Adverse Event AE

1
Adverse Event (AE)

• CTEP, NCI AE Definition
• Any unfavorable and unintended sign (including an
  abnormal laboratory
• finding), symptom, or disease temporally
  associated with the use of a
• medical treatment or procedure regardless of
  whether it is considered
• related to the medical treatment or procedure
  (attribution of unrelated,
• unlikely, possible, probable, or definite). Each
  AE is a unique
• representation of a specific event used for
  medical documentation and
• scientific analysis.

2
Investigator Responsibility

• Clinical investigators and ultimately the
  protocol Principal Investigator (PI) have the
  primary responsibility for AE identification,
  documentation, grading, and assignment of
  attribution. Source documentation is required.

3
CTCAE

• Currently, the CTEP, NCI Common Terminology
  Criteria for Adverse Events (CTCAE v3.0) is the
  tool (an AE dictionary) used to report AEs
• CTCAE v3.0 provides descriptive terminology along
  with a grading (severity) scale for each AE term
• CTCAE v3.0 is mapped to new Medical Dictionary
  for Regulatory Activities (MedDRA) versions each
  year (AdEERS will always be linked to the latest
  version)
• CTCAE v4.0 has been issued for public review and
  comments

4
AE Grade and Attribution

• Grade-
• Refers to the severity of the AE
• Grading Scale-
• 1- Mild AE
• 2- Moderate AE
• 3- Severe AE
• 4- Life threatening or disabling AE
• 5- Death related AE
• Attribution-
• The determination of whether an AE is related to
  protocol treatment(s) or procedure(s) .

5
CTEP Hospitalization Definition

• Hospitalization or prolongation of
  hospitalization associated with
• Grade 3 events, unexpected and expected, and
  regardless of
• attribution, require expedited reporting for
  trials utilizing an agent
• Under a CTEP IND.
• In-patient hospital stay equal to or greater than
  24 hours.
• Hospitalization is used as an indicator of the
  seriousness of the
• adverse event and should be reserved for
  situations where
• the adverse event truly fits this definition
  i.e., not for
• hospitalizations associated with less serious
  events, such as a
• hospital visit where a patient is admitted for
  observation or minor
• treatment (e.g., hydration, cosmetic surgery) and
  released in less than 24
• hours.

6
Adverse Event Expedited Reporting System (AdEERS)
7
Research Associate Responsibility

• Expedited reporting via AdEERs - The AE 24-hour
  notification requirement provides an early
  detection system for potential safety problems.
  AEs that must be reported (initiated) within
  24-hours of learning of the event are dependent
  upon phase of trial, the agent/intervention
  (investigational or commercial), whether the
  event is expected or unepected, the grade and
  attribution.
• AEs that fulfill the 24-hour reporting
  requirement must be reported electronically via
  AdEERS at http//ctep.cancer.gov

8
CTEP AE Reporting Table Phase 1
9
CTEP AE Reporting Table Phase 2,3
10
Acute Myeloid Leukemia (AML) or Myelodysplastic
Syndrome (MDS)

• AML or MDS that is diagnosed during or subsequent
  to treatment on NCI/CTEP-sponsored clinical
  trials must be reported using the NCI/CTEP
  Secondary AML/MDS Report Form available at
  http//ctep.cancer.gov/forms/index.html.
• This report must include the time from original
  diagnosis to development of AML/MDS,
  characterization such as FAB subtype,
  cytogenetics, etc., and protocol identification
  (RTOG study/case number).
• This form will take the place of a report via
  AdEERS system and must be faxed to the
  Investigational Drug Branch, FAX [phone],
  and mailed to RTOG Headquarters within 30 days of
  AML/MDS diagnosis.

11
Protocol-Specific Specialized Reporting (PSSR)

• Some protocols require certain
  medically-important AEs e.g., due to cancer
  being treated, due to protocol-specific
  treatment(s) or procedure(s) to also be reported
  in an expedited fashion via AdEERS.
• For example, often hemorrhage, regardless of
  grade, requirement for hospitalization, or
  attribution should be reported through AdEERS
  according to various protocols.
• The Protocol Rules!

12
Amending AdEERS Reports

• How do I know when to amend an AdEERS report
  versus creating a new report? 
• When events requiring AdEERS reporting occur for
  an individual patient multiple times during
• a single course (cycle), the report is to be
  amended. Additional events (or worsening events)
• will have a causal or temporal relationship to
  the event(s) documented in the Original Report,
• but not always.  However, CTEP physicians review
  every AdEERS report submitted to CTEP as
• part of their monitoring responsibilities for
  investigational agents.  It is essential for CTEP
• physicians to see the entire clinical
  circumstances per course/cycle.  Each course is
• associated with specific agents, dosages, etc. 
  Therefore, it is important to assess AdEERS
• reports by course/cycle.
• If multiple reports are submitted for a patient
  during a single cycle, you will be required to
  withdraw those reports, access the original
  report, and amend it.
• Later is always better than never!
•  

13
Proper Identification

• Proper identification of AdEERS reports,
  supporting documentation, and/or other relevant
• information is imperative and must always
  include RTOG Study and Case Number
• Almost every RTOG Study has a dash
• (e.g., RTOG-0625)
• Please use the RTOG Case Number as the Patient ID
  (i.e., no leading zeroes) in the AdEERS System

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Other Research Associate Responsibilities

• For every study, PLEASE remember to report all
  AdEERS AEs also on our RTOG Adverse Event Data
  Collection Forms. The AE data in our Clinical
  Trial Database must match exactly (especially the
  AE, start date, grade, and attribution).
• Also, please remember if youve amended your
  AdEERS report, if applicable, you must also amend
  the AE data youve reported on our RTOG AE Data
  Collection Forms.
• You will receive queries whenever inconsistencies
  are identified between your AdEERS report data
  and our AE Data Collection Form Data.

15
Guidance and/or Assistance with the AdEERS System

• It is VERY helpful to take the AdEERS Tutorial
  at the following link
• http//ctep.cancer.gov/reporting/adeers.html
• For all medical and policy related issues, please
  contact the AdEERS Content Help Desk by telephone
  [phone] (or email adeersmd_at_tech-res.com )
  
• For all technical and training related issues
  please contact the NCI CTEP Technical Help Desk
  by telephone [phone] (or email
  ncictephelp_at_ctep.nci.nih.gov )

16

• Stephen M. Dorian
• [phone]
• sdorian_at_phila.acr.org

17

• Thank you very much!
• ANY QUESTIONS?