Fulfilling the Promise of Personalized Medicine Systematic Review and Field Synopsis of Pharmacogenetic Studies 英文参考文献.docVIP

FulfillingthePromiseofPersonalizedMedicine? SystematicReviewandFieldSynopsisof PharmacogeneticStudies MichaelV.Holmes1,TinaShah1,ChristineVickery1,LiamSmeeth2,AroonD.Hingorani1,3.*, JuanP.Casas2. * 1Centre for Clinical Pharmacology, University College London, London, United Kingdom, 2Department of Epidemiology and Population Health, London School of HygieneandTropicalMedicine,London,UnitedKingdom,3DepartmentofEpidemiology,UniversityCollegeLondon,London,UnitedKingdom Abstract Background:Studiesofthegeneticbasisofdrugresponsecouldhelpclarifymechanismsofdrugaction/metabolism,and facilitatedevelopmentofgenotype-basedpredictivetestsofefficacyortoxicity(pharmacogenetics). Objectives:Weconductedasystematicreviewandfieldsynopsisofpharmacogeneticstudiestoquantifythescopeand qualityofavailableevidenceinthisfieldinordertoinformfutureresearch. Data Sources: Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/reviewarticlesandU.S.FoodandDrugAdministrationwebsiteofapprovedpharmacogenetictests. Study Eligibility Criteria, Participants, and Intervention Criteria: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. StudyAppraisalandSynthesisMethods:Studycharacteristicsanddatareportedinabstractswererecorded.Wefurther analysedfulltextfromarandom10%subsetofarticlesspanningthedifferentsubclassesofstudy. Results:From102,264Medlinehitsand1,641articlesfromothersources,weidentified1,668primaryresearcharticles(1987 to2007,inclusive).Ahighproportionofremainingarticleswerereviews/commentaries(ratioofreviewstoprimaryresearch approximately 25:1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles,whichdespitesmallsamplesizes(median93[IQR40–222])withnotrendtoani