Economische evaluatie

Diana De Graeve

Faculteit Toegepaste economische WetenschappenUniversiteit Antwerpen

InhoudSituering en definitie van economische evaluatieMethodologie SoortenKostenVerdisconterenData en SensitiviteitsanalyseWenselijkheid van het gebruik van evaluatiestudies

Gezondheids-economieEconomische evaluatie

Financieel belang van de sectorBelangrijke mate van overheidsfinanciering

+ specifieke karakteristieken van gezondheidszorg

Onzekerheid Informatie asymmetrieExternaliteitenMeer dan ooit nodig dat toegekeken wordt dat men waarde krijgt voor zijn geld, dat is de best mogelijke gezondheid en gezondheidszorg met de beschikbare middelen

Economische analyse houdt in Identificatie van alternatieven hun gevolgen en hun kosten de waardes daarvan en hoe ze vergelijken om het beleid te kunnen informeren bij beslissing wat te kiezen

Beoordelingscriteria voor nieuwe therapienKan een therapie werken? EfficacyHeeft een therapie aanvaardbare neveneffecten? VeiligheidWerkt een therapie? EffectiviteitGeeft een therapie waarde voor zijn geld? Efficintie (kosten-effectiviteit)Economische evaluatie

Ont-wik-kelingEBMBeleid

Economische evaluatie = comparatieve analyse van alternatieve interventies in termen van hun kosten en effectenKosten BKeuzeKosten AProgramma AAlternatief BEffecten AEffecten BPERSPECTIEf ...

Basiskenmerkenzowel kosten (K) als effecten (E) opnemen vergelijkend (incrementeel) tussen alternatievenK1 - K0

E1 - E0

Vergelijking van alternatieven: welke?Alle relevante alternatieven Alternatieven om resistentie te verminderen: reclamecampagne om gebruik AB te verminderen;richtlijnen voor gepast gebruik AB; isolatie om verspreiding resistente kiemen te verminderen.Alternatieven voor behandeling pneumokokkeninfectie in het ziekenhuis of thuis met een vroegtijdige overstap naar een oraal antibioticumMet nieuw antibioticum Met het standaard product . Vanuit praktische overwegingen vaak slechts twee tot drie alternatieven Niets doen is ook een alternatief

Welk standpunt aannemen voor de analyse?Alles kanZiekenhuisRIZIVpatintwerkgever...Wel steeds uitdrukkelijk vermeldenMaatschappelijk standpunt verdient de voorkeur

Situering en definitie van economische evaluatieMethodologie SoortenKostenVerdisconterenData en SensitiviteitsanalyseWenselijkheid van het gebruik van evaluatiestudies

Soorten economische evaluatiestudiesKosten-minimeringsanalyseeffecten zijn identiekKosten-effectiviteitsanalyseeffecten gemeten in natuurlijke eenheden (bv levensjaren)Kosten-batenanalyseeffecten gemeten in geldKosten-nutsanalyseeffecten gemeten in nutseenheden (bv Qualy)

Kosten-minimeringsanalyseeffecten zijn identiek voor de verschillende alternatieven, dus kunnen we ons beperken tot een vergelijking van de kosten

welke kosten?directe kosten medische : organisatie- en uitvoeringskost voor gezondheidssector en patintenniet-medische : buiten de gezondheidssector, m.n. patinten en familie en andere sectorenindirecte kosten medische : med. kost tijdens gewonnen levensjarenniet-medische : opportuniteitskost van tijdontastbare kosten (intangibles)Pijn, ongemak

Kosten van antimicrobile resistentieExtra onderzoek en behandelingLangere ligduur en langere afwezigheid op het werkKosten van isolatie, verhoogde surveillantie Kosten van vroegtijdige mortaliteit

Voorbeeld

Belang van het standpunt van de analyseWelke kosten opgenomen worden hangt af van het standpunt van de analyse

Riziv: directe medische kosten van verschillende behandelingenPatint: remgelden en verplaatsingskostenMaatschappelijk standpunt: alle kosten

Alternatieven behandeling CAP 1) gebruik makend van een kritisch pad (pneumonie ernstscore, criteria voor overschakeling van IV naar oraal AB (Levofloxacine), criteria voor ontslag uit het ziekenhuis 2) conventionele behandelingVoorbeeldRef. Palmer, CS., Zhan, C., Elixhauser, A., Economic assessment of the community-acquired pneumonia intervention trial employing levofloxacin. Clinical Therapeutics, 2000; 22(2): 250-264.

Belang van het standpunt van de analyse (bedragen in Can$, 1998)Ref. Palmer, Zhan, Elixhauser, Clinical Therapeutics, 2000.

Hoe kosten waarderen?opportuniteitskost : waarde beste alternatieve aanwendingprijsmarginale kostconstante waarde : effect van inflatie wegnemen aanpassen voor tijdsvoorkeur: verdisconteren

Kosten of tarieven (Cohen et al, 1993)

Kosten versus tarieven ligdagKostenopname0ligdagenontslagHotelkostenhligdagprijsd1

Fine M.J., Pratt H.M.; Obrosky D.S.; Lave J.R.; McIntosh L.J.; Singer D.E.; Coley C.M.; Kapoor W.N., Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia, The American Journal of Medicine, 2000(109): 378-85Totale ziekenhuiskost is hoogst op dag 0, daalt snel tot dag 1 of 2 en daalt nadien geleidelijk verderMediaan ziekenhuiskost per dag: $849Gemiddelde besparingen van een reductie in ligduur met 1 dag: $680 met 2 dagen: $1 408Voorbeeld

Jorissen, De Graeve, Vivet, An empirical analysis into the drivers of resource consumption in Intensive Care Units.

Marginale en incrementele kostenhoeveelheidMKProgramma AProgramma BQ1MK B,Q1MK B,Q2MK A,Q1MK A,Q2IKA-B, Q1IKA-B, Q2

Tijdsverschillen: verdisconterenkosten in de toekomst minder zwaar wegen: reden tijdsvoorkeur economische groei en risico-aversie opportuniteitskostbasis discontovoet = 3% (?)methode: AW= Fn(1+r)-n Met: AW= actuele waarde Fn = toekomstige kost in jaar n r = discontovoet

Actuele waarde van 100 Euro op verschillende tijdstippen

Verdisconteren en resistentieWanneer de kosten van resistentie zich in de (verre) toekomst voordoen, wordt hun actuele waarde klein na verdisconteren

MaarHet gebruik van verdisconteren wordt ter discussie gesteld bij intergenerationele billijkheidDe gevolgen van resistentie zijn er ook nu al

Waar kosten verzamelen: gebruik van klinische proevenklinische omgevingprotocolvergelijkingstherapiesteekproefgrootteobservatieperiodeadditionele variabelenbetrouwbare informatiestatistische analyse van kosten mogelijkclinici + economisten = verhoogde geloofwaar -digheid en impactminimum additionele inspanning voor maximum informatie problemenvoordelen

methodologische aspecten opnemen en waarderen van de indirecte medische kosten (tijdens gewonnen levensjaren) en niet-medische kosten (verloren productiviteit door morbiditeit en mortaliteit) methode van het menselijk kapitaalfrictiekostenmethode

Kosten-effectiviteitsanalysekosten worden gemeten (in geld) en effecten worden gemeten en uitgedrukt in unidimensionele natuurlijke eenheden

Welke Effecten?Mortaliteitgered levengered levensjaarClinische resultaten % stijging in fev1 (asthma) % verlaging cholesterolniveau (hypercholesterolemie)aantal ontdekte kankersSamenvattende maatstaven voor klinische resultatensymptoom-vrije dagepisode-vrije dagsuccessvolle behandelingsweekverminderding asthma aanvallen

Waar worden de effectiviteitsdata gehaald?medische literatuurgrote dubbel blind gerandomiseerde trials (RCTs)kleine RCTsniet-gerandomiseerde studies met controlegroepniet-gerandomiseerde studies met historische controlegroepgeen controlegroep

Verdisconteren van effectenneenlevensjaren nu kunnen niet verhandeld worden in de tijd; het zou toekomstige generaties benadelenjainconsistentiesmen kan wel gezondheid nu verlagen om daarna langer te levenZelfde discontovoet?

Resultaten van de evaluatie: Kosten-effectiviteitsratio (CE-ratio)Incrementele vergelijking van de kosten en effecten van de alternatievenstandaardbehandeling: K1 E1nieuwe therapie:K2E2CE-ratio: K2 - K1 = Kost per eenheid effect E2 - E1

kosten effect (LY)A

Ref: Hunter, P. Moxifloxacin IV-to-oral switch proves cost effective in patients with CAP. Inpharma, 2002; 1(1343): 5-6. (2) IV amoxicillin/clavulanic acid 1.2g 3x daily followed by oral amoxicillin/clavulanic acid 625mg 3x daily clarithromycin voor beide alternatieven omschakeling naar orale therapie bepaald door de arts(1) IV Moxifloxacin 400mg once daily followed by oral Behandeling van ernstig zieke patinten met CAP die parenterale therapie nodig hebben Voorbeeld

Directe medische kosten van beide alternatievenHunter, 20023377205237261870

effectenHunter, 2002

duurderminder duureffectieverminder effectiefDominantie nieuwe therapie (Moxifloxacine)vergelijking nieuwe therapie (Moxifloxacine) t.o.v. standaard (Amoxicilline clavulaanzuur)

tAgeSurvivalprobability1.0with treatment 1 with treatment 0 t refers to current age and Fs to the probability that the individual is still alive at age s, r refers to the discount rate

Average CE ratioC1/E1 Equivalent to an incremental analysis where the alternative is costless and causes immediate death.In general, the use of average ratios will not result in a correct ranking of (mutually exclusive) treatments.

Marginale (syn: incrementele) of gemiddelde analyse?Een analyse van verschillende doses van een cholesterol verlagend middel toont dat 80mg per dag een kosten-effectiviteit geeft van 35,000 per gewonnen levensjaar (LYG)40mg per dag kost 21,000 per LYGDus is het zinvol om 80mg per dag te geven omdat de gemiddelde kost per gewonnen levensjaar redelijk is?Wel...

Marginale analyse = wat is de extra kost Om een extra eenheid effectiveit te behalen?i.e. Verschil in kosten Verschil in effectiviteit

35,000/LYG21,000/LYG85,000/LYG

Strict dominanceandExtended dominanceCalculate incremental ratios for each possible pair: Time consuming.Tricks reduce the number of comparisons.

Pet and Thallium eliminated by strict dominance.Strictly dominated alternatives are more expensive and less efficient than at least one alternative.Garber (1999).

Extended dominance: A linear combination of two alternatives strictly dominates a third alternative.Thallium is dominated by at least one point on a line from ECHO to SPECT.Garber (1999).

CEA van combinatie beta 2-agonist /corticosteroid therapie (BA + CS) met combinatie beta 2-agonist/anticholinergische therapie (BA + AC) in vgl met beta 2-agonist/ placebo therapie (BA + PL) bij volwassenenref.: Rutten-van Mlken M, Van Doorslaer E, Jansen C et. al. Cost-effectiveness of inhaled corticosteroid and bronchodilator therapy in asthma and COPD. Am Rev Respir Crit Care Med 1995; 51:975-82.Voorbeeld

CEA inhaled steroids and bronchodilators inadults with moderate asthma: direct costsRutten-van Mlken et al. Am Rev Respir Crit Care Med 1995710509671

CEA inhaled steroids and bronchodilators inadults with moderate asthma: effects*Rutten-van Mlken et al. Am Rev Respir Crit Care Med 1995

CE ratioKosten BA+CS - Kosten BA+PL Symptoomvrije dagen BA+CS - Symptoom-vrije dagen BA+PL 710 $US- 509 $US121 - 84201 $US37==5.43 $US/Sv dag

duurderminder duureffectieverminder effectiefDominantie Ba + AC beta 2-agonist /corticosteroid therapie (BA + CS) in vgl met combinatie beta 2-agonist/anticholinergische therapie (BA + AC): vergelijking nieuwe therapie t.o.v. standaardcombinatie beta 2-agonist/ anticholinergische therapie (BA + AC) in vgl met beta 2-agonist/ placebo therapie (BA + PL) bij volwassenen5.43 $US per symptoomvrije dag

methodologische aspecten Meten en waarderen van effectenWat betekent een verbetering v/e klinische parameter? Hoe kunnen we vergelijken?Meten en waarderen van indirecte kosten

Andere CE ratios voor BA+CS vs BA+PL

CEA inhaled steroids and bronchodilators inadults with moderate asthma: direct + indirect costsRutten-van Mlken et al. Am Rev Respir Crit Care Med 1995106371011885091554671

WellDeadDeadSickWellSicktt+1TimeThree-State Markov Modela11a12a13a33a23a22a21Where aij represents the transition probability of transitioning from state i to state j.

A decision tree

Kosten-nutsanalyseKosten worden gemeten (in geld) en gezondheidseffecten worden gemeten en gewaardeerd in nutseenheden

Meten van de effectenDe kosten-nutsanalyse houdt gelijktijdig rekening met de kwantiteit en de kwaliteit van het leven. Dit gebeurt door levensjaren te wegen met kaliteitsgewichten1 gezond levensjaar = 1 QALY1 levensjaar in minder goede gezondheid = fractie van een QALYdood = 0 QALY

U(z, T) = 0.5 30 = 15 = No. of QALYs if T = 30.

Voordelen van kosten-nutsanalyse laat toe om een brede waaier van relevante resultaten (levenswinst en diverse aspecten van levenskwaliteit) te beschouwenlaat toe om de uitkomsten te waarderen zodat meer belangrijke resultaten een groter gewicht krijgenlaat toe om een brede vergelijking te maken tussen zeer uiteenlopende gezondheids-programmas

Voorbeeld van een QALY berekeningGewonnen QALYs

Welke techniek?Rating Scale, Category scaling,Visual Analog Scale

Waardering van de gezondheidstoestand middels een kruisje op een thermometer,

0 1I-----------------------------X---------------------------------Idoodgezond

ratio scaling

Waarderen hoeveel keer meer of minder gewenst een gezondheids-toestand is t.o.v. een standaard;

Welke techniek?Equivalentie

bv equivalentie in termen van aantal te genezen patinten (1 gezonde patint redden is equivalent aan het genezen van 10 rolstoelpatinten)

Welke techniek?Standard gamble

Men stelt het individu voor de keuze tussen:- gok met kans 1-p op dood en kans p op genezing (perfecte gezondheid)- verder leven gedurende een bepaalde tijd in een omschreven gezondheidstoestand XMen zoekt de kans p waarbij men juist indifferent is tussen de 2 alternatieven; die kans is de waarde van toestand Xleven in toestand X gedurende y jareninterventie met kans 1-p op doodkans p op leven in perfecte gezondheidgedurende y jarenKeuze:

Welke techniek?Time Trade-off

Men stelt het individu voor de keuze tussen:- een tijdsperiode t leven in een omschreven gezondheidstoestand- een fractie van die tijdsperiode leven in perfecte gezondheid

Men zoekt de fractie waarbij men juist indifferent is tussen de tweealternatieven; de verhouding tussen die fractie en t is de waarde vantoestand xtijdsperiode t in gezondheids-toestand xfractie van t leven in perfecte gezondheidkeuze:

Methoden voor het meten van preferenties

Bestaande classificaties als alternatief voor het meten van gezondheidspreferentiesEuroquol (Dolan et al 1996): time trade-off meetmethode op een aseleccte steekproef van de algemene bevolkingQuality of Well-Being classification system (Kaplan and Anderson, 1996): category scaling meetmethode op een steekproef van de algemene bevolkingHealth Utilities Index mark 1 (2 and 3) classification system...

Een voorbeeldEuroquol

Dimensies en TTO coefficintMobiliteitgeen problemen met rondwandelenenige problemen met rondwandelen (0.074)bedlegerig (0.148)Zelfzorggeen problemen om voor zichzelf te zorgenenige problemen met zichzelf te wassen of aan te kleden (0.083)niet in staat om zichzelf te wassen of aan te kleden (0.166)Dagelijkse activiteiten (bv werk, studie, huishouden, gezins- en vrijetijdsactiviteiten)Geen problemen ... Enige problemen (0.031)Niet in staat uit te voeren (0.062)

vervolgPijn/klachtenGeen pijn of andere klachtenMatige pijn of andere klachten (0.084)Zeer ernstige ... (0.168)Angst/depressieniet angstig of depressief Matig angstig of depressief... (0.103)Erg angstig of depressief... (0.206)

Constante term indien er een niet optimale toestand is: 0.152Term indien er een dimensie is op niveau 3: 0.256

Berekening Euroquol scorepersoon met toestand 12321Geen problemen met rondwandelen (0)Enige problemen met zichzelf te wassen of aan te kleden (0.083)Enige problemen met dagelijkse activiteiten (0.062)Matige pijn of andere klachten (0.084)Niet angstig of depressief score: 1.00 - 0.083 - 0.062 - 0.084 - 0.152 - 0.256 = 0.363

Disability Adjusted Life Years: DALYsProposed by the World Bank in the early 1990s.http://www.worldbank.org/html/extdr/hnp/hddflash/workp/wp_00068.htmlValues included in the Daly Indicator.Duration of time lost due to a death.Disability weights.Age-weights.Time preference (discounting).Health is simply added across individuals.

DALY formula: DALYs lost because of health at age aWith D(x) = disability weight; w(x) = productivity weighting factor for different ages, r = discount rate (0.03), L = assumed life expectancy measure (80 years for men; 82.5 for women)

Age-weighting function.reflects the dependence of the young and the elderly on the adults.

http://www.worldbank.org/html/extdr/hnp/hddflash/workp/wp_00068.htmlC = 0.16243 = 0.04.AgeCxe-x

50,000/QALYWorthwhile to undertake?League tables.Compile a league table of incremental CE/CU ratios of other interventions.If the ratio of our intervention is relatively low: Recommend it.Problem: Methodological differences between the studies in the table.Also: How do we choose the cut-off ratio?

methodologische aspecten Meten en waarderen van effectenMeten qalys de sociale waarde van een gezondheidsprogramma dan wel de productie van gezonde jaren?Hoe worden te beoordelen gezondheidstoestanden voorgesteld?Wie moet waarderen?Welke techniek moet gebruikt worden?

Kosten-batenanalyseKosten en effecten worden uitgedrukt in monetaire eenheden

Toekennen van een monetaire waarde aan gezondheidhet toekennen van een monetaire waarde aan menselijk leven en levenskwaliteit is onethisch zulke waarderingen gebeuren toch, impliciet dan wanneer keuzes gemaakt worden

Methoden om effecten om te zetten in monetaire waardenHuman capital method= waarde van de productiviteitswinst op de marktrevealed preference= op basis van waargenomen gedragcontingent valuation = op basis van enqute met vragen naar betalingsbereidheid voor hypothetische scenarios

loon-risico voorbeeld: revealed preferencejob A: job-gerelateerde jaarlijkse fataliteitsrisico bij ongeval = 2/10.000 en loon is $30.500job B: identiek A, maar fataliteitsrisico bij ongeval is 1/10.000 en loon is $30.000impliciete waarde van leven = $500 * 10.000 = 5.000.000

WTP verzekering: voorbeeld contingent valuation Optie AUw verzekering dekt chemotherapie- veronderstel dat uw kans op kanker in de volgende 5 jaren = 1 op 100- u behoudt uw verzekeringWanneer u kanker krijgt:- krijgt u chemotherapie maar niet GCSF- uw kans op neutropenic fever is 20%- u kan GCFS niet kopen

vervolgOptie B: uw verzekering dekt chemotherapie en GCFS (tegen een additionele premie)- veronderstel dat uw kans op kanker in de volgende 5 jaren = 1 op 100- u behoudt uw verzekeringWanneer u kanker krijgt:- krijgt u chemotherapie met GCSF- uw kans op neutropenic fever is 10%

vervolgWanneer GCSF momenteel niet opgenomen wordt door uw verzekering, bent u dan bereid een additionele premie te betalen?Indien ja, tegen welk bod:1 $1...7$100

Payment card

Amount for medicine A per month in Euro

I am willing to pay this amount monthly for medicine A

DEFINITELY NOT

PROBABLY NOT

YES, PROBABLY

YES, DEFINITELY

2.5 per month

5 per month

7.5 per month

10 per month

.

.

.

72.5 per month

75 per month

More than 75 per month

How much are you then willing to pay ? .

Methodologie: onzekerheidBronnen van onzekerheidvariabiliteit in steekproef data (variabiliteit binnen verschillende bevolkingsgroepen m.b.t. middelengebruik en gezondheidsresultaten)Veralgemening van resultaten (bv van klinische proef naar dagdagelijkse praktijk)Extrapolatie (bv van een intermediair klinisch eindpunt naar finaal (cholesterol) of van een beperkte tijdshorizon naar langere horizonAnalytische methoden (bv tijdsvoorkeur, bepalen qualy gewichten)

Omgaan met onzekerheid: sensitiviteits-analyse en statistische benaderingenEenvoudige Sensitiviteitsanalyse : hoe gevoelig veranderen de resultaten wanneer we de waarden van onzekere parameters veranderenIndividuele parameterwaarden worden veranderd; andere op basiswaardeMeervoudige sensitiviteitsanalyseWorst-case; best case (combinatie van meest ongunstige (gunstige) veronderstellingen en parameter waarden)

Ranges gebruikt in de sensitiviteitsanalyse verantwoorden!

Sensitiviteitsanalyse pneumo-kokken-vaccinatieDe Graeve, Verhagen et al

Chart2

29632.946540326519246.496381925931040.851264059732392.42465852620039.03182211.69721845.749732922933598.648980914719708.276064244639557.617016408421463.184567834335554.534237807

basis

mortaliteit 20%;30%;40%

ligduur 11,5;14,1;15,7

theoretische protectie vaccin = 0,88

Effectiviteit vaccin beter

Effectiviteit vaccin slechter

Vaccin aankoopprijs 13

Vaccin aankoopprijs 22

Vaccin toediening 0

Vaccin toediening 15,2

discontovoet 0%

discontovoet 5%

Figuur 1: Kosten-effectiviteitsratio voor + 65-jarigen(kosten per qaly in ECU 1995)

Calculation

StructurePopulationMortalityHosp rateHospitalCountry1

at31-Dec-94Rateper Agemortality rateHospital

[MRG](HAI)per Agecost per

Age1-Jan-95(MRI)[HM][X]person

651068890.01625050290.00028330.1280.00003626240.01621482841.2507280957

661047400.01645980520.00028330.1280.00003626240.01642413841.2507280957

671014460.01878832090.00028330.1280.00003626240.01875273851.2507280957

681012810.01886829710.00028330.1280.00003626240.01883271761.2507280957

691007960.02168736850.00028330.1280.00003626240.02165189131.2507280957

70979260.02332373420.00028330.1280.00003626240.02328831631.2507280957

71953710.02654895090.00028330.1280.00003626240.026513651.2507280957

72906670.03024253590.00028330.1280.00003626240.03020736891.2507280957

73894030.03276176410.00028330.1280.00003626240.03272668851.2507280957

74859150.03563987660.00028330.1280.00003626240.03560490531.2507280957

75623350.05322852330.00041210.1990.00008200790.05315087422.1060485023

76420620.06478531690.00041210.1990.00008200790.06470861562.1060485023

77397830.05087600230.00041210.1990.00008200790.05079816032.1060485023

78427110.04860574560.00041210.1990.00008200790.04852771732.1060485023

79489620.04922184550.00041210.1990.00008200790.04914386782.1060485023

80537940.05807339110.00041210.1990.00008200790.05799613932.1060485023

81495540.0749081810.00041210.1990.00008200790.07483230992.1060485023

82454740.08428992390.00041210.1990.00008200790.08421482232.1060485023

83390770.10064743970.00041210.1990.00008200790.10057367962.1060485023

84356190.1059827620.00041210.1990.00008200790.10590943952.1060485023

85308560.12107855850.00065360.2630.00017189680.12092744873.6200517249

86271610.1322852620.00065360.2630.00017189680.13213607893.6200517249

87232870.14480182080.00065360.2630.00017189680.14465478973.6200517249

88189990.17537765150.00065360.2630.00017189680.17523587713.6200517249

89155210.19798982020.00065360.2630.00017189680.19785193363.6200517249

90127360.20414572860.00065360.2630.00017189680.20400890033.6200517249

9196380.24154388880.00065360.2630.00017189680.24141349023.6200517249

9274100.26153846150.00065360.2630.00017189680.26141150053.6200517249

9356920.28179901620.00065360.2630.00017189680.28167553853.6200517249

9438300.34986945170.00065360.2630.00017189680.34975767713.6200517249

9526920.37444279350.00065360.2630.00017189680.37433524373.6200517249

9617800.42528089890.00065360.2630.00017189680.42518208953.6200517249

9711790.45547073790.00065360.2630.00017189680.4553771193.6200517249

988180.45110024450.00065360.2630.00017189680.45100587423.6200517249

995080.48425196850.00065360.2630.00017189680.48416329783.6200517249

1003420.50.00065360.2630.00017189680.49991403683.6200517249

1012000.50.00065360.2630.00017189680.49991403683.6200517249

1021200.50.00065360.2630.00017189680.49991403683.6200517249

103700.50.00065360.2630.00017189680.49991403683.6200517249

104500.50.00065360.2630.00017189680.49991403683.6200517249

10500.50.00065360.2630.00017189680.49991403683.6200517249

10600.50.00065360.2630.00017189680.49991403683.6200517249

10700.50.00065360.2630.00017189680.49991403683.6200517249

108010.00065360.2630.000171896813.6200517249

109010.00065360.2630.000171896813.6200517249

Jan van Emmerik:Country numbers:1=Belgium2=France3=Scotland4=Spain5=Sweden

Yweight

66676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109

Age at1234567891011121314151617181920212223242526272829303132333435363738394041424344

31 dec. 1994dec. 1995dec. 1996dec. 1997dec. 1998dec. 1999dec. 2000dec. 2001dec. 2002dec. 2003dec. 2004dec. 2005dec. 2006dec. 2007dec. 2008dec. 2009dec. 2010dec. 2011dec. 2012dec. 2013dec. 2014dec. 2015dec. 2016dec. 2017dec. 2018dec. 2019dec. 2020dec. 2021dec. 2022dec. 2023dec. 2024dec. 2025dec. 2026dec. 2027dec. 2028dec. 2029dec. 2030dec. 2031dec. 2032dec. 2033dec. 2034dec. 2035dec. 2036dec. 2037dec. 2038

650.73786407770.71637289090.69550766110.67525015640.63833050040.61973834990.60168771840.58416283340.56714838190.52086574040.50569489360.49096591610.4766659380.46278246410.40437302690.39259517170.38116036090.37005860280.35928019690.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.16103430850.15634398880.15179028040.14736920430.14307689730.1389096091

660.73786407770.71637289090.69550766110.65748041550.63833050040.61973834990.60168771840.58416283340.53649171260.52086574040.50569489360.49096591610.4766659380.41650421770.40437302690.39259517170.38116036090.37005860280.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.16103430850.15634398880.15179028040.14736920430.14307689730

670.73786407770.71637289090.67720482790.65748041550.63833050040.61973834990.60168771840.5525864640.53649171260.52086574040.50569489360.49096591610.42899934420.41650421770.40437302690.39259517170.38116036090.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.16103430850.15634398880.15179028040.147369204300

680.73786407770.69752097280.67720482790.65748041550.63833050040.61973834990.56916405790.5525864640.53649171260.52086574040.50569489360.44186932450.42899934420.41650421770.40437302690.39259517170.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.16103430850.15634398880.1517902804000

690.71844660190.69752097280.67720482790.65748041550.63833050040.58623897970.56916405790.5525864640.53649171260.52086574040.45512540430.44186932450.42899934420.41650421770.40437302690.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.16103430850.15634398880000

700.71844660190.69752097280.67720482790.65748041550.60382614910.58623897970.56916405790.5525864640.53649171260.46877916640.45512540430.44186932450.42899934420.41650421770.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.16586533770.161034308500000

710.71844660190.69752097280.67720482790.62194093350.60382614910.58623897970.56916405790.5525864640.48284254140.46877916640.45512540430.44186932450.42899934420.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780.1658653377000000

720.71844660190.69752097280.64059916150.62194093350.60382614910.58623897970.56916405790.49732781760.48284254140.46877916640.45512540430.44186932450.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.17596653680.17084129780000000

730.71844660190.65981713640.64059916150.62194093350.60382614910.58623897970.51224765210.49732781760.48284254140.46877916640.45512540430.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.18124553290.175966536800000000

740.67961165050.65981713640.64059916150.62194093350.60382614910.52761508170.51224765210.49732781760.48284254140.46877916640.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890.1812455329000000000

750.67961165050.65981713640.64059916150.62194093350.54344353420.52761508170.51224765210.49732781760.48284254140.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.19228338580.18668289890000000000

760.67961165050.65981713640.64059916150.55974684020.54344353420.52761508170.51224765210.49732781760.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.19805188740.192283385800000000000

770.67961165050.65981713640.57653924540.55974684020.54344353420.52761508170.51224765210.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440.1980518874000000000000

780.67961165050.59383542280.57653924540.55974684020.54344353420.52761508170.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.21011324740.2039934440000000000000

790.61165048540.59383542280.57653924540.55974684020.54344353420.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.21641664480.210113247400000000000000

800.61165048540.59383542280.57653924540.55974684020.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410.2164166448000000000000000

810.61165048540.59383542280.57653924540.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.22959641840.22290914410000000000000000

820.61165048540.59383542280.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.2364843110.229596418400000000000000000

830.61165048540.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030.236484311000000000000000000

840.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.25088620550.24357884030000000000000000000

850.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.25841279170.250886205500000000000000000000

860.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550.2584127917000000000000000000000

870.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.27415013070.26616517550000000000000000000000

880.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.28237463460.274150130700000000000000000000000

890.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370.2823746346000000000000000000000000

900.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.29957124990.29084587370000000000000000000000000

910.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.30855838740.299571249900000000000000000000000000

920.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390.3085583874000000000000000000000000000

930.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.32734959320.3178151390000000000000000000000000000

940.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.3371700810.327349593200000000000000000000000000000

950.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340.337170081000000000000000000000000000000

960.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.35770373890.34728518340000000000000000000000000000000

970.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.36843485110.357703738900000000000000000000000000000000

980.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660.3684348511000000000000000000000000000000000

990.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.39087253350.37948789660000000000000000000000000000000000

1000.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.40259870950.390872533500000000000000000000000000000000000

1010.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080.4025987095000000000000000000000000000000000000

1020.49514563110.48072391370.46672224630.45312839440.439930480.42711697090.41467667080000000000000000000000000000000000000

1030.49514563110.48072391370.46672224630.45312839440.439930480.427116970900000000000000000000000000000000000000

1040.49514563110.48072391370.46672224630.45312839440.43993048000000000000000000000000000000000000000

1050.49514563110.48072391370.46672224630.45312839440000000000000000000000000000000000000000

1060.49514563110.48072391370.466722246300000000000000000000000000000000000000000

1070.49514563110.4807239137000000000000000000000000000000000000000000

1080.49514563110000000000000000000000000000000000000000000

10900000000000000000000000000000000000000000000

Mortrate

NO VACCINATIONMortality rate

Age at

31 dec. 19941995199619971998199920002001

650.01625050291

660.01645980520.0164598052

670.01878832090.01878832090.0187883209

680.01886829710.01886829710.01886829710.0188682971

690.02168736850.02168736850.02168736850.02168736850.0216873685

700.02332373420.02332373420.02332373420.02332373420.02332373420.0233237342

710.02654895090.02654895090.02654895090.02654895090.02654895090.02654895090.0265489509

720.03024253590.03024253590.03024253590.03024253590.03024253590.03024253590.0302425359

730.03276176410.03276176410.03276176410.03276176410.03276176410.03276176410.0327617641

740.03563987660.03563987660.03563987660.03563987660.03563987660.03563987660.0356398766

750.05322852330.05322852330.05322852330.05322852330.05322852330.05322852330.0532285233

760.06478531690.06478531690.06478531690.06478531690.06478531690.06478531690.0647853169

770.05087600230.05087600230.05087600230.05087600230.05087600230.05087600230.0508760023

780.04860574560.04860574560.04860574560.04860574560.04860574560.04860574560.0486057456

790.04922184550.04922184550.04922184550.04922184550.04922184550.04922184550.0492218455

800.05807339110.05807339110.05807339110.05807339110.05807339110.05807339110.0580733911

810.0749081810.0749081810.0749081810.0749081810.0749081810.0749081810.074908181

820.08428992390.08428992390.08428992390.08428992390.08428992390.08428992390.0842899239

830.10064743970.10064743970.10064743970.10064743970.10064743970.10064743970.1006474397

840.1059827620.1059827620.1059827620.1059827620.1059827620.1059827620.105982762

850.12107855850.12107855850.12107855850.12107855850.12107855850.12107855850.1210785585

860.1322852620.1322852620.1322852620.1322852620.1322852620.1322852620.132285262

870.14480182080.14480182080.14480182080.14480182080.14480182080.14480182080.1448018208

880.17537765150.17537765150.17537765150.17537765150.17537765150.17537765150.1753776515

890.19798982020.19798982020.19798982020.19798982020.19798982020.19798982020.1979898202

900.20414572860.20414572860.20414572860.20414572860.20414572860.20414572860.2041457286

910.24154388880.24154388880.24154388880.24154388880.24154388880.24154388880.2415438888

920.26153846150.26153846150.26153846150.26153846150.26153846150.26153846150.2615384615

930.28179901620.28179901620.28179901620.28179901620.28179901620.28179901620.2817990162

940.34986945170.34986945170.34986945170.34986945170.34986945170.34986945170.3498694517

950.37444279350.37444279350.37444279350.37444279350.37444279350.37444279350.3744427935

960.42528089890.42528089890.42528089890.42528089890.42528089890.42528089890.4252808989

970.45547073790.45547073790.45547073790.45547073790.45547073790.45547073790.4554707379

980.45110024450.45110024450.45110024450.45110024450.45110024450.45110024450.4511002445

990.48425196850.48425196850.48425196850.48425196850.48425196850.48425196850.4842519685

1000.50.50.50.50.50.50.5

1010.50.50.50.50.50.50.5

1020.50.50.50.50.50.50.5

1030.50.50.50.50.50.50.5

1040.50.50.50.50.50.50.5

1050.50.50.50.50.50.50.5

1060.50.50.50.50.50.50.5

1070.50.50.50.50.50.50.5

1081111111

VaccinationMortality rate[MRV]

Age at

31 dec. 19941995199619971998199920002001

650.01622363

660.01643293810.0164344761

670.01876151740.01876305170.018764586

680.01884149580.018843030.01884456420.0188460984

690.02166064420.0216621740.02166370380.02166523360.0216667634

700.02329705460.02329858190.02330010910.02330163630.02330316350.0233046907

710.02652235940.02652388160.02652540380.0265269260.02652844810.02652997030.0265489509

720.03021604530.03021756170.03021907810.03022059450.03022211090.03022362730.0302425359

730.03273534240.03273685480.03273836730.03273987970.03274139220.03274290470.0327617641

740.03561353350.03561504140.03561654940.03561805730.03561956530.03562107330.0356398766

750.05317659160.05318205810.05318752460.05319299110.05319845760.05320392410.0532285233

760.06473401910.06473941890.06474481860.06475021840.06475561820.06476101790.0647853169

770.05082394150.05082942160.05083490170.05084038180.05084586190.0508513420.0508760023

780.04855356030.04855905350.04856454670.04857003990.04857553310.04858102620.0486057456

790.0491696940.04917518360.04918067330.04918616290.04919165250.04919714220.0492218455

800.05802172510.05802716360.05803260220.05803804070.05804347920.05804891770.0580733911

810.07485743840.07486277970.07486812110.07487346240.07487880370.0748841450.074908181

820.08423969590.08424498310.08425027030.08425555740.08426084460.08426613170.0842899239

830.10059810890.10060330160.10060849440.10061368710.10061887980.10062407250.1006474397

840.10593372390.10593888580.10594404770.10594920960.10595437150.10595953340.105982762

850.12099677790.12101406480.12103135180.12104863870.12106592570.12107855850.1210785585

860.13220452410.13222159060.13223865720.13225572370.13227279030.1322852620.132285262

870.14472224750.14473906790.14475588820.14477270860.1447895290.14480182080.1448018208

880.17530092320.17531714220.17533336120.17534958010.17536579910.17537765150.1753776515

890.1979151960.19793097020.19794674440.19796251870.19797829290.19798982020.1979898202

900.20407167720.20408733030.20410298350.20411863660.20413428980.20414572860.2041457286

910.24147331710.24148823470.24150315230.24151806990.24153298750.24154388880.2415438888

920.26146975020.26148427460.26149879890.26151332330.26152784760.26153846150.2615384615

930.281732190.28174631590.28176044170.28177456760.28178869340.28179901620.2817990162

940.34980895930.34982174630.34983453330.34984732030.34986010730.34986945170.3498694517

950.37438458750.37439689120.37440919490.37442149860.37443380230.37444279350.3744427935

960.42522742330.4252387270.42525003080.42526133460.42527263840.42528089890.4252808989

970.45542007130.45543078140.45544149140.45545220140.45546291140.45547073790.4554707379

980.45104917130.45105996720.45107076320.45108155920.45109235510.45110024450.4511002445

990.48420397990.48421412390.48422426780.48423441170.48424455560.48425196850.4842519685

1000.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1010.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1020.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1030.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1040.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1050.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1060.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1070.49995347670.49996331090.49997314510.49998297930.49999281350.50.5

1081111111

Cohortmeth

NO VACCINATIONSurvivars

Age at1234567891011121314151617181920212223242526272829303132333435363738394041424344


65105152103421.218560244101478.10752012699563.388436873197404.120538117295132.292715995892606.630143967689805.970809758286863.76877513183767.954773042279309.11024048574171.04439945770397.518173066366975.794314404963679.122113561159981.059551142155487.987487255550810.909243893345696.921321170740853.835384243235907.311888147431157.303728870726645.669419008921972.614494847817622.260500732214024.751290469710637.1583246877855.13230130735641.56374696843667.75293210222294.3892784771318.6293437539718.0322635199394.1277338881203.2706029108101.635301455450.817650727725.408825363812.70441268196.3522063413.17610317051.58805158520.79402579260

66103016101080.50233621899173.285385709297022.477795594994759.551307377992243.7846287289454.098663021986523.424580675883439.740403686578998.366237336573880.432045031370121.691013456466713.373939542563429.618553849659746.045509230755270.577919727150611.825112269845517.87449767440693.764437629735766.62210100231035.225127072526541.268021026721886.522768852317553.214060091113969.800385763410595.48047519517824.35481245185619.45932419243653.38217160292285.39954568321313.4627726033715.2189143438392.5834872132202.474160728101.23708036450.61854018225.30927009112.65463504556.32731752283.16365876141.58182938070.7909146903

679954097661.849705275495543.821177796893315.382483577990837.956972170688090.78679980785204.777219181882168.089471464577794.403406391672754.468327640869053.011828755765696.638703413362462.928902440658835.494804005454428.23491151549840.483132128244824.16611294440073.577183542235221.526225617830562.237402354926136.769780044621552.964479391417285.696916401313756.895724296810434.00163359727705.10889865645533.8167915863597.70334492142250.56925440111293.4451389058704.3187270378386.600377066199.388383447499.694191723749.847095861924.923547930912.46177396556.23088698273.11544349141.55772174570.77886087280

689937097214.926187547194947.511084179792426.75427062989631.534838971886695.047634478183605.246833025979155.063003845274026.977161862470260.780500584766845.702878444963555.434018164559864.55444288255380.209564729350712.215914256345608.161222474240774.482325962835837.566783773431096.78487389926593.913804427321929.935658401117588.031639441813997.510105008110616.49708109667839.8747675795630.60577123383660.62881732962289.93273714081316.068084323716.637582812393.3621939885202.8757772146101.437888607350.718944303625.359472151812.67973607596.3398680383.1699340191.58496700950.79248350470

699861096310.046565774293753.1158645790917.783894827487939.15690213284805.01619987680290.970418995475089.294455138271269.051336791267804.965958898464467.480399465760723.635197994756174.938143166551439.956881285946262.65692442941359.612765701436351.850473354331543.036410883826975.547306340522244.639173032117840.42706178114198.380079947610768.84814115147952.38016577335711.4072589043713.16033281222322.79420522131334.9541977199726.9216242037399.007101794205.7871273032102.893563651651.446781825825.723390912912.86169545646.43084772823.21542386411.60771193210.8038559660

709564293102.805234295590287.140307117687329.174310903384216.773312940479734.038832274174568.443857761570774.699535611167334.642495599764020.307125018560302.43079199755785.285393040551083.147931820445941.759882178641072.725278309236099.698909377331324.240782600226788.433683406322090.341097843417716.678434762914099.894206560710694.15092861167897.21914728245671.79056115433687.40430738232306.68233790191325.6943998166721.8793932844396.2394224752204.3597021427102.179851071451.089925535725.544962767812.77248138396.3862406923.1931203461.5965601730.79828008650

719283990031.313212083887081.728562819383978.146500788879508.113772953474357.155425007670574.160613650667143.850917461363838.906660464460131.564867563955627.218724197150938.404690466945811.58467747740956.34640134735997.411019073431235.484072660226712.529106670122027.748487509917666.478524097914059.942393236210663.84923164117874.84250951965655.71963789813676.9561092342300.14639225491321.9380670094719.8339601527395.1166847293203.7806523604101.890326180250.945163090125.47258154512.73629077256.36814538633.18407269311.59203634660.79601817330

728792585044.421887408782013.449183931577647.994393006972617.544468587168923.054108271965572.997674829262345.373713464558724.766443492754325.801011070649746.683377358344739.807063333439998.158739009735155.239337631130504.719292709726087.580397402621512.401815153817253.165246764713731.005256062110414.3648497427690.60788904035523.4021522133590.93246971552246.33368462141291.0108760493702.9931996808385.8727954238199.013134647799.506567323949.753283661924.87664183112.43832091556.21916045773.10958022891.55479011440.77739505720

738647483392.077308968278953.240178765973838.229492466370081.635558053366675.265409414363393.385795904159711.916910407555239.005832160950582.914233562345491.873424887140670.519030351935746.191214128331017.496945420926526.10691235721874.020579814517543.187177213513961.82044819710589.42804278067819.88532389965616.24933311693651.29525834492284.09406205531312.7124862262714.8103614565392.3592326332202.3585018699101.179250934950.589625467525.294812733712.64740636696.32370318343.16185159171.58092579590.79046289790

748285378442.857158899573360.911798288969628.601879988866244.251771050662983.587444261859325.916938705954881.920416195650255.92752013945197.797086976140407.609714974235515.114579663630816.988344078426354.632321566621732.618800041217429.781510399713871.566063867110520.97405342077769.3346856035579.94381495873627.69193191832269.32883111091304.2266259699710.189562233389.8228770692201.0503814806100.525190740350.262595370125.131297685112.56564884256.28282442133.14141221061.57070610530.78535305270

755901755193.564951737952385.537013615749839.298928806947386.116656464644634.244171897641290.774131818437810.377921956534004.860191141630400.931186353226720.03026231223185.364059576919828.081128804716350.67882756913113.410865638710436.3640494757915.52409230785845.3100989354198.10746388722729.31790733141707.3444858641981.2434882241534.3157925699293.285807902151.261578091275.630789045637.815394522818.90769726149.45384863074.72692431542.36346215771.18173107880.59086553940

763933737335.690697031435520.961613492333772.554328485231811.267573044329428.343384661226947.830559895224235.600409370221667.044539037719043.630020051316524.438434246514131.669661958111653.29062550129346.05770931257438.09994830335641.47236170344166.01035941182992.03273880451945.21188501911216.8413129169699.3419455696380.8121535672209.0276979849107.805623763953.902811881926.95140594113.47570297056.73785148523.36892574261.68446287130.84223143570.42111571780

773775935923.695652173934155.465054532132171.94137474729761.999767953227253.363072026624510.381856419521912.703889379919259.545290380516711.791296479814291.893488615811785.41477373259452.02262118567522.43257603155705.43495857964213.2442771053025.95618496221967.266553671230.6377698292707.271032885385.129773632211.3976385829109.02791596254.51395798127.256978990513.62848949536.81424474763.40712237381.70356118690.85178059350.42589029670

784063538634.870307585536391.212374713833665.212852274930827.574622456427724.858165458124786.50112077421785.387295676418903.501630444416166.240175647413331.042940779410691.63214527558508.9811105936453.68872363924765.80090361053422.80289774422225.26872464311392.0328871839800.0278896568435.6385964034239.1219190527123.32665903961.663329519530.831664759815.41583237997.70791618993.8539580951.92697904750.96348952370.48174476190

794655243848.56749823440563.951068612937144.818719446533406.287818313329865.797166859526249.689498484222777.242446900919479.05626873516062.865127757812882.581348516810252.65739231837776.19065551435742.41771484144124.21005240192681.27494268421677.2908631056963.9710971669524.910470213288.1232287599148.598988061274.299494030637.149747015318.57487350779.28743675384.64371837692.32185918851.16092959420.58046479710

805067046874.402470032742923.362652386738603.236099380134511.958515080730333.300328266526320.651748337122509.373451631118561.732399952914886.698338677511847.64245923648985.91682683326635.75396443064765.80502575413098.39543449811938.22359275441113.9341210044606.5697249235332.9459737049171.716230532985.858115266442.929057633221.464528816610.73226440835.36613220422.68306610211.3415330510.67076652550

814584241977.981308000237753.004966818333751.837226293929665.213429384625740.942899883522013.607499943318152.912716543614558.820790898411586.69971235458788.00320578046489.60236734554660.83880493823030.15368780581895.53447632431089.3998703819593.2101075362325.6128829875167.934203430583.967101715341.983550857620.991775428810.49588771445.24794385722.62397192861.31198596430.65599298220

824164137449.939964685133480.89189015529427.073763968325534.30560248921836.891659448118007.188885129414441.948794671211493.6866349558717.45686880286437.50661080824623.42358133943005.82890797261880.31793500221080.654633431588.4480701126322.99900181166.586099358783.293049679341.646524839720.823262419810.41163120995.2058156052.60290780251.30145390120.65072695060

833514431419.341811954327615.133197439723962.058068453320492.308431023616898.415505492213552.701257159210785.97518393268180.68879378996041.12403233724338.74122350572820.7482105821764.53937095841014.1144811744552.2150101052303.1106840308156.328738614378.164369307239.082184653619.54109232689.77054616344.88527308172.44263654081.22131827040.61065913520

843184427988.374384236524285.924947081720769.278795943317126.811458289613735.877136317810931.75648977058291.25751610526122.77478112394397.38287161532858.87293742091788.38856857981027.8210705939559.6786491275307.2074736653158.441649803879.220824901939.610412450919.80520622559.90260311274.95130155642.47565077821.23782538910.61891269450

852712023532.423695740220124.885897739816595.430673187513309.70433733910592.58504736718034.01086286095932.8080218054260.94855817622770.17282241741732.9015724186995.9316340361542.3139177703297.675976869153.525799093976.762899546938.381449773519.19072488679.59536244344.79768122172.39884061081.19942030540.59971015270

862356820155.310688366916620.519635488413329.825940503810608.59891119248046.15667574365941.77723747224267.39025769262774.3607680561735.5213719934997.4372828929543.1337876312298.1260032352153.757899306476.878949653238.439474826619.21973741339.60986870664.80493435332.40246717671.20123358830.60061679420

871991516422.354071266913170.89514072110482.11315533517950.22278123055870.93374613944216.5103925192741.28221341311714.8288437547985.5448916635536.6580326107294.5714628878151.924652119375.962326059637.981163029818.99058151499.49529075754.74764537872.37382268941.18691134470.59345567230

881566712565.09348624449999.98332102497584.54846199345600.89732577974022.56996974482615.19562001691635.9544666079940.214280528511.9741883791281.0225068242144.936804700772.468402350336.234201175218.11710058769.05855029384.52927514692.26463757341.13231878670.56615939340

89124489906.79396984927513.8684290935548.70283994563985.08383866792590.82474106611620.7090876505931.4524700374507.2031261781278.4036719486143.586145768871.793072884435.896536442217.94826822118.97413411054.48706705532.24353352761.12176676380.56088338190

90101367687.71114339085677.07899819624077.28372182472650.76670165631658.2062130718953.0027842542518.9379028763284.8448880091146.908190272473.454095136236.727047568118.36352378419.1817618924.5908809462.2954404731.14772023650.57386011830

9173105398.15384615383876.9594032112520.52974255751576.73554475906.1800349883493.4415457697270.8499438271139.690325359769.845162679834.922581339917.461290678.7306453354.36532266752.18266133371.09133066690.54566533340

9254723929.99578355592555.01031359121598.3051144456918.5764786954500.191772114274.5551414171141.60127372370.800636861535.400318430817.70015921548.85007960774.42503980382.21251990191.1062599510.55312997550

9340882657.73368146211662.5644574971955.5075505728520.3018214315285.5935425706147.294307388873.647153694436.823576847218.41178842369.20589421184.60294710592.30147355291.15073677650.57536838820

9424901557.6374442794895.2039918527487.4647691004267.5692925747137.998335934268.999167967134.499583983517.24979199188.62489599594.31244799792.1562239991.07811199950.53905599970

951684967.8269662921527.0101037825289.2757171129149.193381660674.596690830337.298345415118.64917270769.32458635384.66229317692.33114658841.16557329420.58278664710

961023557.0534351145305.7664943355157.69846755178.849233775539.424616887719.71230844399.85615422194.9280771112.46403855551.23201927770.61600963890

97642352.3936430318181.746327705490.873163852745.436581926322.718290963211.35914548165.67957274082.83978637041.41989318520.70994659260

98449231.5708661417115.785433070957.892716535428.946358267714.47317913397.23658956693.61829478351.80914739170.90457369590

9926213165.532.7516.3758.18754.093752.0468751.02343750

10017185.542.7521.37510.68755.343752.6718751.33593750

101100502512.56.253.1251.56250

1026030157.53.751.8750

1033517.58.754.3752.18750

1042512.56.253.1250

1050000

106000

10700

1080

VaccinationSurvivars

Age at1234567891011121314151617181920212223242526272829303132333435363738394041424344


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Differencesin Survivars

Age at1234567891011121314151617181920212223242526272829303132333435363738394041424344


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10500000000000000000000000000000000000000000000

10600000000000000000000000000000000000000000000

10700000000000000000000000000000000000000000000

10800000000000000000000000000000000000000000000

Gain in QALY

survivants

Age at1234567891011121314151617181920212223242526272829303132333435363738394041424344


652.11944736113.93189367015.45299629726.71552399737.52035024598.28071841947.82609129367.36835965726.91937786016.12823466395.63304639065.1146676654.71306196224.35337871023.61668702753.30743082

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