The Life Cycle of a Protocol Review Process

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The Life Cycle of a Protocol Review Process

• Office of Research Integrity
• Institutional Review Board
• Presented by the IRB Administrators
• Weill Cornell Medical College
• (Updated Feb. 2007)

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The Life Cycle of a PROTOCOL Review IRB Process

• Disposition/Status
• Approved
• Non-substantive
• Substantive
• Deferred
• Disapproved

New protocols Can be either dropped off at the
IRB office OR can be left at A-128 for pick up
and delivery to the IRB office by the deadline.
Submissions are then entered into the database
and assigned an IRB .
Issues letters are drafted and sent to the IRB
Director for final review and then sent to the
IRB Chair for signature.
IRB Administration receives response from the PI.
Issues letters are sent to the Principal
Investigator (P.I.)
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New IRB Protocols/Applications

• Expedite Protocols/Applications are pre-reviewed
  by IRB Administration and then are sent to the
  IRB Chair or Vice-Chair for an official review
  and approval. Expedite protocols are not reviewed
  at Committee meetings, therefore do not follow
  meeting deadlines.
• Research activities that (1) present no more than
  minimal risk to human subjects, and (2) involve
  only procedures listed in one or more of the
  categories found at the Office for Human
  Research Protection (OHRP) website
• http//www.hhs.gov/ohrp/humansubjects/guidance/ex
  pedited98.htm
• The expedited review procedure may not be used
  where identification of the subjects and/or their
  responses would reasonably place them at risk of
  criminal or civil liability or be damaging to the
  subjects financial standing, employability,
  insurability, reputation, or be stigmatizing,
  unless reasonable and appropriate protections
  will be implemented so that risks related to
  invasion of privacy and breach of confidentiality
  are no greater than minimal.
• How many copies of a new expedite protocol do I
  need to submit? Submit 1 original IRB expedite
  protocol/application and 3 copies of the
  following expedite protocol application,
  written consent, oral consent (if applicable),
  Study Specific Financial Disclosure Forms (for
  all investigators listed), the appropriate HIPAA
  forms, any questionnaires, data collection
  sheets, etc. 1 copy of the Human Research Billing
  Analysis Form (HRBAF) (the IRB office is
  responsible for collecting and forwarding this
  form to the Institute for Clinical Research)
• Expedite protocol/applications are assigned and
  reviewed by the following IRB Administrator
• P.I.s last name from A-L Lucie Koppelman at
  212-821-0650
• P.I.s last name from M-Z Cecilia Mero at
  212-821-0639

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New IRB Protocols/Applications

• Full Board Protocols/Applications are
  pre-reviewed by IRB administration (you may
  receive a call asking for any missing documents)
  and then prepared and assigned to an agenda for a
  full board committee review. Full board IRB
  protocols/applications must follow committee
  deadlines. IRB Committee deadlines are located at
  the IRB.
• http//www.med.cornell.edu/research/rea_com/irbsch
  edule.html.
• How many copies of a new protocol do I need to
  submit? Submit 1 original IRB protocol/application
  (the original is the copy with the Principal
  Investigator and the Department Chair signatures)
  and 26 copies of the IRB protocol/application and
  Consent/Assent Form (s). The IRB also requires 4
  copies of the following cover letter addressed
  to the IRB, Investigator Brochure (if
  applicable), Sponsor Protocol (if applicable),
  questionnaires, advertisement, surveys and,
  diaries etc., Study Specific Financial Disclosure
  Forms (for all investigators listed including the
  PI), the appropriate HIPAA forms, and the Human
  Research Billing Analysis Form (HRBAF) (the IRB
  office is responsible for collecting and
  forwarding this form to the Institute for
  Clinical Research)
• Can I submit the protocol without the Department
  Chair's signature? Yes. Do not hold up submitting
  an IRB protocol/application. We realize
  Department Chairs may not be available, so the
  signature page can be submitted after the
  deadline and should be submitted as soon as
  possible to the IRB office. All we need is the
  original signature page not 26 copies of it.
• Full Board Protocols/Applications are assigned
  and pre-reviewed by IRB Administration
• IRB Committee I Lucie Koppelman at 212-821-0650
• IRB Committee II Cecilia Mero at 212-821-0639

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Substantive/Deferred/Disapproved response to
questions must go through the following steps
After the IRB office receives the response from
the P.I. the Response to Questions are
pre-reviewed by IRB administration then the
response is assigned to the original Committee
that raised the issues.
APPROVED If response is approved IRB
administration sends the approval letter, stamped
consent/assent (s), and supplemental materials to
the P.I. If the contract is not finalized then a
notification memo is sent to the PI. The approved
documents are not released.

• Disposition/Status
• Approved
• Substantive
• Deferred
• Disapproved
• Non-substantive

OR
Issues letter sent
Non-Sub follows a different cycle
IRB Administration receives the response
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Response to Questions

• Please keep in mind that the IRB deadlines are
  set to provide appropriate time for IRB
  administration and IRB members to review the
  responses.
• How many copies do I submit? Submit 2 copies of
  the following (1 copy highlighted and 1 clean
  copy), cover letter (including a point-by-point
  response to all IRB issues that were raised), all
  revised documents as requested by the IRB issues
  letter highlighted with a yellow marker (for
  easier identification and reviewing), IRB
  protocol/application, consent/assent (s) forms,
  advertisementsetc.
• 2 copies of any other additional required
  documents requested by the IRB (sponsor
  materials, collaboration letters, e-mail
  correspondence, etc.)
• Deadline schedule http//www.med.cornell.edu/rese
  arch/rea_com/irbschedule.html
• Full board responses should be addressed
  accordingly
• IRB I Cheri Betancourt 212 821-0646
• IRB II Arlene Valentin 212 821-0619

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Disapproved Protocols

• If an IRB protocol/application is disapproved at
  a Committee meeting the P.I. will receive an
  issues letter detailing the reasons for
  disapproval.
• The IRB Committee will require a new
  protocol/application submission including a
  point-by-point response to the disapproval
  letter.
• Submission will be the same as a new
  protocol/application review the original and 26
  copies would have to be re-submitted.
• Upon receipt of new submission the new
  protocol/application will will receive a new IRB
  protocol/application number.

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Approved Pending

• Although a protocol/application may be approved,
  (having no outstanding issues with the IRB) the
  IRB office must have the following documents on
  file before the final approval letter and consent
  form(s) is released.
• Contract Execution if this is a sponsored
  research study of if you are receiving for the
  purpose of this study any drugs, devices, data,
  or material from a third party collaborator or
  subcontractor, please confer with the Institute
  for Clinical Research and/or the Grants and
  Contracts office regarding whether a written
  agreement must be executed before you may begin
  the study.
• Study Specific Financial Disclosure Forms
  disclosure forms for all investigators listed on
  the protocol/application are required. If there
  is a conflict the disclosure form along with a
  copy of the consent form are forwarded to the
  Conflicts Management office for review and
  approval.
• CITI Course in The Protection of Human Research
  Subjects all investigators listed are required
  to complete this exam.

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All protocols that have Non-Substantive Issues
must go through the following steps
Once IRB administration receives the response
from the P.I.
NON-SUBSTANTIVE Response to Questions go to IRB
Office. IRB administration sends the response to
the IRB Chair for review and approval or further
issues.
If IRB Chair determines status remains
NON-SUBSTANTIVE, then IRB staff sends out a minor
revisions letter
If IRB Chair Approves
IRB Chair Review
APPROVED If response is APPROVED IRB staff sends
out approval letter, stamped consent/assent(s),
and any supplemental documents.
PI response goes back to the IRB office for
review. This cycle continues until all issues
are approved.
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Review Process forRevisions/Continuing
Reviews/IRB Grant Reviews
APPROVED If response is APPROVED IRB
administration sends the approval letter, stamped
consent/assent(s), and any supplemental
documents.
OR
Major Revisions Continuing Review Grant
Review For Full Board meeting.

• Disposition
• Substantive, Non-substantive Deferred, Disapproved

Revisions/Continuing Reviews that qualify for
expedite review are reviewed and approved by the
IRB Chair or Vice-Chair. They do not require
review at a Full Board meeting.
After response are approved by Chairman
PI is sent an issues letter
Responses are assigned to the Committee that
raised the issues.
IRB Receives Response Letter from the PI.
Non-Substantive response go to the IRB Chair
OR
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Major Revisions

• Major revisions are changes to the design of the
  research plan, or major changes to the
  consent/assent form(s).
• If the submission needs to be reviewed at a full
  board committee meeting, the revision/amendment
  request will be put on the agenda on which ever
  committee is meeting next. All coordinators are
  welcome to call the IRB office at any time to ask
  which committee will be reviewing their revision
  request submission.
• Your cover letter should always include as much
  detail as possible, and most importantly list all
  changes that are being made and the rationale for
  doing so. For sponsor studies do not submit the
  sponsors summary of changes without a rationale
  written in the cover letter. Major changes to the
  study should always be incorporated into the IRB
  application and consent/assent(s) in the
  appropriate sections.
• Submit one copy of every document with any and
  all changes highlighted (yellow) and one clean
  copy for stamping, including the cover letter and
  any sponsor materials if applicable. Also please
  include two clean copies of the consent/assent
  form(s).
• Make sure that your clean copies are in fact
  truly clean to ensure that your documents can
  be returned to you in a timely fashion once the
  protocol has been officially approved.
• If you have any questions call
• IRB I Cheri Betancourt 212 821-0646
  IRB II - Arlene Valentin 212 821-0619

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Continuing Review

• If the protocol is Open (even if closed for
  subject accrual) Please submit 26 copies of this
  renewal form, 26 copies of the current IRB
  stamped consent form(s), 3 copies (two clean, one
  highlighted) of revised consent forms for
  stamping purposes (see question 25 of the
  Continuing Review Form), 3 copies of the Adverse
  Event Summary Table, GCRC Addendum, and DSMB
  reports (when applicable), 3 copies of the Study
  Specific Financial Disclosure Form for each
  investigator, one copy of the Research Billing
  Analysis Form and 3 copies of the IRB approved
  protocol application.
• If the protocol is Open, Data Analysis Only
  Please submit 3 copies of the renewal form, 3
  copies of the most recent stamped consent form,
  three copies of the Adverse Event Summary Table,
  GCRC Addendum, and DSMB reports (when
  applicable), 3 copies of the Study Specific
  Financial Disclosure Form for each investigator,
  one copy of the Research Billing Analysis Form,
  and 3 copies of the IRB approved protocol
  application.
• If the protocol is being terminated Please
  submit one copy of the renewal form.
• If you have any questions call
• Charles Castel at the IRB office 212-821-0645

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IRB Grant/Protocol Review

• Department of Health and Human Services (HHS)
  regulations at 45 CFR 46.103(f) require that each
  grant application or proposal for HHS-supported
  human subject research be reviewed and approved
  by the Institutional Review Board (IRB). The
  IRB's review ensures that all research described
  in the grant application or proposal is entirely
  consistent with any corresponding
  protocols/applications submitted to the IRB.
• Over the past several years, OHRP has identified
  numerous instances in which human subject
  research described in an application for HHS
  support differed significantly from the
  IRB-approved protocol that was claimed by the
  investigator to constitute the research in the
  application. In each case, the application added
  important elements (e.g., targeting of vulnerable
  subjects additional treatment arms different
  drug dosages additional collaborators or
  performance sites) that were ultimately
  implemented without IRB review and approval.
• How many copies do I submit? Submit 2 copies of
  the grant, 2 copies of a cover letter and 2
  copies of the IRB protocol/application
• IRB grant/protocol reviews are submitted to the
  next scheduled IRB Committee meeting.
• IRB I Cheri Betancourt 212 821-0646
  IRB II - Arlene Valentin 212 821-0619

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Minor Revision/Amendments requests

• Once the IRB office receives a request for a
  minor revision/amendment the submission is
  pre-reviewed by IRB administration and then a
  determination is made whether or not the revision
  request qualifies as a minor revision. If the
  revision submission qualifies for an expedite
  review the request is prepared for review and
  sent to either the IRB Chair or Vice Chair for an
  official review and approval.
• Some examples of minor revisions are minor word
  changes to the consent form, advertisement
  (flyers, posters, electronic advertisement), IRB
  protocol/application, and addition or deletion of
  co-investigators.etc.
• Any translated IRB approved consent form may
  qualify for an expedite review. However, any
  additions of consent forms to a protocol must be
  reviewed at a full board meeting.
• How many copies do I need to submit? Send a cover
  letter outlining the change. Attach a highlighted
  copy outlining exactly what is to be changed.
  Attach a clean copy (non-highlighted) for
  stamping.
• If you have any questions call
• Anika Penn at the IRB office 212-821-0656

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Adverse Eventshttp//www.med.cornell.edu/research
/rea_com/irb_adv.html

• Reporting Obligations
• Investigators must notify the NYPH-WMC IRB in
  writing within 5 working days of the occurrence
  of all serious and/or unexpected adverse events
  (AEs) in NYPH-WMC research subjects, whether or
  not the events are considered study-related. A
  summary table of serious and/or unexpected
  adverse events MUST accompany each report.
• All serious and/or unexpected adverse events that
  warrant reporting by the above definitions must
  also be summarized in the Continuing Review. The
  Continuing Review should contain an assessment of
  any AEs reported by the investigator to the FDA
  and other regulatory agencies since the time of
  the last review, whether or not the events were
  considered serious or unexpected at the time of
  their occurrence. In some circumstances,
  investigators may petition the IRB for an
  exemption from the routine reporting of specific
  adverse events. Exemptions may be granted from
  the reporting of events that would otherwise be
  considered serious, if they can be shown to be
  frequent and expected occurrences in the
  population under study.
• If you have any questions call
• Anika Penn at the IRB office 212-821-0656

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Contacts at the IRBResearch Subject Protection
IRB Office Main [phone]
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The End
Designed by Arlene Valentin