IRBSHARE: STREAMLINING IRB REVIEW FOR MULTI-SITE STUDIES

BACKGROUNDThe need to streamline IRB review

IRBshare Development Considerations

• Flexibility in federal regulations (OHRP 45 CFR 46.114 and FDA 21 CRF 56.114)

• Institutions can use a “joint review” arrangement and “rely upon the review of another qualified IRB…avoiding duplication of effort”

• Lessons learned from centralized models• Disease-specific models are inherently restrictive• Numerous contractual agreements (i.e., study-specific MOUs) can be

burdensome• CIRBs can have intensive startup costs and/or ongoing overhead• CIRBs provide little flexibility for local IRBs• Ongoing debate regarding external IRB’s ability to fully understand

local context issues

Conference Series Grant Support• Vanderbilt awarded R13: “Novel IRB Review Models

for Efficient Multisite Review”• Three meetings from 2011-2013

• Goal was to develop, build, and pilot new model(s) of IRB review of multisite studies

• Multiple stakeholders• Individuals from nearly 2/3s of the CTSAs, OHRP, FDA, NCATS• Regulatory, legal, ethics, and clinical trial experts

• Iterative development• Ongoing evaluation• Start small: establish reliance for initial study review first, then expand

THE IRBshare MODELHow IRBs use IRBshare

IRBshare: General Features• Universal terms of use preclude lengthy negotiations

• All institutions sign a one-time master agreement without site-specific modifications or study-specific language

• Inclusive consortia broadens model utilization • IRBshare network is open to any FWA-holding organization and

any area of research• Low cost strengthens sustainability

• IRBshare network is free to join and has little to no overhead or startup costs

IRBshare: Shared Review Model

Local investigator submits study to local IRB; study

reviewed by convened IRB

upload

IRBshare SystemIRB Approved Documents

Local investigator submits study to local IRB; study reviewed by local subcommittee (>1 IRB member)

using IRBshare documents

FULL BOARD REVIEW SITE SHARED REVIEW SITE

Committee Responsibility: Determine whether study

meets all federal regulatory guidelines for approval of

research (e.g., 45 CFR 46.111)

Subcommittee Responsibility:Verify full board review site’s

determination + review for site’s own local context issues

IRB applicationConsent form(s)

Protocol + IB/Device ManualMeeting minutes (redacted)

Determination letter

download

Discuss, review, and approve changes to the

protocol, Investigator Brochure and/or Device

Manual based on reported events/problemsCC disseminates study-

related materials and updates

Local investigator submits to local IRB, who can then download IRB approval

documents from IRBshare and review and approve the study via a local subcommittee. No

documents are uploaded to IRBshare by the Shared

Review Sites. The direction of the arrows is indicative of the

information flow.

Local IRB--now a Full Board Review Site--uploads IRB

approval documents to

IRBshare

Study Coordinating Center (CC)

(e.g., CRO, lead site)DSMB

Local Investigator, Institution A Local

Investigator, Institution B

Local Investigator, Institution C

Local IRBLocal IRB

Local IRB

IRBshare Web-based

System

Local investigator reports adverse

events/unanticipated problems to local IRB, and

then the CC(if necessary)

IRBshare Information Flow for Multicenter Study

IRBshare: Reliance Model Features• Reliance model enables simultaneous IRB approval

• Once IRB approval uploaded to IRBshare, all study sites can seek approval • Flexible reliance options support local autonomy

• “Lead” IRB established organically on study-by-study basis• Studies may have more than one “lead” IRB • IRBs always have the option to review study locally• Local submission processes and forms do not have to change

• Dynamic IRB responsibilities address local IRB oversight concerns• Local context review is always the responsibility of the local IRB • Local IRB regains study oversight after relying on Full Board Review Site• All study-related events are reported locally, with study-wide issues also reported

broadly via the mechanism established for the study• Shared IRB documents minimize submission requirements at local

IRBs• Once IRB approval documents uploaded to IRBshare, local IRBs can accept

shortened IRB applications (e.g., local context only) from local investigators

IRBshare: Additional Features• Transparency enables continuing education and

dialogue • Sharing IRB documentation enables continuing education and

dialogue between IRBs• Shared documents creates opportunity to utilize shared expertise,

consult other IRBs, and promote consistency in the IRB review process

IRBshare TO DATEOctober 2012 to present

Who Can Use IRBshare?• Any institution with a Federalwide Assurance with OHRP

(i.e., most institutions)• Any industry-sponsored or investigator-initiated multi-site

study• Any number of institutions (>1 up to ∞)• Greater than minimal risk studies (i.e., full board

review required)

IRBshare Network (n=36)

*AAHRPP accredited; †CTSA institution or affiliate

Baystate Health* University of Alabama Birmingham*†

Boston University Medical Center*† University of Arkansas for Medical Sciences*†

Children’s National Medical Center*† University of California San Diego†

Duke University*† University of Illinois Chicago*†

Maine Medical Center* University of Iowa*†

Marshall University* University of Kansas*†

Medical University of South Carolina*† University of Kentucky*†

Meharry Medical College† University of Miami†

Mississippi State University* University of Minnesota*†

Mount Sinai Medical School*† University of North Carolina at Chapel Hill *†

New York University School of Medicine*† University of Pittsburgh*†

North Shore LIH Health System University of Southern California*†

Seattle Children’s Hospital University of Texas HSC at San Antonio*†

Stanford University*† University of Texas Southwestern Medical Center†

The Scripps Research Institute† University of Washington†

The University of Utah*† Vanderbilt University*†

Tufts Medical Center† Virginia Commonwealth University*†

Tufts University † Washington University (St. Louis) *†

Preliminary Results • Regulatory Acknowledgement (OHRP, FDA, AAHRPP)• 4 active studies with shared reviews conducted

• ISCHEMIA Trial: Duke relied on Vanderbilt• Days from Submission to Approval: 6

• MENDS II: Baystate relied on Vanderbilt• Days from Submission to Approval: 42

• Vitamin D & Type 2 Diabetes: MUSC relied on Tufts• Days from Submission to Approval: 27

• Neonatal Abstinence Syndrome Study: Vanderbilt relied on Tufts• Days from Submission to Approval: 16

• Recommended use mentioned in federal RFAs• Recent U54 Rare Disease RFA stated that “applicants are strongly

encouraged to consider models that will facilitate “shared review” such as IRBshare or a central IRB of record for multisite trials and provide plans for implementation.”

IRBshare FOR STUDY TEAMS AND INVESTIGATORS

Applying for a multicenter grant?1. Utilize the grant template language

IRBshare.org/#resources2. List the # of study sites in IRBshare3. Recruit non-IRBshare sites

a) Ask site PIs to email their IRB Director re: IRBshare and CC: emily.sheffer@IRBshare.org

b) Email emily.sheffer@irbshare.orgi. Study titleii. Study sitesiii. Site PI names and emailsiv. IRB Director names and emails

c) IRBshare can help reach out to site IRB Director(s)

Want to encourage an institution to join IRBshare?• Encourage your colleagues at other institutions to talk to their IRB Director about IRBshare

• Sites join by having their Institutional Official sign the IRBshare Master Agreement (IMA)

• CC emily.sheffer@IRBshare.org

Not sure if a study is in IRBshare?• Visit https://IRBshare.org/#studies • Contact your IRBshare Liaison (https://IRBshare.org/#participants) or email emily.sheffer@irbshare.org

Lead site for a multi-site study?• Notify your IRBshare Liaison ASAP (https

://IRBshare.org/#participants)• Submit a cover letter with your IRB submission• Tell collaborating PIs to contact their IRBshare liaison

ASAP

Participating in study that has IRB approval in IRBshare? • Contact your IRBshare liaison ASAP• Submit your IRB application as usual to your IRB• Include a cover letter indicating that an approval is in

IRBshare

IRBshare Checklist for Study Teamshttps://www.ctsacentral.org/editor/index.php?doc_id=3843

IRBshare FOR INDUSTRY SPONSORED STUDIESEnsure Proper Access to Study Documents

Overview• IRBshare can be used with industry sponsored study with

the approval of the sponsor• IRBshare will obtain study sites from the sponsor and

enable only IRBs at those sites to view study documents.• Sites can be added/removed as needed

Creating Industry-Sponsored Studies

If sponsor isn’t listed in IRBshare…

• IRBshare users can request that new sponsors be added

• IRBshare administrator will contact sponsor to verify study should be added to IRBshare + confirm study sites

Access to Industry-sponsored Studies is Limited

• IRBshare administrator can quickly and easily• indicate which

IRBshare institutions are study sites

• remove sites that drop from the study, as directed by Sponsor