Protocol and Information Office (PIO) An Overview Cancer Therapy Evaluation Program

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Protocol and Information Office (PIO)An
OverviewCancer Therapy Evaluation Program
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National Cancer Institute

• The National Cancer Institute (NCI) is
• The largest of the Institutes that constitute the
  National Institutes of Health
• The largest sponsor of research on anti-cancer
  agent development
• Organized into the Office of the Director, one
  Center, and six Divisions, each specializing in a
  different aspect of cancer research.

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Protocol and Information Office (PIO)

• The Protocol and Information Office was created
  to serve as the central hub of information
  processing for maintaining the official files of
  all protocols in which CTEP is involved.

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Protocol and Information Office (PIO) (continued)

• The PIO manages the entire protocol process.
  Protocol processing begins with the submission of
  a clinical study via either a Letter of Intent
  (LOI) or a Concept Review. The PIO follows each
  protocol through the steps of the review and
  approval processes. Amendment changes,
  monitoring, correspondence, and receipt of a
  final published report are additional tasks of
  the PIO throughout the lifecycle of the protocol.

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Mission of the PIO

• The primary mission of the PIO is to facilitate
  the development of quality clinical trials in the
  most efficient and expeditious manner possible
  and to relieve the administrative burden related
  to clinical trial development and management on
  CTEP staff and the extramural community.

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PIO Operations

• In order to assist in meeting the mission of
  CTEP, the following services are in full
  operation
• Document management
• Keywords and milestones abstraction into the
  Enterprise System (CTEPs database for all
  protocol related activities)
• Education of all concerned parties regarding NCI
  programs, policies, and objectives related to
  clinical trial development and management
• Training of PIO staff, extramural investigators,
  and CTEP reviewers
• Administrative support, including document
  tracking, scientific writing, and technological
  discovery to streamline the protocol development
  process

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PIO Operations (continued)

• Support CTEP committees by organizing and
  preparing protocols for weekly Protocol Review
  Committee (PRC) and Investigational Drug
  Committee (IDB) meeting in which drug development
  strategies and related issues are discussed.
• Documentation accuracy and quality assurance (QA)
  to ensure that all official documentation is
  correctly noted and filed in database.
• Correspondence between CTEP and its investigators
  (protocol approval, Safety/Action Letters, etc.)
• Responding to questions from clinical sites

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The PIO Staff

• The PIO staff is comprised of
• 3 government staff
• Head of PIO
• Deputy Head of PIO
• Technical Assistant
• 10 contract staff
• Program Manager
• Deputy Program Manager
• LOI/Concept Coordinator
• 6 Protocol Specialists
• 1 Support Staff

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Types of Submissions - LOIs

• Letter of Intent (LOI)
• An investigators declaration of interest in
  conducting a Phase I or Phase II trial with an
  investigational drug
• LOIs should be submitted for all Phase I or Phase
  II trials that will utilize Division of Cancer
  Treatment and Diagnosis, CTEP supplied IND agents
• Once an LOI is approved by CTEP, a protocol
  submission is expected within 30 days
• LOI submission form (MS Word ) can be found on
  the CTEP Web site at http//ctep.cancer.gov/forms

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Types of Submissions - Concepts

• Concept
• Disease oriented Phase III proposals that are not
  fully developed research protocols
• Once a Concept is approved by CTEP, the Concept
  Coordinator guides the investigator to the timely
  30 day delivery of a protocol submission.
• Concept submission form (MS Word) can be found on
  the CTEP Web site at http//ctep.cancer.gov/forms
  

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Types of Submissions New Protocols

• New CTEP Protocol
• The detailed written plans of a clinical trial or
  experiment. A protocol must be approved by CTEP
  and the local IRB before any patients are
  enrolled (accrued/treated).
• Templates for all Phases of Clinical Trials are
  available on the Web site at http//ctep.cancer.g
  ov/guidelines/templates.html
• Initial submission of a protocol must include the
  following
• Cover letter from the Protocol Chair or PI
  stating the intent of the new submission
• Protocol Submission Worksheet (PSW) current
  version available on the web site at
  http//ctep.cancer.gov.forms/PSW
• One electronic paginated, legible protocol,
  including all appendices, if applicable

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Types of Submissions - New Protocols (continued)

• Patient Informed Consent (guidelines available on
  the web site at http//www.cancer.gov/ClinicalTri
  als/AGuidetoUnderstandingInformedConsent)
• The Protocol document should contain the
  following
• Title page including the title of the study,
  version date, local protocol number (if
  applicable), PI/Protocol Chair including name,
  address, phone number, fax number, and e-mail
  address and for DCTD-supplied IND drugs, a
  listing of each drug by name and NSC number
• Table of Contents (titles should match the body
  of the protocol)
• Body of Protocol (objectives, background,
  eligibility, etc.)
• Appendices (if applicable)
• Model Patient Informed Consent (if applicable)

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Types of Submissions - Revisions

• Revision
• Any protocol changes which occur before CTEP
  approval.
• All revised protocols submissions should include
• Cover letter from the Protocol Chair or PI
  identify by page AND section each change made to
  a protocol document. All responses to the
  Consensus Review/Follow-up Review or additional
  changes shall be described in a point-by-point
  format (i.e. Page 3, section 1.2, replace xyz
  and insert abc). The original change request
  letter shall be attached.
• A revised un-marked (without handwritten notes or
  highlights) copy of the protocol document
  INCLUDING all protocol attachments listed in the
  table of contents regardless of whether any
  changes occurred to these sections.

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Types of Submissions Revisions (continued)

• Informed Consent regardless of whether any
  changes occurred to this document.
• Protocol title page must include a Version Date
  that reflects the time-point of the most recent
  change to the document.
• OPTIONAL In addition to the above, you may
  include a revised copy of the protocol with all
  changes specified in the Revision cover letter
  highlighted throughout the document utilizing a
  word-processing program.

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Administrative Life of a Protocol at CTEP
3. Protocol is Sent to FDA and Distributed to
PDQ and Other Contractors

• PRC Reviewers Interact with
• the PI Through Consensus Review /
• Follow-Up Reviews
• Until Protocol is Approved
• (Revision Process)

4. Protocol is Activated By PI
5. Amendments are Received, Reviewed and
Approved/ Disapproved

• Status Updates
• Closures and Complete

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New Protocol Received

• PIO contacts PI requesting missing or corrected
  pieces of the protocol.
• Protocol processing is stopped until document is
  correct and complete

NO
Complete ?
Y E S

• Acknowledgement letter sent to PI and MAILTO
• Abstract data in database including CTEP
  Reviewers
• Copies distributed to Reviewers on Friday
• Schedule for Protocol Review Committee Meeting
  (PRC) in 2 weeks

PRC (every Thursday)
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PRC
Approved or Approved with Recommendations or Di
sapproved
Issues ?
NO
Letter to PI
Y E S
Pending
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Pending

• Consensus/ Follow-up Review sent to PI
  outlining changes
• that must be made prior to approval as well as
• recommendations which may or may not be made
• Site has 30 days to respond to CR and 2 weeks
  to
• respond to follow-up review

Complete?
Yes
NO

• Abstract data into Pats
• including the CTEP reviewers
• Quality Check
• Routed to reviewers

• PIO contacts PI requesting missing or corrected
  pieces of the protocol.
• Protocol processing is stopped until document is
  correct and complete

Approved or Approved with Recommendations or
Issues?
No
Yes
Letter to PI
Disapproved
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Types of Submissions - Amendments

• Amendment
• Any protocol changes which occur after CTEP
  approval.
• Amendment guidelines can be found on the CTEP Web
  site

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Types of Submissions- Amendments (continued)

• The following documentation MUST be included with
  every Amendment-request submission
• Cover letter from the Protocol Chair or PI
  identify by page AND section each change made to
  a protocol document. All changes shall be
  described in a point-by-point format (i.e. Page
  3, section 1.2, replace xyz and insert abc).
  When appropriate a brief justification for the
  change should be included.
• A revised un-marked (without handwritten notes or
  highlights) copy of the protocol document
  regardless of whether any changes occurred to the
  protocol INCLUDING all protocol attachments
  listed in the table of contents.
• Informed Consent regardless of which changes
  occurred to this document.
• Protocol title page shall include a Version date
  that reflects the time-point of the most recent
  change to the document.
• If the amendment is in response to a CTEP or FDA
  request for change the original change request
  letter shall be attached.
• OPTIONAL In addition to the above, you may
  include a revised copy of the protocol with all
  changes specified in the Amendment-request cover
  letter highlighted throughout the document
  utilizing a word-processing program.

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Amendment Received in PIO

• PIO contacts PI requesting missing or corrected
  pieces of the protocol.
• Protocol processing is stopped until document is
  correct and complete

NO
Y E S

• Abstract data in database
• Routed to appropriate reviewers
• Approved
• To FDA if appropriate

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Types of Submissions- Miscellaneous

• Status Notice/Protocol Status Update
• These are notices received in the PIO stating the
  status of a protocol (active, closed to accrual,
  closed to accrual and treatment, administratively
  completed, completed, or publication citation).
• Protocol Status Update form is available on the
  web site at http//ctep.cancer.gov/guidelines/tem
  plates.html
• IRB Approval
• Each investigator must meet the requirement of
  the Federal regulations for human subjects
  assurances and informed consent and for IRB
  review and approval.
• Evidence of IRB approval may be submitted to CTEP
  at any time in the review process. Each protocol
  must have documentation of IRB approval prior to
  CTEP approval.

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CTEP Web site and PIO Web page

• In order to better disseminate accurate and
  current information, the CTEP Web page is
  available to the public, investigators, and other
  Government officials as a resource
• ctep.cancer.gov
• E-mail is the preferred method of communication
  with the PIO
• PIO_at_ctep.nci.nih.gov
• Include the NCI Protocol number (if any) in the
  subject line of the e-mail.