1. 1 MTN-003 Training Follow-up Visit Scheduling and Visit Coding SSP Sections 14.3.2 and 14.3.3

2. 2 MTN-003 Follow-up Period For the study overall: –Duration of follow-up will depend on how long it takes to observe the required number of HIV infections (endpoints) across sites For planning purposes as of now, follow-up is expected to continue for 14 months after completion of accrual Will be monitored by the SMC and DSMB Protocol Team will use SMC and DSMB guidance to set a final study end date which will be communicated to all sites

3. 3 MTN-003 Follow-up Period Each participant will be followed: –1) For a minimum of 12 months on product plus 2 months off product –2) For a maximum of 33 months on product plus 2 months off product OR –3) Through the study end date Therefore, the overall follow-up period for each participant is expected to range from 14- 35 months

4. 4 Though participants are seen monthly, the type of visit performed will vary: –MONTHLY visits are performed at months 1,2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19, 20, 22, 23, 25, 26, 28, 29, 31, and 32 –QUARTERLY visits are performed at months 3, 9, 15, 21, and 27 –SEMI-ANNUAL visits are performed at months 6, 18, and 30 –ANNUAL visits are performed at months 12 and 24 MTN-003 Required Follow-up Visits

5. 5 The second-to-last scheduled visit is called the PRODUCT USE END VISIT (PUEV) The PUEV is –A participants last routine monthly follow-up visit –Conducted at month 12 for participants who are followed for the minimum required time –Conducted at month 33 for participants who are followed for the maximum allowed time –For participants who are followed for between the minimum and maximum, the Protocol Team will instruct sites when PUEVs should occur based on the study end date MTN-003 Required Follow-up Visits

6. 6 The last scheduled visit is called the TERMINATION VISIT: –Also called the Study Exit visit –Occurs ~8 weeks (2 months) after the participants PUEV At month 14 (12+2) for participants who are followed for the minimum required time At month 35 (33+2) for participants who are followed for the maximum allowed time At a month to be determined for participants who are followed for between the minimum and maximum amounts of time MTN-003 Required Follow-up Visits

7. 7 Two clarifications about the PUEV: –For participants who terminate early from the study (e.g., due to participant choice), whenever possible, conduct a PUEV as the participants last follow-up visit –For participants who permanently discontinue product use during follow-up but stay in the study, the PUEV is still conducted as the second-to-last follow-up visit For these participants, the PUEV is not the visit when product use is permanently discontinued Ex. A participant is found to have an AE at Month 23 that requires perm d/c. The Month 23 visit is performed as a monthly visit, not a PUEV. The participant continues in follow-up per her original visit schedule MTN-003 Required Follow-up Visits

8. 8 Follow-up Visit Target Days Routine follow-up visits are targeted to occur every 28 days after Enrollment (Day 0) –Month 1 Target Day = Day 28 –Month 2 Target Day = Day 56 –Month 3 Target Day = Day 84…… Whenever possible, conduct the follow-up visit on the target day If not possible, conduct within the Visit Window

9. 9 Follow-up Visit Windows Visit Windows are ~4 weeks long and are contiguous from visit to visit –For each visit, the window starts 14 days before the target day and ends 13 days after the target day

10. 10 Target days and visit windows do not change – they stay the same even if visits are not conducted on the target day A participant is considered retained and will be listed as completed on-time in the MTN-003 Retention Report if the visit is completed within the visit window (even if not completed on the target day) Follow-up Visit Windows

11. 11 Follow-up Visit Schedule List of Follow-up visits, visit codes, target days, and windows

12. 12 Tools for Determining Participants Follow-up Visit Schedule SCHARP developed an Excel file that you can use to create a participant study visit schedule/calendar Requires a small amount of information to be entered (PTID, Enrollment Date) The target dates and visit windows will be programmed into the tool such that a visit schedule is created for the participant The visit schedule can be printed and placed in the participants MTN-003 study notebook

13. 13 Visit Calendar Tool

14. 14 Things to Consider When Scheduling Follow-up Visits Target Days and Visit Windows Product Supply The participants schedule (e.g. any plans to be away from the clinic area) The participants menstrual cycle (e.g. for visits where pelvic exams are required) Contraceptive needs Other considerations?

15. 15 Visit Codes for Required Visits SSP Section 14, Tables 14-1 and 14-2 Whole numbers (0 to the right of the decimal point) –Screening Part 1 = 01.0 –Screening Part 2 = 02.0 –Enrollment (Day 0) = 03.0 For follow-up visits, add 3 to the follow-up visit month to calculate the visit code –Month 1 = 04.0 –Month 2 = 05.0 –Month 3 = 06.0 PUEV visit code is the visit code associated with the month in which this visit occurs The Study Exit/Termination visit is assigned a special visit code of 89.0

16. 16 Split Visits Per protocol, required study visits (EXCEPT enrollment) may take place over multiple days (split visits) All days must be within the visit window All CRFs completed for the visit are assigned the same whole-number visit code –Ex: Ppt completes all required Month 6 visit evaluations on the target day except for the pelvic exam; she returns 5 days later and completes the pelvic exam –All CRFs, including the Follow-up Pelvic Exam form, are assigned the Month 6 visit code (09.0) –A QC will not be generated for CRFs with different dates but the same visit code as long as all visit dates are within the same visit window

17. 17 Missed Visits A follow-up visit is missed when a participant does not complete any part of the visit during the visit window Missed visits are documented using the MTN-003 Missed Visit case report form Once the visit window has closed, complete and fax a Missed Visit form. Do not complete or fax any other CRFs for that visit The Missed Visit form will let DataFax know not to expect any other forms for that participant for that particular visit

18. 18 Missed Visit CRF Record the target visit date and the main reason the visit was missed Page 69 of your form packet

19. 19 Missed Visits - continued When a follow-up visit is missed, some procedures must be made up at the next visit –Pelvic exam –Dipstick urinalysis for protein and glucose –Serum chemistries –Complete blood count –Plasma archive No other missed procedures are made up at the next visit

20. 20 Interim Visits Definition: separate visit or phone call that is conducted to perform additional procedures other than regularly scheduled visit procedures Reasons may be –Administrative (e.g., ppt has questions for staff) –Product-related (e.g., ppt returning product) –Lab-related (e.g., to confirm phosphate value) –Clinical (e.g., to report new symptoms/AE) Interim visits may occur anytime during follow- up

21. 21 Interim Visits Not all interim visits are assigned interim visit codes Assign an interim visit code when the interim visit: 1) Warrants completion of a new DataFax CRF e.g., AE Log, Product Hold/Discontinuation (PH) Log –OR – 2) Results in product resumption after a hold update to items 4-4a on PH Log If an interim visit code is assigned, an Interim Visit (IV-1) CRF must be completed

22. 22 Interim Visit Example 1 A participants Month 1 target visit date is 02-SEP-09. She completes all required evaluations for the visit on 01-SEP-09. On 03-SEP-09 she calls the clinic to report new symptoms, which result in the reporting of a new adverse event (AE). Although she is still within the visit window, she has already completed all required visit evaluations. Thus, the 03-SEP-09 phone contact is an Interim Visit. Assign an interim visit code only if the new AE meets protocol reporting criteria, and is reported on a new AE Log form.

23. 23 Interim Visit Example 2 A participants Month 3 target visit date is 11-NOV-09. She completes all required evaluations for the visit on 10-NOV- 09. On 13-NOV-09 the site clinic receives her safety lab results, and one of the results warrants a product hold. The site clinician calls the participant to instruct her to hold study product and return to the clinic as soon as possible for clinical management. Although she is still within the visit window, she has already completed all the required visit evaluations. The 13-NOV- 09 phone contact results in completion of a new PH Log. Thus, the phone contact is an Interim Visit and is assigned an interim visit code.

24. 24 Interim Visit Example 3 Mary completes her Month 2 visit on the target visit date. Two weeks later (on the day her Month 3 visit window opens), Mary comes to the site clinic with a friend, who is also a participant, and Mary returns some unused study product that she forgot to return at her previous visit. Site staff decide not to conduct her Month 3 Visit at this time, as it is early in the visit window, and the Mary is known to be reliable with her visit attendance. No regularly scheduled visit procedures are conducted at this time. The visit results in completion of a new Product Returns and Dispensations form to document product return. Thus, the visit is an Interim Visit and is assigned an interim visit code.

25. 25 Record the reason for the interim visit, what DataFax forms are being faxed for the visit, the pregnancy test result (if done), and Hep B vaccine info Interim Visit CRF Page 62 of your form packet

26. 26 Interim Visit Codes Use visit code of the most recent required visit (or most recently-completed interim visit) and add 1 to the digit in the box to the right of the decimal Scheduled Visit. Visit Code First Interim Visit. Visit Code 0 40 0 41 Second Interim Visit. Visit Code 0 2 4

27. 27 Assigning Visit Codes to Interim Visits What interim visit code is used for the following? See SSP section 13, Table 14-2 a. A participant returns 2 days after enrollment to report she has lost her study product. She is dispensed more product at this visit. 03.1 b. A participant completes the Month 2 visit on the target day, but returns 3 days later to request additional STI testing 05.1

28. 28 Questions?