DAIDS Safety Workshop: Part III Expedited Reporting via DAERS

1. DAIDS Safety Workshop: Part IIIExpedited 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) Total = 507

7. EAE Reports Submitted by Protocol(Jan 2011 – Mar 2012) Total = 507

8. Average DAERS Usage(Jan 2011 – Mar 2012)

9. DAERS Usage by Protocol(Jan 2011 – Mar 2012)

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

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

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 • 17 Jun 2011 • Date site aware event occurred at a reportable level • 17 Jun 2011

18. Case Study: Intrauterine Fetal Demise Timeline for Submission: Must submit within 3 ‘reporting days’ of site awareness June 2011 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 • Primary Adverse Event • 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

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 E-mail

31. Case Study: Intrauterine Fetal Demise • Reporter: Completes and sends the report for final review • Submitter: Reviews and submits the Report to DAIDS • E-mail 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: https://daidses.niaid.nih.gov/Phoenix • For emergency use only: • FAX: +1-301-897-1710 or 1-800-275-7619 (USA only) • E-mail: DAIDSRSCSafetyOffice@tech-res.com • If e-mailing, scan or FAX signature page

36. Confirmation of Receipt • DAERS will send a confirmation e-mail for all SAE reports • It is the site’s responsibility to follow up if they do not receive a confirmation e-mail

37. Where to Get Help • RSC Safety Office: • E-mail: DAIDSRSCSafetyOffice@tech-res.com • Telephone: +1-301-897-1709 or 1-800-537-9979 (USA only) • FAX: +1-301-897-1710 or 1-800-275-7619 (USA only) • RSC Website:https://rsc.tech-res.com • DAIDS-ES Support: • E-mail: DAIDS-ESSupport@niaid.nih.gov • Telephone: +1-240-499-2239 or 1-866-337-1605 (USA only) • FAX: +1-301-948-2242

38. Questions?