Proposed Terms

Below the reader will find, first, a draft list of proposed definitions by Richard Scheuermann, Werner Ceusters, and Barry Smith for the meeting titled: Signs, Symptoms and Findings: First Steps Toward an Ontology of Clinical Phenotypes (September 3-4, 2008). Then, the reader will find emails with comments pertaining to the proposed definitions from a few of those who participated in the meeting.

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From: Barry Smith [1] Sent: Sunday, August 31, 2008 8:07 PM Subject: comments on diseases, signs and symptoms?

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Diseases, Signs and Symptoms: Draft List of Proposed Definitions Richard Scheuermann, Werner Ceusters, Barry Smith

We use ‘abnormal’ to designate those bodily structures, processes or qualities which are associated to a significant degree with pain and other feelings of illness or with enhanced morbidity (the threshold degree of significance being determined by the community of clinicians).

Homeostasis =def. The events transpiring within the body fall within the range which allows bodily functioning to be sustained, and the bodily mechanisms for restoring values within the interior of this range are unimpaired.

Pathological Process =def. A biological process in a human being that is of a type standardly classified by the community of clinicians as abnormal.

Acute Pathological Process =def. A pathological process beginning with a deviation from and terminating with a return to normal homeostasis.

Disorder =def. The physical result of a change in some part of the patient that is associated with a pathological process.

Acute Disorder =def. The physical result of a change in some part of the patient that is associated with an acute pathological process.

Chronic Pathological Process =def. A pathological process that results in an adaptation on the part of the patient to a level of abnormal homeostasis.

Chronic Disorder =def. The physical result of a change in some part of the patient that is associated, absent intervention, with a chronic pathological process.

Progressive Pathological Process =def. A pathological process that begins with a deviation from homeostasis and which continues to deviate in such a way as to preclude the re-establishment of homeostasis.

Progressive Disorder =def. The physical result of a change in the patient that is associated, absent intervention, with a progressive pathological process.

[2] Types of Pathological Process

Physical Examination =def. A sequence of acts of observing and measuring the physical responses of a patient on the part of a physician occurring in the context of a clinical encounter.

Sign =def. A process or quality that is observed in a physical examination and is hypothesized by the clinician as a manifestion of a disorder.

Symptom =def. A quality of the patient that is observed and can be observed only by the patient and is of the type that can be hypothesized by the patient as a manifestion of a disorder.

Laboratory Test =def. A laboratory assay that is used to test a hypothesis about a given patient, and has input: a specimen derived from the patient, and output: a certain result which represents a quality of that patient.

Laboratory Test Result =def. A representation of a quality of a specimen that is the output of a laboratory test.

Finding =def. The result of either a laboratory test or a patient self-assessment (representation, by the clinician, of a symptom as reported by the patient, in the form of an assertion that this patient has this symptom) or a clinical examination (representation, by the clinician, of a sign, in the form of an assertion that this patient manifests this sign).

Clinical Phenotype =def. A constellation of those qualities associated with a disease at each stage of its development.

Clinical Picture A representation of a clinical phenotype inferred from the constellation of findings available to the clinician about a given a patient at any given stage.

Diagnosis =def. The result of an interpretive process which has input: a clinical picture of a given patient and conclusion: an assertion of the form ‘this patient has disease or disorder such and such’.

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From: Xia, Ashley (NIH/NIAID) [E] [3] Sent: Tuesday, September 02, 2008 10:54 AM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Hi Richard

I would like to suggest to add a concept of Homeostatic Profile. The current concept of Homeostatic Range is good for a single measure of a sign, symptom or finding. Homeostatic Profile is good for a collection of homeostatic ranges of a homeostatic state.

Ashley

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From: Kent Spackman [4] Sent: Tuesday, September 02, 2008 2:00 PM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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I haven’t spent much time examining these proposed definitions, but thought I would give you my initial ‘off-the-cuff’ reaction in the form of questions (see attached). There may be good answers to some of these questions – in fact I hope there are. But I suspect I can generate a number of additional difficult questions on further reflection. The general ‘gist’ of the terms is easy to grasp, of course, but I think it would be unwise to underestimate the degree of difficulty of getting good definitions – and getting consensus about the meanings.

I would prefer to back up a step and try to answer two questions: 1) What are the fundamental types of things for which we need ontological categories? (Do we really need to differentiate “signs” from “symptoms”?) 2) What are the criteria by which we can judge whether we have good categories and good definitions? And I’d like to propose one important criterion. It is: the degree to which ordinary clinicians can understand and reproducibly apply the definitions.

Kent Spackman

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From: Sivaram Arabandi [5] Sent: Tuesday, September 02, 2008 3:00 PM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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I can see that the discussion is already getting off the ground and want to add a couple of thoughts. The workshop and the definitions of terms here (like 'Normal Homeostasis', 'Disorder' etc) are focused with the context 'human beings'. However the terms themselves are equally applicable in the more general sense to all animals. It may be useful to provide a broader definition because of the interplay between humans and animals (infectious diseases and their accompanying signs and symptoms - eg. rabies) as well as translational research.

Sivaram

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From: Anita Burgun-Parenthoine [6] Sent: Tuesday, September 02, 2008 4:14 PM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Thanks for sharing these questions. I have two comments: - phenotypes (as well as observable entities) may be normal. It's interesting to mention that in MPO the synonyms for normal phenotype are 'viable' and 'fertile'.... - As Kent already said, some distinctions are difficult to get. For example, the distinction between chronic disorder and progressive disorder is difficult in practice as many chronic diseases end up with complications. Looking forward to the workshop, Anita

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From: John Armstrong [7] Sent: Tuesday, September 02, 2008 5:34 PM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Richard,

From the content of the document you distributed involving disorders, findings, signs, symptoms, and processes, I gather that we will be facing some difficult conceptual issues related to classifying subsumption relations for which there do not appear to be intuitive child-parent links (e.g. those relating findings and disorders.) This is a constant challenge we face at Lead Horse Technologies, whether we are browsing SNOMED-CT or developing and editing our own, proprietary ontologies. There are approaches aimed at solving this dilemma, used by us and others, but they often can involve labor intensive curation and constant editing. If it’s not too late, I’d like to propose that topics discussed at the workshop this week include the idea that dilemmas like the one described here may be approached through tying the curation of intraontological relations not to intelligent design but to evolution – that is, linking the curation of subsumption relationships to actual clinical enquiries received from practicing clinicians rather than to the efforts of ontology development professionals such SNOMED-CT editors. This would boil down to applying a wiki-approach to ontology evolution and it is one that we are working on at Lead Horse. Food for discussion, even if only over a glass of wine.

Thanks, and I’m looking forward to the workshop. John

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From: Colombo Gianluca [8] Sent: Tuesday, September 02, 2008 7:34 PM Subject: R: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Dear all, it is a pleasure to contribute to the discussion.

We would like to bring up two general points, and then proceed to a more detailed discussion of the proposed definitions.

First of all, a remarkable aspect of the diagnostic activity is that certain observations are performed, in order to reconstruct the state of a patient; the state itself is not fully/directly observable (e.g. diabetes cannot be observed per se); the observables collected during the diagnostic activity are interpreted by the clinician, according to some explicit theory and/or his experience, in order to fully reconstruct such state. We therefore deem important to disinguish between what is observed and what is inferred/reconstructed. Also the methodology/istrumentation for the observation, and the criteria for the inference/reconstruction play an importat role. Second, looks like that the notion of disorder plays a pivotal role. A disorder must ncessarily be an anomaly of structure. What is the rationale behind this choice?

Best, Gianluca Colombo Daniele Merico

HERE ARE OUR COMMENTS:

We use ‘clinically normal’ to designate bodily features of a human being that are typically not associated with pain or other feelings of illness, with dysfunction, or with other indications of enhanced morbidity.

>How is dysfunction defined?

Clinical Phenotype =def.

>A constellation of those types of bodily features that are associated with a disorder at each stage of its development. 1) Is there a relevance criterion in the association? Since the Clinical Phenotype refers to bodily feature, any feature may be included. 2) A bodily feature can be a structure; hence a structure can be a clinical phenotype; in other ontologies/works, it is usually preferred to define a phenotype as a property bore by a structure (f. Bard et al., Nature Reviews Genetics 2004).

Clinical Picture =def. A representation of a clinical phenotype as instantiated in a given patient that is inferred from the constellation of laboratory and clinical findings available to the clinician about a given a patient at any given stage.

>Why are Clinical Picture and Clinical Phenotype two distinct concepts? Why is only the former related to Laboratory/Clinical Findings and not simply Bodily Features? Does that imply being observable (directly, or by means of instrumentation) in antithesis to being reconstructed/inferred? Or is the difference related to significance according to the clinician? Indeed, Clinical Findings must be of clinical significance for the clinician (but not Laboratory Findings).

Diagnosis =def. The conclusion of an interpretive process that has as input a clinical picture of a given patient and as output an assertion to the effect that the patient has a disorder of such and such a type.

>If a disorder is neuter with respect to causes and effects, is a diagnosis neuter to causes and effects as well? Declining this definition on a specific example, is Diabetes Mellitus Type-I a diagnosis? Is Diabetes Mellitus Type-I a disorder? Or is rather the absence of insulin-producing beta cells of the pancreas the disorder? Or is it the absence of insulin the disorder? Or is it the abnormally high level of glucose in the blood? Glucose is a blood component, and thus is a bodily structure.

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From: goldberg@buffalo.edu [9] Sent: Wednesday, September 03, 2008 8:44 AM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Homeostatic and homeostasis are old and venerable terms and everyone more or less knows what they mean but they are misleading. None of the states they refer to are static in any way. Alternate terms that have been suggested are homeodynamic and homeokinetic.

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From: Zhangzhi Hu [10] Sent: Wednesday, September 03, 2008 9:42 AM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

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Just throw in my 2 cents:

- We should add "Etiology" besides "Etiological Process", just like there is Homeostasis as opposed to "homeostatic process" (already a GO term, GO:0042592)".

- We also should add Prognosis as opposed to Diagnosis.

- Perhaps we also consider Progression and Remission...

- Also there seems to be already a Symptoms Ontology, but not sure about its content:

http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?tp=&arnumber=1647635&isnumber=34552

Zhangzhi