STRATEGIES FOR EQUITABLE PHARMACOGENOMIC-GUIDED WARFARIN DOSING AMONG EUROPEAN AND AFRICAN AMERICAN INDIVIDUALS IN A CLINICAL POPULATION
By L. K. Wiley, J. VanHouten, David C. Samuels, M. Aldrich, D. Roden, J. Peterson, Joshua Charles Denny. 2017
9 citations recorded by the source corpus.
The blood thinner warfarin has a narrow therapeutic range and high inter- and intra-patient variability in therapeutic doses. Several studies have shown that pharmacogenomic variants help predict stable warfarin dosing. However, retrospective and randomized controlled trials that employ dosing algorithms incorporating pharmacogenomic variants under perform in African Americans. This study sought to determine if: 1) including additional variants associated with warfarin dose in African Americans, 2) predicting within single ancestry groups rather than a combined population, or 3) using percentage African ancestry rather than observed race, would improve warfarin dosing algorithms in African Americans. Using BioVU, the Vanderbilt University Medical Center biobank linked to electronic medical records, we compared 25 modeling strategies to existing algorithms using a cohort of 2,181 warfarin users (1,928 whites, 253 blacks). We found that approaches incorporating additional variants increased model accuracy, but not in clinically significant ways. Race stratification increased model fidelity for African Americans, but the improvement was small and not likely to be clinically significant. Use of percent African ancestry improved model fit in the context of race misclassification.
Subfields: Immunology, Pharmacology, Statistics and Probability
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In Statistics and Probability
- Brett K. Beaulieu-Jones
- Zhiyong Lu
- Anne E Carpenter
- Jinbo Xu
- Casey S. Greene
- Yifan Peng
- Marwin H. S. Segler
- Michael M. Hoffman
Citations in the corpus
- Opportunities and obstacles for deep learning in biology and medicine (2017, background): “[108] showed that warfarin dosing algorithms often under-perform in African Americans, illustrating that some of these issues are unresolved even at a treatment best practices level.”