title: Should pharmacogenomic studies be required for new drug approval?
abstract: The field of pharmacogenetics has existed since the 1950s, when it was demonstrated that some drug effects could differ substantially among race and ethnic groups, and that some drug metabolizing enzyme activities were inherited. During the 1990s, application of molecular biology to the study of inherited drug-related phenotypes proved the genetic basis of several genetic polymorphisms. Genomic technology has now demonstrated that germline genetic variability among humans is extremely common. The combined weight of proven examples whereby pharmacogenetics affects drugs, and the possibility of even more examples being elucidated in the coming decades, dictates that pharmacogenetics be incorporated into the drug approval process. It is our contention that minimal pharmacogenetic testing should be required for all new drug applications to the Food and Drug Administration (FDA). This would include a requirement for germline DNA to be prospectively collected from all subjects participating in preapproval clinical trials. For drugs that are metabolized by enzymes whose genes have clearly inactivating polymorphisms, clinical trial participants should be genotyped for those polymorphisms.
authors.affiliation: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA. mary.relling@stjude.org
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
mesh_terms: D004247:DNA / Q000235:genetics; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics / Q000331:legislation & jurisprudence* / Q000639:trends*; D010641:Phenotype; D013048:Specimen Handling; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004247:DNA