Transcript CDISC SDTM-BRIDG Mapping

CDISC SDTM-BRIDG Mapping
TA, TE and TS Discussion
March 4, 2014 Conference Call
Prepared by Wendy Ver Hoef, Samvit Solutions, Inc.
Agenda
• Discuss and resolve proposed new resolution for TABRANCH issues
•
•
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Assumptions and data example
Proposed BRIDG model additions
Instance diagrams
Proposed definitions
• Discuss and resolve proposed new resolutions for TATRANS issues
• Discuss and resolve issues identified with TE mappings
• Review evaluation of TSPARMCD values in EVS
• NOTE: In the old mapping, both TABRANCH and TATRANS were marked as
Deferred until further TDM work was completed, so these are truly new
mappings.
TABRANCH
Assumptions
• Screen, Drug A & Drug B are all
essentially elements that contain
an allocation activity, probably
near/at the end
• TABRANCH is an attribute of the
association between that
allocation activity and the next
step in the path for that arm
(etc.)
4 Arms
5 Defined
Activities
Description of allocation result
1..*
PlannedCritGroup
Planned0..1
Contingentprerequisite
On1..*
DefinedObsResult
Relationship
0..1
Current Classes
StudyProtocolVersion
DefinedActivity
1
0..*
DefinedAdministrativeActivity
1..0
1..*
1..*
0..*
1contingent
0..1
ActivityContext
1
0..*
prerequisite
prerequisite
PlannedActivity
PlannedRandomizationBookAllocation
1
1..*
DefinedExperimentalUnitAllocation
RandomizationBookEntry
(evaluation criteria)
Proposed
StudyProtocolVersion
DefinedActivity
1
0..*
1..*
PlannedCritGroup
Planned0..1
Contingentprerequisite
On1..*
DefinedObsResult
Relationship
0..1
1..0
1..*
1..*
0..*
1contingent
0..1
ActivityContext
1
0..*
prerequisite
PlannedActivity
Computably represents the branches
1
(path)
(element)
DefinedAdministrativeActivity
prerequisite
PlannedExperimentalUnitAllocation
1
(allocation activity)
Re-parented to new super class
DefinedExperimentalUnitAllocation
PlannedRandomizationBookAllocation
1
1..*
RandomizationBookEntry
Planned0..* Experimental
-UnitAllocationResult
0..*
(option)
Instance Diagram
Study1
(StudyProtVrsn)
PlnDrugAinStudy1
(PlanSubjActGrp)
Result 1
(PlnEUAllocResult)
TE Screen Element (DefinedActivity)
Test1
TestN
Randomization
…
(DefinedActivity) (DefinedActivity) (DefEUAlloc)
DefRandinStudy1
(ActivityContext)
PlanRandinStudy1
(PlanEUAllocation)
- description=TABRANCH
Result 2
(PlnEUAllocResult)
DefDrugBinStudy1
(ActivityContext)
PlnDrugBinStudy1
(PlanSubjActGrp)
- description=TABRANCH
TE Drug A Element (DefinedSubjActGrp)
DefDrugAAdmin
TestX
RsltBasedAlloc
…
(DefSubjActGrp)
(DefObservation) (DefEUAlloc)
And so on…
Questions
• Is there any difference between the “Open A” segment as it appears
in the “A-Open A” arm vs in the “B-Open A” arm (aside from what
precedes it)?
Issues
• BRIDG has a way to say an activity repeats for some duration, repeats
X times, repeats with a frequency of Y, or repeats until some
condition occurs, but it does not currently have a way to say an
activity is repeating indefinitely (i.e. without one of those other
aspects). Would there ever be a reason to have a indefinitely
repeating activity that has no limitations?
Proposed Definition #1 – Allocation Class
PlannedRandomizationBookAllocation (as is)
DEFINITION:
(for reference only)
DefinedExperimentalUnitAllocation (as is)
DEFINITION:
(for reference only)
PlannedExperimentalUnitAllocation (new)
DEFINITION:
An activity that is intended to occur at some
point in the context of a particular study and
that is the assignment of an experimental unit to
a portion of the study, such as an arm or a
portion of an arm (when secondary allocations
may occur) based on a randomization book.
An administrative activity defined at a
global library level that is the assignment
of an experimental unit to a portion of the
study, such as an arm or a portion of an
arm (when secondary allocations may
occur).
An activity that is intended to occur at
some point in the context of a particular
study and that is the assignment of an
experimental unit to a portion of the study,
such as an arm or a portion of an arm
(when secondary allocations may occur).
EXAMPLE(S):
EXAMPLE(S):
EXAMPLE(S):
A study has two treatment arms, A and B, to
which study subjects will be evenly distributed.
The first study subject to be randomized
received treatment Arm A and that was
documented as part of the Randomization Book,
the next study subject to be randomized will
receive the next open treatment, which is Arm B.
randomization, direct assignment based on
eligibility criteria, etc.
randomization, direct assignment based on
eligibility criteria, etc.
"Escalating dose cohort studies" enroll
subjects in successive arms, i.e., one arm is
completely filled before any subjects are
enrolled in the next arm. In such a study,
allocation depends on which arms have
been fully enrolled and which are currently
open for enrollment. Note that this
example assumes that the experimental
unit is the subject (rather than a part of a
subject or a group of subjects).
"Escalating dose cohort studies" enroll
subjects in successive arms, i.e., one arm is
completely filled before any subjects are
enrolled in the next arm. In such a study,
allocation depends on which arms have
been fully enrolled and which are currently
open for enrollment. Note that this
example assumes that the experimental
unit is the subject (rather than a part of a
subject or a group of subjects).
OTHER NAME(S):
OTHER NAME(S):
NOTE(S):
NOTE(S):
OTHER NAME(S):
NOTE(S):
A randomization book is a predefined set of
assignments to portions of a study based on
criteria, such as stratum group for example, that
ensures a desired distribution of experimental
units across those portions of the study. For
example, the book entries indicate which arm a
given experimental unit, Joe, is assigned to
based on the fact that he's the 5th person in
stratum group #2.
Proposed Definition #2 – Option Class
PlannedContingentOnRelationship (as is)
DEFINITION:
(for reference only)
A relationship between a planned activity and some criteria to determine if the activity should occur where all
activities are intended to occur at some point in the context of a particular study or experiment.
PlannedExperimentalUnitAllocationResult (new)
DEFINITION:
Only perform a certain lab test if drug X was administered. (target = another activity)
A possible outcome, of a planned
experimental unit allocation activity,
which indicates a path to which an
experimental unit may be assigned.
Only perform a substance administration of drug X if the blood pressure was over some threshold number. (target =
observation result from another activity that is an observation)
EXAMPLE(S):
EXAMPLE(S):
Only perform a substance administration of drug Y if the blood pressure was over some threshold number and either
the result of a certain lab test was positive or the subject's temperature was elevated, i.e. "(A and (B or C))".
OTHER NAME(S):
NOTE(S):
The criteria may be one of the following:
- another planned activity where the source activity does not occur unless the target activity has occurred
- the defined outcome of another planned activity where the source activity does not occur unless the target activity
outcome has occurred
- a planned group of other criteria that may be composed of a mix of other activities, observation results and/or other
groups
To evaluate whether the contingency was satisfied, the simple existence of a PerformedActivity (or subclass) related to
the DefinedActivity (or subclass) is not enough by itself. The PerformedActivity.statusCode and
PerformedActivity.negationIndicator must also be checked to ensure that the activity was actually performed.
PerformedActivity.statusCode must be "Completed" and PerformedActivity.negationIndicator must not be "true".
A randomization activity may assign
subjects to one of several drug
treatments, a direct assignment may
assign subjects to surgery based on a
positive response to a preparatory
regimen
OTHER NAME(S):
branch
NOTE(S):
Any evaluation criteria associated
with this allocation result is
represented by a
PlannedContingentOnRelationship
related to the PlannedActivity that is
linked to this result.
Proposed Associations
PlannedExperimentalUnitAllocationResult [assignedExperimentalUnitAllocationResult] (0..*) assign experimental units
to / is an option for (1) [assigningPlannedExperimentalUnitAllocation] PlannedExperimentalUnitAllocation
PlannedExperimentalUnitAllocation
-Result (new)
DESCRIPTION:
Each PlannedExperimentalUnitAllocationResult always is an option for one PlannedExperimentalUnitAllocation. Each
PlannedExperimentalUnitAllocation might assign experimental units to one or more
PlannedExperimentalUnitAllocationResult.
DEFINITION:
DEFINITION:
This association identifies a relationship between an allocation activity and an option to which experimental units will
be assigned.
EXAMPLE(S):
OTHER NAME(S):
NOTE(S):
PlannedExperimentalUnitAllocationResult [assigningPlannedExperimentalUnitAllocationResult] (0..*) be the activity
executed for / is an option through which experimental units are assigned to (1) [assignedPlannedActivity]
PlannedActivity
DESCRIPTION:
Each PlannedExperimentalUnitAllocationResult always is an option by which experimental units are assigned to one
PlannedActivity. Each PlannedActivity might be the path executed for one or more
PlannedExperimentalUnitAllocationResult.
DEFINITION:
This association identifies a relationship between an allocation option and the path through which an experimental unit
will go if assigned to this option.
EXAMPLE(S):
OTHER NAME(S):
NOTE(S):
A possible outcome, of a planned
experimental unit allocation activity,
which indicates a path to which an
experimental unit may be assigned.
EXAMPLE(S):
A randomization activity may assign
subjects to one of several drug
treatments, a direct assignment may
assign subjects to surgery based on a
positive response to a preparatory
regimen
OTHER NAME(S):
branch
NOTE(S):
Any evaluation criteria associated
with this allocation result is
represented by a
PlannedContingentOnRelationship
related to the PlannedActivity that is
linked to this result
Proposed Attribute
PlannedExperimentalUnitAllocationResult.description
DEFINITION:
The textual representation of the experimental unit allocation
result.
EXAMPLE(S):
In SDTM, the TABRANCH variable may contain a description such
as "Randomized to Placebo - 5 mg - 10 mg “, “Randomized to
Drug A“, “Assigned to Rescue on basis of response evaluation”.
OTHER NAME(S):
NOTE(S):
PlannedExperimentalUnitAllocation
-Result (new)
DEFINITION:
A possible outcome, of a planned
experimental unit allocation activity,
which indicates a path to which an
experimental unit may be assigned.
EXAMPLE(S):
A randomization activity may assign
subjects to one of several drug
treatments, a direct assignment may
assign subjects to surgery based on a
positive response to a preparatory
regimen
OTHER NAME(S):
branch
NOTE(S):
Any evaluation criteria associated
with this allocation result is
represented by a
PlannedContingentOnRelationship
related to the PlannedActivity that is
linked to this result
TATRANS
Question from Mapping Spreadsheet
• TATRANS Definition: ROLE: Rule NOTES/DESCRIPTION: If the trial design
allows a subject to transition to an Element other than the next Element in
sequence, then the conditions for transitioning to those other Elements, and
the alternative Element sequences, are specified in this rule (e.g., Responders
go to washout).
• Q from Wendy: this sounds like a combination description covering both
conditions and destinations - is that correct? If so, it doesn't exist in BRIDG
currently per se, but might correspond to a new attribute on the
PlannedActivity, though the SCC might have concerns about conflating several
different concepts (condition and destination) and instances (sounds like there
can be more than one element sequence).
• Proposed Mapping: Arm > PlannedActivity.transitionDescription (new attr)
• Rationale: This isn’t really the regular description, but it does belong on the
PlannedActivity because it deals with several possible paths & isn’t computable
Examples of TATRANS
Most examples show a
single “If…” statement, but…
It is possible to have
more than one.
Proposed Attribute Definition
PlannedActivity.transitionDescription(ST)
DEFINITION:
The textual representation of the possible alternative paths or sequences of elements through
which the subject may traverse.
EXAMPLE(S):
“If disease progression, go to Follow-up Epoch.”
“If progression, skip to Follow-up. If no progression, but subject is ineligible for or does not consent
to surgery, skip to Addl Chemo.”
OTHER NAME(S):
NOTE(S):
Example Trial 7 – Computable Representation
5 Options…
…But only 2 arms
BRIDG can handle that with existing model elements, representing the “If” conditions
as “contingent on” criteria for elements, e.g. within the 3rd study cell in the CRS arm.
TE Mappings
Issue with TE Mappings
• TE variables were initially mapped to PlannedSubjectActivityGroup,
but it turns out that ActivityContext seems a better fit because that
can be used in more than one place in a study, whereas a planned
activity is located in one Epoch only (though it may span >1 Arm)
• PlannedSubjectActivityGroup is a composite activity at a particular
point in the context of a study
• ActivityContext is a defined activity that is associated with a particular
study but not yet placed at a particular point, can be referenced many
times by planned activities placed throughout a study
• Proposal: Update all TE mappings to be anchored at ActivityContext
Proposed New Mappings
• (domain level) = ActivityContext
• ELEMENT = ActivityContext >
DefinedSubjectActivityGroup.code(CD).displayName
• ETCD = ActivityContext > DefinedSubjectActivityGroup.code(CD).code
• STUDYID = ActivityContext > StudyProtocolVersion >
StudyProtocolDocumentVersion > StudyProtocolDocument >
DocumentIdentifier.identifier
• TEDUR = ActivityContext > DefinedSubjectActivityGroup.duration –new
attribute, old mapping was to PlanSubjActGrp.duration, but that doesn’t
work if this is an element that can be used in more than one place in the
study.
• Implementation-Specific variables: DOMAIN, TEENRL & TESTRL
Proposed Attribute Definition
DefinedSubjectActivityGroup.duration(PQ.TIME)
DEFINITION:
The intended period of time for the activity.
EXAMPLE(S):
6 weeks may be the duration for a composite activity.
P7D may be used to represent a duration of 7 days.
OTHER NAME(S):
NOTE(S):
Note that due to the data type used
here, it is assumed that the ISO 8601
format for duration can be converted
to the HL7 format.
TSPARMCD Comparison
TSPARMCD Value
Comparison
Proposing dropping/leaving out
everything in this category. Any
concerns?
Actually AGEU was in the SDTM Terminology in EVS but was
not a value under TSPARMCD, but rather it’s own set of terms.
Is it safe to assume that AGEU is therefore not to be included?
For Reference
Example Trial 1: Parallel
Design Study Schema
Example Trial 4: Cyclical
Chemotherapy Study Schema
Example Trial 2: Crossover Trial Study Schema
Example Trial 3: Multiple
Branches Study Schema
Example Trial 5: Different Chemo Durations Study Schema
Example Trial 7: TROG 93-09 Study Schema
with 5 “options”
Example Trial 6: Different Cycle Durations Study Schema