個人房屋租賃合同書規(guī)范標(biāo)準(zhǔn)課件_第1頁
個人房屋租賃合同書規(guī)范標(biāo)準(zhǔn)課件_第2頁
個人房屋租賃合同書規(guī)范標(biāo)準(zhǔn)課件_第3頁
個人房屋租賃合同書規(guī)范標(biāo)準(zhǔn)課件_第4頁
個人房屋租賃合同書規(guī)范標(biāo)準(zhǔn)課件_第5頁
已閱讀5頁，還剩51頁未讀， 繼續(xù)免費閱讀

下載本文檔

版權(quán)說明：本文檔由用戶提供并上傳，收益歸屬內(nèi)容提供方，若內(nèi)容存在侵權(quán)，請進行舉報或認(rèn)領(lǐng)

文檔簡介

JointMeetingoftheArthritisandDrugSafetyandRiskManagementAdvisoryCommittees

February16-18,2005P-1JointMeetingoftheArthritisLeonardM.Baum,RPhVicePresident,RegulatoryAffairsBayerHealthCareConsumerCareDivisionP-2LeonardM.Baum,RPhVicePresiAgendaRegulatoryOverviewNaproxenADAPTTrial SafetyEvaluationClinicalPharmacologyClinicalStudiesPostmarketingSurveillanceObservationalStudiesConclusions3AgendaRegulatoryOverview3Roche/BayerPresentersandRespondersPresenters:

LeonardM.Baum,RPhVicePresident,RegulatoryAffairsBayerHealthCareMartinH.Huber,M.D.VicePresident,GlobalHeadDrugSafetyRiskManagementHoffmannLa-RocheInc.Responders:SusanSacks,Ph.D. GlobalHead,EpidemiologyHoffmannLa-RocheInc.BharatThakrar,Ph.D.SeniorEpidemiologistHoffmannLa-RocheInc.ErnstWeidmann,M.D.Head,GlobalSafetyBayerHealthCareSteveZlotnick,Pharm.D.Director,MedicalAffairs

BayerHealthCare4Roche/BayerPresentersandResOutsideExpertsKayBrune,M.D.ProfessorandChairmanDepartmentofExperimentalandClinicalPharmacologyandToxicologyFriedrich-AlexanderUniversityErlangen-NurembergIanM.Gralnek,M.D.,MSHSAssistantProfessorofMedicine,DivisionofDigestiveDiseasesDavidGeffenSchoolofMedicineatUCLA5OutsideExpertsKayBrune,M.D.RegulatoryOverview

NaproxenavailableintheUnitedStatessince1976PrescriptioncurrentlymarketedbymultiplemanufacturersforthetreatmentofRA,OA,ankylosingspondylitis,gout,juvenileRA,dysmenorrhea,tendinitis,bursitis,andpainAleve(OTC)approvedin1994

CurrentlymarketedbyBayerHealthCarefortemporaryreliefofminorachesandpains,andforthetemporaryreductionoffeverMultiplegenericversions6RegulatoryOverview6NaproxenNaproxen,anonsteroidalanti-inflammatorydrug(NSAID),belongstothechemicalclasspropionicacidderivativesNaproxenhasanti-inflammatory,analgesicandantipyreticpropertiesNaproxenknowntoinhibitplateletaggregationThemajordifferencesbetweenmembersoftheNSAIDclassarepotencyandpharmacokinetics7NaproxenNaproxen,anonsteroidClassesofNSAIDSSalicylicacidderivativesAspirin,sodiumsalicylate,cholinemagnesiumtrisalicylate,salsalate,diflunisalPara-aminophenolderivativesAcetaminophenIndoleandindeneaceticacidsIndomethacin,sulindacHeteroarylaceticacidsTolmetin,diclofenac,ketorolacPropionicacidsNaproxen,ibuprofen,flurbiprofen,ketoprofen,fenoprofen,oxaprozinAnthranilicacids(fenamates)Mefenamicacid,meclofenamicacidEnolicacidsOxicams(piroxicam,meloxicam)AlkanonesNabumetoneCoxibsCelecoxib,valdecoxib,rofecoxib(withdrawn)Source:GoodmanandGilman’sThePharmacologicalBasisofTherapeutics,10thedition8ClassesofNSAIDSSalicylicaciRelevanceofNaproxenDataThesafetyprofilefornaproxeniswellknownNaproxenisareferencedrugformanyanalgesicclinicaltrialsNaproxenandothernon-selectiveNSAIDs,areimportanttreatmentoptionsforabroadrangeofpatientsandconditions9RelevanceofNaproxenDataTheNaproxenExposureData(RxandOTC)550,000,000coursesoftherapy*110,000,000ptsPost-marketing -->80,000ptsObservationalStudies>8,000pts>10,000ptsClinicalTrialsOTCRX*coursesoftherapy(2tabx10days)10NaproxenExposureData(RxandTheADAPTTrialNIHsponsoredstudyBayerprovidednaproxensodiumforinvestigationaluseStudyDesignNaproxensodium220mgbidCelecoxib200mgbidPlaceboPatientPopulation2400patients,age70yearsorolder,forpreventionofAlzheimer’sdiseaseStudyDurationBeganin2001,plannedfor7years,suspendedafter3yearsSources:NIHNewsDec20,2004;WFeb1,2005,writtenbyWoloshinSetal.11TheADAPTTrialSources:NIHNePubliclyReportedEventsLeadingtotheSuspensionofADAPT

DSMBreviewonDec.10,2004didnotrecommendstoppingthestudyTheAPCstudywassuspendedduetoindicationsofanincreaseincardiovascularandcerebrovascularriskofcelecoxibvs.placebo(Dec.17,2004)NIAannouncedADAPTtrialsuspension(Dec.20,2004)Informationreleasedtopublicbystudygroup,werebasedonpreliminaryfindings,notthroughpeer-reviewedjournalsSources:CelebrexNewsReleaseDec17,2004;NIHNewsDec20,2004;WFeb1,2005,writtenbyWoloshinSetal.12PubliclyReportedEventsLeadiSummaryNaproxenisanon-selectiveCOX-1/COX-2inhibitorWidelyusedEstablishedsafetyprofileReferencestandardUnadjudicatedpreliminaryfindingsofADAPTneedstobelookedatincontextofthewidebodyofdataonnaproxen13SummaryNaproxenisanon-selecMartinH.Huber,MDGlobalHead,DrugSafetyHoffmann-LaRocheInc.P-14MartinH.Huber,MDGlobalHeadSafetyEvaluationClinicalPharmacologyClinicalStudiesPost-MarketingSafetySurveillancePost-MarketingClinicalStudiesObservationalStudies15SafetyEvaluationClinicalPharPharmacologicalDifferencebetweenNaproxenandCOX-2InhibitorsNaproxenisanon-selectiveCOX-1/COX-2inhibitorNaproxenisknowntoinhibitplateletaggregationandthus,isnotexpectedtohaveanincreasedriskofmyocardialinfarction16PharmacologicalDifferencebetClinicalTrialsandPost-MarketingSurveillanceClinicaltrialsintheprescriptionandOTCnaproxenNDAsdidnotprovideanyevidenceofanincreasedriskofmyocardialinfarctionorstrokeAreviewofpostmarketingsurveillancedatashowednosignalforMIorcerebrovascularaccidentwithexposurestoprescriptionnaproxenofmorethan110,000,000patientsAreviewOTCpostmarketingsurveillancedatadidnotidentifyasignalforMIorCVAwithanestimateof550,000,000coursesoftherapy17ClinicalTrialsandPost-MarkeProportionalReportingRate(PRR)EventPRRSignificance(Pvalue)Ischemiccoronaryarterydisorders(high-levelterm)0.16<0.05MI(preferredterms)0.18<0.05CNShemorrhagesandcerebrovascularaccidents(highlevelterm)0.16<0.05Source:EvansSetal.PharmacoepidemiologyandDrugSafety2001;10:483-8618ProportionalReportingRate(PPost-MarketingClinicalTrialsVIGORRandomizedRApatients≥50yo(or≥40yoandreceivinglong-termglucocorticoidtherapy)intoeitherrofecoxib50mgqd(N=4,047)ornaproxen500mgbid(N=4,029)OverallrateofcardiovasculareventsreportedinassociationwithnaproxenisconsistentwiththatexpectedinthispopulationMI:Rofecoxib(0.4%)vs.naproxen(0.1%)Ischemiccerebrovascularevents:0.2%inbotharmsSource:BombardierCetal.NEJM2000;343:1520-819Post-MarketingClinicalTrialsPost-MarketingClinicalTrialsTARGETRandomizedOApatients≥50yointoeitherlumiracoxib400mgqd(N=9,156),naproxen500mgbid(N=4,754)oribuprofen800mgtid(N=4,415)NaproxenarmshowedlowerratesforcerebrovasculareventsandMI:Stroke:Lumiracoxib(0.34%)vs.naproxen(0.25%)Ischemicstroke:Lumiracoxib(0.32%)vs.naproxen(0.23%)Hemorrhagicstroke:0.02%inbotharmsAcuteMI:Lumiracoxib(0.38%)vs.naproxen(0.23%)Source:FarkouhMEetal.Lancet2004;364:675-8420Post-MarketingClinicalTrialsPost-MarketingClinicalTrialsTARGET(cont.)RateofMIeventswaslowerfornaproxenthanibuprofen,usinglumiracoxibasthereferencepointforbothstudiesEvent*LumiracoxibIbuprofenCVdeath0.18%0.23%AllMI0.11%0.16%Stroke0.18%0.20%Source:FarkouhMEetal.Lancet2004;364:675-84*GiveninpercentofpatientswithconfirmedorprobablecardiovascularandcerebrovasculareventsLumiracoxibNaproxen0.23%0.17%0.38%0.21%0.34%0.25%21Post-MarketingClinicalTrialsAdditionalPost-MarketingClinicalTrialsAlzheimer’sTrialRandomizedmildtomoderateADpatients(meanage:74yo)intoeitherrofecoxib25mgqd,naproxensodium220mgbid,orplaceboSource:AisenPSetal.JAMA2003;289:2819-26EventsPlacebo(n=111)Naproxen(N=118)Rofecoxib(N=122)Death112MI103Stroke/TIA13322AdditionalPost-MarketingClinTrialswithCelecoxib

Pooledanalysisof41celecoxibclinicaltrials(Whiteetal)2271naproxenpatients1non-fatalstroke1fatalstroke2non-fatalMIsNaproxen(relativetocelecoxib):4/393(1.01per100patientyears)Celecoxib(relativetoNSAIDs):56/4,969(1.13per100patientyears)Placebo(relativetocelecoxib):3/200(1.5per100patientyears)ThereisnoevidenceofanincreasedriskofMIorstrokecomparedtoeithercelecoxiborplaceboSource:Whiteetal.AmJCardiology2003;92:411-1823TrialswithCelecoxib PooledaObservationalStudies

CasecontrolstudiesandretrospectivecohortstudiescanbeperformedinashorterperiodoftimeOpportunitytodetect/evaluaterelativelyinfrequenteventsReflect“realworld”useofthedrugMoreheterogeneouspopulationsConcomitantmedications,concurrentillnessesValueofobservationalstudiesincreaseswhenthesestudiesaredoneinmultiplepopulationsSource:StromB,Pharmacoepidemiology2000;WileyandSons24ObservationalStudies CaseconSummaryofobservationalstudiesofnaproxenandMISource:Junietal.Lancet2004;364:2021-2925SummaryofobservationalstudiSensitivityAnalysisofObservationalStudiesMeta-analysisincludedmultiplestudiesfromsamedatabasesPerformedanalysisincludingonlyonestudyfromGPRDandonestudyfromTennesseeMedicaidExcludedJick,Watson,SchliengerstudieswithGPRDandRay(Lancet2002,359:118-23)studywithTennesseeMedicaidResultingpooledRR:0.87(0.72-1.03)NomaterialchangeinconclusionsofJunietal.26SensitivityAnalysisofObservSummaryAreviewoftheobservationalstudiesshowsnoincreasedriskofMIwithnaproxenAreviewofthepostmarketingsurveillancedatashowsnosignalforMIorcerebrovasculareventsThepublishedclinicaltrialsdonotprovideevidenceofanincreasedriskofMIorcerebrovasculareventsUnadjudicatedpreliminaryfindingsofADAPTareinconsistentwiththeknowndataandpharmacologicpropertiesofnaproxen27SummaryAreviewoftheobservaConclusionsThevastmajorityofdatacollectedforover30yearsindicatesnosignalfornaproxenandmyocardialinfarctionorcerebrovascularaccidents.NaproxenRxandAleveOTCremainsafeandeffectiveNaproxenremainsanimportanttreatmentoptionforpatients28ConclusionsThevastmajorityoJointMeetingoftheArthritisandDrugSafetyandRiskManagementAdvisoryCommittees

February16-18,2005P-29JointMeetingoftheArthritisLeonardM.Baum,RPhVicePresident,RegulatoryAffairsBayerHealthCareConsumerCareDivisionP-30LeonardM.Baum,RPhVicePresiAgendaRegulatoryOverviewNaproxenADAPTTrial SafetyEvaluationClinicalPharmacologyClinicalStudiesPostmarketingSurveillanceObservationalStudiesConclusions31AgendaRegulatoryOverview3Roche/BayerPresentersandRespondersPresenters:

LeonardM.Baum,RPhVicePresident,RegulatoryAffairsBayerHealthCareMartinH.Huber,M.D.VicePresident,GlobalHeadDrugSafetyRiskManagementHoffmannLa-RocheInc.Responders:SusanSacks,Ph.D. GlobalHead,EpidemiologyHoffmannLa-RocheInc.BharatThakrar,Ph.D.SeniorEpidemiologistHoffmannLa-RocheInc.ErnstWeidmann,M.D.Head,GlobalSafetyBayerHealthCareSteveZlotnick,Pharm.D.Director,MedicalAffairs

BayerHealthCare32Roche/BayerPresentersandResOutsideExpertsKayBrune,M.D.ProfessorandChairmanDepartmentofExperimentalandClinicalPharmacologyandToxicologyFriedrich-AlexanderUniversityErlangen-NurembergIanM.Gralnek,M.D.,MSHSAssistantProfessorofMedicine,DivisionofDigestiveDiseasesDavidGeffenSchoolofMedicineatUCLA33OutsideExpertsKayBrune,M.D.RegulatoryOverview

NaproxenavailableintheUnitedStatessince1976PrescriptioncurrentlymarketedbymultiplemanufacturersforthetreatmentofRA,OA,ankylosingspondylitis,gout,juvenileRA,dysmenorrhea,tendinitis,bursitis,andpainAleve(OTC)approvedin1994

CurrentlymarketedbyBayerHealthCarefortemporaryreliefofminorachesandpains,andforthetemporaryreductionoffeverMultiplegenericversions34RegulatoryOverview6NaproxenNaproxen,anonsteroidalanti-inflammatorydrug(NSAID),belongstothechemicalclasspropionicacidderivativesNaproxenhasanti-inflammatory,analgesicandantipyreticpropertiesNaproxenknowntoinhibitplateletaggregationThemajordifferencesbetweenmembersoftheNSAIDclassarepotencyandpharmacokinetics35NaproxenNaproxen,anonsteroidClassesofNSAIDSSalicylicacidderivativesAspirin,sodiumsalicylate,cholinemagnesiumtrisalicylate,salsalate,diflunisalPara-aminophenolderivativesAcetaminophenIndoleandindeneaceticacidsIndomethacin,sulindacHeteroarylaceticacidsTolmetin,diclofenac,ketorolacPropionicacidsNaproxen,ibuprofen,flurbiprofen,ketoprofen,fenoprofen,oxaprozinAnthranilicacids(fenamates)Mefenamicacid,meclofenamicacidEnolicacidsOxicams(piroxicam,meloxicam)AlkanonesNabumetoneCoxibsCelecoxib,valdecoxib,rofecoxib(withdrawn)Source:GoodmanandGilman’sThePharmacologicalBasisofTherapeutics,10thedition36ClassesofNSAIDSSalicylicaciRelevanceofNaproxenDataThesafetyprofilefornaproxeniswellknownNaproxenisareferencedrugformanyanalgesicclinicaltrialsNaproxenandothernon-selectiveNSAIDs,areimportanttreatmentoptionsforabroadrangeofpatientsandconditions37RelevanceofNaproxenDataTheNaproxenExposureData(RxandOTC)550,000,000coursesoftherapy*110,000,000ptsPost-marketing -->80,000ptsObservationalStudies>8,000pts>10,000ptsClinicalTrialsOTCRX*coursesoftherapy(2tabx10days)38NaproxenExposureData(RxandTheADAPTTrialNIHsponsoredstudyBayerprovidednaproxensodiumforinvestigationaluseStudyDesignNaproxensodium220mgbidCelecoxib200mgbidPlaceboPatientPopulation2400patients,age70yearsorolder,forpreventionofAlzheimer’sdiseaseStudyDurationBeganin2001,plannedfor7years,suspendedafter3yearsSources:NIHNewsDec20,2004;WFeb1,2005,writtenbyWoloshinSetal.39TheADAPTTrialSources:NIHNePubliclyReportedEventsLeadingtotheSuspensionofADAPT

DSMBreviewonDec.10,2004didnotrecommendstoppingthestudyTheAPCstudywassuspendedduetoindicationsofanincreaseincardiovascularandcerebrovascularriskofcelecoxibvs.placebo(Dec.17,2004)NIAannouncedADAPTtrialsuspension(Dec.20,2004)Informationreleasedtopublicbystudygroup,werebasedonpreliminaryfindings,notthroughpeer-reviewedjournalsSources:CelebrexNewsReleaseDec17,2004;NIHNewsDec20,2004;WFeb1,2005,writtenbyWoloshinSetal.40PubliclyReportedEventsLeadiSummaryNaproxenisanon-selectiveCOX-1/COX-2inhibitorWidelyusedEstablishedsafetyprofileReferencestandardUnadjudicatedpreliminaryfindingsofADAPTneedstobelookedatincontextofthewidebodyofdataonnaproxen41SummaryNaproxenisanon-selecMartinH.Huber,MDGlobalHead,DrugSafetyHoffmann-LaRocheInc.P-42MartinH.Huber,MDGlobalHeadSafetyEvaluationClinicalPharmacologyClinicalStudiesPost-MarketingSafetySurveillancePost-MarketingClinicalStudiesObservationalStudies43SafetyEvaluationClinicalPharPharmacologicalDifferencebetweenNaproxenandCOX-2InhibitorsNaproxenisanon-selectiveCOX-1/COX-2inhibitorNaproxenisknowntoinhibitplateletaggregationandthus,isnotexpectedtohaveanincreasedriskofmyocardialinfarction44PharmacologicalDifferencebetClinicalTrialsandPost-MarketingSurveillanceClinicaltrialsintheprescriptionandOTCnaproxenNDAsdidnotprovideanyevidenceofanincreasedriskofmyocardialinfarctionorstrokeAreviewofpostmarketingsurveillancedatashowednosignalforMIorcerebrovascularaccidentwithexposurestoprescriptionnaproxenofmorethan110,000,000patientsAreviewOTCpostmarketingsurveillancedatadidnotidentifyasignalforMIorCVAwithanestimateof550,000,000coursesoftherapy45ClinicalTrialsandPost-MarkeProportionalReportingRate(PRR)EventPRRSignificance(Pvalue)Ischemiccoronaryarterydisorders(high-levelterm)0.16<0.05MI(preferredterms)0.18<0.05CNShemorrhagesandcerebrovascularaccidents(highlevelterm)0.16<0.05Source:EvansSetal.PharmacoepidemiologyandDrugSafety2001;10:483-8646ProportionalReportingRate(PPost-MarketingClinicalTrialsVIGORRandomizedRApatients≥50yo(or≥40yoandreceivinglong-termglucocorticoidtherapy)intoeitherrofecoxib50mgqd(N=4,047)ornaproxen500mgbid(N=4,029)OverallrateofcardiovasculareventsreportedinassociationwithnaproxenisconsistentwiththatexpectedinthispopulationMI:Rofecoxib(0.4%)vs.naproxen(0.1%)Ischemiccerebrovascularevents:0.2%inbotharmsSource:BombardierCetal.NEJM2000;343:1520-847Post-MarketingClinicalTrialsPost-MarketingClinicalTrialsTARGETRandomizedOApatients≥50yointoeitherlumiracoxib400mgqd(N=9,156),naproxen500mgbid(N=4,754)oribuprofen800mgtid(N=4,415)NaproxenarmshowedlowerratesforcerebrovasculareventsandMI:Stroke:Lumiracoxib(0.34%)vs.naproxen(0.25%)Ischemicstroke:Lumiracoxib(0.32%)vs.naproxen(0.23%)Hemorrhagicstroke:0.02%inbotharmsAcuteMI:Lumiracoxib(0.38%)vs.naproxen(0.23%)Source:FarkouhMEetal.Lancet2004;364:675-8448Post-MarketingClinicalTrialsPost-MarketingClinicalTrialsTARGET(cont.)RateofMIeventswaslowerfornaproxenthanibuprofen,usinglumiracoxibasthereferencepointforbothstudiesEvent*LumiracoxibIbuprofenCVdeath0.18%0.23%AllMI0.11%0.16%Stroke0.18%0.20%Source:FarkouhMEetal.Lancet2004;364:675-84*GiveninpercentofpatientswithconfirmedorprobablecardiovascularandcerebrovasculareventsLumiracoxibNaproxen0.23%0.17%0.38%0.21%0.34%0.25%49Post-MarketingClinicalTrialsAdditionalPost-MarketingClinicalTrialsAlzheimer’sTrialRandomizedmildtomoderateADpatients(meanage:74yo)intoeitherrofecoxib25mgqd,naproxensodium220mgbid,orplaceboSource:AisenPSetal.JAMA2003;289:2819-26EventsPlacebo(n=111)Naproxen(N=118)Rofecoxib(N=122)Death112MI103Stroke/TIA13350AdditionalPost-MarketingClinTrialswithCelecoxib

Pooledanalysisof41celecoxibclinicaltrials(Whiteetal)2271naproxenpatients1non-fatalstroke1fatalstroke2non-fatalMIsNaproxen(relativetocelecoxib):4/393(1.01per100patientyears)Celecoxib(relativetoNSAIDs):56/4,969(1.13p

溫馨提示

  • 1. 本站所有資源如無特殊說明，都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請下載最新的WinRAR軟件解壓。
  • 2. 本站的文檔不包含任何第三方提供的附件圖紙等，如果需要附件，請聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
  • 3. 本站RAR壓縮包中若帶圖紙，網(wǎng)頁內(nèi)容里面會有圖紙預(yù)覽，若沒有圖紙預(yù)覽就沒有圖紙。
  • 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
  • 5. 人人文庫網(wǎng)僅提供信息存儲空間，僅對用戶上傳內(nèi)容的表現(xiàn)方式做保護處理，對用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯，并不能對任何下載內(nèi)容負(fù)責(zé)。
  • 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容，請與我們聯(lián)系，我們立即糾正。
  • 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時也不承擔(dān)用戶因使用這些下載資源對自己和他人造成任何形式的傷害或損失。

評論

0/150

提交評論