The genetics of drug efficacy: opportunities and challenges

To date, there have been at least 76 genome-wide association studies and a large number of candidate gene studies of drug efficacy. From these, there are at least 12 drugs with high-confidence genetic predictors of drug efficacy.Genetic predictors of drug efficacy are mostly common variants with a range of effect sizes; most have been discovered through studies of sensitive quantitative measures of drug response, and all but one were discovered following drug approval.Less than 20% of drugs are estimated to have common genetic predictors of efficacy that are large enough to inform clinical decision making.There are limited scenarios in which genetics can 'rescue' a trial that fails owing to lack of efficacy. However, advances in genetic technologies can allow for cost-effective screening for genetic predictors with potential clinical utility during the course of clinical development.Pharmaceutical and academic researchers should combine resources to study the efficacy pharmacogenetics of marketed drugs.