藥物經濟學基本概念與基本研究方法簡介

藥物經濟學基本概念

與基本研究方法簡介張延軍2015年7月3日上海概要衛(wèi)生經濟學和健康結果研究，HealthEconomicsandOutcomesResearch(HEOR)衛(wèi)生技術評估,HealthTechnologyAssessment(HTA)藥物經濟學，Pharmacoeconomics視角(perspective)、成本分類、時間范圍(timehorizon)、貼現(xiàn)(discounting)、敏感性分析藥物經濟學研究的基本方法成本最小化分析,cost-minimizationanalysis(CMA)成本-效果分析,cost-effectivenessanalysis(CEA)成本-效用分析,cost-utilityanalysis(CUA)成本-效益分析,cost-benefitanalysis(CBA)疾病成本研究,costofillness預算影響分析,budgetimpactanalysis(BIA)臨床試驗(RCT)、數據庫(database)決策樹,decisiontree;馬可夫模型,MarkovmodelTreeAge,MSExcel,R...合理用藥與藥品價值合理用藥：安全、有效、經濟臨床價值+經濟價值安全性療效（臨床試驗、臨床實踐）成本-效果比Demonstratingproductvalue安全性:Benefit/risk(harm)eg,苯丙醇胺（PPA）、羅非昔布（萬絡，Vioxx）經濟性，Cost-effectiveness/journals/cpm/2008/04-April%202008/023-IMS.pdfDemonstratingproductvalue–cont’dEfficacy:療效（隨機對照臨床試驗，RCT）“Caninterventionworkintheidealstudysetting?”Effectiveness:效果（真實世界數據、證據）“Doesitwork,generalizedtoreal-worldsettingsandappliedtoindividualpatients?”Cost-effectiveness“Isitworthitandshoulditbepaidfor?”Source:Djulbegovic,B.andA.Paul,Fromefficacytoeffectivenessinthefaceofuncertainty:indicationcreepandpreventioncreep.JAMA,2011.305(19):p.2005-6.EBM,HTA,andCERSource:LuceBR,DrummondM,JonssonB,etal.EBM,HTA,andCER:clearingtheconfusion.MilbankQ2010;88:256-76.HealthEconomicsandOutcomesResearchWhyHEORandPE?更加有效地配置有限的衛(wèi)生資源（少花錢，多辦事，辦好事；性價比高）健康結果(Healthoutcomes)：ECHO模型人文結果，又稱健康相關生活質量(HealthRelatedQualityofLife,HRQoL)及患者報告的健康結果(Patient-ReportedOutcomes,PROs)ClinicalOutcomesHumanisticOutcomesEconomicOutcomesHRQoL研究表明在結直腸癌繼發(fā)肝癌患者中，健康相關生活質量(HRQoL)是比CT掃描和腫瘤大小測定都更強及更好的生存預測因素。1HRQoL在慢性髓性白血病(CML)研究中已經成為一個重要的研究興趣。2EarlamS,GloverC,FordyC,BurkeD,Allen-MershTG.Relationbetweentumorsize,qualityoflife,andsurvivalinpatientswithcolorectallivermetastases.JClinOncol1996;14:171–175.Guilhot,J.,etal.,Definitions,methodologicalandstatisticalissuesforphase3clinicaltrialsinchronicmyeloidleukemia:aproposalbytheEuropeanLeukemiaNet.Blood,2012.119(25):p.5963-71.Pharmacoeconomics

Definition藥物經濟學是對藥物治療相對于醫(yī)藥衛(wèi)生系統(tǒng)及社會的成本（和結果）的描述和分析。藥物經濟學研究識別、測量、比較藥品和藥學服務的成本（即消費的資源）和結果。TownsendRJ,PostmarketingDrugResearchandDevelopmentDrugIntellClinPharm,1987:21COSTS($)RXOUTCOMESCosts=costsassociatedw/providingpharmacyproductorserviceRx

=pharmacyproductorserviceOutcomes=outcomeoftheproductorservicePharmacoeconomicsRelationshipofPharmacoeconomicstoOtherResearchPharmacy-relatedclinicalorhumanisticoutcomesresearch

Healthcareeconomics

Pharmaco-economicsWhentodoeconomicevaluation?Source:CoxER,SchafermeyerKW.Chapter18--Pharmacoeconomics.In:McCarthyRL,SchafermeyerKW,eds.IntroductiontoHealthCareDelivery:APrimerforPharmacists.Sudbury,MA:JonesandBartlettPublishers;2007:481-508.成本：

研究視角、分類、貼現(xiàn)社會Society患者Patient醫(yī)院Hospital保險商Insurer政府GovernmentHealthCareProfessionalPerspective藥物經濟學評價可能的研究視角成本(cost)的分類成本分為：直接成本直接醫(yī)療成本(directmedicalcost)直接非醫(yī)療成本(directnon-medicalcost)間接成本(indirectcost)無形成本/隱性成本(intangiblecost)另一成本分類：衛(wèi)生服務部門的成本(coststohealthcaresector)其他部門的成本(coststoothersectors)患者及其家庭的成本(patientandfamilycosts)生產力成本(productivitycosts)視角/角度(perspective)直接醫(yī)療成本(DirectMedicalCosts)Medications藥品Medicationmonitoring藥物監(jiān)測Medicationadministration給藥Patientcounseling&consultations患者咨詢Diagnostictests診斷測試Hospitalizations住院（含ICU）Clinicvisits門診/診所EmergencyDept.visits急診Homemedicalvisits家庭醫(yī)療服務Ambulanceservices救護車直接非醫(yī)療成本(DirectNonmedicalCosts)Travelcoststoreceivehealthcare差旅Nonmedicalassistancerelatedtocondition非醫(yī)療救助，如對殘疾人患者的生活服務等Hotelstaysforpatientorfamilyrelatedtocondition住宿Childcareservicesforchildrenofparents由于父/母患病而對未成年人的監(jiān)護間接成本(IndirectCosts)Nomoneyisexchanged.沒有金錢的交換Lostproductivityforpatient患者失去的生產力Lostproductivityforunpaidcaregiver未支付報酬的護理人員失去的生產力Lostproductivitybecauseofprematuremortality早亡而導致的失去生產力隱性成本(IntangibleCosts)Painandsuffering疼痛和痛苦Fatigue疲乏Anxiety焦慮金錢的時間價值今天借出￥10,000,對方5年后歸還￥10,000Inflation?Deflation?Stagflation?通貨膨脹/通貨緊縮/滯脹（經濟停滯、高通脹）Discountrate（貼現(xiàn)率）將不同年份的金錢價值轉化為當前價值“如果疾病治療的時間超過一年，就應該對成本進行貼現(xiàn)。貼現(xiàn)率（DiscountRate）一般為市場利率，建議采用一年期的國家指導利率或國債利率進行貼現(xiàn)。貼現(xiàn)率應該進行敏感性分析，波動范圍建議在0%~8%之間?！?國家統(tǒng)計局發(fā)布的CPI及GDP折算Source:中國藥物經濟學評價指南.http:///PEguidelines/source/China-Guidelines-for-Pharmacoeconomic-Evaluations_2011_Chinese.pdfAnExampleTotalhospitalcostsin2004$22,538.10Convertingto2007USDMedicalComponentofCPI2004=4.4% 2005=4.3%2006=4.1% 2007=4.1%Formula$???in2007USD藥物經濟學研究的基本方法PharmacoeconomicMethodologiesMethodofAnalysisCostOutcomeMeasurementCostminimization$AssumedequalCostbenefit$$/$(netbenefit)Costeffectiveness$$/outcome-goalCostutility$$/qualityoflifeindex[Quality-AdjustedLifeYear(QALY)]質量調整生命年(QALY)QALY等于剩余的生命年數乘以這段時間內的健康效用值綜合反映生命的“質”和“量”的變化計算QALY的關鍵在健康效用值的測量上健康效用值的測量工具：直接間接：歐洲五維健康量表（EuroQol-5Dimensions，EQ-5D）、短表36（shortform36,SF-36）及疾病專用量表等HRQoL/PROHRQoL包括對身體、社交、職業(yè)、心理、情緒等方面的健康調查。HRQoL是而且應當是患者報告的健康情況，而不能是由醫(yī)藥衛(wèi)生專業(yè)人員通過她/他的主觀判斷而進行的測定。Patient-ReportedOutcomeMeasures:UseinMedicalProductDevelopmenttoSupportLabelingClaimshttp:///downloads/Drugs/Guidances/UCM193282.pdfHRQoL通用和特定疾病專用量表SF-36,EQ-5D;FunctionalAssessmentofCancerTherapy-General(FACT-G),CancerTherapySatisfactionQuestionnaire(CTSQ),MDAndersonSymptomInventory-CML(MDASI-CML)“當沒有相應中文版量表時應按規(guī)定先進行漢化，漢化完后才可以使用。漢化時需要依據翻譯（Translation）、回譯（BackTranslation）、文化調試（CultureAdjustment）和跨文化驗證（Cross-cultureValidation）等步驟來進行”(Ref:中國藥物經濟學評價指南.2011)http:///PEguidelines/index.aspApproachestoConductingPEStudiesRandomizedcontrolledtrialsDecisionanalysisInformationpooledfrommultiplesources(e.g.,RCT,NIR,expertopinion,…)Twomodels:decisiontree&MarkovmodelRetrospectiveanalysis(claimsdatabase)InformationsourcesSystematicreview,meta-analysis(Lancet,JAMA,BMJ,AnnInternMed...)(RC)T(NEJM...)Cohortstudy,case-controlstudy(database...)NIR=non-interventionalresearch,orobservationalresearch（非干預性研究，觀察性研究）Caseseries,casereportExpertopinions/wiki/Research_designDatabasesMEPS(MedicalExpenditurePanelSurvey,/mepsweb/)NHANES(NationalHealthandNutritionExaminationSurvey)Claimsdatabases(MarketScan?，中國醫(yī)保數據...)GPRD(GeneralPracticeResearchDatabase,1994–2012,followedbyCPRD,ClinicalPracticeResearchDatalink)臺灣全民健康保險（全民健保）研究數據庫(Taiwan’snationalhealthinsuranceresearchdatabase,NHIRD)*ElectronicHealth/MedicalRecord(EHR/EMR)NationalDrugCode(NDC),ICD-9/ICD-10,CurrentProceduralTerminology(CPT)...ChenYC,WuJC,ChenTJ,WetterT.Apubliclyavailabledatabaseacceleratesacademicproduction.BMJ.2011;342:d637.Databases–cont’dDeidentified(identifier?)InstitutionalReviewBoard(IRB)/EthicalCommitteereviewandapprovalSAS,SPSS,Stata...Demographic(age,gender),socioeconomic(employment,income,healthinsurance)datasetsMedicalconditions,healthservices(outpatientvisit,emergencyroomvisit,hospitalization,expense),pharmacydatasetsDocumentation,codebook...DecisiontreeSource:CoxER,SchafermeyerKW.Chapter18--Pharmacoeconomics.In:McCarthyRL,SchafermeyerKW,eds.IntroductiontoHealthCareDelivery:APrimerforPharmacists.Sudbury,MA:JonesandBartlettPublishers;2007:481-508.Decisiontree–cont’dDrugCPhysicianofficevisitSour