Design and Analysis Issues in Pharmaco-genetics/-genomics Studies

• Activity Number: 394
• Type: Invited
• Date/Time: Thursday, August 12, 2004 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): John S. Witte*+
• Companies: University of California, San Francisco
• Keywords: clinical trials ; pharmacogeneitcs ; pharmacogenomics ; sample size ; power

Abstract

Incorporating information on genetic variants that impact disease susceptibility or drug efficacy may reduce clinical trial size and duration. Moreover, knowledge about genes that result in adverse drug reactions can help focus drug development and prescription. We first discuss the different study designs one can use to incorporate genetic information into trials. In particular, whether genotypes are screened prospectively or retrospectively, and whether one takes a candidate gene versus a genome-wide approach. Then we quantify the effects of including genetic information on the sample sizes and time required to detect differences between trial arms. Our calculations indicate that, depending on allele frequency and gene action, pharmacogenetic clinical trials can yield significant sampling/cost savings over traditional trials. Finally, we show how these benefits will depend on numerous factors, including ease of patient recruitment, cost of genotyping, long-term costs of study, and the magnitude of the effect.