The Population Attributable Fraction as a Measure of the Impact of Warfarin Pharmacogenetic Testing

Abstract

We aimed to estimate the population impact of warfarin pharmacogenetic testing (WPGT) across multiple populations. We used the expanded International Warfarin Pharmacogenetics Consortium data set and genotype frequencies from HapMap to simulate dose distributions for each CYP2C9/VKORC1 genotype combination in the different races, and calculated the population attributable fraction as a measure of population impact of WPGT. WPGT was compared to both clinical and fixed-dose algorithms to estimate the benefits of WPGT. Our dose simulation revealed different dose requirements in difference races and considerable overlap in dose distributions of different genotype combinations. Population attributable fraction calculations suggest that complete implementation of WPGT can reduce inaccurate dosing by 18-24% in white individuals. However black, Japanese and Chinese patients do not benefit from WPGT, especially when compared against a race-specific fixed dose. Our findings support WPGT in white individuals but not in black, Japanese and Chinese individuals.