Different Strategies for the Treatment of Age-Related Macular Degeneration in China: An Economic ...

13 Pages·2016·1.33 MB·English

Hindawi Publishing Corporation
Journal of Ophthalmology
Volume 2016, Article ID 7689862, 12 pages
http://dx.doi.org/10.1155/2016/7689862
Research Article
Different Strategies for the Treatment of Age-Related Macular
Degeneration in China: An Economic Evaluation
BinWu,1JinLi,2HouwenLin,1andHaixiangWu3,4
1MedicalDecisionandEconomicGroup,DepartmentofPharmacy,RenJiHospital,SouthCampus,SchoolofMedicine,
ShanghaiJiaotongUniversity,Shanghai201114,China
2DepartmentofOphthalmology,RenJiHospital,SchoolofMedicine,ShanghaiJiaotongUniversity,Shanghai200127,China
3DepartmentofOphthalmology,Eye&ENTHospital,FudanUniversity,Shanghai200031,China
4ShanghaiKeyLaboratoryofVisualImpairmentandRestoration,Eye&ENTHospital,FudanUniversity,Shanghai200031,China
CorrespondenceshouldbeaddressedtoHaixiangWu;[email protected]
Received7December2015;Revised29March2016;Accepted30March2016
AcademicEditor:BijuB.Thomas
Copyright©2016BinWuetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Purpose.Toassessthecost-effectiveness ofbevacizumab comparedtoranibizumab, verteporfinphotodynamictherapy(PDT),
andusualcareforthetreatmentofage-relatedmaculardegeneration(AMD)inChina.Methods.AMarkovmodelwasdeveloped
accordingtopatientvisualacuity(VA)inthebetter-seeingeye(Snellenscale).Fourcohortsofpatientsweretreatedwithoneof
thefollowingtherapies:bevacizumab,ranibizumab,PDT,orusualcare.Clinicaldatarelatedtotreatmentswereobtainedfrom
publishedrandomizedclinicaltrials.DirectmedicalcostsandresourceutilizationintheChinesehealthcaresettingweretaken
intoaccount.Healthandeconomicoutcomeswereevaluatedoveralifetimehorizon.Sensitivityanalyseswereperformed.Results.
Treatmentwithranibizumabprovidedthegreatestgainsinquality-adjustedlife-years(QALYs).ThecostpermarginalQALYgained
with bevacizumab over usual care was $1,258, $3,803, and $2,066 for the predominantly classic, minimally classic, and occult
lesions,respectively.One-waysensitivityanalysisshowedconsiderablyinfluentialfactors,suchasutilityvaluesandeffectiveness
data.Probabilisticsensitivityanalysisindicatedthat,comparedtousualcare,PDTandranibizumabmostcaseswouldbecost-
effectiveinthebevacizumabarmatathresholdof$7,480/QALY.Conclusion.Bevacizumabcanbeacost-effectiveoptionforthe
treatmentofAMDintheChinesesetting.
1.Introduction becomeoneofthemostimportanthealthchallengesinChina
[5].
Age-related macular degeneration (AMD) is a progressive MostvisuallossoccursinthelatestagesofAMDinone
chronic macular disease of the central retina that leads to oftwoforms:geographicatrophy(“latedry”)orneovascular
visionlossandsignificantfunctionalimpairmentworldwide (“wet”) AMD. Although only an estimated 10%–15% of all
[1]. In the white population aged 40 years and older, the AMD cases take the neovascular form, it is responsible for
prevalence of early and late AMD is nearly 6.8% and 1.5%, morethan80%ofseverevisualloss(visualacuityof20/200
respectively[2].Theage-specificprevalenceoflateAMDin orworse)duetochoroidalneovascularization,whichresults
Asianswaslargelysimilartothatinwhitepeople[3].Ageis inhemorrhageandfluidleakageandfibrosis[6].Basedonthe
oneofthemainriskfactorsforAMD;accordingtoareport patternoflesions,wetAMDcanbeclassifiedintothreesub-
by the World Health Organization (WHO), the estimated types:occult(35%–73%ofpatients),minimallyclassic(35%),
number of cases will double by 2020 due to trends in the andpredominantlyclassic(20%–44%)[7–9].Severalbiolog-
growth of aging populations [4]. In China, the prevalence ical mechanisms are thought to be involved in the patho-
ofAMDintheearly1990swasnearly5%,andoverthelast genesis of AMD, particularly vascular endothelial growth
decade, the prevalence has increased nearly twofold in the factor(VEGF).VEGFisakeyregulatorofangiogenesis,and
agingpopulation.Atpresent,blindnesscausedbyAMDhas overexpression can block vascular growth and neovascular
2 JournalofOphthalmology
regression [10]. In last decade, new agents targeted against least3lines,orworsenby3to6linesand>6lines.Patients
VEGF,suchasbevacizumab(Avastin,Genentech/Roche)and could transition to the death state from any health state
ranibizumab(Lucentis,Genentech/Novartis),havesubstan- in the model. The R statistical environment (version 3.2.2;
tially changed the patterns of therapies for wet AMD. They R Development Core Team, Vienna, Austria) was used to
havebeenshowntobesuperiortoconventionaltreatments developandsolvethemodel.
(e.g., photodynamic therapy [PDT]) in improving visual The baseline characteristics of the hypothetical cohorts
acuitygainandpreventingvisualacuitylossinpatientswith are based on a previously published study [21]. All patients
wetAMD[5,6,11–15]. were newly diagnosed with wet AMD and the starting age
Thesenewagentshaveimprovedclinicaloutcomesaswell for treatment at the base case was 73.6 years. Due to a
asreducingthehumanandsocioeconomicconsequencesof lack of China-specific data, the initial SCVA was derived
AMD.Visualimpairmentcanresultinsubstantialfunctional from a previously published study based on a Chinese
loss, reduced quality of life, and increased risk of comor- patientcohort[22].Patientswouldreceiveoneoffourofthe
bidities, such as depression and falls, which can increase followingtreatments:bevacizumab,ranibizumab,PDTwith
thesocioeconomicburdenonpatientsandsocieties[16–18]. verteporfin, or usual care. In the model, active treatments
Evidence from US medical claims data shows that the total wereassumedtotakeupto2years.
annualdirectcostofAMDis575–733milliondollars[10].In The cost and health outcome were measured for each
WesternEurope,theyearlybudgetaryimpactofAMDin2002 treatment in patients with wet AMD; the quality-adjusted
wasfrom€51.3to€101.1million[19].Thereareanumberof life-year (QALY) gained was used as the primary health
published economic analyses comparing different therapies outcome. A cost-utility analysis was conducted and the
forAMD,includinglaserphotocoagulation,verteporfinwith incrementalcost-effectivenessratio(ICER)wasestimatedby
PDT, pegaptanib, bevacizumab, and ranibizumab, which comparingtwotreatments.BasedonaWHOrecommenda-
showthatthesetherapieshaveimprovedhealthoutcomesand tion,thepercapitagrossdomesticproduct(GDP)ofChina
reducedresourceconsumptionassociatedwithvisualimpair- perQALYwasusedasacost-effectivenessthresholdinthis
ment[20].However,nopublishedstudieshaveinvestigated analysis[23–25].
thecost-effectivenessofthesetherapiesinahealthresource- Inthecurrentanalysis,ayearlydiscountrateof3%was
limitedsetting. appliedtobothcostsandQALYs,whichisageneralapproach
Verteporfin and ranibizumab have been licensed for intheChinesesetting.
AMD treatment in China. However, these agents are not
coveredby medicalinsurance. Thehighercost ofthesetwo
2.2. Clinical Efficacy. The clinical data for each AMD treat-
agents has limited their widespread use in Chinese clinical
mentweretakenfrompublishedclinicaltrials(Table1).Based
practice. At present, bevacizumab has also been approved
ontheopinionsofChineseophthalmologists,itwasassumed
to treat cancers. However, its similar efficacy and much
thatPDTwasadministeredtoallAMDpatientsregardlessof
lower cost than ranibizumab have stimulated the off-label
lesionsubtypeforethicalreasons,althoughPDTisindicated
use of bevacizumab for wet AMD [5]. The objective of this
inpatientswithpredominantlyclassiclesions.TheVIPand
studywastoevaluatethecost-effectivenessofbevacizumab,
TAPtrialsreportedthepercentagesofpatientsexperiencing
ranibizumab, and verteporfin with PDT versus usual care
a3-linegain,3-to6-lineloss,and>6-linelossamongpatients
for the predominantly classic, minimally classic, and occult
receivingPDTwithverteporfinandaplacebo(usualcare)at1
AMD populations. The usual care in the current analysis
and2years[9,26–29].Anexponentialdistributionwasused
is the supportive care based on Chinese ophthalmologist’s
forthe3-monthtransitionprobabilitiesbetweenhealthstates.
opinion, which would annually include two outpatients'
Thus,the3-monthtransitionprobabilitiescouldbecalculated
visit for an ophthalmologist with one optical coherence
bythedensitymethod[30].Toextrapolateeffectsbeyondthe
tomography. The perspective of the Chinese health care
timehorizonofthe trials,estimated transitionprobabilities
system, representative of a health resource-limited setting,
foryear2intheusualcarecohortwereappliedtoeachstate
was adopted in this analysis, and only direct costs were
of the model from year 3 until death. The MARINA trial
considered.
comparedtheefficacyofranibizumabtousualcareinpatients
withminimallyclassicandoccultlesionsandtheANCHOR
trial made a comparison between ranibizumab and PDT
2.Methods
for predominantly classic lesions [11, 14]. Due to a lack
of published studies directly comparing the four treatment
2.1.ModelOverview. AMarkovmodelwasusedtosimulate
strategies, an indirectcomparisonwas performedusingthe
the lifetime disease course of wet AMD for a cohort of
risk ratio in cumulative probabilities between ranibizumab
patients.ThemodelstructureisshowninFigure1,including
andPDTorusualcaretoprojectthemodeloutput.Theresults
thedeathstateandthefivehealthstatesbasedontheSnellen
of the CATT trial were used to estimate the RR between
chart of visual acuity (SCVA) in the better-seeing eye as
bevacizumabandranibizumabforthethreetypesoflesions
follows: SCVA >20/40, 20/40 to >20/80, 20/80 to >20/200,
[13].
20/200 to >20/400, and ≤20/400 (light perception only).
Transitions between the health states can occur every 3
monthsaccordingtospecifiedprobabilities.Aftereachcycle, 2.3. Resource Utilization and Costs. This analysis was con-
the SCVA could remain in the current state, improve by at ducted from the perspective of the Chinese health care
JournalofOphthalmology 3
SCVA > 20/40
Death
(treated eyes)
SCVA 20/40 to >20/80
(treated eyes)
SCVA 20/80 to >20/200
(treated eyes)
SCVA 20/200 to >20/400
(treated eyes)
SCVA≤20/400
(treated eyes)
Figure1:OverviewoftheMarkovmodelstructure.HealthstatesaredefinedbySnellenchartvisualacuity(SCVA)inthetreatedeye.Patients
haveariskofdeathatanystateinthemodel.
system. Costs are presented in 2012 US dollars ($). Direct ofpatientsreceivingthetreatmentandbytheaveragecostof
medical costs were incorporated into the model, including treatment.Age-specificnaturalmortalityrateswereobtained
costsrelatedtoAMDtreatmentandfollow-up,directmedical fromthelifetablesforWHOmemberstates(2011)[33].
costsrelatedtoAMDcomorbidities,anddirectnonmedical- TheunitcostsofmanagingSAEs(e.g.,endophthalmitis,
relatedcosts.Allofthehealthresourceunitcostswereesti- traumatic injury to the lens, and retinal detachment) were
matedusingdatafromlocalhealthsystemsortheNational estimated based on the treatment path recommended by a
Development and Reform Commission (NDRC) of China panelofChineseclinicalophthalmologists.TheratesofSAEs
[31]. wereobtainedfromtheclinicaltrials(Table2).
WithregardtomedicalcostsassociatedwithAMDtreat- Lowvisionincreasestherisksofnumerouscomorbidities,
ment, unit costs for physician consultations and diagnostic such as depression, falls, and the need for assisted living
procedures were estimated from a previous study [32]. The [9,34].Themodelestimatedthecostsassociatedwithcomor-
model assumed that patients in the usual care arm would bidities for patients with varying degrees of visual acuity.
receiveroutinefollow-upandsupportivecarebutnotactive The prevalence of depression in China was derived from a
treatment. The average number of treatments with PDT in community-based study reported by Chen et al. [35]. The
years 1 and 2 was obtained from the VISION trial, which incidence of a one-time fall is nearly 18% according to the
showed that patients receiving treatment with PDT at the literature[36].Basedoninterviewswithclinicalexperts,the
physician’sdiscretionhad2.05and1.54drugadministrations probabilityofreceivingassistedlivingserviceswasassumed
inyears1and2,respectively[12].Ranibizumabwasadmin- to be similar to that in the report published by Earnshaw
isteredatadosageof0.5mgasanoutpatientprocedure.The etal.[9].Sensitivityanalysiswasperformedtoexaminethe
frequencyofinjectionswaseightinthefirstyearandsixin impact of this assumption. The unit costs associated with
the second year, which was derived from data obtained in comorbiditiesaredepictedinTable2.
theANCHORandMARINAtrials[11,14].Forbevacizumab,
the administered dosage was 1.25mg and the frequency of
injections was assumed to be similar to ranibizumab per 2.4.HealthUtilities. DuetotheabsenceofreportedChinese-
their equivalent effects on visual acuity when administered specificutilityscoresastoanydegreeofVAimpairment,the
according to the same schedule [13]. The annual mean utilityvaluesofthefiveVAstateswerederivedfromthestudy
cost associated with PDT, bevacizumab, and ranibizumab reported by Brown et al. using the time-tradeoff method
treatment in these arms was measured by multiplying the [37]anditisassumedthattheyalsorepresentlocalpatients
average frequency of treatments per year by the percentage (Table 3). In the current analysis, only the bilateral disease
4 JournalofOphthalmology
Table1:CumulativeprobabilityandRRoflosingorgainingvisualacuity.
Parameters Predominantlyclassic Minimallyclassic Occultwithnoclassic
Cumulativeprobabilityofchangeinvision
Usualcareat1year
Gainof>3lines 2.41% 1.92% 2.17%
Lossof3–6lines 23.10% 28.85% 22.83%
Lossof>6lines 29.14% 16.35% 32.61%
Usualcareat2years
Gainof>3lines 1.48% 2.89% 1.71%
Lossof3–6lines 6.33% 6.33% 6.33%
Lossof>6lines 4.21% 10.57% 14.13%
PDTat1year
Gainof>3lines 5.66% 6.44% 3.01%
Lossof3–6lines 26.51% 27.23% 28.92%
Lossof>6lines 13.46% 16.83% 22.29%
PDTat2years
Gainof>3lines 1.75% 1.98% 1.81%
Lossof3–6lines 6.35% 5.44% 8.16%
Lossof>6lines 3.00% 2.97% 6.63%
RRofranibizumabversusPDT
at1year
Gainof>3lines 7.2 N/A N/A
Lossof3–6lines 0.1 N/A N/A
Lossof>6lines 0 N/A N/A
at2years
Gainof>3lines 0.49 N/A N/A
Lossof3–6lines 4.35 N/A N/A
Lossof>6lines 0.06 N/A N/A
RRofranibizumabversususualcare
at1year
Gainof>3lines N/A 6.69 6.69
Lossof3–6lines N/A 0.17 0.17
Lossof>6lines N/A 0.09 0.09
at2years
Gainof>3lines N/A 0.42 0.42
Lossof3–6lines N/A 3.78 3.78
Lossof>6lines N/A 0.14 0.14
RRofbevacizumabversusranibizumab
at1and2years
Gainof>3lines 0.92 0.92 0.92
Lossof3–6lines 1.07 1.07 1.07
Lossof>6lines 1.07 1.07 1.07
RR:riskratio.
N/A:notapplicable.
treatment in the better-seeing eye was evaluated because (i.e.,toensurethatitisrobust)andtoassesshowoutcomesare
thereisamorenotablecorrelationbetweenutilityvaluesand substantiallyaffectedwhenspecificparametersarechanged.
VA for the better-seeing eye than for the poorer-seeing eye One-waysensitivityanalyseswereconductedtoexaminethe
[37]. impact of input parameters in the model on the robustness
of results over the ranges shown in Tables 1–3 or assuming
±20% of mean values. A probabilistic sensitivity analysis
2.5. Sensitivity Analyses. Sensitivity analyses are typically (second-orderMonteCarlosimulation)wasconductedusing
conductedtotestwhetheramodelhasanystructuralerrors acohortof1000simulationstosimultaneouslyexaminethe
JournalofOphthalmology 5
e e e e e e eee
ddg g g g g g ggg
Source[32][32][32][32][32]alculatealculatecalchar calchar calchar calchar calchar calchar calcharcalcharcalchar
CCo o o o o o ooo
L L L L L L LLL
st
o
nualmeantotalc12.8126.8234.8 5694.5at1year4277.8at2years 12190.4at1year9142.8at2years84at1year63at2years 22.244.4 6.36.3 5.75.7 32377.9
n
A
AMDtreatmentandcomorbidities. Averagenumber(range)1timepercycle1timepercycle2timesperyear 2.05(1.5375–2.5625)at1year1.54(1.155–1.925)at2years 8(6–12)at1year6(4.5–12)at2years8(6–12)at1year6(4.5–12)at2years 1.4%(1.05%–1.75%)during1year2.8%(2.1%–3.5%)during1year 0.4%(0.3%–0.5%)during1year0.4%(0.3%–0.5%)during1year 0.3%(0.23%–0.38%)during1year0.3%(0.23%–0.38%)during1year 2.2%(1.65%–2.75%)during1year18%(14.50%–28.60%)during1year2.1%(1.58%–2.63%)during1year
o
t
d
e
at
el
r
∗Table2:Directcosts Medianunitcost(range)3.2(0.8–47.6)31.7(23.8–39.7)58.7(44–73.4)#2539.7(1904.8–3174.6)238.1(158.7–317.5) 41.3(31–51.6) #1523.8(1142.9–1904.8) #10.5(7.9–13.1) 130.6(111.2–156.4)1093.9(364.6–1823.2)432.7(324.5–540.8) US$=CYN6.30).
e,
at
r
e
g
n
a
h
n) xc
o e
eractivati nuary2015alysis.
ParametersOphthalmologistconsultationOpticalcoherencetomographyFluoresceinangiographyVerteporfinper15mgLaseractivation PDT(verteporfinper15mg+las Intravitrealinjection Ranibizumabper0.5mg Bevacizumabper1.25mg AdversereactionsEndophthalmitisRanibizumabarmBevacizumabarmLensdamageRanibizumabarmBevacizumabarmRetinaldetachmentRanibizumabarmBevacizumabarmComorbiditiesDepressionFallAssistedliving∗CostsarepresentedasUSdollars(Ja#Therangewasusedforsensitivityan
6 JournalofOphthalmology
Table3:Utilitiesforeachvisualacuitystate. 4.Discussion
Visualacuity Utilityvalue There was great excitement among ophthalmologists and
>20/40 0.89(0.82–0.96) patientsafterclinicaltrialsdemonstratedthemedicalbenefits
≤20/40to>20/80 0.81(0.73–0.89) of ranibizumab and bevacizumab. However, in the context
≤20/80to>20/200 0.57(0.47–0.67) of limited health care resources, the widespread use of new
≤20/200to>20/400 0.52(0.38–0.66) drugs, especially those that are more effective but more
≤20/400 0.40(0.29–0.50) expensive than the competing alternatives, would increase
thesocioeconomicburdenonpeopleandsocieties.Thus,the
economicevaluationofranibizumabandbevacizumabinthe
clinicalsettingisurgentlyneeded.Inthislight,weconducted
a cost-effectiveness analysis of three active treatments for
impact of uncertainty across all parameters. Proportions,
patients with AMD in the Chinese health care setting:
probabilities, and utilities were subject to beta distribution,
bevacizumab,ranibizumab,andverteporfinwithPDTversus
whereascostwassampledfromlognormaldistributionwith
usualcare.
an assumed standard deviation of 20% from mean values.
ResultsoftheanalysisindicatedthatthecostperQALY
The results are shown on a cost-effectiveness plane. The
gainedwithbevacizumabtherapyoverusualcareinalifetime
outcomes projected from all 1000 simulations were used to
horizon was $1,258, $3,803, and $2,066 for predominantly
plotacceptabilitycurves,whichestimatedthewillingnessto
classical,minimallyclassical,andoccultlesions,respectively,
pay(WTP)thresholdforanincrementalunitofeffectiveness.
justbelowthepercapitaGDPofChina($7,480in2011),which
ishighlycost-effectiveaccordingtoWHOrecommendations
[24,25].Anotheranti-VEGFdrug,ranibizumab,yieldedthe
3.Results
greatestclinicaloutcomescomparedtothealternativesunder
examination,butatahighercost.TheICERsofranibizumab
3.1. Base-Case Analysis. In the base-case analysis (Table 4),
over usual care were all greater than three times the per
treating AMD patients with ranibizumab, compared to the
capita GDP of China, which indicates that ranibizumab is
other three alternatives, provided the greatest clinical out-
notacost-effectiveoptionintheChinesesetting.Verteporfin
comesatahighercostforalltypesoflesionsinthelifetime
with PDT was dominated by bevacizumab due to its lower
horizon.Inpatientswithpredominantlyclassical,minimally
healthoutcomesandhighercost.Thisoutcome,however,was
classical, and occult types of lesions, the estimated lifetime
affected by alternative scenarios explored in the sensitivity
costs for the ranibizumab arm were notably 240% higher
analyses. They corroborated calculations that showed that
than usual care, 61% higher than PDT, and 219% higher
the administration of bevacizumab was cost-effective in
thanbevacizumab;therespectiveprojectedmarginalgainsin
nearly 95.4%, 77.6%, and 95.2% of predominantly classical,
QALYsforpatientswithpredominantlyclassical,minimally
minimally classical, and occult lesion cases, respectively. In
classical,andocculttypesoflesionswere15%,5%,and9%for
additiontoaprobabilisticsensitivityanalysis,multipleone-
usualcare;9%,3%,and6%forPDT;and2%,1%,and1%for
waysensitivityanalyseswereperformedtotesttherobustness
bevacizumab.PDTwaslesscost-effectivethanbevacizumab
of the model. The results of the majority of these analyses
andwasdominatedduetofewerhealthbenefitsandhigher
didresultintheICERsofbevacizumabexceedingthe$7,480
costs regardless of lesion type. The ICERs of bevacizumab
threshold; thus, the robustness of the main analysis was
over usual care ranged from $1,258 for predominantly clas-
further strengthened (Table 5). The time horizon of the
sicalto$3,803forminimallyclassical,whichwerelowerthan
analysis had a substantial impact on model output, partly
thetwootheractivetreatmentalternatives.
because short time horizons could not reflect subsequent
long-termhealthbenefits.
3.2. Sensitivity Analysis. The one-way sensitivity analyses Thisstudyisoneofthefeweconomicanalysestocompare
showedthatsomemodelvariableshadasubstantialimpact costsandhealthoutcomesofbevacizumab,ranibizumab,and
ontheresults,whicharepresentedinTable5.Thesubstan- verteporfin with PDT. Our conclusion was similar to the
tiallyinfluentialvariablesincludedage,utilityvalues,RRof report recently published by Patel et al. [38]. The authors
bevacizumab over ranibizumab, frequency of bevacizumab evaluated the cost-effectiveness of bevacizumab relative to
injections, and the cost of bevacizumab and intravitreal ranibizumabforAMDbasedonafour-stateMarkovmodel
injection.Otherparameters,suchasthecostandprobability for20years.TheyfoundthattheICERforbevacizumabwas
of SAEs, produced little model output sensitivity. One-way dominant compared with ranibizumab. However, different
sensitivity analyses also showed that the ICERs of active typesoflesionswerenottakenintoaccountintheiranalysis;
treatment were more favorable in patients with VA ≤20/40 the ICER of bevacizumab was −$54,649 over ranibizumab
to>20/80forallthreetypesoflesions(Figure2). permarginalQALYbecausebevacizumabyielded3.48more
Pursuanttoaprobabilisticsensitivityanalysis,acceptabil- QALYs than ranibizumab, and the cost for bevacizumab
ity curves showed that AMD treatment with bevacizumab, treatment was $190,300 lower than ranibizumab. These
compared to usual care, PDT, and bevacizumab, yielded findings were notably different than our results. In our
acceptableICERsinmostcasesatthe$7,480/QALYthreshold analysis,treatmentwithranibizumabproducedmorehealth
forallpatients,regardlessoflesiontype(Figure3). outcomes than bevacizumab because the mean change in
JournalofOphthalmology 7
Table4:Lifetimeresultsforthereferencecase.
Treatmentarms Costs($) Vision-years QALYs ICERversususualcare Comments
Predominantlyclassic
Usualcare 8,618.5 2.38 3.97
PDT 18,292.5 3.23 4.19 44,333 Dominated
Ranibizumab 29,468.3 4.16 4.55 36,089 Notcost-effective
Bevacizumab 9,232.8 3.92 4.46 1,258 Cost-effective
Minimallyclassic
Usualcare 8,663.5 2.80 4.10
PDT 18,289.1 3.11 4.19 112,992 Dominated
Ranibizumab 29,480.0 3.77 4.31 102,828 Notcost-effective
Bevacizumab 9,242.8 3.59 4.26 3,803 Cost-effective
Occultwithnoclassic
Usualcare 8,594.9 2.08 3.90
PDT 18,240.1 2.43 4.01 91,424 Dominated
Ranibizumab 29,465.1 3.61 4.26 58,790 Notcost-effective
Bevacizumab 9,227.8 3.44 4.21 2,066 Cost-effective
visual acuity score favored treatment with ranibizumab, and $2,972, respectively. These findings suggest that early
althoughnostatisticalanalysiswasdetectedaccordingtothe community screening and intervention may be attractive.
results of the CATT trial [13]. One of the potential reasons Recently, a system for automated detection of early AMD
for this difference is that the study reported by Patel et signsfromretinalphotographswasreported,withsensitivity
al. used a different model design and did not adjust the and specificity rates of 75% [42]. Such progress makes the
data from varied sources before incorporating it into the earlydetectionofAMDmorefeasible.
model.Inadditiontothecomparisonbetweenbevacizumab Similar to all modeling analyses, our study had several
and ranibizumab, several published studies have evaluated limitations that require consideration. First, the current
the cost-effectiveness of ranibizumab relative to PDT and analysis used an indirect method to evaluate the health
usualcare[20,39,40].Thesestudiesfoundthatranibizumab and economic outcomes of the four treatments due to the
can be a cost-effective option in comparison with selected absences of direct head-to-head studies comparing beva-
alternatives because the ICERs were relatively lower than cizumab,ranibizumab,andverteporfinwithPDTwithusual
the corresponding threshold recommended by their local care.Thiswouldleadtoinevitableuncertaintyintheresults
health care systems. It should be noted that these studies because the data from the varied studies had a high degree
were conducted with regard to developed countries, which of heterogeneity, given the different study designs, patient
had relatively rich health resources and a higher threshold cohorts, and dosing schedules. To examine the robustness
thandevelopingcountries,suchasChina.Tothebestofour ofthemodel,sensitivityanalyseswereconductedbyvarying
knowledge, our analysis is the first economic investigation model parameters. Future analyses should be performed if
associated with the treatment of AMD. Our findings might thedatafromhead-to-headtrialsbecomeavailable.Second,
supply some reference information for patients, physicians, duetotheunavailabilityofChinese-specificdata,especially
anddecision-makersfromdevelopingregions. efficacyandutilitydata,thecurrentanalysisuseddatamainly
The results of this analysis also showed that early treat- obtained from literature published abroad, which would
ment was accompanied by improved clinical outcomes at a produce a degree of uncertainty with respect to Chinese
lower cost with respect to all three types of lesions and the data,pursuanttothehypothesisthatforeignobservationsare
greatestincrementalbenefitswereobservedinthehealthstate similar to those in a Chinese setting. However, one recent
with VA ≤20/40 to >20/80 (Figure 2). This result parallels study showed that the efficacy of bevacizumab outcomes
the findings of a cost-effective analysis reported by Javitt compared favorably to a Chinese population, which would
etal.,whichshowedthattreatmentwithpegaptanibshould result in the underestimation of the cost-effectiveness of
be started as early as possible to maximize clinical and bevacizumab [5]; moreover, as suggested by some Chinese
economic benefits [41]. In addition to the early VA health ophthalmologists,thequalityoflifeofAMDpatientsinChina
state, results from one-way sensitivity analysis found that should not be significantly different from that of external
younger patients could achieve more favorable economic AMD patients. Although efficacy and utilities had some
outcomes in cases of predominantly classical and occult impact on our results, the results of the sensitivity analysis
lesions(Table3).WhenapatientwithVA≤20/40to>20/80 indicatedthattheirinfluencewaslimited.Third,wedidnot
was diagnosed with AMD at 50 years old, the ICERs of examine the “continuous treatment effect” approach under
bevacizumabtherapyoverusualcarefellto$1,148and$2,032 which active treatments, especially the bevacizumab and
for predominantly classical and occult lesions, respectively; ranibizumabtreatments,wouldbeadministeredbeyondthe
whenapatientwas88yearsold,theICERsincreasedto$1,774 trialtimeframesbecausetheefficacyofcontinuoustreatment
8 JournalofOphthalmology
Table5:One-waysensitivityresultsofbevacizumab.
ICER(versususualcare)
Parameters
Predominantly Minimally Occult
Age
55 1,148 11,278 2,032
88 1,774 4,368 2,972
RR(bevacizumabversusranibizumab)
Gainof>3linesat1year
Base−20% 1,604 4,700 2,308
Base+20% 1,023 3,183 1,883
Lossof3–6linesat1year
Base−20% 1,256 3,677 2,052
Base+20% 1,272 3,937 2,101
Lossof>6linesat1year
Base−20% 1,263 3,579 1,982
Base+20% 1,265 4,052 2,177
Gainof>3linesat2years
Base−20% 1,264 3,802 2,076
Base+20% 1,264 3,802 2,076
Lossof3–6linesat2years
Base−20% 975 2,142 1,572
Base+20% 1,708 12,922 2,921
Lossof>6linesat2years
Base−20% 1,264 3,802 2,076
Base+20% 1,264 3,802 2,076
Utility
>20/40
0.82 1,296 3,841 2,088
0.96 1,234 3,763 2,064
≤20/40to>20/80
0.73 1,477 4,364 2,271
0.89 1,104 3,368 1,912
≤20/80to>20/200
0.47 1,405 5,762 3,088
0.67 1,149 2,837 1,563
≤20/200to>20/400
0.38 1,155 2,791 1,984
0.66 1,396 5,961 2,177
≤20/400
0.29 993 2,963 1,430
0.5 1,681 5,118 3,523
Cost($)
Bevacizumabper1.25mg
7.9 1,191 3,571 1,960
13.1 1,336 4,033 2,191
Intravitrealinjection
31 1,102 3,287 1,818
51.6 1,426 4,317 2,334
Frequencyofbevacizumabinjectionsat1year
6 1,221 3,666 2,008
12 1,349 4,074 2,212
Frequencyofbevacizumabinjectionsat2years
4.5 1,234 3,707 2,029
12 1,383 4,181 2,266
Timehorizon
2years 3,935 8,498 7,227
10years 1,277 3,353 2,064
JournalofOphthalmology 9
150000 Predominantly 150000 Minimally
d) d)
e e
n n
ual careALY gai 100000 ual careALY gai 100000
usQ usQ
ER versus additional 50000 ER versus additional 50000
ICer ICer
p p
$, $,
( (
0 0
0 0 0 0 0 0 0 0 0 0
4 8 0 0 0 4 8 0 0 0
20/ 20/ 0/2 0/4 0/4 20/ 20/ 0/2 0/4 0/4
> > 2 2 2 > > 2 2 2
40 to 0 to > 0 to > ≤ 40 to 0 to > 0 to > ≤
≤20/ 20/8 0/20 ≤20/ 20/8 0/20
≤ 2 ≤ 2
≤ ≤
Initial health state Initial health state
Occult
150000
d)
e
n
ual careALY gai 100000
usQ
ER versus additional 50000
ICer
p
$,
(
0
0 0 0 0 0
4 8 0 0 0
20/ 20/ 0/2 0/4 0/4
> > 2 2 2
40 to 0 to > 0 to > ≤
≤20/ 20/8 0/20
≤ 2
≤
Initial health state
Treatment:
Bevacizumab
PDT
Ranibizumab
Figure2:Sensitivityanalysisoftheeffectsoftheinitialhealthstates.Valuesareindicated(𝑦-axis)ascostperadditionalquality-adjusted
life-year(QALY)gained.
beyond 2 years is still unclear. Fourth, this study excluded verteporfin with PDT were both mild and infrequent; this
indirect costs, such as the loss of productivity, which may hadlittleimpactontheoutcomesasdepictedbyBrownetal.
have resulted in a substantial social economic burden for [43].Nevertheless,weareconfidentthatthemodelfaithfully
a patient’s family and society. If these indirect costs were represented the common clinical conditions of AMD in a
considered, this analysis would have underestimated the healthresource-limitedsetting.Webelievethatthisstudyhas
cost-effectiveness of active treatment, which would become thepotentialtobeanimportantreferencepointfordecision-
morecost-effectivebecauseindirectcostswouldbedecreased makers.
by active treatments. Finally, to simplify the model, utility Inconclusion,althoughbevacizumabisnotlicensedfor
decrements for adverse events were not taken into account thetreatmentofAMDinChina,bevacizumabishighlycost-
becausetheadverseeventsofbevacizumab,ranibizumab,and effective compared with ranibizumab and verteporfin with
10 JournalofOphthalmology
Predominantly Minimally
1.00 1.00
e e
v v
cti cti
e e
ff ff
e e
ost- 0.75 ost- 0.75
c c
n is n is
o o
nti nti
e 0.50 e 0.50
v v
er er
nt nt
at i at i
h h
y t 0.25 y t 0.25
bilit bilit
a a
b b
o o
Pr Pr
0.00 0.00
0 2500 5000 7500 10000 0 2500 5000 7500 10000
Willingness-to-pay thresholds ($/QALY) Willingness-to-pay thresholds ($/QALY)
Occult
1.00
e
v
cti
e
ff
e
ost- 0.75
c
n is
o
nti
e 0.50
v
er
nt
at i
h
y t 0.25
bilit
a
b
o
Pr
0.00
0 2500 5000 7500 10000
Willingness-to-pay thresholds ($/QALY)
Treatment:
Usual care Ranibizumab
PDT Bevacizumab
Figure3:Thecost-effectivenessacceptabilitycurvesforthefourtreatmentstrategies.The𝑦-axisindicatestheprobabilitythatastrategyis
cost-effectiveagainstthewillingnesstopayperQALYgained(𝑥-axis).TheverticaldottedlinerepresentsthethresholdsforChina.
PDT because of the more favorable ICER in the Chinese CompetingInterests
health care setting. To reduce the financial burden related
to AMD, we suggest that the government license off-label Theauthorsdeclarenocompetinginterests.
use of bevacizumab and set strict rules for avoiding sterile
endophthalmitis[44,45].Earlyinterventionwouldimprove
thecost-effectivenessofactivetreatments.
Acknowledgments
Disclosure ThisstudywassupportedbygrantsfromtheNationalNatural
Science Foundation of China (nos. 71373160 and 81300781)
The funding agency had no role in the study design, data andtheFourthRoundofThree-YearActionPlanonPublic
collectionandanalysis,decisiontopublish,orpreparationof HealthDisciplineandTalentProgram(Evidence-BasedPub-
thepaper. licHealthandHealthEconomics,no.15GWZK0901).