1

MTN-003 MTN-003 Study Specific TrainingStudy Specific Training

Randomization Overview

2

Why Randomize?• Ensures that all study groups in a clinical trial

are comparable with regard to factors that could affect study outcomes (e.g., risk of HIV infection)– Age and other demographics– Past medical history and pre-existing conditions– Sexual behaviors and condom use

• Ensures that the study team will be able to clearly interpret the final study results– E.g. If the study drug has an effect in reducing HIV,

the effect of the drug is due to the drug itself and not some other factor

3

What Randomization AchievesActive Drug Placebo

Mean Age (yrs) 21 22

Mean Education (yrs)

11 11

Ever Pregnant 85% 84%

Married 5% 5%

Vaginal sex acts in last 7 days

5 5

Condom use in last 7 days

89% 89%

4

MTN-003 Randomization SchemeMTN-003 Randomization Scheme

AllParticipants

(4200)

Oral Tablet (2520)

Vaginal Gel(1680)

TruvadaTablet(840)

TenofovirTablet(840)

PlaceboTablet(840)

Tenofovir Gel

(840)

Placebo Gel

(840)

Not Blinded

Blinded

5

How Will the Randomization Process Work?How Will the Randomization Process Work?

• Envelope randomization will be used• SCHARP will provide two sets of envelopes

to each site1) Clinic Randomization Envelopes2) Pharmacy Randomization Envelopes

• Each set of envelopes will be numbered sequentially

• Each clinic envelope will have a matching pharmacy envelope (matched by envelope number)

6

• Each participant will be assigned a clinic randomization envelope and the matching pharmacy randomization envelope (e.g., a participant assigned clinic envelope 0100 will be assigned pharmacy envelope 0100, etc.)

• Assignment of the clinic envelope is the effective act of enrollment in MTN-003

Once a clinic envelope is assigned, the participant is considered officially enrolled in the study

How Will the Randomization Process Work?How Will the Randomization Process Work?

7

Importance of Sequential Clinic Importance of Sequential Clinic Envelope AssignmentEnvelope Assignment

• It is critical to the integrity of the study that clinic randomization envelopes are assigned in sequential order– If not assigned in proper order (even just one), this could

have a serious impact on validity of study results.

• SCHARP will provide clinic and pharmacy envelope tracking records to document envelope assignments– This will help ensure that envelopes are assigned

sequentially

8

Clinic Envelope Tracking RecordClinic Envelope Tracking Record

9

Randomization EnvelopesRandomization Envelopes• Clinic envelopes sent to site clinics• Pharmacy envelopes sent to site pharmacies• Envelope specifications:

– Large enough to contain A4 size paper– Opaque: manila folder inside each envelope– Tamper evident: sealed with blue tape– Labeled as “Clinic” or “Pharmacy” with site

information, study number, envelope number

• All envelopes assembled and reviewed for at SCHARP before shipment to sites

10

Clinic Randomization EnvelopesClinic Randomization Envelopes• Maintained by clinic staff

CLINIC MTN 003-Randomization Envelope DAIDS Site ID: 30302 CRS Name: R.K. Khan Hospital

CRS Location: Durban, South AfricaEnvelope Number: 0001

11

Pharmacy Randomization EnvelopesPharmacy Randomization Envelopes• Maintained by pharmacy staff• Look exactly like clinic envelopes, except

labeled as “PHARMACY”

PHARMACY MTN-003 Randomization Envelope DAIDS Site ID: 30302 CRS Name: R.K. Khan Hospital

CRS Location: Durban, South AfricaEnvelope Number: 0001

12

13

14

Clinic Randomization EnvelopesClinic Randomization Envelopes• Contain one MTN-003 prescription:

– Two-part, no carbon required (NCR) form• original (top part) is white• copy (bottom part) is yellow

– Assignment to “Oral Tablets” or “Vaginal Gel”

• Authorized prescriber or other designated clinic staff should complete information on prescription (e.g., PTID, Date Assigned)

• Signature of authorized prescriber is required• Dispensing instructions for pharmacy staff• Once completed, white (original) goes to pharmacy,

yellow (copy) is filed, along with opened envelope, in the participant study notebook

15

Gel Gel PrescriptionPrescription

16

Tablet Tablet PrescriptionPrescription

17

Pharmacy Randomization EnvelopesPharmacy Randomization Envelopes

• Contain study product dispensing records that will be completed by pharmacy staff

• Dispensing records are linked to prescriptions by envelope number

– The prescription from the clinic envelope will have the clinic envelope number pre-printed on it

– The pharmacy will receive the prescription and assign the pharmacy envelope with this same number to the participant

– Pharmacy staff will then dispense the assigned study product to the participant and record this information on the dispensing record.

18

• Confirm participant’s eligibility for the study

• Complete the enrollment informed consent process

• Administer the Baseline Behavior Assessment CRF and Baseline ACASI questionnaire

• Obtain blood for plasma archive• If applicable, administer Hepatitis B

vaccine

Before You Randomize…..

19

SCHARP Monitoring of RandomizationSCHARP Monitoring of Randomization

• Both clinic and pharmacy staff will record randomization information on CRFs and fax these CRFs to SCHARP

• Based on these CRFs, SCHARP will verify sequential assignment of clinic envelopes and proper random assignment to either oral tablets or vaginal gel

• SCHARP will also verify that the correct product was dispensed at the Enrollment Visit– SCHARP will monitor on-study dispensing as well

20

SCHARP Monitoring of RandomizationSCHARP Monitoring of Randomization

• If CRF data indicate a randomization error, SCHARP will contact the site clinic and/or pharmacy immediately to verify the information recorded on the CRF

• If it is determined that a randomization error has occurred, the Protocol Team will be notified and the site will be provided guidance on how to address the error

21

Operational ConsiderationsOperational Considerations• Each site must establish an MTN-003 SOP for

randomization (clinic procedures only) to specify:– Who will receive clinic randomization envelopes from

SCHARP– Where clinic randomization envelopes and tracking

record will be kept (secure location)– How clinic envelopes will be assigned and who will

assign them– Who will complete prescriptions– Where opened envelopes and yellow (clinic) copies

of prescriptions will be filed– Who will QA/QC randomization documentation and

how often this will occur

22

If the site identifies a If the site identifies a randomization error…randomization error…• Immediately contact the MTN-003

SCHARP Project Managers and FHI Clinical Research Managers and explain the situation– mtn003mgmt@mtnstopshiv.org

• Follow guidance provided by SCHARP and the Protocol Team– randomizations may need to be halted

during this time

23

Questions???Questions???