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IRBchoice: Increasing Flexibility in Reliance
Todd W. Rice, MD, MSc | Vanderbilt University Medical Center | Assistant Professor of Medicine | Medical Director, IRB
The Push for Streamlined IRB Review
2001: NCI CIRB launches1
2008: VA CIRB launches1
2010: OHRP Director (Menikoff) notes that sponsors could require use of CIRBs2
2011: NCATS funds R13 that leads to development of IRBshare (launch 2012)
2012: NINDS’s NeuroNEXT CIRB launches1
2013: NCI requires use of NCI CIRB for some studies
2014: NINDS’s StrokeNET CIRB launches3
2014: NCATS funds development of IRB Reliance Agreement
2014: NIH R01 RFA calls for empirical research on CIRBs (IRBchoice awarded)4
What do we know about CIRBs?
Goal Streamline the review of multisite studies by reducing
duplication of effort
Evidence Empirical evidence of CIRB efficiency is lacking5, 6
CIRBs are by default limited in scope (disease and/or funder specific)
CIRBs require significant start up and ongoing costs7, 8, 9
CIRBs may not be faster than local review (local IRB experience)
A significant burden is imposed on the CIRB CIRB models have communication and documentation
challenges8
An Alternative to CIRBs: IRB Reliance Agreements
Most are agreements between institutions in close geographic proximity California (Reciprocal IRB Authorization Agreement for Multi-Site Human Subjects Research) 10
Iowa, Kansas, Missouri, Minnesota, Nebraska, & Wisconsin (Greater Plains IRB Consortium) 11
Indiana, Minnesota, Ohio, and Wisconsin (Midwest IRB Consortium) 12
New England (The New England (formerly Harvard Catalyst) Reciprocal Common IRB Reliance Agreement) 13
Ohio (The Ohio CTSA Consortium Reliant Review)14
Texas (UT IRB Reciprocal Agreement) 11
What do we know about IRB Reliance Agreements?
Features Single agreement between all institutions AAHRPP accreditation required to be Reviewing IRB (and in some cases participate at all) Reviewing IRB rotates based on institutional (PI) and IRB expertise Member institutions are relatively static (exception: New England) Allows for streamlined investigator submission process
Concerns Lengthy contract negotiations required for each agreement Reliance only applies to a small proportion of an institution’s multisite studies (i.e., those involving
sites in the agreement) Responsibilities of Reviewing and Relying IRBs varies across agreements, creating the need for
administrative management within each IRB when multiple reliances are executed Utilization and efficiency data are not widely available
Another Alternative: IRBshare
Pros Reduce duplication of effort for relying IRBs
No additional burden for lead IRB
Each IRB maintains local oversight
Applicable to all institutions with FWA, all studies (disease neutral), and all types of funders
Cons Streamlining submission for investigators needs adoption
Reliance is optional
Potential for variation in consent form given local approval
Institutional Use of Reliance Models is Increasing
NCI, NeuroNEXT and StrokeNET require the use of respective CIRB
IRBshare utilization expected to increase 26% of IRBshare sites* that HAVE NOT used
IRBshare said they were waiting for CRs/Amendments to be included
60% of IRBshare sites* report use will increase if more requests came from funders, institutional leaders, and investigators
*Of those responding to user survey1-5 sites
6-10 sites
11-15 sites
>15 sites
0
5
10
15
20
25
30
35
IRBshare Sites that Cede IRB Review (n=33 of 37)
Overlap between Institutions in IRBshare and CIRBs / Reliance Agreements
CIRBs/Reliance Agreements (totalsignatories)
# IRBshare Institutions in CIRB/Agreement
NCI CIRB (n=>300) 30 NeuroNEXT CIRB (n=25) 11StrokeNET CIRB (n=25) 13California Reliance (n=10) 1Greater Plains IRB Consortium (n=10) 5Midwest IRB Consortium (n=6) 1New England Reliance (n=24) 2Ohio Reliance (n=13) 3Texas Reliance (n=10) 4
As of 5/21/2014 or current CIRB website
Reducing duplicative reviews increases IRB
workload when multiple reliance models are
implemented
IRBchoice Goals
To leverage successes and challenges learned from all reliance models’ (CIRB + reliance agreements)
To provide multiple reliance models under a single IT system and single reliance agreement
To allow flexibility in identifying the IRB review model that works best for a given study
To conduct a natural experiment of IRB reliance preferences
IRBchoice Process: Lead IRB Choices
a. Upload study approval to IRBchoice + agree to serve as IRB of Record for interested sites for a given study
b. Upload study approval to IRBchoice + allow others to rely upon the approval using the Shared Review (Sharing IRB)
IRBchoice Process: Relying IRB Choices
IF Lead IRB uploads study approval to IRBchoice + agrees to serve as IRB of Record for interested sites…The Relying IRBs have the option toa. Cede regulatory review to Lead IRB
b. Use shared review and maintain local oversight of study
c. Review via local policies and procedures
IRBchoice Process: Relying IRB Choices
IF Lead IRB uploads study approval to IRBchoice + allows others to rely upon the approval using the Shared Review (Sharing IRB)…The Relying IRBs have the option toa. Use shared review and maintain local oversight of study
b. Review via local policies and procedures
IRBchoice Infrastructure
Single Informatics PlatformExpand existing IRBshare system Allow Lead IRBs to indicate their role (IRB of
Record or Sharing IRB)
Allow Relying IRBs to indicate reliance type
Build institutional profiles to capture “static” local context issues (e.g., state laws)
Explore ways to decrease investigator burden Use of common “abbreviated application” to
minimize investigator burden for any reliance
Allow investigators to confirm (instead of submit) supporting documents
Single Reliance AgreementExpand upon IRBshare Master Agreement IRBshare Master Agreement
Covers ‘legal’ issues (e.g., confidentiality, scope, indemnification, insurance)
Covers responsibilities when using the Shared Review
Two-page MOU Outline responsibilities of Lead IRB when
serving as the IRB of Record Outline responsibilities of Relying IRB when
ceding review Allow institutions to sign on to be IRB of
Record AND/OR Relying IRB
IRBchoice Research Question 1
What factors influence institutions’ review model selection? Why do IRBs decide to serve as the IRB of Record, Sharing IRB or not at all?
Why do IRBs decide to use the ceded, shared, or local review procedures for a given study?
Lead IRB: Why serve as IRB of Record or a Sharing IRB?
Serve as IRB of Record Local investigator is study PI Coordinating center will centralize all study activity Little procedural variation from site to site Minimal variation between local laws Number of study sites is manageable given local IRB resources + compensation Have capacity to serve as IRB of Record
Serve as Sharing IRB No lead coordinating center to centralize study activity Do not have local capacity to serve as IRB of Record Number of study sites is too large to serve as IRB of Record Study has multiple ancillary studies Institutional policy prohibits serving as IRB of Record
Welcome!
IRBshare Site Experience Serving as “Lead IRB”
Simple operationally, no significant
problems22%
Complex operationally,
but doable78% Significant
challenges; will not attempt
again0%
IRBshare Sites Experience Serving as Lead IRB (n=9 of 38)
Relying IRBs: Why select a ceded or shared reliance or review the study locally?
Rationale may differ between IRBs for the same study
Ceded Shared LocalStudy well suited to centralized review
(little site procedural variation) X
IRB prefers full reliance model XLocal IRB lacks expertise to review study X X
Funder required use of specific reliance model X XInvestigator preferred specific reliance model X X X
Study does not have a coordinating center X XStudy requires significant local review due to local laws
(e.g., surrogate consent) X X
Prefer oversight due to problematic investigator/group X XPrefer oversight due to unknown risks (e.g., neonatal surgery) X X
Prefer not to cede review/maintain local control X XAncillary studies being conducted X X
Institutional policy to rely on AAHRPP accredited IRBs X XNot satisfied with Lead IRB review X
Welcome!
User Survey: Relying IRBs’ Reliance Model Preference
17
14
4
0
2
4
6
8
10
12
14
16
18
Ceded Review Shared Review Local Review
Study developed by a representative steering committee with little site
variation
User Survey: Relying IRBs’ Reliance Model Preference
0
11
23
0
5
10
15
20
25
Ceded Review Shared Review Local Review
Study involves surrogate consent (laws vary from state to state)
User Survey: Relying IRBs’ Reliance Model Preference
2 3
30
0
5
10
15
20
25
30
35
Ceded Review Shared Review Local Review
Study requiring more frequent review due to unknown risks (fetal surgery)
IRBchoice Research Question 2
Do models differ in their efficiency, the quality of review, and/or user satisfaction?
Evaluation (briefly)
Rationale for review model selection Lead IRB
Relying IRB
Efficiency: captured in IRBchoice system Days from IRB submission to approval
Days from IRB review to approval
Cost for each review
Quality: record IRB meetings reviewing IRBchoice studies and assess compliance with regulatory criteria
Satisfaction Surveys to and telephone interviews with IRBs,
study teams, institutional leadership, funders
Capturing Rational Via IRBchoice System
Possibility for Randomization
When an institution agrees to serve as the CIRB, randomize willing institutions to either the Ceded or Shared reliance
Randomize institutions to either receive guidance (tip sheet) on what types of studies and scenarios are well suited to each review model or not
Timeline
Year 1: Face-to-face meeting to discuss logistics and workflow challenges and finalize evaluation plan Outreach to funders, investigators, and institutional leadership IT development MOU development Template SOPs for IRBs of Record Secure commitments to serve as IRB of Record when possible Identify potential studies for IRBchoice Measure development (including validation)
Years 2 and 3: Enroll studies Evaluate research questions
Challenges to Address in Year 1
Issue Potential SolutionLow utilization 1. Seek institutional commitment to use IRBchoice
2. Establish utilization goals with IRBs (e.g., 25% of studies in Year 2, 50% of studies n Y3)
3. Prioritize outreach efforts to funders, institutional leadership, and investigators
4. Template SOPs for Lead and Relying IRBs when using the ceded and shared models
5. Hold frequent educational sessions for various audiences (IRBs, investigators, institutional leadership, and funders)
Streamline investigator submissions when at a Relying IRB
1. Streamline submission for ceded and shared models2. Explore creation of electronic abbreviated applications3. Allow investigators to “confirm” supporting documents in
IRBshare rather than submit each one locally
Collaborators
Communication and Infrastructure Expertise: Gordon Bernard and Jill Pulley (PI and Executive Director of the CTSA Consortium CC)
Informatics Expertise: Paul Harris (developer of REDCap, IRBshare, and ResearchMatch)
CIRB + Reliance Agreement Experts: Mike Linke (U Cincinnati, StrokeNET)
Eric Mah (UCSF, UC BRAID Reciprocal Reliance Agreement)
Evaluation Expertise: Leonard Bickman (former director of the Center for Evaluation and Program Improvement at
Vanderbilt)
References
1. Kaufmann P, Cudkowicz M, Cates KL, et al. Opportunities and challenges for use of central Institutional Review Boards.2. Menikoff J. The paradoxical problem with multiple-IRB review. N Engl J Med. 2010;363(17):1591-1593. doi:10.1056/NEJMp1005101.3. National Institution of Neurological Disorders and Stroke. NINDS Stroke Trials Network. Retrieved from
http://www.ninds.nih.gov/research/clinical_research/NINDS_stroke_trials_network.htm4. National Institutions of Health. Empirical research on ethical issues related to central IRBs and consent for research using clinical records. Retrieved from
http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-14-002.html5. Check DK, Weinfurt KP, Dombeck CB, Kramer JM, Flynn KE. Use of central institutional review boards for multicenter clinical trials in the United States: a
review of the literature. Clin Trials Lond Engl. 2013;10(4):560-567. doi:10.1177/1740774513484393.6. Abbott L, Grady C. A systematic review of the empirical literature evaluating IRBs: what we know and what we still need to learn. J Empir Res Hum Res
Ethics JERHRE. 2011;6(1):3-19. doi:10.1525/jer.2011.6.1.3.7. Wagner TH, Murray C, Goldberg J, Adler JM, Abrams J. Costs and benefits of the national cancer institute central institutional review board. J Clin Oncol
Off J Am Soc Clin Oncol. 2010;28(4):662-666. doi:10.1200/JCO.2009.23.2470.8. Kaufmann P, Cudkowicz M, Cates KL, et al. Opportunities and challenges for use of central Institutional Review Boards.9. Mascette AM, Bernard GR, Dimichele D, et al. Are central institutional review boards the solution? The National Heart, Lung, and Blood Institute Working
Group’s report on optimizing the IRB process. Acad Med J Assoc Am Med Coll. 2012;87(12):1710-1714. doi:10.1097/ACM.0b013e3182720859.10. Campuses unite to bring medical breakthroughs to patients more quickly. UCLA Today. http://www.today.ucla.edu/portal/ut/PRN-ucla-uc-braid-
217183.aspx. Published 2014.11. NCATS IRB Reliance Project. Conference held in Chicago, IL on May 21, 2014.12. CTSI Partners Sign IRB Master Reliance Agreement. Clinical and Translational Science Institute of Southeast Wisconsin. https://ctsi.mcw.edu/blog/news-
events/news/about-ctsi/ctsi-partners-sign-irb-master-reliance-agreement/. Published January 20, 2012.13. Proposed Reciprocal IRB Reliance Agreement Across Harvard Institutions. Harvard Catalyst National Clinical and Translational Science Awards (CTSA)
Consortium News. http://catalyst.harvard.edu/news/news.html?p=38&title=Proposed+Reciprocal+IRB+Reliance+Agreement+Across+Harvard+Institutions. Published September 3, 2008.
14. Three Major Ohio Universities Establish Statewide Research Collaboration. Case Western Reserve University Clinical & Translational Science Collaborative (CTSC) News. http://casemed.case.edu/ctsc/calendar/news/statewide-irb-release.cfm. Published August 17, 2012.
