2015
DOI: 10.1002/psp4.53
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A Mixture Dose–Response Model for Identifying High‐Dimensional Drug Interaction Effects on Myopathy Using Electronic Medical Record Databases

Abstract: Interactions between multiple drugs may yield excessive risk of adverse effects. This increased risk is not uniform for all combinations, although some combinations may have constant adverse effect risks. We developed a statistical model using medical record data to identify drug combinations that induce myopathy risk. Such combinations are revealed using a novel mixture model, comprised of a constant risk model and a dose–response risk model. The dose represents the number of drug combinations. Using an empir… Show more

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Cited by 12 publications
(33 citation statements)
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“…For the drugs in the top‐four super‐combo‐drugs that have OR > 2, both budesonide and formoterol cause myalgia and cramp muscle; clotrimazole causes cramp muscle; medroxyprogesterone acetate causes muscular weakness and myalgia; glyburide, niacin, and hydroxychloroquine cause myalgia and myopathy. Some of the identified super‐combo‐drugs, that is, dexamethasone, omeprazole, and acetaminophen, are concordance with previous research findings as well . Thus, drug interactions may exist within these drug combinations.…”
Section: An Application To the Myopathy Studysupporting
confidence: 88%
See 1 more Smart Citation
“…For the drugs in the top‐four super‐combo‐drugs that have OR > 2, both budesonide and formoterol cause myalgia and cramp muscle; clotrimazole causes cramp muscle; medroxyprogesterone acetate causes muscular weakness and myalgia; glyburide, niacin, and hydroxychloroquine cause myalgia and myopathy. Some of the identified super‐combo‐drugs, that is, dexamethasone, omeprazole, and acetaminophen, are concordance with previous research findings as well . Thus, drug interactions may exist within these drug combinations.…”
Section: An Application To the Myopathy Studysupporting
confidence: 88%
“…Our method was motivated by a case‐control study on myopathy, and its data were extracted from a deidentified dataset from the INPC, which is health information exchange data warehouse of electronic health records for over 15 million patients from the state of Indiana. The deidentified dataset contains coded prescriptions, diagnoses, and lab test data for over five million patients between the year 2004 and 2009 . The cases are patients with myopathy symptoms.…”
Section: An Application To the Myopathy Studymentioning
confidence: 99%
“…This combination has been ranked in the second place in the list of top 3-drug combinations showing increased risk based on false-discovery rate (FDR) values, reported in the companion article 16. In this example, no matter which path was taken from the baseline to the 3-drug combination, each single step always increased myopathy risk to various degrees of effect size.…”
Section: Resultsmentioning
confidence: 99%
“…Although PS‐adjusted analysis is clearly supreme to the unadjusted analysis in FAERS data analysis, there are other situations that unadjusted analysis is probably better. For example, if the pharmaco‐epidemiological study is designed from a longitudinal cohort, such as the electronic health record (EHR) dataset, the confounding variables, such as demographics, comedications, or comorbidity can be matched and adjusted through nested case‐control study design . In this case, in analyzing DDI‐ADE associations, the unadjusted analysis is a proper choice.…”
Section: Conclusion and Discussionmentioning
confidence: 99%