I.
Manual:
Section:
Policy #:
Approval Date:
Institutional Review Board
N/A
RR 406
August 2014
Effective Date: August 2014
Revision Due Date: August 2017
PURPOSE
A.
Indiana University (IU) Health Bloomington requires that all human subjects research conducted at or on behalf of the institution, regardless of funding, be reviewed and approved by an appropriate Institutional Review Board (IRB) prior to initiation.
B.
The Code of Federal Regulations, 45 CFR 56.114 (21 CFR 56.114,
Cooperative Research), provide that institutions involved in multi-institutional studies may use joint review, reliance upon the review of another qualified
IRB, or similar arrangements aimed at avoidance of duplication of effort.
C.
A centralized IRB review process involves an agreement under which multiple study sites in a multicenter trial may rely in whole or in part on the review of an IRB other that the IRB affiliated with the research site.
D.
In order to promote efficiency and consistency across multiple research sites, alternative models of IRB review are available to IU Health Bloomington investigators. IU Health Bloomington may rely on an external IRB, meaning the IRB of another institution, organization or a commercial IRB, for review and approval of human subjects research if such reliance benefits IU Health
Bloomington, its investigators and/or its research participants. Examples of when such reliance may be considered include: research in which IU Health
Bloomington as an institution has a conflicting interest; multi-site research in which IU Health Bloomington employees are involved in minimal risk study activities; Phase II, III or IV multi-site, industry-sponsored research; and federally sponsored research for which a federally sponsored external IRB is duly constituted.
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II.
SCOPE
These policies and procedures apply to all research that IU Health Bloomington IRB has deferred oversight to or has accepted oversight responsibility from.
Type of Reliance - Institutional IRB/IU
Statewide IRB, Academia, Private Practice, etc. (Page 4)
Type of Reliance – Commercial IRB (Page 8)
Type of Reliance - Organizational
IRB/National Cancer Institute Central
Institutional Review Board (NCI CIRB), etc.
(Page 4)
III.
EXCEPTIONS
None
IV.
DEFINITIONS
See Attachment I: Definitions
V.
POLICY STATEMENTS
A.
Reliance on External IRBs for Minimal Risk Research
1.
The IU Health Bloomington IRB may rely upon the IRB review and approval provided by an external IRB for minimal risk research (i.e. defer to an external institution, organization or institution).
2.
The IU Health Bloomington IRB may provide review for non-IU Health
Bloomington investigators outside of the institution that are participating in minimal risk research conducted at or on behalf of IU
Health Bloomington.
3.
Considerations for determining appropriateness of deferrals for minimal risk include: a.
Roles of the investigators and/or institutions; b.
Federalwide assurance status of the external institution; and/or c.
Accreditation status of the reviewing IRB.
4.
IU Health Bloomington reliance upon an external IRB, or external reliance on the IU Health Bloomington IRB, must be documented by an
IRB Authorization Agreement. a.
IRB Authorization Agreement may be written to cover one research project, or to cover research projects on a case-bycase basis, or to cover a program of research. b.
The IRB Authorization Agreement includes a description of the regulatory requirements for which each party will assume responsibility.
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B.
Reliance on External IRBs for Research Greater than Minimal Risk
1.
IU Health Bloomington may rely upon the IRB review and approval provided by an external IRB for greater than minimal risk research (i.e. defer to an external institution, organization or institution). a.
Before deferral is granted, the IU Health Bloomington IRB must determine: i.
The external IRB has adequate policies and procedures in place to protect human research participants; and ii.
The external IRB is better qualified to provide the review, deferral of IRB review will provide increased efficiency, deferral of IRB review is required to avoid a potential institutional conflict of interest, or IU Health Bloomington investigators have received a grant (or other federals funds) and contracted out all human subjects research to employees or agents at an external institution. b.
When determining appropriateness of deferral to an external institution, the IRB will consider the following items.
Appropriateness will be considered in whole, and insufficiency in a single area does not prohibit deferral. i.
Accreditation status of the reviewing IRB; ii.
Federalwide assurance status of the reviewing institution; iii.
Whether the reviewing institution has received OHRP determination letters or FDA warning letters in the last year; iv.
Whether the external IRB’s membership satisfies the requirements of 45 CFR 46.107 and 21 CFR 56.10; v.
Whether policies and procedures for the external IRB are publicly available for review; vi.
The process for notifying IU Health Bloomington of approval, determinations, reportable events, suspensions, and terminations; and vii.
Overall adequacy of the external institution and their
IRB.
2.
IU Health Bloomington may provide IRB review for non-IU Health
Bloomington investigators or external sties participating in greater than minimal risk research conducted at or on behalf of IU Health
Bloomington and its affiliates when: a.
The review by the IU Health Bloomington IRB will provide increased efficiency; and b.
The external institution has an active Federalwide assurance.
3.
IU Health Bloomington reliance upon an external IRB, or external reliance on the IU Health Bloomington IRB, must be documented by an
IRB Authorization Agreement.
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a.
IRB Authorization Agreement may be written to cover one research project, or to cover research projects on a case-bycase basis, or to cover a program of research. b.
The IRB Authorization Agreement includes a description of the regulatory requirements for which each party will assume responsibility.
C.
Type of Reliance - Institutional IRB/IU Statewide IRB, Academia, Private
Practice, etc.
1. IU Health Bloomington enters into various research projects with outside institutions and entities (e.g. Indiana University, Purdue
University and other academic institutions and entities).
2. IU Health Bloomington reliance upon an external IRB, or external reliance on the IU Health Bloomington IRB must be documented by an IRB Authorization Agreement which describes a description of the regulatory requirements for which each party will assume responsibility.
D. Type of Reliance - Organizational IRB/National Cancer Institute Central
Institutional Review Board (NCI CIRB), etc.
1. IU Health Bloomington participates in the NCI CIRB Independent Model of review for adult clinical trials.
2.
The following division of responsibilities as defined by the IRB
Authorization Agreement/Division of Responsibilities Between the NCI
Central Institutional Review Board and IUHB is based on the premise that the CIRB’s primary function is initial and continuing review of adult and pediatric research protocols and that the local institution’s primary function is limited oversight.
3.
The following division of responsibilities is based on the premise that the CIRB’s primary function is initial and continuing review of adult and pediatric research protocols and that the local institution’s primary function is limited oversight. a.
The following division of responsibilities is based on the premise that the CIRB’s primary function is initial and continuing review of adult and pediatric research protocols and that the local institution’s primary function is limited oversight. b.
Conduct initial, amendment, and continuing review of studies c.
as well as review of any other study-specific documents submitted by the Study Chair to the NCI CIRB;
Conduct review of local context considerations; d.
Conduct review of potential unanticipated problems and/or serious or continuing noncompliance when the Signatory
Institution or other entity reports an incident, experience, or outcome to the CIRB;
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e.
Conduct review of individual Adverse Event Reports for studies without a Data and Safety Monitoring Board (DSMB) or f.
equivalent monitoring body;
Post all study-specific documents related to CIRB reviews to the g.
restricted access side of the CIRB website;
Notify research staff and institutional designees of all CIRB actions, per written procedures, via institution-specific correspondence, broadcast emails, and access to the restricted area of the CIRB website; h.
Notify the Signatory Institution immediately if there is ever a suspension or restriction of the CIRB’s authorization to review a i.
study; and
Notify the Signatory Institution immediately if there is ever a suspension or restriction of the CIRB’s authorization to review a study; and j.
Post the NCI CIRB Standard Operating Procedures on the public side of the CIRB website.
4. The responsibilities of the Signatory Institution (IU Health
Bloomington) are to: a.
Comply with the NCI CIRB’s requirements and directives; b.
Report to the NCI CIRB the names of any Component or Affiliate
Institutions that rely on the Signatory Institution’s IRB as defined by the Authorization Agreement/Division of c.
Responsibilities Between the NCI Central Institutional Review
Board and IUHB.
Report to the NCI CIRB the names of any Component or Affiliate
Institutions that rely on the Signatory Institution’s IRB as defined by the Authorization Agreement/Division of
Responsibilities Between the NCI Central Institutional Review
Board and IU Health Bloomington. d.
Report to the NCI CIRB the names of any Component or Affiliate
Institutions that rely on the Signatory Institution’s IRB as defined by the Authorization Agreement/Division of
Responsibilities Between the NCI Central Institutional Review
Board and IU Health Bloomington. i.
Ensuring the initial and ongoing qualifications of investigators and research staff; ii.
Overseeing the conduct of the research; iii.
Monitoring protocol compliance; iv.
Maintaining compliance with state, local or institutional requirements related to the protection of human subjects; v.
Providing a mechanism to receive and address concerns from local study participants and others about the conduct of the research;
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vi.
Investigating, managing, and providing notification to the
NCI CIRB of any study-specific incidence, experience, or outcome that seems to rise to the level of an unanticipated problem and/or serious or continuing noncompliance, the institution must provide a plan to manage the incident, experience, or outcome, including measures to prevent similar occurrences. vii.
As part of ensuring safe and appropriate performance of research the Signatory Institution has the authority to observe any aspect of the research process including observing the consent process and to conduct audits.
The CIRB retains the authority to direct this to be done when necessary. e.
Provide updates in a timely manner to the NCI CIRB whenever a
Signatory Institution (PI) is no longer the responsible party for a f.
study under the purview of the NCI CIRB;
Notify the NCI CIRB when a regulatory deficiency has been cited on an audit that occurred during the time that the NCI CIRB was responsible for study review;
Complete and submit the Annual Institution Worksheet About g.
Local Context, the Annual Investigator Worksheet About Local
Context, and any other worksheets/forms required by the NCI
CIRB for participation; h.
Decide on a study-by-study basis whether to open the study through the NCI CIRB or to conduct its own local IRB full Board review. Indicate the decision to open a study through the NCI i.
j.
CIRB by submitting a Study – Specific Worksheet About Local
Context;
In the local consent form: i. Incorporate NCI CIRB-approved boilerplate language into the NCI CIRB- approved model consent form; ii. Make no language changes to the consent form with the exception of NCI CIRB-approved boilerplate language; iii. Obtain NCI CIRB approval of changes to the boilerplate language prior to implementation; iv. Obtain NCI CIRB approval of translations of the consent form prior to implementation; v. Including HIPAA Authorization language as part of boilerplate language is permitted. The NCI CIRB does not approve the HIPAA Authorization language as it does not function as a Privacy Board, however, the NCI CIRB will accept HIPAA Authorization language when submitted as part of the boilerplate language.
Maintain regulatory file for each study under NCI CIRB purview as per local institution and sponsor policy;
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k.
Conduct full board review of any study enrolling prisoners, since the NCI CIRB is not constituted to review studies enrolling prisoners.
5. NCI CIRB Independent Review Process a.
The purpose of the local IRB review is to determine whether any local context issues exist which would suggest that local IRB review and oversight should be required. b.
The PI must conduct all procedures in accordance with NCI c.
CIRB policy (www.ncicirb.org)
The following items should be submitted to the local IRB for review, as applicable: i.
The principal investigator will provide IU Health
Bloomington IRB with the completed NCI CIRB Review
Cover Sheet; protocol; informed consent; and HIPAA
Authorization for all new studies which are approved by the NCI CIRB and will be conducted locally. ii.
Local requirements (e.g., CITI completion,
Conflict of Interest completion, CV) must still be met even though there is a request for CIRB to serve as the
IRB of Record. iii.
A local annual Continuing Review update, current informed consent and NCI CIRB Continuing Review approval letter; iv. Any unanticipated events involving risks to IU Health
Bloomington subjects or personnel; and v. A closeout report. d.
Local IRB review of new studies may result in one of three decisions: i.
Approved as submitted. The NCI CIRB Independent review process is accepted. The NCI CIRB will be designated as the IRB of Record and is responsible for the duties outlined above. ii.
Approved with provisions. The IRB Chair or designee is suggesting provisions to the submission and the submission may be finally approved after a response to such provisions is accepted. Upon final approval, the
NCI CIRB will be designated as the IRB of record and is responsible for the duties outlined above. iii.
Not approved. This protocol must undergo full board review and is not accepted for NCI CIRB Independent review. Full IU Health Bloomington IRB oversight is required. e.
Acceptance from the local IRB Chair or designee will be documented via signature on the NCI CIRB Registration Form.
The PI will be notified of the review results.
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f. Once new studies are accepted by the IU Health Bloomington
IRB reviewer, the IRB Office will accept the review of the protocol by visiting the NCI CIRB website, clicking on the
“Independent Review Acceptance” button, and completing the acceptance form for the applicable protocol. This acceptance designates the NCI CIRB as the IRB of Record.
E.
Type of Reliance – Commercial IRB
1.
IU Health Bloomington has agreed that research may be submitted to a commercial IRB if it has been determined that review by an independent IRB meets the following criteria: a.
The protocol meets the NIH definition of a clinical trial; b. The protocol is industry-sponsored and has been designed and c.
written by the industry sponsor, or designee;
The industry sponsor holds all IND/IDEs for the protocol, as applicable; d.
The protocol is an adult Phase II/III/IV clinical trial designed to evaluate prospectively the safety and/or effectiveness of new drugs, devices, biologics or disease outcomes; e.
The protocol is a pediatric Phase III/IV clinical trial designed to evaluate prospectively the safety and/or effectiveness of new drugs, devices, biologics or disease outcomes; and f.
The investigator has not previously submitted the study to another IRB.
2.
The following protocols are not eligible for review by a central IRB: a.
Investigator-initiated clinical trials regardless of funding; b.
Protocols receiving funds from a federal or other not-for-profit funding agency; c.
Protocols with industry sponsors who refuse to pay commercial
IRB fees; d.
Studies involving special local, social, economic, political or cultural concerns, including but not limited to xenotransplantations, gene transfer, and/or embryonic stem cells; e.
Protocols requiring emergency use/review; f.
g.
Research requesting waivers of informed consent; or
Phase I/II research involving children.
3.
When a commercial IRB serves as the IRB of Record, their primary function is initial and continuing oversight of the human subjects research and IU Health Bloomington’s primary function is determination of eligibility for submission to an independent IRB and limited local oversight. The IRB Authorization Agreement will provide a description of the regulatory requirements for which each party will assume responsibility.
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4.
When submitting a protocol to a central IRB for review, the local institutions PI or designee will provide the local IRB with the following information, as applicable: a.
Registration Form for the Use of a Central IRB, locally required documents (e.g., CITI completion, Conflict of Interest completion, CV), protocol, informed consent, HIPAA
Authorization, and the central IRB decision letter approving the local site. b.
A local annual Continuing Review update, current informed consent, and central IRB Continuing Review approval letter; c.
Any unanticipated events involving risks to IU Health
Bloomington subjects or personnel; and d.
A closeout report.
VI.
PROCEDURES
A.
Process for receipt of a request from the investigator to defer research to an external IRB or to request that IU Health Bloomington act as the IRB of
Record:
1.
Assign an IRB# to the submission;
2.
Process the submission and forward to the IRB Chair or designee for review. a.
The investigative site will provide the protocol, informed consent temple or revised local informed consent, HIPAA
Authorization and other applicable documents with the submission. The informed consent should be revised according to local boilerplate language, as applicable. b.
Local requirements (e.g. CITI, Conflict Of Interest & CV) must still be met when there is either a request for deferral or IU
Health Bloomington is being asked to be the IRB of Record. c.
An IRB Authorization Agreement between IU Health Bloomington and the external IRB must be in place.
3.
Institutional or Organization IRB: Review will be conducted by either the
Chair or designee for either a request to defer to an institutional or organizational IRB or for a request for IU Health Bloomington to act as the IRB of Record of another institution or organization. a.
The submitted materials will be reviewed to determine whether or not there are local concerns that need to be addressed and whether or not to accept or defer the application as submitted.
This person(s) has been given the authority by the IRB to review/propose additions to the protocol or to make minor word additions or substitutions to the informed consent, particularly to facilitate better comprehension by the local population, as long as the proposed changes do not alter the meaning of the external IRB’s approved documents. These proposed changes will be discussed with the external IRB before being made.
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Additional risks may be proposed to be included to the informed consent. If more revisions are thought to be required other than the ones described above, the full board must review at the local level and the external IRB will not be designated the IRB of
Record. b.
The IRB reviewer will designate the request to defer to an external IRB or act as the IRB of Record as:
i. Protocol Not Accepted; c.
ii.
Provisional Approval/Minor Modifications are required before a final determination can be made; or iii.
Approved (Protocol Accepted). The external IRB will be designated as the IRB of Record or IU Health Bloomington will be designated as the IRB of Record.
The IRB Office will send the investigative site documentation of the decision as a means of providing confirmation of the IU
Health Bloomington IRB determination.
4.
Commercial IRB: The process for the request to defer to a commercial
IRB is as follows: a. The IRB Administrator will receive and assign the administrative review of the Registration Form for Deferral to a Commercial
IRB to the IRB Chair or designee for acknowledgement of the use of a central IRB. b.
The investigator will submit the application directly to the commercial IRB.
5.
The request to collaborate with an external IRB is added to the IRB
Agenda.
VII.
CROSS REFERENCES
This policy affects all other IRB policies.
VIII.
REFERENCES/CITATIONS
Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research, 45 CFR 46.110, 2009.
Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research, 21 CFR 56.110, 2013.
Cooperative research, 45 CFR 46.114, 2009.
Cooperative research, 21 CFR 56.114, 2013.
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IX. FORMS/APPENDICES
RR 406-A NCI CIRB Review Cover Sheet
RR 406-B Registration Form for Protocol Review by a Commercial Institutional
Review Board
RR 406-C Commercial IRB Report Cover Sheet
FO 301-L Request for Deferral
Attachment I - Definitions
X.
RESPONSIBILITY
IRB Chairperson
IRB Administrator
XI.
APPROVAL BODY
IRB Director
XII.
APPROVAL SIGNATURES
___________________________________
Name
Title
Indiana University Health Bloomington
_________________
Date
XIII.
DATES
Approval Date:
Effective Date:
August 2006
August 2006
Review/Revision Dates: October 2006, July 2012, August 2013
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