Can Animal Models of Disease Reliably Inform Human Studies 英文参考文献.docVIP

ResearchinTranslation CanAnimalModelsofDiseaseReliablyInformHuman Studies? H.BartvanderWorp1*,DavidW.Howells2,EmilyS.Sena2,3,MichelleJ.Porritt2,SarahRewell2 ,Victoria O’Collins2,MalcolmR.Macleod3 1DepartmentofNeurology,RudolfMagnusInstituteofNeuroscience,UniversityMedicalCentreUtrecht,Utrecht,TheNetherlands,2NationalStrokeResearchInstitute UniversityofMelbourneDepartmentofMedicine,AustinHealth,Melbourne,Australia,3DepartmentofClinicalNeurosciences,UniversityofEdinburgh,Edinburgh,United Kingdom Animal experiments have contributed muchtoourunderstandingofmechanisms ofdisease,buttheirvalueinpredictingthe effectiveness of treatment strategies in clinical trials has remained controversial [1–3]. In fact, clinical trials are essential becauseanimalstudiesdonotpredictwith sufficient certainty what will happen in humans. In a review of animal studies published in seven leading scientific jour- nalsofhighimpact,aboutone-thirdofthe studies translated at the level of human randomised trials, and one-tenth of the interventions,weresubsequentlyapproved for use in patients [1]. However, these were studies of high impact (median citation count, 889), and less frequently citedanimalresearchprobablyhasalower likelihood of translation to the clinic. De- pendingonone’sperspective,thisattrition rate of 90% may be viewed as either a failure or as a success, but it serves to illustrate the magnitude of the difficulties in translation that beset even findings of highimpact. LinkedResearchArticle understudy. Forpractical orcommercial purposes, the designs of some clinical trials havealso failed toacknowledge the limitations ofefficacy observed inanimal studies, for example by allowing therapy at later time points when the window of opportunity has passed [10,11]. Second- ly, the failure of apparently promising interventions to translate to the clinic may also be caused by inadequate ani- mal data and overoptimistic conclusions about efficacy drawn from methodologi- cally flawed anim