1. Overview of Follow-up Procedures
Follow-up Visit Types & Procedures
M1&2
Quarterly
PUEV/Term
Follow-up HIV Prevention Options Counseling (consistency in counseling)
Month 3 Considerations (transition to quarterly visits)
Social Benefits/Harms (potentially add in)

2. HOPE Follow-up Visit Schedule
Screen
Enroll M1 M2 M3 M6 M9
PUEV
Study Exit
Follow-up visits are targeted to occur monthly for the first three months, then quarterly thereafter. All participants will also be scheduled for a Product Use End Visit (PUEV) at Month 12 followed by a Study Exit/Termination Visit approximately 4 weeks later.

3. Visit Types Interim Interim Interim Monthly Quarterly PUEV Study Exit
Scheduled visits are those study visits required per protocol. 4 Types of scheduled F/U visits (Monthly/Quarterly/PUEV/Study Exit)
Interim visits are those visits that take place between scheduled visits.
SCHARP will discuss follow-up visit target dates/allowable/target windows, as well as interim visits in more detail later on in the training.

4. Visit Locations Clinic Off-Site
MTN-025 study visits will typically be completed at the study clinic. When necessary, follow-up visits may be conducted off-site at the participant’s home or location suitable to the participant with documented participant consent and allowable per site-specific SOPs. More information will be provided in a separate presentation about off-site visits later today.
Clinic
Off-Site

5. Month 1 & 2 Procedures Administrative: Review/Update Locator
Schedule Next Visit
Reimbursement
Clinical:
Medical/Menstrual History
Provide Test Results
Record/Update AEs
Concomitant Meds*
Offer/Provide Contraceptives*
Treatment/referrals*
Physical Exam*
Pelvic Exam*
Lab:
Urine:
Pregnancy
Urine culture*
GC and CT*
Blood:
HIV-1 Testing
Plasma Storage
Syphilis Serology*
CBC with platelets*
Serum Chemistries*
Pelvic/Other:
Vaginal Fluid (self)
Hair
Used VR*
Trich or other samples if ind*
Behavioral (Counseling):
Contraceptive
HIV pre-/post test
Options Counseling (HIV/STI risk reduction and adherence)
Required Monthly Procedures = BLUE (procedures that are if indicated are grey).
Note the following procedures were added as part of LoA#1: Hair, Plasma at M1&2, Ring-related procedures updated to allow for choice of rings
Study Product/Supplies:
Offer Condoms
Offer New VR
Provision of new VR*
Remove/Collect VR*
VR instructions*
Digital Exam*
Behavioral (Assessments):
Adherence

6. Quarterly Procedures Administrative: Review/Update Locator
Schedule Next Visit
Reimbursement
Clinical:
Medical/Menstrual History
Provide Test Results
Record/Update AEs
Concomitant Meds*
Offer/Provide Contraceptives*
Treatment/referrals*
Physical Exam*
Pelvic Exam*
Lab:
Urine:
Pregnancy
Urine culture*
GC and CT*
Blood:
HIV-1 Testing
Plasma Storage
Syphilis Serology*
CBC with platelets*
Serum Chemistries*
Pelvic/Other:
Vaginal Fluid (self)
Hair
Used VR*
Trich or other samples if ind*
Behavioral (Counseling):
Contraceptive
HIV pre-/post test
Options Counseling (HIV/STI risk reduction and adherence)
Required Quarterly Procedures = RED (procedures that are if indicated are grey).
NOTE THE ONLY ADDITIONAL ASSESSMENTS AT QUARTERLY VISITS ARE BEHAVIORAL
Study Product/Supplies:
Offer Condoms
Offer New VR
Provision of new VR*
Remove/Collect VR*
VR instructions*
Digital Exam*
Behavioral (Assessments):
Adherence
Behavioral
Social Harms
ACASI (M3)

7. Differences from ASPIRE?
What do you observe as key differences in follow-up procedures between ASPIRE and HOPE?

8. Differences from ASPIRE?
More frequent sample collection for adherence measurements (and more sample types!)
Less frequent required physical/pelvic exams
No unique set of procedures for “semi-annual” visits
Rationale:
More frequent sample collection/types = to better understand objective adherence measurements (more frequent plasma/used rings from study start) and explore alternative markers of adherence (hair)
Less frequent pelvic/physical exams = ASPIRE demonstrated that the ring was very safe; clinically indicated exams always done as needed
No semi-annual visits = due to different in study follow-up time

9. Visit Checklists
Instructions: The “Required at visits” column indicates when the item is required during follow-up per-protocol. Procedures do not have to be conducted in the order in which they appear in the checklist. When an item is performed, complete “Staff Initials” cell. If not done but required, write “ND” and staff initials in “Staff Initials” cell, and provide more details in the chart notes as needed. Do not initial for other staff members. If other staff members are not available to initial items themselves, write and initial/ date a note documenting who completed the procedure, e.g., “done by {name}” or “done by nurse.” If visit procedures are split across more than one date, ensure the date is captured in the comments cell for procedures conducted on a date different than that provided above.
Note: Due to the minimal differences between monthly and quarterly visits, recommend not splitting this up and using a universal checklist for follow-up visits. There is a separate checklist for PUEV/Term visits.

10. Sequence of Procedures
Modify to maximize efficiency of clinic flow
Very few procedures have required order:
Pelvic Exams
Behavioral Assessments before Counseling (but counseling still early on!)
Ideally, vaginal fluid swab with ring still in place
Ring provision toward end of visit (after clinical/lab assessments and counseling)
Recommend pairing Vaginal Ring (VR) removal/insertion
Flexibility is encouraged
The sequence of procedures presented on the visit checklists is a suggested ordering.
In consultation with the MTN CORE (FHI 360), it is encouraged that site staff modify the checklists to maximize the efficiency of site-specific study operations.
Sites may alter the sequence of procedures, with the listed exceptions.
Can discuss/prompt for rationale:
Pelvic – sample collection order important
Neutral/unbiased assessments more likely b/f counseling (behavioral assessment include ACASI/questionnaires)
Fluid – want levels to reflective of past month (will spike with disturbance/new insertion
Ring towards end of visit – need to make sure product hold not required and that participant wants to continue (or start/stop ring use) before dispensing
Pairing removal/insertion – less burden on participant

11. Why is efficiency important?
Clinic Flow
Why is efficiency important?
What are some strategies that may help improve clinic flow?
Regular internal reviews of systems is key - proactive rather than reactive
Prompt audience with questions – quick, 1-2 minute brainstorm (nothing long). Can note after the brainstorm that will touch on clinic flow more during the retention session later in the day.
Why: study visit length has the potential to negatively impact both participants (i.e. experiences could lead to poor retention), and staff (i.e. stress, fatigue, longer hours, low morale)
Strategies: Minimizing movement (to/from waiting room) by grouping procedures, task sharing/shifting, have well trained/experienced staff (provide opportunities for training when needed), recognize/avoid bottlenecks, minimize waiting room time, reduce/avoid redundancies in procedures (i.e. if checklist is sufficient, don’t also chart note)

12. Study Procedures for Non-Acceptors
With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring.
Including collection of blood, swabs, hair
Clinical holds

13. Minimum Procedures for VR dispensation:
AE assessment and reporting (verbal report of symptoms is acceptable; if symptoms indicate that further evaluation is necessary, this must be conducted prior to dispensing study product)
HIV testing and counseling (including RR counseling) and pregnancy testing are required for product dispensation if this has not been done within the past 90 days
Collection of Used Ring (and unused, if applicable), if available
Adherence Counseling/Product Use Instructions, as needed
While conducting all visit procedures for each scheduled visit is ideal, it is acknowledged that this might not always be possible. At a minimum, all of the following procedures must be conducted in order to dispense study product.
Highlight rationale during these next few slides = Priority is Ring Coverage/Providing the opportunity for high adherence
Knowing this set of minimal procedures is important for understanding options for ring provision at interim visits, split visits, or off-site visits to deliver a ring. Highlight the rationale behind the pregnancy/HIV testing being within 90 days (NEW FOR HOPE B/C of QUARTERLY VISITS)

14. Making up Missed Procedures
MTN-025 visit windows are contiguous, as such no procedures are required to be “made-up” at subsequent scheduled visits
Effort should be made to make up missed procedures as part of a split visit
Note that in the event of a missed visit, an interim visit may be required to resupply rings (and conduct associated safety assessments and counseling as needed)
If a participant misses her Month 3 visit, ACASI will be considered missed and will not be made up at subsequent quarterly visits
SCHARP will discuss missed, split and interim visits during .their presentation later in the day

15. Modified Procedures in the Event of Clinical Hold/Discontinuation
Modified procedures for HIV/pregnancy covered during separate training modules
For all other holds/discontinuations, the only modifications are:
Discontinue ring provision and associated instructions
HIV prevention options counseling will continue and will be tailored to focus on HIV risk reduction plans that do not involve the vaginal ring 
Only resume offering study product should the participant be clinically eligible

16. HIV Prevention Options Counseling During Follow-Up
Provide residual drug feedback, starting at M3
Explore how participant is doing with ring use and/or other HIV prevention methods
What went well or did not go well, how the participant is feeling about her HIV prevention approach(es)
If feasible for your clinic, make effort for participants to routinely see the same counselor

17. HIV Prevention Options Counseling During Follow-Up
Develop HIV risk reduction plan for the coming month(s)
Including her desire to start or continue using the ring as part of her HIV prevention strategy (if relevant), and assessment of confidence in plan
Check-in on attendance to study visits
Provide informational support, as needed

18. Residual Drug Feedback
Counseling Session
Residual Drug Data Available
Month 3
First Month of Use (i.e. ring collected at Month 1)
Month 6
Rings from Months 2-3
Month 9
Rings from Months 4-6
Month 12 (PUEV)
Rings from Months 6-9
Residual drug data will be provided to sites through Medidata RAVE. Interpretation of these results will occur either by the SDMC. Counselors will be provided residual drug information in a format that aligns with drug level counseling messages (i.e. low, medium, or high amount of drug released into the body).

19. HIV Prevention Options Counseling Documentation
Chart notes or site-specific
worksheet
Document after the session
NOT a summary of
procedural steps – focus on
capturing participant-specific
information
Include enough detail to inform and guide participant’s next session
Mark that counseling was done on visit checklist and whether the participant chooses to use the ring
Having this item on the checklist communicates the participants choice to others without them having to re-hash this conversation with multiple staff.
Note: The clinician can confirm the participant’s ring decision when the prescription is written.

20. Month 3 Counseling Considerations
Risk reduction plans should take into account that it may be three months before the participant returns to the clinic for her next visit
Discuss how the participant feels about accepting additional rings at her quarterly visits moving forward
After the month 3 follow-up visit, participants will transition from a monthly to a quarterly visit schedule. Additional guidance about this schedule shift may need to be incorporated into the HOPE counseling sessions that occur at the month 3 visit.

21. Month 3 Considerations (Cont.)
Where the participant will store her unused rings and used rings post-removal
Why it is important to change the ring on time each month and how the participant will remember when it is time to change her ring
The importance of not sharing rings with friends or family members

22. Month 3 Considerations (Cont.)
Any questions or concerns the participant has about having extra rings in her possession
Alternatives to accepting additional rings at this visit, as needed (namely, that participants have the option to return to the clinic each month to pick up a new ring if she feels uncomfortable having a supply of two unused rings in her home)
Participants who do not want to receive 3 rings at their quarterly visits are permitted to come to the clinic each month to obtain a new vaginal ring each month instead (e.g., if they do not feel comfortable having a supply of two additional unused rings at home). Note that monthly ring pick-ups should not be routine across the participant population, rather, they should be offered in the unique situation that a participant does not feel able to take 3 rings at a time.

23. Month 3 Considerations (cont.)
Provide instructions for tracking order of ring use and information that will be requested about each ring at her next visit
Rate how well she felt she was able to use each ring
Approximately how many days each ring was removed
Staff responsible for providing the rings to the participant should review the process for removing rings and storing in the appropriate used ring bag (i.e. in numerical order, see section above). Staff should emphasize that while we are asking the participant to track the order in which she uses the rings to the best of her abilities, we expect that this may not always be possible, and she will not be penalized for her inability to do.
Should the participant wish to use tools to help her remember this information (e.g. making a note in her diary or on a calendar), this is acceptable, however, these tools will not be collected or stored in the participant record nor are they expected to be routinely implemented across study participants or reconciled with residual drug data later.

24. Month 3 Considerations (cont.)
Contraceptive method/next dose
What to do in case of suspected pregnancy between visits
What to do in case of suspected HIV exposure between visits
If she will be due for contraception provision prior to her next scheduled study visit, staff should work with her to arrange for contraceptive coverage, either by scheduling an appointment at the clinic, providing additional coverage at the current visit (e.g. extra packs of oral contraceptive pills or condoms), or making sure she can access family planning services through the public sector, if that is where she prefers to receive her contraceptive method.
Participants should be encouraged to contact the study clinic any time they have a suspected or confirmed pregnancy and should be invited to the clinic for a confirmatory test any time. Staff should reassure participants that continued product use is ok unless or until a positive pregnancy test is received.
Participant should be counseled on what the signs and symptoms of acute HIV are, and encouraged to contact the clinic if she suspects HIV infection, and invited to the clinic for HIV testing at any point per clinician discretion.

25. Considerations for Interim Contacts During Quarterly Follow-up Schedule
Consider strategies for supporting participants between quarterly visits with interim contacts such as by phone or through SMS
The goals of these contacts could range from general check-ins, to supporting retention (visit reminders), to supporting ring use or reminders to change rings.
Permission from participant must be provided/documented (e.g. on site locator)
Frequency/content determined by site
Ensure IRB approvals in place, if required
The frequency of contacts can be determined by the site team (e.g. monthly), however, routine contacts should not be so frequent as to be bothersome to the participant (e.g. daily).
Confidentiality should be considered when determining the content of any SMS messages, e.g. not to include information that would unwittingly disclose her study participation or ring use to others.
If required by IRBs, regulatory approvals of SMS as a contact method and/or messages contained must be obtained prior to implementation.

26. Visits to Pick Up Rings During Quarterly Follow-up Schedule
Visits for the sole purpose of picking up a new ring during a quarterly schedule should be streamlined
The only procedures required are those necessary to collect her used ring and dispense a new ring
Document as an interim visit
What strategies will you use for flagging/fast tracking these visits?
What are your plans for reimbursement of these visits?
The only procedures required are those necessary to collect her used ring (i.e. completing ring storage procedures and accountability documentation) and dispense a new ring (i.e. verbal check-in on AEs, negative HIV/pregnancy tests within 90 days, completing a ring request slip or new prescription, if applicable).
Each site should determine their plan for reimbursement of visits to pick up rings. While visits exclusively for the purpose of picking up rings should not be at a cost to the participant, the amount reimbursed should not be so much as to incentivize participants to pick up rings on a monthly schedule.

27. PUEV Procedures Administrative: Review/Update Locator
Schedule Next Visit
Reimbursement
Clinical:
Medical/Menstrual History
Provide Test Results
Record/Update AEs
Physical Exam
Pelvic Exam
Concomitant Meds*
Offer/Provide Contraceptives*
Treatment/referrals*
Lab:
Urine:
Pregnancy
GC and CT
Urine culture*
Blood:
HIV-1 Testing
Plasma Storage
Syphilis Serology
CBC with platelets
Serum Chemistries
Pelvic/Other:
Vaginal Fluid (self)
Hair
Trich
Used VR*
Other samples if ind*
Behavioral (Counseling):
Contraceptive
HIV pre-/post test
Options Counseling (HIV/STI risk reduction)
Note that detailed guidance and retraining about PUEV procedures will be provided closer to completion of study follow-up
Required PUEV Procedures = Purple (procedures that are if indicated are grey).
Product Use End Visit (PUEV) procedures include most monthly and quarterly visit procedures, with the following modifications:  
HIV prevention options counseling will be modified to focus on risk reduction plans once the dapivirine ring is no longer accessible
No vaginal rings are offered
A physical and pelvic exam are required
Testing for GC/CT, Syphilis, and Trichomonas is completed
Blood for serum chemistries and CBC with platelets is collected
PUEV ACASI is completed
Study Product/Supplies:
Offer Condoms
Remove/Collect VR*
Behavioral (Assessments):
Adherence
Behavioral
Social Harms
ACASI (PUEV)

28. Study Exit Procedures Administrative: Review/Update Locator
Reimbursement
Schedule Next Visit*
Clinical:
Medical/Menstrual History
Provide Test Results
Record/Update AEs
Concomitant Meds*
Offer/Provide Contraceptives*
Treatment/referrals*
Physical Exam*
Pelvic Exam*
Lab:
Urine:
Pregnancy
Urine culture*
GC and CT*
Blood:
HIV-1 Testing
Plasma Storage
Syphilis Serology*
CBC with platelets*
Serum Chemistries*
Pelvic/Other:
Vaginal Fluid (self)
Hair
Trich or other samples if ind*
Behavioral (Counseling):
HIV pre-/post test
HIV/STI risk reduction
Contraceptive*
Study Exit/Termination Visit procedures include most monthly visit procedures, with the following modifications:
No HIV prevention options counseling is completed, however, participants still receive HIV risk reduction counseling per site SOPs
No vaginal rings are offered or collected
A behavioral assessment is completed
Contraceptive counseling only occurs if indicated
Next visit scheduling only occurs if indicated
Study Product/Supplies:
Offer Condoms
Behavioral (Assessments):
Study Exit Assessment

29. Follow-up Pop Quiz
Get out your quiz paper!

30. 1. Which of these procedures is required at all scheduled follow-up visits?
Physical Exam
Pelvic Exam
Collection of blood, swabs and hair for adherence measurements
Behavioral Assessments

31. 2. What is the primary difference between monthly and quarterly visit procedures?

32. 3. True or False: With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring.

33. 4. Name one consideration for counseling at a participant’s Month 3 visit

34. 5. Which of the following procedures is required prior to providing a ring?
AE assessment and reporting
HIV testing and counseling and pregnancy testing if this has not been done within the past 90 days
Collection of Used Ring (and unused, if applicable), if available
Adherence Counseling/Product Use Instructions, as needed
All of the Above

35. How did you do??
1. Required at all visits: Collection of blood, swabs, hair
Primary difference between monthly/quarterly: Behavioral assessments done at quarterly visit
True: With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring.
Month 3 Considerations: Varied responses
Minimum procedures required to provide a ring: (E) All of the above

36. Questions?