SSP Manual Updates for Study Implementation

1. SSP Manual Update31 January 2014Version 1.3 Overview of changes which affect implementation

2. Overview and Version Control Document • While most SSP sections are now at V1.3, remember that not every SSP section is updated each time • Current version number and release date of each section is listed in the version control document • Comments column highlights main updates for that section, if applicable. • Minor updates may not be detailed in the comments column.

3. Section Updates Affecting Implementation • The following slides provide an overview of the SSP Manual updates which affect study implementation. • Updates incorporate previous guidance provided through priority emails, operational guidance, data communiques, etc. • Some updates may be more administrative in nature and will not be covered in this presentation. • All sites are responsible to review the SSP changes in full.

4. Section 2 - Protocol • This section was updated to include Clarification Memo #1, issued 7 August 2013, in the list of current protocol documents.

5. Section 3 - Documentation • Section 3.2.2: Added guidance to specify that addendums made to chart notes should be signed and dated using the date they were written • Section 3.2.4: Bold text was added to reflect CM#1 language: • Any lists, appointment books, or other documents that link PTIDs to other participant identifiers (such as the PTID/Name Link Log) should be stored securely (locked cabinet/drawer if hard copy; password protected if electronic) and it is recommended in a location separate from individual participant records (that identify participant by either PTID or name). 

6. Section 3 - Documentation • Appendix 3-1: Suggested Filing Structure for MTN-020 Essential Documents, was updated to include a File/Binder forData Collection Tools, as these are not included in the SSP Section 14 for ASPIRE. • Case Report Forms (CRFs) • Other data collection tools, as needed (e.g. In Depth Interview (IDI) guides) • Please ensure these are printed and filed somewhere in your essential documents.

7. Section 5 – Informed Consent • Section 5.9: Added guidance clarifying that if a participant signs her name in a form that deviates from the specifications outlined in the DAIDS Source Doc SOP (e.g. she uses initials for both her first and last names, or signs only using her first name), sites should acknowledge this deviation and verify that the mark represents the participant’s signature as she wrote it. Sites may work with OCSO to develop a standard memo to document these deviations, if desired.

8. Section 5 – Informed Consent • 5.10.1: If a participant changes her mind about participating in one of the optional components of the ASPIRE study (off site visits, qualitative component, long term specimen storage): • Use the most current version of the appropriate ICF and review the information pertinent to the participant’s decision (e.g. if a participant changes her mind about off site visits, review this section of the consent). • If the current ICF differs in any way from the version the participant originally signed, these changes should be reviewed with her as well. • If reconsentingprocedures are being conducted using an enrollment informed consent that contains signature blocks allitems should be reviewed and re-signed based on the participant’s current preferences. • The signature lines at the end of the consent for participant, staff, and witness (if applicable) must also be completed in full.

9. Section 6 – Participant Follow-up • Section 6.4.3: Added guidance to specify that while there is no formal restriction, sites should aim to do no more than 3 consecutive off-site visits for a participant due to the inability to complete full safety evaluations (e.g. physical and pelvic exams) during these visits. • Section 6.5.3: Added reminder that sites must adhere to all guidance provided by the LC for follow-up HIV testing plans for participants who have positive rapid HIV tests that are confirmed HIV negative by subsequent testing. • For example, the LC may recommend using alternate approved HIV rapid tests moving forward for these participants. • Section 6.8: Added reminder that language fluency should be considered in instances of participant transfer.

10. Section 7 – Visit Checklists • Updates to 7.1: • For items on the checklist that contain checkboxes, one set of initials is sufficient, even if multiple boxes are checked. • Entering multiple sets of initials for one procedure should be avoided as much as possible. If this is happening on a regular basis, the site should consider splitting the task into multiple items on the checklist so each procedure receives only one set of initials. • Updated appendices (previously posted to website): Follow-up and Seroconversion checklists Version 1.3, and PUEV version 1.4 to PDF

11. Section 8 - Retention • Section 8.4: Updated to specify that SMS and other means of communication with participants may be used throughout the ASPIRE trial assuming participant permission is provided (e.g. via the locator form, or documentation in chart notes, or a site-specific tracking tool). All means of communication must be in line with local IRB guidelines. • Section 8.7: Redundant text relating to voluntary withdrawals was removed as it is more fully addressed in section 6.9.

12. Section 9 – Study Product • Section 9.3.2 (Preparing Used Rings for Storage) was updated to reflect the ring collection procedures that were issued per Operational Guidance #6. • Section 9.6 was updated to reflect instructions for completing the MTN-020 Vaginal Ring Request Slip version 2.0 (removed guidance for version 1.0 completion). • All sites should be using V2.0 request slips – please contact Cindy Jacobson and SCHARP if you need these supplied.

13. Section 10 – Clinical Considerations • Section 10.3.1, the following guidance was added regarding trade names for medications (DC#9): • It is preferable to record the trade name of a medication on the CRF. • If the trade name is not available or not reportable per national guidelines, you may record the generic name of the medication. • A combination medication can be recorded as one entry using the generic name. • If a combination medication does not have a generic name or the generic name is unknown, each active ingredient must be reported as a separate entry in order to be accurately coded at SCHARP.

14. Section 10 – Clinical Considerations • Section 10.4.5 (Documentation of Exam Findings) was updated to include guidance about documentation of IUCD strings • IUCD strings may be visible upon exam and are also considered a normal finding. If documented, they should be present on the non-DataFax Pelvic Exam Diagrams form. Sites may determine whether they choose to consistently document the presence of IUCD strings (best practice) or not. It is recommended that if a participant has an IUCD but the string not visible upon exam, this be documented and followed up on.

15. Section 10 – Clinical Considerations • Section 10.6.1 (Participant Report and Clinician Assessment of Genital Bleeding) includes updates about identification and documentation of genital bleeding-related events (i.e. bleeding AEs, menses, and unexplained infrequent bleeding) • As with all SSP updates, relevant staff should ensure the section updates are reviewed in full • PLEASE SEE separate training slide set for genital bleeding updates

16. Section 11 – AEs • Details about reporting Vaginal Odor as an AE were added to Section 11.3.1 (Reporting Genital, Genitourinary, and Reproductive System AEs) • Per the FGGT, odor is listed as a symptom and should be documented as an AE if different from baseline and not due to a larger diagnosis. This is based on participant report of the symptom, and grading based on the participant’s perception of severity. • The timeframe for ‘normal’ postpartum bleeding was clarified in Section 11.3.3 (Reporting Considerations for Pregnant Participants) – bold text added: • In general, bleeding associated with delivery and the postpartum state (the 6 weeks following delivery) is not considered an AE, provided the bleeding does not exceed the expected amount

17. Section 11 – AEs • A new section (Section 11.3.7) on Reporting HIV Infection Illness was added. This guidance is the same that was put out in Data Communique #10. • “HIV infection” should not be reported as an AE or written anywhere on an AE/GAE Log CRF (it is a primary endpoint) • However, if a participant seroconverts and develops one or more signs or symptoms of acute HIV- infection, it is appropriate to report these sign(s)/symptom(s) as a single AE using ONLY the term “seroconversion illness” for item 1 on the AE/GAE Log CRF. • Use the comments section of the AE/GAE Log CRF to describe each HIV-related sign/symptom (e.g., fatigue, pharyngitis). • See section text for full details

18. Section 12 – Counseling Considerations • Added clarification to 12.1: Condom provision is understood to mean that condoms are offered to participants at each visit even though participants are under no obligation to accept this offer and may decline study-provided condoms at any time and for any reason. • 12.2: Copper bearing IUD added to WHO-recommended methods of emergency contraception. Site staff are encouraged to incorporate information about emergency contraception into the monthly contraceptive counseling sessions in ASPIRE to increase participant understanding of how emergency contraception works and its availability at the clinical research site.

19. Section 13 - Lab • Changed “Network Laboratory (NL)” to new name “Laboratory Center (LC)”. This is new standard terminology from DAIDS. • Added guidance that all HIV testing queries and algorithm related notifications should be sent to mtnvirology@mtnstopshiv.orgusing the MTN Network Lab HIV Query Form (Appendix 13-5). • Section 13.8.8 (Intra-Vaginal Ring Storage) was updated to reflect the ring collection procedures that were issued per Operational Guidance #6. • Updated that MRC will be reading gram stains on site. • References to associated text in SSP section 10 (clinical considerations) was added to relevant sections.

20. Section 14: Data Management • Addition of the Specimen Storage CRF to the CRFs required at monthly visits for vaginal ring storage in Table 14-3 – Schedule of Forms • Removal of AE-1 form completion guidance for related AEs within section 14.4. Guidance within subsequent Data Communiques to replace and clarify this guidance for all AEs reported to SCHARP • Data Communiques #9 and 10 form completion instructions added to sub-section 14.2.1

21. Section 16 - ACASI • Guidance regarding the timing of ACASI after permanent discontinuation that was only relevant before LoA#2 was removed. • All sites should now be operating under the following schedule: …complete the PUEV/Discontinuers ACASI questionnaire and the Ring Worries CRF at the visit the discontinuation is initiated (or next regularly scheduled visit if this is done at an interim visit). • Other minor corrections made to figure labeling and contact emails

22. Section 17: Study Reporting Plan • Retention Report (Item 10) in section 17.2 has been updated. The retention report now includes a row to provide the number of participants, excluding those who have early terminated, who have completed each study visit month. • Section 17.2 now includes the AE Data Listing, which provides MTN-020 Safety Physicians with a cumulative listing of AEs for purposes of safety monitoring.

23. Section 17: Study Reporting Plan • New Retention Report Summary added to SDMC Reports Posted on Atlas (Table 17-2 and Item 11) • This new Summary Report includes: • Cumulative visit retention over all expected visits, by site • Cumulative visit retention for the last 3 months, by site • Retention rates excluding participants who have terminated early

24. Section 18 - Qualitative Component • Clarifications were made about proceeding with 2nd or 3rd serial interviews in the event a participant is on product hold or declining product • These should generally proceed, eligibility criteria about being on product only apply to 1st interview, but QMT can always be consulted. • Clarifications about when to approach participants who are terminating early about participation in a single IDI, and how to document this conversation, were made.  • Most important thing is it should be documented clearly in the chart notes that the participant is withdrawing consent, but is agreeing to participate in one final interview and when this interview will occur.  Interview should occur prior to termination.  Alternatively, if she is not willing, document this.

25. Section 18 - Qualitative Component • All interviewer-administered guides should be administered in the preferred language of the participant.  • This may be different than the language she provided informed consent in, as long as fluency is confirmed/documented in both languages (e.g. on the IC coversheet and/or chart notes).  • To maintain neutrality and promote an open/free environment, interviewers should be independent from (i.e. not involved in) any study procedures that will be discussed during the IDI or FGD.

26. Section 18 - Qualitative Component • Referral of issues identified during interview: • Timing: If the issue is ongoing, ideally follow-up should occur after the interview is complete.  However, if the issue is historical/resolved at the time of the interview, follow-up may occur at the next scheduled visit, per the discretion of the IoR. • Maintaining rapport: Although the interviewer is required to share information about these events with other appropriate ASPIRE staff, she should aim to maintain a sense of trust, discretion and rapport with the participant by explaining this referral.  Some sample language is provided in the SSP updates. • Type of issues needing referral: was expanded to include misunderstanding of key concepts that relate to study participation/informed consent (e.g. placebo, randomization).

27. Section 18 - Qualitative Component • Updates were made to the Transcription/Translation Process: • QC should involve checks against the audio file.  • While it is ideal to have a staff member different from the interviewer conduct the transcription/translation, it is recognized this may not be feasible.  If the interviewer does conduct the transcription/translation, a separate staff member fluent in both languages must QC these documents.  • Staff responsible for transcription must provide verification that the transcript is an accurate and complete representation of the original audio file through use of a coversheet.  A template audio transcription certification coversheet is available on the ASPIRE website under MTN-020 Qualitative.

28. Questions??? • Please contact the ASPIRE management team (mtn020mgmt@mtnstopshiv.org) with any questions regarding SSP v1.3 updates