Automated Off-label Drug Use Detection from User Generated Content

Off-label drug use refers to using marketed drugs for indications that are not listed in their FDA labeling information. Such uses are very common and sometimes inevitable in clinical practice. To some extent, off-label drug uses provide a pathway for clinical innovation, however, they could cause serious adverse effects due to lacking scientific research and tests. Since identifying the off-label uses can provide a clue to the stakeholders including healthcare providers, patients, and medication manufacturers to further the investigation on drug efficacy and safety, it raises the demand for a systematic way to detect off-label uses. Given data contributed by health consumers in online health communities (OHCs), we developed an automated approach to detect off-label drug uses based on heterogeneous network mining. We constructed a heterogeneous healthcare network with medical entities (e.g. disease, drug, adverse drug reaction) mined from the text corpus, which involved 50 diseases, 1,297 drugs, and 185 ADRs, and determined 13 meta paths between the drugs and diseases. We developed three metrics to represent the meta-path-based topological features. With the network features, we trained the binary classifiers built on Random Forest algorithm to recognize the known drug-disease associations. The best classification model that used lift to measure path weights obtained F1-score of 0.87, based on which, we identified 1,009 candidates of off-label drug uses and examined their potential by searching evidence from PubMed and FAERS.

[1]  Ryen W. White,et al.  Web-scale pharmacovigilance: listening to signals from the crowd , 2013, J. Am. Medical Informatics Assoc..

[2]  Nigam H. Shah,et al.  Automated Detection of Off-Label Drug Use , 2014, PloS one.

[3]  Rong Xu,et al.  Large-scale extraction of accurate drug-disease treatment pairs from biomedical literature for drug repurposing , 2013, BMC Bioinformatics.

[4]  Jiawei Han,et al.  Mining heterogeneous information networks , 2010, Proceedings of the 16th ACM SIGKDD international conference on Knowledge discovery and data mining - KDD '10.

[5]  Christopher C. Yang,et al.  Expanding Consumer Health Vocabularies by Learning Consumer Health Expressions from Online Health Social Media , 2015, SBP.

[6]  Christopher C. Yang,et al.  Discovering Drug-Drug Interactions and Associated Adverse Drug Reactions with Triad Prediction in Heterogeneous Healthcare Networks , 2016, 2016 IEEE International Conference on Healthcare Informatics (ICHI).

[7]  Christopher M. Burkle,et al.  Ten common questions (and their answers) about off-label drug use. , 2012, Mayo Clinic proceedings.

[8]  R. Sharan,et al.  PREDICT: a method for inferring novel drug indications with application to personalized medicine , 2011, Molecular systems biology.

[9]  Maurizio Bonati,et al.  Survey of unlicensed and off label drug use in paediatric wards in European countries , 2000, BMJ : British Medical Journal.

[10]  Gaël Varoquaux,et al.  Scikit-learn: Machine Learning in Python , 2011, J. Mach. Learn. Res..

[11]  Harald Herkner,et al.  Search strategies to identify reports on “off-label” drug use in EMBASE , 2012, BMC Medical Research Methodology.

[12]  Margaret M. Barry,et al.  A literature review on health information-seeking behaviour on the web: a health consumer and health , 2011 .

[13]  Taysir Hassan A. Soliman,et al.  Mining Multi Drug-Pathways via A Probabilistic Heterogeneous Network Multi-label Classifier , 2014 .

[14]  Jaehoon Choi,et al.  Drug-drug interaction analysis using heterogeneous biological information network , 2012, 2012 IEEE International Conference on Bioinformatics and Biomedicine.

[15]  Lin Gao,et al.  Inferring drug-disease associations based on known protein complexes , 2015, BMC Medical Genomics.

[16]  J. Kao White Paper: Pharmaceutical Regulation and Off-Label Uses , 2017 .

[17]  R. Rosenheck,et al.  Off-label use of antipsychotic medications in Medicaid. , 2012, The American journal of managed care.

[18]  Qing Zeng-Treitler,et al.  Exploring and developing consumer health vocabularies. , 2006, Journal of the American Medical Informatics Association : JAMIA.

[19]  Hsiang-Yuan Yeh,et al.  Inferring drug-disease associations from integration of chemical, genomic and phenotype data using network propagation , 2013, BMC Medical Genomics.

[20]  Kenneth Jung,et al.  Automated Detection of Systematic Off-label Drug Use in Free Text of Electronic Medical Records , 2013, AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science.

[21]  Xiao-Ying Yan,et al.  Prediction of drug-target interaction by label propagation with mutual interaction information derived from heterogeneous network. , 2016, Molecular bioSystems.

[22]  Xing Chen,et al.  Drug-target interaction prediction by random walk on the heterogeneous network. , 2012, Molecular bioSystems.

[23]  Dina Demner-Fushman,et al.  Extracting drug indication information from structured product labels using natural language processing , 2013, J. Am. Medical Informatics Assoc..