EAE Training EAE Reporting and Assessment Overview

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EAE TrainingEAE Reporting and Assessment Overview

• DAIDS Regional Training Event,
• Regulatory Compliance Center
• Kampala, Uganda, September 2009

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Objectives

• Definitions
• Assessment of Adverse Events
• EAE Reporting

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EAE Reporting Materials

• EAE Manual
• EAE Reporting Form
• EAE Reporting FormCompletion Instructions
• AE Grading Table
• Protocol

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Definitions
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Expedited Adverse Event (EAE)

• An adverse event that meets the criteria for
  expedited reporting to Division of AIDS (DAIDS).
• DAIDS recognizes there are differences between
  events that require expedited reporting to DAIDS
  and SAEs as defined by ICH.

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Suspected Adverse Drug Reaction (SADR)

• All noxious and unintended responses to a
  pharmaceutical product related to any dose, and
  to which a causal relationship between the
  product and the event cannot be ruled out.

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Serious Adverse Event (SAE)

• Definition for SAE is per ICH E2A
• Certain DAIDS protocols will have expedited
  reporting of all SAEs
• Protocols A5241, MTN 003, P1066, P1060, to
  mention a few.
• Protocols in development pharma partners have
  reporting obligations as the MAHs of their drugs

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Assessment ofAdverse Events
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Assessment

• Study physician listed on the1572 / Investigator
  of Record (IoR)
  Agreement assesses the
  events
• Seriousness
• Severity
• Relationship
• Expectedness(only applies to Targeted)

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Serious versus Severe

• Seriousness is based on outcome of the AE and is
  a factor in determining reportability (this is a
  regulatory definition)
• Results in death or is life-threatening
• Hospitalization
• Disability or Congenital Anomaly
• Medically important
• Severity refers to the intensity of the
  experience (this is a medical description of the
  AE)
• (e.g. Mild, moderate, or severe headache)

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Severity

• Events are graded on a severity scale of 1-5
• 1 Mild
• 2 Moderate
• 3 Severe
• 4 Potentially Life-threatening
• 5 Death

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Grading Severity of Events

• Division of AIDS (DAIDS) Table for Grading the
  Severity of Adult and Pediatric Adverse Events
  (Version 1.0) December 2004
• Web Site http//rcc.tech-res.com

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EXAMPLE FROM THE DIVISION OF AIDS TABLE FOR
GRADING THE SEVERITY OF ADULT AND PEDIATRIC
ADVERSE EVENTS
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EXAMPLE FROM THE DIVISION OF AIDS TABLE FOR
GRADING THE SEVERITY OF ADULT AND PEDIATRIC
ADVERSE EVENTS
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EXAMPLE FROM THE DIVISION OF AIDS TABLE FOR
GRADING THE SEVERITY OF ADULT AND PEDIATRIC
ADVERSE EVENTS
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Relatedness

• Judgment of a relationship between AE and study
  agent.
• An event is assessed as
• Definitely related
• Probably related
• Possibly related
• Probably not related
• Not related
• Pending relationship
• to the study agent

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Relatedness

• Pending
• Only for a death and while information about
  death is being obtained.
• Updated relationship assessment required within 3
  business days or the event will automatically be
  coded as Possibly Related.
• Follow-up information should be submitted when
  available, especially if it results in a change
  to the relationship assessment.

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Levels of AdverseEvent Reporting

• The protocol will specifyone of three levels
  ofadverse event reporting
• Standard
• Intensive
• Targeted

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Levels of AdverseEvent Reporting - Summary
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Additional Adverse Events To Be Reported

• Serious Adverse Events associated with study
  participation or procedure.
• SADRs that do not meet the protocol specific
  reporting criteria, but that the investigator
  believes are of significant concern to be
  reported on an expedited basis to DAIDS.

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EAE Reporting Period

• Entire study duration for an individual subject
  (from enrollment until study completion or
  discontinuation for that particular subject).
• or as specified in the protocol.

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EAE Reporting Period

• After the EAE Reporting Period, only the
  following should be reported
• Unexpected, Serious, Clinical SADRs
  If the study staff becomes aware of
  their occurrence on a passive basis (i.e. through
  publicly available information, not active follow
  up)
• Example Obituary in the newspaper

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EAE Study Physician signature

• Physician signature signifies physician review
  and sign off
• The EAE report may be sent in without the study
  physician signature, if necessary.
• BUT
• The completed signature page must be submitted to
  the RCC Safety Office within 3 business days of
  submitting the original EAE.

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EAE Reporting Timeframe

• Within 3 business days of site awareness that an
  event has occurred at a reportable level.

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Confirmation Of Receipt

• The RCC Safety Office sends a confirmation email
  for all new reports.
• It is the sites responsibility to follow-up if
  they do not receive a confirmation email.

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New vs. Follow-up reports

• New
• A reportable event first occurs.
• An ongoing event increases in severity to a
  higher grade than previously reported.
• An event fully resolves to baseline status and
  then recurs at a reportable level.

• Follow-up
• DAIDS requests additional information.
• Study physician changes assessment of
  relationship to study agent.
• Additional significant information becomes
  available (e.g. autopsy report, death
  certificate).
• Results of rechallenge.

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How to Report EAEs

• Reports must be submitted on theEAE form
  available on the RCC Web sitehttp//rcc.tech-res.
  com/.
• DAERS DAIDS AE Reporting System web-based
  electronic submission
• If reporting via DAERS, no paper form needed

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How to Report EAEs

• Reports may be submitted via FAX, E-mail or
  DAERS
• FAX [phone] or 1-800-275-7619 (USA
  only)
• RCCSafetyOffice_at_tech-res.com
• If e-mailing, scan or FAX signature page
• DAERS via web

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Overview of Reporting Timelines
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Where to Get Help

• RCC Safety Office
• E-mail RCCSafetyOffice_at_tech-res.com
• Telephone [phone] or 1-800-537-9979
  (US Only)
• FAX [phone] or 1 -800-275-7619 (US
  Only)
• RCC Web Site http//rcc.tech-res.com