clinical trials in vulnerable populations

1、ofthesedisparities.Regardlessofthecausethelackofparticipationofthesegroupsinclinicaltrialsraisesimptantquestionsaboutthequalityethicsofclinicalresearch.Thegoalofthisdocumentistodiscusstheevidencereasonsbehinddisparitiesi

2、nclinicaltrialparticipation.Wealsoprovideadiscourseonpotentialmechanismstoaddressdisparitiesinclinicaltrialaccrualincludingtheethicalconsiderationsoffinancialincentivestheimpactofamestringentpolicyreviewprocessfproductap

3、provalfromtheFoodDrugAdministration(FDA)includingadiversitymatewithanassociatedpopulationblackboxwarning.2.EvidenceofdisparityamongracialethnicminitiesThecompositionofminitiesinclinicaltrialshashisticalbeenlow.Between199

4、62002blacksrepresentedonaverage9.3%ofthetotalnumberofenrolleesincancerclinicaltrials[1].Thatnumberpeakedat11%in1996steadilydeclinedto7.9%in2002[1].SimilarlyHispanicsonaveragerepresentedonaverage3.1%ofthetotalnumberofenro

5、lleesincancerclinicaltrialsbetween19962002[1].Notonlyareminitiesunderrepresentedinclinicaltrialsbuttheoverallracialethniccompositionofclinicaltrialsisnotreptedatanacceptablerate.Between19902000only35.1%oftreatmentstudies

6、amongcancerclinicaltrialsreptedraceethnicity[2].Thisnumberincreasedto51.6%from2001thru2010butthepercentageofblacksincludedintheanalysisftheseconddecadedecreasedby42%[2].Thelackofdiversitygoesbeyondraceethnicity.Similartr

7、endsarefoundinwomenwheretheyonlyrepresented26.5%ofthepopulationinpreventionstudiesbetween20012010[2].Thedisparityinclinicaltrialparticipationisnotlimitedtocancerclinicaltrialsthescientificimpactcanbesignificantintermsofo

8、utcomes.AfricanAmericansaredisproptionatelyaffectedbyhepatitisCvirus(HCV)intheUnitedStatesHCVinfectionistheleadingcauseofcirrhosishepatocellularcarcinomathemostcommonindicationflivertransplantationintheUnitedStates[3].Al

9、thoughAfricanAmericanscompriseapproximately13%oftheUSpopulationtheymakeupapproximately23%ofAmericanswithhepatitisC[4].TherateofapositiveHCVantibodytestwashigherinblacksthaninwhites(3.2%versus1.5%)blackmenhadhigherratesof

10、infectionwiththehighestprevalencerate(9.8%)amongblackmenages40–49years[56].HCVtreatmenthasundergonearapidevolutionintreatmentwiththefirstgenerationproteaseinhibitsreleasedin2011nowmultipledirectactingantiviralsregimenswi

11、thamazingoutcomes[78].WeperfmedametaanalysisofclinicaltrialsonhepatitisCtreatmentbetweenJanuary2000December2011[9]toevaluatetheparticipationofAfricanAmericansinhepatitisCclinicaltrialsgiventhetremendousburdenofthatdiseas

12、ewithinthispopulation.Wereviewed588romizedcontrolledclinicaltrialsonhepatitisCtreatmentwithinterferon2a2bbetweenJanuary2000December2011.Ofthe588reviewed314(53.4%)fitinclusioncriteria[9].Thismetaanalysisshowedthatofthe314

13、RCT’sthatmetsearchcriteriaonly123(39.2%)actuallyreptedrace.WeevaluatedclinicaltrialsinNthAmericanEuropefoundsignificantdifferences.TheclinicaltrialsperfmedinNthAmericaweremelikelytoreptracialdatathanEuropeantrialsalthoug