IMPAACT 2010 Screening Visits

Protocol References Section Title 6.1 Screening Visits Appendix 1 Schedule of Evaluations ─ Antepartum

Screening Visits Key operational reminders: Screening may be initiated after written informed consent is obtained Screening procedures must be performed within 14 days prior to enrollment Screening procedures may be performed on multiple days, including on the date of enrollment Screening procedures may be repeated, with the latest outcome used for eligibility determination

Repeat Screening Attempts If the 14-day screening period is exceeded, the screening process may be repeated, if adequate time remains to permit enrollment within 14 days of non-study ART initiation. In this case, all procedures listed in protocol Section 6.1, including the informed consent process, must be repeated except: New PIDs should not be assigned Confirmatory HIV testing need not be repeated Fetal ultrasound need not be repeated Previously documented medical and medications history information should be reviewed and updated through the date of re-screening (it is not necessary to re-record history information that was previously documented) Section 6.1, bottom of page 54

A mother’s baseline medical history is first recorded at the Screening Visit. True False

Where in the protocol can you find the required elements of the maternal baseline medical history? Section 6.11 Text and Table 3

A complete maternal physical exam is required at the Screening Visit True False

Where in the protocol can you find the required elements of the complete maternal physical exam? Section 6.12

Fetal ultrasound must be performed within 14 days prior to enrolment. True False

Fetal Ultrasound Fetal ultrasound should be performed if possible during the study screening period to: Estimate gestational age Assess for multiple gestation and fetal anomalies If ultrasound is performed during the screening period, results must be considered for purposes of eligibility determination If ultrasound cannot be performed during the screening period (should be rare), the best available method should be used to perform these assessments for purposes of eligibility determination Reminder this is the original wording in protocol Version 1.0 (CM #2 on next slide)

Fetal Ultrasound Per CM #2 … ultrasound scans performed during the current pregnancy prior to the study screening period may also be used for study purposes, provided the result reports from such scans meet the minimum requirements specified in protocol Section 6.13. This is an exception to the protocol specification that screening procedures must be performed within 14 days prior to enrollment. When a prior ultrasound scan result report that meets protocol requirements is available, it is not necessary to perform an additional scan for study purposes. When more than one ultrasound result report that meets protocol requirements is available, the earliest available results should be entered into eCRFs for estimation of gestational age.

Report Requirements Per CM #2 Date of scan Number of fetuses Estimated fetal weight if greater than 20 completed weeks gestation Biometry measures If less than 14 completed weeks gestation Crown-rump length If 14 or more completed weeks gestation Femur length Abdominal circumference Biparietal diameter and/or head circumference Ultrasound-based gestational age on the date of the scan or ultrasound-based estimated date of delivery

Fetal Ultrasound If a fetal ultrasound is not performed prior to entry, it must be done as soon as possible and within 14 days after study entry Ultrasound findings will then be used in algorithms to calculate gestational age at study entry and at delivery If a fetal ultrasound is performed after entry, enrolled participants will not be withdrawn from the study if the ultrasound identifies an exclusionary condition

AST and ALT test results must be available prior to enrollment. True False 4.1.4

If an exclusionary ALT result is obtained at screening, the test may be repeated, with the latest outcome used for eligibility determination. True False 4.1.4

When can enrollment occur? SUN MON TUE WED THU FRI SAT 1 Starts ART 2 3 Screening Visit 4 5 6 7 8 Screening lab results received 9 10 11 12 13 14 Last day to enroll 15 16 17 18 19 20 21 22 23 24 25 26 In this example, we have the same ART initiation and screening visit dates as in previous examples, so we know that the last day to enroll falls on the 14th of the month. We have also noted in this example that screening lab results are received on the 8th of the month. Looking at the calendar, we need to consider whether there enough time to recall the participant to the clinic and repeat the tests, with results received before the last day to enroll. This may or may not be possible, depending on when lab test results are received, and this example highlights the importance of coordination and communication between the clinic and the lab during the study screening period.

Plasma stored at the Screening Visit should be kept for all mothers who are screened, regardless of whether they enroll the study. True False

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IMPAACT 2010 Entry Visits

Protocol References Section Title 6.2 Entry Visit Appendix 1 Schedule of Evaluations ─ Antepartum

Entry Visits Key operational reminders For eligible mother-infant pairs, enrollment must occur at 14-28 weeks gestation and within 14 days of the mother initiating ART in the current pregnancy All Entry Visit procedures are expected to be performed on the day of enrollment Procedures that may provide information relevant to eligibility for the study (e.g., medical history, physical examination) should be performed first, prior to final eligibility determination.

Entry Visits Key operational reminders Final eligibility determination and confirmation must precede enrollment Enrollment must precede prescribing of study drug Prescribing must precede dispensing of study drug Blood collection should ideally precede enrollment and must precede ingestion of the first dose of study drug

VESTED FAQ The protocol indicates that, at the Entry Visit, blood collection should ideally precede enrollment and must precede ingestion of the first dose of study drug. This poses a problem for us because our understanding is that blood specimens collected at the Entry Visit should be labeled with both the PID and the SID, and the SID is assigned at enrollment. Therefore, it may not be possible to collect blood prior to enrolment. The protocol team acknowledges that SID numbers are needed to label specimens collected at the Entry Visit and agrees that is acceptable to collect blood at the Entry Visit after enrollment/ randomization. Per protocol, blood collection must still occur before each mother takes (ingests) her first dose of study drug.

A mother is considered enrolled in the study when … She provides written informed consent She and her infant are found to meet all study eligibility criteria She and her infant are assigned SIDs by the Subject Enrollment System

An infant is considered enrolled in the study when … The infant’s mother provides written informed consent The mother and infant are found to meet all study eligibility criteria The mother and infant are assigned SIDs by the Subject Enrollment System The infant is born

Entry Visit Activity

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