Transcript Clinical Trial Ontology Achieving Consensus Barry Smith Clinical Trial Ontology and Clinical Trial Information Models Achieving Consensus Barry Smith ontologist.com.

Clinical Trial Ontology
Achieving Consensus
Barry Smith
1
Clinical Trial Ontology and
Clinical Trial Information Models
Achieving Consensus
Barry Smith
ontologist.com
2
Two types of ontology
Natural-science ontologies
capture terminology-level knowledge used by
best current science
vs.
Administrative ontologies
for billing, bloodbank, lab workflow
research informatics / healthcare informatics
3
Scientific ontologies have special
features
each term must be such that the developers
of the ontology believe it to refer to some
entity on the basis of the best current
evidence
4
For scientific ontologies
reusability by different groups of users and
for different purposes is crucial
compatibility with neighboring scientific
ontologies is crucial
5
For scientific ontologies
the issue of how the ontology will be used
is not a factor relevant for determining
which entities will be acknowledged by the
ontology
If ontologies are built to address specific
logical practical purposes, this will thwart
their purpose to foster global
communication
6
Hence scientific ontologies
are relatively unsophisticated from a
computational point of view
7
For administrative ontologies
entities may be brought into existence by the
ontology itself, or by administrative policy
(‘surgical procedure not performed
because of patient request’)
The ontology is task-dependent – reusability
and compatibility with other ontologies not
(always) important
8
Scientific ontologies
utilize the scientific method; are
incremental and cumulative; rest on
empirical testing, openness and public
criticism; should be modular, but
interdependent ----- descriptive
Administrative ontologies
employ the methods of administrators; can
rest on commanding and cajoling; can
create law ----- ~prescriptive
9
maps have legends
10
scientific ontologies are legends for data
11
legends for images
12
13
14
15
ontology terms = natural
language labels
organized in a graph-theoretic structure,
designed to make data
– cognitively accessible to human beings
– algorithmically accessible to machines
– and linked up to other data resources because
the same labels have been used
16
Knowledge Environments for
Biomedical Research (KEBR)
1.
2.
3.
4.
Sustainability
Adaptability
Interoperability
Evolvability
http://www.esi-bethesda.com/ncrrworkshops/kebr/index.aspx.
17
through annotations in sciencebased ontologies e.g. of phenotypic
qualities
the results of clinical trials can be integrated
together and made available for querying
on disease terms
logical structure of ontology should help to
ensure quality of annotations and enhance
effectiveness of queries (head  cranium)
18
The methodology of annotations
– is proving very successful in domains such as
molecular biology
– is empirical, modular, incremental
– truly works with very many kinds of heterogeneous
data; supports data integration without the need
for expensive data standardization
Can it be extended to clinical research, which
spans the boundary between biological
science and administration?
19
There can be scientific ontologies
of administrative domains
Reflecting the ways administrative domains
actually are, rather than imposing rules as
to how they should be
There can be scientific ontologies of data
and information objects.
20
CTO
= that part of the OBO Foundry which covers
the broadly administrative/informational
aspects of clinical research
works with interoperable Foundry ontologies
to cover the biological, clinical parts
(need additional ontologies for clinical
procedures, drugs, drug effects ...)
21
Scientific ontology approach to a
scientific domain
Clinical trials are scientific experiments
cohort, randomization, placebo, response,
efficacy, control, protocol, null hypothesis,
confidence interval, finding, biomarker,
primary outcome, secondary outcome,
intervention group, confounder
22
EXPO
The Ontology of Experiments
L. Soldatova, R. King
23
EXPO Formalisation of Science
The goal of science is to increase our
knowledge of the natural world through the
performance of experiments.
This knowledge should, ideally, be
expressed in a formal logical language, to
promote the free exchange of scientific
knowledge and simplifies scientific
reasoning.
24
EXPO: Experiment Ontology
25
equipment part_of experimental design
(confuses object with specification)
26
Clinical trials are in part administrative
entities (analogous to bank accounts)
27
There can be a scientific ontology
approach to an administrative
domain
cohort, randomization, protocol, group,
intervention, placebo, response, efficacy,
control, null hypothesis, confidence
interval, finding, biomarker, primary
outcome, secondary outcome, confounder
28
There can be a scientific ontology
approach to an administrative
domain
cohort, randomization, protocol, group,
intervention, placebo, response, efficacy,
control, null hypothesis, confidence
interval, finding, biomarker, primary
outcome, secondary outcome, confounder
29
CTO, EXPO, OBI work like the
Gene Ontology
all are built to reflect a pre-existing domain:
– we have data
– we need to make it available for semantic
search and algorithmic processing
– we create a consensus-based ontology for
annotating the data
– and make it work with ontologies for
neighboring domains
No role for administrative fiat in transforming
the object-domains of these ontologies
30
General recommendation
rely as far as possible on the methodology
of scientific ontologies
The greater the degree to which your data
regimentation relies on good science
(including a good scientific understanding
of scientific experimentation itself), the
more likely is this regimentation to support
good science in the future and to survive
the changes brought by scientific advance
31
(Modest) Goals of the Clinical
Trial Ontology Initiative
To fully and faithfully capture the types of entities
and relationships involved in clinical trials of any
experimental design comprehending terms
drawn from resources such as the CDISC
glossary and all terms needed for the task of
meta-analysis of clinical trials;
To organize these terms in a structured way,
providing definitions and logical relations
designed to enhance retrieval of, reasoning with,
and integration of the data annotated in its
terms, in ways which will support trial bank
interoperation.
32
In the domain of clinical research,
scientific ontology is not enough
1. privacy, security, liability
2. incentive
3. regulatory issues
4. trial management
33
34
Why (Data) Standards?
Improve time to market for safe and effective
treatments (increased patient safety and
reduced costs)
Improves efficiency of evaluation of safety and
efficacy of investigational treatments
• Facilitates communication between regulatory
authority and applicant
• Facilitates development of efficient review
environment (e.g., training, analysis tools)
35
Efficient Review Environment
Standards provide
– common structure and terminology
– single data source for review (less redundant
data)
Standards allow
– use of common tools and techniques
– common training
– single validation of data
36
Problems with standards
standards have costs
—people will need to transform their data
management habits in a costly process
37
Problems with standards
Not all ISO standards are of high quality
ISO 15926: Oil and gas ontology
ISO 18308: Health informatics
Once a bad standard is set in stone you are
creating problems for your children and for
all your children’s children
38
The administrative approach
a standard is built to change the domain,
e.g. in order to make data available for a
clinical data repository such as Janus
the standard here performs double-duty, it
needs both to reflect existing work
processes, and to transform them into
something more well-integrated
– much more difficult to achieve, especially
on a large scale
39
40
patient
PAYER
Secondary
users
portal
Allied
health
other
provider
HILS
Imaging lab
PAS
DSS
UPDATE
QUERY
Enterprise
Msg gateway
Patient
Record
Multimedia
genetics
EHR
Online
Demographic
registries
Clinical
models
Interactions DS
Local
modelling
Online drug,
Interactions DB
LAB
workflow
realtime
gateway
demographics
Clinical
ref data
Path lab
notifications
Comprehensive Basic
identity
ECG etc
billing
terms
guidelines
protocols
telemedicine
Online
terminology
Online
archetypes
41
42
Given the complexity of the clinical
trial domain
and given features such as security of
patient data, role of regulatory bodies,
payers, funders, ...
both approaches are needed;
– scientific approach e.g. for clinical terminology
(SNOMED, ...)
– administrative approach e.g. for billing,
ordering ...
43
Clinical trial research
will need to have a clinical trial ontology that
will work together with ontologies for other
domains within biomedicine
44
Alan Rector: Medical IT’s odd
organisational structure
Separate development
of medical ontologies / terminologies such as
SNOMED
and medical information models such as
HL7 RIM
Rector, et al., Binding Ontologies and Coding Systems to Electronic
Health Records and Messages
45
Statements about the world:
All diabetes are metabolic diseases
John has diabetes and it is brittle and long
standing
Valid Specifications for data structures:
Valid diabetic data structures have a diagnosis
code that is diabetes or one of its subcodes
46
Ontologies vs. data structures
Ontology: All persons have a sex
Data structure may have a header for people but no
field for sex
The data structure determines a world in which people
have no sex.
Valid data structures can be exhaustively and
completely described  closed world assumption
Ontologies are intrinsically open; they must be able to
change with new scientific discoveries
– We can never describe the world completely
47
Purpose of an Information Model like HL7
to specify valid data structures to carry
information – valid, for example, for
billing or regulatory purposes
to constrain the data structures to just
those which a given software system
can process
48
The Term Binding Problem
closed world
open world
49
What happens when scientific methods change,
for example new paradigms for testing drug
efficacy are developed?
50
Administrative ontologies vs.
scientific ontologies
CDISC / BRIDG vs. CTO / OBO Foundry
Both share at least one goal in common: to
support high-level information-based
scientific research and clinical care
Can we make the two support each other?
Do we really need both?
Does CDISC / BRIDG already include an
ontology of clinical trials?
51
Does the BRIDG/HL7-style methodology
work, given the problems of achieving
compromise and of maintaining
consistency? (... sort of fits together ...)
Does the OBO / CTO-style methodology not
have analogous problems if all those
separate modules and separate groups
are truly to work together?
52
CDISC = Clinical Data Interchange
Standards Consortium
creating worldwide industry standards to
support the electronic acquisition, exchange,
submission and archiving of clinical trials
data and metadata for medical and
biopharmaceutical product development
53
CDISC, HL7, and caBIG collaboration: The Cancer
Biomedical Informatics Grid Structured Protocol
Representation
caSPR
HL7/CDISC/caBIG
SPR
caBIG
caSPR module analysis
model
caSPR CDE
UML loader
caDSR candidate CDEs
The Clinical Data Interchange Standards Consortium (CDISC) Domain Space Analysis Modeling (DSAM) effort is a strategic initiative between CDISC, Health
Level Seven (HL7) and caBIG to develop, support, influence and harmonize standards for data representation and exchange in clinical research.
A requirement for seamless syntactic and semantic interoperability in clinical research is a common, shared data representation. Such an exchange standard
will facilitate data sharing and help to speed the delivery of innovative solutions to the cancer patient based on biological research, improve the efficiency and
timeliness of data reporting, enhance patient safety during clinical trials, and improve the shared care of oncology patients.
Currently, there are two major standards for data exchange in healthcare. The CDISC group has focused on data exchange and reporting among
pharmaceutical companies engaged in clinical research, while HL7 has developed healthcare messaging standards for all aspects of patient care. The caBIG
community is playing an aggressive part in the activities associated with harmonizing these two models, and constructing a common model that can be shared
among CDISC, HL7, and caBIG members. Specifically, caBIG participants have:
1. Participated in development of the CDISC Clinical Trials DSAM , a UML class model representing the common shared concepts of clinical research across
the key communities – pharmaceutical companies, federal agencies and academic medical centers.
2. Supported the mapping of the CDISC DSAM to the HL7 v3 Reference Information Model (RIM) at the detail attribute level. This will ensure that all caBIG
and CDISC data exchange requirements are addressed by the HL7 v3 messaging standards. Concepts identified in CDISC modeling may uncover new
additions for the RIM, in turn making the RIM more robust
3. Participated in the CDISC Protocol Representation Group to develop a common terminology and vocabulary in support of clinical research data exchange
standards. The CDSIC vocabulary is being maintained in the NCI’s Cancer Data Standards Repository (caDSR) and will harmonize with the NCICB’s
Common Data Elements (CDEs).
This presentation focuses on the first of these three activities – the development of the UML DSAM, representing many hours of intensive interactive modeling
by domain experts and modeling experts from pharmaceutical companies, HL7, and caBIG. The goal of the model is not only to facilitate seamless data
exchange, but also to explore a computable representation of a clinical trial for planning, execution and analysis of clinical trials. In addition to data exchange, it
is hoped this shared model will form the backbone for the applications developed in caBIG’s Clinical Trials Management Systems (CTMS) domain-specific
workspace. Such applications could include advanced protocol authoring tools, tools for data reporting and submissions, clinical trials management, and
interfaces to clinical systems.
This initiative furthers the caBIG vision to provide a common informatics platform to exchange standardized data between disparate systems to support the
cancer research community. The focus to promote data standardization and ability to exchange data seamlessly among the various stakeholders will put
critical information in the hands of researchers, thus enabling them to broaden the scope of their research and allow hitherto unaddressable research directions
to be pursued.
caPRI input module
HL7
CDSIC
Increasing specificity and computability
Participants
Christo Andonyadis
Greg Anglin
Lisa Chatterjee
Julie Evans
Douglas B Fridsma
Smita Hastak
Ray Heimbuch
Charlie Mead
Documentation
Joyce Niland
And authoring
John Speakman
Cara Willoughby
Diane Wold Registration and Reporting
Protocol::StudyBackground (the "why")
+
+
+
+
+
+
+
+
+
+
+
+
description: PSMDescription
summaryOfPrevi ousFindings: PSMDescription
summaryOfRis ksAndBenefits: PSMDescription
justificationOfObjectives: PSMDescription
justificationOfApproach: PSMDescription
populationDescription: PSMDescription
rationaleForEndpoints: PSMDescription
rationaleForDesign: PSMDescription
rationaleForMasking: PSMDescription
rationaleForControl: PSMDescription
rationaleForAnalysisApproach: PSMDescription
Attribute1:
Tracking and Protocol Management
Protocol::
ProtocolReview
*
+
+
Protocol::
SupplementalMaterial
date:
result:
+
+
+
+
1..*
Protocol::
ClinicalDevelopmentPlan
-ConceptProposal
-Protocol 0..*
1
type:
description: PSMDescription
version:
ID: SET PSMID
*
1
Protocol::StudyObligation
+
+
+
+
Protocol::StudyProtocol
-_DevelopmentPlan
1
*
Protocol::
IntegratedDevelopmentPlan
*
+
+
shortTitle: TEXT
statementOfPurpose: TEXT
Protocol::Masking
type: ENUMERATED
description: PSMDescription
commissioningParty:
responsibleParty:
+
+
+
+
-?????
Protocol::
Amendment
Protocol::
CommunicationRecord
0..*
Protocol::
Control
level:
objectOfMasking (set):
procedureToBreak:
unmaskTriggerEvent (set):
1
1
*
*
Protocol::StudyPlan (the "how",
"where", "when", "who")
*
1..*
1
1..*
+
+
+
+
+
+
+
Protocol::StudyObjective (the "what")
Protocol::Document
+
+
+
+
+
+
+
+
+
+
+
+
+
+
version:
author: SET
ID: SET PSMID
documentID:
type: ENUMERATED = formal plus non...
description: PSMDescription
title:
status: PSMStatus
confidentialityCode: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
description: PSMDescription
intentCode: SET ENUMERATED
objectiveType: ENUM{Primary,Secondar y,Ancillar y}
id: PSMID
-source
objective
1
*
+correlativeStudy 0..*
+source 1
Entities and
Roles::
ResearchProgram
+
+
+
+
+
+target
0..*
+
+
+
+
type:
+primaryStudy 1
startDate:
endDate:
studyID: SET PSMID
name:
type:
subtype:
status:
randomizedIndicator:
otherStudyCharacteristics:
description: PSMDescription
functionalRole:
effectiveStartDate:
effectiveEndDate:
authorizingID:
synopsis:
type: test value domain = a,d,f,g
summaryDescription:
summaryCode:
detailedMethodDescription:
detailedMethodCode:
Protocol::Scope
code:
description: TEXT
type: ENUMERATED = primary, secondary
threshold:
Protocol::Concurrency
Protocol::Randomization
+
+
1..*1
minimumBloc kSi ze:
maximumBloc kSize:
Protocol::
Measure
*
Protocol::StudyObjectiveRelationship
1
+
type: PSMCodedConcept
0..1
Entities and Roles::
Study
Protocol::AnalysisTask
+
+
+
Entities and Roles::Role
Entities and Roles::Place
+
-
Entities and Roles::Entity
gpsText:
mobileInd: boolean
addr:
directionsText:
positionText:
+
+
+
+
+
+
+
+
+
-
Entities and Roles::
Organization
+
+
+
1
instantiationType: ENUM {Placeholder, Actual}
id: SET <PSMID>
name: string
code: PSMCodedConcept
quantity: int
description: PSMDescription
statusCode: PSMStatus
existenceTime: PSMInterval
riskCode: PSMCodedConcept
handlingCode: PSMCodedConcept
contactInformation: SET <PSMContactAddr>
*
1
+
+
+
+
+
+
+
+
+
id:
code: PSMCodedConcept
name:
status:
effectiveStartDate:
effectiveEndDate:
geographicAddress:
electronicCommAddr:
certificate/licenseText:
1..*
*
1
geographicAddress:
electronicCommAddr:
standardIndustryClassCode:
Entities and Roles::Employee
+
birthTime:
sex:
deceasedInd: boolean
deceasedTime:
multipleBirthInd: boolean
multipleBirthOrderNumber:
organDonorInd: boolean
+
formCode:
-
Entities and Roles::
Access
lotNumberText: string
expirationTime:
stabilityTime:
Study Design
and Data
Collection::
Procedure
Entities and Roles::Person
+
+
+
+
geographicAddress:
maritalStatusCode:
educationLevelCode:
raceCode:
disabilityCode:
livingArrangementCdoe:
electronicCommAddr:
religiousAffiliationCode:
ethnicGroupCode:
Entities and Roles::
NonPersonLivingEntity
+
-
strain:
genderStatusCode:
Entities and Roles::Device
-
Protocol::
ActivityManagementPlan
*
+
clinicalJustification: TEXT
Study Design and Data
Collection::
SubjectDataEventDefinition-???
+
+
+
+
name:
description:
scheduled(Y/N):
planned(Y/N):
1
Protocol::
SiteSubjectManagementProjectPlan
*
Protocol::HypothesisTest
-source
activity
+target activity
+
+
+
+
1..*
Study Design and Data Collection::Activity
name: TEXT
description: PSMDescription
businessProcessMode: PSMBusinessProcessMode
id: PSMID
code: PSMCodedConcept
negationIndicator: BOOLEAN
derivationExpression: TEXT
status: PSMCodedConcept
effectiveTime: GeneralTimingSpecification
activityTime: GeneralTimingSpecification
availabilityTime: TimingSpecification
priorityCode: PSMCodedConcept
confidentialityCode: PSMCodedConcept
repeatNumber: rangeOfIntegers
interruptibleIndicator: BOOLEAN
uncertaintyCode: CodedConcept
reasonCode: PSMCodedConcept
Protocol::
StatisticalAnalysisPlan
1
significanceLevel:
rejectionRegion:
testStatistic:
comparisonType: ENUM{Superiority,Equivalence,N on-Infer iority}
Protocol::
SiteStudyManagementProjectPlan
*
+TerminatingActivity 1..*
Protocol::
SponsorStudyManagementProjectPlan
0..1
Protocol::StatisticalModel
+EndEvent 1
1
+
+
+
+
1..*
+StartEvent 1
description: PSMDescription
modelAlgorithm: Algorithm
id: PSMID
assumption: SET[TEXT]
+FirstActivity 1..*
Protocol::AnalysisVariableC ollectio n
+
+
+
+
Study Design
and Data
Collection::
Observation
+
Study Design
and Data
Collection::
SubjectEncounter
manufacturerModelName:
softwareName:
localRemoteControlStateCode:
alertLevelCode:
lastCalibrationTime:
Protocol::
SampleSizeCalculation
inputAnalysisVariables: AnalysisVariableCollection
outputAnalysisVariables: AnalysisVariableCollection
analysisType: ENUM{inferential,estimational,descri pti ve}
1
analysis
task
*
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Study Design and Data
Collection::
SubstanceAdministration
ProtocolStructure::
ElectronicSystem
-target
analysis
- task
source
*
*
1..*
1
source
activity
confidentialityCode:
int
Entities and Roles::
ManufacturedMaterial
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
priorityNumber: NUMBER
pauseCriterion:
checkpointCode:
splitCode:
joinCode:
negationIndicator: BOOLEAN
conjunctionCode:
*
jobCode: PSMCodedConcept
Entities and Roles::
Patient
+
+
+
+
+
+
+
+
+
+
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
negationIndicator: BOOLEAN
time: TimingSpecification
contactMediumCode: PSMCodedConcept
targetRoleAwarenessCode: PSMCodedConcept
signatureCode: PSMCodedConcept
signature: PSMDescription
slotReservationIndicator: BOOLEAN
substitionConditionCode: PSMCodedConcept
id: PSMID
status: PSMCodedConcept
Entities and
Roles::
Material
Entities and Roles::
LivingEntity
+
+
+
+
-
+
+
+
+
+
+
+
+
+
+
+
+
target
task
Study Design and Data Collection::
ActivityRelationship
1..*
1
Entities and Roles::ActivityRoleRelationship
1
Protocol::Bias
Protocol::Endpoint
1
Protocol::Study
+
+
+
+
+
+
+
+
+
+
Protocol::
StudyAssignment
Protocol::
Configuration
Protocol::DesignCharacteristic
description: PSMDescription
AnalysisVariable: SET[PSMAnalysisVariable]
id: PSMID
description: PSMDescription
type: ENUM{Determined,Undeter mined}
value: ANY
Study Design
and Data
Collection::
DiagnosticImage
1..*
*
cd Comprehensive Logical Model
Name:
Author:
Version:
Created:
Updated:
Comprehensive Logical Model
Fridsma
1.0
8/13/2001 12:00:00 AM
4/4/2005 1:31:38 PM
+IsContainedIn
Pt eligibility determination and
business rules
1..*
+targetActivity
+sourceActivity
1
+passedTo
+contains
1
+generates
0..*
Study Design and Data
Collection::StudyDesign
ProtocolStructure::
ActivityDerivedData
ProtocolStructure::
ResponsibilityPartition
cd Comprehensive Logical Model
+sourceActivity
+
description: PSMDescription
Study Design and Data
Collection::
StudyDesignElement
1
Protocol::
BusinessRule
+
Protocol::
Milestone
Protocol::
Variance
Protocol::
Waiver
Study Design and Data Collection::
StudyDesignState
1
ProtocolStructure::
ProtocolControlStructure
+
+
+
+
Protocol::
Constraint
1..*
Study Design and Data
Collection::
StudyDesignArmSeg ment
+
sequenceNumber: INTEGER
name: TEXT
entryTransition: SET [TRANSITION]
exitTransition: SET [TRANSITION]
description: TEXT
1..*
Protocol::
Resource
Protocol::
EligibilityCriterion
sequenceNumber: INTEGER
1..*
+targetActivity
Protocol::
ExclusionCriterion
Study Design and Data Collection::
EncounterDefinitionList--???
+
listOfDataCollectionInstruments:
1..*
Study Design and
Data Collection::
StudyDesignEpoch
Protocol Design
ProtocolStructure::
ActivityConnector
-
ProtocolStructure:
:DecisionPoint
ProtocolStructure:
:BranchPoint
ProtocolStructure:
:MergePoint
Rule: PSMTransition
+processes
+IsProcessedby
1
0..*
ProtocolStructure::NotificationEvent
-
type: ENUMERATED = Sent, Received
Study Design and Data Collection::
StudyDesignArm
+
+
targetAccrual: INTEGER
name: TEXT
Statistical Analysis
54
A gigantic integration challenge
what shall serve as benchmark for integration?
for some things (drive on right!) no benchmark is
needed – the choice can be arbirtary
for most things we need rules which must be
somehow grounded in a larger, intuitively
intelligible framework
OBO Foundry: the real world (our best current
scientific knowledge) (is already integrated)
CDISC / CTOM / BRIDG: ?
55
UML
UML primarily designed as a language to be used
by humans to document and communicate
software designs.
Thus main notation of UML is a graphical model
rather than a formal language.
UML is the union of different preexisting proposals
aiming at maximal expressivity. Thus it uses
different interacting model types each covering a
specific aspect of the overall system.
56
UML
Used as a documentation, design, analysis,
communication, clarification, collaboration
tool. Typically for complicated interactions
between components, or when a
method/object is too big to hold in your
mind.
57
Advantages of UML
single standard framework including facilities to
represent both static and dynamic features of
reality
well-connected to software development
communities
can do justice to the way in which in a domain like
clinical trials dynamic aspects are increasingly
both inside and outside the computer
advances software coupling
58
UML consistency/validation
UML provides several kinds of diagrams to
model the behavior and structure of a
system under development. A consistency
problem can arise due to the fact that
some aspects of the model may be
described by more than one diagram.
59
Add to UML the dimension of HL7
ANSI / ISO standard
provides a common, highly general benchmark
relatively stable, hard to change, large body of
adherents
provides the needed pathway for integration
has created incentives for use (NCI)
60
Good parts of HL7
are based in reality: Clinical Document
Architecture (CDA)
61
Problems of consistency of not so
good parts of HL7
• Sometimes ‘Act’ means real-world action
• Sometimes ‘Act’ means information
object = act qua documented, either
– in an actual document (reflecting the
subjective view of some author), or
– in some postulated HL7-conformant absolute
documentation
Recall double role of ontology and prescriptive
standard
62
HL7 Axiom
“... there is no distinction between an
activity and its documentation. Every
Act includes both to varying degrees.”
(RIM 3.1.1)
63
For the clinical research domain
Reports
Observations
Entities observed
Adverse event = observation of adverse event
events and observations may take place on
different continents
use-case for CTO (what CTO can add to RCT
Schema)
64
Problems of coordination of large
standards development efforts
‘As different people edit parts of the [HL7]
specification, inconsistencies in form and
quality may emerge; as some ambiguities
are clarified, other previous systematic
ideas may be corrupted; and well-meant
glossary entities may cause confusion.’
Gunther Schadow MIE 2006, p. 154
65
So:
On the one hand HL7 is to facilitate
agreement on consistent meanings across
the entire range of clinical domains.
On the other hand HL7 own collaborating
authors cannot reach agreement even
amongst themselves.
Yet the resultant inconsistent ‘normative’
recommendations are approved by ISO as
an international standard
66
Everything in HL7 is an act, an
entity, or a relation
Definition of Entity:
A physical thing, group of physical things
or an organization capable of participating
in Acts, while in a role. (HL7V3 Ballot 2006-9: RIM)
Entity = persons, places, organizations,
material
67
Problems of scope
No processes (verb-like items) outside Act
How can HL7 deal with disease processes,
drug interactions, traffic accidents, snake
bits, other adverse events?
Answer: it identifies them with acts of
observation
68
Problems of scope
No things (noun-like items) outside Entity
How can HL7 deal with wounds, fractures?
69
Diseases in HL7
... are not Acts
... are not Entities
... are not Roles, Participations, Role-Links ...
So what are they?
Answer: they are Acts of Observation
A case of pneumonia is an Act of
Observation of a case of pneumonia
70
To solve these problems of scope
add to HL7 new upper-level types:
process (with act as sub-type)
condition (with disease ... as subtype)
drug interactions are processes, not acts
diseases are conditions on the side of patients, not
acts of observation by clinicians
accepted by some inside HL7
71
The HL7 ballotting methodology
vs. scientific method
– welcoming of open criticism
– secondary literature
– incremental testing
– cumulation of results
72
BRIDG= Biomedical Research
Integrated Domain Group
a domain analysis model representing
protocol-driven biomedical/clinical
research. It was developed to provide an
overarching model that could readily be
understood by domain experts and would
provide the basis for harmonization among
standards within the clinical research
domain and between biomedical/clinical
research and healthcare.
73
BRIDG
The BRIDG model defines standard
entities, roles, attributes, and activities for
the business processes in standard clinical
trials. It could be used as a core data
standard for managing the workflow in
clinical trials and for generating clinical trial
software applications that share the same
semantics and thus can exchange data
more readily.
74
BRIDG
How is BRIDG different from previous
structured clinical trial protocol models?
– most previous protocol models are
• document-oriented
• focused on protocol knowledge structure
• built through a specific knowledge representation tool.
In contrast, BRIDG is independent from any
implementation software and defines only
semantics for the clinical trial research
domain. Therefore, BRIDG has the potential
to facilitate clinical trials across organizations
and software platforms.
75
cd Comprehensiv e Logical Model
Design Concepts::Masking
+
+
+
+
Protocol
Concepts::
Control
HasSubElements
the BRIDG model
Name:
Author:
Version:
Created:
Updated:
level:
objectOfMasking (set):
procedureToBreak:
unmaskTriggerEvent (set):
AbstractActivity
«Period»
Design Concepts::Element
Protocol Concepts::DesignCharacteristic
Comprehensive Logical Model
Fridsma
1.0
7/22/2005 2:53:51 PM
7/29/2005 2:33:32 PM
+
+
+
+
+
+
Protocol
Concepts::
Scope
-
Protocol
Concepts::
Configuration
synopsis:
type: test value domain = a,d,f,g
summaryDescription:
summaryCode:
detailedMethodDescription:
detailedMethodCode:
Children: Set
epochType: EpochTypes
AbstractActivity
displayName: char[]
whoPerforms: int
sequence: int
procDefID: PSMCodedConcept
sourceText: char[]
SubjectEvent
Protocol Concepts::StudyBackground(w hy)
+
+
+
+
+
+
+
+
+
+
+
hasElements
hasScheduledEvents
Design Concepts::PlannedTask
-
Protocol
Concepts::Bias
Design Concepts::Arm
Design Concepts::ProtocolEv ent
description: PSMDescription
summaryOfPreviousFindings: PSMDescription
summaryOfRisksAndBenefits: PSMDescription
justificationOfObjectives: PSMDescription
justificationOfApproach: PSMDescription
populationDescription: PSMDescription
rationaleForEndpoints: PSMDescription
rationaleForDesign: PSMDescription
rationaleForMasking: PSMDescription
rationaleForControl: PSMDescription
rationaleForAnalysisApproach: PSMDescription
hasElements
Protocol Concepts::StudyObligation
+
+
+
+
1
type: ENUMERATED
description: PSMDescription
commissioningParty:
responsibleParty:
Design Concepts::
Randomization
+
+
Protocol Concepts::
Concurrency
-
-
parent: AbstractActivity
eventType: ScheduledEventType
studyOffset: PSMInterval
studyDayOrTime: char
nameOfArm: char[]
plannedEnrollmentPerArm: char[]
randomizationWeightForArn: int
associatedSchedules: Set
tasksPerformedThisSchedule
taskAtEvent
hasOngoingEvents
minimumBlockSize:
maximumBlockSize:
1..*
AbstractActivity
+correlativeStudy 0..*
Design Concepts::Ev entTask
BusinessObj ects::Study
BusinessObj ects::
ClinicalDev elopmentPlan
-_DevelopmentPlan
+
+
+
+
+
+
BusinessObj ects:
:Amendment
*
-
+primaryStudy 1
startDate: Date
endDate: Date
type: PSMCodedConcept
phase: PSMCodedConcept
randomizedIndicator: Text
SubjectType: PSMCodedConcept
hasArms
Design Concepts::StudySchedule
localFacilityType: LocalFacilityType
centralFacilitityType: CentralFacilitiyType
eventID: OID
taskID: OID
purposes: Set
-
Periods: Set
Tasks: Set
TaskVisits: Set
associatedArms: Set
hasUnscheduledEvents
Protocol Concepts::StudyObj ectiv e(w hat)
+
+
+
+
1
+
SubjectEvent
Design Concepts::UnscheduledEv ent
BusinessObj ects::
Activ itySchedule (the "how ",
"w here", "w hen", "w ho")
BusinessObj ects::
IntegratedDev elopmentPlan
-
eventType: UnscheduledEventType
-
activityID: OID
description: PSMDescription
description: PSMDescription
intentCode: SET ENUMERATED
objectiveType: ENUM{Primary,Secondary,Ancillary}
id: PSMID
hasPurposes
«execution mode»
*
Design Concepts::
StudyActiv ityRef
Scheduled Sub Activities
0..*
-source
objective
Protocol Concepts::StudyDocument
+
+
+
+
+
+
+
+
+
+
+
+
1
Protocol Concepts::Outcome
BusinessObj ects::
ProtocolDocument
effectiveEndDate: DATETIME
version:
author: SET
effectiveStartDate: DATETIME
ID: SET PSMID
documentID:
type: ENUMERATED = formal plus non...
description: PSMDescription
title:
status: PSMStatus
confidentialityCode: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
1..*
1..* -
BusinessObj ects::
ClinicalStudyReport
description: BRIDGDescription
ranking: OutcomeRank
associatedObjective: Set
analyticMethods: Set
asMeasuredBy: Set
outcomeVariable:
threshold:
Defined By
as Measured By
-
Design Concepts::Ev entTaskPurpose
BasicTypes::StudyDatum
isBaseline: boolean
purposeType: PurposeType
associatedOutcome:
-
+
type:
+
+
+
+
-
-
BasicTypes::RIMActiv ityRelationship
subjectID: int
BasicTypes::StudyVariable
-
«ODM:ItemData»
Design Concepts::
TreatmentConfirmed
Statistical Concepts::StatisticalConceptArea
Entities and Roles::Organization
+
+
+
instantiationType: ENUM {Placeholder, Actual}
id: SET <PSMID>
1
name: string
code: PSMCodedConcept
quantity: int
description: PSMDescription
statusCode: BRIDGStatus
1
existenceTime: BRIDGInterval
riskCode: PSMCodedConcept
handlingCode: PSMCodedConcept
contactInformation: SET <PSMContactAddr>
BusinessObj ects::
StatisticalAnalysisPlan
*
1
Entities and Roles::Role
* +
+
+
+
+
+
+
+
+
Entities and Roles::Activ ityRoleRelationship
id:
code: PSMCodedConcept
name:
status:
effectiveStartDate:
effectiveEndDate:
geographicAddress:
electronicCommAddr:
certificate/licenseText:
+
+
+
+
+
* +
+
+
+
+
+
+
1
geographicAddress:
electronicCommAddr:
standardIndustryClassCode:
1
+
+
+
+
-
birthTime:
sex:
deceasedInd: boolean
deceasedTime:
multipleBirthInd: boolean
multipleBirthOrderNumber: int
organDonorInd: boolean
+
hasHypotheses
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
negationIndicator: BOOLEAN
time: TimingSpecification
contactMediumCode: PSMCodedConcept
targetRoleAwarenessCode: PSMCodedConcept
signatureCode: PSMCodedConcept
signature: PSMDescription
slotReservationIndicator: BOOLEAN
substitionConditionCode: PSMCodedConcept
id: PSMID
status: PSMCodedConcept
+
+
+
+
+
+
#
+
Entities and Roles::
ManufacturedMaterial
jobCode: PSMCodedConcept
-source
activity
confidentialityCode:
Entities and Roles::
Access
Entities and Roles::Person
significanceLevel: double
lowerRejectionRegion: int
upperRejectionRegion: int
testStatistic:
comparisonType: AnalyticComparisonTypes
associatedSummaryVariables:
BasicTypes::ActActRelation
hasAnalysisSets
hasAnalyses
geographicAddress:
maritalStatusCode:
educationLevelCode:
raceCode:
disabilityCode:
livingArrangementCdoe:
electronicCommAddr:
religiousAffiliationCode:
ethnicGroupCode:
«property» relationQualifier() : PSMCodedConcept
«property» sourceAct() : AbstractActivity
«property» destAct() : AbstractActivity
kindOfActRelation
kindOfAnalysis
kindOfAnalysis
-_StatisticalAnalysisSet
*
Statistical Concepts::
StatisticalAssumption
*
Protocol Concepts::StudyObj ectiv eRelationship
+
type: PSMCodedConcept
+
-
statement: PSMDescription
associatedObjective:
clinicallySignificantDiff: char
AbstractActivity
-_Hypothesis
*
hasAnalyses
+
BasicTypes::
AbstractRule
description: PSMDescription
Statistical Concepts::Analysis
+
+
+
+
#
#
description: PSMDescription
analysisType: Set{AnalysisTypes}
analysisRole:
rationaleForAnalysisApproach: PSMDescription
associatedStrategy:
associatedHypotheses:
hasStrategy
-
isExclusive: bool
+
run() : bool
hasAssumptions
hasModel
Statistical Concepts::StatisticalModel
+
#
-
description: PSMDescription
outputStatistic: StudyVariable
computations: Set
assumptions: Set
implements
Implements
*
manufacturerModelName:
softwareName:
localRemoteControlStateCode:
alertLevelCode:
lastCalibrationTime:
+IsContainedIn
+contains 1
1
OProtocolStructure::
ResponsibilityAssignment
1..* +targetActivity
+sourceActivity 1
«implementationClass»
Design Concepts::
TemporalRule
Statistical Concepts::
SequentialAnalysisStrategy
+
+
+
+
alphaSpendingFunction:
timingFunction:
analysis:
trialAdjustmentRule:
AbstractActivity
«implementationClass»
BusinessObj ects::
BusinessRule
Statistical Concepts::Computation
-
description: PSMDescription
algorithm: char
input: AbstractStatisticalParameter
output: AbstractStatisticalParameter
+passedTo
+generates 0..*
OProtocolStructure::
Activ ityDeriv edData
hasSchedules
Plans::Protocol/Plan
BusinessObj ects::
SiteSubj ectManagementProj ectPlan
1..*
1
BusinessObj ects::
SiteStudyManagementProj ectPlan
BusinessObj ects::
SponsorStudyManagementProj ectPlan
OStudy Design and Data Collection::
OBRIDGDeriv ationExpression
BasicTypes::BRIDGInterv al
BasicTypes::BRIDGBusinessProcessMode
+
modeValue: ENUM {Plan, Execute}
+
startTime: timestamp
endTime: timestamp
+
+
+
+
BusinessObj ects:
:
RegulatoryRecord
type: ENUM{transformation, selection}
rule: TEXT
id: PSMID
name: TEXT
+
+
+
source: Text
version: Text
value: Text
+
+
BusinessObj ects::
ClinicalTrialMaterialPlans
BusinessObj ects::
RandomizationAssignment
code: TEXT
codeSystem:
codeSystemName: TEXT
codeSystemVersion: NUMBER
displayName: TEXT
originalText: TEXT
translation: SET{PSMCodedConcept}
criterion: RULE
eventName: TEXT
+
+
+
BusinessObj ects::
EnrollmentRecord
randomizationCode:
subjectID:
assignmentDateTime:
BusinessObj ects::Guide
+
+
+
+
BusinessObj ects::
DataMonitoringCommitteePlan
BusinessObj ects::BiospecimenPlan
BusinessObj ects::
DataManagementPlan
BasicTypes::BRIDGAnalysisVariable
BasicTypes::BRIDGCodedConcept
-
1 1..*
BusinessObj ects::Inv estigatorRecruitmentPlan
OStudy Design and Data Collection::OBRIDGTransition
BasicTypes::BRIDGID
BusinessObj ects::AssayProcedures
name: TEXT
value:
controlledName: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
BusinessObj ects::
FinalRandomizationAssignment
BusinessObj ects::
Waiv er
BusinessObj ects::
Adv erseEv entPlan
BusinessObj ects::
ContingencyPlan
Protocol Concepts::Constraint
OStudy Design and Data Collection::
OEncounterDefinitionList--???
BasicTypes::BRIDGStatus
+
+
+
effectiveEndDate:
effectiveStartDate:
statusValue:
implements
hasComputations
Entities and Roles::Dev ice
-
+
+
+
clinicalJustification: TEXT
Statistical Concepts::Hypothesis
hasChildAnalyses
strain:
genderStatusCode:
description: BRIDGDescription
relationQualifier: BRIDGCodedConcept
mode: PSMBusinessProcessMode
effectiveTime: BRIDGInterval
priorityNumber: NUMBER
negationRule: AbstractRule
detail: char
sourceAct: AbstractActivity
destAct: AbstractActivity
sequence: int
AbstractActivity
businessProcessMode: PSMBusinessProcessMode
code: PSMCodedConcept
derivationExpression: TEXT
status: PSMCodedConcept
+TerminatingActivity 1..*
availabilityTime: TimingSpecification
priorityCode: PSMCodedConcept
confidentialityCode: PSMCodedConcept
repeatNumber: rangeOfIntegers
+EndEvent 1
interruptibleIndicator: BOOLEAN
uncertaintyCode: CodedConcept
+StartEvent 1
reasonCode: PSMCodedConcept
Entities and Roles::
NonPersonLiv ingEntity
+
-
+
-
Statistical Concepts::
SampleSizeCalculation
+FirstActivity 1..*
+
+
+
+
description: char
subgroupVariable: StudyDatum
sequence: int
+
BasicTypes::RIMActivity
+
+
+
+
+
+
+
+
+
+
+
OProtocolStructure::
ElectronicSystem
lotNumberText: string
expirationTime:
stabilityTime:
description: PSMDescription
scopeType: AnalysisScopeTypes
hasCriteria
-source
activity
+target activity
1
-
+
-
Statistical Concepts::HypothesisTest
Entities and Roles::Patient
«ODM:ItemDef»
Design Concepts::
PlannedObserv ation
Statistical Concepts::
StatisticalAnalysisSet
hasAnalysisSets
evaluableSubjectDefinition: char
intentToTreatPopulation: char
clinicallyMeaningfulDifference: char
proceduresForMissingData: char
statSoftware: char
methodForMinimizingBias: char
subjectReplacementStrategy: char
randAndStratificationProcedures: char
Statistical Concepts::AnalysisSetCriterion
Entities and Roles::Employee
formCode:
-
-
1..*
Entities and
Roles::Material
Entities and Roles::Liv ingEntity
OID: long
Name: char
unitOfMeasureID: OID
minValid:
maxValid:
controlledName: ENUM
restates Objective
*
1..*
+
+
+
+
+
+
+
+
+
+
+
kindOfActivityRelation
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
pauseCriterion:
checkpointCode:
splitCode:
joinCode:
negationIndicator: BOOLEAN
conjunctionCode:
Entities and Roles::Entity
gpsText:
mobileInd: boolean
addr:
directionsText:
positionText:
roleInAnalysis: RoleInAnalysisTypes
transactionType:
«ODM ItemData»
Design Concepts::
DiagnosticImage
Entities and Roles::
Study
+
-
«ODM:ItemDef»
Design Concepts::
PlannedInterv ention
kindOf
«abstract»
Design
Concepts::
StudyActivityDef
«ODM:ItemData»
Design Concepts::
SubjectDatum
-
type:
description: PSMDescription
version:
ID: SET PSMID
+
+
+
+
+
+
+
+
Entities and Roles::Place
AbstractActivity
BusinessObj ects::
SupplementalMaterial
+source 1
+target 0..*
Defined By
isKindOf
BasicTypes::AnalysisVariableInst
associatedVariable
«ODM ItemData»
Design Concepts::Observ ation
BusinessObj ects::
CommunicationRecord
Entities and
Roles::
ResearchProgram
complete: bool
value: Value
timestamp: timestamp
itemOID:
BasicTypes::BRIDGContactAddr
«abstraction»
+
+
+
type: PSMCodedConcept
effectiveTime: BRIDGInterval
usage: PSMCodedConcept
+
Protocol Concepts::
EligibilityCriterion
listOfDataCollectionInstruments:
Protocol Concepts::
Variance
Protocol Concepts::
ExclusionCriterion
BusinessObj ects:
:ProtocolRev iew
+
+
date:
result:
Protocol Concepts::
Milestone
BusinessObj ects::
Subj ectRecruitmentPlan
BusinessObj ects::SafetyMonitoringPlan
76
«implementationClass»
Design Concepts::
ClinicalDecision
cd Comprehensiv e Logical Model
Clinical Trial Design
Design Concepts::Masking
+ level:
+ objectOfMasking (set):
+ procedureToBreak:
+ unmaskTriggerEvent (set):
Protocol
Concepts::
Control
HasSubElements
AbstractActivity
«Period»
Design Concepts::Element
Name:
Author:
Version:
Created:
Updated:
Protocol Authoring
and Documentation
Comprehensive Logical Model
Fridsma
1.0
7/22/2005 2:53:51 PM
7/29/2005 2:33:32 PM
Protocol Concepts::DesignCharacteristic
Protocol
Concepts::
Scope
-
Protocol
Concepts::
Configuration
+ synopsis:
+ type: test value domain = a,d,f,g
+ summaryDescription:
+ summaryCode:
+ detailedMethodDescription:
+ detailedMethodCode:
Children: Set
epochType: EpochTypes
AbstractActivity
+
+
+
+
+
+
+
+
+
+
+
hasElements
hasScheduledEvents
Design Concepts::PlannedTask
-
Protocol
Concepts::Bias
displayName: char[]
whoPerforms: int
sequence: int
procDefID: PSMCodedConcept
sourceText: char[]
SubjectEvent
Protocol Concepts::StudyBackground(w hy)
Design Concepts::Arm
Design Concepts::ProtocolEv ent
description: PSMDescription
summaryOfPreviousFindings: PSMDescription
summaryOfRisksAndBenefits: PSMDescription
justificationOfObjectives: PSMDescription
justificationOfApproach: PSMDescription
populationDescription: PSMDescription
rationaleForEndpoints: PSMDescription
rationaleForDesign: PSMDescription
rationaleForMasking: PSMDescription
rationaleForControl: PSMDescription
rationaleForAnalysisApproach: PSMDescription
hasElements
Protocol Concepts::StudyObligation
1
+ type: ENUMERATED
+ description: PSMDescription
+ commissioningParty:
+ responsibleParty:
Design Concepts::
Randomization
Protocol Concepts::
Concurrency
-
-
parent: AbstractActivity
eventType: ScheduledEventType
studyOffset: PSMInterval
studyDayOrTime: char
nameOfArm: char[]
plannedEnrollmentPerArm: char[]
randomizationWeightForArn: int
associatedSchedules: Set
tasksPerformedThisSchedule
taskAtEvent
hasOngoingEvents
+ minimumBlockSize:
+ maximumBlockSize:
1..*
AbstractActivity
+correlativeStudy 0..*
Design Concepts::Ev entTask
BusinessObj ects::Study
BusinessObj ects::
ClinicalDev elopmentPlan
-_DevelopmentPlan
Protocol Concepts::StudyObj ectiv e(w hat)
-
+
+
+
+
+
+
+
+
+
+
+
+
+ type:
-source
objective
1
1..* -
BusinessObj ects::
ClinicalStudyReport
description: BRIDGDescription
ranking: OutcomeRank
associatedObjective: Set
analyticMethods: Set
asMeasuredBy: Set
outcomeVariable:
threshold:
-
Design Concepts::Ev entTaskPurpose
BasicTypes::StudyDatum
isBaseline: boolean
purposeType: PurposeType
associatedOutcome:
-
+target 0..*
-
complete: bool
value: Value
timestamp: timestamp
itemOID:
Defined By
«ODM:ItemData»
Design Concepts::
SubjectDatum
«ODM ItemData»
Design Concepts::
DiagnosticImage
-
BasicTypes::RIMActiv ityRelationship
«ODM:ItemData»
Design Concepts::
TreatmentConfirmed
1
+ geographicAddress:
+ electronicCommAddr:
+ standardIndustryClassCode:
1
BusinessObj ects::
StatisticalAnalysisPlan
hasHypotheses
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
negationIndicator: BOOLEAN
time: TimingSpecification
contactMediumCode: PSMCodedConcept
targetRoleAwarenessCode: PSMCodedConcept
signatureCode: PSMCodedConcept
signature: PSMDescription
slotReservationIndicator: BOOLEAN
substitionConditionCode: PSMCodedConcept
id: PSMID
status: PSMCodedConcept
+ significanceLevel: double
+ lowerRejectionRegion: int
+ upperRejectionRegion: int
+ testStatistic:
+ comparisonType: AnalyticComparisonTypes
# associatedSummaryVariables:
Entities and Roles::Employee
-source
activity
OProtocolStructure::
ElectronicSystem
lotNumberText: string
expirationTime:
stabilityTime:
Entities and Roles::
Access
Entities and Roles::Person
geographicAddress:
maritalStatusCode:
educationLevelCode:
raceCode:
disabilityCode:
livingArrangementCdoe:
electronicCommAddr:
religiousAffiliationCode:
ethnicGroupCode:
Statistical Concepts::
SampleSizeCalculation
kindOfActRelation
AbstractActivity
kindOfAnalysis
kindOfAnalysis
businessProcessMode: PSMBusinessProcessMode
code: PSMCodedConcept
derivationExpression: TEXT
status: PSMCodedConcept
+TerminatingActivity 1..*
availabilityTime: TimingSpecification
priorityCode: PSMCodedConcept
confidentialityCode: PSMCodedConcept
repeatNumber: rangeOfIntegers
+EndEvent 1
interruptibleIndicator: BOOLEAN
uncertaintyCode: CodedConcept
+StartEvent 1
reasonCode: PSMCodedConcept
-_StatisticalAnalysisSet
*
Statistical Concepts::
StatisticalAssumption
Statistical Concepts::Hypothesis
*
Protocol Concepts::StudyObj ectiv eRelationship
+ statement: PSMDescription
- associatedObjective:
- clinicallySignificantDiff: char
AbstractActivity
-_Hypothesis
*
hasAnalyses
+ type: PSMCodedConcept
hasStrategy
+contains 1
BasicTypes::BRIDGInterv al
- startTime: timestamp
+ endTime: timestamp
OStudy Design and Data Collection::
OBRIDGDeriv ationExpression
+ source: Text
+ version: Text
+ value: Text
BasicTypes::BRIDGCodedConcept
-
code: TEXT
codeSystem:
codeSystemName: TEXT
codeSystemVersion: NUMBER
displayName: TEXT
originalText: TEXT
translation: SET{PSMCodedConcept}
«abstraction»
implements
Implements
implements
OProtocolStructure::
ResponsibilityAssignment
+ randomizationCode:
+ subjectID:
+ assignmentDateTime:
«implementationClass»
BusinessObj ects::
BusinessRule
«implementationClass»
Design Concepts::
ClinicalDecision
description: PSMDescription
algorithm: char
input: AbstractStatisticalParameter
output: AbstractStatisticalParameter
+passedTo
+generates 0..*
OProtocolStructure::
Activ ityDeriv edData
hasSchedules
Plans::Protocol/Plan
BusinessObj ects::
SiteSubj ectManagementProj ectPlan
1..*
1
BusinessObj ects::
SiteStudyManagementProj ectPlan
BusinessObj ects::
SponsorStudyManagementProj ectPlan
1 1..*
BusinessObj ects::
EnrollmentRecord
BusinessObj ects::Guide
BusinessObj ects::
DataMonitoringCommitteePlan
BusinessObj ects::BiospecimenPlan
Structured
Statistical Analysis
BusinessObj ects::
DataManagementPlan
BasicTypes::BRIDGAnalysisVariable
BusinessObj ects::AssayProcedures
+ name: TEXT
+ value:
+ controlledName: PSMCodedConcept
+ businessProcessMode: PSMBusinessProcessMode
BusinessObj ects::
FinalRandomizationAssignment
BusinessObj ects::
Waiv er
BasicTypes::BRIDGContactAddr
+ type: PSMCodedConcept
+ effectiveTime: BRIDGInterval
+ usage: PSMCodedConcept
«implementationClass»
Design Concepts::
TemporalRule
AbstractActivity
Statistical Concepts::Computation
-
BusinessObj ects::
ClinicalTrialMaterialPlans
BusinessObj ects::
RandomizationAssignment
+ criterion: RULE
+ eventName: TEXT
OStudy Design and Data Collection::
OEncounterDefinitionList--???
+ effectiveEndDate:
+ effectiveStartDate:
+ statusValue:
Statistical Concepts::StatisticalModel
+ description: PSMDescription
# outputStatistic: StudyVariable
- computations: Set
- assumptions: Set
BusinessObj ects::Inv estigatorRecruitmentPlan
Protocol Concepts::Constraint
BasicTypes::BRIDGStatus
hasModel
Statistical Concepts::
SequentialAnalysisStrategy
+ alphaSpendingFunction:
+ timingFunction:
+ analysis:
+ trialAdjustmentRule:
1..* +targetActivity
+sourceActivity 1
Protocol activities and
Safety monitoring (AE)
BusinessObj ects:
:
RegulatoryRecord
+ type: ENUM{transformation, selection}
+ rule: TEXT
+ id: PSMID
+ name: TEXT
OStudy Design and Data Collection::OBRIDGTransition
BasicTypes::BRIDGID
isExclusive: bool
+ run() : bool
hasComputations
*
1
BasicTypes::BRIDGBusinessProcessMode
-
hasAssumptions
Entities and Roles::Dev ice
manufacturerModelName:
softwareName:
localRemoteControlStateCode:
alertLevelCode:
lastCalibrationTime:
+IsContainedIn
+ modeValue: ENUM {Plan, Execute}
BasicTypes::
AbstractRule
+ description: PSMDescription
Statistical Concepts::Analysis
+ description: PSMDescription
+ analysisType: Set{AnalysisTypes}
+ analysisRole:
+ rationaleForAnalysisApproach: PSMDescription
# associatedStrategy:
# associatedHypotheses:
hasChildAnalyses
-
description: BRIDGDescription
relationQualifier: BRIDGCodedConcept
mode: PSMBusinessProcessMode
effectiveTime: BRIDGInterval
priorityNumber: NUMBER
negationRule: AbstractRule
detail: char
sourceAct: AbstractActivity
destAct: AbstractActivity
sequence: int
+ «property» relationQualifier() : PSMCodedConcept
+ «property» sourceAct() : AbstractActivity
+ «property» destAct() : AbstractActivity
hasAnalyses
Entities and Roles::
NonPersonLiv ingEntity
+ strain:
- genderStatusCode:
description: char
subgroupVariable: StudyDatum
sequence: int
hasAnalysisSets
+FirstActivity 1..*
+
+
+
+
+
-
+ clinicalJustification: TEXT
BasicTypes::RIMActivity
+
+
+
+
+
+
+
+
+
+
+
+ confidentialityCode:
Entities and Roles::
ManufacturedMaterial
BasicTypes::ActActRelation
hasCriteria
-source
activity
+target activity
1
-
+ description: PSMDescription
- scopeType: AnalysisScopeTypes
-
Entities and Roles::Patient
«ODM:ItemDef»
Design Concepts::
PlannedObserv ation
Statistical Concepts::
StatisticalAnalysisSet
hasAnalysisSets
evaluableSubjectDefinition: char
intentToTreatPopulation: char
clinicallyMeaningfulDifference: char
proceduresForMissingData: char
statSoftware: char
methodForMinimizingBias: char
subjectReplacementStrategy: char
randAndStratificationProcedures: char
Statistical Concepts::HypothesisTest
+ jobCode: PSMCodedConcept
+ formCode:
-
Statistical Concepts::AnalysisSetCriterion
1..*
Entities and
Roles::Material
OID: long
Name: char
unitOfMeasureID: OID
minValid:
maxValid:
controlledName: ENUM
restates Objective
*
Entities and Roles::Activ ityRoleRelationship
+
+
+
+
+
* +
+
+
+
+
+
+
kindOfActivityRelation
BasicTypes::StudyVariable
-
Statistical Concepts::StatisticalConceptArea
Entities and Roles::Role
roleInAnalysis: RoleInAnalysisTypes
subjectID: int
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
pauseCriterion:
checkpointCode:
splitCode:
joinCode:
negationIndicator: BOOLEAN
conjunctionCode:
1
id:
code: PSMCodedConcept
name:
status:
effectiveStartDate:
effectiveEndDate:
geographicAddress:
electronicCommAddr:
certificate/licenseText:
«ODM:ItemDef»
Design Concepts::
PlannedInterv ention
kindOf
«abstract»
Design
Concepts::
StudyActivityDef
BusinessObj ects::
SupplementalMaterial
+ type:
+ description: PSMDescription
+ version:
+ ID: SET PSMID
*
* +
+
+
+
+
+
+
+
+
AbstractActivity
isKindOf
transactionType:
-
1..*
birthTime:
sex:
deceasedInd: boolean
deceasedTime:
multipleBirthInd: boolean
multipleBirthOrderNumber: int
organDonorInd: boolean
Design Concepts::
StudyActiv ityRef
BasicTypes::AnalysisVariableInst
Entities and Roles::Entity
Entities and Roles::Liv ingEntity
activityID: OID
Defined By
as Measured By
associatedVariable
«ODM ItemData»
Design Concepts::Observ ation
Entities and Roles::
Study
+
+
+
+
-
-
«execution mode»
1..*
Protocol Concepts::Outcome
BusinessObj ects::
ProtocolDocument
effectiveEndDate: DATETIME
version:
author: SET
effectiveStartDate: DATETIME
ID: SET PSMID
documentID:
type: ENUMERATED = formal plus non...
description: PSMDescription
title:
status: PSMStatus
confidentialityCode: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
+
+
+
+
+
+
+
+
Entities and Roles::Organization
eventType: UnscheduledEventType
Scheduled Sub Activities
+source 1
instantiationType: ENUM {Placeholder, Actual}
id: SET <PSMID>
1
name: string
code: PSMCodedConcept
quantity: int
description: PSMDescription
statusCode: BRIDGStatus
1
existenceTime: BRIDGInterval
riskCode: PSMCodedConcept
handlingCode: PSMCodedConcept
contactInformation: SET <PSMContactAddr>
SubjectEvent
Design Concepts::UnscheduledEv ent
-
0..*
Protocol Concepts::StudyDocument
Entities and
Roles::
ResearchProgram
+
+
+
+
+
+
+
+
+
+
+
hasUnscheduledEvents
hasPurposes
*
BusinessObj ects::
CommunicationRecord
Entities and Roles::Place
Periods: Set
Tasks: Set
TaskVisits: Set
associatedArms: Set
+ description: PSMDescription
+ description: PSMDescription
+ intentCode: SET ENUMERATED
+ objectiveType: ENUM{Primary,Secondary,Ancillary}
+ id: PSMID
1
+ gpsText:
- mobileInd: boolean
- addr:
- directionsText:
- positionText:
hasArms
Design Concepts::StudySchedule
localFacilityType: LocalFacilityType
centralFacilitityType: CentralFacilitiyType
eventID: OID
taskID: OID
purposes: Set
BusinessObj ects::
Activ itySchedule (the "how ",
"w here", "w hen", "w ho")
BusinessObj ects::
IntegratedDev elopmentPlan
Clinical Trial
Registration
-
+primaryStudy 1
+ startDate: Date
+ endDate: Date
+ type: PSMCodedConcept
+ phase: PSMCodedConcept
+ randomizedIndicator: Text
+ SubjectType: PSMCodedConcept
BusinessObj ects:
:Amendment
*
+ listOfDataCollectionInstruments:
Protocol Concepts::
EligibilityCriterion
Protocol Concepts::
Variance
Protocol Concepts::
ExclusionCriterion
BusinessObj ects:
:ProtocolRev iew
+ date:
+ result:
Protocol Concepts::
Milestone
Eligibility
Determination
BusinessObj ects::
Adv erseEv entPlan
BusinessObj ects::
ContingencyPlan
BusinessObj ects::
Subj ectRecruitmentPlan
BusinessObj ects::SafetyMonitoringPlan
77
BRIDG
The development of BRIDG was initiated by
the CDISC Consortium and guided by the
HL7 Development Framework (HDF)
methodology.
Purpose: to create computable
interoperability
– support software authoring and integration
78
Business case
the FDA and the entire pharma industry
see that they can benefit from some
standard
industry will be motivated to create
software to make the standard useable
even by those who do not understand it
79
What happens when scientific methods change,
for example new paradigms for testing drug
efficacy are developed?
80
what is the incentive for all this
modeling?
Bob: There needs to be a business case to
justify doing the mapping. The most
powerful business case would be that the
NCI required cancer centers to do it.
81
BRIDG p. 670
DCI Definition v 2.4.6::ExplicitItemRefRepetition
Type:
Class
Status:
Proposed. Version 1.0. Phase 1.0.
Package: DCI Definition v 2.4.6
Details:
Created on 7/8/2005 5:09:15 PM. Modified on 7/13/2006 9:01:27 AM.
Author: Don Kacher
This class repesents a repeat of an ItemRef within a GroupRef. If the GroupRef owning
an ItemRef is non-repeating (i.e., if its MaximumItemRefRepeats is zero), no
ExplicitItemRefRepetitions are allowed.
If repeating is enabled for the GroupRef, an ExplicitItemRefRepetition is still not
mandatory for every repetition of every ItemRef in the GroupRef.
An ExplicitItemRefRepetition is necessary only if either (or both) of these reasons
obtain:
o you want to specify a default value for the repeat,
o you want to specify a Triggered Action for the the repeat,
Repeats of its ItermRefs without ExplictItemRefRepetitions are called implicit repeats.
If you supply ExplicitItemRefRepetitions with RepeatSequenceNumber greater than
the GroupRef's MaximumItemRefRepeats, the excess repetitions will be ignored.
82
Achieving consensus
OBO Foundry / OBI / CTO modular,
incremental, modest, connected to reality
– terms are included only if they have instances
Identify corresponding modules within
BRIDG, and test for alignment with CTO
– non-performed performed observation
– disease response is_a assessment
Are there corresponding items within CTO?
If so, they will be fixed immediately.
83
the balance of opposing powers often
keeps each within reason and sanity
(John Stuart Mill)
84