Transcript Randomization Overview

MTN-003
Study Specific Training
Randomization Overview
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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
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What Randomization Achieves
Active Drug
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Placebo
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Ever Pregnant
85%
84%
Married
5%
5%
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5
89%
89%
Mean Age (yrs)
Mean Education
(yrs)
Vaginal sex acts in
last 7 days
Condom use in
last 7 days
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MTN-003 Randomization Scheme
All
Participants
(4200)
Blinded
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Not
Blinded
Oral Tablet
(2520)
Truvada
Tablet
(840)
Tenofovir
Tablet
(840)
Vaginal Gel
(1680)
Placebo
Tablet
(840)
Tenofovir
Gel
(840)
Placebo
Gel
(840)
How Will the Randomization Process
Work?
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Envelope randomization will be used
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SCHARP will provide two sets of envelopes
to each site
1) Clinic Randomization Envelopes
2) Pharmacy Randomization Envelopes
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•
Each set of envelopes will be numbered
sequentially
•
Each clinic envelope will have a matching
pharmacy envelope (matched by envelope
number)
How Will the Randomization Process
Work?
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•
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
Importance of Sequential Clinic
Envelope 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
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Clinic Envelope Tracking Record
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Randomization Envelopes
• Clinic envelopes sent to site clinics
• Pharmacy envelopes sent to site pharmacies
• Envelope specifications:
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–
–
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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
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Clinic 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 Africa
Envelope Number: 0001
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Pharmacy 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 Africa
Envelope Number: 0001
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Clinic Randomization Envelopes
•
Contain one MTN-003 prescription:
–
Two-part, no carbon required (NCR) form
• original (top part) is white
• copy (bottom part) is yellow
–
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Assignment to “Oral Tablets” or “Vaginal Gel”
•
Authorized prescriber or other designated clinic staff
should complete information on prescription (e.g.,
PTID, Date Assigned)
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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
Gel
Prescription
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Tablet
Prescription
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Pharmacy 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.
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Before You Randomize…..
• 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
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SCHARP 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
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SCHARP 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
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Operational 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
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If the site identifies a
randomization error…
• Immediately contact the MTN-003
SCHARP Project Managers and FHI
Clinical Research Managers and explain
the situation
– [email protected]
• Follow guidance provided by SCHARP
and the Protocol Team
– randomizations may need to be halted
during this time
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Questions???
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