1. Dynamic Enhancement
of Drug Product Labels
Through Semantic Web
Technologies
(A W3C HCLS IG Use Case)
Richard Boyce, University of Pittsburgh
Oktie Hassanzadeh, IBM Research
Jyotishman Pathak, Mayo Clinic
Jodi Schneider, DERI, Galway
Maria Liakata, Aberystwyh University/EMBL-EBI
Anita de Waard, Elsevier
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Department of Biomedical Informatics

2. The problem
• Drug product labels are a key source of
information
– Drug efficacy, effectiveness, safety, use
• However, much of the information in drug
product labeling is incomplete or not up to
date with the scientific literature
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3. Missing drug-drug interactions
• Example:
– “Both clopidogrel and ticlopidine significantly inhibited the
CYP2B6-catalyzed bupropion hydroxylation. Patients
receiving either clopidogrel or ticlopidine are likely to require
dose adjustments when treated with drugs primarily
metabolized by CYP2B6.” [1]
• Search bupropion product labels for
“clopidogrel”
– No mention at all in Aplenzin ER insert [2]
– Mention in the generic tablet insert [3], but refers only
to hypothetical interaction
1. Turpeinen M, Tolonen A, Uusitalo J, Jalonen J, Pelkonen O, Laine K. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by
bupropion hydroxylation. Clin Pharmacol Ther. 2005 Jun;77(6):553-9.
2. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2315d6e5-144d-4163-9711-f855c759cf8e
3. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e537ed50-6677-45eb-9e62-af62d3831f19
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4. Other notable incomplete information
• Clinical effectiveness
– Ex: Switch to venlafaxine in adolescents:
• “A switch to another SSRI was just as efficacious as a
switch to venlafaxine and resulted in fewer adverse
effects.” [1]
• Age-related clearance data
– Product labels rarely have this information even
when published [2]
• Metabolic inhibition
– Numerous examples of missing information [3]
1. Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, Vitiello B, Ritz L, Iyengar S, Abebe K, irmaher B, Ryan N, Kennard B, Hughes C, DeBar L, McCracken J,
Strober M, Suddath R, Spirito A, Leonard H, Melhem N, Porta G, Onorato M, Zelazny J. Switching to another SSRI or to venlafaxine with or without cognitive behavioral
therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA. 2008 Feb 27;299(8):901-13.
2. Boyce RD, Handler SM, Karp JF, Hanlon JT. Age-Related Changes in Antidepressant Pharmacokinetics and Potential Drug-Drug Interactions: A
Comparison of Evidence-Based Literature and Package Insert Information. Am J Geriatr Pharmacother. 2012 Apr;10(2):139-50
3. Boyce R, Harkema H, Conway M. Leveraging the semantic web and natural language processing to enhance drug-mechanism knowledge in drug product
labels. In: Proceedings of the 1st ACM International Health Informatics Symposium. IHI ’10. New York, NY, USA: ACM; 2010:492–496.
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5. Current use of product labels

6. What are we suggesting then?
• “…build a linked open data store of scientific
information that updates or elaborates on
medication safety statements present in drug
product labels.”
- W3C HCLS IG Use Case (http://goo.gl/wP4Mz)
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7. Proposed innovation – take claims present in
semantic web resources….

8. …create a linked dataset that merges those claims
and identifies where they should be located in the
product label….

9. …create customized views of the new linked dataset
tailored toward various drug experts and decision
support tools

10. Proof of concept
• http://tinyurl.com/c53skm4
– 29 psychotropic drug products
– Created using four Semantic Web nodes
1. http://thedatahub.org/dataset/linked-structured-product-labels
2. http://thedatahub.org/dataset/linkedct
3. http://bioportal.bioontology.org/ontologies/47101
4. http://thedatahub.org/dataset/the-drug-interaction-knowledge-base
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11. Preliminary results
Drug ClinicalTrials.gov DDIs apparently novel to the Drug
relevant to the Interactions section
Clinical Studies NDF-RT DIKB
section Critical Significant
Antidepressants
Bupropion 5 2 4 0
Citalopram 4 8 20 1
Venlafaxine 2 6 21 3
…
Antipsychotics
Risperidone 23 0 10 3
Ziprasidone 1 23 55 0
…
Sedative Hypnotics
Eszopiclone 3 0 2 0
…
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12. Issues to be addressed
• Ensuring the quality of the claims linked to the
package insert sections
– Provenance is key
– Could a drug information “knowledge market” could
be created?
• Technical issues with some existing linked
open drug data nodes
– Now is the time to improve linked open drug data
• Correct RDF mappings, accurate encodings
• Graph and data provenance
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13. Want more information?
• Use Case description
– http://goo.gl/wP4Mz
• Google code project
– code.google.com/p/swat-4-med-safety/
• Proof of concept
– http://tinyurl.com/c53skm4
• Linked data nodes used in the proof of concept
– http://thedatahub.org/dataset/linked-structured-product-labels
– http://thedatahub.org/dataset/the-drug-interaction-knowledge-base
– http://thedatahub.org/dataset/linkedct
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14. Discussion/questions
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15. Acknowledgements
• The Drug Interaction Knowledge Base team
– John Horn Pharm.D, Carol Collins MD, Greg
Gardner, Rob Guzman
• W3C LODD Task Force
• Early comments on the Use Case:
– Michel Dumontier and several others who attend
W3C HCLS calls
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