then BUMC is engaged in the research; and BUMC IRB review is needed even if all the research activities are taking place at the VA.  The VA does not allow reliance agreements for IRB review.  

Risks (What are the risks and where are the risks?): The level of risk of the study is typically the most significant consideration for the institution in determining whether delegation of IRB review to another institution’s IRB (or acceptance of delegation of review from another institution to the BUMC IRB) is appropriate. Investigators need to clearly describe all the risks of the study and clearly delineate where each of the risks will occur. For example, if a clinical trial involves a risky procedure such as implantation of an investigational device, but the only BUMC involvement is that a BUMC investigator will serve as the study statistician who is analyzing identifiable data, then delegation of IRB review may be appropriate. On the other hand, if consent was being obtained and implantation of the device was being done at BMC, then the institution would be less likely to allow delegation of IRB review to the other institution’s IRB.  

Conflicts of Interest:   If any of the investigators from either institution has a conflict of interest, then, even with a COI management plan, the institution is less willing to enter into a reliance agreement.   

Consent forms:  The procedures for delegation of IRB review are less complicated when the site that is requesting to delegate review is not obtaining informed consent.  Although this is not necessarily a deal breaker, there are definitely process issues that have to be worked out between institutions related to informed consent if delegation of review requires the IRB of the reviewing institution to review and validate the consent forms for the relying institution. Issues such as institutional consent template language, HIPAA language, compensation for research-related injury language, etc. must be worked out.

Genetic research and genetic repositories:  Currently there is not good consensus regarding institutions’ requirements for IRB review of repository and genetic research. Therefore, there is significant variation among institutions regarding the way that they review genetic/repository research. BUMC will not agree to delegate IRB review for these studies if the other institution’s IRB review standards for this type of research are not consistent with BUMC’s.

International Research:   Research that involves engagement by international sites require local (international) IRB review.  The BUMC IRB relies on the reviews by the local (in-country) IRBs to help inform them about local context and appropriateness of consent processes.  BUMC does not delegate its review responsibilities to local (international) IRBs and does not accept delegation of IRB review from local (international) IRBs.

Standard Operating Procedures (SOPs)

Step One: BUMC investigators who are requesting reliance agreements (either for delegation of IRB review or for BUMC acceptance of delegation of IRB review) must submit a protocol to the IRB via INSPIR for review.  (Note: See details at the end of this article for specific INSPIR instructions.)

Step Two: The IRB Director or designee makes a determination as to whether a reliance agreement is appropriate for the study.

Step Three: Even when a reliance agreement is allowed, there are a number of responsibilities that are retained by the investigator’s “home” institution.  In most instances, the reliance agreements will specify that, even if BUMC delegates IRB review, the following activities are still the responsibility of BUMC.  Conversely, when BUMC accepts IRB review, the following activities are usually the responsibility of the delegating institution.

• Human subjects training: (certification and recertification): In most cases, investigators must meet their own institution’s requirements.
• COI review: in most cases, COI disclosures are submitted to the investigator’s home institutions.  If there is a COI management plan and a reliance agreement is allowed, then the management plan must be shared with the reviewing IRB.
• Institutional signoffs:  Ensuring that appropriate signoffs are obtained (i.e.,  by the PI’s department chair, Investigational Pharmacy, Radiation Safety, Radiology, IBC, faculty advisors, etc.) is usually the responsibility of the investigator’s institution.
• Consent form language: Frequently, the delegating IRB conducts a pre-review of any consent forms to ensure that institution-specific template language, including compensation for injury language, is included.
• HIPAA:  Both institutions must agree on the appropriate HIPAA language for the consent forms, and how HIPAA waivers will be reviewed/honored
• Reporting of unanticipated problems, serious and continuing noncompliance, and study suspensions:   Institutions, under their Federalwide Assurances, are required to report these “incidents” to OHRP.  Even when there is a reliance agreement in place, institutions retain this responsibility. Therefore, there must be a clear plan in place for timely notification of both institutions when these incidents occur, and a plan for who is responsible for reporting.
• Quality assurance monitoring and oversight:  Usually, an institution retains the responsibility for ensuring that their investigators are compliant with regulatory requirements, even when it delegates review to another institution’s IRB through a reliance agreement.  Also, the delegating institution must be able to track the protocol and monitor the approval status.

Site-specific information

The following is some specific information related to reliance agreements with sites commonly requested by BUMC investigators.

Instructions for completing the INSPIR application for studies with Reliance Agreements are found at this link.

Summary

The decision as to whether BUMC will enter into a reliance agreement with another institution is a complicated one.  A number of factors go into the decision to either delegate IRB review to another institution, or to accept delegation of IRB review to cover investigators from another institution.  This article provides an overview of some of these issues, as well as a description of the SOPs for situations when reliance agreements might be appropriate.

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