Adverse Event Reporting

1. Adverse Event Reporting

2. Reporting Adverse Events • Adverse Events (AEs) are “. . . any untoward medical occurrence in a subject that was not previously identified which does not necessarily have a causal relationship to the study drug…” • Events existing prior to randomization should not be reported as AEs, unless there is a change in severity • AEs (both serious and non-serious) are reported on Form 05: Adverse Event CRF

3. Reporting Adverse Events • Report the diagnosis, not the symptoms: Fever, cough, chest pain, crackles = pneumonia • Death, surgery, intubation, etc. are not adverse events. They are outcomes of adverse events

4. Reporting Adverse Events • One AE = One AE CRF • New AEs should be documented on a new AE CRF • Follow up reports to previously submitted AEs need to be documented on the original AE CRF

5. Reporting Adverse Events From Randomization through 24 hrs: • Report all AEs From 24 hours through EOS: • Report only serious AEs • Follow any previously reported, unresolved AEs to resolution or end of study (whichever comes first)

6. Reporting Adverse Events Serious Adverse Events are: • Fatal, • Life-Threatening, • Result in hospitalization (prolonged hospitalization), • Result in disability/congenital anomaly, or • Require intervention to prevent permanent impairment or damage

7. Data Entry Time Lines for AEs • Non-serious AEs must be submitted into WebDCUTM within 5 days of data collection. • Serious AEs must be submitted into WebDCUTM within 24 hours of discovery - In addition, any other relevant data collected for that subject should be entered into WebDCUTM

8. Reporting SAEs SAEs require additional information to be submitted: 1. Detailed description of the event (Description of what happened and a summary of all relevant clinical information -medical status prior to the event, signs and/or symptoms, differential diagnosis for the event, clinical course, treatment outcome, etc) 2. Relevant tests/laboratory data 3. Relevant history and pre-existing conditions 4. Concomitant meds

9. Reporting SAEs • These narratives assist the Medical • Safety Monitor in reviewing the event • Narratives are pre-populated into the MedWatch form, if expedited reporting is required • Do not identify any subject, physician, or institution by name.

10. Reporting SAEs • Site data enters and submits AE CRF into WebDCUTM • Automatic e-mail notification to Project Manager (PM) and Internal Medical Monitor (IMM) • PM and IMM review narrative - - If AE data is sufficient, an automatic email notification will be sent to the Medical Safety Monitor (MSM) • MSM blindly reviews the event (consults site if necessary) and indicates whether the event is serious, unexpected, and study drug related • Within 72 hrs. of MSM notification, PM closes review process

11. MedWatch Reports • FDA requires expedited reporting for AEs that are serious, unexpected, and study drug related • If the MSM determines that the AE meets all 3 elements (serious, unexpected, and related to study drug), WebDCUTM generates an online pre-populated MedWatch form and sends an automatic email notification to the hub coordinator.

12. MedWatch Reports • Hub staff completes the MedWatch ASAP • PM reviews MedWatch and contacts the site for corrections, if necessary • Once the MedWatch passes PM review, the PM: • Submits MedWatch to FDA • Submits MedWatch to DSMB (through the NINDS liaison) • Notifies all hubs of MedWatch posting on WebDCUTM • Each clinical site PI is responsible for reporting the SAE to their IRB/REB according to their local requirements.

13. MedWatch Reports Fatal or life threatening SAEs: - PM submits initial form & cover letter within 7 days of discovery - PM submits complete form within 15 days of discovery Non-fatal and non-life threatening SAEs: - PM submits most complete form possible & cover letter within 15 days of discovery Follow Up Reporting - PI responsible for obtaining any follow-up information and submitting that data into WebDCUTM as soon as it becomes available.

14. Pop Quiz!

15. How do you report a SAE? • Call the RAMPART Hotline • Call the RAMPART hotline and data enter the AE CRF • Data enter the AE CRF D. Data enter and submit the AE CRF

16. How do you report a SAE? A. Call the RAMPART Hotline B. Call the RAMPART hotline and data enter the AE CRF C. Data enter the AE CRF D. Data enter and submit the AE CRF

17. What are the timelines for submission of SAE data? • 3 days from first knowledge of the event • B. 5 days from first knowledge of the event • C. 24 hours from first knowledge of the event • D. 48 hours from first knowledge of the event

18. What are the timelines for submission of SAE data? A. 3 days from first knowledge of the event B. 5 days from first knowledge of the event C. 24 hours from first knowledge of the event D. 48 hours from first knowledge of the event

19. Which AEs must be reported on a MedWatch? • Serious AEs B. Serious AEs that result in death C. Serious AEs that are study related D. Serious AEs that are study related and unexpected

20. Which AEs must be reported on a MedWatch? • Serious AEs B. Serious AEs that result in death C. Serious AEs that are study related D. Serious AEs that are study related and unexpected

21. True or False:‘Death’ is a serious adverse event A. True B. False

22. True or False:‘Death’ is a serious adverse event A. True B. False