Breaching the study design barrier to pharmacogenetics in drug R&D

For the pharmacokinetics of many drugs, genotype to genotype variability often exceeds the conventional bioequivelence window of 80-125%. Nevertheless, drug development, government-regulated drug labeling, and clinical practice do not systematically incorporate pharmacogenetic data into decision-making. Systematic use of standardized clinical trials designs for examining pharmacogenetics will help to bring the benefits of molecular medicine to patients. [Continue]

A recent article in Nature Reviews Drug Discovery states that the classic randomized, controlled clinical trial typical of Phases 2 and 3 in the drug development process can be transformed into the most effective and valid pharmacogenetic study design by adding on an analysis of the differences in outcomes related to genotype, as determined with a pharmacogenetic diagnostic test. When a pharmacogenetic diagnostic test is not available, the ideal study design for co-development of the test and the drug is a three-armed trial. The first arm is a control, either placebo or active control, a second arm is the test compound given without guidance from a pharmacogenetic test, and the third arm is the test compound and test. Another application of pharmacogenetic diagnostics to drug development is to use test results as inclusion and exclusion criteria in clinial trials. This could decrease variability and consequently increase statistical power and reduce the number of study subjects required in a clinical trial.