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Purpose: To critically assess the role and added value of knowledge graphs in pharmacovigilance, focusing on their ability to predict adverse drug reactions., Methods: A systematic scoping review was conducted in which detailed information, including objectives, technology, data sources, methodology, and performance metrics, were extracted from a set of peer-reviewed publications reporting the use of knowledge graphs to support pharmacovigilance signal detection., Findings: The review, which included 47 peer-reviewed articles, found knowledge graphs were utilized for detecting/predicting single-drug adverse reactions and drug-drug interactions, with variable reported performance and sparse comparisons to legacy methods., Implications: Research to date suggests that knowledge graphs have the potential to augment predictive signal detection in pharmacovigilance, but further research using more reliable reference sets of adverse drug reactions and comparison with legacy pharmacovigilance methods are needed to more clearly define best practices and to establish their place in holistic pharmacovigilance systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: At the time of manuscript submission Manfred Hauben was a full time employee of Pfizer Inc., New York, New York, USA; he has also won stocks in pharmaceutical companies that may manufacture or market drugs mentioned in the article. However, he reports no other conflicts of interest that are directly relevant to the content of this manuscript. Mazin Rafi, a former Summer Associate of Pfizer Incorporated, is currently pursuing an MSc in Data Science through Rutgers University, New Brunswick, USA. He has no other conflicts of interest that are relevant to the content of this manuscript. Ibrahim Abdelaziz is affiliated with IBM Research - Yorktown Heights, Yorktown Heights, NY, USA. He reports no conflicts of interest that are relevant to the content of this manuscript. Oktie Hassanzadeh is also affiliated with IBM Research - Yorktown Heights, Yorktown Heights, NY, USA. He reports no conflicts of interest that are relevant to the content of this manuscript., (Published by Elsevier Inc.)

Despite the significant health impacts of adverse events associated with drug-drug interactions, no standard models exist for managing and sharing evidence describing potential interactions between medications. Minimal information models have been used in other communities to establish community consensus around simple models capable of communicating useful information. This paper reports on a new minimal information model for describing potential drug-drug interactions. A task force of the Semantic Web in Health Care and Life Sciences Community Group of the World-Wide Web consortium engaged informaticians and drug-drug interaction experts in in-depth examination of recent literature and specific potential interactions. A consensus set of information items was identified, along with example descriptions of selected potential drug-drug interactions (PDDIs). User profiles and use cases were developed to demonstrate the applicability of the model. Ten core information items were identified: drugs involved, clinical consequences, seriousness, operational classification statement, recommended action, mechanism of interaction, contextual information/modifying factors, evidence about a suspected drug-drug interaction, frequency of exposure, and frequency of harm to exposed persons. Eight best practice recommendations suggest how PDDI knowledge artifact creators can best use the 10 information items when synthesizing drug interaction evidence into artifacts intended to aid clinicians. This model has been included in a proposed implementation guide developed by the HL7 Clinical Decision Support Workgroup and in PDDIs published in the CDS Connect repository. The complete description of the model can be found at https://w3id.org/hclscg/pddi., Competing Interests: Author EG was employed by the company Pharmacy Consulting International. Author OH was employed by IBM. Author BH was employed by Genelex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hochheiser, Jing, Garcia, Ayvaz, Sahay, Dumontier, Banda, Beyan, Brochhausen, Draper, Habiel, Hassanzadeh, Herrero-Zazo, Hocum, Horn, LeBaron, Malone, Nytrø, Reese, Romagnoli, Schneider, Zhang and Boyce.)

Although potential drug-drug interactions (PDDIs) are a significant source of preventable drug-related harm, there is currently no single complete source of PDDI information. In the current study, all publically available sources of PDDI information that could be identified using a comprehensive and broad search were combined into a single dataset. The combined dataset merged fourteen different sources including 5 clinically-oriented information sources, 4 Natural Language Processing (NLP) Corpora, and 5 Bioinformatics/Pharmacovigilance information sources. As a comprehensive PDDI source, the merged dataset might benefit the pharmacovigilance text mining community by making it possible to compare the representativeness of NLP corpora for PDDI text extraction tasks, and specifying elements that can be useful for future PDDI extraction purposes. An analysis of the overlap between and across the data sources showed that there was little overlap. Even comprehensive PDDI lists such as DrugBank, KEGG, and the NDF-RT had less than 50% overlap with each other. Moreover, all of the comprehensive lists had incomplete coverage of two data sources that focus on PDDIs of interest in most clinical settings. Based on this information, we think that systems that provide access to the comprehensive lists, such as APIs into RxNorm, should be careful to inform users that the lists may be incomplete with respect to PDDIs that drug experts suggest clinicians be aware of. In spite of the low degree of overlap, several dozen cases were identified where PDDI information provided in drug product labeling might be augmented by the merged dataset. Moreover, the combined dataset was also shown to improve the performance of an existing PDDI NLP pipeline and a recently published PDDI pharmacovigilance protocol. Future work will focus on improvement of the methods for mapping between PDDI information sources, identifying methods to improve the use of the merged dataset in PDDI NLP algorithms, integrating high-quality PDDI information from the merged dataset into Wikidata, and making the combined dataset accessible as Semantic Web Linked Data., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Structured Product Labels (SPLs) contain information about drugs that can be valuable to clinical and translational research, especially if it can be linked to other sources that provide data about drug targets, chemical properties, interactions, and biological pathways. Unfortunately, SPLs currently provide coarsely-structured drug information and lack the detailed annotation that is required to support computational use cases. To help address this issue we created LinkedSPLs, a Linked Data resource that extends the "web of drug identity" using information extracted from SPLs. In this paper we describe the mapping that LinkedSPLs provides between SPL active ingredients and DrugBank chemical entities. These mappings were created using three approaches: InChI chemical structure descriptors comparison, exact string matching based on the chemical name, and automatic (unsupervised) linkage identification. Comparison of the approaches found that, while these three approaches are complementary, the automatic approach performs well in terms of precision and recall.

Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug's efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File - Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug interaction claims linked to the Drug Interactions section for a drug were potentially novel. The baseline performance characteristics of the proof-of-concept will enable further technical and user-centered research on robust methods for scaling the approach to the many thousands of product labels currently on the market.