New eSAE Reporting Process

1. New eSAE Reporting Process Training for Investigators Trial: xxxx.xx Date of Training:

2. Training Objectives • Understanding the new eSAE reporting process • Understanding the Investigator/site role within the eSAE reporting process SAE Reporting for Investigators (eSAE process)

3. Agenda • Provide overview of the RAPID project • Review of the eSAE workflow and responsibilities • Review eSAE processes: • Entering the eSAE case form • Query • Case deletion • DEDP (Drug Exposure During Pregnancy) • Emergency unblinding • Contingency plan • Contact information • Training • Review questions SAE Reporting for Investigators (eSAE process)

4. Overview of RAPID(RDC ARISg Process Interface for Drug Development) • Scope of the RAPID Project: • Implement one system for entry and reporting of Serious Adverse Events (SAEs) in clinical trials by using existing information sources O*C/RDC and ARISg. • Advantages: • Avoid inconsistencies among the two information sources (eCRF and paper SAE form), by reducing information source to one • New eSAE form added to RDC. No paper SAE form will be used. • Reconciliation no longer needed between Drug Safety and Clinical databases. • Allow for a well documented and auditable query process. • Decrease duplication of processes (Coding of data performed only once). • Provide efficiency since the sites are already familiar with providing clinical trial data via RDC. SAE Reporting for Investigators (eSAE process)

5. Information flow from RDC to ARISg RDC Oracle Database -Inv . enters data into RDC -Inv. creates an eSAE case form in RDC -Inv. approves information in RDC ARISg Database -Receives RDC information directly into designated fields of the data entry workflow Interface transfer Coding completion Queries entered into RDC SAE Reporting for Investigators (eSAE process)

6. SAE Reporting in RDC Clinical Trials • eSAE CASE FORM MUST BE APPROVED IN A TIMELY MANNER • Approval of eSAE information in RDC (both initial and follow-up) should adhere to current BI timelines for reporting of SAEs (within 24 hours or the next business day whichever is shorter) • The information provided should capture all relevant SAE information to allow for adequate assessment of the case in order to fulfill regulatory reporting requirements SAE Reporting for Investigators (eSAE process)

7. CRA and CML Responsibilities • CRA is responsible to verify that the eSAE form is • complete and correctly entered in RDC • approved by the investigator in RDC and each update is to be re-approved * please note that updates to the eSAE case form will not transfer to ARISg unless they are approved • CML is responsible to follow-up on outstanding queries upon notification from Drug Safety SAE Reporting for Investigators (eSAE process)

8. Enter AE CRF for each event that is part of case for the patient (serious and non-serious, if applicable) Assure that entry of demographics, baseline conditions and concomitant therapies is up-to-date for this patient Create a new eSAE case form Investigator reviews form contents and approves eSAE case form as soon as all the information is complete Update SAE case information as necessary and obtain re-approval by investigator Process for New eSAE Case SAE Reporting for Investigators (eSAE process)

9. Entering the eSAE Case Form in RDC • Link associated AE CRFs • Complete case-specific information on eSAE case form • Add onset date for Baseline Conditions • Link relevant CT CRFs SAE Reporting for Investigators (eSAE process)

10. Entering the eSAE Case Form in RDC (cont’d.) • Add any additional medications not on a CT CRF • Review derived AE information SAE Reporting for Investigators (eSAE process)

11. Query Process in RDC • All queries are posted in RDC • For urgent queries sites may receive an e-mail and/or phone call from Drug Safety requiring further clarification in addition to the posting in RDC. (see example query below) • “An urgent query is present in RDC regarding data entered for Trial #, Site #, Patient #, CRF Name: Please access RDC to review this urgent query and make the necessary updates.” • All responses to queries must be entered in RDC and should not be sent via e-mail or answered by phone to Drug Safety. • When responding to discrepancies please return the discrepancy to the originator before re approving the form. This means that after all changes have been made and all discrepancies have been addressed the last step is to approve the form. SAE Reporting for Investigators (eSAE process)

12. Queries from Drug Safety • Drug Safety queries can be entered on the eSAE case form and also on related forms (i.e., AE, CT Demographics and Baseline Conditions). • These queries will be identified as having been entered into RDC by Drug Safety personnel. • There is a new Action added “Send to Drug Safety”. Any queries from Drug Safety must have responses returned to them. SAE Reporting for Investigators (eSAE process)

13. New deletion selection criteria are available in RDC for SAEs They have been added to the bottom of the standard drop down list Deletion of eSAE Case Form SAE Reporting for Investigators (eSAE process)

14. The investigator should provide any additional details regarding the deletion in the text box field. If the reason for deletion is duplicate case, please delete the later case and keep the earlier case in the database. Deletion of eSAE Case Form (cont’d.) SAE Reporting for Investigators (eSAE process)

15. Reporting Drug Exposure during Pregnancy • Drug Exposure During Pregnancy (DEDP) reports will remain the same using the paper Pregnancy Monitoring form for clinical trials. • When filling out the Pregnancy Monitoring form for clinical trials be sure to only include the study drug exposure information. • File the DEDP form in the ISF. • The complete Pregnancy Monitoring form must be faxed to the local CML/CSO immediately. • Do not include any SAE information. All SAEs must be entered in RDC via the eSAE case form. SAE Reporting for Investigators (eSAE process)

16. Emergency Unblinding • If a patient needs to be unblinded for emergency reasons at site level then the actual unblinded treatment must be documented on the eSAE case form as follows: SAE Reporting for Investigators (eSAE process)

17. Contingency Plan • In case of system unavailability for more than 24 hours this contingency plan must be followed: • The paper SAE form located in the ISF must be filled out. The instructions for form completion can be found in the ISF. • The complete paper SAE form must be faxed to the local CML/CSO immediately. The centralized process is to be followed. As soon as the system is available again, the information must be entered into RDC. • After removal of access to RDC at the end of the trial • The complete paper SAE form must be faxed to the local CML/CSO as described above. SAE Reporting for Investigators (eSAE process)

18. Contact Information • For RDC system related questions/technical difficulties: Contact RDC help desk. See the flyer: RDC Onsite: Getting RDC Assistance • For SAE related or protocol specific questions: Contact your responsible CML or designee. SAE Reporting for Investigators (eSAE process)

19. Training for eSAE Case Form • This presentation is available also on the WBT site: • There is a special chapter in the WBT(see next slide) describing the entry of the eSAE form in RDC. • A PDF of this chapter is available there for printing. SAE Reporting for Investigators (eSAE process)

20. Web based training (WBT) for eSAE Case Form • Sites that have completed the RDC training (for another trial) are required to complete the Electronic SAE Reporting Process chapter. • There is a certificate that must be printed, signed and filed locally that is only for this new chapter. There is still the usual training confirmation in RDC for RDC training. • http://bi20.luvit.se/RDConsite SAE Reporting for Investigators (eSAE process)

21. Questions and Answers • Are sites required to print out the patient data report for the SAE case form? • No . However, the form can be printed following the instructions in the WBT • Should responses to urgent queries be sent to Drug Safety via e-mail? • No – all responses to queries must be entered into RDC • Will DEDP cases be entered in RDC? • No – the DEDP cases will be reported using the paper Pregnancy Monitoring Form and faxed to the local CML/CSO • Is approval needed for the initial eSAE case form and all updates? • Yes – the Investigator must approve both initial and all updates in RDC. This is extremely important in order to have the information transfer into ARISg SAE Reporting for Investigators (eSAE process)

22. Questions? SAE Reporting for Investigators (eSAE process)