RAPID R DC A RISg P rocess I nterface for D rug Development

1. RAPIDRDC ARISg Process Interface for Drug Development Prototype Pilot Training for Investigators Date of Training:

2. Agenda • Provide overview of the RAPID project • Review of the RAPID workflow • Review RAPID prototype processes: • Query • Case deletion • DEDP (Drug Exposure During Pregnancy) • Review of new SAE case page in RDC • Emergency unblinding • Contingency plan • Process at the end of trial (EOT) • BI Fax numbers and contact information • Next Steps

3. Training Objectives • Understanding the Prototype Pilot Process • Understanding the Investigator/site role within the Prototype Pilot

4. Overview of RAPID • Scope of the RAPID Project: • To design and implement one system for entry and reporting of Serious Adverse Events in clinical trials, using already existing information sources O*C/RDC and ARISg. • Advantages: • Avoid inconsistencies among the two information sources (eCRF and paper SAE form), reduce information source to one. • Allows for a well documented and auditable query process. • Reconciliation no longer needed between Drug Safety and Clinical databases. • Provides efficiency since the sites are already familiar with providing clinical trial data via RDC. • New SAE case page added to RDC. No paper SAE form will be used in future.

5. RAPID Workflow

6. Overview of RAPID Prototype • During the pilot phase SAEs have to be entered in RDC and printed out in parallel. • Site must print out the SAE case form, attach a cover page, sign and fax it to the respective Global Pharmacovigilance Center (EU or US) or Regional Center Vienna. • Sites must retain the initial and follow-up SAE case forms and fax cover sheets for archiving in the ISF. • BI will notify all sites involved in the RAPID Prototype pilot when the pilot has been completed and the sites no longer need to fax the SAE case page to BI. • SAE CASE FORM MUST BE APPROVED IN A TIMELY MANNER AND SIGNED BY THE INVESTIGATOR PRIOR TO SUBMISSION TO BI. • Approval of SAE information 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

7. Query Process • Drug safety will post queries in RDC in addition to auto generated discrepancies and those queries entered by other functions. • For urgent queries the 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.

8. Queries from Drug Safety • Drug Safety queries can be entered on the SAE case form and also on related forms (i.e., AE, CT 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.

9. Deletion of SAE Case Form • New deletion selection criteria are available in RDC for SAEs • They have been added to the bottom of the standard drop down list

10. Deletion of SAE Case Form (cont’d.) • 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.

11. 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. • Do not include any SAE information. All SAEs must be entered in RDC via the SAE case form.

12. 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 SAE case form Investigator reviews form contents and approves SAE case form Update SAE case information as necessary and re-approval by investigator Process for New SAE Case

13. Entering the SAE Case Form in RDC • Link associated AE CRFs • Complete case-specific information on SAE case form • Add onset date for Baseline Conditions • Link relevant CT CRFs

14. Entering the SAE Case Form in RDC (cont’d.) • Add any additional medications not on a CT CRF • Review derived AE information • In the rationale for causality section enter the causality for the event including other possible causes.

15. 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 SAE case form as follows:

16. Contingency Plan • In case of system unavailability for more than 24 hours, this contingency plan must be followed: • The blank SAE case form located in the ISF must be filled out manually (same process as the general RDC contingency plan). • The instructions for the manual completion can be found in the ISF. • The completed SAE form must be signed and faxed immediately to Drug Safety (refer to BI fax numbers).

17. Process at the End of Trial • At the end of the trial after access to your trial in RDC has been removed, the blank SAE case form located in the ISF must be filled out manually for any new cases or follow ups. • The instructions for the manual completion of the SAE Form can be found in the ISF. • The completed SAE form must be signed and faxed immediately to Drug Safety (refer to BI fax numbers).

18. BI Fax Numbers

19. Contact Information • For RDC system related questions/technical difficulties: Contact RDC help desk. • For SAE related or protocol specific questions: Contact the CML or designee.

20. Training for RAPID • This presentation is available also on the WBT site: • There is a special chapter for the pilot trials (see next slide) describing the entry of the SAE form in RDC. A PDF of this chapter is available there for printing. • 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. Sites that have already completed the WBT must go back and complete this new chapter and print the certificate.

21. Where to Find WBT (web based training) for SAE Case Form

22. Questions?