Adverse Event Reporting

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Adverse Event Reporting

• Kathleen M. Swanson, M.S., R.Ph.
• Assistant Center Director,
• Regulatory Affairs and Clinical Compliance Group
• Cooperative Studies Program

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Objectives

• Protect human subjects involved in research
• Roles in reporting
• Policies, regulations, and guidelines
• Communication pathway
• Examples

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Protect Human Subjects

• Why report safety information
• Protect rights and well-being of human subjects
• Accurate verifiable data collected according to
  protocol

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Roles in Reporting

• Role of three parties in safety reporting
• Site investigator
• Investigational Review Board (IRB)
• Sponsor (investigator, drug company, Cooperative
  Studies Program)

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Roles in Reporting

• Role of site investigator
• Provides appropriate medical and scientific
  judgment of adverse events
• Serious
• Related
• Report adverse events identified in the research
  to sponsor and local IRB

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Roles in Reporting

• Role of site investigator
• Related
• The most important problem in assessing adverse
  drug reactions (ADRs) is whether there is a
  causal relationship between the drug and the
  untoward clinical event.
• Naranjo, CA, et al. A method for estimating the
  probability of adverse drug reactions. Clin
  Pharmacol Ther 1981 30(2)239-45.

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Roles in Reporting

• Challenges of site investigator
• Definition of serious event
• Differences in data collection between protocol
  and IRB requirements
• Time frames for reporting
• Association between event and investigational
  treatment (relatedness)
• Reporting events from sponsor

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Roles in Reporting

• Interface site investigator and local facility
• Relatedness
• Known versus unknown risks to patient
• Documentation in patients medical record
• Changes to informed consent
• Continuation of research

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Roles in Reporting

• Role of Investigational Review Board (IRB)
• Review safety of trial
• Conduct continuing review of ongoing trials
• May review Data Safety and Monitoring Report
• Unblinded data
• May request additional information
• Ensure communication

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Roles in Reporting

• Challenges of Investigational Review Board
• Complement but not duplicate sponsors activities
• Impact on patient care
• Information sharing
• Multi-center trials

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Roles in Reporting

• Interface IRB and local facility
• Communication
• Patient Safety Department
• Patient Care
• Chief of Staff/Director
• Timely decisions
• Systems approach

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Roles in Reporting

• Role of sponsor
• Promptly review serious adverse event information
  from any source
• Expedited reporting when required
• Report changes in safety profile to local
  investigators

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Roles in Reporting

• Challenges of sponsor
• Complete and accurate reporting of adverse event
  data
• Timeliness of reports
• Determining unexpected events

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Roles in Reporting

• Interface sponsor and local facility
• Contact with local facility is through site
  investigator
• Report all safety data to protect sponsor from
  legal action

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Policies, Regulations Guidelines

• Code of Federal Regulations
• CFR Title 21 Part 50 Protection of Human Subjects
• CFR Title 21 Part 56 Institutional Review Boards
• CFR Title 21 Part 312 Investigational New Drug
  Application
• CFR Title 21 Part 812 Investigational Device
  Exemptions

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Policies, Regulations Guidelines

• International Conference on Harmonization (ICH)
  Guideline
• E6 Good Clinical Practice
• E2A Clinical Safety Data Management Definitions
  and Standards for Expedited Reporting
• VHA Handbook 1200.5 Requirements for the
  Protection of Human Subjects in Research

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Policies, Regulations Guidelines

• VHA Handbook 1058.1 Reporting Adverse Events in
  Research to the Office of Research Oversight
• CSP Global Operating Procedure (SOP 3.6.1)
• These outline
• Role of three parties
• Expedited reporting to sponsor and/or regulatory
  authorities

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New ORO Reporting Guideline

• VHA Handbook 1058.1
• Entitled Reporting Adverse Events in Research
  to the Office of Research Oversight
• Issued Nov 19, 2004
• Facility to report certain adverse events in
  research to ORO

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New ORO Reporting Guideline

• Report
• ALL AEs or imminent threats of AEs that result in
  IRB substantive action or unexpected death
• Policy Definition of AE
• Untoward occurrence, unfavorable or unintended
  event
• Reporting timelines
• 10 working days of IRBs substantive action
• 24 hours of unexpected death

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Proposed FDA Guidelines

• Open Hearing Public Meeting March 21, 2005
• Clinical Trial Adverse Event Reporting to IRB
• CIOMS VI recommendations
• Aggregate data not individual reports
• External information provided in summary form

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Policies, Regulations Guidelines

• Interface policy and local facility
• Clearly define time frames
• Outline responsibilities
• Inform appropriate individuals
• Chief of staff, Director, ORO
• Impact on patient safety activities
• Triaging mechanism for more serious events
• Involvement of investigator

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Communication Pathway

• Site investigator becomes aware of event
• Determination if reportable under protocol
• Determination if reportable to IRB
• Case report form (CFR) completed
• Local IRB paperwork completed

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Communication Pathway

• Communication with other departments and
  individuals
• Decisions status of research, status of impact
  on patient care, role of investigator
• Possible informed consent protocol changes

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Examples

• Local management of serious adverse event
• Local management of information on adverse event
  provided by the sponsor to the site investigator
• Local management of safety data provided in
  summary

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Cracks in the Adverse Event Communication Pathway

• Immediate review
• Ensure safety of patients enrolled in trial
• Communication within the facility
• Communication to sponsor
• Decision to continue research
• Ongoing review of research

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Adverse Event Reporting

• Questions ?