Reliance on the Review of Another IRB
Both OHRP and the FDA permit an IRB the option to rely on the review of another IRB. When this is the intention, the two institutions enter into an agreement referred to variously as either a Cooperative Agreement, an IRB Authorization Agreement or an IRB Reliance Agreement. These agreements are executed between a Reviewing IRB and one or more Relying Institutions and delineate the roles and responsibilities of the involved parties. The agreements can be for a single research study or for multiple studies (e.g., a Master Reliance Agreement). The NIH, study consortia and some funding agencies have increasingly encouraged the designation of central IRB to serve as the Reviewing IRB for all participating sites in multicenter research studies. Going forward, the NIH will require single-IRB (sIRB) review for multi-center Research that they fund.
NIH Mandate for a Single IRB
As of September 25, 2017,the NIH has mandated that all domestic sites participating in multi-center research studies use a single IRB (sIRB). The Final NIH Policy on the Use of a Single Institutional Review Board for Multi- Site Research will apply to all "competing grant applications (new, renewal, revision, or resubmission) with receipt dates on or after September 25, 2017, all contract solicitation issued on or after May 25, 2017, and all NIH Intramural studies submitted for initial IRB review after September 25, 2017." The NIH uses the term sIRB to distinguish between IRBs (generally for-profit) that are structure to serve as the central IRB for multi-center studies and institution-based IRBs whose primary function is to serve the investigators at that institution. . The policy was originally scheduled to take effect as of May 25, 2017 but NIH has issued an extension of the date for implementation which moves the effective date back until September 25, 2017.
The time to arrange a cooperative agreement between institutions is often a time-consuming and drawn out process. It is hoped that more pediatric institutions will sign on the Common Master Reliance Agreement to facilitate the process that is described below.
Resources for NIH Policy on use of a Single IRB
- NIH webpage contains links to the policy, FAQs and other resources Clinical Research Policy - IRB Review. NIH Single IRB (sIRB) Policy
- (NIH) Accelerating Clinical Research by Streamlining Multi-Site Review of Human Subjects Research
- Final NIH Policy on the Use of a Single Institutional Review Board for Multi- Site Research
- Frequently Asked Questions about the NIH policy on use of a single IRB
- From the NEJM Dec 15, 2016: NIH Policy On Single-IRB review – A New Era in Multicenter Studies
- Agreement: may be referred to as a Cooperative Agreement, IRB Authorization Agreement (IAA) or IRB Reliance Agreement. When the agreement is designed to cover all future multi-center studies involving two or more sites, this is usually referred to as a Master Reliance Agreement. For example, Penn and CHOP have a master reliance agreement in place since 2006.
- Determination Form: A determination form is often signed by two institutions who have already entered into a Master Reliance Agreement to document that the Master Reliance Agreement applies to a particular study.
- Multi-center Review: Where one IRB accepts responsibility to serve as the Reviewing IRB (Central IRB) for two or more of the institutions participating in a multi-center research study.
- Overall PI: The principal investigator with ultimate responsibility for the overall conduct, safety, regulatory oversight and data integrity for a multi-center research study.
- Participating Institution: An institution that is a signatory party to the Reliance Agreement.
- Relying Site: A hospital, clinic, doctor's office where research will take place and which will rely on an external IRB (Central IRB) which will serve as the Reviewing IRB for a multi-center study. When academic institutions are involved, this term incorporates the Relying IRB and the Relying Participating Institution
- Reviewing IRB or Central IRB: means the IRB that is responsible for the review, approval and regulatory oversight of a multi-center research study and serving more than one site. Sometimes referred to as the IRB of Record.
- Site PI: A principal investigator who is responsible for the conduct of the Research at their Participating Institution.
Master Reliance Agreements
Research Conducted at both University of Pennsylvania and CHOP
The CHOP IRB has had a Master Reliance Agreement with the University of Pennsylvania since 2005. The most recent agreement was executed December 5, 2016. Hundreds of studies have been included under this agreement benefitting both IRBs and reducing the burden on the CHOP and Penn investigators.
The process works by having the overall PI request that one of the IRBs – either Penn IRB or the CHOP IRB – serve as the Reviewing IRB for both institutions. The request can be made at the time of the initial submission for approval or as part of an amendment later. Research that takes place at Pennsylvania Hospital may also be included under this agreement.
If the CHOP IRB is to be the Reviewing IRB, the CHOP investigator submits the study (or amendment to add the University of Pennsylvania as a site) to the CHOP IRB (in eIRB) and indicates in the application that this is a multi-center study for which "CHOP will serve as the reviewing IRB for one or more other institutions". The completed Penn-CHOP determination form, signed by the investigator, needs to be attached to the application. If the CHOP IRB agrees to serve as the Reviewing IRB, then an IRB chair or designee signs the determination form and forwards it to the the Penn IRB.
If the Penn IRB is to be the Reviewing IRB, the investigator first submits to the Penn IRB (including the completed Penn-CHOP determination form, signed by the investigator). If the Penn IRB agrees to be the Reviewing IRB and signs the determination form, the CHOP PI needs to submit the study and the determination form (now signed by the investigator and the Penn IRB) to the CHOP IRB as a "Research Study involving CHOP reliance on an outside reviewing IRB". This is an abbreviated application in eIRB. Once CHOP agrees to cede review to the Penn IRB, an IRB chair or designee signs the determination form. See the section "If CHOP is asked to cede oversight to an external IRB: What needs to happen?" below for more information.
The Penn-CHOP Determination Form can be found on the IRB Reliance Templates page.
Research reviewed by the NCI Pediatric Central IRB (CIRB)
CHOP has had a long-standing Master Reliance Agreement with the NCI's Pediatric CIRB. Prior to 2011, the PCIRB used a facilitated review model. Since 2011, first as a pilot program and then as a widely-implemented program, the PCIRB has served as the Reviewing IRB for COG clinical trials. The CHOP IRB issues a letter accepting the PCIRB as the Reviewing IRB; there isn't a determination form that must be completed. The investigator is responsible for ensuring that the consent form has been edited so that it complies with CHOP's requirements.
- CIRB-CHOP Institutional Authorization Agreement and Division of Responsibilities
- CIRB-approved "boilerplate" language to be inserted into the CIRB-approved consent form This document provides instructions for editing the CIRB model consent so that it includes CHOP required language and meets all other CHOP requirements.
Master Common Reliance Agreement with Other Pediatric Institutions
CHOP has had numerous reliance agreements for research conducted at other pediatric institutions. As of May 2014, the Boston Children's Hospital, Cincinnati Children's Hospital and CHOP entered into an Master Reliance Agreement for research involving two or more of the institutions. This agreement was then modified and adopted by the other PEDSnet sites. Having a Master Reliance Agreement avoids the need to negotiate individual agreements when two or more of signatories participate in a study together. Aside from the 9 PEDsnet sites, 12 additional pediatric institutions or universities have signed on to participate in this agreement. For each study, a determination form must be completed, on which both the reviewing and relying site agree to apply the master reliance agreement to this particular study.
- Children's Hospital of Philadelphia (CHOP)
- Boston Children’s Hospital (BCH)
- Cincinnati Children’s Hospital and Medical Center (CCHMC)
- Children’s Hospital of Colorado
- Lurie Children's Hospital of Chicago
- Nationwide Children’s Hospital
- Seattle Children’s Hospital
- St Louis Children’s Hospital (Washington University)
- The Nemours Foundation
- Children's Healthcare of Atlanta
- Children’s Hospital Los Angeles
- Children’s Mercy Kansas City
- Children’s National Medical Center (CNMC)
- Dayton Children's Hospital
- Indiana University (Riley Children's Hospital)
- Stanford University
- University of Kentucky
- University of California, Davis
- Massachusetts General Hospital
- University of Utah (including Primary Children's)
- University of Alabama at Birmingham (including The Children's Hospital of Alabama)
- University of Nebraska Medical Center
Download the Master Common Reliance Agreement Determination Form by clicking the hyperlink or from the IRB Reliance Templates page.
Other Master Reliance Agreements
CHOP has a longstanding Master Reliance Agreement with the NCI PCIRB and now has one with the University of Utah that covers studies performed by the PECARN investigators. Given the current regulatory and funding environment, there will undoubtably be other similar agreements developed in the near future.
Reliance Agreements for Research Conducted at both CHOP and another Participating Institution
CHOP is willing to serve as the Reviewing IRB for one or more Relying Sites when the Overall PI is based at CHOP. Conversely, CHOP is willing to enter into a Reliance Agreement to assign another IRB as the Reviewing IRB for multicenter research where an external PI is the Overall PI. There are also situations where a single IRB serves as the Reviewing IRB for a research consortia for all trials, regardless of the institutional affiliation of the PI. A standard CHOP Authorization Agreement form is available on the forms to initiate Reliance Agreements with other sites. The CHOP IRB Authorization Agreement (IAA) should be used when CHOP will serve as the IRB of record for one or more institutions (other than UPenn or when there is a superseding Master Reliance Agreement, in which case a determination form needs to be completed; see above).
If CHOP is asked to cede oversight to an external IRB: What needs to happen?
Complete the CHOP eIRB Application: The CHOP investigator is required to complete an abbreviated eIRB application (check "Research Study involving CHOP reliance on an outside reviewing IRB") that includes amongst other things, a listing of study personnel, study funding, required ancillary committees (e.g., Pharmacy, Radiology, etc.), the recruitment plan (specific to CHOP), the protocol, the consent form as approved by the Reviewing IRB, the approval letter from the Reviewing IRB, and the signed IAA or determination form from the reviewing institution (if available). The investigators listed in the eIRB application also need to submit study-specific conflict of interest disclosures.
Revise the Consent Form for Use at CHOP: The consent form approved by the Reviewing IRB for the main site must be adapted for use at CHOP and must conform to institutional requirements. To ensure that the Reviewing IRB includes all of the CHOP-required elements, the IRB has created instructions for the CHOP investigator and the Reviewing IRB - CHOP Consent Form Requirements: Instructions for the Investigators and the Review IRB (2017).
Finalize the Institutional Sign-Off: After the eIRB application is complete, all ancillary approvals are issued and an approved consent form has been uploaded that conforms to CHOP's requirements, the agreement to cede review can be finalized. A stand-alone IRB Authorization Agreement or, if the study falls under one of CHOP's Master Reliance Agreements, the determination form ceding review to the external IRB can be finalized. The CHOP IRB will issue a letter to the CHOP investigator indicating that CHOP has ceded review to the external IRB.
Keeping the eIRB Application Up to Date: Although the CHOP IRB does not provide any oversight when an external IRB is the Reviewing IRB, the CHOP human subjects protection program remains responsible for all research activities that take place at CHOP. The CHOP Office of Research Compliance requires that all amendments and continuing reviews continue to be uploaded into eIRB to ensure that the study approval hasn't lapsed and that the only the most current, approved documents are being used.
Regulatory and Literature Resources
- OHRP webpage - Use of a Central Institutional Review Board
- FDA Guidance: Using a Central IRB Review Process in Multicenter Clinical Trials
- Flynn KE, et al. Using Central IRBs for Multicenter Clinical Trials in the United States. PLoS One. 2013;8(1):e54999.
- Millum & Menikoff. Streamlining ethical review. Ann Intern Med. 2010, Nov 16;153(10):655-7.
- Wagner et al. Costs and benefits of the national cancer institute central institutional review board. J Clin Oncol. 2010, Feb 1;28(4):662-6.
- Stark et al. Variation among institutional review boards in evaluating the design of a multicenter randomized trial. J Perinatol. 2010, Mar;30(3):163-9.
- Menikoff J. The Paradoxical Problem with Multiple-IRB Review. N Engl J Med. 2010, Oct 13;363(17):1591-3.
- Dilts et al. Steps and time to process clinical trials at the Cancer Therapy Evaluation Program. J Clin Oncol. 2009, Apr 10;27(11):1761-6.