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LabeledIn : Cataloging Labeled Indications for Human Drugs

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LabeledIn : Cataloging Labeled Indications for Human Drugs

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LabeledIn : Cataloging Labeled Indications for Human Drugs

  1. 1. 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 RepurposingEMR 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 16181332 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 92431384 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

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