Pharm-Econogenomics: A New Appraisal

TLDR: A cost-effectiveness analysis of the costs and time scales involved in the discovery of pharmacogenomic variants, their validation, and their incorporation into future clinical guidelines is described.

Abstract: Pharmacogenomics is poised to radically alter the way drugs are designed, developed, and prescribed. Given that much of the variation in drug response can be attributed to genetic differences, tailoring drugs to an individual's unique genetic signature provides the opportunity to reduce adverse drug events, improve drug efficacy, optimize trial design, and prevent costly drug recalls (1). Developing pharmacogenomic strategies to address these issues is critical, given that lack of efficacy and adverse drug events cost the US well over $100 billion annually and that the overall cost for developing a single drug now exceeds $1 billion (2–4). Although genomewide association studies have identified, in general, common sequence variants with increased risks in susceptibility of only 10%–20%, the odds ratios for major side effects or drug responsiveness have been exceptionally large, such as 3- to 20-fold (an increase in risk of 300% to 2000%). This large difference is likely attributable to the fact that humans have been exposed, in evolutionary terms, to most drugs only for a relatively short period of time and that limited genetic selection pressures have been applied (4). Accordingly, exploiting the marked interaction of the genome with drug response represents an exceptional opportunity to enhance the precision and lower the costs of prescription medications. This opportunity has been enhanced by the plummeting cost of sequencing and the recent precedents of accelerated regulatory drug approvals for breakthrough medications developed with genomic guidance (5). Although pharmacogenomics offers the prospect of distinct improvements in drug development and utilization, it is appropriate to ask whether this approach will be cost-effective. In this issue of Clinical Chemistry , Arnaout et al. describe a cost-effectiveness analysis of the costs and time scales involved in the discovery of pharmacogenomic variants, their validation, and their incorporation into future clinical guidelines (3 …