Taking the Plunge:
Facilitating and Monitoring Collaborative Research
and IRB Authorization Agreements
Charles Hite
Director, Biomedical & Research Ethics
Why Rely on Another IRB?
“The federal system for protecting research
subjects was designed decades ago, when most
research studies took place at a single institution.
These days, if a study is conducted at multiple
sites, an ethics review by an institutional review
board (IRB) may be repeated many times. This
practice has been criticized for both wasting
resources and leading to inappropriate delays in
the conduct of research.” – Jerry Menikoff, Director
OHRP
Why Worry?
“ The decision to rely on another IRB raises a
host of issues ranging in complexity from a
simple aversion to giving up institutional control
over the IRB review process to believing that an
institution is more vulnerable to legal and
compliance risks when IRB review is conducted
by another organization. The decision to rely on
another IRB can even be marked by a fear that an
external IRB cannot or will not review research at
a standard that is equivalent to or above those of
one’s own organization.” – “From Resistance to Reliance,”
The HRP Consulting Group.
What Do Regulations Say?
OHRP:
• FDA:
“Cooperative research
• “…institutions involved in
projects are those
multi-institutional studies
projects…which involve
may use joint review,
more than one institution.
reliance upon the
…[An] institution
review of another
participating in a
qualified IRB, or similar
cooperative project may
arrangements aimed at
enter into a joint review
avoidance of duplication
arrangement, rely upon the
of effort.”
review of another qualified
IRB, or make similar
arrangements for avoiding
duplication of effort.”
•
45 CFR 46.114
•
21 CFR 56.114
To Rely on External IRB Use…
•
•
•
 IRB Authorization Agreement (IAA),
also called Reliance Agreement,
negotiated and executed
 Policies and procedures to delineate
responsibilities implemented
 External IRB ensures process and
ability to addresses “local” issues
•
http://www.hhs.gov/ohrp/index.html
Factors to Consider in IAA
Purpose of IAA
• To create a single IRB of Record?
• Protocol-specific reliance
• Reduce administrative burden
Nature of authorization
• Complete reliance
• Partial reliance, e.g., recruitment/consent document
• Dual IRB Review (Collaborative, Independent, or Concurrent?)
Scope of review
•
•
•
•
Exempt Research?
Minimal risk trials only?
Clinical trials?
All studies? Just one study?
Case: Carilion-Virginia Tech IAA
• Tech Researchers Interested in Accessing
Carilion Patients/Data
• Carilion Physician Researches Want to
Collaborate with Tech Colleagues
• Launch of VTC Medical School and
Research Institute 3 Years Ago
Case: Carilion-Virginia Tech
• Initially IAA done on individual studies
• As projects grew, IAA was supplemented
with a Memorandum of Understanding
• MOU basically assigns IRB review
according to degree of “engagement” in
research and where subjects are recruited
and consented
• Both IRBs can choose to review
Issues to Consider in IAAs
• Accreditation: AAHRPP requires
accredited organizations using external
IRBs to ensure the external IRB meets
AAHRPP standards
• Does relying institution have ability to
mandate its consent template language?
• Make sure there is agreement on
identifying and managing financial conflicts
of interest.
Issues to Consider…
• Who is responsible for providing approval
notification and what is the time frame?
• Will approving institution allow for rights to
attend meetings? Will it provide minutes?
• Will approving institution have right to
access relying institution if it is conducting
for cause/not for cause audits, etc.?
Issues to Consider…
• How does the reviewing institution address
local context issues?
• What are the procedures for managing
reportable information and in what time
frame, e.g. serious or continuing noncompliance and unanticipated risks?
Issues to Consider…
• Will both Institutions “uncheck the box”?
If one site has “checked” the box, and another has not, your OHRP
reporting requirements are inconsistent. Consider aligning federal-wide
assurances to both extend your assurance to non-federally funded research
or neither.
• HIPAA status
When reviewing for a covered entity, if your institution is not a covered entity
or if your institution is a hybrid entity, your institution must have the ability to
comply with HIPAA, HITECH and related privacy laws.
• Informed Consent Language on Subject Injury
Clinical Trial Agreement indemnification terms are often incorporated into
the informed consent Will reviewing IRB allow for a modification to the consent
form? In rare instances where Sponsor CTA negotiations cannot achieve agreement,
how will you notify the other IRB?
Other Models of Review
• “…Joint review arrangements…”
•
•
•
•
•
Central IRB Review / Facilitated Review
Decentralized Facilitated Review
Single IRB
Common IRB
…Rely upon the review of another
qualified IRB…”
“
• Commercial IRB
• IRB Deferral/Reciprocal Reliance
• “…Or make similar arrangements…”
• Private/Public Hybrid
• Federation Model
• Network IRB Model
Central IRB Model
Administration/Documentations
• IAA
• Written procedures to describe
how each implements its
responsibilities for the process
CENTRA
L IRB
Central IRB
• Responsible for review
SITE #1
Local
IRB
SITE #2
Local
IRB
SITE #3
Local
IRB
Local IRB
• Local IRB assumes responsibility
for:
- Local context
- Review consent
- Assure compliance with
local laws
Example: National Cancer Institute IRB (http://www.ncicirb.org/)
15
Independent or Commercial IRB
•
•
•
•
•
•
Organized in compliance with OHRP/FDA regs
Outsource IRB functions
Often for-profit
Fee based
Offer a range of services in negotiated contract
Each participating IRB reviews investigator request
to determine if commercial IRB review is appropriate
• Sometimes type of review allowed is limited, e.g.
only phase 3, multi-center industry sponsored trials
Acknowledgement
Some slides and/or concepts courtesy of:
Sabune J. Winkler, JD
Director, Regulatory Affairs Operations
Harvard Cataylst