trial design in the cdisc world albert chau 26 july 2011 1
TRANSCRIPT
Trial Design in the CDISC World
Albert Chau
26 July 2011
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Agenda
How to construct Trial Design datasetso Relationships with other SDTM domains
Challenges for new userso Confusion of definitions/termso Granularity
Case study in oncology
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Trial Design Domains
Information about study designo No subject data
Describe the overall trial design and plan via data representation
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Trial Design Datasets
Trial Arms (TA) Trial Elements (TE) Trial Visits (TV) Trial Inclusion /Exclusion (TI) Trial Summary (TS)
Start thinking about this before you start the other SDTM datasets!
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Trial Summary (TS) Dataset
Summary of trial information No link to subject-level data in SDTM Common questions:
o What need to be included?o Why are we generating this?
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Trial Inclusion/Exclusion (TI)
Not subject-oriented Link to IE domain
o STUDYID, IECAT, IETESTCD, IETESTo Best to create TI first, before you tackle IE
Common questions:o How to truncate if >200 characters?o Protocol amendment: do we need to add to TI only the
changed criteria or all criteria?o Local amendment
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TA / TE / TV datasets
A data representation on the different epochs, arms and visit structure in the study
Where to start? Is there a systematic approach?
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Example 1 – Trial Design Schema
ScreenDrug A
Drug B
Follow-up
Follow-up
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Epoch
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-upEPOCH
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Arm / Treatment Strategy
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-up
AR
M(T
rea
tme
nt
Str
ate
gy)
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2
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Arm / Treatment Strategy
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-up
Study Cell
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2
Screen
Screen
Drug A
Drug B
Follow-up
Follow-up
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Trial Design Matrix
Screening Treatment Follow-up
A
B
Screen
Screen
Drug A
Drug B
Follow-up
Follow-up
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TE (Trial Elements)
What are the elements?o Unique study cell values (=ELEMENT)
Screen
Drug A
Drug B
Follow-up
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TE (Trial Elements)
Assign an element code (ETCD) to each value, define the start of each element (TESTRL) and end of each element (TEENRL or TEDUR)
Screen
Drug A
Drug B
Follow-up
SCRN
A
B
FU
Informed Consent
First dose of drug A
First dose of drug B
1 week after last dose of drug
ETCD ELEMENT TESTRL
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Trial Arms (TA) Dataset
Go back to the Trial Design Matrix 1 study cell = 1 row of record in TA So in our example we expect 6 rows of record ARM / ARMCD
o = Treatment Strategy o Not necessarily the same as the actual drug
names/codes ETCD / ELEMENT
o Must match up with the values in TE
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TE -> SE (Subject Elements)
Shows the trial progress of each subjecto Whether a subject passes through each elemento Timing of each element
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Trial Visit (TV) Dataset
Describe the planned visits in a trial VISITNUM and TRSTRL is required ARMCD expected VISIT and VISITDY permissible 1 record per planned visit per arm
o A “visit” may span over several days (eg screening visit)
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TV -> SV (Subject Visits)
Shows the actual visits of each subjecto Compare against the scheduled/planned visits or
assessments in TVo Include unscheduled visits
Designation of VISITNUM becomes crucialo Whole number for planned visitso Decimals for unscheduled visits in SV – and slot into
right place
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Challenges in 1 oncology study
Leukemiao Drug X (Days 1-4) is the current standard of treatmento Drug A (Days 1-7) is the experimental treatment
Patients to receive:o Drug A+X vs Drug X (1 course of treatment)o If patients on drug X not responding, then option to
“crossover” to drug A+X (1 further course) Follow-up
o Responders: Efficacy follow-up (+ post-remission therapies where applicable)
o Non-responders and relapse: Survival follow-up
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Study schema
Screen
Drug A + X
Drug X
Drug A + X
Efficacy FU (q 1 months)
Survival FU (q 3 months)
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Question 1 – what are the epochs?
1 Treatment epoch or separate into 2? 1 Follow-up epoch or separate into 2?
Screen
Drug A + X
Drug X
Drug A + X
Efficacy FU (q 1 months)
Survival FU (q 3 months)
Screening Treatment Efficacy FU Survival FU
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Question 2 – How many arms?
For the patients on Drug X and then rollover to Drug A+X – should this considered as a separate “arm”?
Screen
Drug A + X
Drug X
Drug A + X
Efficacy FU (q 1 months)
Survival FU (q 3 months)
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Question 3 – Granularity of Elements
Do we model using “Treatment”+”Rest” or simply “Treatment” (which includes rest period)?
Length of “Rest” differs between patients Do we need to distinguish between “Treatment”
and “Rest”?
Treatment(Day 1 - 7)
Rest(Day 8 – ??)
Treatment(Day 1 - 37)
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Question 4 – Describing Trial Visits
How to number the visits, when you don’t know how many visits there are up-front?
Don’t have to be consecutive numbers Example:
o 1st course of treatment: Start with VISITNUM=11o Cross-over: Start with VISITNUM=51o Efficacy follow-up: Start with VISITNUM=201o Survival follow-up: Start with VISITNUM=501
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Question 5 – Varying Trial Visits
During Efficacy Follow-up, patients can receive “post-remission therapies”.
“Reset” follow-up clock from post-remission therapies
How to model Trial Elements and Visits?
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Question 5 – Varying Trial Visits
Suggestion:o Start with VISITNUM=201 for Efficacy Follow-upo Trial Element: Up to the next post-remission therapyo 1st Post-Remission therapy: VISITNUM=250o 2nd Post-Remission therapy: VISITNUM=300o etc
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Question 6 – Post-remission therapies
For post-remission therapies in efficacy follow-up, the choice is down to the treating physician
Can potentially be Drug X or any other therapies
Should we create Trial Elements for the different therapies?
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Question 7 – Randomised but not treated
Randomisation usually starts 1-2 days before start of treatment due to logistic reason
What is the start and end of “Screen” and “Drug A”/”Drug A+X” trial elements in TE?
How to capture these patients in SE? Should randomisation be a separate visit in
TV/SV?
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Question 8 – When is a visit no longer “planned”
Planned visits for lab assessments: Day 15, Day 21
A patient had lab taken on Day 17 and Day 22 instead
Should these be put into planned visits of Day 15 and Day 21, or unscheduled visits?
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Other challenges in oncology studies
Post-remission therapy will be given and patients will be followed up “according to institution’s standard treatment practice”
Dose escalation studies – how many arms? Legacy studies: Do we need to provide trial
design datasets?
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Summary
Construction of TA/TE/TVo Study Schema Epoch Arm Study Cellso Unique study cells = rows in TEo All study cells = rows in TAo If all arms have same visits, then 1 set of visits for all
arms. Otherwise 1 set of visits for each arm. Complex study designs
o Systematic approach will make life easiero Think at protocol/CRF design stage – don’t wait till the
endo Details vs ease of use
