Yale University Human Research Protection Program
920 PR.5 Use of National Cancer Institute Central IRB (CIRB) for
Review and Oversight of Research Involving Yale Investigators
Overview ...............................................................................................................................................................1
Protocols Qualifying for CIRB Review .................................................................................................................1
Protocol Submission Process .................................................................................................................................1
Review by Other Committees ................................................................................................................................2
Submission Documents ....................................................................................... Error! Bookmark not defined.
HIC Acceptance of the CIRB-Approved Protocol .................................................................................................3
Post HIC Acceptance of CIRB Approval ..............................................................................................................3
HIC Oversight........................................................................................................................................................4
Transfer of Active Studies .....................................................................................................................................4
Continuing Review Submission ............................................................................................................................4
Amendments ..........................................................................................................................................................4
Protocol Deviation Reporting ................................................................................................................................5
Adverse Event Reports and Unanticipated Problems ............................................................................................5
Overview
This procedure reviews the process for use of the National Cancer Institute’s Central IRB (NCI CIRB) for
IRB review and oversight National Cancer Institute research involving Yale investigators. Yale
designates both CIRBs on its Federal wide Assurance (FWA).
Protocols Qualifying for NCI CIRB Review
The HIC may authorize the acceptance of the NCI CIRB approval for NCI clinical trials.
Protocol Submission Process
Investigators requesting that the HIC authorize the NCI CIRB approval of a protocol are required to use
the protocol review process required by the Yale Cancer Center (YCC). Additionally, protocols utilizing
the services of the YCCI Hospital Research Unit (HRU), Church Street Research Unit (CSRU) and/or
Research Core Laboratory must be assessed for feasibility. Protocols will be assessed for risk and may
be assigned for review by the YCCI Science and Safety Committee (SSC). Protocols reviewed by the
SSC and all other protocols will undergo a resource review prior to issuance of a YCCI approval letter and
prior to the investigator requesting authorization of CIRB approval from the Human Investigation
Committee (HIC). Please refer to the YCCI for assistance. Review by other committees may be required,
as noted below. To open a trial through the NCI CIRB independent model, following steps must be taken:
1. The Principal Investigator (PI) identifies a study from the NCI CIRB website that s/he wishes to
conduct
2. The PI downloads and completes the Study Specific Worksheet
3. The NCI CIRB reviews material, approves Yale PI participation,
4. The NCI CIRB sends the PI an approval letter. The approval letter includes the Yale boilerplate
language that must be included in the consent/compound authorization (heading, HIPAA
language, etc.)
5. The PI downloads and modifies the consent/compound authorization, sends a copy of the
modified consent/compound authorization to the HIC.
6. The following are submitted to the HIC
 Study Specific Worksheet
 PI annual worksheet
 HRPP 920 FR 1 NCI CIRB Protocol Application Addendum
920. PR.5 Use of the National Cancer Institute Central IRB (CIRB)for Review and Oversight of Research Involving Yale
Investigators
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HRPP 920 FR 5 NCI CIRB Protocol Submission Face Sheet
Yale modified CIRB Consent/Compound Authorization form (2 copies)
All internal approvals (PRC, etc)
The CIRB approval letter
Any other CIRB documents received by the PI to open the study
7. The HIC reviews the materials, Reg analyst verifies training and COI; HIC I chair/co-chair
reviews and signs off
8. HIC stamps ICF/Compound Auth with acknowledgment stamp
9. The HIC generates a letter to the PI, noting CIRB approval and including any HIPAA waiver given
(e.g., for recruitment)
10. Study is now fully IRB approved.
The HIC is required to verify compliance with University training and financial disclosure requirements for
the study that the investigator wishes to conduct at the University. In addition, the HIC reviews specific
local information regarding pre-submission committee approvals, hospital billing and credentialing, data
and safety monitoring, targeted enrollment and confidentiality and security. This review is conducted by a
HIC Chairperson or a designated voting member of the HIC. The HIC must comply with OHRP guidance
that, "…an institution relying upon another institution's IRB has a responsibility to ensure that the
particular characteristics of its local research context are considered through subsequent review by
appropriate designated institutional officials, such as the Chairperson and/or other members of its local
IRB." To assess local context information, the HIC will review the information provided in the HRPP form
920 FR 1, “NCI CIRB Protocol Application Addendum” ,the CIRB principal investigator local context
information form and the CIRB study-specific local context information form. These forms must be
completed by the Yale Principal Investigator and submitted to the HIC. The Principal Investigator Local
Context form is completed annually. The study-specific form is completed when a new CIRB-reviewed
trial is opened at Yale.
The HIC has the authority to decide not to accept the NCI CIRB review and require that the investigator
submit the protocol for full HIC review. If the designated reviewer(s) does not accept the NCI CIRB
review, the NCI CIRB written materials may still be utilized as resources for the HIC review process.
Additions or deletions to the compound authorization regarding state and local law, institutional
requirements, or Yale and HIC policies are drawn by the NCI CIRB from the Yale boilerplate language
that has been supplied to them. Primary reviews, minutes, notification letters, and any other
correspondence generated by the CIRB are posted in a separate section of the CIRB web site for
participating institutions to access. See http://www.ncicirb.org/ for list of protocols, participating sites and
other information.
The NCI CIRB also conducts continuing reviews and reviews of serious adverse events (SAEs), Data
Safety Monitoring Board (DSMB) reports, protocol amendments, recruiting materials for national
recruitment initiative, etc. The NCI CIRB findings on these actions are posted on the CIRB web site for
prompt access by participating investigators and institutions.
The NCI CIRB distributes protocol activity updates to local investigators and IRBs to notify participating
institutions of status changes in protocols and other information relating to protocols such as, activation
and closure of CIRB protocols and drug notices and safety reports. These updates are provided on a bi
weekly basis. For more information see https://ncicirb.org/cirb/activityUpdates.action Review by Other
Committees
Yale University policies require that the following internal committees review protocols prior to IRB
submission. Documentation of approval from the following committees, when applicable, must be
included in the protocol submission packet submitted by the investigator to the HIC for facilitated review.
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920. PR.5 Use of the National Cancer Institute Central IRB (CIRB)for Review and Oversight of Research Involving Yale
Investigators
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The YCC Clinical Research Steering Committee (CRSC) reviews all concepts for clinical
research studies that will involve the use of YCC-supported centralized resources such as data
management and research nursing.
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Protocol Review Committee (PRC): Reviews all research conducted by Yale University faculty
that involves the use of the Yale Cancer Center. Reviews include new applications, requests for
continuing approval or renewals and major amendments.
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Science and Safety Committee (SSC)): Reviews all research conducted by the Yale University
faculty that utilizes the Hospital Research Unit (HRU) resources located at Yale New Haven
Hospital.
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Gene Transfer Subcommittee of the Institutional Biosafety Committee Reviews all research
involving human gene transfer products under the purview of the Recombinant DNA Advisory
Committee (RAC)
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The following committees must issue approval of studies before any study interventions
may take place. (See HRPP Policy 940 Radiation Safety Committee Review.)
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YNHH Radiation Safety Committee: Reviews all research involving human subjects at YNHH
and which also involves the use of any radioactive isotopes that are approved by the FDA and
used on or off label.
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YNHH Radioactive Drug Research Committee: Oversees the use of radioactive materials
which require no IND or FDA approval and which are prepared at the Yale Medical Center.
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Protocols Utilizing the Magnetic Resonance Research Center at the Anlyan Center:
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Any research protocol involving humans and the use of equipment, supplies, or space in the
Magnetic Resonance Research Center (MRRC) located in the TAC building, whether or not the
scan is standard of care, should be reviewed and approved by the MRRC- Protocol Review
Committee (MRRC-PRC) before the research can commence. Protocols that use magnetic
resonance techniques at other facilities, such as Yale-New Haven Hospital’s clinical facility, are
not subject to review by the MRRC-PRC. Instructions for submitting protocols to the MRRC-PRC
can be found at http://mrrc.yale.edu/users/index.aspx
HIC Acceptance of the CIRB-Approved Protocol
Once the HIC has reviewed the CIRB materials thee HIC will notify the principal investigator that the IRB
review is complete and the study may be opened at Yale.
The NCI CIRB posts a website summary twice each month of all IRB actions taken on the protocol, e.g.,
an SAE report provoking a change in the compound authorization form, an approved protocol
amendment, a change in the protocol/compound authorization resulting from the Continuing Review, etc.
The HIC will retain reviewer findings on each initial submission. The findings will serve as documentation
of requested compound authorization changes. The documentation will also serve as justification that the
proposed study is considered appropriate to be conducted at Yale University.
The HIC will notify NCI CIRB of any outstanding issues noted during reviews.
The investigator must send a copy of the Yale version of the NCI CIRB approved consent form and
appropriate HIC acknowledgement documentation to the Cooperative Group administering the protocol.
Post HIC Acceptance of CIRB Approval
Once a new application has been approved by the NCI CIRB the NCI CIRB is responsible for reviewing
and notifying Yale investigators and IRB staff of any changes, amendments, or modifications approved by
the NCI CIRB. The PI is responsible for ensuring that the NCI CIRB approval is received prior to any
amended procedures being implemented at Yale, and for submitting amendment information to the HIC.
The Yale PI is also responsible for ensuring that only updated and valid compound authorization forms
are used to enroll subjects into Yale protocols. All approved documents and consent forms must be
retained by the PI and/or their appointed study coordinators pursuant to good clinical practice and
confidentiality and security standards.
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920. PR.5 Use of the National Cancer Institute Central IRB (CIRB)for Review and Oversight of Research Involving Yale
Investigators
The NCI CIRB will also notify the Yale Principal Investigator, who is then responsible for notifying the HIC,
of any termination or suspension of a study. Yale will notify the NCI CIRB and the appropriate federal
oversight agencies of instances of serious or continuing noncompliance with the federal regulations.
HIC Oversight
The HIC maintains responsibility for the conduct of the reseach and will assume the local oversight
responsibility and perform local context functions in compliance with federal regulations and University
policy. These responsibilities include, but are not limited to, reviewing potential protocol-related conflicts
of interest, ensuring that all Yale researchers and staff are appropriately qualified to conduct the protocol
and are compliant with University training requirements, monitoring and/or auditing protocol records and
the consent process to ensure compliance with the protocol, ensuring that the protocol is conducted in
accordance with federal and university regulations and policies, and reporting any unanticipated problems
involving risks to subjects or others or any serious or continuing noncompliance to the NCI CIRB and
federal department agencies as required.
Transfer of Active Studies
Transferring IRB approval from the HIC to the NCI CIRB can occur when the following conditions have
been met:
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The study has been listed as approved on the NCI CIRB website.
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The Yale investigator has provided the HIC with the PI annual local context form, the studyspecific local context form, the NCI CIRB approval and the NCI CIRB modified
consent/compound authorization. The Yale investigator must provide appropriate notice to the
HIC that this will “close out” the Yale protocol. The investigator must note on the CIRB face sheet
that he/she wishes to transfer IRB review responsibilities to the NCI CIRB. The HIC reviewer has
reviewed and approved the submitted documentation, acknowledged the informed
consent/compound authorization and notified the PI that the IRB review is now complete.
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The HIC has modified the study record in Coeus.
Continuing Review Submission
The approval duration and anniversary date for an individual protocol is based on the date that the
protocol was reviewed by the NCI CIRB and not the date that Yale was added to the study. The NCI
CIRB will conduct the required subsequent review in such a manner so as to ensure continued approval
of the study.
Yale investigators and/or their appointed study coordinators/correspondents and IRB reviewers and staff
will be provided with an electronic notice of continuing review by the NCI CIRB via the bi-monthly website
posting.
Once the NCI CIRB has issued a notification of continuing review or re-approval, the PI must submit to
the HIC two copies of the NCI CIRB Request for Renewal form 920 FR 3 and the newly approved
compound authorization document in Yale format. The HIC will return to the Principal Investigator a
notice that it has accepted the NCI CIRB re-approval and the validated compound authorization
documents.
Amendments
Yale investigators, their appointed study coordinators/correspondents, IRB reviewers and staff will be
provided with an electronic notice of any changes, amendments, or modifications to protocols approved
by the NCI CIRB via the bi-monthly website posting, and accepted by the HIC,.
Once the NCI CIRB has issued a notification of the approval of an amendment the PI must submit to the
HIC two copies of the NCI CIRB amendment documentation and any newly modified compound
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920. PR.5 Use of the National Cancer Institute Central IRB (CIRB)for Review and Oversight of Research Involving Yale
Investigators
authorization documents in Yale format. An acceptance letter will be sent to the Principal Investigator
along with approved compound authorization document(s).
Personnel amendments Yale do not require CIRB review and must be submitted to the HIC for review.
The HIC maintains responsibility and authority for approval of these submissions.
Protocol Deviation Reporting
Yale Principal Investigators are required to report major protocol deviations and violations to the HIC, NCI
CIRB and as required by the sponsoring Cooperative Group. The HIC’s Protocol Deviation/Unanticipated
Problem Report Form can be found at http://yale.edu/hrpp/forms/index.html .
Adverse Event Reports
Adverse Event reports must be forwarded as required to the Cooperative Groups. Serious AND
unanticipated adverse events that occur at Yale and are possibly, probably or definitely related to the
subject’s participation in research must also be reported to the HIC within 48 hours using Form 710 FR 2
and to the NCI CIRB per NCI CIRB policy requirements.
Unanticipated Problems
Unanticipated problems occurring at Yale sites must be reported to the Cooperative Group, to the NCI
CIRB, and to the HIC as outlined in HRPP Procedure 710 PR 2, “UPIRSO Reporting”. For multi-site
studies where the Yale PI is not the lead PI, Unanticipated problems occurring at other sites do not need
to be submitted to the HIC.
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