title: Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.
abstract: Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.
authors.affiliation: VA Long Beach Medical Center, School of Medicine, University of California, Irvine, Long Beach, CA, USA. m.vural.ozdemir@gmail.com
authors.forename: Vural
authors.initials: V
authors.lastname: Ozdemir
authors.forename: Bryn
authors.initials: B
authors.lastname: Williams-Jones
authors.forename: Janice E
authors.initials: JE
authors.lastname: Graham
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Gripeos
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Glatt
authors.forename: Robert H
authors.initials: RH
authors.lastname: Friis
authors.forename: Christopher
authors.initials: C
authors.lastname: Reist
authors.forename: Sandor
authors.initials: S
authors.lastname: Szabo
authors.forename: James B
authors.initials: JB
authors.lastname: Lohr
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D035843:Biomedical Research / Q000941:ethics / Q000379:methods / Q000592:standards; D017277:Drug Approval / Q000379:methods* / Q000706:statistics & numerical data; D005826:Genetics, Medical / Q000379:methods* / Q000639:trends; D006801:Humans; D033183:Interdisciplinary Communication; D010597:Pharmacogenetics / Q000941:ethics / Q000379:methods* / Q000639:trends; D010601:Pharmacology, Clinical / Q000379:methods; D010641:Phenotype; D011640:Public Policy; D012107:Research Design; D014481:United States