Mixture drug-count response model for the high-dimensional drug combinatory effect on myopathy

Xueying Wang, Pengyue Zhang, Chien Wei Chiang, Hengyi Wu, Li Shen, Xia Ning, Donglin Zeng, Lei Wang, Sara K. Quinney, Weixing Feng, Lang Li

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Drug-drug interactions (DDIs) are a common cause of adverse drug events (ADEs). The electronic medical record (EMR) database and the FDA's adverse event reporting system (FAERS) database are the major data sources for mining and testing the ADE associated DDI signals. Most DDI data mining methods focus on pair-wise drug interactions, and methods to detect high-dimensional DDIs in medical databases are lacking. In this paper, we propose 2 novel mixture drug-count response models for detecting high-dimensional drug combinations that induce myopathy. The “count” indicates the number of drugs in a combination. One model is called fixed probability mixture drug-count response model with a maximum risk threshold (FMDRM-MRT). The other model is called count-dependent probability mixture drug-count response model with a maximum risk threshold (CMDRM-MRT), in which the mixture probability is count dependent. Compared with the previous mixture drug-count response model (MDRM) developed by our group, these 2 new models show a better likelihood in detecting high-dimensional drug combinatory effects on myopathy. CMDRM-MRT identified and validated (54; 374; 637; 442; 131) 2-way to 6-way drug interactions, respectively, which induce myopathy in both EMR and FAERS databases. We further demonstrate FAERS data capture much higher maximum myopathy risk than EMR data do. The consistency of 2 mixture models' parameters and local false discovery rate estimates are evaluated through statistical simulation studies.

Original languageEnglish (US)
Pages (from-to)673-686
Number of pages14
JournalStatistics in Medicine
Volume37
Issue number4
DOIs
StatePublished - Feb 20 2018

Keywords

  • FDA's adverse event reporting system
  • drug-count response model
  • electronic medical record
  • high-dimensional drug interactions
  • myopathy

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

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  • Cite this

    Wang, X., Zhang, P., Chiang, C. W., Wu, H., Shen, L., Ning, X., Zeng, D., Wang, L., Quinney, S. K., Feng, W., & Li, L. (2018). Mixture drug-count response model for the high-dimensional drug combinatory effect on myopathy. Statistics in Medicine, 37(4), 673-686. https://doi.org/10.1002/sim.7545