1. The Role of Phenotypes in Establishing Interoperability in Health Care Asia-Pacific HL7 Conference 2013 October 25-26, 2013 W. Ed Hammond, Ph.D., FACMI, FAIMBE, FHL7, FIMIA Director, Duke Center for Health Informatics Professor, Duke School of Medicine Chair-Emeritus, HL7

2. Components of informatics Data Semantically interoperable, high quality, timely Knowledge Appropriate, accessible, comprehensive, usable Information Actionable, focused, clear, reduces uncertainty Judgment Human input based on experience and observation; an intangible component Wisdom Individuals trained in how to use data, knowledge, and information 2

3. Interoperability Why? To increase information about a subject How? By reducing ambiguity It’s all about the data! Knowledge applied to data produces information Computers enable the process Human component and experience adds judgment and wisdom 3

4. The Building Blocks Data Elements – eliminate ambiguity Phenotypes – coupling knowledge to data in computer understandable way 4

5. Data Elements Complete, precise and unambiguous definitions, universally accepted, defined by clinical experts Must be finely grained at the most detailed level to support decision making Must be universal and identified by a unique, meaningless ID ID is the common factor that permits translation (in concept) to any language Must include a rich set of attributes fully defining element, its form and its use 5

6. Data Element Ideally self-defining Is the language for communication and the exchange of data, based on purpose and requirements Enables the global use of knowledge through decision support, clinical guidelines, and disease management protocols 6

7. Attributes … Definition as logic statement for computer validation (where appropriate) Name Preferred name – clinical term Short display name Synonyms Language Category Class/classification 7

8. Attributes … Units Data type How measured Purpose Value set Links (relational, knowledge, use, …) Authoritive source/citation 8

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10. In Lewis Carroll's Through the Looking-Glass, Humpty Dumpty discusses semantics and pragmatics with Alice. 10 "I don't know what you mean by 'glory,' " Alice said. Humpty Dumpty smiled contemptuously. "Of course you don't—till I tell you. I meant 'there's a nice knock-down argument for you!' " "But 'glory' doesn't mean 'a nice knock-down argument'," Alice objected. "When I use a word," Humpty Dumpty said, in rather a scornful tone, "it means just what I choose it to mean—neither more nor less." "The question is," said Alice, "whether you can make words mean so many different things." "The question is," said Humpty Dumpty, "which is to be master that's all." Alice was too much puzzled to say anything, so after a minute Humpty Dumpty began again. "They've a temper, some of them—particularly verbs, they're the proudest—adjectives you can do anything with, but not verbs—however, I can manage the whole lot! Impenetrability! That's what I say!" [

11. A working definition A phenotype represents a trait or characteristic that relates to the topic of interest. Synonyms might include trait, characteristic, attribute, artifact, or other. Phenotype seems to be in most common use. Word is important because of the potential of extracting knowledge from large data sets of electronic health records. Phenotypes may be viewed as a way of packaging knowledge in an understandable and usable way. 11

12. Phenotype suite Phenotype signature Cohort identification Risk factor or disease precursor Trigger for test, treatment or other action Disease progression Outcome evaluation 12

13. Phenotype Signature The set of phenotypes that define a disease or conditions Expression may be a logic expression with AND, OR, NOT. Proposed similar to logic component of Arden Syntax, using XML. With research, components may be assigned weights Sum of weights produce a quantitative certainty factor Phenotypes define the data elements to be collected Weighting factors may vary as a consequence of data not available or logic component not satisfied. 13

14. Cohort Identification Phenotype set that identifies a group of patients as candidates for a particular controlled clinical research trial. Sets will be classified as the diagnostic codes identified by vocabulary source, clinical data, demographic data, environmental data, genomic data, other data, and constraints such as location. Diagnostic code sets will be hierarchically defined and will be defined from multiple controlled terminologies 14

15. Phenotypes sets for risk factors Phenotype set that defines the risk factors or disease precursors with attached waiting factors to the phenotypes Requires research to extract candidate phenotypes from EHRs may be a Big Data type project 15

16. Phenotype Trigger Phenotype set that defines conditions and events that may trigger a type of treatment, test or activity Probably not a new idea and concept is represented by many clinical decision support algorithm. 16

17. Disease Progression Phenotype set that defines indicators for potential progression of disease. Requires research to extract candidate phenotypes from EHRs or verify/challenge Big Data type project 17

18. Outcome Evaluation Phenotype set for defining the outcome measure for a particular course of treatment. Will permit comparison of treatments across different treatments as well as across different institutions. 18

19. Other considerations Propose creating registries of phenotype suites Create standard format for phenotype sets Effectiveness will require the use of a common set of data elements with a rich set of data attributes, freely available Data elements should contain genomic, biomarkers, clinical, environmental, social, economic, geospatial, and any other kind of data that is involved in defining health and health care. Algorithms for expressing algorithms must be flexible and accommodate time and time intervals This approach permits and suggests follow up research projects to define and validate phenotype suites. 19

20. 20 Thank you! This work supported in part by NIH grant1U54AT007748-01