1. 2/13/2009
Clinical Observations Interoperability: - Bridging Clinical Practice and Clinical Research
Helen Chen
February 13, 2009

2. 2/13/2009
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

3. Clinical Observation Interoperability Group
2/13/2009
Clinical Observation Interoperability Group
W3C Semantic Web for Life Sciences and Healthcare Interest Group
Members from CDISC, clinical trial researchers and healthcare IT researchers

4. 2/13/2009
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

5. 2/13/2009
Use Case Step-Through
(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

6. 2/13/2009
Problems
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

7. 2/13/2009
Solution
Transform references described in SDTM classes to references described to HL7 classes via N3 rules
Obtain relavant concepts at different granularity via inferencing
Class->subclasses
Derive new classes (weight loss drug) via <may-treat> mechanism
Transform either…
Relational data into RDF
or SPARQL into SQL via N3 rules
Second approach chosen

8. 2/13/2009
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

9. . . Inclusion Criteria Type 2 diabetes
2/13/2009
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 :takes :metformin . . .

10. 2/13/2009
Exclusion Criteria
Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants. .
?patient doesNotTake anticoagulant . . .

11. 2/13/2009
Medication
:M0271 a sdtm:Medication; spl:classCode 6809 ; #metformin sdtm:subject :P0006; sdtm:dosePerAdministration [ sdtm:hasValue 500; sdtm:hasUnit "mg„ ]; sdtm:startDateTime " T00:00:00"^^xsd:dateTime ; sdtm:endDateTime " T00:00:00"^^xsd:dateTime .

12. Criteria in SPARQL metformin anticoagulant Exclusion Criteria
2/13/2009
Criteria in SPARQL
?medication1 sdtm:subject ?patient ; spl:activeIngredient ?ingredient1 .
?ingredient1 spl:classCode
OPTIONAL {
?medication2 sdtm:subject ?patient ; spl:activeIngredient ?ingredient2 . ?ingredient2 spl:classCode
} FILTER (!BOUND(?medication2))
metformin
anticoagulant
Exclusion Criteria

13. Drug Class Information in CT #8
2/13/2009
Drug Class Information in CT #8
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

14. Prescription Information in Patient Database
2/13/2009
Prescription Information in Patient Database
"132139","131933"," ","GlipiZIDE-Metformin HCl MG Tablet"," ",98630," ","TABS","","MG "," ","15","GlipiZIDE-Metformin HCl ","","GlipiZIDE-Metformin HCl MG Tablet“
"132152","131946"," ","GlipiZIDE-Metformin HCl MG Tablet"," ",98629," ","TABS","","MG "," ","15","GlipiZIDE-Metformin HCl ","","GlipiZIDE-Metformin HCl MG Tablet“
"132407","132201"," ","GlipiZIDE-Metformin HCl MG Tablet"," ",98628," ","TABS","","MG "," ","15","GlipiZIDE-Metformin HCl ","","GlipiZIDE-Metformin HCl MG Tablet“
"132642","132436","C ","GlipiZIDE-Metformin HCl TABS"," ",98630,"","TABS",""," "," ","15","GlipiZIDE-Metformin HCl ","","GlipiZIDE-Metformin HCl TABS"
NDC Code

15. Drug Ontology By Stanford
2/13/2009
Drug Ontology By Stanford
from drug ontology documentation

16. Mapping Between CT and Patient Record
2/13/2009
Mapping Between CT and Patient Record
Drug Ontology
MechanismOfAction
GeneralDrugType CT
metformin,
insulin secretagogue
alpha-glucosidase inhibitors
anticoagulants
uricosuric agents
nonsteroidal anti-inflammatory C C
drugBank: DB00331
RxNORM: 6809 C C
NDC: : GlipiZIDE-Metformin HCl MG Tablet
NDC: : GlipiZIDE-Metformin HCl MG Tablet
NDC: :GlipiZIDE-Metformin HCl TABS

17. SDTM to HL7 Transformation
2/13/2009
SDTM to HL7 Transformation
Clinical Trial Ontology
sdtm:Medication
sdtm:dosePer- Administration
{ ?x a sdtm:Medication ; sdtm:dosePer Administration ?y } => { ?x hl7:Substance Administration ;
hl7:doseQuantity ?y }
hl7:Substance- Administration
hl7:doseQuantity
Clinical Practice Ontology

18. HL7 to EMR Database Transformation
2/13/2009
HL7 to EMR Database Transformation
SPARQL in Clinical Practice Ontology
{ 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 . .}
hl7:Substance- Administration
hl7:doseQuantity
Item_Medication:EntryName ?takes .
Medication:ItemID ?indicItem;
SQL to EMR Database

19. Pushing Query to Database
2/13/2009
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
EMR
HL7 DCM/RIM
CT Eligibility
SPARQL
SPARQL
SQL

20. SPARQL in SDTM PREFIX sdtm: <http://www.sdtm.org/vocabulary#>
2/13/2009
SPARQL in SDTM
PREFIX sdtm: <
PREFIX spl: <
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:standardizedMedicationName ?contra ;
spl:activeIngredient [ spl:classCode ] ;
sdtm:effectiveTime [
sdtm:startDateTimeOfMedication ?contraDate
} FILTER (!BOUND(?contra) && ?code = 6809) }

21. SDTM-HL7 Mapping Rules CONSTRUCT { ?patient a sdtm:Patient ;
2/13/2009
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 ?ingred ]
] ;
hl7:effectiveTime [ hl7:start ?start ]
] . }

22. SPARQL in HL7 Via SWtranformer
2/13/2009
SPARQL in HL7 Via SWtranformer
PREFIX hl7: <
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 ) }

23. HL – Database Mapping Rules: Tables
2/13/2009
HL – Database Mapping Rules: Tables
PREFIX xsd: <
PREFIX Person: <
PREFIX Sex_DE: <
PREFIX Item_Medication: <
PREFIX Medication: <
PREFIX Medication_DE: <
PREFIX NDCcodes: <

24. HL – Database Mapping Rules: Schema
2/13/2009
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 . }

25. 2/13/2009
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

26. COI Demo coi svn: Public access: (working in progress)
2/13/2009
COI Demo
coi svn:
Public access: (working in progress)

27. COI Demo – Clinical Trial Eligibility Criteria
2/13/2009
COI Demo – Clinical Trial Eligibility Criteria

28. COI Demo – Selecting Inclusion Criteria
2/13/2009
COI Demo – Selecting Inclusion Criteria
Inclusion in SDTM ontology
SDTM clinical trial ontology

29. COI Demo – Drug Ontology Inference
2/13/2009
COI Demo – Drug Ontology Inference
Subclasses of “anticoagulant”
Drug ontology
Exclusion in Drug ontology

30. COI Demo – Selecting Mapping Rules
2/13/2009
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 :C }
=>
{?D a :WeightLoseDrug}.

31. COI Demo – Getting Right Patients
2/13/2009
COI Demo – Getting Right Patients

32. Benefits of Semantic Web Apporach
2/13/2009
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

33. Challenges Ahead Large Tree Structure Navigation
2/13/2009
Challenges Ahead
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

34. Questions and Suggestions?
2/13/2009
Questions and Suggestions?
Thank You!