Division of AIDS Data Interchange DAIDS ADVERSE EXPERIENCE REPORTING SYSTEM (DAERS) PRODUCTION TRAINING Last Updated: 4/7/2010v Rev.21

Division of AIDS Data Interchange Agenda DAIDS-ES Overview DAERS DAERS Training and Account Information Workflow Selected Features DAERS Terminology Submission Timelines DAERS Changes per new EAE Manual Version 2.0 Maintenance of User Account Information DAERS Additional Information DAERS Contact Information Training Demonstration Last Updated: 4/7/2010v Rev.22

Division of AIDS Data Interchange What is the DAIDS-ES? The DAIDS Enterprise System (DAIDS-ES) is a suite of tools, built on a common framework that enhances clinical research by supporting scientific, administrative and regulatory processes. This enterprise system contains multiple integrated modules for key business areas. Last Updated: 4/72010v Rev.23 DAERS is a Secure, Confidential Web-based system that supports Therapeutic, Vaccines and Prevention EAE Reporting CSM is the single source for all monitoring information that supports standardization of findings and visit reports across networks and non-networks DPRS supports the Electronic Submission and tracking of registration materials

Division of AIDS Data Interchange DAERS Training and Account Information Site Leaders or Site Coordinators must submit a request to DAIDS-ES Support for access to DAERS for all new users through the Site Enrollment module. All Submitters who attend training must also submit the following information to attain access to DAERS: Physician Electronic Signature Attestation Form This form and directions on how to complete and send it may be found on RCC’s website: res.com/safetyandpharmacovigilance/ res.com/safetyandpharmacovigilance/ Completion of training and submission of forms does not automatically generate user account for DAERS. RCC must verify Submitters against the FDA Form 1572/IoR Agreements on file and that the CRS is Protocol Registered for all the protocols listed in the request for access. At least 1 submitter must be trained at a site before account information is sent. Last Updated: 4/7/2010v Rev.24

Division of AIDS Data Interchange High Level DAERS Workflow Last Updated: 9/15/2009v Rev.15 Clinical Research Site (CRS) RCC DAIDS AE Occurs at CRS Review EAE submission Additional Information Required? Report to RCC? Yes No Assess EAE Report Additional Information Required? Sends Query to CRS Create EAE Submit EAE to RCC Update EAE Yes Safety Report Required? Yes No Create Safety Report Yes Notify FDA & CRS Archive Report No Stop No DAERS – EAE Reporting

Division of AIDS Data Interchange DAERS (EAE Reporting) Selected Features Secure, Confidential, Web-based system Assess the reportability of an adverse event Create, Submit and Update EAE reports to RCC electronically Instant access to EAE reports Built-in checks and list of values Protocols CRSs Participant IDs Study Interventions Supports EAE Reporting to the Division of AIDS notification of EAE report submission to CRS Staff and other key stakeholders. Last Updated: 4/7//2010v Rev.26

Division of AIDS Data Interchange DAERS Terminology Roles Reporter – Site study staff who have the ability to create EAE reports. Submitter – Study Physician(s) who have the ability to create, sign and submit EAE reports. To be a submitter, a physician: –Must be listed on the FDA 1572 form or Investigator of Record Agreement. –Must sign the Physician Electronic Signature Attestation Form –Must be formally trained on the DAERS system EAE Report Types Initial – Original EAE report sent to RCC. Update – Once an EAE report has been submitted to RCC, additional information is submitted through an update. Last Updated: 4/7/2010v Rev.27

Division of AIDS Data Interchange DAERS Terminology (cont) Last Updated: 4/7/2010v Rev.28 Reporter, Submitter or RCC Status Definition Notification Recipient Pending Ready for Final Review Submitted to RCC EAE Report Statuses An EAE report has been started by the Reporter or Submitter, but it has not been finished. The EAE report contains all required elements and is ready to be reviewed by the Study Physician. The Study Physician has approved and sent the EAE report to RCC. An EAE Report erroneously submitted to RCC, which is no longer considered an official EAE submission. To: Reporter for EAE, Study Coordinator To: Reporter for EAE, All Study Physicians on protocol at site, Study Coordinator To: RCC, Submitter, Reporter for EAE, All Study Physicians on protocol at site, Study Coordinator, Network’s DMC, and Site’s ICC (where applicable). To: Reporter or Submitter requesting withdrawal. Withdrawn

Division of AIDS Data Interchange DAERS Terminology (cont) Last Updated: 4/7/2010v Rev.29 Indicates the RCC- assigned EAE number prior to the migration Created Unique 6 digit number assigned when report is created Indicates the year the report was submitted Submitted Indicates the version of the updated report created Updated Legacy Migrated

Division of AIDS Data Interchange Submission Timelines EAE Reports are required to be signed and submitted within three reporting days of the site awareness date. Monday through Friday count as reporting days. Holidays that occur on a Monday through Friday count as reporting days. Saturday and Sunday are considered non-reporting days. Reporting days are counted in local time. A reporting day starts at 12:00 am and ends at 11:59 pm. A day is counted as a reporting day regardless of the time of the day that awareness occurred prior to 11:59 pm. The site awareness day shall count as the first reporting day unless it occurs on a non-reporting day (i.e., Saturday or Sunday); in which case, the next reporting day shall count as the first reporting day. Any EAE submitted after the third reporting day shall be considered late. Last Updated: 4/7/2010v Rev.210

Division of AIDS Data Interchange Submission Timelines (cont) Example: Site Awareness: March 13 th at 2:00 PM Report Submission Due: March 17 th at 11:59 PM Last Updated: 4/7/2010v Rev.211 March SundayMondayTuesdayWednesdayThursdayFridaySaturday Site Awareness (2:00pm local time) Report Due (11:59pm local time )

Division of AIDS Data Interchange Past Due Submission Reports that are not submitted within the three reporting days will require an explanation for the delay in submission Last Updated: 4/7/2010v Rev.212

Division of AIDS Data Interchange Submission Timelines (cont) The Alerts web part on the DAERS home screen allows users to quickly identify EAE reports that are either approaching their due date or past their due date. Last Updated: 4/7/2010v Rev.213

Division of AIDS Data Interchange DAERS Changes per EAE Manual Version 2.0 All new protocols will be using the EAE Manual Version 2.0 For existing protocols, sites will be notified by their protocol teams if your protocols will be required to switch to the EAE Manual Version 2.0 DAERS will automatically reflect the changes once a protocol using the EAE Manual Version 2.0 is selected. Last Updated: 4/7/2010v Rev.214

Division of AIDS Data Interchange DAERS Changes per EAE Manual Version 2.0 After a protocol has switched to the EAE Manual Version 2.0: Updates to EAE reports created prior to the switch will continue using EAE Manual Version 1.0 Initial EAEs will use EAE Manual Version 2.0 regardless of the Protocol Version it is reported against Last Updated: 4/7/2010v Rev.215 Switch Submitted Initial EAE EAE Manual Version 1.0 Update EAE EAE Manual Version 1.0 Create Initial EAE EAE Manual Version 2.0 Created Initial EAE EAE Manual Version 1.0 Submit Initial EAE EAE Manual Version 1.0

Division of AIDS Data Interchange Maintenance of User Account Information Adding Users to DAERS The Site Leader or Coordinator must request access for site staff using the Site Enrollment Module in DAERS. Must provide the following information for each added site staff: –User’s Name and contact information ( , phone, fax) –DAERS Role by Protocol All new users must complete training. Reporters Will only have access to report EAEs on protocols that have at least one Physician who also has access to submit EAEs on those protocols. Submitters Must mail the Electronic Signature attestation from to the RCC. Must be listed on the FDA Form 1572 or IoR Agreement. Last Updated: 4/7/2010v Rev.216

Division of AIDS Data Interchange Maintenance of User Account Information Site Leaders and Site Coordinators are responsible for maintaining their DAERS User’s Information through the Site Enrollment Module. This includes the following scenarios: Adding new users to DAERS When additional people join the organization, sites must follow the process to add users to DAERS. Access to newly registered Protocols When a site registers to a new EAE reporting DAIDS protocol, the Site Leader or Site Coordinator must request access for the users who have been identified for the role of Submitter or Reporter for that particular protocol, and submit the associated documentation to DAIDS-ES Support. (Physician Electronic Signature Attestation Form - If the submitter is not a current user of the DAERS system) Adding access rights When a site user requires Reporter access to additional protocols, the Site Leader or Site Coordinator is responsible for modifying this information. When a site user requires Submitter access to additional protocols, Site Leader or Site Coordinator is responsible for modifying this information based off the FDA Form 1572/ IoR Agreement. Removal of Access When a user leaves the site’s organization or is no longer on a protocol, Site Leader or Site Coordinator is responsible for modifying this information. Last Updated: 3/26/2010v Rev.117

Division of AIDS Data Interchange DAERS Additional Information Instructions and necessary documents are found on the RCC website res.com/safetyandpharmacovigilance/ res.com/safetyandpharmacovigilance/ If additional training is required the site should contact DAIDS-ES Support. Last Updated: 4/7/2010v Rev.218

Division of AIDS Data Interchange DAERS Contact Information DAIDS EAE Manual or DAIDS Reporting Requirements Phone: (USA) (International) Fax: (USA) (International) DAERS Phone: (USA) (International) Fax: (USA) (International) Last Updated: 4/7/2010v Rev.219 Questions about … When in doubt, copy both.

Division of AIDS Data Interchange Last Updated: 4/7/2010v Rev.220 Training Demonstration Assessment of an Adverse Event EAE Report Generation and Submission Creating an EAE Report Completing an EAE Report Submitting an EAE Report (Only available to Submitter) Updating an EAE Report Search EAE Report Features Searching EAE Reports Viewing/Modifying an EAE Report Deleting an EAE Report Copying an EAE Report Additional Features Online Help DAIDS-ES Support Site Enrollment Module (Site Leaders and Site Coordinators only) Submit New Request View Existing Requests Adding EAE Notification Recipients (Site Leaders and Site Coordinators only) New!

NIAID, Division of AIDS Appendix – Changes in DAERS per EAE Manual Version 2.0 by Field

Division of AIDS Data Interchange DAERS Changes per New EAE Manual Version 2.0 Last Updated: 4/7/2010v Rev.222 Field and EAE Report Section EAE Manual Version 1.0New EAE Manual Version 2.0 AE Reporting Method (Assessment Tool) EAE SAE (Serious Adverse Event) SUSAR (Suspected, Unexpected Serious Adverse Reactions) Level of Reporting (Assessment Tool) Standard, Targeted, Intensive No Longer Displayed Relationship to Study Product/Protoc ol (Assessment Tool, Study Agents/Vaccine s) Definitely Related Probably Related Possibly Related Probably Not Related Not Related Pending (temporary assignment for death) Related Not Related Expectedness (Assessment Tool) Required for protocols with a Targeted Level of Reporting Expected Unexpected

Division of AIDS Data Interchange DAERS Changes per New EAE Manual Version 2.0 Last Updated: 4/7/2010v Rev.223 Field and EAE Report Section EAE Manual Version 1.0New EAE Manual Version 2.0 Country of AE Origin (Primary Adverse Event) N/A Drop down list that displays all Countries. User selects country where the event occurred. Seriousness Criteria (Assessment Tool, Primary Adverse Event) Death Life-threatening Hospitalization or prolongation of existing hospitalization Persistent or significant disability/incapacity Congenital anomaly/birth defect None of the above, but is a protocol- specific reporting requirement, including Grade 3 events as required by the Intensive level None of the above, but is of sufficient concern to report to DAIDS Results in Death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Other important medical event that may jeopardize the subject or that may require intervention to prevent outcomes listed above None of the above, this is not an SAE, but is a protocol-specific reporting requirement None of the above, this is not an SAE, but is of sufficient concern to report to DAIDS