Clinical utility, cost-effectiveness and provider perceptions of CYP2C9 and VKORC1 genotyping for chronic warfarin therapy

Pharmacogenomics has been hailed as a potential tool to reduce adverse drug events. Warfarin is one of the most common causes of serious adverse drug events in the US. Two genes, CYP2C9 and VKORC1 , influence warfarin dose. The purpose of this study was to determine the utility, cost-effectiveness and provider perceptions of using pharmacogenetic testing for warfarin management.; The first chapter assessed the relative influence of CYP2C9 and VKORC1 on anticoagulation related outcomes such as percentage of time in, above and below therapeutic range, time to stable maintenance dose, number of anticoagulation visits, and overanticoagulation using a retrospective cohort database. For most anticoagulation related outcomes, CYP2C9 seems to have a larger influence than VKORC1, despite VKORC1's larger effect on dose. This may be due to CYP2C9 's influence on warfarin half-life.; The second chapter evaluated the cost-effectiveness of pharmacogenomic-based warfarin initiation. A Markov model was developed to evaluate the cost effectiveness using evidence from a randomized controlled trial. The results indicate that using pharmacogenomics to initiate warfarin therapy may be fairly inexpensive, but only reduces adverse events slightly, for a relatively favorable cost-effectiveness ratio. There is, however, considerable uncertainty around these results. Larger clinical trials are needed to accurately assess the effectiveness of pharmacogenomics-based warfarin initiation.; The third chapter described anticoagulation clinicians' perceptions towards using pharmacogenomics to help manage warfarin therapy using the adoption of innovation framework. A self-administered questionnaire was used to assess the clinicians' opinions about the pharmacogenomics of warfarin, experience, practice setting and management techniques. Clinicians seemed optimistic about the prospect of using pharmacogenomics to help guide warfarin therapy, but they required more evidence, specifically in the form of randomized trials, to adopt it into their practice.