Download HCLS$$ClinicalObservationsInteroperability$coidemo-feb-13

Clinical Observations Interoperability:
- Bridging Clinical Practice and Clinical Research
Helen Chen
February 13, 2009
Motivation
• Pressing need for interoperability between clinical trials and clinical
practice
• Bridge gaps between various standards to connect related fields
• Semantic Web technologies are maturing quickly and getting ready
for prime time
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Helen Chen Feb. 13, 2009
Clinical Observation Interoperability Group
• W3C Semantic Web for Life Sciences and Healthcare Interest
Group
• Members from CDISC, clinical trial researchers and healthcare IT
researchers
• http://esw.w3.org/topic/HCLS/ClinicalObservationsInteroperability
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Helen Chen Feb. 13, 2009
Goals
• Show that Semantic Web technologies can be used to bridge the gap
between the two
• Map across formats
• Reuse existing data
• Develop a proof of concept application that demonstrates the
feasibility of that approach
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Helen Chen Feb. 13, 2009
Use Case Step-Through
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(Textual) specification of the eligibility criteria for a given clinical
trial
Ontology-based translation of the eligibility criteria into SPARQL
queries
Translation of the SPARQL queries into database-specific queries
Execution of the queries at the databases) –
results contain all eligible patients
Return of a list of eligible patients to clinical trial administrator
Helen Chen Feb. 13, 2009
Problems
1.
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Data is not stored only in form of the CDISC SDTM but also in HL7
DCM form
Concepts in SDTM domain do not always have one-one mapping to
HL domain
Drug prescription coded in different drug codes (RxNorm and NDC)
Data is not stored as RDF but in conventional relational databases
Helen Chen Feb. 13, 2009
Solution
•
Transform references described in SDTM classes to references
described to HL7 classes via N3 rules
Obtain relavant concepts at different granularity via inferencing
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Class->subclasses
Derive new classes (weight loss drug) via <may-treat> mechanism
Transform either…
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Relational data into RDF
or SPARQL into SQL via N3 rules
•
Second approach chosen
Helen Chen Feb. 13, 2009
Ontology Modeling
• Develop ontologies for clinical trials and clinical practice based on
CDISC SDTM and HL7 DCM
• Write mapping rules
• Model patient and medication aspects…
• Lab results and observations
• Patient vital signs
• Medications
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Helen Chen Feb. 13, 2009
Inclusion Criteria
Type 2 diabetes
on diet and exercise therapy or monotherapy with metformin, insulin
secretagogue, or alpha-glucosidase inhibitors, or a low-dose
combination of these at 50% maximal dose. Dosing is stable for 8
weeks prior to randomization.
. .?patient
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:takes
:metformin .
Helen Chen Feb. 13, 2009
Exclusion Criteria
Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants.
.
..
?patient doesNotTake anticoagulant .
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Helen Chen Feb. 13, 2009
Medication
:M0271 a sdtm:Medication;
spl:classCode 6809 ; #metformin
sdtm:subject :P0006;
sdtm:dosePerAdministration [
sdtm:hasValue 500;
sdtm:hasUnit "mg„ ];
sdtm:startDateTime
"20070101T00:00:00"^^xsd:dateTime ;
sdtm:endDateTime
"2008-0101T00:00:00"^^xsd:dateTime .
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Helen Chen Feb. 13, 2009
Criteria in SPARQL
?medication1 sdtm:subject ?patient ;
spl:activeIngredient ?ingredient1 .
?ingredient1 spl:classCode 6809 .
OPTIONAL {
?medication2 sdtm:subject ?patient ;
spl:activeIngredient ?ingredient2 .
?ingredient2 spl:classCode 11289 .
} FILTER (!BOUND(?medication2))
metformin
anticoagulant
Exclusion Criteria
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Helen Chen Feb. 13, 2009
Drug Class Information in CT #8
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monotherapy with metformin, insulin secretagogue, or alpha-glucosidase
inhibitors and a low dose combination of all
Long term insulin therapy
Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4
(Byetta), alone or in combination
corticosteroids
weightloss drugs e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim
(phenylpropanol-amine), or similar medications
nonsteroidal anti-inflammatory drugs
Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants
Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other
uricosuric agents
Helen Chen Feb. 13, 2009
Prescription Information in Patient Database
•
"132139","131933","98630 ","GlipiZIDE-Metformin HCl 2.5-250 MG Tablet","54868079500
",98630,"2.5-250
","TABS","","MG
"," ","15","GlipiZIDE-Metformin HCl
","","GlipiZIDEMetformin HCl 2.5-250 MG Tablet“
•
"132152","131946","98629 ","GlipiZIDE-Metformin HCl 2.5-500 MG Tablet","54868518802
",98629,"2.5-500
","TABS","","MG
"," ","15","GlipiZIDE-Metformin HCl
","","GlipiZIDEMetformin HCl 2.5-500 MG Tablet“
•
"132407","132201","98628 ","GlipiZIDE-Metformin HCl 5-500 MG Tablet","54868546702
",98628,"5-500
","TABS","","MG
"," ","15","GlipiZIDE-Metformin HCl
","","GlipiZIDEMetformin HCl 5-500 MG Tablet“
•
"132642","132436","C98630 ","GlipiZIDE-Metformin HCl TABS","54868079500
",98630,"","TABS","","
"," ","15","GlipiZIDE-Metformin HCl
","","GlipiZIDE-Metformin HCl
TABS"
NDC Code
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Helen Chen Feb. 13, 2009
Drug Ontology By Stanford
from drug ontology documentation
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Helen Chen Feb. 13, 2009
Mapping Between CT and Patient Record
Drug Ontology
CT
MechanismOfAction
C1299007
metformin,
insulin secretagogue
GeneralDrugType
nonsteroidal anti-inflammatory
alpha-glucosidase inhibitors
C0050393
C0066535
C0025598
drugBank: DB00331
RxNORM: 6809
anticoagulants
uricosuric agents
NDC:54868079500:
GlipiZIDE-Metformin HCl 2.5-250 MG Tablet
NDC: 54868518802: GlipiZIDE-Metformin HCl 5-500 MG Tablet
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NDC:54868079500:GlipiZIDE-Metformin HCl TABS
Helen Chen Feb. 13, 2009
SDTM to HL7 Transformation
Clinical Trial Ontology
sdtm:Medication
{
sdtm:dosePerAdministration
hl7:SubstanceAdministration
hl7:doseQuantity
?x a sdtm:Medication ;
sdtm:dosePerAdministration ?y
} => {
?x hl7:SubstanceAdministration ;
hl7:doseQuantity ?y
}
Clinical Practice Ontology
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Helen Chen Feb. 13, 2009
HL7 to EMR Database Transformation
SPARQL in Clinical Practice Ontology
hl7:SubstanceAdministration
hl7:doseQuantity
Item_Medication:EntryName
?takes .
Medication:ItemID
?indicItem;
{
hl7:substanceAdministration
[
a
hl7:SubstanceAdministration ;
hl7:consumable [
hl7:displayName
?takes ;
spl:activeIngredient [
spl:classCode ?ingred
]
] ;} => {
{
?indicItem
Item_Medication:PatientID
?person;
Item_Medication:PerformedDTTM
?indicDate ;
Item_Medication:EntryName
?takes .
.}
SQL to EMR Database
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Helen Chen Feb. 13, 2009
Pushing Query to Database
• SPARQL in SDTM ontology to SPARQL in HL7 ontology
• SPARQL in HL7 ontology to SQL in EMR database
List of eligible patients
SPARQL
Helen Chen Feb. 13, 2009
EMR
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HL7 DCM/RIM
CT Eligibility
SPARQL
SQL
SPARQL in SDTM
PREFIX sdtm: <http://www.sdtm.org/vocabulary#>
PREFIX spl: <http://www.hl7.org/v3ballot/xml/infrastructure/vocabulary/vocabulary#>
SELECT ?patient ?dob ?sex ?takes ?indicDate?contra
WHERE {
?patient a sdtm:Patient ;
sdtm:middleName ?middleName ;
sdtm:dateTimeOfBirth ?dob ;
sdtm:sex ?sex .
[
sdtm:subject ?patient ;
sdtm:standardizedMedicationName ?takes ;
spl:activeIngredient [ spl:classCode ?code ] ;
sdtm:startDateTimeOfMedication ?indicDate
].
OPTIONAL {
[
sdtm:subject ?patient ;
sdtm:standardizedMedicationName ?contra ;
spl:activeIngredient [ spl:classCode 11289 ] ;
sdtm:effectiveTime [
sdtm:startDateTimeOfMedication ?contraDate
].
} FILTER (!BOUND(?contra) && ?code = 6809)
}
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Helen Chen Feb. 13, 2009
SDTM-HL7 Mapping Rules
CONSTRUCT {
?patient
a
sdtm:Patient ;
sdtm:middleName
?middleName ;
sdtm:dateTimeOfBirth ?dob ;
sdtm:sex
?sex .
[
a
sdtm:ConcomitantMedication ;
sdtm:subject
?patient ;
sdtm:standardizedMedicationName
?takes ;
spl:activeIngredient [ spl:classCode
?ingred ] ;
sdtm:startDateTimeOfMedication ?start
] .} WHERE {
?patient
a
hl7:Person ;
hl7:entityName
?middleName ;
hl7:livingSubjectBirthTime
?dob ;
hl7:administrativeGenderCodePrintName ?sex ;
hl7:substanceAdministration
[
a
hl7:SubstanceAdministration ;
hl7:consumable [
hl7:displayName
?takes ;
spl:activeIngredient [ spl:classCode
];
hl7:effectiveTime [
hl7:start ?start ]
].
}
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Helen Chen Feb. 13, 2009
?ingred ]
SPARQL in HL7 Via SWtranformer
PREFIX hl7: <http://www.hl7.org/v3ballot/xml/infrastructure/vocabulary/vocabulary#>
SELECT ?patient ?dob ?sex ?takes ?indicDate
WHERE
{
?patient
hl7:entityName
?middleName .
?patient
hl7:livingSubjectBirthTime
?dob .
?patient
hl7:administrativeGenderCodePrintName
?sex .
?patient
a
hl7:Person .
?patient
hl7:substanceAdministration ?b0035D918_gen0 .
?b0035D918_gen0
hl7:consumable
?b0035C798_gen1 .
?b0035D918_gen0
a
hl7:SubstanceAdministration> .
?b0035D918_gen0
hl7:effectiveTime
?b0035C5E8_gen3 .
?b0035C798_gen1
hl7:displayName
?takes .
?b0035C798_gen1
hl7:activeIngredient ?b0035C848_gen2 .
?b0035C848_gen2
hl7:classCode
?code .
?b0035C5E8_gen3
hl7:start
?indicDate .
FILTER ( ?code = 6809 )
}
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Helen Chen Feb. 13, 2009
HL – Database Mapping Rules: Tables
PREFIX xsd: <http://www.w3.org/2001/XMLSchema#>
PREFIX Person: <http://hospital.example/DB/Person#>
PREFIX Sex_DE: <http://hospital.example/DB/Sex_DE#>
PREFIX Item_Medication: <http://hospital.example/DB/Item_Medication#>
PREFIX Medication: <http://hospital.example/DB/Medication#>
PREFIX Medication_DE: <http://hospital.example/DB/Medication_DE#>
PREFIX NDCcodes: <http://hospital.example/DB/NDCcodes#>
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Helen Chen Feb. 13, 2009
HL – Database Mapping Rules: Schema
CONSTRUCT {
?person
a
hl7:Person ;
hl7:entityName
?middleName ;
hl7:livingSubjectBirthTime
?dob ;
hl7:administrativeGenderCodePrintName ?sex ;
hl7:substanceAdministration
[ a
hl7:SubstanceAdministration ;
hl7:consumable [
hl7:displayName
?takes ;
spl:activeIngredient [ spl:classCode ?ingred]
];
hl7:effectiveTime [ hl7:start ?indicDate ]
].
} WHERE {
?person
Person:MiddleName
?middleName ;
Person:DateOfBirth
?dob ;
Person:SexDE
?sexEntry .
OPTIONAL { ?indicItem
Item_Medication:PatientID
?person ;
Item_Medication:PerformedDTTM ?indicDate ;
Item_Medication:EntryName
?takes .
?indicMed
Medication:ItemID
?indicItem ;
Medication:DaysToTake
?indicDuration ;
Medication:MedDictDE
?indicDE .
?indicDE Medication_DE:NDC
?indicNDC .
}
}
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Helen Chen Feb. 13, 2009
SQL to Database
SELECT patient.id AS patient, patient.DateOfBirth AS dob, sexEntry_gen0.EntryName AS sex,
indicItem_gen1.EntryName AS takes, indicItem_gen1.PerformedDTTM AS indicDate
FROM Person AS patient
INNER JOIN Sex_DE AS sexEntry_gen0 ON sexEntry_gen0.id=patient.SexDE
INNER JOIN Item_Medication AS indicItem_gen1 ON indicItem_gen1.PatientID=patient.id
INNER JOIN Medication AS indicMed_gen2 ON indicMed_gen2.ItemID=indicItem_gen1.id
INNER JOIN Medication_DE AS indicDE_gen5 ON
indicDE_gen5.id=indicMed_gen2.MedDictDE
INNER JOIN NDCcodes AS indicCode_gen6 ON indicCode_gen4.ingredient=6809 AND
indicCode_gen6.NDC=indicDE_gen5.NDC
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Helen Chen Feb. 13, 2009
COI Demo
• coi svn:
• http://code.google.com/p/coi/source/checkout
• Public access: (working in progress)
• http://hcls.deri.org/coi/demo/
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Helen Chen Feb. 13, 2009
COI Demo – Clinical Trial Eligibility Criteria
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Helen Chen Feb. 13, 2009
COI Demo – Selecting Inclusion Criteria
Inclusion in SDTM
ontology
SDTM clinical trial
ontology
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Helen Chen Feb. 13, 2009
COI Demo – Drug Ontology Inference
Drug ontology
Exclusion in Drug
ontology
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Helen Chen Feb. 13, 2009
COI Demo – Selecting Mapping Rules
#check all drugs that "may_treat obese"
{?A rdfs:subClassOf ?B; rdfs:label ?D.
?B a owl:Restriction;
owl:onProperty :may_treat;
owl:someValuesFrom :C0028754}
=>
{?D a :WeightLoseDrug}.
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Helen Chen Feb. 13, 2009
COI Demo – Getting Right Patients
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Helen Chen Feb. 13, 2009
Benefits of Semantic Web Apporach
• Unambiguious conceptual model for seperate doamins without early
commitment to a common ontology
• Reusable mapping rules from clinical research domain to Healthcare
domain
• Late bining of coding systems and database schema
• Transform SPARQL to SQL in real time, reflecting real time discovery
and integration needs
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Helen Chen Feb. 13, 2009
Challenges Ahead
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Large Tree Structure Navigation
Reasoning on Large Data
SWTranformer, url processing and “filter” clause implementation
Portability Issues on DERI Server
More patient data to test all proposed scenarios
Helen Chen Feb. 13, 2009
Questions and Suggestions?
Thank You!