1. Electronic Healthcare Record For Clincial Research (EHR4CR) Semantic interoperability framework WP4 C.Daniel INSERM UMRS 872 team 20 January 22, 2013 1 Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe

2. Objective, scope Executive Summary Objectives – EHR4CR platform for reusing EHR data in order to support medical research – Comprehensive business model for governance, acceptance, adoption and sustainability Duration & budget: 4 years – 7 Mons Euros (+ in kind contribution) Partners: 33 European academic and industrial partners – 11 Pharmaceutical Companies (members of EFPIA) – 22 Public Partners (Academia, Hospitals and SMEs) Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 2January 22, 2013

3. Partners Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 3 January 22, 2013

4. Use cases Protocol feasibility Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 4January 22, 2013 1 1 Leverage clinical data to design viable trial protocols and estimate recruitment Patient recruitment 2 2 Detect patients elegible for trials & better utilize recruitment potential Clinical trial execution 3 3 Re-use routine clinical data to pre- populate trial eCRFs Pharmacovigilance 4 4 Detect adverse events & collect/transmit relevant information A loosely coupled SOA, which interconnects independent services implementing EHR4CR usage scenarios

5. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 1 Protocol feasibility 5 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS Eligibility criteria manually formalized into central queries (EHR4CR workbench – SHARE data elements) 1 1 Patient identification Central queries transformed into local queries distributed and executed over EHRs/CDWs Protocol feasibility Number of patients matching eligibility criteria

6. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 2 Patient recruitment 6 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS Protocol content +Eligibility criteria manually formalized into central queries (EHR4CR workbench – SHARE data elements) 2 2 PSM Patient identification Protocol content distributed over local process step managers (including central ->local queries)

7. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 2 Patient recruitment 7 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS 2 2 PSM Patient recruitment process Lists of eligible->screened ->recruited subjects (protocol specific consent) Patient recruitment Number of recruited subjects

8. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 3 Data capture 8 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS Forms Items manually formalized (SHARE data elements) 3 3 PSM

9. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 3 Data capture 9 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS Forms Items manually formalized (SHARE data elements) 3 3 PSM Patient data capture process At each visit, retrieve query extraction specification & form(s) for data capture

10. Clinical research (CDISC) Clinical research (CDISC) CRO n°1 Patient care (HL7-13606) Patient care (HL7-13606) Hospital n°1 CTMS CDMS CTMS CDMS Use case 3 Data capture 10 EHR CDW EHR CDW Hospital n°2 Hospital n°X EHR CDW EHR CDW EHR CDW EHR CDW CRO n°2 CTMS CDMS CTMS CDMS CRO n°x CTMS CDMS CTMS CDMS PSM Data ( Recruited subjects protocol specific consent) 3 3

11. Semantic resources Common EHR4CR clinical information model/meta data repository – A unique global as view schema of the heterogeneous EHRs/CDWs distributed over different pilot sites across Europe. – Shared core data elements Common EHR4CR terminology – Integrate a range of clinical terminologies that are needed to collectively encode the variety of clinical entities (including observations, procedures, substance administration, etc) represented in the EHR4CR information model. – Query expansion and some degree of terminological reasoning Query extraction specification for eligibility determination and data capture Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 11January 22, 2013

12. Semantic resources Frankfurt - WPG2 - 20 october 2011 12 Items in eCRFs Last known weight (kg) Systolic Blood Pressure (mmHG) Hypertension? Yes/No Smoking / Non smoking ? Items in eCRFs Last known weight (kg) Systolic Blood Pressure (mmHG) Hypertension? Yes/No Smoking / Non smoking ? Eligibility criteria Between ages 18 and 56 Hemoglobin A1c value within the diabetic range At least 2/3 systolic blood pressure measurements ≥ 140 mmHg Eligibility criteria Between ages 18 and 56 Hemoglobin A1c value within the diabetic range At least 2/3 systolic blood pressure measurements ≥ 140 mmHg PHARMA (Eligibility criteria, items) HOSPITAL (Clinical data/documents) CDISC-ODM Clinical data/document Age Cardiovascular disease HBP Angor Cardiac failure SBP (mmHG) Weight (kg) Tabacco ? yes/no Hemoglobin A1c Clinical data/document Age Cardiovascular disease HBP Angor Cardiac failure SBP (mmHG) Weight (kg) Tabacco ? yes/no Hemoglobin A1c EHR4CR pivot representation “ Model of meaning” Formal representation of eligibility criteria & clinical data CDISC-SDM HL7 CDA (e.g. CCD)

13. EHR4CR Clinical Information Model Material : “source” models – BRIDG model & HL7 v3 models (HL7 RCRIM WG) «StudyDesign» and «A_SupportingClinicalStatementUniversal» models – I2b2 model Method: Model-driven engineering – Transforming HL7 v3 models in UML models and adapt these models to the purpose and scope of the EHR4CR project Multidimensional EHR4CR Information Model (ISO 21090 datatypes) Standardized data elements (pre-processed eligibility criteria of 10 clinical trials) Tooling: Open Medical Development Framework (OMDF) [Ouagne10] EHR4CR WP7 Meeting Thurs 13th September 2012 13

14. EHR4CR Clinical Information Model EHR4CR WP7 Meeting Thurs 13th September 2012 14

15. EHR4CR meta data repository & terminology (top down) Material – Reference document templates (e.g. CCD, CDA templates) – Reference terminologies – Patient care: clinical findings, test results, labs, or medications, etc. – Clinical research (MedDRA, CDASH/ Ontology of Clinical Research) Method & Tooling – We used Bioportal to upload terminologies – from UMLS (SNOMED CT, LOINC, ICD-10 codes, etc.) – from other sources (e.g for ATC or PathLex) – We developed a data element/value set editor to build a core data element repository EHR4CR WP7 Meeting Thurs 13th September 2012 15

16. 100 CT EHR4CR meta data repository & terminology (bottom up) 16 Scope (Core data elements) Mappings 10 CT 300 data elements 10 CT 300 data elements 4 CT 80 data elements 4 CT 80 data elements Eligibility criteria of clinical trials Execution Standardization

17. Semantic services Protocol feasibility Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 17January 22, 2013

18. Evaluation of the semantic resources 10 clinical trials – 11 pilot sites 23 proofs of concepts 18 Disease Area AP-HP FAU HUG KCL* MUW U936 UCL Univd un UoG uom WWU Total Cardiovascular XXX 3 Oncology XX 2 Nervous system disorders XXX 3 Oncology XX 2 Neurology X 1 onco XX 2 CV/Arrhythmia s X 1 Oncology XXXX 4 XXX 3 Cardiovascular and Metabolic XX 2 Total3232112231323

19. Adoption of standards IHE integration/content profiles Standards – Reference information models (CDISC, HL7) – ISO 11179 Meta data repository – ISO 21090 data types Boolean String Physical Quantity Real Integer Concept Descriptor <code ='271649006' displayName=‘Systolic blood pressure' codeSystem='2.16.840.1.113883.6.96 ' codeSystemName='SNOMEDCT'/> Coded Ordinal

20. Semantic interoperability issues Building/maintaining semantic resources – Sharing core data elements (CDISC SHARE) – Representing consistently complex clinical information models (clinical data structures templates, data elements) including clinical context Antibiograms, anatomic pathology cancer checklists (histologic type, grade, TNM, tumor size, etc) – Supporting the mapping process between pivot/local information models & terminologies Semantic services – Clinical research Formal representation of eligibility criteria & eCRF – Mapping medical concepts in eligibility criteria/eCRFs including highly pre-coordinated terms to standard reference terminologies – Representing temporal constraints – Patient care Mapping local data structures and/or interface terminologies to pivot models Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 20January 22, 2013

21. Project Information Project website : http://www.ehr4cr.eu/ Publications – Ouagne D, Hussain S, Sadou E, Jaulent MC, Daniel C. The Electronic Healthcare Record for Clinical Research (EHR4CR) information model and terminology. Stud Health Technol Inform. 2012;180:534-8 – El Fadly A, Rance B, Lucas N, Mead C, Chatellier G, Lastic PY, Jaulent MC, Daniel C. Integrating clinical research with the Healthcare Enterprise: from the RE-USE project to the EHR4CR platform. J Biomed Inform. 2011 Dec;44 Suppl 1:S94-102. Contact information WP4: Christel.daniel@crc.jussieu.fr Convergence Meeting: Semantic Interoperability for Clinical Research & Patient Safety in Europe 21January 22, 2013