Center of Excellence in Bioinformatics and Life Sciences International Consensus Workshop: Convergence on an Orofacial Pain Taxonomy Ontological Perspectives on the Classification of Pains and Related Entities Miami, FL - March 30 – April 1, 2009 Werner CEUSTERS, MD Center of Excellence in Bioinformatics and Life Sciences University at Buffalo, NY, USA

Three distinct activities Ontology: Discovering what entities exist and how they relate to each other More specific: … which are relevant for pain Terminology: Formulating terms to denote (primarily generic) entities unambiguously Classification: Defining classes which group together examples of generic entities that have similar properties and which serve some specific purpose

One flavor of ontology: Realism-based Ontology Basic assumptions: reality exists objectively in itself, i.e. independent of the perceptions or beliefs of cognitive beings; reality, including its structure, is accessible to us, and can be discovered through (scientific) research; the quality of an ontology is determined at least in part by the accuracy with which it represents the pre-existing structure of reality.

Three levels of reality The world as it is prior to a cognitive agent’s perception thereof: This pain in that patient, the disorder that causes that pain Cognitive representations of the world build up by cognitive agents ‘in their minds’; My diagnosis about that patient’s pain, my diagnosis about his disorder that causes that pain Representational artifacts designed to make these representations publicly accessible in some enduring fashion. This term from that classific 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, November 8, 2006, Baltimore MD, USA

One operationalization: Basic Formal Ontology The world consists of universals (types, kinds) particulars that are either occurrents or continuants, the latter being either dependent or independent, relationships of the form: <particular , universal> e.g. is-instance-of, <particular , particular> e.g. is-part-of <universal , universal> e.g. is_a (is-subtype-of) 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, November 8, 2006, Baltimore MD, USA

Separating the issues: a simplified view Terms Generic entities and configurations Patients

Separating the issues: a simplified view Terms Generic entities and configurations T1 T2 T3 … Patients

Distinct purposes for definitions Terms Generic entities and configurations T1 T2 T3 … 1 to specify the conditions that must be satisfied in some community for a term to be an acceptable designator for an entity Patients

Rules of conduct for term formation Terminological principles and standards E.g. don’t hide relationships in adjectives unless the adjective expresses the relationship clearly. Name things according to what they are “shall we call this ‘arthritis’ or ‘arthralgia’” ? Don’t call a monkey a banana because it eats bananas; There are no ‘probable arthralgias’ although there are ‘clinicians who are not yet sure about whether this patient has arthralgia’. Think wider than the own community since data collections should now serve translational research, not just clinical research. Not easy: IHS migraine classification violates almost all principles.

Distinct purposes for definitions Terms Generic entities and configurations T1 T2 T3 … 2 to describe the ways in which entities of one type differ from entities of another type and what they have in common Patients

Ontological principles There are no infinite number of different sorts. Entities of given sorts can not enter in an infinite number of ways with entities of another sort. Particular entities of certain sorts can not evolve or transform in an infinite number of ways. Something what is now a pain, cannot become later a disorder. The ontological enterprise is about finding what the principles are, and assuring that they are adhered to in our representations.

Distinct purposes for definitions Terms Generic entities and configurations T1 T2 T3 … to provide assistance in determining what type a specific entity belongs to 3 Patients

Patient (‘diagnostic level’) Compare Generic entity level: Patients that have a blood pressure which is too high for their age, have hypertension, versus Patient (‘diagnostic level’) A patient of age 24 with a blood pressure at rest of 18/12 has hypertension.

Classification of patients Terms Generic entities and configurations T1 T2 T3 … Classes and classifications Patients

Attempt to have these classes correspond with generic entities Terms Generic entities and configurations T1 T2 T3 … Classes and classifications Patients

The temporal perspective Terms T1 T2 T3 T4 Generic entities and configurations Classes and classifications Patients

The temporal perspective Terms T1 T2 T3 T4 Generic entities and configurations Classes and classifications No change in this patient There is change in this patient Patients

Further detail

A parallel: the ‘categorical – dimensional’ debate on the classification of mental disorders Rough distinction: “Categorical”: ‘mental disorders’ can be classified as single, discrete and mutually exclusive types, of which a particular patient does or does not exhibit an instance. DSM “Dimensional”: any particular ‘mental disorder’ in a patient is an instance of just one single type and differences between cases are a matter of ‘scale’. ‘Rough’, because the literature is huge and vague descriptions are (philosophically) very incoherent

DSM under fire severely ill inpatients often meet criteria for more than one DSM-IV personality disorder; many outpatients do not meet the criteria for any of the specific categories identified in DSM-IV; patients with the same categorical diagnosis often vary substantially with respect to signs and symptoms; frequent revision of the diagnostic thresholds separating what is normal from what is disordered; a number of the diagnostic categories mentioned in DSM-IV lack any developing scientific base for an understanding of the corresponding disorder types.

But: some dimensionalists also use flawed arguments “Diagnostic categories defined by their syndromes should be regarded as valid only if they have been shown to be discrete entities with natural boundaries that separate them from other disorders.” “there is no empirical evidence for natural boundaries between major syndromes” … “the categorical approach is fundamentally flawed” Kendell R, Jablensky A. Distinguishing between the validity and utility of psychiatric diagnoses. Am J Psychiatry 2003; 160:4–12. Cloninger CR: A new conceptual paradigm from genetics and psychobiology for the science of mental health. Aust N Z J Psychiatry 33:174–186, 1999.

Is there empirical evidence for this boundary ? And if not, do these mountains exist ?

Attempts to resolve the problem Non-arbitrary basis for drawing a categorical distinction No Yes Non-kind Haslam N. Kinds of Kinds: A Conceptual Taxonomy of Psychiatric Categories. Philosophy, Psychiatry, & Psychology, 9 (2002), 203-218 This basis is an objective discontinuity No Yes Practical kind ‘severity’ ‘neuroticism’ The discontinuity is sharp and binary No Yes Fuzzy kind ‘essential hypertension’ ‘depression’ The discontinuity is constituted by an ‘essence’ ‘borderline personality’ No Yes Discrete kind Natural kind ‘melancholia’ ‘Williams syndrome’

Three purposes for definitions to specify the conditions that must be satisfied in some community for a term to be an acceptable designator for an entity; to describe the ways in which entities of one type differ from entities of another type to provide assistance in determining what type a specific entity belongs to.

Towards the full picture (1) Level of biomedical reality: Persons, diseases, pathological structures and formations,... do exist as particulars (p, d, ps, pf, ... ) and universals (P, D, PS, PF, ...), and are related in specific ways prior to our perception; Biomedical reality changes: d’s, p’s, ... come and go; D’s, P’s, ... only come (?) Level of biomedical science and case perception: Mirrors reality only partially Evolves over time towards better understanding

Towards the full picture (2) Level of concretizations Mirrors biomedical science and case perception only partially Editing mistakes Leaving out diseases or pathological behaviours for non-biomedical reasons Smoking Adding non-pathological behaviour as a disease homosexuality

What is a ‘diagnosis’ Any configuration of representational units which is believed to mirror the portion of reality consisting of an organism’s disease and the relationships this disease enjoys with the entities that caused the disease or influence its course, whereby some part of this configuration of representational units refers to the universal of which that disease is believed to be an instance, or the defined class of which it is believed to be a member.

A well-formed diagnosis of ‘pneumococal pneumonia’ A configuration of representational units; Believed to mirror the person’s disease; Believed to mirror the disease’s cause; Refers to the universal of which the disease is believed to be an instance. Disease isa Pneumococcal pneumonia Instance-of at t1 #78 John’s portion of pneumococs #56 John’s Pneumonia caused by

Some motivations and consequences (1) No use of debatable or ambiguous notions such as proposition, statement, assertion, fact, ... The same diagnosis can be expressed in various forms. Disease isa caused by Instance-of at t1 #56 #78 Pneumonia caused by Portion of pneumococs #56 #78 Pneumococcal pneumonia caused by Instance-of at t1

Some motivations and consequences (2) A diagnosis can be of level 2 or level 3, i.e. either in the mind of a cognitive agent, or in some physical form. Allows for a clean interpretation of assertions of the sort ‘these patients have the same diagnosis’:  The configuration of representational units is such that the parts which do not refer to the particulars related to the respective patients, refer to the same portion of reality.

Distinct but similar diagnoses Pneumococcal pneumonia Instance-of at t1 Instance-of at t2 #78 John’s portion of pneumococs #56 John’s Pneumonia #956 Bob’s pneumonia #2087 Bob’s portion of pneumococs caused by caused by

Some motivations and consequences (3) Allows evenly clean interpretations for the wealth of ‘modified’ diagnoses: With respect to the author of the representation: ‘nursing diagnosis’, ‘referral diagnosis’ When created: ‘post-operative diagnosis’, ‘admitting diagnosis’, ‘final diagnosis’ Degree of the belief: ‘uncertain diagnosis’, ‘preliminary diagnosis’

But the definition requires working out: At the level of biomedical reality: What is a disease ? What are the entities that cause a specific disease to exist or influence its course ? What are the relationships between these entities and the disease ? At the level of representational artifacts: How do they relate to reality ? How keeping track of changes in reality ?

Combining Referent Tracking with Ontology instance-of at t Realism-based Ontology RT-based Data model #105 caused by

What we need to do Be precise about what representational units in either an ontology or data repository stand for. Each such unit in an ontology should come with additional information on whether it denotes: an entity at level 1, level 2 or level 3 and a universal, or some kind of class

Representing particular cases Is the generic representation of the portion of reality adequate enough for the description of particular cases? Example: a patient born at time t0 undergoing anti-inflammatory treatment and physiotherapy since t2 for an arthrosis present since t1 develops a stomach ulcer at t3.

Anti-inflammatory treatment with ulcer development IUI Description of particular Properties #1 the patient who is treated #1 member_of C1 (subject of care) since t2 #2 #1’s treatment #2 instance_of C3 (act of care) #2 has_participant #1 since t2 #2 has_agent #3 since t2 #3 the physician responsible for #2 #3 member_of C4 (care giver) since t2 #4 #1’s arthrosis #4 member_of C5 (underlying disease) since t1 #5 #1’s anti-inflammatory treatment #5 part_of #2 #5 member_of C2 since t3 #6 #1’s physiotherapy #6 part_of #2 #7 #1’s stomach #7 member_of C6 (involved structure) since t2 #8 #7’s structure integrity #8 instance_of C8 since t0 #8 inheres_in #7 since t0 #9 #1’s stomach ulcer #9 part_of #7 since t3 #10 coming into existence of #9 #10 has_participant #9 at t3 #11 change brought about by #9 #11 has_agent #9 since t3 #11 has_participant #8 since t3 #11 instance_of C10 at t3 #12 noticing the presence of #9 #12 has_participant #9 at t3+x #12 has_agent #3 at t3+x #13 cognitive representation in #3 about #9 #13 is_about #9 since t3+x

Anti-inflammatory treatment with ulcer development IUI Description of particular Properties #1 the patient who is treated #1 member_of C1 since t2 #2 #1’s treatment #2 instance_of C3 #2 has_participant #1 since t2 #2 has_agent #3 since t2 #3 the physician responsible for #2 #3 member_of C4 since t2 #4 #1’s arthrosis #4 member_of C5 since t1 #5 #1’s anti-inflammatory treatment #5 part_of #2 #5 member_of C2 since t3 #6 #1’s physiotherapy #6 part_of #2 #7 #1’s stomach #7 member_of C6 since t2 #8 #7’s structure integrity #8 instance_of C8 since t0 #8 inheres_in #7 since t0 #9 #1’s stomach ulcer #9 part_of #7 since t3 #10 coming into existence of #9 #10 has_participant #9 at t3 #11 change brought about by #9 #11 has_agent #9 since t3 #11 has_participant #8 since t3 #11 instance_of C10 (harm) at t3 #12 noticing the presence of #9 #12 has_participant #9 at t3+x #12 has_agent #3 at t3+x #13 cognitive representation in #3 about #9 #13 is_about #9 since t3+x

Reality versus beliefs, both in evolution p3 Reality IUI-#3 O-#0 O-#2 Belief O-#1 = “refers to” = what constitutes the meaning of representational units …. Therefore: O-#0 is meaningless

Time line and dependencies (1) the patient (#1) who is treated #1 #1’s stomach #7 #7’s structure integrity #8 structure integrity C8 At t0, the patient is born, and since that time, his stomach is part of him and a structure integrity (C8) inheres in it: #1 instance-of person since t0 #7 part-of #1 since t0 #8 instance_of C8 since t0 #8 inheres_in #7 since t0

Time line and dependencies (2) the patient who is treated #1 #1’s stomach #7 #7’s structure integrity #8 structure integrity C8 #1’s arthrosis #4 underlying disease C5 At t1, the patient acquires arthrosis: #4 member_of C5 since t1 #4 inheres_in #1 since t1

Time line and dependencies (3) the patient who is treated #1 subject of care C1 #1’s stomach #7 involved structure C6 #7’s structure integrity #8 structure integrity C8 #1’s arthrosis #4 underlying disease C5 #1’s treatment #2 act of care C3 #1’s physiotherapy #6 #1’s anti-inflammatory treatment #5 At t2, the patient consults #3 who starts treatment. It is then that the patient becomes a member of the class subject of care (C1) and his stomach a member of the class involved structure (C6) the physician responsible for #2 #3 care giver C4

Time line and dependencies … the patient who is treated #1 subject of care C1 #1’s stomach #7 involved structure C6 #7’s structure integrity #8 structure integrity C8 #1’s arthrosis #4 underlying disease C5 #1’s treatment #2 act of care C3 #1’s physiotherapy #6 #1’s anti-inflammatory treatment #5 act under scrutiny C2 #1’s stomach ulcer #9 change brought about by #9 #11 harm C10 noticing #9 #12 cognitive representation in #3 about #9 #13 the physician responsible for #2 #3 care giver C4