Addressing Barriers to Clinical Implementation of Pharmacogenomics

Abstract

Pharmacogenomics offers one of the best use cases for widespread clinical implementation of genomic medicine, as variants tend to have moderate allele frequencies, many of the affected medications are relatively common, and the magnitude of effect tends to be clinically meaningful. Using pharmacogenomic-guided warfarin dosing as an example, this dissertation addresses potential barriers and solutions to the clinical implementation of pharmacogenomics. Warfarin is a blood thinner that has a narrow therapeutic index and wide dosing variation, with many known pharmacogenomic markers associated with stable warfarin dose. A number of different methods to reduce disparities in pharmacogenomic-guided warfarin dosing among African Americans were tested. Additionally data from Vanderbilt’s clinical implementation of pharmacogenomic-guided warfarin dosing were analyzed to assess process outcomes (e.g. how did the actual warfarin dose ordered compare to the recommended dose) and patient outcomes (e.g., what kinds of clinical events did the patient experience immediately following warfarin initiation). A summary of policy and technological challenges for clinical implementation of precision medicine, along with potential solutions, are presented.