Expedited Reporting/DAERS May 13, 2011 Oluwadamilola Ogunyankin, M.D. Chinedum Abanobi, M.D. DAIDS Regulatory Support Center (RSC) Oluwadamilola Ogunyankin,

Expedited Reporting/DAERS May 13, 2011

Expedited Reporting/DAERS May 13, 2011

Oluwadamilola Ogunyankin, M.D.Chinedum Abanobi, M.D.

DAIDS Regulatory Support Center (RSC)

Oluwadamilola Ogunyankin, M.D.Chinedum Abanobi, M.D.

DAIDS Regulatory Support Center (RSC)

DAERS UsageDAERS 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 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 SinusitisCase Study: Acute Sinusitis

CASE STUDY TO BE REVIEWED FOR 10 MINUTES

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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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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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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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Timeline for Submission: Must submit within 3 ‘reporting days’ of site awareness

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Sunday Monday Tuesday Wednesday

Thursday Friday Saturday

1 2 3 4 5 6 7

8 9 10 11 12 13 14

15 16 17 18 19 20 21

22 23 24 25 26 27 28

29 30 31

Report Due (11: 59 PM Local Time)

April 2011

Site Awareness(2 PM local time)


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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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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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 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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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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•emtricitabine/tenofovir disoproxil fumarate

Study Agent 1

[oral formulation]

•darunavirStudy Agent 2

[oral formulation]

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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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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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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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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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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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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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UPDATE TO BE

REVIEWED FOR 2 MINUTES

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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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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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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 post-discharge

– 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 SitesExamples of RSC Queries to Sites

Ambiguous AE terms which are not codable

The reporting of “hospitalization” as an adverse event instead of reason for hospitalizationThe 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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Documents

Expedited Reporting/DAERS May 13, 2011 Oluwadamilola Ogunyankin, M.D. Chinedum Abanobi, M.D. DAIDS Regulatory Support Center (RSC) Oluwadamilola Ogunyankin,