Testing drug response in the presence of genetic information: sampling issues for clinical trials.

Progress towards construction of a dense map of di-allelic markers across the human genome has generated considerable enthusiasm for pharmacogenomic applications. To date, however, nearly all of the effort on single nucleotide polymorphism (SNP) projects has been focused on marker identification and screening, not on how the SNP genotype data actually can be used in clinical trials to advance medical practice. Here, we explore how different properties of SNPs impact the size, scope and design of clinical trials using a simple trial design. We evaluate the clinical trial sampling requirements under different allele frequencies, gene action, gene effect size and number of markers in a genome screen. Power and sample size calculations suggest that allele frequency and type of gene action can have a dramatic impact on trial sample sizes, in that under some conditions the required sample sizes are too large to be applicable in a costly clinical trial setting. In other situations, however, pharmacogenomic clinical trials can yield significant sampling/cost savings over traditional trials. These properties are discussed with regard to the general usage of genetic information in clinical trial settings.