W. Ceusters1, M. Capolupo2, B. Smith1, G. De Moor3 Medical Informatics Europe – 2009 Oral Paper Session 11: Adverse Drug Events An Evolutionary Approach to the Representation of Adverse Events August 31, 2009 Sarajevo, Bosnia - Herzegovina W. Ceusters1, M. Capolupo2, B. Smith1, G. De Moor3 1 Ontology Research Group, CoE in Bioinformatics & Life Sciences, SUNY at Buffalo 2 Independent consultant, Buffalo, NY 3 RAMIT VZW, Belgium

ReMINE Project

Ontology development in ReMINE support annotation support reasoning higher order logic description logic ReMINE Taxonomies Description of specific adverse event domains (childbirth, patient transfer, ..) as cognized by human beings Realism-based, purpose independent representation of the portion of reality described in the taxonomies Purpose dependent reformulations of the parts of RAEDO which are relevant for a specific domain ReMINE Taxonomies ReMINE Taxonomies ReMINE Taxonomies ReMINE Application Ontology ReMINE Application Ontology ReMINE Adverse Event Domain Ontology ReMINE Application Ontology ReMINE Application Ontologies

Risk Manager’s Event Administration System ReMINE Taxonomy Annotated Events Risk Manager’s Event Administration System

The cognitive model underlying the taxonomies Risky Parameters has Software Situation Environment has_quality occurs_in has_role SHEL entity Time Interval Hardware occurs_in has_quality Contributing Factor causes Adverse_Event Liveware results_in Impact on Patient prevents has_quality Patient Incident Type Mitigation Factor results_in occurs_during has results_in Impact on Organization Primary Diagnosis Process Problem

ReMINE’s notion of adverse event an ‘incident [that] occurred during the past and [is] documented in a database of adverse events’ Stefano Arici, Paolo Bertele. ReMINE Deliverable D4.1 – RAPS Taxonomy: approach and definition. V1.0 (Final) August 8, 2008. (p21) … which is a ‘perdurant’ - ibidem (p26) … ‘that occurs to a patient’ - ibidem (p23) an expectation of some future happening that can be prevented - ibidem (p23)

Terminologists agree, ontologists think … Can something which is an incident be at the same time an expectation ? Can something which is an incident a time t, later become an adverse event simply because it [?] has been entered in a database ? Can adverse events really occur in software ? …

Intermediate conclusion The ReMINE taxonomy (and all concept-based terminologies and ‘ontologies’ in general) provides a distorted view of reality. For good reasons: the distortion is such that it reflects a pragmatic view on what is relevant for the purposes it is designed, it does away with complexities that do not help human beings in doing a better job. But with some negative consequences: reusability out of the ReMINE context is hampered, integration with other descriptive systems becomes cumbersome, and advanced reasoning turns out to be impossible.

Solution: bring philosophical realism in play Basic axioms of realism: There is an external reality which is ‘objectively’ the way it is; That reality is accessible to us; We build in our brains cognitive representations of reality; We communicate with others about what is there, and what we believe there is there. Smith B, Kusnierczyk W, Schober D, Ceusters W. Towards a Reference Terminology for Ontology Research and Development in the Biomedical Domain. Proceedings of KR-MED 2006, Biomedical Ontology in Action, November 8, 2006, Baltimore MD, USA

What is there ? some continuant universal some occurrent universal instanceOf at t instanceOf some continuant particular some occurrent particular

PtoU: instanceOf, lacks, Sorts of relations Unconstrained reasoning UtoU: isa, partOf, … U1 U2 PtoU: instanceOf, lacks, denotes… OWL-DL reasoning PtoP: partOf, denotes, subclassOf,… P1 P2

Universals and Defined Classes Unconstrained reasoning HUMAN BEING extension_of at t instance_of at t E: all human beings at t DC-x: patients at t subclass_of at t I-y OWL-DL reasoning class_member_of at t class_member_of at t

There are way more sorts of classes than universals Fever Rash Tremor Edema Quality Independent continuant Process isa extension_of do not have corresponding universals

Three levels of reality, two sorts of representations beliefs L3 symbolizations ‘about’

Level 2 Diagnoses Interpretations Hypotheses Risk assessments … interpretation documentation Level 1 Primary care processes Secondary processes management research Patients Clinicians Drugs Disorders … Risk Management Ontology Level 3 Patient documentation Protocols Guidelines Event reports Scientific literature … guidance

Using the 3 levels and the particular/universal/class distinctions #1: an incident that happened in the past; Level 2: #2: the interpretation by some cognitive agent that #1 is an adverse event; #3: the expectation by some cognitive agent that similar incidents might happen in the future; Level 3: #4: an entry in the adverse event database concerning #1; #5: an entry in some other system about #3 for mitigation or prevention purposes.

Allows appropriate error management Some possibilities: #1with unjustified absence of #2: #1 was not perceived at all, or not assessed as being an adverse event Unjustified presence of #2: There was no #1 at all, or #1 was not an adverse event Unjustified absence of #4 Same reasons as under (1) above Justified presence of #2 but not reported in the database … Ceusters W, Smith B. A Realism-Based Approach to the Evolution of Biomedical Ontologies. Proceedings of AMIA 2006, Washington DC, 2006;:121-125.

Part of the ReMINE Domain Ontology

Higher order logical representation an incident (#1) that happened at time t2 to a patient (#2) after some intervention (#3 at t1) is judged at t3 to be an adverse event, thereby giving rise to a belief (#4) about #1 on the part of some person (#5, a caregiver as of time t6). This requires the introduction (at t4) of an entry (#6) in the adverse event database (#7, installed at t0).

Back-linking of the ontology to the taxonomies ‘ReM:Insufficient illumination’ is a ReMINE term representing a defined class whose members are all instances of the universal represented by the ReMINE term ‘ReM:illumination’, that universal enjoying an isa relation with the universal represented by the BFO term ‘BFO:Quality’ ‘ReM:international guideline’ is a ReMINE term representing a defined class whose members are all instances of the universal represented by the UCore-SL term ‘UCore:Plan’, that universal enjoying an isa relation with the universal represented by the BFO term ‘BFO:InformationContentEntity’

Advantages Synchronisation of two distinct representations of the same reality: taxonomies: user-oriented view data annotation Domain ontology compatible with OBO-Foundry ontologies: no overlap, easier to re-use. Not only tracking of incidents, but also: how well individual clinicians and organizations manage adverse events, how well one learns from past experiences. ontologies: realism-based view unconstrained reasoning