Trial Design in the CDISC World Albert Chau 26 July 2011 1.
Transcript of Trial Design in the CDISC World Albert Chau 26 July 2011 1.
Trial Design in the CDISC World
Albert Chau
26 July 2011
1
2
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
3
Trial Design Domains
Information about study designo No subject data
Describe the overall trial design and plan via data representation
4
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!
5
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?
6
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
7
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?
8
Example 1 – Trial Design Schema
ScreenDrug A
Drug B
Follow-up
Follow-up
9
Epoch
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-upEPOCH
10
Arm / Treatment Strategy
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-up
AR
M(T
rea
tme
nt
Str
ate
gy)
1
2
11
Arm / Treatment Strategy
ScreenDrug A
Drug B
Follow-up
Follow-up
Screening Treatment Follow-up
Study Cell
1
2
Screen
Screen
Drug A
Drug B
Follow-up
Follow-up
12
Trial Design Matrix
Screening Treatment Follow-up
A
B
Screen
Screen
Drug A
Drug B
Follow-up
Follow-up
13
TE (Trial Elements)
What are the elements?o Unique study cell values (=ELEMENT)
Screen
Drug A
Drug B
Follow-up
14
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
15
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
16
TE -> SE (Subject Elements)
Shows the trial progress of each subjecto Whether a subject passes through each elemento Timing of each element
17
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)
18
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
19
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
20
Study schema
Screen
Drug A + X
Drug X
Drug A + X
Efficacy FU (q 1 months)
Survival FU (q 3 months)
21
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
22
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)
23
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)
24
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
25
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?
26
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
27
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?
28
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?
29
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?
30
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?
31
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