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

CDISC SDTM-BRIDG MappingTA, TE and TS Discussion

March 4, 2014 Conference CallPrepared by Wendy Ver Hoef, Samvit Solutions, Inc.

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.

TABRANCH

Assumptions

4 Arms 5 DefinedActivities

Description of allocation result

(etc.)

• 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

Current Classes

DefinedActivity

DefinedAdministrativeActivity

DefinedExperimentalUnitAllocation

PlannedActivity

PlannedRandomizationBookAllocation

RandomizationBookEntry

1

1..*

ActivityContext

StudyProtocolVersion

0..*1

0..*1

1..0

0..*

Planned-Contingent-

On-Relationship

PlannedCritGroup

DefinedObsResult

1..*

0..1

0..11..*

0..11..*

1..*

1contingent prerequisite

prerequisite

prerequisite

Proposed

DefinedActivity

DefinedAdministrativeActivity

DefinedExperimentalUnitAllocation

PlannedActivity

PlannedRandomizationBookAllocation

RandomizationBookEntry

1

1..*

ActivityContext

StudyProtocolVersion

0..*1

0..*1

1..0

0..*

PlannedExperimentalUnitAllocation

Planned-Experimental

-Unit-Allocation-

Result

Planned-Contingent-

On-Relationship

PlannedCritGroup

DefinedObsResult

1..*

0..1

0..11..*

0..11..*

1..*

1contingent prerequisite

prerequisite

prerequisite

0..*1

0..*1

(option)

Re-parented to new super class

(path)

(allocation activity)

(evaluation criteria)

(element)

Computably represents the branches

Instance Diagram

TE Screen Element (DefinedActivity)

Test1 (DefinedActivity)

TestN (DefinedActivity)

… Randomization (DefEUAlloc)

Result 1(PlnEUAllocResult) - description=TABRANCH

DefRandinStudy1(ActivityContext)

Study1(StudyProtVrsn)

PlanRandinStudy1(PlanEUAllocation)

Result 2(PlnEUAllocResult) - description=TABRANCH

PlnDrugAinStudy1(PlanSubjActGrp)

PlnDrugBinStudy1(PlanSubjActGrp)

DefDrugBinStudy1(ActivityContext)

TE Drug A Element (DefinedSubjActGrp)

DefDrugAAdmin (DefSubjActGrp)

TestX (DefObservation)

… RsltBasedAlloc (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 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):

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.

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)

Proposed Definition #2 – Option ClassPlannedContingentOnRelationship (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 groupsTo 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 regimenOTHER NAME(S):branchNOTE(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)

Proposed AssociationsPlannedExperimentalUnitAllocationResult [assignedExperimentalUnitAllocationResult] (0..*) assign experimental units to / is an option for (1) [assigningPlannedExperimentalUnitAllocation] PlannedExperimentalUnitAllocationDESCRIPTION: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] PlannedActivityDESCRIPTION: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):

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 regimenOTHER NAME(S):branchNOTE(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 AttributePlannedExperimentalUnitAllocationResult.descriptionDEFINITION: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 regimenOTHER NAME(S):branchNOTE(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 TATRANSMost 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 2: Crossover Trial Study Schema Example Trial 3: Multiple Branches Study Schema

Example Trial 4: Cyclical Chemotherapy Study Schema

Example Trial 6: Different Cycle Durations Study Schema

Example Trial 7: TROG 93-09 Study Schema with 5 “options”

Example Trial 5: Different Chemo Durations Study Schema