Study Design and Statistical Issues in Pharmacogenetics Research: From Candidate Genes to Genome-Wide Screens

Pharmacogenetics research focuses on the identification of inherited DNA sequence variations that influence an individual's response to therapeutic agents. Discovering such variations is nontrivial and may require enormous and potentially unrealistic sample sizes for appropriately therapeutic-response powered studies, unless one has sufficient a priori knowledge about genomic regions likely to harbor relevant variations. In addition, once relevant variations have been identified, it is important to evaluate their clinical utility, especially with respect to the appropriate therapeutic agents. In this very basic review we consider strategies for identifying genetic variations that influence response to therapeutic agents. We also consider strategies for evaluating the use of these genetic variations in the design and conduct of clinical trials assessing the utility of these variations in guiding therapeutic decisions.