Single IRB

Rationale Historically, most clinical research studies were carried out at single institutions Increasingly, studies are being conducted at multiple sites to help increase the number and diversity of the participants, improve operational efficiencies, and accelerate the generation of research results. Accelerating clinical research benefits researchers, research participants, and the general public

Rationale Time to move from a sound research idea to the launch of a new, multi-site clinical research study is often too long due to several issues: Grants and contract negotiations/execution Multiple IRB reviews across each site Site start-up processes Recruitment

Institutional Review Board IRBs play a critical role in reviewing and approving studies involving human research participants by evaluating the potential benefits of research and risks to subjects However, for the majority of multi-site studies, the IRB at each participating site continues to conduct an independent review. This review adds time, but generally does not meaningfully enhance protections for the participants. 

NIH policy The NIH Policy on the Use of a Single Institutional Review Board (IRB) for Multi-Site Research sets the expectation that multi-site studies conducting the same protocol use a single IRB to carry out the ethical review of the proposed research. This new NIH policy seeks to end duplicative reviews that slow down the start of the research.

NIH Policy on Use of a sIRB Requires use of a single IRB (sIRB) for qualifying studies. Grant applications must include a plan to identify the sIRB. Applicable to domestic NIH-funded multi-site studies “where each site will conduct the same protocol involving non-exempt human subjects research, whether supported through grants, cooperative agreements, contracts, or the NIH Intramural Research Program. It does NOT apply to career development, research training or fellowship awards.”

NIH Policy on Use of a sIRB NOT applicable to ongoing, non-competing awards until the grantee submits a competing renewal application. Published in the federal registry on June 21, 2016 to take effect on September 25, 2017.

NIH Policy on Use of a sIRB Guidance materials will be issued by the NIH prior to the implementation date to address: responsibilities of the sIRB and sites model IRB reliance agreements (IAAs) process for requesting an exception to the sIRB requirement instructions for charging to direct vs. indirect costs directions for submitting the sIRB plan with applications and proposals

Costs for Use of sIRB Current NIH policy states that initial review of the study must be charged to indirects. Likewise, study-wide amendments and renewals are to be charged to indirects. Site specific amendments, safety events, or correspondence may be charged as direct costs.

Reliance Agreement Contractual mechanism among 2 or more sites. Allows an institution to identify another IRB that is able to review their human subjects research. Establishes the division of responsibilities. Generally does not describe how those responsibilities will be executed. May be specific to one study, a specific consortium or may be a master agreement. Master agreements are becoming the standard.

Typical Terms of a Master IRB Reliance Agreement Qualifications to join defined independent assessment of site’s HRPP conducted (AAHRPP accreditation, OHRP assessment) internal monitoring capability at site possession by site of a Federal Wide Assurance Indemnification of both parties

Typical Terms of a Master IRB Reliance Agreement Relying site responsibilities ensure qualifications of site study team ensure compliance with IRB determinations Maintain institutional SOPs for conduct of research Adequate monitoring and QI/QA programs IRB-of-Record responsibilities IRB review in accordance with all regulations and guidance, including state law of a relying site Prompt reporting of UPIRTSOs and serious/continuing noncompliance to all sites and federal regulatory agencies

Enabling IRB Reliance on a national scale Implement NIH Policy on the Use of a Single IRB for Multi-Site Research JOIN ENABLE HARMONIZE Streamlined, Multisite, Accelerated Resources for Trials - SMARTIRB Aims Harmonize regulatory methods, processes and definitions to accelerate post-IRB approval Enable multisite studies; collect, develop, and disseminate resources to support multisite studies using SMART IRB Join the SMART IRB reliance agreement (CTSAs and affiliates) Funded by NCATS: July 2016-April 2018 Harvard University, University of Wisconsin- Madison & Dartmouth College A team of SMART IRB Ambassadors from CTSAs across the nation

Single IRB review on a national scale

Access Expertise Across the Nation Ambassadors from CTSAs across the nation are available to assist institutions in joining and implementing SMART IRB. Columbia University Duke University Harvard University Medical University of South Carolina Metro Health Oregon Health & Science University Pennsylvania State University Stanford University University of California San Francisco University of Kansas Medical Center University of Kentucky University of New Mexico University of Texas Health Science Center at San Antonio University of Wisconsin-Madison smartirb.org/ambassadors

SMART IRB Communication Model Lead Study Team operates similar to a coordinating center Reviewing IRB Lead Study Team Relying Site Study Team Relying Institution IRB/HRPP

Options for Selecting Review IRB Pre-define one (or more) institutions within the group that will serve as the reviewing IRB for all. Identify a lead institution for each trial and allow that institution ”right first refusal” to be the sIRB for all participating sites. NIH could establish a new NIH IRB for the network/group (e.g. NCI cIRB)

Role of Reviewing IRB The “how” for the IRB that is providing sIRB review…generally includes the following: Process AND mechanism for other institutions to submit to the reviewing IRB. (initial review, amendments, continuing review, etc.) Mechanism for notifying rely institutions of IRB review outcomes. (initial review, amendments, continuing review, etc.) Communication is key

Overall PI & Lead Study Team Overall Principal Investigator Assumes leadership and has ultimate responsibility for conduct of the research Designates Lead Study Team* Lead Study Team Submits materials to the Reviewing IRB for all sites, including study-wide and site-changes of protocol, continuing reviews, and reportable events Provides draft study materials to all site study teams, including proposed consent form template Provides IRB-approved materials/determinations to all sites *The Lead Study Team is often (but not always) the study team at the Reviewing IRB’s institution; may be a coordinating center

Role of Relying Site Often an after thought in efforts to establish sIRB review models. Important to understand what is involved in getting a trial started in a larger university or academic medical center. Role of the relying sites HRPP in this process (may or may not need to involve the local IRB) Lot’s of functions that still need to be completed by the relying site…other than actual IRB review.

Site PIs & Relying Site Study Teams Follow policies and procedures of Reviewing IRB (e.g., for reportable events, personnel changes) Provide information about study progress and local events to Lead Study Team for continuing review (e.g., unanticipated problems, noncompliance) so that it can be reported to the Reviewing IRB Use the Reviewing IRB’s consent form template (excepting limited local language that can be added/changed) Obtain authorization from their institution’s SMART IRB POC(s) (e.g. for personnel changes, COI updates, or changes that may be affected by state law or institutional requirements) In cases where the Lead Study Team is from an institution other than the Reviewing IRB Institution, the roles and responsibilities of the “Relying Site Study Team” also apply to the study team at the Reviewing IRB’s institution.

Any eligible institution may join FWA or IRB Organization: Unless it is an IRB organization, an institution must maintain a Federalwide Assurance (FWA) approved by the Office for Human Research Protections (OHRP) AND provide institutional oversight of all its human subjects research. Quality Assessment: If an institution has an IRB or is an IRB organization, it must have undergone or initiated assessment of the quality of its human research protection program (HRPP) within five years prior to joining. Point of Contact: An institution must establish a Point of Contact (POC) who will be responsible for, and communicate on behalf of, the institution regarding initial and ongoing implementation of the SMART IRB Agreement. Eligibility Criteria Single IRB Authorization Agreement: The SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement needs to be signed just once. Institutions that have joined SMART IRB can then choose to use the SMART IRB Agreement on a study-by-study basis, streamlining the IRB review process and eliminating the time and effort typically required to negotiate an IRB authorization agreement for each new study Institutions can participate in SMART IRB if they meet the eligibility criteria described within the SMART IRB Agreement, as follows:

Institutional Points of Contact (POCs) Serve as local resource for the institution and local study teams Determine whether to serve as Reviewing IRB or cede review Communicate institution decisions regarding IRB reliance requests

Timeline for Adoption & Implementation 50% of CTSA affiliates join SMART IRB V3.0 of Web-based Compendium Evaluate pilot studies of 2-4 Harmonization projects December 1, 2017 Ambassador Kick Off Sept 13-14, 2016 64 CTSA hubs join SMART IRB V1.0 of Web-based Compendium to enable studies using SMART IRB Jan 31, 2017 SMART IRB Website and Joinder Tool Release Sept 15, 2016 2016 Sep Oct Dec 2017 Jan Apr May Dec 2018 Feb Mar May 2018 May 1, 2018 75% of CTSA affiliates Signed On with SMART IRB V4.0 of Web-based Compendium Adoption of common policy, method, process by CTSA Program hubs May 1, 2017 25% of CTSA affiliates join SMART IRB V2.0 of Web-based Compendium Pilot SMART IRB Process LIST OF WHO HAS JOINED TO DATE 10/24/2016 Broad Inst, Inc. Cambridge Health Alliance Forsyth Institute Harvard T.H. Chan School of Public Health Harvard University Harvard University Faculty of Medicine Icahn School of Medicine at Mount Sinai Johns Hopkins University School of Medicine Medical University of South Carolina Stanford University The University of Texas Health Science Center at San Antonio Trustees of Dartmouth College Tufts Medical Ctr, Inc University Hospitals Cleveland Medical Center University of Kansas Medical Center University of Kentucky University of New Mexico Health Sciences Center University of Rochester University of Southern California University of Southern California - Health Science Campus University of Utah University Wisconsin-Madison Vanderbilt University Medical Center 23 institutions had joined 169 institutions including 64 CTSA hubs had joined Join, Enable, Harmonize

Advantages Flexibility This agreement can be used for any domestic study Any signatory institution can either serve as the IRB of record or can rely on another signatory institution Each institution still operates according to it’s own policies with regard to putting reliance in placed 169 institutions have signed Piece of Mind All institutions are required to be AAHRPP or otherwise accredited All institutions share a common agreement

Currently there is no electronic platform Disadvantages Currently there is no electronic platform However, it is coming May 2017 The Smart IRB agreement can still be used without it Single IRB Authorization Agreement: The SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement needs to be signed just once. Institutions that have joined SMART IRB can then choose to use the SMART IRB Agreement on a study-by-study basis, streamlining the IRB review process and eliminating the time and effort typically required to negotiate an IRB authorization agreement for each new study Institutions can participate in SMART IRB if they meet the eligibility criteria described within the SMART IRB Agreement, as follows:

DUHS IRB’s Position on sIRBs Supports the sIRB model and is already functioning as an sIRB for several studies Pilot sIRB for the CARRA registry study under IRBRely Participant in both IRBRely and IRBChoice networks Extensive experience as the sIRB for the Duke Oncology Network Incorporated an external IRB pathway for reliance on another IRB early in the eIRB’s development

DUHS IRB as a sIRB Access to eIRB is not granted to external entities (will be possible through iMEDris) Lead study team at Duke must make eIRB submissions (site-specific amendments, safety events) on behalf of sites and convey DUHS IRB determinations to the sites Most sites prefer to receive a unique approval letter adding them to the study; therefore, batching site additions is usually not possible The DUHS IRB office will have a team of 2-3 individuals who will process site-specific amendments

Responsibilities of the Lead Study Team for DUHS as sIRB Determine which sites will rely on the DUHS IRB and provide this information to the Director of Extramural Programs. Determine which relying sites are signees to SMARTIRB Determine which relying sites wish to use the DUHS IRB as their Privacy Board Provide information to relying sites concerning those sections of the consent form template that can be modified by the site Submit modified consent forms to the DUHS IRB on behalf of relying sites Make all eIRB submissions on behalf of relying sites as long as the current software platform is being utilized (amendments, CRs, safety events, etc.) Collate and submit continuing review information on behalf of the relying sites

IRB Proposal for Duke as sIRB IRB leadership is in discussions with CTSA leadership regarding the formation of a core service group to function as the liaison between Duke lead study teams and the DUHS IRB. This group would make all eIRB submissions and site notifications on behalf of the Duke lead study team and possibly reside within the CTSA trial innovations center.

IRB Proposal for sIRB The group would be notified each time the DUHS IRB agreed to act as a sIRB and would work with the Duke lead study team to complete all eIRB submissions and actions. Advantages: reduction of workload for Duke lead study team; elimination of training redundancies for the DUHS IRB

Process for Using DUHS IRB as sIRB Send an email to jody.power@duke.edu and geeta.swamy@duke.edu with the request. The email should contain the following: - study summary or brief description of the study - PI’s assessment of risk of the study - investigational drugs/device/biologics involved - # of external sites - expected duration of study The IRB will reply within 3 business days. If the IRB agrees to serve as the sIRB, the study should be submitted in the eIRB under the regular pathway. The IRB will be in contact with the Duke study team regarding required site information.

Submitting a sIRB study in eIRB Use the standard New Study pathway Include “-DUHS as sIRB” in the study title List all sites, including those using their own IRBs, in section 5. Contact Minna Pak in the IRB office (minna.pak@duke.edu) to request cede letters for sites that wish to rely on Duke and are SMARTIRB signees. She will also provide Duke’s IAA template to forward to sites that have not signed on to SMARTIRB. Minna will issue cede letters to upload in section 5 IRB expiration dates of relying sites will match that of the Duke site.