van Hoek, AJ; Miller, E

15 Pages·2017·1.05 MB·English

RESEARCHARTICLE
Cost-Effectiveness of Vaccinating
(cid:1)
Immunocompetent 65 Year Olds with the
13-Valent Pneumococcal Conjugate Vaccine
in England
AlbertJanvanHoek1,2*,ElizabethMiller2
1 DepartmentofInfectiousDiseaseEpidemiology,LondonSchoolofHygieneandTropicalMedicine,Keppel
street,WC1E7HT,London,England,2 Immunisation,HepatitisandBloodSafetyDepartment,PublicHealth
a11111 England,61ColindaleAvenue,NW95EQ,London,England
*[email protected]
Abstract
OPENACCESS Background
Citation:vanHoekAJ,MillerE(2016)Cost- Recentlyalargeclinicaltrialshowedthattheuseof13-valentpneumococcalconjugatevac-
EffectivenessofVaccinatingImmunocompetent(cid:1)65 cine(PCV13)amongimmunocompetentindividualsaged65yearsandoverwassafeand
YearOldswiththe13-ValentPneumococcal
efficacious.Theaimofthisstudywastoassessthecost-effectivenessofvaccinatingimmu-
ConjugateVaccineinEngland.PLoSONE11(2):
nocompetent65yearoldswithPCV13vaccineinEngland.Englandisacountrywithuniver-
e0149540.doi:10.1371/journal.pone.0149540
salchildhoodpneumococcalconjugatevaccinationprogrammeinplace(7-valent(PCV7)
Editor:BernardBeall,CentersforDiseaseControl&
since2006andPCV13since2010),aswellasa23-valentpneumococcalpolysaccharide
Prevention,UNITEDSTATES
(PPV23)vaccinationprogrammetargetingclinicalrisk-groupsandthose(cid:1)65years.
Received:November13,2015
Accepted:February2,2016 Method
Published:February25,2016
Astaticcohortcost-effectivenessmodelwasdevelopedtofollowacohortof65yearolds
Copyright:©2016vanHoek,Miller.Thisisanopen untildeath,whichwillbevaccinatedintheautumnof2016withPCV13.Sensitivityanalysis
accessarticledistributedunderthetermsofthe
wasperformedtotesttherobustnessoftheresults.
CreativeCommonsAttributionLicense,whichpermits
unrestricteduse,distribution,andreproductioninany
Results
medium,providedtheoriginalauthorandsourceare
credited. ThechildhoodvaccinationprogrammewithPCV7hasinducedherdprotectionamongolder
DataAvailabilityStatement:Allrelevantdataare unvaccinatedagegroups,witharesultantlowresidualdiseaseburdencausedbyPCV7
withinthepaperanditsSupportingInformationfiles. vaccinetypes.Weshowsimilarherdprotectioneffectsforthe6additionalserotypes
Funding:AJVHwaspartfundedbytheNational includedinPCV13,andprojectanewlowpost-introductionequilibriumofvaccine-typedis-
InstituteforHealthResearchHealthProtection easein2018/19.Applyingtheseincidenceprojectionsforbothinvasivediseaseand
ResearchUnit(NIHRHPRU)inImmunisationatthe
community-acquiredpneumonia(CAP),andusingrecentmeasuresofvaccineefficacy
LondonSchoolofHygieneandTropicalMedicinein
partnershipwithPublicHealthEngland.Theviews againsttheseendpointsfor(cid:1)65yearolds,weestimatethatvaccinationofacohortofimmu-
expressedarethoseoftheauthorsandnot nocompetent65yearoldswithPCV13woulddirectlyprevent26casesofIPD,69casesof
necessarilythoseoftheNHS,theNIHR,the
CAPand15deaths.Theassociatedcost-effectivenessratiois£257,771perQALYgained
DepartmentofHealthorPublicHealthEngland.The
(usinglistpriceof£49.10perdoseand£7.51administrationcosts)andisthereforeconsid-
NIHRhadnoroleinstudydesign,datacollectionand
analysis,decisiontopublish,orpreparationofthe erednotcost-effective.Toobtainacost-effectiveprogrammethepriceperdosewouldneed
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 1/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
manuscript.Therewasnoadditionalexternalfunding tobenegative.Theresultsweresensitivetodiseaseincidence,waningvaccineprotection
receivedforthisstudy. andcasefatalityrate;despitethis,theoverallconclusionwasrobust.
CompetingInterests:Theauthorshavedeclared
thatnocompetinginterestsexist.
Conclusions
Vaccinatingimmunocompetentindividualsaged(cid:1)65yearswithPCV13isefficacious.How-
evertheabsoluteincidenceofvaccine-typediseasewilllikelybecomeverylowduetowider
benefitsofthechildhoodPCV13vaccinationprogramme,suchthataspecificPCV13vacci-
nationprogrammetargetingtheimmunocompetentelderlywouldnotbecost-effective.
Background
Communityacquiredpneumonia(CAP)causesahighdiseaseburdenamongtheagingpopu-
lation.ThebacteriumStreptococcuspneumoniaeisthesinglemostcommonbacterialcauseof
CAP,withanestimated5%-40%ofcasescausedbythispathogen[1–3].Furthermore,S.pneu-
moniaecausesinvasivedisease(IPD)associatedwithahighmortalitydependingonageand
risk-group[4].Forthisreasonmanydevelopedcountrieshaveintroducedapneumococcal
vaccinationprogrammetargetingthoseaged65yearsandoverusingthe23-valentpolysaccha-
ridevaccine(PPV23)whichcovers23ofthe90+knownpneumococcalserotypes.Unfortu-
nately,duetoarelativelylowefficacyandshortdurationofprotectionagainstIPD,andlackof
protectionagainstpneumococcal-attributableCAP,PPV23hashadlittleoverallimpacton
pneumococcaldiseaseinthe65+agegroup.[5–7].
Recentlytheresultsofalargeclinicaltrial[clinicaltrialregistrationnumberNCT00744263]
intheNetherlandsshowedthatthe13-valentpneumococcalconjugatevaccine(PCV13)cur-
rentlyusedinthechildhoodvaccinationprogrammeofmanycountrieshasanefficacyof
45.6%(95%CI21.8%-62.5%)againstvaccine-typeCAPand75%(95%CI41.4%-90.8%)
againstIPDamongthoseaged65yearsandolder[8].
Inthisstudyweinvestigatethecost-effectivenessofaddingPCV13tothecurrentPPV23
vaccinationscheduletargetingthoseaged65yearsandoverinEngland.Tomakearealistic
projectionofthefutureincidenceofvaccine-typeCAPandIPDinthisagegroup,theherdpro-
tectioneffectsfromthechildhoodpneumococcalvaccinationprogramme,inwhichthe
7-valentPCV(PCV7)hasbeenrecommendedforallinfantssinceSeptember2006andPCV13
since2010,weretakenintoaccount.
Methods
Programme
Inthisstudyweinvestigatethecost-effectivenessofofferingPCV13toall65yearoldsin
England.ThiswouldbeanadditiontothecurrentPPV23programmeinwhichadoseof
PPV23isofferedtoany65yearoldwhohasnotpreviouslyreceivedadoseatanytimeinthe
past.Tomakearealisticprojectionofthefutureincidenceofvaccine-typeCAPandIPDinthis
agegroup,theherdprotectioneffectsfromthechildhoodpneumococcalvaccinationpro-
gramme,inwhichthe7-valentPCV(PCV7)hasbeenrecommendedforallinfantssinceSep-
tember2006andPCV13since2010,weretakenintoaccount.ItisassumedthatPCV13willbe
providedatthesametimeasseasonalinfluenzavaccine,butthatPPV23willneedanadditional
visittothegeneralpractitioner(GP)eightweekslater.Thereforethenewprogrammewill
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 2/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
requireoneextraGPvisitcomparedtothecurrentschedule.Thefirstseasonofusewassetto
be2016/2017.
StudyPopulation
Thestudypopulationwassettobeacohortofpeoplewhoreflectthetargetedpopulationof
theclinicaltrial.Thiscohortcomprisedimmunocompetentindividualsincludingthosewith
co-morbiditiessuchasdiabetes,asthma,splenectomyorheart,liverorlungdisease.Theclini-
caltrialexcludedthoselivinginnursinghomesorlongtermcarefacilitiesbutduetolackof
dataonpneumococcaldiseaseburdeninthesegroupsinEnglanditwasnotpossibletoexclude
suchindividualsfromanalysis.
IncidenceofIPD
TheincidenceofIPDbyvaccine-type(PCV7andPCV13minus7)wasbasedontheserotype-
specificsurveillancedatacollatedbyPublicHealthEnglandfortheepidemiologicalyearsJuly
toJunefrom2002/03to2013/2014.DetailsoftheseincidenceestimatesforEnglandandWales
havebeenrecentlypublishedbyWaightet.al.[9].Wecorrectedforchangesinsurveillancesen-
sitivityovertimebyincreasingtheincidenceofIPDbefore2009/10aspreviouslydescribed[9].
IncidenceofCAP
RecentlyRodrigoandcolleagues[10]publishedasurveyofcommunityacquiredpneumonia
intwolargeteachinghospitalsinNottingham(UK).Overaperiodoffiveyears(September
2008untilSeptember2013)urinesampleswerecollectedfromparticipants(aged(cid:1)16years)
followingadmissionwithacutelowerrespiratorysymptoms.Samplesweretestedwithavali-
datedmultipleximmunoassay(detecting14serotypes/groups,includingallPCV13types)and
theimmunochromatographicassaykitBinaxNOW™(Alere)whichdetectspneumococcal
polysaccharide.Inaddition,bloodsampleswereculturedforS.pneumoniaeandpositivessero-
typedbyslideagglutination.Annualincidencesforvaccinetypes(PCV7andPCV13minus7)
wereestimatedusingthepopulationdatafromtheOfficeofNationalStatisticsforthegreater
Nottinghamarea.Toourknowledgethisisthelargestlongitudinalsurveythatdocumentsthe
impactofPCVvaccinationonvaccine-typepneumococcalpneumoniaintheUK,hencewe
usedtheobservationsfromthisstudyinourprojections(seealsoS1Appendix).
ProjectingFutureIncidence
ToestimatethefutureincidenceforIPDandCAPcausedbythePCV7andPCV13minus7
vaccinetypesitwasassumedthat:
a. PCV7typesreachedanewpost-vaccinationequilibriuminIPDin2013/14.
b. Theadditional6typescoveredbyPCV13willexperienceasimilarreductioninIPDasthe
PCV7-types,withasimilarpost-vaccinationsteadystate.(seeS2Appendixforevidencein
supportofthisassumption)
c. TheincidenceofPCV13-VTpneumococcalCAPwillfollowasimilardownwardtrendas
IPD.
ToimplementpartbtheIPDincidencerateratioforPCV7typeswascalculatedforthe
periodsinceintroductionofPCV-7(2006/07untilthemostrecentdata)usingthepre-PCV7
period2002/03-2005/06asbaselineincidence.Subsequentlythisincidencerateratiowasused
toprojecttheIPDincidencefor2014/2015onwardsforthePCV13minusPCV7types,using
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 3/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
thepre-PCV13incidenceintheyears2007–2011asbaseline.ToprojecttheincidenceofPCV7
andPCV13minus7CAPasdescribedinpartc,theratiobetweenCAPandIPDwascalculated
byordinaryleastsquaresfortheperiod2008–2013,theyearsforwhichoverlappingdatawas
available.SubsequentlythisratiowasusedtopredictthefutureincidenceofCAPbasedonthe
projectedIPDincidence.
VaccineEfficacyandCoverage
Intheclinicaltrialpopulation(perprotocolanalysis)theprotectionwas75%against
PCV13-typeIPDand45.6%againstPCV13-typeCAP[8].ForCAPtherewerealsoage-strati-
fiedresults:52.4%(95%CI24.1%-71.0%)protectionamongthoseagedunder75and46.4%
(95%CI-4.3%-73.6%)forthoseage(cid:1)75and<85,andnoefficacyamongthoseage85years
andover(6casesinvaccinearmvs3intheplaceboarm)[8].However,inaprogrammaticset-
tingtheintention-to-treatanalysisismoreapplicable,asthevaccinatedcohortwillinclude
thosewhodevelopimmunocompromisedconditions.Unfortunatelynoagespecificestimates
wereavailableusingtheintention-to-treadanalysis,butastheoverallestimatewaslower
(37.7%)thenon-agespecificestimateof45.6%wasapplied,beingacompromisebetweenthe
youngerageandtheinclusionofthosewhowilldevelopimmunocompromisedconditions.
Theaveragedurationoffollow-upinthetrialwasalmost4years,andinthesefouryearsthere
wasnotanobviousdeclineinprotection(althoughtherewassimultaneouslyadeclineinthe
forceofinfectionofsomePCV13vaccinetypesduetotheherdimmunityimpactofthe10–
valentPCVchildhoodvaccinationprogrammeintroducedintheNetherlandsin2011and
whichcoveredthesameserotypesasPCV13apartfrom3,6Aand19A.)[8].Giventhelimited
durationoffollowupinthetrialpopulationwedidnotassumelifelongprotectionfrom
PCV13.TobeconservativeweusedawaningscenariodevelopedbythemanufacturerPfizer
whichassumesaconstantprotectionforthefirst9yearsafterwhichitdropsevery5yearsuntil
thereisaconstantprotectionfrom20yearsonward(Cost-effectivenessanalysisofadultvacci-
nationwiththe13-valentPneumococcalConjugateVaccineintheUnitedKingdom,unpub-
lishedreportprovidedtotheauthorsbyPfizer).TheprotectionagainstIPDwasrespectively
75%(year1–9),43%(year10–14),9%(year15–19),and5%(years20+);forCAPthiswas
45%,26%,5%and3%.Thevaccineuptakewassettobe69%,inlinewiththeuptakeofthe
PPV23vaccineinthoseaged65yearsandover[11].
Mortality,LifeExpectancyandQualityofLife
ThelossinqualityoflifeduetopneumococcaldiseasewassimilartothatappliedinRozen-
baumetal[12],apreviouscost-effectivenessstudyontheuseofPCV13inhighriskgroups
includingthoseaged(cid:1)65yearsintheUKconductedbeforetheclinicaltrialresultsbecame
availableandwhichassumedinitsbasecasenoprotectionfromPCV13againstvaccine-type
CAP.ForIPDvarioussequelaefrommeningitiswereincludedandadjustedforthefactthat
onepersoncanhavemultiplesequelaeatthesametime.Theassumedrateformeningitiswas
6%[12]andtheassumeddurationofsequelaewaslifelong.TheoverallQALYlossduetoIPD
wasbetween0.14(aged65)and0.01(aged100)dependingonage.TheassumedQALYloss
duetoCAPwasseton0.006[12].Thecasefatalityrate(CFR)wasassumedtobe30%and10%
forIPDandCAPrespectively.Bothparametersareuncertain;theIPDCFRwasbasedona
studyinwhichlaboratoryconfirmedIPDdatawaslinkedtohospitalrecordstoascertain
deathsduringanIPDadmission[4];theCFRforCAPwassetasacompromise,asvarious
sourcesreportgreatdifferencesinrates,from1.8%intheCAPITAtrial[8],6.2%inthe
Rodrigostudyandover20%basedoncomputerisedhospitaldischargedataforadmissions
withacodeforallcausepneumonia[13].TheeffectofvaryingtheCFRforIPDandCAPwas
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 4/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
investigatedinasensitivityanalysis.Thequalityadjustedlifeexpectancywasestimatedusing
themostrecentmortalityrates[14]andthebackgroundqualityoflifewasasestimatedbyPet-
rou[15].Ascenarioanalysiswasperformedusingalongerlifeexpectancyestimatedfora
cohortofnon-riskpeople(excludingallclinicalriskgroupsrecommendedtoreceivePPV23
undertheageof65).Personscouldnotbecomeolderthan105,hencethemaximumfollow-up
fora65yearoldwas40years.
Costs
ThecostofhospitalisationduetoIPDandCAPwasbasedonRozenbaumetal.[12]and
inflatedto2014costsusingtheHospital&CommunityHealthServiceIndex[16].Theprice
forIPDwasbetween£4865(age65)and£4780(age100)and£715forCAP.Thecurrentprice
ofPCV13intheBritishNationalFormularyis£49.10[17]andthispricewasusedinthebase
case.Theadministrationcostsduetotheadditionaldosewassettobe£7.51.
EconomicModel
Astaticcohortmodelwasusedtoestimatethefutureincidence,costanddiseaseburdenfor
specificages.Inthemodelcohortswerefollowedfromtheirpointofentryintheseasonof
2016/2017untildeath.Theincrementalcost-effectivenessratiowascalculatedfromahealth
carepayer’sperspectiveandcostandQALYswerebothdiscountedby3.5%perannum.
Toachieveanunderstandingoftherelationbetweenthecost-effectivenessratioandvaccine
priceweperformedvarioussensitivityanalysestotestthecost-effectivenessratiowithavaccine
priceof£49.10andthepriceatwhichthevaccinebecomescost-effectiveusingathresholdof
£20,000asisrecommendedintheUK[18].Therobustnessoftheoutcomewastestedbyvary-
ingtheassumptionsoncosts,QALYloss,casefatalityrate,incidence,waningofvaccinepro-
tection,ageatfirstdose,lifeexpectancy,timingofintroduction.
ThedecisiontakenbytheUKJointCommitteeonVaccinationImmunisationontheuseof
PCV13inthoseaged65yearsandoverwassplitintotwosteps;firstadecisionontheuseof
PCV13inthegeneral(immunocompetent)populationandsecondlyadecisionontheuseof
thevaccineinclinicalrisk-groups.Inthepresentedbase-caseanalysistheimmunocompetent
populationincludespeopleinclinicalrisk-groups;thereforewehaveaddedascenariowhich
focusesonthecost-effectivenessamongthosewhohavenounderlyingco-morbidity.Theinci-
dencepresentedinWaightetal.[9]isforallindividualsirrespectiveofco-morbidities.To
adjustthispopulationincidencetoreflectthosewhoarenotinaclinical-riskgroupwe
assumedthat55%ofthepopulationaged65yearsandoverisnotinahighriskgroup[4]and
thattheoddsratioofhospitalisationifinariskversusanon-riskgroupis2.7[4].Thisimplies
thattheincidencewouldbe55%lowerinthe“non-risk”group.(SeeS3Appendix)
Results
Theobserved(andprojected)incidenceofinvasivediseaseduetoPCV7serotypeshasbecome
verylow,withanincidencebeloworaround1per100,000(dependingonage),withthehighest
incidenceamongthoseage85yearsandover(seeFig1).Theincidencerateratiocomparedto
thepre-vaccineperiodisaround3%(Table1).TheprojectedincidenceforPCV13minus
PCV7typesisexpectedtoreachitssteadystateintheseason2018/19afterwhenitisassumed
thattheincidencewillremainlow(Table2,Fig2).DuetothehighercirculationofPCV7types
beforeintroductionofthevaccineitisprojectedthatinthelongtermmorediseasewillbe
causedbyPCV7typesthantheadditional6serotypesinPCV13.Theincidencerateratiofor
boththePCV7andPCV13minusPCV7issimilarusingthefirstthreepost-vaccinationyears
(seeFig3).TheincidenceofCAPduetoPCV7andPCV13minus7serotypeswasprojectedto
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 5/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
Fig1.ObservedandprojectedincidenceforinvasivepneumococcaldiseasecausedbythePCV7vaccinetypesper100.000personsforthe
epidemiologicalyears2002/03until2019/20inthreeagegroups65–74(black),75–84(lightgrey)and85andover(darkgreyline).Future
projections,seetext,areshownbyadottedline.
doi:10.1371/journal.pone.0149540.g001
Table1. EstimatedIPDtoCAPincidencerateratioovertheperiod2008/09to2012/2013.
Agegroup PCV7 PCV13minusPCV7
65–74 5.9 3.0
75–84 4.4 2.6
85+ 10.1 4.0
doi:10.1371/journal.pone.0149540.t001
Table2. ProjectedfutureincidenceofInvasivepneumococcaldisease(IPD)andCommunity
AcquiredPneumonia(CAP)causedbythePCV13vaccinetypesper100,000. In2018/2019anew
steadystatewasassumedtobereachedandthesameincidencewascontinuedafter.
2015/2016 2016/2017 2017/2018 2018/2019
ProjectedIPDcausedbyPCV13-types
65–74 1.10 0.88 0.71 0.49
75–84 2.04 1.44 1.15 1.10
85+ 3.76 2.80 1.99 1.62
ProjectedCAPcausedbyPCV13-types
65–74 4.17 3.50 2.95 2.31
75–84 6.55 4.99 4.24 4.13
85+ 21.45 17.59 14.40 12.93
doi:10.1371/journal.pone.0149540.t002
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 6/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
Fig2.ObservedandprojectedincidenceforinvasivepneumococcaldiseasecausedbythePCV13minusPCV7vaccinetypesper100.000
personsfortheepidemiologicalyears2002/03until2019/20inthreeagegroups65–74(blackline),75–84(lightgreyline)and85andover(dark
greyline).Futureprojections,seetext,areshownbyadottedline.Theincidencein2018/19and2019/20willcontinueintothefuture.
doi:10.1371/journal.pone.0149540.g002
Fig3.ObservedincidencerateratiosforPCV7vaccinetypesandPCV13minusPCV7serotypesinthethreeyearsaftervaccinationcomparedto
thefouryearsbeforevaccination(2002/03to2005/06forPCV7and2007/08to2010/2011forPCV13minusPCV7).Thedarkshadedbarsrepresent
PCV7andthelightshadedbarsPCV13minusPCV7types.
doi:10.1371/journal.pone.0149540.g003
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 7/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
Fig4.ObservedandprojectedincidenceforcommunityacquiredpneumoniacausedbyPCV7vaccinetypesper100.000fortheepidemiological
years2008/09until2019/20inthreeagegroups65–74(blackline),75–84(lightgreyline)and85andover(darkgreyline).Modelprojections,seetext,
areshownbyadottedline.Theincidencein2018/19and2019/20willcontinueintothefuture.
doi:10.1371/journal.pone.0149540.g004
reducetolowincidencesinlinewiththereductionsinIPD(Table2,Figs4and5respectively).
Overall,anexpandingherdimmunityeffectinducedbythechildhoodvaccinationprogramme
isobserved,resultinginlowincidencesforvaccinetypedisease(bothIPDandCAP)inthose
age65andover.
Usingtheprojectedincidencesbyage,byyear,andtheassumptionsinthecost-effectiveness
model(Table3)itispossibletoprojectthediseaseburdeninacohortof442,43565yearolds
untildeathfrom2016until2056withavaccineuptakeof69%.Usingtheprojectionitisesti-
matedthattherewillbe82casesofvaccinetypeIPDand426casesofvaccinetypeCAPanda
totalof67deathsinacohortof442,43565yearolds,linkedtoatotalcostofjustover£0.7mil-
lion(£0.4milliondiscounted)and367QALYslost(257discounted).Withavaccinationpro-
grammethiswillbe56casesofIPDandaremaining357casesofCAPandatotalof52deaths,
and£0.5millioncosts(£0.3milliondiscounted)and257QALYs(160discounted).
Assumingavaccinepriceof£49.10perdosetheestimatedcostpergainedQALYis
£257,771andthemaximumpricetoachieveanICERof£20,000liesbelowzero(-£2.83)per
dose(ontopoftheadministrationcosts)(Table4)Theoutcomeisnotverysensitivetothe
assumedcostsandQALYlossforacutedisease;however,itisverysensitivetotheCFR,waning
vaccine-inducedprotection,aswellastheprojectedincidenceofIPD.Theoptimalageofvacci-
nationis75yearsduetothewaningprotectionandtheincreaseinincidencewithage.Even
assumingthatincidenceofPCV13-typeIPDandCAPreducenofurtherafter2015/16,thecost
perQALYavertedis£145,146,andthemaximumpricetoachieveanICERof£20,000is£0.79
(seeTable5).
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 8/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
Fig5.ObservedandprojectedincidenceforcommunityacquiredpneumoniacausedbyPCV13minusPCV7vaccinetypesper100.000forthe
epidemiologicalyears2008/09until2019/20inthreeagegroups65–74(darkline),75–84(lightgreyline)and85andover(darkgreyline).Model
projections,seetext,areshownbyadottedline.Theincidencein2018/19and2019/20willcontinueintothefuture.
doi:10.1371/journal.pone.0149540.g005
Table3. Assumptionsinthebasecasecosteffectivenessanalysis.
Parameter IPD CAP
Vaccineefficacy
Year1–9 75% 45%
Year10–14 43% 26%
Year15–19 9% 5%
Years20+ 5% 3%
Costs
Hospitalisation(incl.sequelae) £4858-£4780(agedependent) £715
Casefatalityrate
CAP 30% 10%
QALYloss
CAP 0.13–0.01(agedependent) 0.006
Discounting Costs QALYs
Costs 3.5% 3.5%
doi:10.1371/journal.pone.0149540.t003
Discussion
Inthisanalysisweinvestigatedascenarioinwhichthereisaresidualburdenofvaccinetype
IPDandCAPdespitetheherdimmunityeffectsofthepaediatricPCVprogramme.Inthebase
case,andunderthemostconservativeassumptionthattherewillbenofurtherreductionin
PCV13typeIPDandCAPafter2015/16,vaccinationoftheimmunocompetentelderlyisvery
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 9/14
Cost-EffectivenessofVaccinating(cid:1)65YearOldswithPCV13
Table4. Resultsofthecosteffectivenessanalysisaccordingtoincrementalcosteffectivenessratio(ICER)andmaximumpriceperdose;base
caseandsensitivityanalysis.
ICERusing£49.10perdoseand£7.51 Maxpriceperdose(aftersubtracting£7.51administrationcosts)
administrationcosts) usingathresholdof£20,000perQALY
Basecase £257,771 -£2.83
Sensitivityanalysis
Doublehospitalcosts £256,431 -£2.53
0.05QALYlossbothIPDCAP £249,357 -£2.68
15%/5%CFRIPD/CAP £512,829 -£5.00
30%/15%CFRIPD/CAP £209,423 -£1.82
Age70 £268,787 -£2.94
Age75 £262,316 -£2.74
Age80 £322,910 -£3.53
Nowaning £169,638 -£0.29
NobackgroundQALYloss £191,863 -£1.33
Extralonglifeexpectancy £228,661 -£2.27
DoubletheCAPincidence £175,664 -£0.71
measuredbyRodrigoetal.
Longtermequilibrium((cid:1)2018) £287,060 -£3.30
Incidence55%,toreflectnorisk £469,861 -£4.93
doi:10.1371/journal.pone.0149540.t004
unlikelytobecost-effectiveunderthecurrentlist-price(£49.10).DuetotheadditionalGPvisit
andtherelatedadministrationcostswhenbothPPV23andPCV13areusedthebudgetwhich
remainsavailabletopurchasethevaccinetranslatesintoacostofbelow£0perdoseinthebase
casescenario.Eveniftheadministrationcostwaszero,thepriceperdosewouldneedtobe
below£5.
Thereareseveraluncertaintiesinourassessment.Thefirstistheappliedfutureincidence
forbothIPDandpneumococcalCAP.Inouranalysisweinvestigatedabasecasewherethe
futurewasbasedontheobservedreducedrateofIPDcausedbyPCV7serotypesinthoseaged
65yearsandoverastheresultofthePCV7andPCV13vaccinationprogrammesforinfants.
Table5. Incidenceofvaccine-typeIPDandCAPasappliedbyyearinthemodel,andthecost-effectivenessandmaximumpriceperdose(thresh-
oldof£20,000)forthecorrespondingincidenceincasethiswouldbethelong-termincidence.
2013/2014 2014/2015 2015/2016 2016/2017 2017/2018 2018/19
VaccinetypeIPD
65–74 2.7 1.7 1.1 0.9 0.7 0.5
75–84 5.2 2.6 2.0 1.4 1.1 1.1
85+ 8.1 4.6 3.8 2.8 2.0 1.6
VaccinetypeCAP
65–74 9.1 6.1 4.2 3.5 3.0 2.3
75–84 14.7 8.0 6.5 5.0 4.2 4.1
85+ 38.5 24.7 21.5 17.6 14.4 12.9
Basecasescenario
ICER £60,664 £98,767 £145,146 £181,667 £222,378 £287,060
Price/dose £12.10 £4.63 £0.79 -£0.87 -£2.08 -£3.30
Scenariorestrictedtonon-riskgrouppopulation
ICER £98,896 £160,491 £234,824 £293,834 £359,560 £462,838
Price/dose £4.55 -£0.05 -£2.39 -£3.42 -£4.17 -£4.91
doi:10.1371/journal.pone.0149540.t005
PLOSONE|DOI:10.1371/journal.pone.0149540 February25,2016 10/14