USING A SINGLE IRB (sIRB) MECHANISM 12/6/2018 Michelle LeMenager, CIP Allison Gerger MPH, CIP Reliance Specialist, HRPO Reliance Specialist, HRPO Irb.reliance@pitt.edu

Disclaimer sIRB is a new and evolving process, locally and nationally Check Pitt “Single IRB Review” webpage often Join our mailing list to receive notices of future sIRB education sessions

Presentation Agenda Common Definitions When is reliance necessary? NIH policy DHHS regulation Collaborative research Types of Reliance Agreements Process of requesting reliance Building an sIRB protocol Pitt cedes Pitt IRB of Record Other Institutional Requirements

Terms you might hear Single IRB Review – a legal arrangement that allows one IRB to review the research on behalf of other engaged institutions Also commonly referred to as “Central IRB” Reliance Agreement – an agreement that outlines the responsibilities of each party when using reliance IRB Authorization Agreement (IAA), IRB Agreement, Reciprocal Agreement, Master IRB Agreement, SmartIRB Master Reciprocal agreement

Reviewing IRB – the IRB that reviews and makes required regulatory determinations Also commonly referred to as “IRB of Record,” “Single IRB” or “Lead IRB Relying Institution – the institution that cedes IRB responsibilities to the reviewing IRB Ceding site, Relying site

A Note of Caution Reliance only covers the IRB review piece Study Initiation Conflict of Interest (COI) Institutional Biosafety Committee (IBC) Institutional Review Board (IRB) Office for Investigator Initiated IND/IDE Support (O3IS) Radioactive Drug Research Committee/Human Use Subcommittee (RDRC/HUSC) Education and Compliance Office (ECO) Stem Cell Research Oversight Committee (SCRO)

When is reliance necessary? Reliance using an sIRB: Required by NIH Required by DHHS Required by research consortium or network Reliance not using an sIRB: Required because engaged collaborator(s) does not have access to an IRB or is completing a subset of the procedures and dual IRB is not practical.

NIH sIRB policy – Historical Perspective Historically, in multi-site studies, each site has its own IRB which conducts an independent review of studies involving human research participants. The use of a single IRB of record for multi-site studies that are conducting the same protocol will help streamline the IRB review process by eliminating the unnecessary repetition of those reviews across sites. Pitt HRPO has been executing reliance agreements for a long time for various reasons.

NIH sIRB Policy - Goals The goal of this policy is to enhance and streamline the IRB review process for multi-site research so that research can proceed as quickly as possible without compromising ethical principles and protections for human research participants.

NIH sIRB Policy NIH funded or supported Competing grant applications (new, renewal, revision, or resubmission) Receipt date on or after January 25, 2018 Non-exempt research Conducted at U.S. domestic sites Multi-site research

The NIH policy only applies to studies where the same research protocol is being conducted at more than one site; it does not apply to studies that involve more than one site but, the sites have different roles in carrying out the research.

Multi site vs. Collaboration Multi-site research refers to two or more research sites executing the same research procedures. Slight variations in procedures, based on local context, are permitted. NIH policy applies Collaborative research involves researchers, at different sites, working on the same project but, the investigators are implementing different research activities. NIH policy does not apply E.g. Data collection occurs at one site, analysis of identifiable data occurs at a different site CC/DCC only – not a data collection site

If it is not clear whether your NIH-funded project falls under the NIH sIRB mandate, contact your NIH Program Officer for confirmation.

DHHS Regulation Supported by any Federal Department or Agency Non-exempt, cooperative research Conducted at domestic sites IRB determined by Federal Agency Exclusions: Required by law Determined by Federal department or agency Effective date: January 20, 2020 45 CFR 46.114

Non-sIRB Reliance: Collaborative Research An investigator changes institutions mid-project Engaged collaborators have access to their own IRB but subset of procedures they are engaged in do not warrant multiple IRB approvals. Engaged collaborators do not have access to their own IRB *May not have to complete all related reliance request steps. Contact irb.reliance@pitt.edu for guidance.

Types of Reliance Agreements IRB Authorization Agreement (IAA) -a written agreement between two or more institutions that is used to document the delegation of IRB review responsibilities. This can also be referred to as a Reliance Agreement or Cede Review Agreement.

SmartIRB Agreement SMART Master Reciprocal Agreement a type of IAA that was developed under an NIH grant and is responsive to new NIH policy requiring the use of a single IRB for multi-site research funded by the agency. The University of Pittsburgh, UPMC, and Magee Women’s Research Institute have all executed the SMART Master Reciprocal Agreement.

SmartIRB…is not an IRB SmartIRB is a platform designed to ease common challenges associated with initiating multisite research and to provide a roadmap for institutions to implement the NIH Single IRB Review policy. Freely available for institutions and investigators. Streamlined, Multisite, Accelerated Resources for Trials Institutional Review Board

A master agreement to support collaboration across the nation 8 CTSAs came together to develop a national IRB reliance agreement Public & private universities Academic healthcare centers Shared with 72 Institutions 25 CTSAs in 19 states Community hospitals Independent/commercial IRBs Shared with 115+ Institutions 64 CTSAs in 33 states NIH agencies What the agreement/joinder is: language from website:  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: FWA or IRB Organization: Unless it is an IRB organization, your institution must maintain a Federalwide Assurance (FWA) approved by the Office for Human Research Protections (OHRP). Quality Assessment: If your institution has an IRB or is an IRB organization, it must have undergone or initiated an assessment of the quality of its human research protection program (HRPP) within five years prior to joining SMART IRB (through accreditation from an external organization, participation in OHRP's Quality Assessment Program, or equivalent approach). Point of Contact: Your institution must establish a Point of Contact (POC) who will be responsible for, and communicate on behalf of, your institution regarding the initial and ongoing implementation of the SMART IRB Agreement. Institutions join by completing the Joinder process at smartirb.org. Regional Ambassadors are available to answer questions and assist in the joinder process.  Collaboratively developed with broad stakeholder input 20

Commercial Master Service Agreement (MSA) – a contract between parties, in which the parties agree to most of the terms that will govern future projects involving both parties. Helps streamline future dealings between the two parties. Pitt/UPMC has MSAs in place with WIRB and Advarra NIH funded – definitely permitted to use a commercial IRB Non-NIH funded – HRPO must take additional step of getting Institutional Official’s permission.

Individual Investigator Agreement (IIA) – a formal agreement, executed between an IRB and an external individual, describing the expectations and responsibilities of the individual in relation to the research project. Used when the individual does not have access to an IRB at their own institution If you need execute a PSA or CSA through Purchasing, also contact the Pitt IRB to determine if an IIA is also necessary. Professional Service Agreement and Contracted Services Agreement

Preparing an NIH sIRB Grant Submission The NIH sIRB mandates requires that investigators now begin communication with the IRB much earlier in the process. The IRB must now be involved while the NIH grant application is being drafted.

sIRB Plan Grant application requires a sIRB plan that includes: Name of the sIRB of record Indication that all sites, including any added after award, agree to rely on sIRB Sites will sign reliance agreement that will include a communication plan Indicate who will maintain records of this agreement

NIH Grant – Letter of Support The Pitt IRB provides a letter of support for inclusion with grant applications. To request a letter of support, use the Qulatrics Reliance Request system. After you have entered the Pitt/UPMC PI & Coordinator contact information, select “Letter of Support for Grant Submission” and follow the prompts.

Grant budget – sIRB Review Costs The IRB of Record is permitted to charge Relying sites for IRB Review. Inquire with the IRB of Record regarding fee structure when constructing grant budget Contact irb.reliance@pitt.edu when formulating a budget where Pitt will act as IRB of Record

Budgetary Considerations - Staffing When Pitt will act as the Reviewing IRB, the Pitt study team has additional responsibilities for managing the project on a national level. Large scale, complex projects should budget to hire both a Reliance Program Manager and a Project Coordinator. Reliance Program Manager -coordinates the project on a national level Project Coordinator is needed to execute the daily needs of Pitt/UPMC acting as a data collection site.

Reliance Request Process

Requesting Use of a Single IRB This is indeed a request, not a demand. The Pitt HRPO reserves the right to determine if sIRB for a specific project is appropriate for our institution. Never commit to using an sIRB mechanism without first communicating with the Pitt HRPO. Any paperwork you receive from sponsor or others should be indicator you need to reach out to the Pitt IRB and begin a reliance request.

Requesting Use of a Single IRB Contact us early in the process! Complete reliance request via Qualtrics Qualtrics Reliance Request link available on “Single IRB Review” webpage Questions?? irb.reliance@pitt.edu Review of paperwork handouts

Weekly sIRB meeting sIRB requests are reviewed at a weekly sIRB meeting Determinations to use sIRB made on case-by-case basis Funding source Site accreditation/expertise Number of sites Research activities Level of risk

NIH Mandate - Priority Given that the NIH sIRB mandate is currently the only enforceable requirement for use of an sIRB, the Pitt HRPO is currently giving reliance priority to these projects.

sIRB Decision – NIH studies If the Pitt HRPO determines sIRB is not appropriate for a project that falls under the NIH sIRB mandate, the study cannot be conducted at our institution.

sIRB Decision: non-NIH studies Prior to January 20, 2020 if the Pitt HRPO determines sIRB is not appropriate for a project that does not fall under the NIH sIRB mandate, reliance will not be executed and the Pitt researcher must submit directly to the Pitt IRB for oversight. On or after January 20, 2020 if the Pitt HRPO determines sIRB is not appropriate for a project that falls under the DHHS sIRB mandate, the study cannot be conducted at our site.

Pitt Cedes Oversight

Pitt cedes - Outside institution is IRB of Record The Pitt IRB will contact the IRB of Record to determine what type of agreement will be executed Drafted from scratch OHRP template SmartIRB Master Reciprocal Agreement Master Service Agreement The agreement must be signed by the Institutional Official at both institutions

Pitt cedes – local context Lead study site sends materials to collect information about local context Institutional policies and procedures State law Purpose: used by the IRB of Record to review for the Relying site The Pitt study team will need to complete this in conjunction with the Pitt IRB Discuss local context sample handout

Pitt cedes – local consent/assent form(s) Lead study site sends a template consent form to insert local language Pitt Study team inserts local language and emails draft to irb.reliance@pitt.edu for Pitt IRB to review The Pitt study team provides the final version of the local consent form to the lead site for submission to the IRB of Record

Pitt cedes – External Pathway (EXT) submission AFTER the IRB of Record approves Pitt as a site A registration application is submitted via “External Pathway” OSIRIS Ensures completion of other institutional requirements (ancillary reviews) Allows tracking of approved studies at institution Research cannot begin until we activate this submission

External (EXT) Pathway submission Materials that must be submitted in EXT application: Approval letter from IRB of Record that states Pitt has been officially approved as a research site IRB-approved protocol IRB-approved local consent/assent form(s) IRB-approved recruitment materials

After External Pathway Activation Only limited information is submitted to Pitt IRB Time of continuing review (Renewal) If the Pitt PI or study staff changes If any procedure related to an ancillary review changes (i.e. adding an x-ray) If the Reviewing IRB makes a determination of serious or continuing non-compliance or unanticipated risk to subjects or others at the Pitt site

PI/Research Team Responsibilities – ceded review Complying with the IRB of Record’s policies and procedures Registering through External Pathway Maintaining a current and accurate study regulatory binder Including correspondence from IRB of Record

Pitt IRB of Record

Pitt as IRB of Record – Agreement Pitt IRB contacts the Relying Site IRBs to determine what type of agreement will be executed Pitt IRB facilitates obtaining agreement signatures

Pitt as IRB of Record – IRB Submission Normal submission through OSIRIS Indicate “(sIRB)” after protocol title First submit as if Pitt is the only research site Do not list other sites in CS15.0 Upload Pitt-specific consent form in 4.9 of OSIRIS Upload consent template in CS11.0 Do not list external personnel in OSIRIS

Consent template Areas of the consent template Relying Sites edit: Institutional letterhead Local staff and contact info Compensation for injury language (if may cause physical injury) HIPAA language A separate authorization document can be used if required by external site policy Data retention policy Discuss consent template handout

Dissemination of materials Pitt study team disseminates to Relying sites and collects completed materials: Initial IRB approval letter IRB-approved consent template IRB-approved protocol Communication Plan sIRB Implementation Checklist Local context form Discuss Communication Plan & Checklist handouts

Onboarding conference call If deemed necessary, an all-site phone conference can be scheduled All study teams All Relying Site IRB Representatives

Onboarding Relying Sites AFTER the following steps have been completed, Pitt Study team submits a Modification to add site(s). Agreement fully executed between sites Local context form completed and returned Local consent template vetted by Relying Site’s IRB

Rolling or Batched Onboarding Pitt Study team can decide: Submit Mods to onboard sites one at a time, as they are ready Batch sites to onboard

PI/Research Team Responsibilities – Pitt IRB of Record Primary contact for all Relying Sites & Pitt IRB Disseminating and collecting all study materials to/from Relying Sites Submitting study into OSIRIS Following provisions of agreement

Other Institutional Requirements

Grants & Contracts - OOR Needs Pitt Cedes Oversight Pitt IRB of Record Fully executed agreement or Letter of acknowledgement (if SmartIRB is used) Initial IRB approval letter External Pathway Activation letter Modification approval letter that on-boarded the Relying Site(s)

Data Use Agreements - OOR Reliance agreements do not include terms regarding data sharing between entities. In addition to a Reliance Agreement, you must still execute a Data Use Agreement (DUA) with the Office of Research. http://www.research.pitt.edu/ccc-data-use-agreements Phone: 412-624-7400

“We are all keenly aware of the inefficiencies of our new efficiency.” -Anonymous Reliance Specialist from an external site

COMING ATTRACTIONS

New System to replace OSIRIS Currently accepting new Exempt/Expedited, non-sIRB submissions January 2019 - new Full Board studies Date TBD – sIRB protocol submissions Simplified submission system Improved questions Built with sIRB needs in mind

Common Rule - 2018 Did you know that the Federal policy for the protection of human subjects (The common rule, subpart A) has major changes coming? https://www.hhs.gov/ohrp/regulations-and- policy/regulations/finalized-revisions-common- rule/index.html HRPO will keep you posted on the revisions and policies

When in Doubt… Call us: 412-383-1480 Set up a consultation appointment Email us: irb.reliance@pitt.edu