1. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Bioinformatics and Technology Applications in Medication Management. Ontology: background and application to Medication Management Buffalo, NY, USA, June 13th, 2008 Werner CEUSTERS, MD Center of Excellence in Bioinformatics and Life Sciences, and National Center for Biomedical Ontology, University at Buffalo, NY, USA

2. New York State Center of Excellence in Bioinformatics & Life Sciences R T U ‘Ontology’ is popular ‘Ontology’ in Buffalo is famous

3. New York State Center of Excellence in Bioinformatics & Life Sciences R T U ‘Ontology’: one word, two meanings In philosophy: –Ontology (no plural) is the study of what entities exist and how they relate to each other; In computer science and (biomedical informatics) applications: –An ontology (plural: ontologies) is a shared and agreed upon conceptualization of a domain; Our ‘realist’ view within the Ontology Research Group combines the two: –We use realism, a specific theory of ontology, as the basis for building high quality ontologies, using reality as benchmark.

4. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Realism-based ontology Basic assumptions: 1.reality exists objectively in itself, i.e. independent of the perceptions or beliefs of cognitive beings; 2.reality, including its structure, is accessible to us, and can be discovered through (scientific) research; 3.the quality of an ontology is at least determined by the accuracy with which its structure mimics the pre-existing structure of reality.

5. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Three major views on reality Basic questions: –What does a general term such as ‘tree’ refer to? –Do generic things exist? yes: in particulars perhaps: in minds no UniversalConceptCollection of particulars RealismConceptualismNominalism

6. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Dominant view in computer science is conceptualism Basic questions: –What does a general term such as ‘tree’ refer to? –Do generic things exist? yes: in particulars perhaps: in minds no UniversalConceptCollection of particulars RealismConceptualismNominalism

7. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Dominant view in computer science is conceptualism RealismConceptualismNominalism Semantic Triangle concept objectterm Embedded in Terminology

8. New York State Center of Excellence in Bioinformatics & Life Sciences R T U ‘Terminology’: one word, two meanings Terminology is the study of identifying and labelling ‘concepts’ pertaining to a subject field. Terminology related activities: –analysing the concepts and concept structures, –identifying the terms assigned to the concepts, –establishing correspondences between terms, possibly in various languages, –compiling a terminology, on paper or in databases, –managing terminology databases, –creating new terms, as required.

9. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Why this interest in biomedical terminologies? ‘Nuances in the English language can be both challenging and amusing, however, when variants in language impact treatment, safety and billing, it is all challenge and no humor. Although English contains a reasonable degree of conformity, divergence in phrasing and meaning can compound comprehension problems and impact patient safety. These language "woes" can be minimized through the use of sophisticated healthcare IT systems with terminology management services.’ Schwend GT. The language of healthcare. Variance in the English language is harming patients and hospitals' bottom lines. Is healthcare IT the solution? Health Manag Technol. 2008 Feb;29(2):14, 16, 18

10. New York State Center of Excellence in Bioinformatics & Life Sciences R T U An example of a terminology: RxNorm What: ‘a standardized nomenclature for the smooth exchange of information between and within organizations’; Goal: ‘to allow various systems using different drug nomenclatures to share data efficiently at the appropriate level of abstraction’; Method: ‘a standard format in the naming of clinical drugs reflecting the active ingredients, strengths, and dose form comprising that drug. When any of these elements vary, a new name is created as a separate concept. An RxNorm name should exist for every strength and dose of every available combination of clinically significant ingredients. http://www.nlm.nih.gov/research/umls/rxnorm/overview.html

11. New York State Center of Excellence in Bioinformatics & Life Sciences R T U RxNorm for expressing similarities in medications Orajel Mouth Sore Rinse 150 MG/ML Mucous Membrane Topical Solution Perimax Perio Rinse 15 MG/ML Mucous Membrane Topical Solution Peroxyl 0.015 MG/MG Oral Gel Peroxyl 15 MG/ML Mucous Membrane Topical Solution Proxacol 30 MG/ML Topical Solution Superoxol 350 MG/ML Topical Solution

12. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Method: standardized name composition Strength Ingredient Form with a cheat for ‘packs’

13. New York State Center of Excellence in Bioinformatics & Life Sciences R T U RxNorm through RxNav

14. New York State Center of Excellence in Bioinformatics & Life Sciences R T U However … Terminology: –solves certain issues related to language use, i.e. with respect to how we talk about entities in reality (if any); Relations between terms / concepts –does not provide an adequate means to represent independent of use what we talk about, i.e. how reality is structured; Women, Fire and Dangerous Things (Lakoff). Ontology (of the right sort) : –Language and perception neutral view on reality. Relations between entities in first-order reality This is the ‘terminology / ontology divide’ independent of use

15. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The semantic triangle revisited concepts termsobjects Representation and Reference First Order Reality about terms concepts

16. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminology Realist Ontology Representation and Reference First Order Reality about representational units universalsparticulars objects terms concepts

17. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminology Realist Ontology Representation and Reference First Order Reality about representational units universalsparticulars objects terms concepts

18. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminology Realist Ontology Representation and Reference First Order Reality about universalsparticulars objects terms concepts cognitive units communicative units representational units

19. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminology Realist Ontology Representation and Reference First Order Reality universalsparticulars cognitive units representational units (1) Entities with objective existence which are not about anything (2) Cognitive entities which are our beliefs about (1) communicative units (3)Representational units in various forms about (1), (2) or (3) Three levels of reality in Realist Ontology

20. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The three levels applied to medication management 1. First-order reality 2. Beliefs (knowledge) GenericSpecific CONTRA-INDICATION INDICATION my doctor’s work plan my doctor’s diagnosis MOLECULE PERSON DISEASE PATHOLOGICAL STRUCTURE PORTION OF PENICILLIN DRUG me my toxic reaction to penicillin my bronchitis my doctor my pharmacist’s computer 3. Representation ‘person’‘drug’‘penicillin’‘W. Ceusters’‘my pneumonia’

21. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Places for ontology in medication management Medication Management Detailed Use Case June 18th, 2007. (www.hhs.gov/healthit/documents/UseCaseMM.pdf)

22. New York State Center of Excellence in Bioinformatics & Life Sciences R T U 1. First-order reality 2. Beliefs (knowledge) GenericSpecific CONTRA-INDICATION my doctor’s work plan MOLECULE INDICATION PERSON my doctor’s diagnosis DISEASE PATHOLOGICAL STRUCTURE me my toxic reaction to penicillin my bronchitis PORTION OF PENICILLIN my doctor DRUG my pharmacist’s computer 3. Representation ‘person’‘drug’‘penicillin’‘W. Ceusters’‘my pneumonia’ Terminology is too reductionist

23. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminology is too reductionist What concepts do we need? How do we name concepts properly?

24. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Terminological versus Ontological approach The terminologist defines: –‘a clinical drug is a pharmaceutical product given to (or taken by) a patient with a therapeutic or diagnostic intent’. (RxNorm) The ontologist thinks: –Does ‘given’ includes ‘prescribed’? –Is manufactured with the intent to … not sufficient? Are newly marketed products – available in the pharmacy, but not yet prescribed – not clinical drugs? Are products stolen from a pharmacy not clinical drugs? What about such products taken by persons that are not patients? –e.g. children mistaking tablets for candies.

25. New York State Center of Excellence in Bioinformatics & Life Sciences R T U RxNorm from an ontological perspective http://www.nlm.nih.gov/research/umls/rxnorm/overview.html Use-mention confusion

26. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Why is this important ? Not as much for humans: –Our ‘minds’ are very good in resolving ambiguities, even at ‘unconscious’ levels. But for machines (computers, software): –They can’t deal with imprecise, vague or ambiguous statements.

27. New York State Center of Excellence in Bioinformatics & Life Sciences R T U Standards for ePrescribing under Medicare Part D Formulary and benefits information: –NCPDP Formulary and Benefits Standard 1.0. Identification of providers: –National Provider Identifier (NPI) Medication history –Medication History Standard in NCPDP SCRIPT 8.1 Fill status notification –RxFill in NCPDP SCRIPT 8.1 42 CFR Part 423. Federal Register / Vol. 73, No. 67 :18917-42/ Monday, April 7, 2008 / Rules and Regulations

28. New York State Center of Excellence in Bioinformatics & Life Sciences R T U A realist ontological view on ‘data’ standards CSC. Record Locator Service Prototype. Medications History Implementation Guide. V0.4. 2005-11-15. Use/mention confusion: is the medication history record dispensed, prescribed, …, or the drug mentioned in he record?

29. New York State Center of Excellence in Bioinformatics & Life Sciences R T U A realist ontological view on ‘data’ standards CSC. Record Locator Service Prototype. Medications History Implementation Guide. V0.4. 2005-11-15. Inconsistent representation: is ‘E.g.’ part of the drug name? Where is the strength and dosage?

30. New York State Center of Excellence in Bioinformatics & Life Sciences R T U A realist ontological view on ‘data’ standards CSC. Record Locator Service Prototype. Medications History Implementation Guide. V0.4. 2005-11-15. Vocabularies with ontologically unclear semantics: 10tablet 15soluble tablet 11enteric coated tablet 150tablet, effervescent 12sustained release tablet 151tablet, extended release 13buccal or sublingual tablet 16tablet unspecified 14chewable tablet 23tablet 21 day supply 147tablet, chewable 24tablet 28 day supply 148tablet, coated particles 72vaginal tablet 149tablet, disintegrating

31. New York State Center of Excellence in Bioinformatics & Life Sciences R T U A realist ontological view on ‘data’ standards CSC. Record Locator Service Prototype. Medications History Implementation Guide. V0.4. 2005-11-15. Mixing types and instances: there is only one NDC (=particular), there are many manufacturers (=defined class)

32. New York State Center of Excellence in Bioinformatics & Life Sciences R T U 557204/07/199026442006closed fracture of shaft of femur 557204/07/199081134009Fracture, closed, spiral 557212/07/199026442006closed fracture of shaft of femur 557212/07/19909001224Accident in public building (supermarket) 557204/07/199079001Essential hypertension 093924/12/1991255174002benign polyp of biliary tract 230921/03/199226442006closed fracture of shaft of femur 230921/03/19929001224Accident in public building (supermarket) 4780403/04/199358298795Other lesion on other specified region 557217/05/199379001Essential hypertension 29822/08/19932909872Closed fracture of radial head 29822/08/19939001224Accident in public building (supermarket) 557201/04/199726442006closed fracture of shaft of femur 557201/04/199779001Essential hypertension PtIDDateObsCodeNarrative 093920/12/1998255087006malignant polyp of biliary tract The cost of ignoring the type/instance distinction

33. New York State Center of Excellence in Bioinformatics & Life Sciences R T U 557204/07/199026442006closed fracture of shaft of femur 557204/07/199081134009Fracture, closed, spiral 557212/07/199026442006closed fracture of shaft of femur 557212/07/19909001224Accident in public building (supermarket) 557204/07/199079001Essential hypertension 093924/12/1991255174002benign polyp of biliary tract 230921/03/199226442006closed fracture of shaft of femur 230921/03/19929001224Accident in public building (supermarket) 4780403/04/199358298795Other lesion on other specified region 557217/05/199379001Essential hypertension 29822/08/19932909872Closed fracture of radial head 29822/08/19939001224Accident in public building (supermarket) 557201/04/199726442006closed fracture of shaft of femur 557201/04/199779001Essential hypertension PtIDDateObsCodeNarrative 093920/12/1998255087006malignant polyp of biliary tract IUI-001 IUI-003 IUI-004 IUI-005 IUI-007 IUI-002 IUI-012 IUI-006 7 distinct disorders Codes for types AND identifiers for instances

34. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The power of realism in ontology design Reality as benchmark ! 1. Is the scientific ‘state of the art’ consistent with biomedical reality ?

35. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The power of realism in ontology design Reality as benchmark ! 2. Is my doctor’s knowledge up to date?

36. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The power of realism in ontology design Reality as benchmark ! 3. Does my doctor have an accurate assessment of my health status?

37. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The power of realism in ontology design Reality as benchmark ! 4. How can we use case studies better to advance the state of the art?

38. New York State Center of Excellence in Bioinformatics & Life Sciences R T U The power of realism in ontology design Reality as benchmark ! 5. Is our terminology rich enough to communicate about all three levels?

39. New York State Center of Excellence in Bioinformatics & Life Sciences R T U In summary Medication management involves many actors and IT systems: semantic interoperability is thus a key issue. Ontologies (of the right sort) provide a deep level of semantic interoperability between IT systems, thereby keeping track: –of what is the case; –of what is known by some actor(s); –of what has been and still needs to be done. Realism-based ontology, as a discipline, helps in creating ontologies of the right sort.