Expedited Reporting/DAERS
May 13, 2011
Oluwadamilola Ogunyankin, M.D.
Chinedum Abanobi, M.D.
DAIDS Regulatory Support Center (RSC)
DAERS Usage
 6 month period (Oct 2010-Mar 2011)
 Protocols: MTN-003, A5257, HPTN 058, iPrEx, P1070
• 85% submitted via DAERS
• 15% required data entry by proxy by RSC
 PI signatures: 415 reports:
• 26 without signatures
– Within 3 reporting days: 15%
– Outside of 3 reporting days: 46%
– Still pending: 38%
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AEs Meeting Reportability Criteria
 Total AEs received: 415
• Meet reporting criteria: 340 (82%)
• Did not meet reporting criteria: 75 (18%)
 Why?
• Important to bring to attention of DAIDS anyway
• Not sure, wanted to be on the safe side
• Only reason for submission is per protocol specifications
for expedited reporting
 RSC can assist with questions on whether an event is reportable
or not
 Sending in just to be sure results in additional work at
RSC/DAIDS
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Case Study: Acute Sinusitis
CASE STUDY TO BE
REVIEWED FOR 10 MINUTES
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Case Study: Acute Sinusitis
 January 16, 2011 subject enrolled into study and
randomized to the oral arm.
 On April18, 2011, subject experienced severe
headache, nausea, dizziness, and loss of
appetite. She took aspirin and was relieved.
 On April 20, 2011, headache worsened, with
fever, face pain, nasal congestion, nasal
drainage, cough, and post nasal dripping.
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Case Study: Acute Sinusitis
 Lab work showed WBC of 15,700 cells/mm3 ,
frontal sinus x-rays showed air-fluid levels, and CT
scan showed thickened mucous membrane.
 She was admitted into the hospital for further work
up and a diagnosis of grade 3 acute sinusitis was
made.
 She was started on pethidine, gentamycin,
ibuprofen, and intravenous fluids.
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Case Study: Acute Sinusitis
 Reporter and Site Information
• Site Awareness Date: The date the site first became
aware of the adverse event occurring at a reportable
level
- Date adverse event (AE) occurred
- 18-Apr-2011
- Date serious adverse event (SAE) occurred
- 20-Apr-2011
- Date site aware event occurred at a reportable level
- 23-Apr-2011
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Case Study: Acute Sinusitis
 Timeline for Submission: Must submit within 3 ‘reporting days’
of site awareness
Sunday
Monday
April 2011
Tuesday
Wednesday
Thursday
Friday
Saturda
y
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2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
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23Site
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25
26
27
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Awareness
(2 PM local
time)
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Report
Due
(11: 59
PM Local
Time)
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Case Study: Acute Sinusitis
 Primary Adverse Event
• Seriousness Criteria
– Select appropriate ICH-SAE criteria
– More than one criteria can be selected
– Requires inpatient hospitalization or prolongation of
existing hospitalization
• Primary Adverse Event
– Acute Sinusitis
• Severity Grade
– 3-Severe
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Case Study: Acute Sinusitis
 Primary Adverse Event (Cont’d)
• Onset Date: The date the primary adverse event first
occurred at the level requiring expedited reporting
– 20-Apr-2011
• Country of AE Origin: The country where the event
occurred; may not necessarily be the same where the
clinical site is located
– South Africa
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Case Study: Acute Sinusitis
 Primary Adverse Event (Cont’d)
• Status Code at Most Recent Observation: The status
code of the subject at the most recent observation
– Not Recovered/Not Resolved
• Status Date: Date of the most recent observation of the
subject
– Date should be on or after site awareness date
• Date of most recent observation for subject status can be at
or after site is aware of the occurrence of the event
– 23-Apr-2011
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Case Study: Acute Sinusitis
 Case Narrative: Provide information on reported
primary AE
–Describe the clinical course, therapeutic
measures, outcome, relevant past medical
history, concomitant medication(s),
alternative etiologies, any contributing
factors and all other relevant information
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Case Study: Acute Sinusitis
 Study Agents
• Not a free text field
– Choices are available from the drop down menu
• To activate the drop down menu, start typing the first
few letters of a study agent
• Choose the specific study agent you are working on
–emtricitabine/tenofovir disoproxil
fumarate
–darunavir
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Case Study: Acute Sinusitis
Study Agent 1
• emtricitabine/tenofovir
[oral
disoproxil fumarate
formulation]
Study Agent 2
[oral
• darunavir
formulation]
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Case Study: Acute Sinusitis
 Study Agents (Cont’d)
• Relationship of Study Agent 1 to Primary AE
– Not Related
• Dose
– 2 tablets per day
• Date of First Dose
– 16-Jan-2011
• Date of Last Dose: The date the subject took the last
dose prior to onset of the adverse event
– Not provided
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Case Study: Acute Sinusitis
 Study Agents (Cont’d)
• Exposure to and duration of use of study
agent important information to assess the
case
• Ensure accuracy of information
• For dates, if you are unsure, please check
that it is an estimated date.
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Case Study: Acute Sinusitis
 Study Agents (Cont’d)
• Action Taken: Enter the study physician’s action taken
with the study agent after awareness of the SAE
– Continued Without Change
• Action Date: Date has to be on or after the site awareness
date i.e. study physician can take an action with the study
agent only after the site is aware the AE has occurred at a
reportable level
– 23-Apr-2010
– If action taken is “Course completed or Off Study Agent
at AE Onset” action date can be left blank
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Case Study: Acute Sinusitis
 Concomitant Medications:
• Aspirin
 Other Events: List other clinically significant
signs and symptoms that more fully describe the
nature, severity, and/or complications of the
primary AE
• Headache Grade 3
• Nasal congestion Grade 2
• Cough Grade 2
• Fever Grade 2
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Case Study: Acute Sinusitis
 Laboratory Tests
• White blood cell count = 15,700 cells/uL (Normal Range:
4,000-11,000)
 Diagnostic Tests
• X-ray of sinuses (21-Apr-2011)
– Frontal sinuses showed evidence of air-fluid levels
• Frontal CT scan (21-Apr-2011)
– Thickened mucous membrane
• X-ray of sinuses (23-Apr-2011)
– Result Pending
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Case Study: Acute Sinusitis
 Reporter: Completes and sends the report for
final review
 Submitter: Reviews and submits the report to
DAIDS
 Email notification of expedited report submission
sent to CRS staff and other key stakeholders
 Site responsibility to ascertain that the report
was in fact submitted
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Case Study: Acute Sinusitis
UPDATE TO BE
REVIEWED FOR 2 MINUTES
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Case Study: Acute Sinusitis
UPDATE
 Subject’s condition improved
 April 23, 2011, follow-up sinus x-ray results were
normal.
 Subject was discharged home from the hospital.
 Subject seen at the study clinic on April 25,
2011, with no complaints and with her discharge
summary.
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Case Study: Acute Sinusitis
 UPDATE
• Primary Adverse Event
– Status Code: Recovered/Resolved
– Status Date: 25-Apr-2011
• Case Narrative
• Diagnostic Tests
– X-ray (23-Apr-2011) Normal with absence of air-fluid
levels
• Additional Information
– Upload copy of the discharge summary (if available)
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Case Study: Acute Sinusitis
 Submission of UPDATE
• Update status code and status date
• Update case narrative
– Provide information on subject’s clinical course in hospital
– Provide information on subject’s assessment in clinic postdischarge
– Provide information on action taken with study agents by the
study physician post-discharge
• Additional Information
– Upload discharge summary and other relevant records
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Questions?
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Examples of RSC Queries to Sites
Ambiguous AE terms which are not codable
The reporting of “hospitalization” as an adverse event instead of reason for
hospitalization
The reporting of “death” as an adverse event instead of cause of death.
Wrong dates e.g. DOB, awareness, start, inconsistent with narrative
Errors in the selection of the SAE criteria e.g. Life threatening anemia but
assigned as Grade 2
Accurate information about study drugs e.g. dose, schedule, start, stop
dates
Missing information e.g. lab results, diagnostic test results, con meds,
supporting information such as progress notes, death certificates
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