肺癌发病机制及防治对策

肺癌发病机制及防治对策

1.U2004范围

内部化是最常见的类型的内部化，也是授权的领域的内部化。

Accordingtohistologycategories,NSCLCisdividedintosquamousandnon-

squamouscel1carcinoma,andthelatteraccountsforalargepercentageof

totalcases.Boththeregimenanditsefficacyvarydependingonhistology

categories.Onlythreecytotoxicagents,gemcitabine(GEM),pemetrexed(PEM)and

docetaxel(DOC),arerecommendedbytheNationalComprehensiveCancer

Network(NCCN)guidelinesforsecond-1inechemotherapyinnon-squamousNSCLC(ns-

NSCLC)

Meanwhile,thediseaseburdenofcancerisexpect2dtoincrease

worldwide,especiallyindevelopingcountries

Inthepresentstudy,weaimedtocomparetheeconomicoutcomesofsecond-line

chemotherapystrategiesforadvancedns-NSCLCfromtheperspectiveofthe

Chinesehealthcaresystem.

2.杏仁杏仁

2.1.面向中方/回配的whichrellingingwrt和

khitchratisongrage“两g”.

Astate-transitionMarkovmodelbasedontheclinicalsettinginChinaand

NCCNguidelinesforNSCLCwasconstructedtosimulatethediseaseprogression

ofpatientswithadvancedns-NSCLC

Inthisstudy,wefocusedondirectmedicalcostsfromtheperspectiveofthe

ChineseHealthCareSystem.Thetimehorizonwassetto6years,whichreflected

thenatureofdiseaseprognosis.Morethan99%ofpatientsdiedintheanalysis

timeframe.Theprimaryoutcomesincludedlife-yearsgained(LYGs),quality-

adjustedlifeyears(Q/\LYs),andcost.CostandQALYswerediscountedat.an

annualrateof3%,inlinewithChineseguidelinesforpharmacogenomics

evciluations.Incrementalcosteffectivenessrcitios(ICERs)werecalculatedasa

costperadditionalQ?\LYgained.The3Xpercapitagrossdomestic

product(GDP)ofChinain2018($29383)wasusedasthewillingness-to-

pay(WTP)threshold,asoneofthemostoftenusedmethodtomeasurethecost-

effectivenessoftreatmentstrategies

2.2.服务平台相关程序

Weperformedaliteraturesearchtoidentifyclinicaltrialsonsecond-line

chemotherapyinpatientswithns-NSCLCusingfourelectronic

databases:PubMcd,EMBASE,theCochraneLibrary,andtheNationalLibraryof

ScienceandTechnology.

Basedonthesurvivaldatafromclinicaltrials,thedecliningexponential

approximationoflifeexpectancy(DEALE)wasemployedtocalculatethe

transitionprobabilitiesofeachhealthstateduringthecycles

Transitionprobabi1ity=1n(surviva1rate)/mediantimeinprogression

andadjustedtofitthetreatmentperiods.

2.3.patitionmortiece人pysiphen体pysiphenge,khsiphen行动国

J^l,lacysirapcrenges.cyles国际专家，khratchratchs.krace.关于

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Thedirectmedicalcostsincludedchemotherapy(costsofmedicationand

administration),AEtreatment,examination(CTscanandlaboratorytests),and

bestsupportcare(BSC),sincetheindirectcostswereusual]yuncertainorlost

Thecostcalculationofpre-medication,CTscan,andlaboratorytestswasbased

onthedruglabelsandNCCNguideline

Laboratoryexaminationsforpatientsconsistedofacompletebloodcount,a

biochemicalanalysis,andNSCLC-relatedtumormarkers,whichwereperformedat

eachcycleaccordingtotheNCCNguideline.ACTscanwasperformedeverytwo

cycles.Alltheexaminationsmentionedaboveshouldberepeatedevery3

months.Thecompletebloodcountwasdetectedperdaywhengradefour

myelosuppressionoccurred.

BasedontheassumptionthatpatientsonlyacceptedBSCinthePSstate,only

thecostofthePSstateaccountedfortheexpenditureforBSC,approximately

US$14159peryear

Al1costswereconvertedintoUSdollarsusingtneaverage2018exchange

rate(CNY6.61=US$1).Al1costparametersareshowninTable2.

2.4.utiliti坚持sofficidingswrafts结果

QALYsandLYGswereemployedastreatmentoutcomesinthisstudy.Thehealth

utilityvaluesofthePFSandPSstateswerederivedfromtheliterature

2.5.sivititivititiviti基因回复突变

asitysensitkivitirivitichisi

Eachkeyparameterwasfittedwitharangeofvaluesandaspecific

distributiontoevaluatethemodelrobustnessbyone-waysensitivityanalysis

andprobabilisticsensitivityemalysis(Table2).One-waysensitivityeinalysis

resultswerepresentedasatornadodiagrambasedontheimpactofeach

variableontheICERoutcomes,withitsrespectiveWTP.Probabilistic

sensitivityanalysis(PSA)wasusedtosimultaneouslyevaluatetheimpactofcill

parameters.AMonteCarlosimulationwith1000iterationsanditsoutcomeswere

presentedbythecost-effectivenessacceptabilitycurve(CEAC)andthescatter

plotofthecosteffeetivenessgraph.

3.影响的神圣迪迪斯运营

3.1.pemga现行年5月，属性基因第4.3・

Theproposedmodelestimatedthecostsandhealtnoutcomesofthedifferent

strategies.Overthe6-yearsofanalysis,totalhealthcarecostswere$5321.02

forGEM,$12143.94forPEM,and$9479.42forDOC.QALYswere0.233,0.417and

0.272forPEM,DOCandGEM,respectively.GEMgainedtheleastQALYswiththe

cheapestexpenditure,whileitwasthemostcost-effectivechemotherapy

strategy(Table3).Conversely,PEMyieldedthegreatestQALYsamongthethree

regimensbutatthehighestcost.RelativetoGEM,theincrementalcostperQALY

gainedbyPEMandDOC($37081.09and$106625.64,respectively)bothexceededthe

WTP($29383),especiallyDOC.

stratestratestratestratestratestratesrratestrategatchingforac

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rowellingsoratestratestratestratestratestratestratestratestra

testratestratestratestratestratestratestratestratestrategatch

ingsoratestrates,whichsot-

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cestracestrates,whichsoracestracestratestrates,kratchingoffic

iciph+pems,kratchings,kratchingofficiciph+pems,kratchings,kra

tchingofficicititoritys,kratchingofficici供给的

s.cools,kratchings,kratchingofficici供给的s.

Withtheprogressiveincreaseinthediseaseeconomicburdenand

morLaliLy,phaiiiiacoeconomicanalysisoflungcancerinChinahasbecomealopic

ofintenseinterest.Sofar,onlyafeweconomicevaluationshavebeenperformed

onadvancedNSCLC

TheresultsshowedthatascomparedwithGEM,overa6-yearhorizon,PEMandDOC

potentiallyguaranteedamoderateimprovementinQALYs(approximatelyO.184and

0.039QALYs,respectively)butsignificantlyincreasedtreatmentcosts($6822.92

and$4158.40,respectively).TheICERsperQALYsgainedfromPEMandDOCas

comparedwithGEMwcrc$37081.09and$106625.64,respectively.BothPEMandDOC

exceededtheWTPthreshold,whichdemonstratedthatGEMwasthemostcost

effectivechemotherapystrategy.IthasbeensuggestedthatPEMhasanegative

pharmacocconomicprofileinanelementaryanalysisemployingtheWTPbasedon

overallGDPofChina.However,inareaswithexcellenteconomicdevelopment,such

asBeijingandShanghai,PEMmaybeamorecost-effectiveoption.So,resultsmay

varyinregionswithextremelyhighorlowGDP.Generally,theproposedmodel

wasrelativelyrobusttosensitivitydetection.

Thecostasdefinedinthepresentanalysismainlycoveredchemotherapy,AE

treatment,examination,andBSC,andchemotherapycostwasthemajorcost

component.Thelengthofstayinaparticularstateexertedasignificant

impactontotalcosts.PatientstreatedwithPEMmightstayinthePFSandPS

stateslongerthanthosetreatedwithGEM,whichcontributestohighermedical

expenditure.ThedrugcostofPEMwasdoublecomparedwiththatofGEM,which

wastheprimarydriverofthehighcostofthePEMstrategy.Asapotential

option,decreasingthepriceofPEMorgivingadiscountforitmight

significantlydecreasetheICERandimprovethecosteffectivenessofPEM.AE

treatments,whichsignificantlycontributetototalcosts,areobtainedfrom

publicsourceswithintheChineseHealthdatabase

One-waysensitivityanalysisshowedthatthetoptwosensitiveparametersin

PEMandGEMstrategiesweretheBSCcostofPEMandtheuti1ityvalueofPEM

inthePSstate.TheICERsgrowth,rangingfromthelowertotheupper

limit,suggestedthatadecreaseofthesetwoparameterscouldincreasethe

cost-effectivenessofPEM.NomatterhowtheICERsvariedinthemodel,itwas

neverlowerthantheWTP,whichconfirmedtherobastnessofthe

model.Moreover,whencomparingDOCandGEM,themostsensitiveparameter

impactingontheICERwasthetransitionprobabi1ityofthePStodeathof

DOC.Whenitrangedfronthelowertotheupperlimit,theTCERincreased.The

smallertheprobabi1ityofPStodeathindicatedlongerpatientstayinthe

PS,whichresultedinpoorcost-effectivenessofDOC.

TheresultsofthePSAindicatedthatatthethresholdoftheWTP,about

50.2%simulationssupportedthatGEMhadanadditionalbenefitcomparedwith

PEM.TheCEACdemonstratedthatwhentheWTPwasincreased,thecost­

effectivenessprobabilityofGEMwasdecreased.PEMwouldnotbeacost-

effectiveagentuntiltheWTPwasincreasedtoabout$40000.DOCshowedalow

probabilityofbeingacost-effectivestrategyregardlessofthevalueof

WTP.Theresultsuggestedthatthegovernment,suchasdrugpriceadministration

bureau,couldconsiderloweringthepriceofPEM,A'hichwou1dachieveabetter

QALYforcancerpatients.

Oureconomicanalysishasseverallimitations.Firstofall,different

analyticalperspectivesmaygeneratedifferentoutcomes.Inthisstudy,indirect

andnon-medicalcostswereexcludedfromtheanalysis.Infact,incorporating

productivitylossmayincreasetheadditionalburde