SMART Study Closeout Washington ICC Meeting 03 June 2007

1. SMART Study Closeout Washington ICC Meeting 03 June 2007

2. SMART ‘Closeout Materials’ • Closeout Materials located on INSIGHT website -you must login to obtain materials: • Access INSIGHT website at www.insight-trials.org • Click “Member log-in” and enter assigned User Name and Password • Click “Studies” • Click “SMART” • Click “Reports” • Select your ICC, SCC, and then your site • Click “Closeout Materials”

4. SMART ‘Closeout Materials’ • Closeout memo • Closeout Status Verification CRF • Notes on Completing 065-CLO-1 • Clinical Profiles (SCC and Site-specific) • Remaining Visit Window Report (Site-specific) • Outstanding Specimen Report (Site-specific)

5. Closeout MemoTimeline • 11 July 2007 • Last day of study follow-up • Last day for enrollment into Genomics 065H • 12 July 2007 • First day to complete and submit Closeout Status Verification CRFs • 01 AUG 2007 • All ECGs electronically transmitted (or mailed) to EPICARE • 13 OCT 2007 • All specimens shipped to ABML • Last day for submission of all CRFs to SDMC • 31 December 2007 • All data queries resolved

6. Closeout MemoAttachments • “Dear Participant Letter” – requires IRB/IEC approval prior to distribution • Give to participant at last study visit or through other means • DAIDS memo re: retention of ECG and BIA machines

7. Study Follow-up Visits • ‘Remaining Visit Window Report’ • Complete all study visits with windows open prior to 12 July 2007 • Special emphasis on annual visits • Submit completed study CRF or Missed Visit Report as soon as possible. • Consider participant for enrollment into SMART Genomics substudy 065H

9. ECG Data

10. ECG Data • Carefully review INSIGHT website for missed or poor quality ECGs • Can conduct an annual ECG until the next annual visit window opens • Participant completed annual visit, but missed ECG, and visit window closed: Collect ECG at next visit, transmit it to EPICARE, submit error corrected ECG section of annual CRF • Poor Quality ECG or Missed Visits : Collect ECG, transmit, and complete “Unconventional ECG form” from Web – do not error correct annual visit CRF

12. Closeout Status Verification

13. Closeout Status Verification CRFPurpose • To verify up until and including 11 July 2007: • Event status (AIDS-related Illnesses, Supplemental Diagnoses, Grade 4 events) • HIV antiretroviral regimen history • Vital Status • Exceptions: • Patients for whom Death Report Form has been received at SDMC • Can start to complete CRF on 12 July 2007

14. Closeout Status VerificationProcess • Closeout Status Verification CRF (065-CLO-1) • Participant-specific Clinical Profile and patient’s medical chart or records • Notes on Completing 065-CLO-1

17. ‘Clinical Profile’ • Clinical Profile generated daily by SDMC and posted to INSIGHT website as .ZIP files • Lists all received events • Lists all received changes in ART • Check Clinical Profile against each participant’s medical record to ensure all protocol-defined events have been reported • Contact patient or review medical records to verify status as of 11 July 2007

20. Notes on Completing the Closeout Status Verification CRF 065-CLO-1 • Very Important to have Notes on Completing available while completing CRF. • Example 1: • Comparison of Clinical Profile against the patient’s medical record indicates that the SDMC did not receive AIDS-related illness module for Histoplasmosis

22. Closeout Status VerificationNotes on Completing • If item 2 is marked “No”, follow these instructions: • Report each unreported event by completing an AIDS-Related Illnesses CRF (065-ARI-1) and the associated AIDS-related illness module. More than one unreported event can be reported on the same AIDS-Related Illnesses CRF. On the AIDS-Related Illnesses CRF, record the date of the Closeout Status Verification CRF (“Date Form Completed”) as the “Date of Visit”.

24. Closeout Status VerificationNotes on Completing • Example 2: • Comparison of Clinical Profile against patient’s medical record indicates that the SDMC did not receive all changes in ART

25. Closeout Status VerificationNotes on Completing • If item 8 is marked “No”, follow these instructions: • To report each unreported change in ART, either complete a new Antiretroviral Therapy Change CRF (065-ARC-1) if none was completed with the follow-up visit when the change occurred, or error correct the 065-ARC-1 where the change should have been noted. If a new Antiretroviral Therapy Change CRF is completed, record “99” for follow-up visit month or mark the “Death” box, if submitting this CRF with a Death Report Form (065-DRP-1). Remember to complete the “Page Number” boxes and record the date of the Closeout Status Verification CRF (“Date Form Completed”) as the “Date of Visit”.

27. Closeout Status VerificationNotes on Completing • What was the patient’s vital status on 11 July 2007? • Section A, Items 9 -10:Mark the “Alive” box if the participant is known to be alive on 12 July 2007 or later. Mark the “Dead” box if the participant died on or before 11 July 2007. Mark the “Unknown” box if the date the participant was last known to be alive is before 11 July 2007. The “Unknown” box can only be marked after every effort has been made to locate the participant. If the “Unknown” box is marked, record the last known alive date in Item 10.

28. Specimen Shipping • “Outstanding Specimen Report” – updated on the web approximately every 2 weeks • It is a good idea to verify the report against the listed “Visit” CRF, i.e. CRF may have been completed in error • All Laboratory specimens must be received by ABML by 13 October 2007- ICCs have developed a shipping plan with their SCC/sites to ensure on-time completion of shipping

30. SMART ‘Closeout Materials’Review -1 • Closeout memo • Timeline • Closeout Status Verification CRF (065-CLO-1) • Purpose to verify that all study-defined events and changes in ART occurring between randomization and up until and including 11 July 2007 have been reported • Report participants vital status as of 11 July 2007 • Clinical Profiles • Need to use profile while reviewing patient’s medical chart/records and completing 065-CLO-1

31. SMART ‘Closeout Materials’Review -2 • Notes on Completing 065-CLO-1 • Specific instructions on how to report unreported events, changes in ART, vital status • Remaining Visit Window Report (Site-specific) • Lists remaining visit windows up until and including 11 July 2007 • Outstanding Specimen Report (Site-specific) • Lists, by PID, outstanding specimens. Check report against listed CRF and, if necessary, error correct CRF

32. Data Queries • Address queries promptly • If you don’t understand a query, please contact your SCC/ICC • All queries must be resolved by 31 December 2007

33. SMART Study Closeout -1 • Checklist in development will include: • All Status Verification CRFs completed and received by SDMC • All data queries resolved • All outstanding specimens received at ABML • All ECGs (electronic or hardcopy) received by EPICARE • All monitoring issues resolved

34. SMART Site Closeout - 2 • IRB/EC notified re SMART Study closure • Site has submitted to Protocol Registration Office through ICC • Completed Pro Reg checklist marked “deregistration” • IRB/EC letter stating study has been closed out OR • Letter from IoR PI requesting deregistration from SMART 065 • Deregistration notice received from Pro Reg

35. SMART Study Closeout - 3 • There will NOT be a common protocol deregistration date for SMART • Sites will deregister through the SCC/ICC when they have completed all closeout requirements