Transcript Trials and Tribulations of SDTM Trial Design 2011

Trials and Tribulations
of SDTM Trial Design
Mary Lenzen
Octagon Research Solutions
ESUG Telecon
July 26, 2011
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Why Do Trial Design
• Rapidly understanding the design of the study
• Standard and relatively simple data structures
• Relatively small number of rows of data and
easy to comprehend
• Useful for both FDA reviewers and internal
sponsor use
• Information can be centrally accessible and
searchable
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Trial Design: Overview
Ordered by Complexity
• Trial Inclusion/Exclusion Criteria (Lookup table)
• Trial Summary (Descriptive attributes of trial)
• Trial Visits (Planned)
• Trial Arms (Planned)
• Trial Elements (Planned)
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Inclusion/Exclusion
• Challenge of 200 character limit
• Truncation – potential for duplicate IETEST
values
• Need protocol or CRF for complete IETEST
values
• Subject IETEST/IETESTDC must match Trial
Inclusion/Exclusion IETEST/IETESTCD
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Summary
• Key details about the trial
• One record per parameter value
• TSGRPID used to group multiple related parameters
such as Dose, Units, Frequency etc
• TSSEQ used as a key for multiple records with the
same parameters
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Visits
• Planned schedule of Visits
• Timing variables: VISITNUM, VISIT, and
VISITDY
• What is really the start and end of a visit?
• Create Subject Visits dataset from Visit based
SDTM datasets
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Visits (2)
• Planned schedule of Visits
• Challenge is in defining start and end of a visit
• ARM/ARMCD can be used if schedule varies by Arm
STUDYID
DOMAIN
VISITNUM
VISIT
VISITDY
ARMCD
ARM
TVSTRL
1999001
TV
1
Visit 1
Signing of
informed consent
1999001
TV
2
Visit 2
30 minutes
before receipt of
Run-In drug
1999001
TV
3
Visit 3
30 minutes
before receipt of
blinded treatment
1999001
TV
4
Visit 4
1 week after
receipt of blinded
treatment
1999001
TV
5
Visit 5
2 weeks after
receipt of blinded
treatment
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
TVENRL
Completion of
lab draw
30 minutes
after receipt of
blinded
treatment
Completion of
final
disposition
page
Creating Subject Visits
Subject Visits comes from the data, rather than the
Visit Start and End Rules.
STUDYID DOMAIN USUBJID VISITNUM VISIT VISITDY
SVSTDTC
SVENDTC
1999001
SV
145-011
0
2003-04-01 2003-04-01
1999001
SV
145-011
1
2003-04-16 2003-04-16
1999001
SV
145-011
2
2003-05-01 2003-05-02
1999001
SV
145-011
4
2003-06-01 2003-06-01
1999001
SV
145-011
5
2003-06-16 2003-06-16
1999001
SV
145-011
5.1
SVUPDES
2003-06-17 2003-06-17 Evaluate severe
rash
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Trial Arms and Elements Overview
Trial Elements describes the
Elements and the rules for
the start and end of each.
Trial Arms
describes the
Elements in each
Arm, their order
and Epoch, and
any branching or
transition rules.
Screen
Drug A
Run-in
Placebo
Drug B
Placebo
Screen
Run-In
Placebo
Drug A
Screen
Run-In
Drug A
Drug B
Screen
Run-In
Drug B
Run-In
Treatment
Epochs are described only in Trial
Arms, and have no separate table.
Screening
Trial Visits describes the
planned Visits for each Arm,
Visit 1
Visit 2
Visit 3
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2011
Octagon
Research
Solutions,
Inc.
All
Rights
Reserved.
and any start and The
end
rules.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Visit 4
Visit 5
Creating Trial Arms (1)
STUDYID
Placebo
Screen
Run-In
Placebo
Drug A
Screen
Run-In
Drug A
Drug B
Screen
Run-In
Drug B
DOMAIN
ARMCD
ARM
TAETORD
ETCD
TABRANCH
EPOCH
1999001
TA
P
Placebo
1
SCRN
1999001
TA
P
Placebo
2
RUNIN
1999001
TA
P
Placebo
3
PLAC
Treatment
1999001
TA
A
Drug A
1
SCREEN
Screen
1999001
TA
A
Drug A
2
RUNIN
1999001
TA
A
Drug A
3
DRUGA
Treatment
1999001
TA
A
Drug B
1
SCREEN
Screen
1999001
TA
A
Drug B
2
RUNIN
1999001
TA
Screen
Randomized to
Placebo
Randomized to
Drug A
Randomized to
Drug B
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010
Octagon
Research Solutions,
Inc. All DRUGB
Rights Reserved.
Drug
B are
TheAcontents of this
document
confidential3and proprietary
to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Run-In
Run-In
Run-In
Treatment
Creating Trial Arms (2)
• High level treatment plan
• Composed of Elements from Trial Elements
• Planned ARM values in DM correspond to
ARM values in Trial Arms
• Names of ARM should reflect the protocol
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Elements (1)
• Usually the most challenging dataset
• Not a duplication of EX (Exposure)
• Start rules are the most important
– Subject data must exist to support the creation of
these
– Start of next element defines end of previous
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Elements (2)
• Simple as possible
• Screening Element – use date of informed
consent for Start Rule
• First Treatment Element - date/time of the first
administration of that treatment.
• End of the last Element usually coincides with
the date/time the subject completes the study
• Use pseudocode to facilitate and ensure
creation of Subject Elements data
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
Creating Trial Elements (2)
Trial Elements describes the
Elements and the rules for
the start and end of each.
ETCD
Screen
Run-in
Drug A
TESTRL
Drug B
STUDYID
DOMAIN
1999001
TE
SCRN
Screen
Informed consent
signed
Start of next
element or date
subject dropped
P2W
1999001
TE
RUNIN
Run-in
First dose of run-in
drug
Start of next
element or date
subject dropped
P1W
1999001
TE
PLAC
Placebo
First dose of placebo
Start of next
element or date
subject dropped
or completed
P2W
Example pseudocode:
DSSTDTC where DSDECOD
= INFORMED CONSENT
ELEMENT
Placebo
TEENRL
Example pseudocode:
EXSTDTC where EXTRT =
RUN-IN DRUG
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
TEDUR
Creating Subject Elements (3)
STUDYID DOMAIN USUBJID SESEQ
ETCD
ELEMENT
SESTDTC
SEENDTC
1999001
SE
145-011
1
SCRN
Screen
2003-04-01
2003-04-15
1999001
SE
145-011
2
RUNIN
Run-In
2003-04-15
2003-04-22
1999001
SE
145-011
3
PLAC
Placebo
2003-04-22
2003-05-06
DSSTDTC where DSDECOD
= INFORMED CONSENT
EXSTDTC where EXTRT =
RUN-IN DRUG
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
SEUPDES
Trial Design Challenges
Retrospective creation can be difficult
– Finding the information
• Protocol
• CRFs
• Actual Subject Data
– Inconsistency in information
– Authored by different people
– Interpretation
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
TDM Best Practices
• SIMPLE and informative
• Create Trial Summary first to become familiar
with the Study
• Use a Trial Design Template
• Use Controlled Terminology
© 2011 Octagon Research Solutions, Inc. All Rights Reserved.
© 2010 Octagon Research Solutions, Inc. All Rights Reserved.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.
The contents of this document are confidential and proprietary to Octagon Research Solutions, Inc.