NCI

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NCIs Role as Sponsor of ACRIN Clinical Trials
Regulatory Considerations
American College of Radiology Imaging
Network Fall Meeting

• Barbara A. Galen, MSN, CRNP, CNMT
• Cancer Imaging Program, National Cancer
  Institute, U.S.A.

October 2-5, 2008 Pentagon City, Arlington,
Virginia
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Outline

• NCIs Relationship to ACRIN- sponsor and grantee
• Basis for regulation and oversight
• Key U.S. regulatory groups and regulations
• Cornerstones of government oversight
• Dr. Anna Edouard Current AE reporting process
• Ms. Shanda Finnigan New AdEERS imaging pathway
  for electronic AE reporting

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Division of Cancer Treatment and Diagnosis
Office of the Director, DCTD Biometric Research
Branch
Cancer Therapy Evaluation Program
Cancer Imaging Program
Radiation Research Program
Cancer Diagnosis Program
Developmental Therapeutics Program
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Sponsor and Grantee Cooperative Agreement-
linked U01s

• Partnership
• Stewardship
• Advice
• Technical assistance
• Coordination
• Programmatic/scientific functions
• Oversight of quality assurance and monitoring

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Basis for regulation/oversight

• To protect and ensure patient safety and data
  accuracy validity
• Principles of bioethics (The Belmont Report)
• Beneficence
• Duty to protect the welfare of participants
• Risk/benefits to individuals and communities
• Study design? Valid Findings? If not, NO BENEFIT
• Respect for persons
• Duty to respect autonomous persons, their
  choices, and their information
• Informed consent/Privacy of persons and
  confidentiality of information/Voluntary
• HIPAA
• Justice
• Duty to distribute benefits and burdens fairly
• Fair selection of individual/populations/
  opposite is exploitation

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U.S. Regulations

• 1991 adopted by 17 US federal agencies as
  Common Rule
• CFR Title 45 Part 46 Protection of Human Subjects
  Revised June 23, 2005
• 21 CFR 50 and 56
• Health Insurance Portability and Accountability
  Act 1996 (HIPAA)
• Office for Human Research Protections (OHRP)
• Food and Drug Administration (FDA)
• Centers for Medicare and Medicaid Services (CMS)
• Office of Civil Rights (OCR)

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Government Oversight

• The Common Rule (Title 45 CFR Part 46, Subpart A)
• Governed by Office for Human Research Protections
  (OHRP) 17 Fed Dept /Agencies
• Enforced by Office of Civil Rights (OCR)
• Sets standards for
• Informed Consent Process
• Formation and function of Institutional Review
  Boards
• Involvement of prisoners, children, and other
  vulnerable groups
• NIH and OHRP together strengthened in 2000
• Education and Training in human subjects
  protection
• Data and safety monitoring plans-all /boards for
  Phase III trials
• Audit informed consent process
• Clarify regulations regarding conflict of
  interest

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Government Oversight

• Title 21 CFR Parts 50 and 56
• Enforced by the Food and Drug Administration
  (FDA)
• IRB review
• Informed consent
• Participant protection
• Apply to any clinical trial that involves
• Investigational drug or imaging agent
• Biological product, or
• Device regulated by FDA- regardless of Federal
  Funding
• Periodically inspects IRB records and operations

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Protecting Participants

• Protection of Participants before the Trial
  Begins
• Scientific Review by the Sponsor
• Significance, Approach, Innovation, Investigator,
  Environment
• Institutional Review Board (IRB) Approval
• Informed Consent Document/Process
• Legal, regulatory, ethical concept

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Protecting Participants

• Protecting Participants During a Clinical Trial
• Informed Consent Process
• IRB- approval/monitor progress
• DSMB-monitoring/oversight
• Quality Assurance Monitoring
• Data quality/integrity
• Auditing
• Adverse Event Reporting

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Resources on the Web

• Cancer Imaging Program (CIP) http//imaging.cancer
  .gov
• The NCI Clinical Trials http//www.cancer.gov/clin
  icaltrials
• Human Subject Protections Education-web-based
  http//cme.cancer.gov/clinicaltrials/learning/huma
  nparticipant-protections.asp
• CFR Title 45 Part 46 Protection of Human Subjects
  Revised June 23, 2005
• http//www.access.gpo.gov/nara/cfr/waisidx_01/45c
  fr46_01.html
• 21 CFR 50 and 56 http//www.access.gpo.gov/nara/cf
  rwaisidx_01/21cfr50_01.html Also see sections
  12.1.1 and 12.1.2
• Agencies
• FDA http//www.fda.gov/
• CMS http//www.cms.hhs.gov/
• OHRP http//www.hhs.gov/ohrp/
• OCR http//www.hhs.gov/ocr/hipaa

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NCI Contacts

• Ms. Irenna Zubal 301-496-9531 zubalire_at_mail.nih.go
  v
• Ms. Barbara Galen 301- 496-9531
  bgalen_at_mail.nih.gov
• Dr. Lalitha Shankar 301- 496-9531
• shankarl_at_mail.nih.gov

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American College of Radiology Imaging
NetworkFall Meeting

• Current SAE Reporting Process Cancer Imaging
  Program Non-IND Studies

Dr. Anna Edouard Senior Safety and
Pharmacovigilance Specialist, Contractor Technical
Resources International, Inc October 2, 2008
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CIP SAE Reporting
Clinical Site
Requests Information (source documents)
Submits SAE report
TRI
Notifies (SAE receipt, info request)
Triages packet (SAE report, source documents)
ACRIN
Assesses SAE report
CIP
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CIP SAE Reporting

• Clinical site fills out appropriate sections of
  the SAE submission form
• Note For a 24-hour phone notification, follows
  up with a faxed SAE submission within 5 business
  days.
• Faxes SAE submission form with any additional
  information (supporting source documents) to
  [phone], attention CIP SAE Team.

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CIP SAE Reporting

• Clinical site follows up with an email to
  CIPSAEReporting_at_tech-res.com notifying team that
  an SAE form has been faxed.

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CIP SAE Reporting

• TRI retrieves the faxed documents (SAE report),
  notifies ACRIN and the CIP staff/ Medical Monitor
  (MM) of receipt, and triages the packet.
• TRI requests from the site any pertinent medical
  information necessary to evaluate the report.
• Sends SAE report, supporting documents, and
  newly-created tracking record to CIP staff via
  email for assessment.

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CIP SAE Reporting

• CIP staff reviews SAE report, signs Part A of
  tracking record electronically, and sends back to
  TRI who logs in the information and status of the
  report.
• CIP may request that TRI send a follow-up query
  to the site for additional information. ACRIN
  and CIP are copied on any emails sent to site
  requesting additional information.

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CIP SAE Reporting

• Once TRI is satisfied that all pertinent
  information has been received, the SAE report,
  tracking record, and supporting documents are
  forwarded via email to the MM for assessment. MM
  completes Part C of the tracking record and signs
  electronically. MM emails this tracking record
  back to TRI.

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CIP SAE Reporting

• Upon receipt of tracking record via email, TRI
  completes Part D and files the completed report
  electronically. The original hardcopy is sent to
  CIP for filing.

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Lessons Learned

• Follow-up email from clinical site to TRI after
  submission of paper document is inconsistent.
• Situations in which there are 2 or more SAEs
  being reported require a separate report to be
  completed for each event.
• Attributions for each SAE must be indicated on
  submitted reports (select 1-5 to indicate
  unrelated, unlikely, possible, probable,
  definite).

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Contact Information

• Anna Edouard, MD
• Tel. [phone]
• Fax [phone]
• Email aedouard_at_tech-res.com
• James Murray, PhD
• (CTEP AE Team Manager)
• Tel. [phone]
• Fax [phone]
• Email jmurray_at_tech-res.com

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Contact Information

• AdEERS Helpdesk (AdEERSMD)
• Tel. [phone]
• Email adeersmd_at_tech-res.com
• CIP SAE Reporting Desk
• Fax [phone]
• Email CIPSAEReporting_at_tech-res.com
• Adverse Event Expedited Reporting System (AdEERS)
• http//ctep.info.nih.gov Find clinical trial
  resources on right-hand side and click on AdEERS.

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American College of Radiology Imaging
NetworkFall Meeting

• AdEERS New electronic imaging pathway
  CIP/CTEP/CTIS

Shanda Finnigan, RN, BSN, CCRC Health Program
Specialist Contractor CTEP, DCTD, NCI October 2,
2008
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CTEPs Adverse Event page http//ctep.cancer.gov/
reporting/adeers.html
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AdEERS Application https//webapps.ctep.nci.nih.g
ov/openapps/plsql/gadeers_main.startup
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Contact Information

• Medical Questions/Help
• email adeersmd_at_tech-res.com
• phone [phone]
• fax [phone]
• Technical Questions/Help
• email ncictephelp_at_ctep.nci.nih.gov
• phone [phone]
• fax [phone]
• Shanda Finnigan, RN, BSN, CCRC
• email finnigas_at_mail.nih.gov