Stromectol is indicated for the treatment of Strongyloidiasis of the intestinal tract and Onchocerciasis due to nematode parasite. This indication is based on randomized double blind, placebo controlled and comparative studies.
Ketorolac tromethamine tablets are indicated for short term management of moderate to severe pain that requires analgesia at the opioid level.
ACULAR ophthalmic solution is indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. It is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract surgery.
LabeledIn: Cataloging Labeled Indications for Human Drugs Ritu Khare1, Jiao Li1,2, Zhiyong Lu1
1National Center for Biotechnology Information, National Library of Medicine, NIH 2Institute of Medical Information, Chinese Academy of Medical Sciences
Background Semi-Automated Annotation Pipeline
Results: LabeledIn
Drug Label Selection Manual Indication Annotation (Experts A1 and A2 - Two Rounds)
Drug Indication Resource
(LabeledIn)
#Drugs #Drug-Indication Pairs
IN (249) 1,318
IN+DF (611) 2,997
IN+DF+ST (1,513)
7,805
Fig 3 The Annotation Framework with Three Components
LabeledIn Highlights
Computable Structured and Normalized
Human-Validated
Kappa agreement:
Round-1 77.48%
Round-2 88.35%
Source Linked Offsets in drug labels
Source Coverage ~50% Human Rx Drug Labels
Drug Coverage >65% drug searches on PubMed Health
Data Availability Multiple Formats
Related Publications
Khare R, Wei C-H, Lu Z, Annotating FDA Drug Labels for Drug Indications, AMIA Summits on Translational Sciences, 2014
Khare R, Li J, Lu Z, Toward Creating a Gold Standard of Drug Indications, IEEE International Conference on Health Informatics, 2013
Future Directions
Increase drug coverage: machine learning & crowdsourcing
Integrate with other resources (e.g. EMRs)
Most existing “gold standard” repositories on drugs and their indications are unstructured and do not support computer processing or semantic interoperability. Text mining efforts to automatically extract structured indications from free text are limited due to NLP challenges.
Fig 2 Using Existing Disease NER Tools for Indication Recognition
We propose a semi-automatic annotation framework and present a unique resource – LabeledIn – which contains information about drugs and their marketed indications and has the following key properties:
DailyMed (XML/HTML) (FDA Drug Labels)
Motivation
Disease 1
Disease 2
Disease 3
Disease
Drug Indications e.g. What are the indicated usages of
Fluoxetine
Disease Treatments e.g. What drugs may be prescribed for
hypertension
Fig 1 Applications of Drug-Disease Treatment Relationships
Question and Answering e.g. Google Knowledge Graph
Enrich Hyperlinks in Online Resources
Computational Drug Repurposing EMR Decision Support and
Error Control
1. Computable Structured Normalized (UMLS, RxNorm)
2. Accurate Source Linked Precise “Azithromycin 250 mg oral tablet” instead of
“Azithromycin” “Respiratory Tract Infections” instead of “Infections”
Our Contributions
Human Judgment
Automatic Disease Recognition
IN = ingredient DF = dose form ST = strength
Clonazepam(Klonopin) Azithromycin(Zithromax)
16,621
8,151 500
All Human Rx
250 most searched ingredients
Representative labels for annotation
DailyMed Current Medication Information
Round-1: Accept/Reject Pre-annotations
Round-2: Improve Previous Judgments
Fig 4 Applying the Annotation Framework on DailyMed August 2012 Version
Acknowledgments
This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The investigators would like to thank the three human annotators for their efforts.
Rejected Accepted Additionally Suggested
Using Disease Recognition for Indication Extraction
Precision Recall F1-measure
0.55 0.94 0.69
ACULAR ophthalmic solution is indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. It is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract surgery.
Ketorolac tromethamine tablets are indicated for short term management of moderate to severe pain that requires analgesia at the opioid level.
Diltiazem hydrochloride extended release capsules USP are indicated for the treatment of hypertension. Diltiazem hydrochloride extended release capsules is indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Diltiazem hydrochloride extended release capsules USP are indicated for the treatment of hypertension. Diltiazem hydrochloride extended release capsules is indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Diltiazem hydrochloride extended release capsules USP are indicated for the treatment of hypertension. Diltiazem hydrochloride extended release capsules is indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Legend: Current Selected Not Selected
Legend: Previously Selected by A1 only Previously Selected by A2 only
1618 1332 97
LabeledIn Pre-annotations
Fig 5 Computer pre-annotations Vs. Human Annotations
Fig 6 Comparison of LabeledIn and SIDER 2 (50 drug labels)
LabeledIn SIDER 2
92 431 384 56%
9%
14%
21%
Unique Pairs in LabeledIn
23%
49%
12%
10% 3% 3%
Unique Pairs in SIDER
● More Specific ● CUI Different ● Disjoint Mention ● Missed by SIDER
● Other Context ● Generic Overlapping ● Less Specific ● Non-Disease ● CUI Different ● Side Effect /Contraindication
x
x
#DrugLabel-Disease Pairs
#DrugLabel-Disease Pairs
LabeledIn vs. Computer Pre-annotations LabeledIn vs. SIDER 2 Indications