Remote Monitoring of Adverse Events Dee Blumberg, PhD

Adverse Events An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related (21 CFR 312.32). FDA 21 312.32 Code of Federal Regulations

Serious Adverse Event An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the investigator or sponsor, it results in any of the following outcomes (21 CFR 312.32): death a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions a congenital anomaly/birth defect important medical events Important medical events that based on medical judgment may jeopardize the patient and require medical intervention to prevent one of the outcomes in the definition…

AE/SAE Reporting Timelines All AEs and SAEs are entered in the EDC AEs- within 7 days of site becoming aware SAEs- within 24 hrs of site becoming aware The report generates an email notification to Safety Monitor, Data Manager, Protocol Specialist, Sponsor and Investigators (can be customized to include DSMB, pharma companies and any others) Timing of 7 days for AEs is a pretty standard time, 24 hours for SAEs is fixed

Automated Notification

Add that all rest of conversation is documented through edc, give eg of another email in my box or comm. With safety monitor…

AE/SAE Review AEs documented in 3 linked eCRFs: The Adverse Events form (AD1)- the main adverse events form captures information for AEs meeting protocol specified reporting criteria. The Serious Adverse Events Summary form (AD2)- captures safety data for those events associated with serious adverse event criteria. Serious Adverse Event Medical Reviewer form (AD3)- captures medical monitor determinations about each serious adverse event and requests made by the medical monitors for further information about the event. Don’t get into too much detail here…. At Emmes the medical monitor review is also documented in the system- that is different from most places… nothing else is unique

Adverse Events Form- AD1 The Adverse Events form - (AD1) is the main adverse events form and captures information for adverse events meeting protocol specified reporting criteria. SAE determination is made by the system

Serious Adverse Events Summary Form- AD2 SAE and supporting documents are available for the safety team to review (it asks for them to upload docs into the system) If a serious adverse event is reported on the Adverse Event form (AD1), the link "Serious Adverse Events Summary" in the toolbar of the form becomes available (see below). Click on the link to navigate to the form and enter in all available information into the appropriate fields. Additional Medical Monitor Information: Question 7 (Additional information requested by the Medical Monitor) is a read-only field that indicates what, if any, further information about the event has been requested by the Medical Monitor. Provide follow-up information in question 6 (follow-up) if the Medical Monitor requests it after initial SAE review. Once the requests in this field have been addressed in question 6, indicate this by checking the “Have all Medical Monitor requests been addressed” checkbox underneath question 7. As long as this field remains checked, no further requests have been made by the Medical Monitor.

AD2 Cont. Qu. 7 is a read only field that indicates what info is requested by the MM. Need to provide follow up info in Qu6 if MM requests it after initial SAE review. Once all requests in this field (7) have been addressed (in 6) check the box at the bottom- that all MM requests have been addressed. Documents can be attached to this form (associated with Qu 1 or 6)- no peronally identifying info (PHI) like name or initials…

Serious Adverse Events Medical Reviewer Form - AD3 Medical monitor reviews SAEs directly in the EDC This is where medical monitor review is documented…. Serious Adverse Event Medical Reviewer form - (AD3) captures medical monitor determinations about each serious adverse event and requests made by the medical monitors for further information about the event. The form is read only for everyone but the MM.

Monitoring AEs via Weekly Reports Clinical Coordinating Center receive weekly system- generated reports of AEs Reports are formatted as Excel documents Can be sorted as needed Highlighted as needed (e.g., certain severity) Clinical Coordinating Center (CCC) Staff (e.g., Safety Monitor) receive weekly system-generated reports of Aes

Conclusions Advantages: Real time attention to SAEs Medical Monitor reviews directly in the EDC and Communicates to research staff Medical Monitor locks reviewed SAEs Patterns trends from weekly reports… Weekly AE reports just like PD report– allow for monitoring the events that happens all week. Look for trends… training as needed… Screenshot of weekly report where causality is YES and circle/highlight that to show attnetion to it… So email notification and weekly reports- 2 ways of monitoring…

Questions? Comments?

Thank you!