Acquiring and representing drug-drug interaction

knowledge and evidence Jodi Schneider

TRIADS lab, University of Pittsburgh2016-03-25

Problem

o Thousands of preventable medication errors occur each year.

o Clinicians rely on information in drug compendia (Physician’s Desk Reference, Medscape, Micromedex, Epocrates, …).

o Compendia have information quality problems:• differ significantly in their coverage, accuracy, and

agreement• often fail to provide essential management

recommendations about prescription drugs

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Prescribers check for known drug interactions.

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Prescribers consult drug interaction references which are maintained by expert pharmacists.

Medscape EpocratesMicromedex 2.0

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Prescribers consult drug interaction references which are maintained by expert pharmacists.

Medscape EpocratesMicromedex 2.0

Significant discrepancies on drug interactions!

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Goals

o Long-term, provide drug compendia editors with better information and better tools, to create the information clinicians use.

o This talk focuses on how we might efficiently acquire and represent • knowledge claims about medication safety• and their supporting evidence

o in a standard computable format.

MEDICATION SAFETY DOMAIN

Definitions

o Drug-drug interactiono Potential drug-drug interaction

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Existing approaches: RepresentationBradford-Hill criteria (1965)

1. Strength2. Consistency3. Specificity4. Temporality5. Biological gradient6. Plausibility7. Coherence

Bradford-Hill A. The Environment and Disease: Association or Causation?. Proc R Soc Med. 1965;58:295-300.

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Existing approaches: RepresentationRoyal Dutch Association for the Advancement of Pharmacy (2005)

1. Existence & quality of evidence on the interaction2. Clinical relevance of the potential adverse

reaction resulting from the interaction3. Risk factors identifying patient, medication or

disease characteristics for which the interaction is of special importance

4. The incidence of the adverse reaction

Van Roon, E.N. et al: Clinical relevance of drug-drug interactions: a structured assessment procedure. Drug Saf. 2005;28(12):1131-9.

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Existing approaches: Representation

Boyce, DIKB, 2006-present

Existing approaches: Acquisition

o Evidence

12Boyce, DIKB, circa 2006

DATA MODEL: REPESENTING KNOWLEDGE

Why is a new data model needed?o Need computer integrationo Want a COMPUTABLE model that can make

inferences

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Multiple layers of evidence

Medication Safety Studies

Layer

Human Subjects Studies Layer

Scientific Evidence Layer

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Scientific Evidence Layer: Micropublications

16Clark, Ciccarese, Goble (2014) Micropublications: a semantic model for claims, evidence, arguments and annotations in biomedical communications

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Medication Safety Studies Layer: DIDEO

Brochhausen et al, work in progress, example of Clinical Trial

DIDEO: Drug-drug Interaction and Drug-drug Interaction Evidence Ontology

27https://github.com/DIDEO

EVIDENCE CURATION: ACQUIRING KNOWLEDGE

Hand-extracting knowledge claims and evidence

o Sources• Primary research literature• Case reports• FDA-approved drug labels

o Process• Spreadsheets• PDF annotation

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DIRECTIONS & FUTURE WORK

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Quotes in context!

Implications

o Implications for evidence modeling & curationo Implications for ontology development.o Implications for improving medication safety.

Implications for evidence modeling & curationo Evidence modeling & curation is a general

process.o Analogous processes could be used in other

fields.o Biomedical curation is most mature:

structured nature of the evidence interpretation, existing ontologies, trained curators, information extraction and natural language processing pipelines

o Curation pipelines need to be designed with stakeholders in mind.

Thanks to collaborators & funderso Training grant 5T15LM007059-29 from the

National Library of Medicine and the National Institute of Dental and Craniofacial Research

o The entire “Addressing gaps in clinically useful evidence on drug-drug interactions” team from U.S. National Library of Medicine R01 grant (PI, Richard Boyce; 1R01LM011838-01)

o Other collaborators: Paolo Ciccarese, Tim Clark

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“Addressing gaps in clinically useful evidence on drug-drug interactions”

4-year project, U.S. National Library of Medicine R01 grant (PI, Richard Boyce; 1R01LM011838-01)o Evidence panel of domain experts: Carol

Collins, Amy Grizzle, Lisa Hines, John R Horn, Phil Empey, Dan Malone

o Informaticists: Jodi Schneider, Harry Hochheiser, Katrina Romagnoli, Samuel Rosko

o Ontologists: Mathias Brochhausen, Bill Hogano Programmers: Yifan Ning, Wen Zhang

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o Evidence

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7.19 Drugs Metabolized by Cytochrome P4502D6In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6.