2. Academic Validation
  3. Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China

Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China

  • Sci Rep. 2017 Oct 23;7(1):13819. doi: 10.1038/s41598-017-12580-4.
Liwei Wang 1 2,  Mei Li 3,  Jiangan Xie 4 5,  Yuying Cao 6,  Hongfang Liu 7,  Yongqun He 8 9
Affiliations

Affiliations

  • 1 Department of Medical Informatics, School of Public Health, Jilin University, Changchun, 130021, China. wang.liwei@mayo.edu.
  • 2 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55901, USA. wang.liwei@mayo.edu.
  • 3 Library, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China.
  • 4 Unit for Laboratory Animal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • 5 School of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, 400065, China.
  • 6 Department of Medical Informatics, School of Public Health, Jilin University, Changchun, 130021, China.
  • 7 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55901, USA.
  • 8 Unit for Laboratory Animal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@umich.edu.
  • 9 Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@umich.edu.
PMID: 29061976 DOI: 10.1038/s41598-017-12580-4
Abstract

With increased usage of cardiovascular drugs (CVDs) for treating cardiovascular diseases, it is important to analyze CVD-associated adverse events (AEs). In this study, we systematically collected package insert-reported AEs associated with CVDs used in China, and developed and analyzed an Ontology of Cardiovascular Drug AEs (OCVDAE). Extending the Ontology of AEs (OAE) and NDF-RT, OCVDAE includes 194 CVDs, CVD ingredients, mechanisms of actions (MoAs), and CVD-associated 736 AEs. An AE-specific drug class effect is defined to exist when all the drugs (drug chemical ingredients or drug products) in a drug class are associated with an AE, which is formulated as a new proportional class level ratio ("PCR") = 1. Our PCR-based heatmap analysis identified many class level drug effects on different AE classes such as behavioral and neurological AE and digestive system AE. Additional drug-AE correlation tests (i.e., class-level PRR, Chi-squared, and minimal case reports) were also modified and applied to further detect statistically significant drug class effects. Two drug ingredient classes and three CVD MoA classes were found to have statistically significant class effects on 13 AEs. For example, the CVD Active Transporter Interactions class (including reserpine, indapamide, digoxin, and deslanoside) has statistically significant class effect on anorexia and diarrhea AEs.

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