1. CDISC SDTM-BRIDG Mapping
TA, TE and TS Discussion
March 4, 2014 Conference Call
Prepared by Wendy Ver Hoef, Samvit Solutions, Inc.

2. Agenda Discuss and resolve proposed new resolution for TABRANCH issues
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.

3. TABRANCH

4. 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
4 Arms
5 Defined Activities
Description of allocation result
(etc.)

5. Current Classes PlannedCritGroup Planned-Contingent- On-Relationship
1..*
PlannedCritGroup
Planned-Contingent-
On-Relationship
0..1
prerequisite
StudyProtocolVersion
1..*
DefinedObsResult
0..1
1..0
1..*
1..*
prerequisite
0..* 1
contingent
0..1
prerequisite
DefinedActivity 1
ActivityContext 1
PlannedActivity
0..*
0..*
DefinedAdministrativeActivity
PlannedRandomizationBookAllocation 1
1..*
DefinedExperimentalUnitAllocation
RandomizationBookEntry

6. Proposed PlannedCritGroup Planned-Contingent- On-Relationship
(evaluation criteria)
1..*
PlannedCritGroup
Planned-Contingent-
On-Relationship
0..1
prerequisite
StudyProtocolVersion
1..*
DefinedObsResult
0..1
1..0
1..*
1..*
prerequisite
0..* 1
contingent
0..1
prerequisite
Computably represents the branches
DefinedActivity 1
ActivityContext 1
PlannedActivity
Planned-Experimental-Unit-Allocation-Result 1
0..*
0..*
0..*
(element)
(path)
DefinedAdministrativeActivity
PlannedExperimentalUnitAllocation 1
0..*
(allocation activity)
(option)
Re-parented to new super class
DefinedExperimentalUnitAllocation
PlannedRandomizationBookAllocation 1
1..*
RandomizationBookEntry

7. Instance Diagram Study1 (StudyProtVrsn) PlnDrugAinStudy1
(PlanSubjActGrp)
Result 1
(PlnEUAllocResult)
- description=TABRANCH
TE Screen Element (DefinedActivity)
Test1
(DefinedActivity)
TestN
(DefinedActivity)
Randomization
(DefEUAlloc)
DefRandinStudy1
(ActivityContext)
PlanRandinStudy1
(PlanEUAllocation) …
Result 2
(PlnEUAllocResult)
- description=TABRANCH
DefDrugBinStudy1
(ActivityContext)
PlnDrugBinStudy1
(PlanSubjActGrp)
TE Drug A Element (DefinedSubjActGrp)
DefDrugAAdmin
(DefSubjActGrp)
TestX
(DefObservation)
RsltBasedAlloc
(DefEUAlloc) …
And so on…

8. 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)?

9. 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?

10. Proposed Definition #1 – Allocation Class
PlannedRandomizationBookAllocation (as is)
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.
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.
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.
DefinedExperimentalUnitAllocation (as is) DEFINITION: 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). EXAMPLE(S): 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). OTHER NAME(S): NOTE(S):
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).
EXAMPLE(S):
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).
OTHER NAME(S):
NOTE(S):
(for reference only)
(for reference only)

11. Proposed Definition #2 – Option Class
PlannedContingentOnRelationship (as is)
DEFINITION:
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.
EXAMPLE(S):
Only perform a certain lab test if drug X was administered. (target = another activity)
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)
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".
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.
(for reference only)

12. Proposed Associations
PlannedExperimentalUnitAllocationResult [assignedExperimentalUnitAllocationResult] (0..*) assign experimental units to / is an option for (1) [assigningPlannedExperimentalUnitAllocation] PlannedExperimentalUnitAllocation
DESCRIPTION: Each PlannedExperimentalUnitAllocationResult always is an option for one PlannedExperimentalUnitAllocation. Each PlannedExperimentalUnitAllocation might assign experimental units to one or more PlannedExperimentalUnitAllocationResult.
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.
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

13. 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

14. TATRANS

15. 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

16. Examples of TATRANS Most examples show a single “If…” statement, but…
It is possible to have more than one.

17. 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):

18. 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.

19. TE Mappings

20. 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

21. 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

22. 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.

23. TSPARMCD Comparison

24. 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?

25. For Reference

26. Example Trial 1: Parallel Design Study Schema
Example Trial 2: Crossover Trial Study Schema
Example Trial 3: Multiple Branches Study Schema
Example Trial 4: Cyclical Chemotherapy Study Schema
Example Trial 5: Different Chemo Durations Study Schema
Example Trial 7: TROG Study Schema with 5 “options”
Example Trial 6: Different Cycle Durations Study Schema