2. ECO R European Centre for Ontological Research Practical implementations of realism-based ontologies: Referent Tracking in Electronic Health Records MIE 2005 tutorial #35 on Ontology Design (part 4) Geneva, Switzerland, August 28, 2005 Dr. W. Ceusters European Centre for Ontological Research Saarland University Saarbrücken - Germany

3. ECO R European Centre for Ontological Research Three models for a Comprehensive Patient Care Information System * Information model of the medical record: What can be said ? Process model of clinical care: What ought to occur ? Inferred model of the state of the patient: What actually occurs. * Rector AL, Nolan WA, and Kay S. Foundations for an Electronic Medical Record. Methods of Information in Medicine 30: 179-86, 1991. (Figure 1) requirements inferences modification Inferred model of the state of the patient: What actually occurs. ?

4. ECO R European Centre for Ontological Research What ‘event’ occurred in my left hand being a part of my left arm ? Is ‘saying that an event has occurred’ a requirement for the event to have occurred ? An event model of medical information representation * ‘The real world consist of objects (or entities)’ ‘Objects interact with other objects and can be associated with other objects by relationships’ ‘When two or more objects interact in the real world, an ‘event’ is said to have occurred’ * Huff SM, Rocha RA, Bray BE, Warner HR, and Haug PJ. An Event Model of Medical Information Representation. J Am Med Informatics Assoc. 1995;2:116-134. ?

5. ECO R European Centre for Ontological Research Observation Event Instance Created from the Statement ‘ Surgical clips are again seen along the right mediastinum ’ * * Huff SM, Rocha RA, Bray BE, Warner HR, and Haug PJ. An Event Model of Medical Information Representation. J Am Med Informatics Assoc. 1995;2:116-134. ? Are the clips there because they have been observed ? Is the observation located in the mediastinum ?

6. ECO R European Centre for Ontological Research What is wrong in both cases (and so many others) ? Further clues to the answer: – Huff SM, Rocha RA, Bray BE, Warner HR, and Haug PJ. An Event Model of Medical Information Representation. J Am Med Informatics Assoc. 1995;2:116-134. – Rector et al.’s paper: Many of the difficulties experienced in attempting to generalize existing [patient record] systems stem from the fact that they have pre- selected and distorted information in order to fit into particular applications, usually clinical research and epidemiology. The models emit much of the information actually used in clinical care and do not accurately reflect the real status of the data they record. Further clues to the answer: – Huff SM, Rocha RA, Bray BE, Warner HR, and Haug PJ. An Event Model of Medical Information Representation. J Am Med Informatics Assoc. 1995;2:116-134. – Rector et al.’s paper: Many of the difficulties experienced in attempting to generalize existing [patient record] systems stem from the fact that they have pre- selected and distorted information in order to fit into particular applications, usually clinical research and epidemiology. The models emit much of the information actually used in clinical care and do not accurately reflect the real status of the data they record.

7. ECO R European Centre for Ontological Research What is wrong (continued) ? An overemphasis on data and information and too little attention to reality: – “data modelling” – “information modelling” Is the “Object Oriented” model approach any better, since, after all, objects are said to be those things that exist in reality ? – The object-oriented model is based on a collection of objects – An object contains values stored in instance variables within the object. – Unlike the record-oriented models, these values are themselves objects.

8. ECO R European Centre for Ontological Research The story of Jane Smith an old case, well known in the literature...

9. ECO R European Centre for Ontological Research Jane’s favourite supermarket July 4th, 1990: Jane goes shopping: The freezer section of Jane’s favourite supermarket The only available warning sign used outside A very suspiciously shaped upper leg

10. ECO R European Centre for Ontological Research A visit to the hospital City Health Centre Dr. Peters (City HC) Dr. Longley

11. ECO R European Centre for Ontological Research Diagnosis: a severe spiral fracture of the femur

12. ECO R European Centre for Ontological Research The City HC’s medical record Main principles: – a faithful record of the clinicians’ observations: what they have heard, seen, thought and done. – captures in a structured form all of the ‘clinically significant’ information in the narrative notes, where by clinically significant they mean the information which is within the medical domain rather than the domain of everyday life. Rector AL, Nowlan WA, Kay S, Goble CA, Howkins TJ. A framework for modelling the electronic medical record. Methods Inf Med. 1993 Apr;32(2):109-19.

13. ECO R European Centre for Ontological Research City HC’s EHR model Rector AL, Nowlan WA, Kay S, Goble CA, Howkins TJ. A framework for modelling the electronic medical record. Methods Inf Med. 1993 Apr;32(2):109-19.

14. ECO R European Centre for Ontological Research CityHC’s representation formalism (for statements in records) Rector AL, Nowlan WA, Kay S, Goble CA, Howkins TJ. A framework for modelling the electronic medical record. Methods Inf Med. 1993 Apr;32(2):109-19. Categories: “ represent concepts and are analogous to classes in other formalisms ” Individuals: “ concrete instances of categories which persist in space and time ” Occurrences: “ are specific occurrences of individuals and must be situated in space and time. The most important group of occurrences are observations — i.e. agents ’ observations of individuals. ”

15. ECO R European Centre for Ontological Research Note: Mixing statements and entities “Every occurrence level statement concerning the Jane Smith’s Fracture of the Femur is an observation of the corresponding individual.”

16. ECO R European Centre for Ontological Research 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 A look at the database: Use of SNOMED codes for ‘unambiguous’ understanding * * * * cause, not disorder How many disorders have patients 5572, 2309 and 298 each had thus far in their lifetime ? How many numerically different disorders are listed here ? How many different types of disorders are listed here ?

17. ECO R European Centre for Ontological Research 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 Same patient, same hypertension code: Same (numerically identical) hypertension ? Different patients, same fracture codes: Same (numerically identical) fracture ? Same patient, different dates, same fracture codes: same (numerically identical) fracture ? Same patient, same date, 2 different fracture codes: same (numerically identical) fracture ? Would the terms help ? Different patients. Same supermarket? Maybe the same (irrelevant ?) freezer section ? Or different supermarkets, but always in the freezer sections ? Same patient, different dates, Different codes. Same (numerically identical) polyp ?

18. ECO R European Centre for Ontological Research Main problem areas for CityHC’s EHR Statements refer only very implicitly to the concrete entities about which they give information. Idiosyncracies of concept-based terminologies – tell us only that some instance of the class the codes refer to, is refered to in the statement, but not what instance precisely. – Are usually confused about classes and individuals. “Country” and “Belgium”. Mixing up the act of observation and the thing observed. Mixing up statements and the entities these statements refer to.

19. ECO R European Centre for Ontological Research Consequences Very difficult to: – Count the number of (numerically) different diseases Bad statistics on incidence, prevalence,... Bad basis for health cost containment – Relate (numerically same or different) causal factors to disorders: – Dangerous public places (specific work floors, swimming pools), dogs with rabies, HIV contaminated blood from donors, food from unhygienic source,... Hampers prevention –...

20. ECO R European Centre for Ontological Research Proposed solution: Referent Tracking Purpose: – explicit reference to the concrete individual entities relevant to the accurate description of each patient’s condition, therapies, outcomes,... Method: – Introduce an Instance Unique Identifier (IUI) for each relevant individual (= particular, = instance). – Distinguish between IUI assignment: for instances that do exist IUI reservation: for entities expected to come into existence in the future

21. ECO R European Centre for Ontological Research Ontology ‘An ontology’ is a representation of some pre- existing domain of reality which – (1) reflects the properties of the objects within its domain in such a way that there obtains a systematic correlation between reality and the representation itself, – (2) is intelligible to a domain expert – (3) is formalized in a way that allows it to support automatic information processing ‘ontological’ (as adjective): – Within an ontology. – Derived by applying the methodology of ontology –...

22. ECO R European Centre for Ontological Research An ontological analysis continuants City HC The freezer section of Jane’s favourite supermarket Jane’s left femur Jane’s left femur fracture Jane Smith Dr. Peters Jane’s left femur Jane’s fracture’s image Dr. Longley City HC’s EHR system t Jane’s falling Jane’s femur breaking Dr. Peter’s examination of Jane’s fracture Dr. Peter’s ordering of an X-ray Shooting the pictures of Jane’s leg occurrents Jane’s fracture’s healing Dr. Peter’s diagnosis making Jane dies Freezer section dismantled Dr. Longley’s examination of Jane’ s fracture Jane’s fracture as seen by Dr. Peters Jane’s fracture as seen by Dr. Longley Instances of Jane’s fracture Universals EHR system HC Freezer section Person Femur Fracture Image

23. ECO R European Centre for Ontological Research Ontological recategorisation CityHCDr. Peters Jane Smith Jane Smith’s Fracture Of Femur Fracture Of Femur Severe Spiral City HC exists on 4th July 1990 Dr. Peters located at City HC on 4th July 1990 Jane Smith’s consultation with Dr. Peters at City HC on 4th July 1990 Dr. Peters’ assessment of Jane Smith’s fracture of femur at City HC on 4th July 1990 Jane Smith’s Fracture Of Femur’s severity Jane Smith’s Fracture Of Femur’s shape

24. ECO R European Centre for Ontological Research Essentials of Referent Tracking Generation of universally unique identifiers; deciding what particulars should receive a IUI; finding out whether or not a particular has already been assigned a IUI (each particular should receive maximally one IUI); using IUIs in the EHR, i.e. issues concerning the syntax and semantics of statements containing IUIs; determining the truth values of statements in which IUIs are used; correcting errors in the assignment of IUIs.

25. ECO R European Centre for Ontological Research Architecture of a Referent Tracking System (RTS) RTS: system in which all statements referring to particulars contain the IUIs for those particulars judged to be relevant. Ideally set up as broad as possible: – some metrics: % of particulars referred to by means of IUI % of HCs active in a region – Geographic region – functional region: defined by contacts amongst patients % of patients referred to within a region Services: – IUI generator – IUI repository: statements about assignments and reservations – Referent Tracking ‘Database’ (RTDB): index (LSID) to statements relating instances to instances and classes

26. ECO R European Centre for Ontological Research IUI generation Universally Unique IDs: – recently standardized through ISO/IEC 9834- 8:2004, – specifies format and generation rules enabling users to produce 128-bit identifiers that are either guaranteed or have a high probability of being globally unique – Meaningless strings – Central management or certification not needed to guarantee uniqueness (But use as IUI requires this)

27. ECO R European Centre for Ontological Research IUI assignment = an act carried out by the first ‘cognitive agent’ feeling the need to acknowledge the existence of a particular it has information about by labelling it with a UUID. ‘cognitive agent’: – A person; – An organisation; – A device or software agent, e.g. Bank note printer, Image analysis software.

28. ECO R European Centre for Ontological Research Criteria for IUI assignment (1) 1. The particular’s existence must be determined: – Easy for persons in front of you, body parts,... – Easy for ‘planned acts’: they do not exist before the plan is executed ! Only the plan exists and possibly the statements made about the future execution of the plan – More difficult: subjective symptoms But the statements the patient makes about them do exist ! – However: no need to know what the particular exactly is, i.e. which universal it instantiates No need to be able to point to it precisely – One bee out of a particular swarm that stung the patient, one pain out of a series of pain attacks that made the patient worried. – But: this is not a matter of choice, not ‘any’ out of...

29. ECO R European Centre for Ontological Research Criteria for IUI assignment (2) 2. The particular’s existence ‘may not already have been determined as the existence of something else’: Morning star and evening star Himalaya Multiple sclerosis 3. May not have already been assigned a IUI. 4. It must be relevant to do so: Personal decision, (scientific) community guideline,... Possibilities offered by the EHR system If a IUI has been assigned by somebody, everybody else making statements about the particular should use it

30. ECO R European Centre for Ontological Research Assertion of assignments IUI assignment is an act of which the execution has to be asserted in the IUI-repository: – D i = IUI d IUI of the registering agent A i the assertion of the assignment » IUI a IUI of the author of the assertion » IUI p IUI of the particular » t ap time of the assignment t d time of registering A i in the IUI-repository Neither t d or t ap give any information about when # IUI p started to exist ! That might be asserted in statements providing information about # IUI p.

31. ECO R European Centre for Ontological Research Management of the IUI-repository Adequate safety and security provisions – Access authorisation, control, read/write,... – Pseudonymisation Deletionless but facilities for correcting mistakes. Registration of assertion ASAP after IUI assignment (virtual, e.g. LSID) central management with adequate search facilities.

32. ECO R European Centre for Ontological Research Representation in the EHR Relevant particulars referred to using IUIs Relationships that obtain between particulars at time t expressed using relations from an ontology (type OBO) Statements describing for each particular, at time t: – Of what universal from an ontology it is an instance of – AND/OR (if one insists): – By means of what concept from a concept-based system it can sensibly be described CityHCDr. Peters Jane Smith Jane Smith’s Fracture Of Femur Fracture Of Femur Severe Spiral Jane Smith’s consultation with Dr. Peters at City HC on 4th July 1990 Dr. Peters’ assessment of Jane Smith’s fracture of femur at City HC on 4th July 1990 Jane Smith’s Fracture Of Femur’s severity Jane Smith’s Fracture Of Femur’s shape 4th July 1990 particulars

33. ECO R European Centre for Ontological Research PtoP statements - particular to particular ordered sextuples of the form R i = IUI a is the IUI of the author of the statement, t a a reference to the time when the statement is made, r a reference to a relationship (available in o) obtaining between the particulars referred to in P, o a reference to the ontology from which r is taken, P an ordered list of IUIs referring to the particulars between which r obtains, and, t r a reference to the time at which the relationship obtains. P contains as much IUIs as required by the arity of r. In most cases, P will be an ordered pair such that r obtains between the particular represented by the first IUI and the one referred to by the second IUI. As with A statements, these statements must also be accompanied by a meta-statement capturing when the sextuple became available to the referent tracking system.

34. ECO R European Centre for Ontological Research PtoU statements – particular to universal U i = IUI a is the IUI of the author of the statement, t a a reference to the time when the statement is made, inst a reference to an instance relationship available in o obtaining between p and cl, o a reference to the ontology from which inst and u are taken, IUI p the IUI referring to the particular whose inst relationship with u is asserted, u the universal in o to which p enjoys the inst relationship, and, t r a reference to the time at which the relationship obtains.

35. ECO R European Centre for Ontological Research PtoCO statements particular to concept code Co i = IUI a is the IUI of the author of the statement, t a a reference to the time when the statement is made, cbs a reference to the concept-based system from which co is taken, IUI p the IUI referring to the particular which the author associates with co, co the concept-code in cbs which the author associates with p, and, t r a reference to the time at which the author considers the association appropriate,

36. ECO R European Centre for Ontological Research Interpretation of PtoCO statements must be interpreted as simple indexes to terms in a dictionary. All that such a statement tells us, is that within the linguistic and scientific community in which cbs is used, the terms associated with co may - i.e. are acceptable to - be used to denote p in their determinative version.

37. ECO R European Centre for Ontological Research A SNOMED-CT example #IUI-0945: author of the statement #IUI-1921: the left testicle of patient #IUI-78127 367720001: the SNOMED concept-code to which “left testis” is (in SNOMED) attached as term So we can denote #IUI-1921 by means of that left testis that entire left testis that testicle, that male gonad, that testis that genital structure that physical anatomical entity BUT NOT: that SNOMED-CT concept

38. ECO R European Centre for Ontological Research Pragmatics of IUIs in EHRs IUI assignment requires an additional effort In principle no difference qua (or just a little bit more) effort compared to using directly codes from concept-based systems – A search for concept-codes is replaced by a search for the appropriate IUI using exactly the same mechanisms Browsing Code-finder software Auto-coding software (CLEF NLP software Andrea Setzer) – With that IUI comes a wealth of already registered information – If for the same patient different IUIs apply, the user must make the decision which one is the one under scrutiny, or whether it is again a new instance A tranfert or reference mechanism makes the statements visible through the RTDB

39. ECO R European Centre for Ontological Research Advantage: better reality representation 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

40. ECO R European Centre for Ontological Research Other Advantages mapping as by-product of tracking – Descriptions about the same particular using different ontologies/concept-based systems Quality control of ontologies and cbs – Systematic “inconsistent” descriptions in or cross terminologies may indicate poor definition of the respective terms

41. ECO R European Centre for Ontological Research A case study Double goal: – Application of referent tracking to a concrete patient story – Ontological analysis of what is involved The latter is NOT to be performed to the same extent when referent tracking is used as an alternative to coding using concept- based systems. So, don’t go home with the idea: “that’s all too cumbersome and time cosuming”

42. ECO R European Centre for Ontological Research Jim Cimino’s Woods Hole case Jane Smith is a 30 year old, Native American female who presents to the emergency room with the chief complaint of cough and chest pain.The patient reports that she has had a productive cough for three days but that chest pain developed one hour ago. She gives a history of hypertension. She also reports that she was treated in the past for tuberculosis while she was pregnant. The patient reports an allergy to Bufferin. Physical examination revealed a well-developed, well-nourished female in moderate respiratory distress. Vital signs showed a pulse of 90, a respiratory rate of 22, an oral temperature of 100.3, and a blood pressure of 150/100. Examination revealed rales and rhonchi in the left upper chest. Abdominal exam revealed a tender, palpable liver edge. Labs: Chem7 (serum): Glucose 100 (70-105) Chem7 (plasma): Glucose 150 (75-110) CBC: Hgb 15 (12.0-15.8), Hct 45 (42.4-48.0), WBC 11,000 (3,540- 9,060), Platelets 145,000 (165,000-415,000) A fingerstick blood sugar was 80 Urinalysis showed protein of 1+ and glucose of 0. A blood culture was positive for methicillin-resistant Staphylococcus aureus (MRSA)

43. ECO R European Centre for Ontological Research case study continued... ECG - Sinus Rhythm, 74BPM, Axis -30 degrees, ST segment 2mm elevated andT-waves down in leads I, L, V5 and V6 Chest X-ray Left upper lobe infiltrate, left ventricular hypertrophy The patients nurse reported that the patient seemed depressed about her condition. On questioning, the nurse found that the patient was caringfor her elderly father and was concerned that she would no longer be able to manage caring for herself and him. The nurse asked the patients physician to consider an antidepressant and a social work consult. A medical student reviewing the case is concerned about the risk of MRSA in patients with pneumonia and a recent myocardial infarction. She decides to do a literature search.

44. ECO R European Centre for Ontological Research Step 1: identify the phrases referring to particulars Jane Smith is a 50 year old, Native American female who presents to the emergency room with the chief complaint of cough and chest pain. Question: What if the patient is not telling the truth ?

45. ECO R European Centre for Ontological Research Jane Smith is a 50 year old, Native American female who presents to the emergency room with the chief complaint of cough and chest pain. Step 2: indentify to what particulars these phrases refer Jane SmithJane Smith’s age Jane Smith’s raceJane SmithJane Smith’ s gender Jane Smith ’s showing up at... A specific emergency room of health facility XYZ Jane Smith’s complaining primarily about... A temporal part of Jane Smith’s life marked by happenings of coughs Jane Smith’s chest A specific pain experienced by Jane Smith

46. ECO R European Centre for Ontological Research Compare with simple clinical coding in juxtaposition Jane Smith is a 50 year old, Native American female who presents to the emergency room with the chief complaint of cough and chest pain. “Jane Smith” CS1-age CS1-native-american CS1-female- gender CS1-emergency room CS1-chief-complaint CS1-coughingCS1-chest-pain CS2-woman CS2-pain CS2-chest

47. ECO R European Centre for Ontological Research Compare with the output of the perfect semantic analyser we all would dream of CS3-50 years old Has-Age CS3-woman Is-A CS3-native american Is-A CS3-complaining “Jane Smith” Has-Sayer CS3-chest pain Has-Saying CS3-coughing Has-Saying CS3-consultation Has- happening- during CS3-Em.Room Has-Loc Has- participant Compare with the output of the NAIVE !!! semantic analyser we all would dream of

48. ECO R European Centre for Ontological Research What it (more or less) should be CS3-complaining CS3-chest pain Has-Saying CS3-coughing Has-Saying “chest-pain” Has-’referent’ “coughing” Has-’referent’

49. ECO R European Centre for Ontological Research Most important difference: Use of generic terms Use of concrete particulars

50. ECO R European Centre for Ontological Research Step 3: are relevant and necessary particulars missing ? Referred to: – Jane Smith – Jane Smith’s age – Jane Smith’s race – Jane Smith’s gender – Jane Smith’s showing up at... – The specific emergency room in the health facility – Jane Smith’s primarily complaining... – The temporal part... coughs – Jane Smith’s chest – Jane Smith’s particular pain Missing: – The health facility – The healthcare worker she consulted – The particular coughs (under the condition she tells the objective truth) – The underlying disorder (under whatever state of affairs)

51. ECO R European Centre for Ontological Research Step 4: IUI assignment Assumptions: – the RTS contains already: IUI-1 Jane Smith Co i = IUI-1.1 R i = Co i = IUI-1.2 Co i = R i = IUI-1.3 Co i = R i = –All dates in the statements are 2 years earlier than now What to do with: Jane Smith Jane Smith’s race (CS1: native American) Jane Smith’s gender (CS1: female) Jane Smith’s chest pain (CS3: chest pain) Jane Smith’s age (50)

52. ECO R European Centre for Ontological Research Conclusion Referent tracking can solve a number of problems in an elegant way. Existing (or emerging) technologies can be used for the implementation. Old technologies (cbs) can play an interesting role. Big Brother feeling is to be expected but with adequate measures easy to fight. The proof of the pudding is in the eating – Pilote is going to be set up