Epoch Ontological Framework to
support Clinical Trial Management
Ravi Shankar
Stanford Medical Informatics
Stanford University
Overview
ƒ
Clinical trials are used to determine whether new
drugs or treatments are both safe and effective.
ƒ
Complex clinical trials involve collaboration among
many groups using different software applications.
ƒ
Lack of standardization and reduced efficiency
leads to poor productivity.
ƒ
We are building an ontological framework called
Epoch to improve semantic interoperability among
clinical trial management applications.
The Immune Tolerance Network
ƒ
ƒ
ITN is an international collaboration designed to
accelerate the development of immune tolerance
therapies
Funds, plans, implements, monitors, and assesses
investigator-initiated clinical trials of novel
tolerance-promoting therapies in
Autoimmune diseases
• Transplantation
• Allergy and Asthma
•
ƒ
Provides services to undertake comprehensive
mechanistic studies that complement each trial
Schedule of Events
Schedule of Events
Period
Temporal
Constraint
Visit
Time
Anchor
Activity
Annotation
Specimen Table
Specimen Table
Processing
Instruction
Mechanistic
Study
Specimen
Container
Specimen
Workflow
Assay
Specimen Workflow
RT PCR
Core
1 x 0.5 cryovial
(kidney RNA)
1 x 0.5ml cryovial
(kidney RNA)
RNA Processing
Core
1 x cryovial
(kidney)
Barcode Suffix –E21
Lab
1 x cryovial
(kidney)
Fisher
1 x cryomold
(kidney)
Specimen
Collection
Point
1 x cryomold
(kidney)
Barcode Suffix – E22
Kidney
Core
Specimen
Disposal
Point
Specimen Workflow
Core
lab
RT PCR
Core
1 x 0.5 cryovial
(kidney RNA)
1 x 0.5ml cryovial
(kidney RNA)
Site
Lab
Lab
RNA Processing
Core
1 x cryovial
(kidney)
Barcode Suffix –E21
1 x cryovial
(kidney)
Fisher
1 x cryomold
(kidney)
Specimen
Collection
Point
Specimen
Container
BioRepository
1 x cryomold
(kidney)
Barcode Suffix – E22
Kidney
Core
Specimen
Disposal
Point
Challenges in Trials Management
ƒ
Knowledge about protocols, assays,
and specimen flow is captured in
documents and spreadsheets
Plan
Implement
Monitor
Core
Assess
CRF
Tracking
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
Protocol
Group 0
Schedule
of Events
Assay
0
Group
Specimen
Table
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
CRO Day 0, Transplant
CRF
Protocol
Group 0
Schedule
of Events
Assay
0
Group
Specimen
Table
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
CRO Day 0, Transplant
CRF
Protocol
Group 0
Schedule
of Events
Assay
0
Group
Specimen
Table
Operations
v0
Group
Tube
Table
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
CRO Day 0, Transplant
CRF
Protocol
Group 0
Schedule
of Events
Assay
0
Group
Specimen
Table
Operations
v0
Group
Tube
Table
Fisher v 0
Kit
Report
Cimarron v0, Visit 0
ImmunoTrak
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
CRO Day 0, Transplant
CRF
Core
Labs v0
Assays
Protocol
Group 0
Schedule
of Events
Assay
0
Group
Specimen
Table
Operations
v0
Group
Tube
Table
Fisher v 0
Kit
Report
Cimarron v0, Visit 0
ImmunoTrak
What is in a visit name?
Visit 0, v0, v 0, 0, Day 0, Transplant
CRO Day 0, Transplant
CRF
Core
Labs v0
Assays
Protocol
Group 0
Schedule
of Events
Assay
Group 0
Data
Center
(FK)
reID(FK)
FK)
ETLMappingHeader
MapHdrID
MappingName
Source
Version
Dt
(FK)
Specimen
Table
Operations
v0
Group
Tube
Table
Fisher v 0
mpleID (FK)
D (FK)
D(FK)
FK)
D(FK)
(FK)
me
eID(FK)
t
Dt
(FK)
ETLMappingDetail
MapDtlID
SourceColumn
TargetTable
TargetColumnType
MapHdrID
HLABusinessRuleDetail
BRDetailID
TargetTable
TargetColumn
BRValue
TargetColumnType
BRHdrID
HLAEvertLog
HLAEventLogID
EventDesc
RecordDt
OperatorID
GLBatchID
HLADataImportLog
ImportLogID
ConfigParameter
ConfigParameterID
ProcessID(FK)
Name
Value
RecordDt
UserID(FK)
Archive
ArchiveID
Kit
Report
HLABusinessRuleHeader
BRHdrID
Version
BRName
CoreID (FK)
ProcessID(FK)
Name
Directory
RecordDt
UserID (FK)
Source
SourceID
CoreID(FK)
Version
Description
StartDt
EndDt
RecordDt
UserID(FK)
pcrResult_Qual
CoreSampleid (FK)
TestID (FK)
ReplicateID
BaseVisitID (FK)
Qualifier
AtLeast
SampleQuality
CalibratorQuality
RecordDt
UserID (FK)
FileName
StudyNum
Code
VisitNum
SpecimenType
ParticipantID
Barcode
Description
RecordDt
OperatorID
AccessionID
GenericLoad
GenLoadID
FileName
FileDir
RowNumber
ColumnName
CellValue
Source
Version
dtEntered
LoadID
GenericLoadBatch
GLBatchID
Code
ConvNum
IsLocalLab
IRBApprovedlDt
ITNApprovedDt
BudgetApprovedDt
ActivationDt
RecordDt
UserID(FK)
Accession
AccessionID
CoreID(FK)
Filename
TransmissionDt
TransactionCodeID(FK)
RecordDt
UserID(FK)
Description
RecordDt
UserID(FK)
Core_Contacts
CoreSampleID
StudyID(FK)
AccessionID(FK)
ProcessingCodeID (FK)
SampleTypeID(FK)
RecdDt
AnalysisDt
Techname
Filename
ExternalID
BarcodeID9
SpecimenTypeID (FK)
RecordDt
UserID (FK)
CoreSampleID(FK)
BarcodeID (FK)
QCSampleID(FK)
ValidationCodeID(FK)
ValidationDt
RecordDt
UserID(FK)
CoreID(FK)
ContactTypeID (FK)
UserID(FK)
RecordDt
Barcode
BarcodeID
StudyID(FK)
SubjectID (FK)
VisitID(FK)
Barcode
CollectionDt
RecordDt
UserID(FK)
CoreSample_Detail
FileDir
RecordDt
FileName
CoreSample
Subject
SubjectID
SiteID(FK)
ParticipantID
StudyGroupID(FK)
RecordDt
UserID (FK)
ProcessID
Name
RecordDt
UserID(FK)
Core_Issues
IssueID
Core
Study
CoresampleID
RequestedBy
Description
RequestDt
Response
Status
CoreSampleID(FK)
Source_Fields
SourceFieldID
SourceID(FK)
FieldID (FK)
Ordinal
RecordDt
SkipFlag
RecordDt
UserID (FK)
DevCode
DevCodeID
Code
Description
GetComments
RecordDt
UserID (FK)
Field
FieldID
Name
Description
RecordDt
UserID (FK)
TransactionCode
TransactionCodeID
Code
Description
RecordDt
UserID (FK)
CoreSample_DevCode
CoreSampleID(FK)
DevCodeID (FK)
Notes
RecordDt
UserID (FK)
rptDataExtractRequest
RequestNumber
DtOfRequest
DtRequiredBy
RequestorName
RequestorPhone
StudyNum
Core
StudyData
QCSamples
ResearchDevelopment
StartDt
EndDt
VisitsDetail
DataFormat
IncludeDeviationCodes
IncludeTrtCohort
IncludeUnvalidatedSamples
SpecialInstructions
AssignedTo
AssignedDt
PlanStatus
DtPlanAvailable
DtPlanFinal
RequestClosedBy
ClosedDt
SiteDetails
InformaticsNote
RecUpdatedBy
RecUpdatedOn
DataExtractType
SampleType
SampleTypeID
Name
RecordDt
UserID (FK)
ValidationCode
ValidationCodeID
Code
Description
RecordDt
UserID (FK)
Core_Assays
CoreID(FK)
AssayID(FK)
SpecimenTypeID(FK)
RecordDt
UserID(FK)
FileRequestList
FileRequestListID
Status
FileName
Directory
RequestID(FK)
Message
FileRequest
Database
Process
Cimarron v0, Visit 0
ImmunoTrak
Sc ee g t
EnrollmentDt
StudyGroupID(FK)
DonorID
RecipientID
RecordDt
ScreeningFailureResasonID
ScreeningFailureComment
UserID(FK)
RequestID
RequestDt
CompletedDt
EmailAddress
Status
FileName
FileType
Message
ArchiveID(FK)
UserName
SMS_Issues
IssueId
CoreSampleID(FK)
TextMsg
Status
RecordDt
SMS_Acc
Study_ID
Site_ID
Participan
Visit_Num
Collection
Collection
Barcode
Specimen
Lab
Site_Dev_
Core_Dev
O_Study_
O_Site_ID
O_Partici
O_Visit_N
O_Collec
O_Collec
O_Specim
InvalidSta
InvalidCo
InvalidCo
InvalidSID
InvalidPID
InvalidEn
RecordDt
SMS_Qu
ProcessingCode
ProcessingCodeID
Code
Description
RecordDt
UserID (FK)
Transplant
TransplantId
Recipient_SubjectId
Donor_SubjectId
Organ
RecordDt
Operator
StudyId
SMS_Issued_Queries
IssueID (FK)
Query_ID(FK)
RecordDt
Resolved
ScreeningFailureReason
ScreeningFailureReasonID
Code
Description
Enabled
StudyID
Query
Study
Query
Site_q
Query
Query
Query
Query
Date_
Date_
Date_
Initiat
Resol
Extern
Resol
Date_
Query
What is in a visit name?
fcAntib_LotNum
AntibID(FK)
LotNum
CatalogNum
Manufacturer
StartDt
EndDt
RecordDt
UserID(FK)
fcTubeType
TubeTypeID
Name
RecordDt
UserID(FK)
fcAntib
fcRegion
AntibID
Name
IsDump
RecordDt
UserID (FK)
fcTube_Region_Matrix
TubeID(FK)
RegionID(FK)
MatrixID(FK)
RecordDt
UserID(FK)
fcMatrix
RegionID
Name
RecordDt
UserID(FK)
ITN_BioMed V5
Schema
MatrixID
NoOfColors
Label
RecordDt
UserID(FK)
HLAResult
HLAResultID
A_1
A_2
B_1
B_2
Cw_1
Cw_2
DRB1_1
DRB1_2
DRB3_1
DRB3_2
DRB4_1
DRB4_2
DRB5_1
DRB5_2
DQA1_1
DQA1_2
DQB1_1
DQB1_2
HLAComments
HLAComments_Analysis
RecordDt
OperatorID
CoreSampleID
fcMatrix_Components
MatrixID(FK)
Ordinal
State
RecordDt
UserID(FK)
fcRegion_Matrix_Standard
NoOfColors
RegionID(FK)
MatrixID(FK)
RecordDt
UserID(FK)
fcTrt
fcTube
TubeID
fcGate
GateID
Name
RecordDt
UserID(FK)
fcResult
pcrBaseVisit
fcMGFile
CoreSampleID(FK)
PanelID(FK)
Filename
ArchiveID(FK)
Content
RecordDt
UserID(FK)
BatchId
BatchNumber
StudyID(FK)
ShipDate
RecordDt
UserID(FK)
StudyID (FK)
VisitID(FK)
RecordDt
UserID(FK)
pcrSet
ComparisonID
OligoID (FK)
BaseMethod
Threshold
RecordDt
UserID(FK)
SetID
BatchID
CoreSampleID(FK)
SetName
PlateBarcode
InstrumentBarcode
RecordDt
AnalysisDt
UserID (FK)
pcrWell
WellID
WellPosition
RecordDt
OperatorID
pcrQCData
QCDataID
ReportName
BatchID
Filename
ArchiveID(FK)
RecordDT
UserID(FK)
FluorochromeID
Name
RecordDt
UserID(FK)
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
MeasureID(FK)
Name (FK)
StartDt
EndDt
RecordDt
UserID(FK)
0
fcSFile
CoreSampleID(FK)
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
Name (FK)
Filename
ArchiveID(FK)
Content
RecordDt
UserID(FK)
pcrResult
CoreSampleId (FK)
TestID(FK)
ReplicateID
BaseVisitID(FK)
MeasureID(FK)
Value
RecordDt
UserID(FK)
ETLMappingDetail
MapDtlID
SourceColumn
TargetTable
TargetColumnType
MapHdrID
HLABusinessRuleDetail
BRDetailID
TargetTable
TargetColumn
BRValue
TargetColumnType
BRHdrID
Archive
ArchiveID
v0
OligoID
Name
SeqAcs
Description
Classification
RecordDt
UserID(FK)
pcrSDSFile
CoreSampleID(FK)
SetID(FK)
TestID(FK)
CoreID(FK)
ProcessID(FK)
Name
Directory
RecordDt
UserID(FK)
Source
SourceID
CoreID(FK)
Version
Description
StartDt
EndDt
RecordDt
UserID(FK)
pcrResult_Qual
CoreSampleid (FK)
TestID(FK)
ReplicateID
BaseVisitID(FK)
Qualifier
AtLeast
SampleQuality
CalibratorQuality
RecordDt
UserID(FK)
ScheduleType
ScheduleTypeID
Name
RecordDt
UserID(FK)
CoreSampleID(FK)
TestID(FK)
MeasureID (FK)
Value
RecordDt
UserID(FK)
StudyID(FK)
ScheduleTypeId (FK)
Ordinal
VisitNum
Description
RecordDt
UserID(FK)
FileName
StudyNum
Code
VisitNum
SpecimenType
ParticipantID
Barcode
Description
RecordDt
OperatorID
AccessionID
Process
ProcessID
Name
RecordDt
UserID(FK)
GenericLoadBatch
GLBatchID
CoreSampleID
StudyID(FK)
AccessionID(FK)
ProcessingCodeID(FK)
SampleTypeID(FK)
RecdDt
AnalysisDt
Techname
Filename
ExternalID
BarcodeID9
SpecimenTypeID(FK)
RecordDt
UserID(FK)
Source_Fields
SourceFieldID
SourceID(FK)
FieldID(FK)
Ordinal
RecordDt
SkipFlag
RecordDt
UserID(FK)
DevCode
DevCodeID
Code
Description
GetComments
RecordDt
UserID(FK)
Field
FieldID
Name
Description
RecordDt
UserID(FK)
TransactionCode
TransactionCodeID
Code
Description
RecordDt
UserID(FK)
SiteID
ShortName
StudyID(FK)
LocationID(FK)
Code
ConvNum
IsLocalLab
IRBApprovedlDt
ITNApprovedDt
BudgetApprovedDt
ActivationDt
RecordDt
UserID(FK)
StudyTypeID
Name
RecordDt
UserID(FK)
TherapeuticArea
TherapeuticAreaID
Name
RecordDt
UserID(FK)
CoreSample_DevCode
CoreSampleID(FK)
DevCodeID(FK)
Notes
RecordDt
UserID(FK)
EnrollmentID
SiteID(FK)
ScreeningID
ParticipantID
ScreeningDt
EnrollmentDt
StudyGroupID(FK)
DonorID
RecipientID
RecordDt
ScreeningFailureResasonID
ScreeningFailureComment
UserID(FK)
Study_A
Stud
Assa
Spec
Reco
User
Study_
Stu
Con
Loc
Use
AccessionID
CoreID(FK)
Filename
TransmissionDt
TransactionCodeID(FK)
RecordDt
UserID(FK)
CoreID
LocationID(FK)
Code
Description
RecordDt
UserID(FK)
rptDataExtractRequest
RequestNumber
StudyID(FK)
SubjectID(FK)
VisitID(FK)
Barcode
CollectionDt
RecordDt
UserID(FK)
Subject
SubjectID
SiteID(FK)
ParticipantID
StudyGroupID(FK)
RecordDt
UserID(FK)
SampleType
SampleTypeID
Transplant
DtOfRequest
DtRequiredBy
RequestorName
RequestorPhone
StudyNum
Core
StudyData
QCSamples
ResearchDevelopment
StartDt
EndDt
VisitsDetail
DataFormat
IncludeDeviationCodes
IncludeTrtCohort
IncludeUnvalidatedSamples
SpecialInstructions
AssignedTo
AssignedDt
PlanStatus
DtPlanAvailable
DtPlanFinal
RequestClosedBy
ClosedDt
SiteDetails
InformaticsNote
RecUpdatedBy
RecUpdatedOn
DataExtractType
ContactTypeID
Name
RecordDt
UserID(FK)
Loc
Core_Contacts
CoreID(FK)
ContactTypeID(FK)
UserID(FK)
RecordDt
Visit 0
CoreSampleID(FK)
BarcodeID(FK)
QCSampleID(FK)
ValidationCodeID(FK)
ValidationDt
RecordDt
UserID(FK)
Rec
ContactType
Core
Barcode
BarcodeID
Accession
CoreSample_Detail
FileDir
RecordDt
FileName
CoreSample
Core_Issues
IssueID
Core
Study
CoresampleID
RequestedBy
Description
RequestDt
Response
Status
CoreSampleID(FK)
Stu
StudyID
StudyNum
ShortTitle
LongTitle
StartDt
Phase
TherapeuticAreaID(FK)
NoOfParticipants
StudyTypeID(FK)
IsApproved
IsOpen
DurationMo
FollowUpMo
AccrualMo
NoEnrolled
NoExtension
TreatmentPlan
State
StudyStatusID
RecordDt
UserID(FK)
Enrollment
Site
GenericLoad
GenLoadID
FileName
FileDir
RowNumber
ColumnName
CellValue
Source
Version
dtEntered
LoadID
HLADataImportLog
ImportLogID
Study
StudyStatusID
Description
RecordDt
UserID(FK)
StudyType
Location
LocationID
Name
Organization
Address1
Address2
City
State
Zip
Region
Country
RecordDt
UserID(FK)
Visit
VisitID
TestResult
StudyStatus
MeasureID
Name
Abbreviation
RecordDt
UserID(FK)
Test
TestID
StudyID(FK)
AssayID(FK)
LabTypeID(FK)
Name
RecordDt
UserID(FK)
Day 0
v0
SetID(FK)
OligoID(FK)
ComparisonID(FK)
WellID (FK)
CalibratorSample
CalibratorPlate
RecordDt
OperatorID
ArchiveID(FK)
Filename
RecordDt
UserID(FK)
HLABusinessRuleHeader
BRHdrID
Version
BRName
ConfigParameter
ConfigParameterID
ProcessID(FK)
Name
Value
RecordDt
UserID(FK)
pcrReplicate
ReplicateID
pcrOligo
ETLMappingHeader
MapHdrID
MappingName
Source
Version
HLAEvertLog
HLAEventLogID
EventDesc
RecordDt
OperatorID
GLBatchID
pcrBatch
BaseVisitID
pcrComparison
fcFluorochrome
fcPanel_Measures
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
StartDt
Name (FK)
Ordinal
EndDt
Comments
RecordDt
UserID(FK)
AntibID(FK)
TubeID(FK)
FluorochromeID(FK)
Ordinal
RecordDt
UserID(FK)
Name
TrtID
RecordDt
UserID(FK)
PanelID
TestID(FK)
HasMGFile
RecordDt
UserID(FK)
TubeTypeID(FK)
Name
NoOfColors
RecordDt
UserID(FK)
fcPanel_Components
fcTube_Components
CoreSampleID(FK)
PanelID (FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
RegionID(FK)
MeasureID(FK)
Name (FK)
Value
RecordDt
UserID(FK)
fcPanel
LabType
LabTypeID
Name
Description
RecordDt
UserID(FK)
Measure
Name
RecordDt
UserID(FK)
ValidationCode
ValidationCodeID
Code
Description
RecordDt
UserID(FK)
Core_Assays
CoreID(FK)
AssayID(FK)
SpecimenTypeID(FK)
RecordDt
UserID(FK)
FileRequestList
FileRequestListID
Status
FileName
Directory
RequestID(FK)
Message
FileRequest
RequestID
RequestDt
CompletedDt
EmailAddress
Status
FileName
FileType
Message
ArchiveID(FK)
UserName
SMS_Issues
IssueId
CoreSampleID(FK)
TextMsg
Status
RecordDt
SMS_Acc
Study_ID
Site_ID
Participan
Visit_Num
Collection
Collection
Barcode
Specimen
Lab
Site_Dev_
Core_Dev
O_Study_
O_Site_ID
O_Partici
O_Visit_N
O_Collec
O_Collec
O_Specim
InvalidSta
InvalidCo
InvalidCo
InvalidSID
InvalidPID
InvalidEn
RecordDt
SMS_Qu
ProcessingCode
ProcessingCodeID
Code
Description
RecordDt
UserID(FK)
Transplant
TransplantId
Recipient_SubjectId
Donor_SubjectId
Organ
RecordDt
Operator
StudyId
SMS_Issued_Queries
IssueID(FK)
Query_ID(FK)
RecordDt
Resolved
ScreeningFailureReason
ScreeningFailureReasonID
Code
Description
Enabled
StudyID
Query
Study
Query
Site_q
Query
Query
Query
Query
Date_
Date_
Date_
Initiat
Resol
Extern
Resol
Date_
Query
What is in a visit name?
fcAntib_LotNum
AntibID(FK)
LotNum
CatalogNum
Manufacturer
StartDt
EndDt
RecordDt
UserID(FK)
fcTubeType
TubeTypeID
Name
RecordDt
UserID(FK)
fcAntib
fcRegion
AntibID
Name
IsDump
RecordDt
UserID (FK)
fcTube_Region_Matrix
TubeID(FK)
RegionID(FK)
MatrixID(FK)
RecordDt
UserID(FK)
V5
How many ITN_BioMed
participants
Schema
have had transplants
so far
and what are the results of
the assays performed at
the time of transplant?
fcMatrix
RegionID
Name
RecordDt
UserID(FK)
Measure
MatrixID
NoOfColors
Label
RecordDt
UserID(FK)
HLAResult
HLAResultID
A_1
A_2
B_1
B_2
Cw_1
Cw_2
DRB1_1
DRB1_2
DRB3_1
DRB3_2
DRB4_1
DRB4_2
DRB5_1
DRB5_2
DQA1_1
DQA1_2
DQB1_1
DQB1_2
HLAComments
HLAComments_Analysis
RecordDt
OperatorID
CoreSampleID
fcMatrix_Components
MatrixID(FK)
Ordinal
State
RecordDt
UserID(FK)
fcRegion_Matrix_Standard
NoOfColors
RegionID(FK)
MatrixID(FK)
RecordDt
UserID(FK)
fcTrt
fcTube
TubeID
fcGate
GateID
Name
RecordDt
UserID(FK)
TubeTypeID(FK)
Name
NoOfColors
RecordDt
UserID(FK)
fcPanel_Components
fcTube_Components
fcResult
pcrBaseVisit
fcMGFile
CoreSampleID(FK)
PanelID(FK)
Filename
ArchiveID(FK)
Content
RecordDt
UserID(FK)
BatchId
BatchNumber
StudyID(FK)
ShipDate
RecordDt
UserID(FK)
StudyID (FK)
VisitID(FK)
RecordDt
UserID(FK)
pcrSet
ComparisonID
OligoID (FK)
BaseMethod
Threshold
RecordDt
UserID(FK)
SetID
BatchID
CoreSampleID(FK)
SetName
PlateBarcode
InstrumentBarcode
RecordDt
AnalysisDt
UserID (FK)
pcrWell
WellID
WellPosition
RecordDt
OperatorID
pcrQCData
QCDataID
ReportName
BatchID
Filename
ArchiveID(FK)
RecordDT
UserID(FK)
fcFluorochrome
FluorochromeID
Name
RecordDt
UserID(FK)
fcPanel_Measures
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
MeasureID(FK)
Name (FK)
StartDt
EndDt
RecordDt
UserID(FK)
0
fcSFile
CoreSampleID(FK)
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
Name (FK)
Filename
ArchiveID(FK)
Content
RecordDt
UserID(FK)
pcrResult
CoreSampleId (FK)
TestID(FK)
ReplicateID
BaseVisitID(FK)
MeasureID(FK)
Value
RecordDt
UserID(FK)
ETLMappingDetail
MapDtlID
SourceColumn
TargetTable
TargetColumnType
MapHdrID
HLABusinessRuleDetail
BRDetailID
TargetTable
TargetColumn
BRValue
TargetColumnType
BRHdrID
Archive
ArchiveID
v0
OligoID
Name
SeqAcs
Description
Classification
RecordDt
UserID(FK)
pcrSDSFile
CoreSampleID(FK)
SetID(FK)
TestID(FK)
CoreID(FK)
ProcessID(FK)
Name
Directory
RecordDt
UserID(FK)
Source
SourceID
CoreID(FK)
Version
Description
StartDt
EndDt
RecordDt
UserID(FK)
pcrResult_Qual
CoreSampleid (FK)
TestID(FK)
ReplicateID
BaseVisitID(FK)
Qualifier
AtLeast
SampleQuality
CalibratorQuality
RecordDt
UserID(FK)
Test
TestID
StudyID(FK)
AssayID(FK)
LabTypeID(FK)
Name
RecordDt
UserID(FK)
ScheduleType
ScheduleTypeID
Name
RecordDt
UserID(FK)
StudyID(FK)
ScheduleTypeId (FK)
Ordinal
VisitNum
Description
RecordDt
UserID(FK)
TestResult
CoreSampleID(FK)
TestID(FK)
MeasureID (FK)
Value
RecordDt
UserID(FK)
FileName
StudyNum
Code
VisitNum
SpecimenType
ParticipantID
Barcode
Description
RecordDt
OperatorID
AccessionID
Process
ProcessID
Name
RecordDt
UserID(FK)
GenericLoadBatch
GLBatchID
CoreSampleID
StudyID(FK)
AccessionID(FK)
ProcessingCodeID(FK)
SampleTypeID(FK)
RecdDt
AnalysisDt
Techname
Filename
ExternalID
BarcodeID9
SpecimenTypeID(FK)
RecordDt
UserID(FK)
Source_Fields
SourceFieldID
SourceID(FK)
FieldID(FK)
Ordinal
RecordDt
SkipFlag
RecordDt
UserID(FK)
DevCode
DevCodeID
Code
Description
GetComments
RecordDt
UserID(FK)
Field
FieldID
Name
Description
RecordDt
UserID(FK)
TransactionCode
TransactionCodeID
Code
Description
RecordDt
UserID(FK)
SiteID
ShortName
StudyID(FK)
LocationID(FK)
Code
ConvNum
IsLocalLab
IRBApprovedlDt
ITNApprovedDt
BudgetApprovedDt
ActivationDt
RecordDt
UserID(FK)
StudyTypeID
Name
RecordDt
UserID(FK)
TherapeuticArea
TherapeuticAreaID
Name
RecordDt
UserID(FK)
CoreSample_DevCode
CoreSampleID(FK)
DevCodeID(FK)
Notes
RecordDt
UserID(FK)
EnrollmentID
SiteID(FK)
ScreeningID
ParticipantID
ScreeningDt
EnrollmentDt
StudyGroupID(FK)
DonorID
RecipientID
RecordDt
ScreeningFailureResasonID
ScreeningFailureComment
UserID(FK)
Study_A
Stud
Assa
Spec
Reco
User
Study_
Stu
Con
Loc
Use
AccessionID
CoreID(FK)
Filename
TransmissionDt
TransactionCodeID(FK)
RecordDt
UserID(FK)
CoreID
LocationID(FK)
Code
Description
RecordDt
UserID(FK)
rptDataExtractRequest
RequestNumber
StudyID(FK)
SubjectID(FK)
VisitID(FK)
Barcode
CollectionDt
RecordDt
UserID(FK)
Subject
SubjectID
SiteID(FK)
ParticipantID
StudyGroupID(FK)
RecordDt
UserID(FK)
SampleType
SampleTypeID
Transplant
DtOfRequest
DtRequiredBy
RequestorName
RequestorPhone
StudyNum
Core
StudyData
QCSamples
ResearchDevelopment
StartDt
EndDt
VisitsDetail
DataFormat
IncludeDeviationCodes
IncludeTrtCohort
IncludeUnvalidatedSamples
SpecialInstructions
AssignedTo
AssignedDt
PlanStatus
DtPlanAvailable
DtPlanFinal
RequestClosedBy
ClosedDt
SiteDetails
InformaticsNote
RecUpdatedBy
RecUpdatedOn
DataExtractType
ContactTypeID
Name
RecordDt
UserID(FK)
Loc
Core_Contacts
CoreID(FK)
ContactTypeID(FK)
UserID(FK)
RecordDt
Visit 0
CoreSampleID(FK)
BarcodeID(FK)
QCSampleID(FK)
ValidationCodeID(FK)
ValidationDt
RecordDt
UserID(FK)
Rec
ContactType
Core
Barcode
BarcodeID
Accession
CoreSample_Detail
FileDir
RecordDt
FileName
CoreSample
Core_Issues
IssueID
Core
Study
CoresampleID
RequestedBy
Description
RequestDt
Response
Status
CoreSampleID(FK)
Stu
StudyID
StudyNum
ShortTitle
LongTitle
StartDt
Phase
TherapeuticAreaID(FK)
NoOfParticipants
StudyTypeID(FK)
IsApproved
IsOpen
DurationMo
FollowUpMo
AccrualMo
NoEnrolled
NoExtension
TreatmentPlan
State
StudyStatusID
RecordDt
UserID(FK)
Enrollment
Site
GenericLoad
GenLoadID
FileName
FileDir
RowNumber
ColumnName
CellValue
Source
Version
dtEntered
LoadID
HLADataImportLog
ImportLogID
Study
StudyStatusID
Description
RecordDt
UserID(FK)
StudyType
Location
LocationID
Name
Organization
Address1
Address2
City
State
Zip
Region
Country
RecordDt
UserID(FK)
Visit
VisitID
Day 0
v0
SetID(FK)
OligoID(FK)
ComparisonID(FK)
WellID (FK)
CalibratorSample
CalibratorPlate
RecordDt
OperatorID
ArchiveID(FK)
Filename
RecordDt
UserID(FK)
HLABusinessRuleHeader
BRHdrID
Version
BRName
ConfigParameter
ConfigParameterID
ProcessID(FK)
Name
Value
RecordDt
UserID(FK)
pcrReplicate
ReplicateID
pcrOligo
ETLMappingHeader
MapHdrID
MappingName
Source
Version
HLAEvertLog
HLAEventLogID
EventDesc
RecordDt
OperatorID
GLBatchID
pcrBatch
BaseVisitID
pcrComparison
Name
TrtID
RecordDt
UserID(FK)
PanelID
TestID(FK)
HasMGFile
RecordDt
UserID(FK)
PanelID(FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
StartDt
Name (FK)
Ordinal
EndDt
Comments
RecordDt
UserID(FK)
AntibID(FK)
TubeID(FK)
FluorochromeID(FK)
Ordinal
RecordDt
UserID(FK)
CoreSampleID(FK)
PanelID (FK)
TubeID(FK)
TrtID(FK)
GateID(FK)
RegionID(FK)
MeasureID(FK)
Name (FK)
Value
RecordDt
UserID(FK)
fcPanel
LabType
LabTypeID
Name
Description
RecordDt
UserID(FK)
StudyStatus
MeasureID
Name
Abbreviation
RecordDt
UserID(FK)
Name
RecordDt
UserID(FK)
ValidationCode
ValidationCodeID
Code
Description
RecordDt
UserID(FK)
Core_Assays
CoreID(FK)
AssayID(FK)
SpecimenTypeID(FK)
RecordDt
UserID(FK)
FileRequestList
FileRequestListID
Status
FileName
Directory
RequestID(FK)
Message
FileRequest
RequestID
RequestDt
CompletedDt
EmailAddress
Status
FileName
FileType
Message
ArchiveID(FK)
UserName
SMS_Issues
IssueId
CoreSampleID(FK)
TextMsg
Status
RecordDt
SMS_Acc
Study_ID
Site_ID
Participan
Visit_Num
Collection
Collection
Barcode
Specimen
Lab
Site_Dev_
Core_Dev
O_Study_
O_Site_ID
O_Partici
O_Visit_N
O_Collec
O_Collec
O_Specim
InvalidSta
InvalidCo
InvalidCo
InvalidSID
InvalidPID
InvalidEn
RecordDt
SMS_Qu
ProcessingCode
ProcessingCodeID
Code
Description
RecordDt
UserID(FK)
Transplant
TransplantId
Recipient_SubjectId
Donor_SubjectId
Organ
RecordDt
Operator
StudyId
SMS_Issued_Queries
IssueID(FK)
Query_ID(FK)
RecordDt
Resolved
ScreeningFailureReason
ScreeningFailureReasonID
Code
Description
Enabled
StudyID
Query
Study
Query
Site_q
Query
Query
Query
Query
Date_
Date_
Date_
Initiat
Resol
Extern
Resol
Date_
Query
Challenges in Trials Management
ƒ
Enterprise-wide knowledge about
trials management is not formally
encoded, leading to challenges in
•
•
•
•
ƒ
Standardization
Data integrity
Data analysis
Data integration
Significant efforts may be needed to
resolve inconsistencies after a trial
has started
ITN Informatics Core at Stanford
Epoch
An Ontological Framework for Clinical
Trials Management
ITN Informatics Core at Stanford
The goals of our collaboration are to
ƒ
ƒ
ƒ
Design tools to help acquire and maintain
knowledge about protocol and assay
designs
Use this knowledge to drive data collection
during a trial
Implement querying methods to support
trial management, and ad hoc data
analysis
Building Ontologies for ITN — Epoch
RT PCR
Core
1 x 0.5 cryovial
(kidney RNA)
1 x 0.5ml cryovial
(kidney RNA)
RNA Processing
Core
1 x cryovial
(kidney)
Barcode Suffix –E21
Lab
Specimen
Collection
Point
1 x cryovial
(kidney)
1 x cryomold
(kidney)
Fisher
1 x cryomold
(kidney)
Barcode Suffix – E22
Kidney
Core
Specimen
Disposal
Point
Building Ontologies for ITN — Epoch
ITN
CDISC
specifications
SAGE
EON
BRIDG
Epoch
Epoch Ontologies
Protocol
Model
Epoch Ontologies
Protocol
Schema
Protocol
Model
Mechanistic
Study Plan
Epoch Ontologies
Protocol
Schema
Protocol
Model
Mechanistic
Study Plan
Visit
Activity
Epoch Ontologies
Protocol
Schema
Protocol
Model
Mechanistic
Study Plan
Visit
Activity
Clinical
Model
Epoch Ontologies
Protocol
Schema
Protocol
Model
Visit
Assay
Mechanistic
Study Plan
Specimen
Container
Set
Specimen
Workflow
Activity
Clinical
Model
Epoch Ontologies
Protocol
Schema
Protocol
Model
Visit
Assay
Mechanistic
Study Plan
Specimen
Container
Set
Specimen
Workflow
Activity
Assay
Model
Clinical
Model
Epoch Ontologies
Protocol
Schema
Protocol
Model
Visit
Assay
Mechanistic
Study Plan
Specimen
Container
Set
Specimen
Workflow
Clinical
Model
Activity
Assay
Model
Specimen
Container
Model
Site
Model
Epoch Ontologies
Protocol
Schema
Protocol
Model
Visit
Assay
Mechanistic
Study Plan
Specimen
Container
Set
Specimen
Workflow
Clinical
Model
Activity
Assay
Model
Specimen
Container
Model
Site
Model
Virtual
Trial
Data
Model
Knowledge-Acquisition Environment
OWL (the Web Ontology Language proposed by
W3C)
SWRL (the Semantic Web Rule Language) to
specify constraints and queries
Protégé-OWL editor to enter ontologies in OWL
and SWRL
Epoch Protocol Model
Epoch Protocol Model
Schedule of Events
Period
Temporal
Constraint
Visit
Time
Anchor
Activity
Annotation
Protocol Model – Study Schema
Study Schema
Study Schema – a Temporal Sequence
of Periods
Visit Flow – a Temporal Sequence of
Visits
Visit
Visit – different Visit names
Specimen Table
Processing
Instruction
Mechanistic
Study
Specimen
Container
Specimen
Workflow
Assay
Protocol Model - Mechanistic Study Plan
Mechanistic Study Plan
Mechanistic Study Plan
Mechanistic Study Plan
A Mechanistic Study
A Mechanistic Study
Specimen Workflow
Specimen Workflow
Mechanistic Study Plan
Specimen Container Set
Specimen Container Set
Specimen Container Set
Specimen Container Set
Specimen Container Ontology – using
OWL Full meta model
Specimen Container Ontology – using
OWL Full meta model
Specimen Container Ontology – using
OWL Full meta model
Specimen Container Ontology
A Hierarchy of Specimen Containers
A Specimen Container
Assay Ontology – using OWL Full meta
model
Assay Ontology – using OWL Full meta
model
Assay Ontology
Assay Ontology
An Assay
Virtual Trial Data Model - Observation
Virtual Trial Data Model - VisitRecord
Anchor Point - Transplant
SWRL Rule to set Transplant Time
Visit Time Window
Visit Time constraint as a SWRL rule
Check if the participant's visits occurred within the
visit time window specifications
Constraints expressed as SWRL rules
On days that both immunotherapy and omalizumab are
administered, omalizumab will be injected 60 minutes
after the immunotherapy.
ITN Informatics Core at Stanford
The goals of our collaboration are to
ƒ
ƒ
ƒ
Design tools to help acquire and maintain
knowledge about protocol and assay
designs
Use this knowledge to drive data collection
during a trial
Implement querying methods to support
trial monitoring, protocol tracking, and ad
hoc data analysis
Epoch Architectural Plan
OWL | SWRL
Epoch Knowledge Base
Epoch Architectural Plan
API
Knowledge Base Server
OWL | SWRL
Epoch Knowledge Base
Epoch Architectural Plan
API
Model-Database
Mapper
Knowledge Base Server
OWL | SWRL
Epoch Knowledge Base
Clinical
Trial
Database
Epoch Architectural Plan
Query / Rule Engine
SWRL | JESS
API
Model-Database
Mapper
Knowledge Base Server
OWL | SWRL
Epoch Knowledge Base
Clinical
Trial
Database
Epoch Architectural Plan
Query / Rule Engine
Utility
Functions
API
SWRL | JESS
Model-Database
Mapper
Knowledge Base Server
OWL | SWRL
Epoch Knowledge Base
Clinical
Trial
Database
Epoch Architectural Plan
Clinical Trials Management Applications
Query / Rule Engine
Utility
Functions
API
SWRL | JESS
Model-Database
Mapper
Knowledge Base Server
OWL | SWRL
Epoch Knowledge Base
Clinical
Trial
Database
Configuration of ImmunoTrak – the
Specimen Workflow Application
ImmunoTrak Configuration File
Configuration of ImmunoTrak – the
Specimen Workflow Application
ImmunoTrak ―
Specimen Workflow
2
1
ImmunoTrak
Configuration
Epoch
Knowledge
Base
Ontology Mapping to generate XML
Document
SWRL
Epoch
Ontology
XML Document
Ontology
ImmunoTrak
Configuration XML
Protocol(?p) ^ hasSitePlan(?p, ?sp) ^ hasStudySites(?sp, ?site) ^
hasSiteID(?site, ?siteID) ^ hasParticipant(?site, ?participants) ^
hasParticipantIDs(?participant, ?participantID) ^
hasStudyInformation(?sp, ?studyInfo) ^ hasStudyID(?studyInfo,
?hasStudyID)
-> XMLDocument(?p) ^ hasNodeName(?p, "Study") ^
XMLComponent(?participant) ^ hasNodeName(?participant,
"Participant") ^ hasComponents(?p, ?participant) ^
hasAttribute(?participant, ?participantID) ^
hasAttributeName(?participantID, "id">
Electronic
CRF
Clinical
Ontology
Generic
Protocol
Model
Protocol+
Protocol
Protocol
Specimen
Table
Assay
Ontology
Protocol
Specific
Protocol
Assays
Container
Ontology
Protocol
Specific
Protocol
Kits
Site
Ontology
Protocol
Specific
Protocol
Sites
Protégé
OWL
Epoch
Ontologies
Applications for
Knowledge
Specification
Participant
Visits
CRF
Tracking
Specimen
Identification
Core
Specimen
Workflow
Applications for
Data Collection
Data
Repository
Applications for
Clinical Trials
Management
What our approach buys us
ƒ
ƒ
ƒ
ƒ
A centralized, modifiable repository of
the knowledge to drive site-oriented
applications
The ability to use reference ontologies
to structure ITN knowledge
A scaleable architecture that can lead
to computer-supported trial design
The ability to use logic for inferring
relationships among the data