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CTSA Profi le
yet effi ciently conducting that research remains problematic. 3,4
Challenges include the high costs of conducting research, a
shortage of qualified investigators, 5 low subject enrollment
rates, 6,7 slow dissemination of results, 8 reduced funding, 3 lagging
IT systems, 9 and increased regulatory burden. 10,11 A priority
for the National Center for the Advancement of Translational
Science (NCATS), and its Clinical Translational Science Award
(CTSA) Consortium, is to address this last concern regarding
regulatory burden. Specifi cally the focus is on the improvement
of Institutional Review Board (IRB) processes; especially
novel models for regulatory review of multicenter clinical and
translational research studies. Th e three Ohio CTSA sites, housed
at Case Western Reserve University (CWRU) in Cleveland, Th e
Ohio State University (OSU) in Columbus, and the University of
Cincinnati (UC), have collaborated to create a novel IRB review
concept with the hopes of addressing this concern and achieving
a more eff ective and effi cient IRB review of multicentered clinical
ff ective clinical and translational research is an essential
component of improving human health as delineated
in the National Institutes of Health (NIH) roadmap, 1,2
To date a number of diff erent methods have been used to streamline
IRB review of multisite studies. Th e central IRB model, where a
“for-profi t,” independent IRB (e.g., Western or Chesapeake) acts
as the IRB of record for regulatory review processes, is commonly
used for a large number of industry initiated and sponsored
clinical trials. Federated IRBs are another type of review model
in which one existing IRB within a network of sites serves as the
IRB of Record for studies conducted within that network (e.g.,
Harvard Catalyst is the IRB of Record for all studies within the
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNext network). A simpler and less formalized model of
reciprocal review involves the use of individual “Institutional
IRB Authorizations” (IIA) between collaborating organizations
whereby one organization can “authorize” a second organization’s
IRB to act as the IRB of Record for one or more studies conducted
at their organization. In an eff ort to create a “hybrid” model, the
IRB Administration Offi ces within the Clinical Translational
Science Collaborative (CTSC) based at CWRU and including
University Hospitals Case Medical Center, MetroHealth Medical
Center and the Cleveland Clinic Foundation, moved from a type
of bilateral, inter-institutional agreement to a broader agreement
amongst partners allowing the lead CTSC site to act as the IRB
of Record for a multisite clinical research protocol conducted
at any of the partner CTSC sites in late 2009. Th e CTSC named
this process “facilitated review” as this model allowed for any
participating IRB to serve as the IRB of Record for protocols
conducted by any combination of participating sites while at
the same time allowing each site to retain local context review
and oversight. More importantly, to address the fact of disparate
electronic IRB review systems, the CTSC IRB Advisory Group
developed a centralized electronic IRB hub as the main point of
interface for each application to further promotes effi ciency in
IRB review processes while facilitating document storage and
communication across research sites amongst CTSC regulatory
administrators and investigators alike.
In June 2011, 18 months aft er implementation of the initial
facilitated review process and IRB electronic “hub,” reports of
the CTSC facilitated review model, and information related to
use and successes within the CWRU CTSC were presented at the
annual Clinical Research Management Workshop sponsored by
the CTSA consortium. Th ree months later, use of this type of
model received signifi cant support by the political leadership
in the State of Ohio when the Governor of Ohio and the leader
of “JobsOhio” (an economic growth engine for job creation)
convened a meeting focused on leveraging healthcare and medical
strengths in Ohio to catalyze industry interest and spur economic
growth. One result of that meeting was a three-prong charge from
the governor to the three Ohio CTSA sites to collaboratively
develop Ohio as a recognized destination for clinical research, to
foster more effi ciencies within the translational research process,
and to attract more pharmaceutical and device industries with
the goal being improved human health. 12,13
Th e partner organizations that comprise the Ohio CTSA
consortium ( Table 1 ) discussed ways to collaborate shortly aft er
initial discussions with the governor and conceptualized full IRB
collaboration. Th e group immediately followed up with a face-to-
face meeting (October 2011) where the CTSC “facilitated review”
process and IRB electronic “hub” platform were demonstrated.
Following that discussion, the CTSAs across Ohio agreed to
move towards the reliant model of IRB review. Members of the
Ohio CTSA Consortium IRB Working Group agreed that each
institution within the collaborative would participate and exercise
authority of the proposed “reliant” IRB review model when
investigator collaboration existed among one or more of the Ohio
CTSA institutions (i.e., investigator synergy is the starting point).
Using current partnerships within the group (the Cleveland
CTSC, the IAA between Cincinnati Children’s Hospital Medical
Center and the University of Cincinnati, and the IRB reciprocity
agreement between Th e Ohio State University and Nationwide
Children’s Hospital.) as well as other models of collaborative
review (Harvard Catalyst Reciprocity Agreement) as a foundation
1 University Hospitals Case Medical Center/Clinical Translational Science Collaborative , Case Western Reserve University , Cleveland , Ohio , USA ; 2 The Center for Clinical & Translational
Science , The Ohio State University , Columbus , Ohio , USA ; 3 Center for Clinical & Translational Science & Training , University of Cincinnati , Cincinnati , Ohio , USA .
Correspondence: Philip A. Cola ( firstname.lastname@example.org )
[Correction added after online publication 10-July 2013. Author name corrected to Strasser.]
Ohio CTSAs Implement a Reliant IRB
Model for Investigator-Initiated
Multicenter Clinical Trials
Philip A. Cola , M.A. 1 , Carson Reider , Ph.D. 2 , and Jane E. Strasser , Ph.D. 3
VOLUME 6 • ISSUE 3WWW.CTSJOURNAL.COM
for legal agreement discussions, a decision was made to execute
a single a single IIA signed by all eight participating institutions
to clarify and solidify expectations. Th e total timeframe for
the Ohio CTSA Consortium IRB Working Group to achieve a
fully executed agreement was approximately 9 months. Much
was accomplished in this timeframe without wavering from the
ultimate goal of reduction of regulatory burden for investigators
through reliant IRB review.
Reliant IRB Review Model
Specifi c requirements of the reliance model
include that “each institution agrees to
maintain a registered IRB and an OHRP
approved Federalwide Assurance (FWA)
for human subject research.” In order to
serve as the “designated IRB of Record” for
State of Ohio consortium-wide projects, the
designated IRB of Record’s institution must
have achieved AAHRPP or other accepted
accreditation.” Th at IRB will then perform
the ”initial and continuing review and review
of amendments; unanticipated problems
that may involve risks to subjects or others;
and other documents/information related
to the approval and continuing oversight of
the research (as applicable).” Th e quotations
emanate from the executed IIA.
The relying institutions within the
Ohio CTSC accept the IRB of Record’s
review, approval, and continuing oversight
of research covered by the IAA, but retain
primary and ultimate responsibility for the
protection of human subjects with respect
to the conduct of the research covered by
this agreement and agree to comply with
applicable federal, state and local laws and
applicable FWA requirements; as well as to
review and manage appropriate education
and confl ict of interest requirements and any
resolutions thereof, and to communicate any
events or actions aff ecting that institution’s
compliance to the designated IRB of Record.
A “reliant IRB” workfl ow, initially adopted from the CTSC’s
“facilitated review model” initiative has now been extensively
modifi ed and access expanded for more broadly to the Ohio CTSA
Consortium ( Figure 1 ). Each participating institution in this model
is part of an Academic Medical Center (AMC) and a key driver
of such organizations is investigator-initiated clinical research
resulting in the focus on executing that part of the institutional
mission for each entity in this model. Th e agreements and the
process fl ow can also be used when and where applicable for
industry, foundation, and other sponsored project research activity
in order to reduce redundant reviews or improve effi ciencies.
Th e strength of the agreement is in its simplicity, as it is strictly
focused on IRB activities and responsibilities as defi ned by
Human Subject Protection Regulations and promulgated by the
Department of Health and Human Services and the US Food and
Drug Administration described in 45 CFR 46 and 45 CFR 50 and
56. It does not extend into additional institutional specifi c human
research protection plan requirements beyond those required for
FWA and/or AAHRPP accreditation, it does not address grants
administration, nor does it delve into HIPAA requirements and
confl icts of interest. Th e purpose of focusing on only IRB related
matters was to ensure that other institutional processes were not
altered by IRB collaboration. Each institution is also responsible
for managing budgets and contracts as such diff ers between public
and private institutions.
Institutions Participating in Ohio Collaborative IRB Review
(1) Case Western Reserve University
(2) Cleveland Clinic
(3) Cincinnati Children’s Hospital
(4) MetroHealth Medical Center
(5) Nationwide Children’s Hospital
(6) The Ohio State University
(7) University Hospitals Case Medical Center
(8) University of Cincinnati
* Eight legally separate institutions that constitute three separate CTSA funded entities.
Table 1. Participating Institutions
Figure 1. Ohio CTSA IRB workgroup - reliant IRB operations workfl ow for multicenter studies. *
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VOLUME 6 • ISSUE 3WWW.CTSJOURNAL.COM
Th e process fl ow of this model is being refi ned, but this is
an encouraging example that each of these AMCs has been able
to agree on basic principles and simplifi ed legal approaches to
solve long standing regulatory challenges for conducting multisite
clinical research. Th e model will continue to be refi ned and tested
throughout Ohio. With the continued input and collaboration of
its originators, our goal is to expand across the national CTSA
consortium, and to also include non-CTSA sites.
We anticipate that the economic impact of this regulatory
initiative will be positive, accelerating the initiation of clinical
and translational research at participating institutions. Metrics are
currently being gathered that will quantify protocol review and
approval times; and whether use of this approach and electronic
system has shortened study timelines. Th ese improvements will
likely result in ancillary successes including increased study
revenues, increased job opportunities for research coordinators,
study nurses and other allied research professionals in regions
where institutions participate, increased subject enrollment as
patients travel to regulatory effi cient sites for access to innovative
trials not open for enrollment (or not available) elsewhere;
increased clinical volumes due to stimulated clinical trial activity,
and fi nally the reduction of IRB regulatory burden will move
innovative treatments more effi ciently to the practice of medicine.
Th e authors wish to acknowledge the collaborative eff orts of all of
the members of the Ohio CTSA Consortium’s IRB working group:
Jeannie Bailey, Daniel Beyer, Jeremy Corsmo, Debbie Fine, Anthony
Gardner, Karen Hale, Missi Hart-Kothari, Kathleen Lawry, Sandra
Meadows, Karya Ottey, Ginger Pomiecko, Isabel Sanchez, Kim
Volarcik, and Erin Zaletel; without which this model would not
exist. Finally, thanks to the Harvard Catalyst for providing their
Reciprocity Agreement for review during this process.
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Sources of Financial Support
Eff orts of the authors were supported by the National Center for
the Advancement of Translational Science (NCATS) through
the following grants UL1 TR000077, 8UL1TR000090-05 and