HOPE STUDY PRODUCT TRAINING Cindy Jacobson, PharmD

Overview Prescriptions Study Product at Enrollment and monthly until month 3 Quarterly ring supplies (and monthly if applicable) Follow-up visits Request Slip Study Product Accountability

Study Tools & References Site Pharmacists and Pharmacy Staff MTN-025 Protocol, Version 2.0, December 16, 2014 MTN-025 SSP, Section 9 Clinic SOPs (accountability and off site visits)

Enrollment Visit VRs are dispensed only upon receipt of a written prescription from an authorized prescriber MTN pharmacists will provide clinic staff with prescriptions Prescriptions will be produced as two-part NCR forms Top white sent to pharmacy, bottom yellow stays in ppt binder

PRESCRIPTION - TOP

**New PTID Format – 9 digits** Rave will generate the Participant Number using a custom function. Pharmacy (and LDO and LDMS) will use a truncated 9 character PTID that contains the Site ID and Participant Number (e.g., 103-000001). Other SCHARP systems will be modified to accommodate the new 15 character PTID structure. 3 Character Site ID# - 6 Character Participant-Specific Number

Prescription Completion The person who marks the informed consent check box is responsible for confirming the presence of a properly signed/marked and dated informed consent form for enrollment prior to recording his/her initials beside these boxes.

PRESCRIPTION – MIDDLE Box can be checked at the first visit if the participant states this preference. Otherwise, if at any time the participant states a preference for monthly, a new prescription will need to be completed with this box checked.

PRESCRIPTION - BOTTOM The clinic staff should only initial and date after reviewing the prescription to verify it is completed with authorized signature.

Prescription Completion Double-check the accuracy of all entries and then separate the two parts of the completed prescription. Be sure all signatures and initials are complete. Retain the yellow (clinic) copy in the participant study notebook. Deliver the white (pharmacy) original prescription to the study pharmacy.

VR DISPENSING The pharmacist will review the prescription for completion and accuracy. In the event that pharmacy staff identifies possible errors on the original prescription, they will return the original prescription to clinic staff for clarification or correction. If corrections are required, corrections must be made on both the white original prescription and the yellow copy. It is really important that any changes be made by the appropriate person (i.e. clinic staff or authorized prescriber) depending on the change and BOTH copies are done the same.

VR DISPENSING A signed and dated note explaining the corrections also should be recorded on both copies. Identical corrections and notes should be recorded on both copies, on the same date, by the same person. Corrections should only be made by study staff authorized to complete original prescriptions, and fully documented in the participant’s chart notes.

VR DISPENSING Only one vaginal ring may be dispensed at the enrollment visit. If a participant requests more than one ring due to inability to make it to her month 1 visit, effort should be made to reschedule the participant for enrollment on a date when she will also be able to make it to her scheduled month 1 visit.

VR DISPENSING Dispensing takes place on the day of enrollment and each scheduled follow-up visit (except PUEV and Termination) During the monthly visits, the decision to dispense >1 ring is up to the IoR and must be documented fully During the quarterly phase 3 rings will be provided (maximum dispensed = 3 rings) If >3 needed ppt needs to return during the quarter for additional ring at IoR discretion

VR DISPENSING AT MONTH 3 At month 3 visit participants will receive either 3 rings (quarterly) or 1 ring (monthly) At this visit ring(s) will be provided to the participant in a cosmetic bag Only one bag per participant!

VR DISPENSING Participant has the option to return monthly, preference is documented on the prescription ● This is NOT expected to be the “norm” ● These visits should be “fast-tracked”

VR DISPENSING Change in preference requires a new prescription If a participant requires and additional ring for any reason at a time other than when scheduled, additional VR (s) may be dispensed at IoR discretion This should be documented in writing (i.e. ppt chart) by IoR or documentation of verbal approval If IoR is and authorized prescriber, the signed Request Slip is sufficient documentation

PRESCRIPTION – MIDDLE

VR DISPENSATION The pharmacist will prepare the vaginal ring for dispensation. The VR should be picked-up by clinic staff for accountability Allowance made to dispense to runner providing documentation outlined in Chain of Custody SOP Participants receiving ring monthly will need to go through the clinic

VR and RETURN BAG DISPENSATION Each VR will be dispensed with a white zip return bag If 3 rings are dispensed, 3 bags will also be dispensed The pharmacist will apply a ring code recorded on a sticker to each pouch label He/she will also apply a sticker with a corresponding ring code to each bag

RING CODES Each VR dispensed for a participant will be numbered in sequential order Numbers will be 01.0, 02.0 and so on This number will be designated as a “Ring Code” Pharmacy staff will write or type the ring code on the sticker __ __ . __

RING CODES At an interim visit, if a ring must be dispensed (i.e., participant left next sequential ring at home) a decimal (0.1-0.9) in the Ring Code (e.g. 05.1) is necessary In most cases, the pharmacist will always dispense the next sequential whole numbered Ring Code (decimal is 0; e.g. 0.3.0) for the vaginal ring, because the participants are counseled to use the vaginal rings in sequential order

RING CODES The Vaginal Ring Request Slip will indicate if the ring requested is for an interim visit. The previously used ring code should also be provided. If that used ring code is not known, the pharmacist will need to determine the most likely previously used ring code based on the Participant Dispensing Record and the date of the interim visit ring request.

MTN-025 PARTICIPANT RING RETURN BAG When the vaginal ring is dispensed the pharmacist will also provide a white zip bag with this preprinted label. The pharmacist will complete the date and PTID. Clinic staff must complete the emergency contact information Ring code sticker placed here

CHAIN OF CUSTODY AND ACCOUNTABILITY MTN-025 Record of Receipts of Participant-Specific Study Product completed when picking up VR(s) and bags from pharmacy Begins documentation of CoC from the pharmacy to the clinic

Record of Receipts

Clinic Study Product Accountability The clinic responsibilities for accountability and tracking of study product will begin at the time the study product is dispensed to clinic staff by the site pharmacy To achieve the goals of the protocol and maintain compliance with regulatory requirements, a standardized process of tracking and accountability will be adopted and followed by all HOPE sites.

Clinic Study Product Accountability Clinic staff (or runner from clinic) takes the ring to the clinic Documentation for Clinic Product Accountability is completed which includes: 1. Clinic Participant-Specific Ring Accountability Log 2. Ring Collection/Insertion CRF 3. Ring Tracking Log CRF

Clinic Participant-Specific Clinic Study Product Accountability Log Process designed to preserve and document the chain of custody of the vaginal ring at the site clinic. 1. tracking the date it is distributed to the study participant 2. date of return of used ring to the clinic or unused ring to pharmacy 3. shipment to an outside laboratory for further testing or destruction

Clinic Participant-Specific Clinic Study Product Accountability Log This log is maintained and completed as outlined in the Clinic SOP The SOP defines who is responsible for updating, where stored and how/when QC’d

Documentation of Clinic Accountability 1. Clinic Participant-Specific Ring Accountability Log 2. Ring Collection/Insertion CRF 3. Ring Tracking Log CRF

MTN-025 Clinic Participant-Specific Ring Accountability Log As previously mentioned, this log must remain in the clinic and is used to document providing a ring to the participant as well as the return of that ring.

MTN-025 Clinic Participant-Specific Ring Accountability Log Once the ring has been dispensed by pharmacy to clinic staff, the “Provided” portion of the log is completed. This includes the date the ring is provided to the participant, the PTI, # of rings provided, visit code and clinic staff initials. (AJM: NOT SURE IF YOU ARE GOING TO USE THESE NOTES, BUT SOME OF THEM NEED UPDATING)

MTN-025 Clinic Participant-Specific Ring Accountability Log Focusing on the return portion of the log, the first step is to complete the RETRUNED section of the Clinic Accountability log. The information the must be completed includes the date the ring is returned/removed, visit code, # rings returned to the pharmacy if UNUSED), # used rings returned, # used rings stored for lab, date the ring sent to lab, # rings placed in destruction container and the container code. In order to complete the product destruction container code, sites will need to determine (in their SOP) how they want to code the containers. The used rings will need to be place in a container that will be destroyed. The final columns include clinic staff initials and a place for comments if applicable.

Ring Collection/Insertion, and Vaginal Ring Tracking Log CRFs The Ring Collection/Insertion and Vaginal Ring Tracking Log CRFs must also be completed by sites for documenting all study product provision and returns The Ring Collection/ Insertion and Vaginal Ring Tracking Log CRFs will be used by site staff to document study product returns as well as the Clinic Study Product Accountability Log described above.

Ring Collection/Insertion, and Vaginal Ring Tracking Log CRFs After documenting return of used rings on the CRFs and clinic log, clinic staff should store the rings per the SSP and site’s SOP for Study Product Accountability in the Clinic. In the unusual event that a ring was dispensed but never inserted, the returned (unused) VR must be returned to the clinic and documented by study staff on the Ring Collection/Insertion and Vaginal Ring Tracking Log CRFs and the Clinic Study Product Accountability Log

Ring Collection/Insertion, and Vaginal Ring Tracking Log CRFs The unused ring should be returned to the pharmacy for quarantine Only unused rings may be returned to the pharmacy All returned used rings will be sent to the laboratory for storage ● To be discussed in lab section

Documentation of Clinic Accountability 1. Clinic Participant-Specific Ring Accountability Log 2. Ring Tracking Log CRF 3. Ring Collection/Insertion CRF

Documentation of Clinic Accountability 1. Clinic Participant-Specific Ring Accountability Log 2. Ring Tracking Log CRF 3. Ring Collection/Insertion CRF

Ring Collection/Insertion CRF

Ring Collection/Insertion CRF (page 2)

Used Ring Destruction Log This log (on HOPE website) should be completed to document destruction of the specific waste container This will be the final documentation required for documenting the accountability of the used ring that is not destined for further testing in the laboratory It should be rare that a ring will be placed in a container for destruction

Used Ring Destruction Log

Study Product Supply at Follow-Up The MTN-025 Vaginal Ring Request Slip is completed and sent to the pharmacy to obtain a vaginal ring(s) at follow-up visits Like with the prescription: ►Be sure all signatures and initials are complete ►Retain the yellow (clinic) copy in the participant study notebook ►Deliver the white (pharmacy) original prescription to the study pharmacy

This is what the entire form looks like but the next few slides will focus on specific sections. Will highlight only used if a prescription has ever previously sent.

MTN-025 Vaginal Ring Request Slip The MTN-025 Vaginal Ring Request Slips will be provided to the sites from MTN pharmacist. To complete the form the site will need to complete the CRS name and PTID. To obtain a vaginal ring from pharmacy at follow-up the Re-Supply box should be checked and the quantity to be dispensed should be circled.

MTN-025 Vaginal Ring Request Slip Indicate follow-up or interim If interim, most recently used ring code if known

MTN-025 VAGINAL RING REQUEST SLIP These are all of things that clinic staff can communicate to the pharmacy a follow-up. In addition to resupply this form is used to indicate a product hold. This box is checked only if the clinician determines that the product should be held for a clinical (site-initiated) reason or other concern. The pharmacy will not dispense product to that participant again until another request slip is sent with the resume box checked and the quantity circled. If the participant decides to hold the product or declines use then the participant decline is checked and no product will be dispensed. When the participant agrees to continue the request slip is sent and the resupply checked and quantity circled. If the participant is permanently discontinued from vaginal ring use this box in checked, a reason provided and NO further rings will be dispensed. When the participant is no longer in the study this box is checked and no further product will be dispensed.

MTN-025 VAGINAL RING REQUEST SLIP This is the bottom of the MTN-025 Vaginal Ring Request Slip which requires the printed name and signature of the clinic staff and date that the form is completed.

Product Retrieval for Hold Study product use may be temporarily held at the request of the clinician Product must be retrieved within 5 working days for product hold due to pregnancy or permanent discontinuation for any other reason or IoR discretion Product must be retrieved within 7 working days if held for reasons other than pregnancy with expected duration of more than 7 days

Product Retrieval for Discontinuation Study product use may be discontinued or temporarily due to potential HIV seroconversion and requires product retrieval within 24 hours For all study product holds due to seroconversion, pregnancy or other safety related concerns, if product is not retrieved within the timeframe noted, the PSRT must be notified

VR Complaints VR problem may be noted by pharmacy, clinic, and/or participant. May concern dosage form (VR), packaging (overwrap), or other aspect. Clinic staff will make thorough record of clinic staff or participant complaint. Clinic staff member will email complaint to pharmacy Date of observed issue, date issue was reported, date VR was dispensed, did adverse event occur, nature of issue, picture (if possible and applicable), any other necessary details Photo is at all possible

CONDOMS All participants will be offered condoms Study staff may offer guidance on the use of female condoms Condoms must be supplied by the site If you have condoms remaining from ASPIRE you may use them (check expiration)