1. DAIDS Safety Workshop: Part III Expedited Reporting via DAERS
Albert Yoyin, M.D. and Archita Chatterjee, M.S.
DAIDS RSC Safety Office
Johannesburg, South Africa
29 Aug 2012

2. Objectives DAERS Overview New DAERS Features for v2.0 DAERS Usage
Common queries to sites
Case Study

3. DAERS DAERS: DAIDS Adverse Experience Reporting System
An integrated module that is part of the DAIDS Enterprise System (DAIDS-ES)
A secure, confidential, web-based system through which sites are required to submit expedited reports to DAIDS
For sites where DAERS has been implemented, all SAEs and supporting information will be submitted to DAIDS using the DAERS, unless the system is unavailable for technical reasons
Use DAIDS EAE Reporting Form if DAERS is not implemented

4. DAERS Overview DAERS system planning initiated in 2005
DAERS v1.0 online Jun 2008
Updates to the system ~q6 mos; v2.0 as of Jun 2012
DAERS Integration Group (DIG) meets regularly to address current technical issues and system changes
SMEs (DAIDS MOs, SPT, and RSC personnel) provide input to DAIDS-ES programmers
Monthly calls with all collaborators group (site personnel, DMCs, network representatives)

5. New Features in DAERS (v2.0 update)
DAERS Version 2.0 was implemented on 22 Jun 2012
Site-specific features:
Make specific fields (such as severity grade, status code, and status date) optional if event is not an SAE but is required to be reported to DAIDS, or is of sufficient concern to warrant informing DAIDS
Date of death field added; only required when the event being submitted indicates “Death”; otherwise field is disabled/grayed out
Force change of status date when changing status code/outcome for update reports

6. EAE Reports Submitted by Networks (Jan 2011 – Mar 2012)
Region-specific data – local to DRTE location
Total = 507

7. EAE Reports Submitted by Protocol (Jan 2011 – Mar 2012)
Region-specific data – local to DRTE location
Total = 507

8. Average DAERS Usage (Jan 2011 – Mar 2012)
Region-specific data – local to DRTE location

9. DAERS Usage by Protocol (Jan 2011 – Mar 2012)
Region-specific data – local to DRTE location

10. Non-DAERS Usage Sites unable to access DAERS
Inability to connect to Internet
DAERS system unavailable (e.g., down for maintenance)
Site personnel not authorized to access DAERS (e.g., have not taken DAERS training; no Physician Electronic Signature Attestation Form received for submitter)
Site personnel unable to access DAERS (e.g., forgot password)
Sites reporting on older “SAE” reporting category protocols (e.g., P1020A and P1026s)

11. Late Submissions to RSC
Waiting for additional information (e.g., discharge summary, lab reports, etc.)
Reportability (e.g., questions regarding the reportability of an event; sites unaware that multiple reports are required when multiple Primary AEs were identified)
System access (e.g., inability to connect to the Internet or to DAERS)
SAE was overlooked as needing to be reported
No back-up submitter available

12. RSC Queries to Sites Total = 109
3 months worth of data from 5 different sites in the DRTE area
Total = 109

13. Breakdown of RSC Queries to Sites
Narrative (e.g., medical history/event details; AE status/resolution; treatment/management for AE)
Reportability (e.g., justification for ICH SAE criteria, severity grade, and/or relationship assessment)
Primary AE term (e.g., reporting ambiguous terms or multiple AEs in one term; ICH SAE criteria as AEs)
Missing info (e.g., source documents, con meds, CD4 count/viral load, enrollment date)
Other (e.g., PI signature, amending onset date, amending status/status date)

14. Examples of RSC Queries to Sites
Ambiguous AE terms which cannot be coded in MedDRA
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 and stop dates)
Missing information (e.g. lab results, diagnostic test results, con meds, supporting information such as progress notes, death certificates)

15. Case Study: Intrauterine Fetal Demise
CASE STUDY TO BE REVIEWED FOR 5 MINUTES

16. Case Study: Intrauterine Fetal Demise
6 Jun 2011: 31 year old, HIV infected Black female enrolled in 1077BF (PROMISE)
17 Jun 2011: subject was ~ 20 wks. pregnant and presented to the hospital with lower abdominal pain (Grade 2), vaginal bleeding (Grade 2), and abdominal contractions
BP: 142/72 mmHg, Pulse: 140 bpm, T: 35.9°C, and Hgb: 9.5 g/dL
US confirmed no fetal heartbeat and no liquor
Later on the same day, the subject’s fetus was expelled; the placenta and membranes were noted as healthy and complete

17. Case Study: Intrauterine Fetal Demise
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
17 Jun 2011
Date serious adverse event (SAE) occurred
Date site aware event occurred at a reportable level

18. Case Study: Intrauterine Fetal Demise
Timeline for Submission: Must submit within 3 ‘reporting days’ of site awareness
June 2011
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
Site
Awareness
(2 PM local time)
Report Due
(11: 59 PM Local Time)

19. Case Study: Intrauterine Fetal Demise
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
Intrauterine fetal demise
Severity Grade
Grade 3 (Severe)

20. Case Study: Intrauterine Fetal Demise
Primary Adverse Event (cont’d)
Onset Date: The date the primary adverse event first occurred at the level requiring expedited reporting
17 Jun 2011
Country of AE Origin: The country where the event occurred; may not necessarily be where the site is located
South Africa

21. Case Study: Intrauterine Fetal Demise
Primary Adverse Event (cont’d)
Status Code at Most Recent Observation: The status code of the subject at the most recent observation
Recovering/Resolving
Status Date: Date of the most recent observation of the subject
Date should be on or after the site awareness date
Date of most recent observation for subject status can be at or after the site is aware of the occurrence of the event
17 Jun 2011

22. Case Study: Intrauterine Fetal Demise
Case Narrative
Provide information on reported Primary AE
Describe:
clinical course
therapeutic measures
outcome
relevant past medical history
concomitant medication(s)
alternative etiologies
any contributing factors
all other relevant information

23. Case Study: Intrauterine Fetal Demise
Study Agent 1
Lopinavir/Ritonavir
Study Agent 2
Lamivudine/Zidovudine

24. Case Study: Intrauterine Fetal Demise
Study Agents
Not a free text field
Choose study agent from drop down menu of smart text field
Study Agent 1: Lopinavir/Ritonavir
Study Agent 2: Lamivudine/Zidovudine

25. Case Study: Intrauterine Fetal Demise
Study Agents (cont’d)
Relationship of Study Agent 1 to Primary AE
Related
Dose and Unit of Measurement
200/50 mg
Date of First Dose
6 Jun 2011
Date of Last Dose: The date the subject took the last dose prior to the onset of the adverse event
16 Jun 2011

26. Case Study: Intrauterine Fetal Demise
Study Agents (cont’d)
Exposure to and duration of use of study agent is important information to assess the case
Ensure accuracy of information
If unsure, please notate that the date is estimated

27. Case Study: Intrauterine Fetal Demise
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 action with the study agent only after the site is aware the AE has occurred at a reportable level
17 Jun 2011
If action taken is “Course completed or Off Study Agent at AE Onset,” action taken can be left blank

28. Case Study: Intrauterine Fetal Demise
Concomitant Medications:
Folic Acid
Ferrous Sulfate
Amoxicillin
Other Events: List other clinically significant signs and symptoms that more fully describe the nature, severity, and/or complications of the Primary AE
Abdominal Pain
Vaginal Bleeding

29. Case Study: Intrauterine Fetal Demise
Laboratory Tests:
Hemoglobin
Diagnostic Tests:
Abdominal ultrasonography

30. Teaching Points
Mandatory reporting fields for DAERS does not equal adequate information about the case
Not just what the system (i.e., DAERS) requires as mandatory fields:
Participant ID Site ID Protocol ID
Protocol version Site Awareness date SAE Criteria
Primary AE Severity Grade Onset Date
Status Code Status Date Narrative
Study Agent/Product Relationship Dosing details
Other events Reporter name Reporter

31. Case Study: Intrauterine Fetal Demise
Reporter: Completes and sends the report for final review
Submitter: Reviews and submits the Report to DAIDS
notification of expedited report submission sent to CRS staff and other key stakeholders
Site responsibility to ascertain that the report was, in fact, submitted

32. Case Study: Intrauterine Fetal Demise
UPDATE

33. Case Study: Intrauterine Fetal Demise
Primary Adverse Event
Status Code at Most Recent Observation:
Recovered/Resolved
Status Date: Date of the most recent observation of the subject
20 Jun 2011
Case Narrative
18 Jun 2011: discharged from hospital
20 Jun 2011: evaluated in study clinic
Additional Information
Upload discharge summary

34. Case Study: Intrauterine Fetal Demise
Submission of UPDATE
Completion Check to put the EAE Report in “Ready for Final Review Status”
Click “View PDF Report” to verify your edits have been made
Update status code and status date
Update case narrative
Additional Information
Submitter will review the report and Submit through DAERS

35. How to Report to DAIDS Reports must be submitted via DAERS:
DAERS via web:
For emergency use only:
FAX:
or (USA only)
If ing, scan or FAX signature page

36. Confirmation of Receipt
DAERS will send a confirmation for all SAE reports
It is the site’s responsibility to follow up if they do not receive a confirmation
**An is generated from DAERS both for getting the EAE Report in Ready for Final Review status (Reporter and Submitter only) as well as when the EAE Report is Submitted by the Submitter (CRS Coordinator, CRS Leader, Submitter, Reporter, anyone else indicated in the system on the Submission page)

37. Where to Get Help RSC Safety Office:
Telephone:
or (USA only)
FAX:
or (USA only)
RSC Website:
DAIDS-ES Support:
Telephone:
or (USA only)
FAX:
For reporting and timeline questions – RSC Safety Office
For DAERS system/technical questions – DAIDS-ES Support

38. Questions?