HOPE SSP Updates May 2017

Reminders Version control document and updated sections available for download on HOPE website. New sections should be printed and filed on site. Superseded versions should be maintained in archive. Document staff training on SSP updates for regulatory filing.

Section 1: Introduction Added new guidance on uploading the Protocol Signature Page to DPRS (Effective August 1, 2017) PSP must be signed by IoR and uploaded to DPRS for all initial protocol versions, full amendments, and letters of amendment No action needed at this time for HOPE - sites will be contacted with additional guidance regarding retrospective uploading of PSPs, as needed

Section 1: Introduction Added requirements for change of IoR regarding training, and DoA and form completion for incoming & outgoing IoRs, including: Outgoing IoR Notify FHI 360, MTN Regulatory, and their OCSO PO of the change Complete End of Study FD Sign off on all DoA entries Incoming IoR Complete IoR Training Complete MTN FD Complete HANC FD, as needed Update 1572 Complete new PSP Complete new DoA

Section 3: Documentation Requirements Added guidance related to protocol deviations for screening or pre-screening participants who are not yet within Medidata “If a protocol deviation related to a screening or pre-screening participant who is not yet in the Medidata Rave database occurs, a paper-based protocol deviation log should be completed. If this participant enrolls into HOPE, the CRF must be entered into the database. If the potential participant never enrolls into HOPE (i.e. screen failure), the paper CRF should be scanned/emailed to the MTN-025 CDMs.”

Section 4: Participant Accrual, Screening, and Enrollment Specified official guidance on end of formal accrual period and modified follow-up schedules for participants who enroll after this date 15 September 2017 is end of formal accrual period: Complete enrollment of all eligible HOPE participants Submit a brief summary of recruitment activities to HOPE management Cease formal recruitment activities Submit Pre-Screening Outcome for all former ASPIRE participants Site teams are expected to make every effort to complete enrollment of all eligible HOPE participants and submit a brief summary of recruitment activities by 15 Sept. 2017. At this point, sites should cease formal recruitment activities and a Pre-Screening Outcome CRF should be submitted for each ASPIRE participant.

Section 4: Participant Accrual, Screening, and Enrollment (continued) 25 May 2018 is last possible date for any HOPE enrollments: Site may continue to enroll women after the end of the formal recruitment period However, formal recruitment efforts should not take place between 15 Sept. 2017 and 25 May 2018 More active follow-up may be conducted with participants who previously expressed interest in enrollment but had a clinical condition that prevented enrollment (e.g. breastfeeding) In an effort to provide women with the maximum ability to access the vaginal ring, sites may continue to enroll women who become eligible or are interested in HOPE participation through 25 May, 2018. Formal recruitment efforts should not take place between 15 Sept. 2017 and 25 May 2018, but sites may conduct more active follow-up with participants who previously expressed interest in enrollment but had a clinical condition that prevented their enrollment.

Section 4: Participant Accrual, Screening, and Enrollment (continued) Shortened follow-up for participants who enroll after 15 Sept. 2017: Use visit scheduling tool to determine the target day and visit window for the Month 1 visit. Schedule M1 visit for participant. Contact HOPE management team to receive the participant-specific modified follow-up schedule and PUEV date. Inform late-enrolling participants that participation will be shorter than 1 year, with study exit around Sept/Oct 2018. For participants who enroll after 15 Sept. 2017, sites should use the visit scheduling tool to determine the target day and visit window for the Month 1 visit. However, site staff should inform the HOPE management team of the enrollment to receive guidance on the modified follow-up schedule and PUEV. Sites should also be sure to inform late-enrolling participants that their study time will be shorter than 1 year and that they will exit the study around Sept/October 2018.

Section 4: Participant Accrual, Screening, and Enrollment (continued) Example #1: A participant who was previously ineligible due to breastfeeding anticipates she will stop nursing in December 2017, after the formal accrual period has ended. The site takes note and contacts her around this time, and she confirms that she wants to join HOPE, even though her time on study will be shorter and end around September/October 2018. It is acceptable to enroll this participant up until May 25th, 2018.

Section 4: Participant Accrual, Screening, and Enrollment (continued) Example #2: A participant whom the site has previously been unable to contact hears about HOPE through her friends. She presents to the site in February of 2018 and is interested in screening for the study. It is acceptable to enroll her up until May 25th, 2018. She should be informed prior to enrollment that her time on study will be shorter, and will end around September/October 2018.

Section 6: Participant Follow-Up Added reference to modified follow-up schedules for participants enrolled after the formal recruitment period Clarified that pregnancy outcome form should be completed within the visit folder at which pregnancy was originally reported Updated requirements for prescription completion in instances of transferring participant to different country

Section 7: ACASI and Behavioral Assessments Updated guidance for follow-up on issues raised during behavioral form administration: No counseling or correction of misinformation should ever be provided during the interview/data collection process. However, it is recognized that some information reported during the interview may prompt further action (see next slide)

Section 7: ACASI and Behavioral Assessments If issue relates directly to participant’s safety and well-being: Specifically, if violence/abuse, sexual assault, social harms, food insecurity, or AEs are reported Follow up on an individual level to collect additional information as needed and to provide referrals for the well-being of the participant. This should be done after the interview and by a separate staff member. If related to any other issue or misunderstanding: Do not counsel directly regarding these issues Rather, to prevent future bias in responses, these topics should be addressed at a group or site-level through generalized education or counseling. See also SSP section 11 for further management of AEs, social harms, IPV, or sexual assault.

Section 7: ACASI and Behavioral Assessments Added reference to new sexual assault questions on BBA and BA CRFs Clarified that Social Benefits Log should be completed for spontaneous reporting and that one form should be completed for each benefit reported Section 7.8 - Added guidance that ACASI data should only be merged to site-assigned data manager computer.

Section 9: Study Product Considerations Clarifications made about the supply of prescriptions and vaginal ring request slips Guidance about ring dispensation on modified (shortened) follow-up schedule added Enough study product should be dispensed to account for the time only until the next scheduled visit. Section 9.2.1 - Specified that Participant Specific Ring Accountability Log should be completed in paper

Section 11: Adverse Event Reporting and Safety Monitoring 11.1.2: Additional guidance about reporting congenital anomalies as SAEs If still enrolled in MTN-025 at pregnancy outcome: Report congenital anomaly on AE log form If exited from MTN-025 at pregnancy outcome: Record congenital anomaly on pregnancy outcome form and report to DAIDS, per protocol Section 8.4.4 Note: If enrolled in MTN-016, may need to report congenital anomaly as suspected major malformation and vice versa. 11.3.9: Added reference to site- and study-specific SOPs on IPV

Section 12: Counseling Considerations Section 12.2.2.3 updated with information from Operational Guidance #2, including new categories for residual drug feedback Results provided on a scale: 0, 1, 2, 3 “0” reflects probable low or no use/no HIV protection. “3” reflects probable high use/high HIV protection.

Section 12: Counseling Considerations Use RD to open a conversation with the participant, but emphasize the importance of the participant’s reported experience and regard her as the most reliable source of this information. Sometimes women may not use the ring all the time but still get good levels of protection; depending on how and when a participant used the ring, results in categories 1-3 could all represent achieving adequate protection from HIV-1 based on her needs and circumstances. For more information on RD feedback and Options Counseling, see Operational Guidance Documents #1 and #2 and the April HOPE Protocol Team Call recording.

Section 12: Counseling Considerations 12.2.5 updated with descriptions of new counseling demonstration videos and added clarification about schedule for reviewing recorded sessions Videos currently available (see HOPE website) include the following scenarios: Visit 1, Yes to Ring Visit 1, No to Ring Follow up visit, Drug Level 0 Follow up visit, Drug Level 2 Follow up visit, Drug Level 3 Follow-up visit, Drug Level 1, participant insists she used the ring

Section 13: Laboratory Considerations Section 13.9: Removed guidance on the Zimbabwe hair PK validation protocol

Section 14: Data Collection Section 16: Reporting Plan Training slides on updates are available on the MTN-025 Medidata Resource webpage on Atlas: https://atlas.scharp.org/cpas/project/MTN/025/_medidata_training/begin.view

Section 17: Qualitative Component 17.3.2: Modified guidance on SIDI accrual by interview type. Acceptors: Participants who accept study product at enrollment. Sites should accrue six acceptors. Non-Acceptors: Participants who do not accept study product at enrollment. Sites should accrue six non-acceptors. Product Switchers: Participants who accept study product at enrollment, but later decline to use the ring. If needed, sites may supplement their non-acceptor accrual with product switchers.

Section 17: Qualitative Component More on product switchers (17.5.1): Count toward a site’s non-acceptor accrual target Approach for an interview as soon as she declines study product. Use SIDI1 guide. If she receives/has received residual drug feedback, conduct a DF-IDI during the visit window when she received these results. Conduct SIDI2 on or around the PUEV visit.

Section 17: Qualitative Component Product switchers cont. Interview mode names used to name files for upload are as follows for serial interviews (17.8.2): SIDI for serial IDI with an A for acceptor or N for non-acceptor or NPS for non-acceptor product switcher (SIDI1A, SIDI1N, SIDI1NPS and SIDI2A, SIDI2N, SIDI2NPS) 17.3.4: To document product switchers on the QPL, record in the Non-Acceptor section with the notation “PS” after their PTID. Note: Some product switchers may have three interviews instead of the two that non-acceptors receive.

Section 17: Qualitative Component 17.5.1: Timing of SIDI2 for all serial IDI participants has been shifted from Study Exit/Termination to PUEV. M12: PUEV M13:Exit SIDI2

Thank you!