One of the issues facing those wishing to implement these approaches is identifying variants for which a change from routine dosing would be recommended for specific drugs. Early adopter programs generated lists of actionable variants by internal review of extant data, but the task has now been made easier by the Clinical Pharmacogenomics Implementation Consortium (CPIC) that publishes specific drug-genotype guidelines on which genotypes, or in some cases diplotypes, alter protein function and thus merit changes from routine drug dosing.61 CPIC specifically avoids the question of whether patients should be genotyped but rather examines the question that if a genotype result is available, what actions should be considered. Implementation recommendations are made based on multiple types of evidence, such as whether a drug is metabolized exclusively by a single pathway, what the clinical consequences of unusually high or low concentrations of parent drug or metabolite might be, and whether alternate treatment approaches are available.
