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1.47(1.04-2.09)
IOP(21,<21mmHg*) 1.67(1.19-2.35)
1.70(1.18-2.43)
PatternSD(-4,>-4*) 1.46(1.04-2.05)
1.58(1.10-2.28)
Pseudoexfoliation(yes,no*) 3.15(1.93-5.15)
2.22(1.31-3.74)
Botheyeseligible(yes,no*) 1.92(1.34-2.75)
1.96(1.36-2.82)
IOPatfrstfollow-upvisit(permmHg ) 1.11(1.06-1.17)
MeanIOPatallfollow-upvisits(permmHg ) 1.13(1.07-1.19)
*Referencecategoryformultivariateanalysis;P0.05;P<0.005;P<0.001;
||
AdjustedforbaselineIOP,
pseudoexfoliation,numberofeligibleeye,meandeviationandage.
(a)Haemorrhagesorbleedingaroundtheopticnervecanindicateongoingdamagetotheopticnerveandinadequate
controlofglaucoma.
Source:reproducedfromLeskeetal,(2003)
3.2: AGL
Theprevalenceofglaucomaincreasesmarkedlywithage(Figure3.2).Intheirliterature
reviewofprogressionrates,Friedmanetal,(2004)foundthattherewasstrongevidenceofa
linkbetweenolderageandtheriskofprogressionfromOHTtoglaucoma(Table3.1)andfor
progressionofglaucoma(Table3.3).TheOHTSGroupandtheEuropeanGlaucomaprevention
StudyGroupetal,(2007)confrmedthatage(bydecade)isasignifcantriskfactorfor
progressionfromOHTtoglaucoma(Table3.2).
fIGURE 3.2: DEMOGRAPhIC DISTRIBUTION Of GLAUCOMA, AUSTRALIANS OVER 40
Source:Taylor(2001)
The prevalence of
glaucoma increases
markedly with age.
Undiagnosed
Diagnosed
P
e
r
c
e
n
t
10%
8%
6%
4%
2%
0%
Age
40-49 50-59 60-69 70-79 80-89 90+
3. Risk factors
The cost of eye
care will continue
to increase as the
population ages.
16
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3.3: CU-1O-DISC kA1IO
Theopticdiscistheregionoftheeyewherethenervefbresconvergetoformtheopticnerve
andexitthebackoftheeyeintotheorbit.Theopticcupisthecentreportionoftheopticdisc
andissmallerbycomparison.The loss of optic nerve cells causes the cup to become larger
relativetotheopticdisc,increasingthecup-to-discratio.
4
Thecuptodiscratiocompares
thediameterofthecuptotheentirediameteroftheopticdisc.Thecup-to-discratioisoften
measuredbothintheverticalandhorizontalpositiontoestimatetheamountofcuppingand
amountofopticnervedamage.Thecuptodiscratioalsoincreasesinnon-glaucomatousnerves
withincreasingdiscdiameter(Crowstonetal,2004).
Largecup-to-discratioshavebeenidentifedasabaselineriskfactorfordiseaseprogressionwith
valuesof>0.4and0.5associatedwithanincreasedriskofprogression.Theunivariateanalysis
completedintheOHTSshowsthattheriskofglaucomaissignifcantlyincreasedwithincreases
incup-to-discratios(Table3.1)asdidtheOHTSGroupandtheEuropeanGlaucomaprevention
StudyGroupetal,(2007)(Table3.2).However,largercup-to-discratiosinocularhypertensive
patientsmaybeanindicationofearlystructuraldamageandthereforeserveasadiseasemarker
ratherthanariskfactor.
fIGURE 3.3: CUP-TO-DISK RATIO
Cup-to-diskratioreferstotheratioofthecupdiameter
totheverticaldiscdiameter.
Source:http://hubnet.buffalo.edu/ophthalmology/site/Home/
Physical_Exam/Cup-to-Disc_ratio_normal_.jpgaccessed
September2006
3.4: CLN1kAL COkNLAL 1HICkNLSS
Athincentralcorneahasbeenshowntohaveastrongassociationwiththeprogressionfrom
ocularhypertensiontoPOAG(Table3.1andTable3.2).Thisrelationshiphasbeenexplainedby
thepossibilitythatlowcornealthicknessmaybeassociatedwithstructuraldifferencesinthe
opticnervearchitecturethatpredisposetothedevelopmentofglaucoma.Anotherexplanation
isthatmeasurementofIOPisaffectedbythethicknessofthecornea.Inthickercorneas,the
trueIOPislowerthanthemeasuredIOP.Ontheotherhand,inthinnercorneas,thetrueIOPis
higherthanthemeasuredIOP.IntheOHTS,thinnercorneaswereassociatedwithahigherrisk
ofdiseaseprogression(Gordonetal,2002).
A thin central cornea
has been shown to
have an independent
association with the
progression from
ocular hypertension
to POAG
4
Axonsfromtheopticnerveformtheopticrim.Centralexcavation(thecup)isfreefromopticnerveaxons.Theneuroretinal
rimthinsfocallyordiffuselyduetoaxonlossinglaucoma.Thisleadstoenlargementofthecupinrelationtotheopticnerve
(increasingthecuptodiscratio).
3. Risk factors
Centre for Eye Research Australia
17 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
fIGURE 3.4: CORNEAL ThICKNESS
Source:UniversityofIllinoisEyeand
EarInfrmaryPositions,TheEyeDigest,
http://www.agingeye.net/mainnews/
glaucomapachymetry.php
3.5: IAMILY HIS1OkY AND GLNL1ICS
first-degree relatives of individuals with primary open-angle glaucoma have up to an eight-
fold increase in the risk of developing the diseasecomparedtothegeneralpopulation(Wolfs
etal,1998;Tielschetal,1994).Weihetal,(2001)foundthat,inmultivariatelogisticregression
modelsandadjustedforage,thestrongestriskfactorforglaucomawasafamilyhistoryof
glaucoma(OddsRatio-OR3.5,95%CI:1.9to6.7).Friedmanetal,(2004)ontheotherhand
concludedthatstrongsupportforanassociationbetweenfamilyhistoryandprogressionfrom
OHTtoPOAGislacking,refectingthatmanystudiesofthelinkbetweenfamilyhistoryand
POAGmaybeaffectedbyascertainmentbiasduetopoorrecallorlackofknowledgeoffamily
history.Forexample,McNaughtetal,(2000)foundthat27%ofpreviouslydiagnosedPOAG
patientswereunawareoftheirpositivefamilyhistory,suggestingthatahigherpercentageof
adultPOAGmaybeinheritedthanhithertoreported.
POAGhasanapparentcomplexormultifactorialaetiology(WeinrebandKhaw,2004).The
chromosomallocationsofseveralgenesthatcanindependentlycausethediseasehavebeen
mapped.More than 43 different glaucoma gene mutationshavebeenreportedinopen-angle
glaucomapatients,andseverallargestudieshavesuggestedthatasagroupthesemutations
areassociated with 3-4% of patients withtheconditioninpopulationsworldwide(Fingertet
al,2002).TheglaucomageneatGLC1Alocus(myocilin)hasbeenshowntobeassociatedwith
bothjuvenileandadult-onsetprimaryopen-angleglaucoma(Sheffeldetal,1993;Stoneetal,
1997;Alwardetal,1998;Fingertetal,1999;Polanskyetal,2000;Clarketal,2001).Thelow
attributableriskportionofgeneticfactorsindicatesthatnon-geneticfactorsplayaninfuential
roleinthedevelopmentandprogressionofglaucoma.
3.6: L1HNICI1Y
Ethnicityhasbeenproposedasariskfactorinmanystudies.Inparticular,Americanbased
studieshavenotedahigherprevalenceandrateofprogressioninAfrican-Americanpopulations.
ResultsfromtheOHTSsuggestthattheAfrican-Americanraceitselfdoesnotincreasethe
riskofglaucomaprogressionbutrefectsahigherprevalenceofotherriskfactorswithinthat
population.AfricanAmericanstendtohavethinnercorneas,higherIOPandlargercuptodisc
ratiosonaveragethanCaucasians(Friedmanetal,2004).
3. Risk factors
POAG has a complex,
multifactorial
aetiology.
first degree relatives
of OAG patients have
an 8-fold increased
risk of developing
glaucoma.
Corneal thickness
18
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3.7: DIA8L1LS MLLLI1US
TheOHTSshowedthatdiabetesmellitusmayprotectagainstprogressionfromOHTtoPOAG
-(hazardratio0.37inmultivariateanalysis,p<0.05)-however,thepeoplewithdiabetes
enrolledinthestudywerecarefullyselected(thosewithdiabeticretinopathywereexcluded)
andmayrepresentanunusuallyhealthydiabeticpopulation(OHTSGroup;EuropeanGlaucoma
PreventionStudyGroupetal,2006).
Twoglaucomamanagementtrialsshowedalinkbetweenthelikelihoodofglaucomaprogression
andthepresenceofdiabetesmellitus(theAdvancedGlaucomaInterventionStudy(AGIS,2002)
andtheCollaborativeInitialGlaucomaTreatmentStudy-CIGTS(Lichteretal,2001)),while
manyothershaveeitherexcludedindividualswithdiabetesornotexaminedanyrelationships
(Friedmanetal,2004).
Populationbasedstudiesaswellasretrospectiveandprospectivecohortstudiesalsoprovide
mixedresults(seeTable3.4)-includingpopulationbasedstudiesinAustralia.WhileMitchell
etal(1997)foundanincreasedprevalenceofglaucomaforthosewithdiabetes(OR=2.12)and
OHT(OR=1.86),astudybyWeihetal,(2001)foundthatwithadjustmentforage,therewas
nosignifcantdifferenceintheprevalenceofglaucomaamongthosewithdiabetesandthose
without(resultsfordiabetesnotpresentedinthearticle).
VariationsinthedefnitionofPOAGmayexplainsomeofthedifferentfndings(deVoogdetal,
2006).Forexample,deVoogdetal,(2006)notethatarevisionintheirdefnitionofPOAGled
toarevisionintheresultsfromtheRotterdamEyeStudy-fromaninitiallysignifcantrelative
risk(RR)oftheprevalenceofPOAGinparticipantswithdiabetesmellitusof3.11(95%CI1.12
to8.66)toanon-signifcantRRof1.40(95%CI0.96to2.03)(DeVoogdetal,2006:1830).De
Voogdetal,(2006)alsonotedthattheresultsfromthemetaanalysisbyBonovasetal(2004)
(seeTable3.4)werebasedonpreviousworkfromtheRotterdamEyeStudywhichhasbeen
revisedbasedonanewdefnitionofPOAG
5
.
The association
between POAG and
Diabetes is not clear.
3. Risk factors
5
TheresultschangedfromaninitiallysignifcantRRoftheprevalenceofPOAGinparticipantswithdiabetesmellitusof
3.11(95%CI1.12to8.66)toanon-signifcantRRof1.40(95%CI0.96to2.03).(DeVoogdetal,2006:1830).
Over 40 gene
mutations have been
reported in POAG.
Centre for Eye Research Australia
19 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
TABLE 3.4: ASSOCIATION BETWEEN DIABETES MELLITUS AND GLAUCOMA
Source Details Assoc.
Bonovasetal,2004
*
Statisticallysignifcantassociationassumingarandomeffects 3
model(OR=1.50,95%CI1.16to1.93)orfxedeffectsmodel
(OR=1.27,95%CI1.10to1.45)
deVoogdetal,2006
RRofincidentopen-angleglaucomawithdiabeteswas0.82 x
(95%CI0.33to2.05)
Dielemansetal,1996
Associationbetweennewlydiagnoseddiabetesmellitusandhighlevelsof 3
bloodglucosewithhigh-tensionglaucoma,OR=3.11(95%CI,1.12to8.66)
Kleinetal,1994
Open-angleglaucomaincreasedwithage-relateddiabetes ?^
(4.2%versus2.0%,inpeoplewithdiabetesversuspeoplewithout)
Weihetal,2001 Withadjustmentforage,morepeoplewithselfreporteddiabetes x
hadpossible,probablyordefniteglaucoma(12/230,5.2%)than
thosewithoutdiabetes(175/4392,2.5%)butthedifferencewas
notstatisticallysignifcant(chisqtest,1df=0.86,p=0.36)
Mitchelletal,1997
PrevalenceofglaucomaandOHTincreasedinpeoplewithdiabetes 3
OR=2.12,95%CI1.18to3.79)(OHT:OR=1.86,95%CI1.09to3.20)
Tielschetal,1995
#
DiabeteswasnotassociatedwithPOAG(OR=1.03,95%CI0.85to1.25)
Pasqualeetal,2006 Type2diabeteswasassociatedtoPOAGinwomenwitha 3
RR=1.82(95%CI,1.23to2.70)
Zghaletal,2000 volutionofopen-angleglaucomaindiabetesdidnot x
signifcantlydifferenttopeoplewithoutdiabetes
Buddeetal,1998 Patientswithorwithoutdiabetesdidnotsignifcantly x
differinthemorphologyoftheopticdisc
Zeiteretal,1994 Peoplewithprimaryopen-angleglaucomaandpredominantly 3
inferiorVFdefectsinoneorbotheyesaremorelikelytohavediabetes
*-Meta-analysis;-RotterdamStudy;-BeaverDamEyeStudy;-BMES;#-BaltimoreEyeSurvey
^Theseresultswereobtainedfromthestudyabstract.Itwasunclearwhetheragewascontrolledinthiscomparison,
thereforetheresultcannotbedeterminedtobeeithersupportiveonnon-supportiveofanassociation.
Withsuchmixedresults,theassociationbetweendiabetesmellitusandglaucomahasnotbeen
modelledhere.Asfuturestudiesarecompletedthisassociationwillbecomebetterunderstood
andcanthusbeincludedinmodellingsomeindirectinterventionscenariossuchasimproved
diagnosisofdiabetesandbetterglycemiccontrol.
3.8: O1HLk O1LN1IAL kISk IAC1OkS
Anumberofotherpotentialriskfactorshavebeenhighlightedincluding:
migraine:theOHTSshowedapositiveassociationalthoughnotstatisticallysignifcant;
myopia(nearsightedness);
hyperopia(farsightedness);
pseudoexfoliation:foundtobeamajorriskfactorforprogressionintheEMGTwhich
includedasmallnumberofpatientswiththiscondition;
outfowfacility:confictingresultsfromprogressionstudies;
malegender;
opticdischaemorrhage;
sleepapnoea;and
peripheralvasospasm
6
.
Ingeneral,thelimitednumberofstudiesinwhichtheseadditionalsuspectedriskfactorswere
evaluateddoesnotsupportfrmconclusionsconcerningtheirrelativeimportance.
3. Risk factors
6
Aperipheralvasospasmisacontractionofabloodvesselreducingitsinternaldiameterandbloodfow
intheouterpartofthevisualfeld.
Figure3.5:Pseudoexfoliation
pupilmargin.
20
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Centre for Eye Research Australia
The effect of the
disease and its
treatment on a
patients health
and quality of life
is a key outcome
for measuring the
economic impact
of disease.
In this section, the characteristics of the disease are discussed - remission, mortality, progression
and nally, prevalence and incidence. Estimates of prevalence and incidence were modelled
based on Melbourne Visual Impairment Project (MVIP) and BMES data and knowledge of
remission, and mortality drawn from the literature. Progression rates were modelled based on
the literature, previous modelling work and taking into account the available data on prevalence
and incidence by age and visual impairment.
The key outcome for measuring the economic impact of disease is the effect of the disease and
its treatment on a patients health and quality of life. For eye disease, the key outcome is vision
loss. Deterioration in vision is a fundamental determinant of the costs of glaucoma (particularly
indirect costs such as participation in the workforce, need for care and vision aids, as well as
quality of life). In the case of glaucoma, however, non-vision, physiological changes (changes in
IOP or optic disc for example) may also determine treatment, and therefore health system costs.
While the costs of the disease are measured and incurred by individuals, diagnosis and quality
of life depend on the interrelationship between vision in each eye. In some patients, glaucoma
may affect only one eye. If it affects both eyes, disease severity and progression in each eye can
differ, so there is often a better eye and a worse eye. Further, eyes that were originally better
may become the worse eye over time. While a diagnosis of glaucoma is based on the worst
eye, quality of life - on the other hand - is determined by the best eye (Brown, 1999, Kobelt
et al, 2006:369).
4.1: DEFINITION OF DISEASE STAGE
There are ve disease stages in the model which are discussed and dened throughout the text
below. For ease of reference, a summary of the disease stages is provided in Table 4.8.
4.2: REMISSION
Currently there is no natural remission in open angle glaucoma (to either no disease or
an earlier stage of the disease), nor any current treatments that improve VF or acuity.
Consequently the remission rate for every stage of the disease is nil.
4.3: MORTALITY
General population mortality rate forecasts are from the Access Economics Demographic Model
(AE-DEM) of the Australian population (see Section 4.4 for more information).
The rate of mortality from glaucoma is assumed to be determined by the persons level of visual
impairment people do not die from glaucoma itself but from associated complications such
as higher rates of accidental falls, isolation and depression (which are implicit in the calculation
of the RR of mortality). McCarty et al, (2001) estimated that visual impairment (best corrected
visual acuity of <6/12) was associated with a signicantly increased risk of mortality (OR
adjusted for age, sex, country of birth, smoking, hypertension and arthritis of 2.34), which
converted to a RR is 2.15.
The RRs of mortality from vision loss by disease stage used in the model are loosely based on
McCarty et al (2001)
7
and fall with age as per Table 4.1.
4. Epidemiology
7
2.34 plus 0.67 (the difference between 1 and 1.67 or between 1.67 and 2.34).
21 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
The impact of disease
on vision determines
the impact on health
and quality of life.
TABLE 4.1: RELATIVE RISK OF MORTALITY BY STAGE OF VISUAL IMPAIRMENT
Age OHT/EDS Mild Moderate Severe
40-44 1.00 1.67 2.33 3.00
45-49 1.00 1.67 2.33 3.00
50-54 1.00 1.67 2.33 2.99
55-59 1.00 1.66 2.32 2.98
60-64 1.00 1.66 2.31 2.95
65-69 1.00 1.65 2.29 2.91
70-74 1.00 1.64 2.26 2.85
75-79 1.00 1.62 2.20 2.75
80-84 1.00 1.59 2.11 2.59
85-89 1.00 1.53 1.98 2.37
90+ 1.00 1.45 1.79 2.06
Source: Loosely based on McCarty et al, (2001).
The aetiological fraction for mortality due to glaucoma (as opposed to the number of
people who died) is 1.27% based on the same techniques used in CERA (2004: 37) but using
updated data.
4.4: POPULATION
Forecasts of the Australian population are fromAE-DEM which uses a combination of fertility,
mortality and migration rates to project the future Australian population. Base fertility and
mortality proles for each age and gender (for mortality) are sourced from Productivity
Commission (2005), and adjust over time to match the projection for the total value. Migration
rates are projected in line with the assumptions in the Australian Bureau of Statistics (ABS)
publications: Australian Demographic Statistics (catalogue number 3101.0) and Overseas
Arrivals and Departures (catalogue number 3401.0), with adjustments for changes to Australias
migration program and to reect the latest actual migration (international and interstate) results.
4.5: PROGRESSION
For this dynamic study, a key parameter is the rate at which POAG causes vision to deteriorate
(the rate of disease progression). The impact of disease on vision determines the impact on
health and quality of life. Unfortunately, in studies of glaucoma, disease progression is not
always measured in terms of vision loss. Clinical studies often use a combination of changes in
VF, IOP and optic disc as indicators of progression. As IOP is the focus of treatment, treatment
efcacy is generally measured according to its impact on IOP. Further, denitions of vision loss
vary across researchers.
4. Epidemiology
22
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Centre for Eye Research Australia
Measuring and grading glaucomatous vision loss
MeasuringtheprogressionofVFLinglaucomaiscomplex(seeBox3foranexplanationofthe
methodoftestingVF).
Glaucomatouschangeneedstobeisolatedfromotherfactorssuchaschangesinlens
opacityduetocataract,orphysiologicalchangeduetoageing.
Therecanbesubstantialmeasurementvariability(causedforexamplebylossoffxation),
andthereisalearningeffect,bothofwhichneedtobeaccommodatedwhenexamining
patients.
Glaucomatousvisiondeteriorationisveryslow.Evenwhenachangeinfeldisdetectedvia
perimetry,thepatientmaynotnoticeanyvisionloss.Clinicalstudieshavefoundthatonlya
subsetofpatientswithOHTdevelopglaucoma,andofthese,asmallproportionlose
functionalvisionduringthecourseoftheirlifetime.
Further,differentresearchershavedevelopeddifferentgradingsystemstomeasureprogression.
Forexample,theAGIS,EMGTandCIGTSalluseddifferentgradingsystemstomeasure
progression.OthergradingsystemsincludethosedevelopedbyAnderson,Blumenthal,and
Hodapp-Anderson-Parrish(HAP).
Differentgradingsystemsshowdifferentratesofprogressioninthesamepopulation(Zahariet
al,2006,Wilsonetal,2002).Thereisnogoldstandard,soitisdiffculttocompareprogression
ratesderivedfromstudiesusingdifferentmethodologies(Katzetal,1999).Comparisonsof
progressionratessuggestthatratesproducedusingtheAGISmethodmightrepresentalower
boundinjudgingprogression,andtheCIGTSandEMGTmethodsproducerelativelysimilar
results(Katzetal,1999,Wilsonetal,2002,Zaharietal,2006).
Weinrebetal,(2004)developedamethodologyforovercomingthisproblem(section4.5.1.).
8ox 3: Measuring change in VI
VFistestedbyexaminingapatientsabilitytodetectlightatvariousintensitiesatvarious
testlocationsintheVF.Thedimmerthelightdetected,thebetterthevisionatthatpoint
inthefeld.Theresultsoftestsaregenerallyexpressedinadecibelscalederivedfrom
thereciprocalofthelogintensityofthelightprojected.Thusdetectionofdimmerlight
(representingbettervision)isindicatedbyhighernumbers.Thesenumberscanbeusedto
createagradingsystemforVFL.ParametersfromVFtestsusedtomeasurefeldlossare:
a) Meandeviationordefect-themeasurementofhowthemeanofthepatientsresponses
variesfromthemeanoftheresponsesofaseriesofnormalpatientsofsimilarageunder
similartestingconditions.Meandeviationisaffectedbymediaopacity,refractiveerror
andglaucoma.
b) PatternSD,alsoknownascorrectedlossvariance,representsnon-uniformlossoffeld
thusprovidinganindicationoffocaldefectsasoccuringlaucoma.
4. Epidemiology
Patients enrolled in
clinical trials do not
necessarily represent
the community norm.
Where possible
population-based
data has been used.
23 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
4. Epidemiology
The importance of study population characteristics in selecting progression
rates for modelling
Ideally,inselectingprogressionratesformodelling,dataneedtobedrawnfromstudiesthat
arebasedonpopulationswithsimilarcharacteristicstothatbeingmodelled.Asnotedin
section3,anumberoffactorscanaffectprogressionratesincludingage,IOP,centralcorneal
thicknessandcuptodiscratio,orAfricanAmericanorigin(forexample).Inaddition,patients
withpseudoexfoliationsyndromeandpigmentaryglaucomaareoftenincludedtogetherwith
POAGpatientsinstudiesoftreatmenteffcacyanddiseaseprogression.Whiletheidealwould
involverecalculationoftheresultswheretheinclusionofthesepatientshasamaterialimpact
ontheprogressionestimates,thereportedresultsoftenprecludere-calculationexcludingthese
participants.
Further,theparametersselectedforthemodellingneedtorefectthelikelyoutcomesof
administeringtherapyinthecommunity,ratherthansimplyreplicatingthetrials.Progression
ratesbasedonestimatesfromclinicaltrialsdonotnecessarilyrefecttheexperienceinthe
community.Those enrolled in clinical trials often do nothavediseaseriskproflesorhealth
serviceutilisationhabitsthatrepresent the average or community norm.Asanexample,
Hensonetal,(2006)suggestedthatglaucomaprogressionratesfoundinretrospectivestudies
tendtobehigherthanratesderivedfromprospectivestudiesbecausepatientswillingtoenrol
inprospectivestudiesmaybemoreconcernedabouttheirconditionandarelikelytobemore
attentive,demandingandcompliantwiththeirtherapythanaverage.
Constant or variable linear progression
Somestudieshavefoundthatprogressionratesspeedupasdamageworsens(forexample,
Martusetal,2005),whileothershavefoundtheopposite(eg.Raskeretal2000).Thereisalso
someevidencethatprogressionisepisodicratherthanconstant,forexample,Kwonetal,(2001)
foundthataround25%patientsshowednon-lineardiseaseprogression.
4.5.1: NATURAL (UNTREATED) PROGRESSION
Dataondiseaseprogressioninuntreatedpatientsisavailablefromtheplaceboorobservation
armsofclinicaltrials(withtheprovisoabovethattheexperienceofparticipantsinclinicaltrials
maynotmatchthatofthecommunityatlarge).Inaddition,JayandMurdoch(1993)estimated
untreatedprogressionandWilsonetal,(2002)examineduntreatedprogressioninblackpatients.
ThesestudiesaresummarisedinTable4.3.Despiteexaminingprogressionratesintreated
patients,Hattenhaueretal,(1998)isincludedinthetableforthereasonsoutlinedbelow.
ThedatainthetablesuggestthefollowingnaturalpopulationprogressionratesforOhT to
POAG(notingthatthedistinctionbetweenOHTandglaucomaisbasedonclinicianobservation
ofclinicalsignsaswellasinmostcasesdetectionofVFL):
DatafromtheOHTSsuggestprogressionratesforwhitepatientsof2%peryear.
Forallparticipants,theratewasjustunder2%peryear.
DatafromtheEGPSsuggestannualprogressionratesforOHTtoPOAGofaround3.4%.
24
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Centre for Eye Research Australia
4. Epidemiology
DatafromTable4.3suggestthefollowingprogression rates for POAG(notingthatprogression
isdefnedindifferentwaysasperthediscussionabove):
FortheEMGT,themostrecentdata(Leskeetal,2007)suggestannualprogressionrates
ofbetween9and10%,whereasLeskeetal,(2003)foundannualprogressionratesof
justover10%.
FromWilsonetal(2002),progressiontoatleastunilateralblindnessinblackpatientswas
1.6%peryearaccordingtotheAGIScriteria,and3.5%accordingtotheCIGTScriteria.
DatafromtheCNTGSsuggestanannualprogressionrateof6.6%.
Weinrebetal,(2004)synthesisedtheseresultsbymodellingtheriskofblindnessinpatients
withOHTusingtheOHTS,Hattenhaueratal,(1998),andWilsonetal,(2002).Theselected
endpointwasunilateralblindnessasanindicatoroftheseverityofVFdeteriorationthatcanbe
comparedacrossdifferentstudies.Weinrebetal,(2004)assumedthatprogressionratesfrom
OHTtoblindnesscanbeestimatedbyaddingthetimereportedforprogressionofOHTto
glaucomafromonestudywiththetimereportedforprogressionfromglaucomatoblindness
inanotherstudy(Weinrebetal,2004:462).Inaddition,progressionwasassumedtobelinear
(Weinrebetal,2004:462).ProgressionratesfromHattenhaueretal,(1998)werealsoused
despiteostensiblybeingbasedontreatedpatients.Weinrebetal,(2004)arguedthatthe
treatmentregimensintheHattenhauerpopulationbasedonpatientsnewlydiagnosedwith
POAGbetween1965and1980maynotrefectcurrentorevenrecenttherapyandthus
thesepatientscouldbeconsideredonlypartiallytreatedoruntreated.TheHattenhaueretal
(1998)progressionratesmightalsobeerroneouslyhighbecauseoflackofdataonothercauses
ofvisionloss,thusWeinrebetal,(2004:465)usedtheseasanupperbound.Theestimatesof
theprobabilityofapatientwithOHTdevelopingglaucomaandfnallybecomingblindinone
eyeover15yearscalculatedbyWeinrebetal,(2004)were:
1.5%OHTSandWilsonetal,(2002)AGIS;
2.6%OHTSandHattenhaueretal,(1998);
3.3%OHTSandWilsonetal,(2002)CIGTS;and
10.5%Hattenhaueretal,(1998).
ResultsfromtheEGPS(2005)werenotavailablefortheWeinrebanalysis.Ifthese
aresubstitutedfortheOHTS,thecalculatedprobabilitiesare:2.7%,4.5%,5.9%
and10.5%respectively.
ItisworthnotingthattherelativevalueofHattenhaueretal,(1998)isthatthedatawere
drawnfromadatabaseofmedicalrecordsforallsourcesofmedicalcareusedbythelocal
populationofOlmstedCounty(USA).Asapopulationbasedstudy,theresultsareprobably
morerefectiveofexperienceinthecommunity.Bycomparison,longitudinalstudiesofmedical
recordsfromspecifcmedicalcentresmaybebiasedbecauseofthetypesofpatientspresenting
totheclinic,orbecauseofthetreatmentapproachattheclinic(forexample,treatmentmaybe
moreaggressive).
Centre for Eye Research Australia
25 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
TwoexamplesofratesmarkedlylowerthanthoseofHattenhaueretal,(1998)arebelow:
Chen(2003)examinedrecordsfor186patients,(82%white),diagnosedwithPOAGin1975
orlaterandwhopresentedtoatertiaryreferralclinic(UniversityofWashingtonMedical
Centre).Heestimatedthattheprobabilityofprogressionfromglaucomatounilateral
blindnessat15yearswas14.6%(95%CI7.6-21.6)andtobilateralblindnesswas6.4%
(95%CI0-14.4).
Similarly,Kwonetal,(2001)studied40eyesof40patientsfollowedataUniversityclinic
since1972withPOAGandfoundthataround13%ofeyeswerelegallyblindafter15years,
noting,however,thattheselectionofpatientsmayhavebeenbiasedtowardsthosewith
worseglaucoma.
Table4.2providesasummaryofthefndingsofthestudiesofnaturalprogression.Notably,
progressionfromOHTtounilateralblindnessislowerthanfromPOAGtounilateralblindness
sincesomeofthosewithdetectedOHTdonotprogresstoglaucoma.
TABLE 4.2: NATURAL PROGRESSION RATES (CUMULATIVE PROBABILITY) 15 YEAR PERIOD
Start point Unilateral blindness Bilateral Blindness
OHT 1.5%to10.5%(Weinrebetal,2004) 3%(Hattenhaueretal,1998)
Glaucoma 40.5%(Hattenhaueretal,1998) 16.5%(Hattenhaueretal,1998)
Initially, the approach was to apply the progression rates from the Weinreb et al, (2004)
synthesis in the modelling. Unfortunately,itwasnotpossibletomatchtheWeinrebetal,
(2004)rateswiththeavailableincidenceandprevalencedatafromtheMVIPandBMESto
obtainsensibleprojections(seeSection4.6).Inaddition,forthemodelitwasnecessaryto
measureprogressofmildormoderatevisionloss,buttheWeinrebetal,(2004)rateswereonly
forblindnessasdefnedintheUSA.TheestimatesoftheproportionofpeoplewithPOAGin
eachvisualimpairmentseveritygroup(earlystage,mild,moderateandsevere)fromMVIP/BMES
datawerebasedonsmallsamplesizes.Further,MVIPandBMESdataarebasedonamixed
populationwithbothtreatedanduntreateddisease.
final progression rates were therefore derived using the available MVIP and BMES incidence
and prevalence data and the splits of disease severity(themethodologyisoutlinedinmore
detailinSection4.6below).Smoothedprevalencerateswereused,andthediagnosisratewas
setat50%(consistentwithresearchfndings).Thisledtoannualprogressionratesthatarefor
themostpartsubstantiallyhigherthanexpected(andhigherthanWeinrebetal,(2004))but
internallyconsistentwiththeotherparametersfromtheliteratureandpopulationstudiesused
inthemodel.Clearlymoreresearchandpopulationstudiesinvestigatingincidence,prevalence
andprogressionofbasedonstandardclassifcationsofvisualimpairmentareclearlyrequired.
4. Epidemiology
26
Tunne l Vi s i on
Centre for Eye Research Australia
Insummaryandforthepurposesofmodelling,the annual natural progression rates are:
OHTtoEDS:31.2%oftheOHTpopulationperannum(markedlyhigherthan
studiessuggest)
8
;
NormotensivetoEDS:approximateaverageof0.22%oftheAustralianpopulation
perannum;
EDStoMild:1.5%ofthosewithPOAGperannum(intherangeofwhatstudiessuggest);
MildtoModerate:85.0%(markedlyhigherthanstudiessuggest);and
Moderatetosevere:30.0%(markedlyhigherthanstudiessuggest).
4. Epidemiology
8
Whilethisnumberappearshigh,itisimportanttonotethattheprevalenceofOHTwasonlyrecordedforindividuals
thatwere40yearsandoverandasdiscussedearlierinSection2theaetiologyofPOAGresemblesthatofacontinuum.
Itisthereforeverylikelythat,byonlyincludingpeopleagedover40yearsofage,thetotalprevalenceofOHTisbeing
underestimated.
Centre for Eye Research Australia
27 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
T
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28
Tunne l Vi s i on
Centre for Eye Research Australia
T
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34
Tunne l Vi s i on
Centre for Eye Research Australia
Current treatment regimens centre on the only known treatable risk factor for glaucoma
- intraocular pressure (IOP). Management is directed at establishing and maintaining targets
for reducing IOP. No level of IOP is safe for every patient. In general, the initial target aims to
achieve a 20-50% reduction from the initial pressure at which damage occurred.
Patients with a lower than average risk of glaucoma (<5%) could be observed and monitored
without treatment. For those patients who are at moderate risk of glaucoma (5% to 15%),
a well-informed patient can decide with his or her physician whether to treat or not.
In patients with a higher than average risk (>15%), treatment for all should be considered
(Weinreb et al, 2004).
Clinicians attempt to achieve IOP reductions and control glaucoma by stepping patients through
the following course of treatment:
1) Medication;
2) laser therapy (ALT or Selective Laser Trabeculoplasty (SLT) and medication combined;
and nally
3) surgery.
The treatment pattern in most cases is the same regardless of the stage at which the disease
is diagnosed - that is, patients presenting with both early stage disease and severe disease
commence treatment with medication. Occasionally, laser (if compliance is likely to be poor)
or surgery (if medical therapy is likely to fail or not be tolerated) are used as rst line therapy.
The side effects of treatment are discussed later in Section 5.6.
5.1: MEDICATION
Medication is the rst stage of treatment, usually in a topical form (eye drops), but an oral form
also exists. A range of medications are available for the reduction of IOP, summarised in Table
5.1. Prostaglandin analogues and beta ()-adrenergic antagonists are the most frequently used,
with topical prostaglandins now the drug of choice in Australia - Lumigan (bimatoprost), Xalatan
(latanoprost), Travatan (travoprost). The proportions of medication types used have shifted over
time, particularly since the introduction of prostaglandin analogues in 1997 (Figure 5.1). Based
on MVIP data, Weih et al (1998) found that the most common glaucoma medications used were
()-adrenergic antagonists (63%), followed by sympathomimetics (18%) and cholinergic agents
(16%). The authors also noted the shift to ()-adrenergic antagonists and away from the use of
pilocarpine over the previous 20 years.
Medications reduce the amount of aqueous humour being produced and/or increase the outow
of aqueous humour from the eye. This can be via the conventional outow pathway through
the trabecular meshwork or by the non-conventional outow pathway (uveo-scleral outow
pathway). Some medications do both.
A topical medication can enter the blood supply through the naso-lacrimal drainage system
leading to systemic side-effects (ie. side effects in the rest of the body as well as the eye).
Systemic side-effects can be reduced substantially with the use of punctal occlusion and gentle
eye lid closure for more than two minutes. Side effects are discussed in Section 5.6.
5. Treatment
Current treatment
regimens centre
on the only known
treatable risk factor
for glaucoma -
intraocular pressure
(IOP).
35 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
TABLE 5.1: IOP LOWERING MEDICATIONS
Medication Features
Prostaglandin analogues (prostamides) Improve the ow of aqueous humour out of the eye through
the non-conventional (uveo-scleral) outow pathway.
First-line treatment. Once daily application. Effective IOP
reduction (bimatoprost, latanoprost, travoprost)
adrenergic blockers Reduces the production of aqueous humour (betaxolol,
carteolol, levobunolol, metipranolol, timolol).
Alpha () 2 adrenergic agonists Reduce secretion of aqueous humour, and increase aqueous
outow. Less effective in reducing IOP than prostaglandin
analogues (apraclonidine, brimonidine).
Carbonic anhydrase inhibitors Reduce aqueous secretion, used two to four times a day
(dorzolamide and brinzolamide - topical - acetazolamide
and methazolamide - oral).
Topical forms are not as effective as oral forms.
Cholinergic agonists Increase aqueous outow through the conventional outow
pathway, used up to four times daily (pilocarpine, carbachol).
Source: Weinreb and Khaw (2004:1716).
FIGURE 5.1: GLAUCOMA MEDICATION DISPENSED BY YEAR AND TYPE OF SCRIPT
(% OF TOTAL SCRIPTS)
Source: Australian Statistics on Medicine 1997, 1998, 1999-2000, 2001-2002, 2003.
If a medication fails to reduce IOP, it is generally replaced with an alternative agent or combined
with other agents until effective IOP control is established. Some recent studies
10
from the
literature show the number of medications taken in combination (Table 5.3).
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1997 1998 1999 2000 2001 2002 2003
%
t
o
t
a
l
s
c
r
i
p
t
s
Other Anti Glaucoma
Preparations
Carbonic Anhyrase
Inhibitors
Cholinergic Agonists
2 Adrenergic Agonists
Beta Blocking Agents
Prostaglandin
Analogues
5. Treatment
10
Recent studies are preferred because medication efcacy has been improving over time.
36
Tunne l Vi s i on
Centre for Eye Research Australia
Ingeneral,mostpatientsaretakingtwoormoremedicationsbythetimetheyareconsidered
inneedoflasertreatmentorsurgery.Formodelling,thetotalcostsofmedicationsusedwere
dividedbythenumberofpeopleaffected(thisisexplainedinsection6.3.2).Theproportionof
eachmedicationtypedispensedwastakenintoaccountinthecalculationfortotalmedication
costs,withsimilarproportionsofmedicationsreportedbystateandterritory.
TABLE 5.2: PROPORTION Of EACh DRUG CLASS BY STATE, 2005
Prostaglandin b-blocker Carbonic a2 Cholinergic
Anhydrase Adrenergic Agonist
Inhibitor Agent
NSW 51.2 26.2 12.4 7.2 3.0
VIC 53.6 24.2 12.5 7.5 2.3
QLD 55.4 26.4 10.4 4.6 3.3
SA 54.2 28.9 8.5 5.8 2.6
WA 52.9 29.0 10.2 5.9 2.0
TAS 54.2 29.5 9.5 5.2 1.8
ACT 56.2 22.6 14.3 4.4 2.4
NT 61.8 19.6 11.3 5.5 1.7
Source:PBSItemdatabase.
5. Treatment
Centre for Eye Research Australia
37 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
TABLE 5.3: NUMBER Of MEDICATIONS TAKEN IN COMBINATION
Source Number medications in combination
OHTS(Kassetal,2002) SeeBox4foradescriptionoftheOHTS.At60months,inthe
medicationgroup,39.7%ofparticipantswerereceivingtwoor
moremedicationsand9.3%werereceivingthreeormore.
WeinandandAlthen(2006) Nonrandomisedprospectivenon-comparativeclinicalstudyof
52eyesof52patientsoftheeffectofSLTasanadjunctivetreat
mentoneyeswithadvancedglaucomatousdamage.Patients
wereincludediftheyhaduncontrolledIOP(20mmHg)onmaxi
mumtolerablemedicaltherapy,orhadfailedpreviousALT.
Patientshadalonghistoryofglaucomatreatmentandweresent
forfurthertreatmenttothehospitalandsomaybeconsidered
tohaveglaucomathatismorediffculttocontrol.Theaverage
numberofhypotensivemedicationstakenincombinationprior
totreatmentwas2.5.
Damjietal,(2006)(a) InCanada,176eyesof152patientswereincludedina
randomisedclinicaltrialcomparingALTandSLTintermsoftheir
abilitytolowerIOPinpatientswithOAG.Patientsweregiven
laseriftheyhaduncontrolledIOP(16mmHg),wereon
maximummedicaltherapyorhadfailedprevious180/360ALT
(>6monthspreviously),wereover18andhadtwosightedeyes.
PatientswereexcludediftheyhadadvancedVFdefectwithin
10degreesoffxation,orhadpreviousglaucomasurgery.
Themeannumberofmedicationspretreatmentwas2.4for
ALTpatientsand2.6forSLTpatients.
Fontanaetal,(2006)(a) 292eyesand225patientswereincludedinaretrospective
cohortstudyofphakicpatientswithOAGwhounderwentinitial
trabeculectomywithadjunctiveMitomycinC(MMC)between
August1997andDecember2003.Eyesthathadundergone
previoussurgeryforcataractorglaucomawereexcluded.
97%ofeyeswerereceivingmedicaltreatmentbeforesurgery
withameanof2.7medications(SD1.0).
Ehrnroothetal,(2002)(a) InFinland,aretrospectiveevaluationofpatientsundergoing
trabeculectomywithoutantimetaboliteswasconducted.
IndicationsfortrabeculectomywereuncontrolledIOPdespite
maximaltoleratedmedicationanddiseaseprogression.Priorto
surgery,POAGpatientshadbeenonglaucomamedicationfora
mean(SD)of7.8(5.6)years.Around2%ofpatientswereon
zeromedication,12-15%ononemedication,55-64%ontwo
medications,20-29%onthreemedications.Around55%were
onoralmedications.
(a)Theremaybeselectionbiasinthesestudiesandthereforeahigherrateofprescribing.
5.1.1: COMPLIANCE AND PERSISTENCE WITh MEDICATIONS
Thedefnitionsofadherence,complianceandpersistenceinthissectionaredrawnfromthe
journalarticlesthemselves.Defnitionsandmethodsofmeasurementdifferacrossstudies.
Adequate treatment of glaucoma and preservation of vision requires adherence to therapy
(Schwartz,2005;Chen,2003),althoughtheexactrelationshipbetweencomplianceand
38
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Centre for Eye Research Australia
progressionofdiseasehasnotbeenquantifed(Olthoffetal,2005).Studiesindicate relatively
poor adherence to therapy in one-third or more of patients,dependingonthemedications
used(AAO,2005:13).
Nordstrometal,(2005)calculatedthedurationofcontinuoustreatmentwiththeinitially
prescribedmedication(defnedinthearticleaspersistence)andtheprevalenceofuseofthe
initialmedicationatvarioustimepoints(defnedinthearticleasadherence)fromhealth
insuranceclaimsdata.Claimsfrom3,623peoplewithnewlydiagnosedglaucomaand
from1,677glaucomasuspectswereexamined.Fourdrugclasseswereincluded:
beta-blockers,alpha-agonists,carbonicanhydraseinhibitors,andprostaglandinanalogs.
Nearlyhalfofthosewhohadflledaglaucomaprescriptiondiscontinuedalltopical
hypotensivetherapywithinsixmonths,and37%hadreflledtheirinitialmedicationat3
yearsafterthefrstdispensing.Prostaglandinswereassociatedwithbetterpersistenceand
betteradherencethanotherdrugs.Patientswithdiagnosedglaucomaweremorelikelyto
adheretotreatmentthanglaucomasuspects.
Schwartz(2005)conductedaliteraturereviewofresearchpublishedbetween1980and
October2004oncomplianceandpersistencewithtreatmentbypatientswithPOAGor
OHT.Compliancewasdefnedastheextenttowhichpatientsbehaviourscorresponded
withprovidersrecommendations.Schwartz(2005)foundthatnon-complianceratesof
25%werecommonlyreported.Usingelectronicmonitoring(themostaccuratemethodof
estimatingpatientcompliance),non-complianceratesrangedfrom14%to24%.Persistence
over12months(thetotaltimeontherapy)wasaround25%(rangingfrom20%to64%).
Olthoffetal,(2005)conductedaliteraturereviewofarticlespublishedfrom1970to
February2004oncompliancewithglaucomamedications.(POAGaswellasothertypes
ofglaucomawereincluded.)Compliancewasdefnedasthedegreeofcorrespondence
betweentheprescribedtreatmentregimeandthepatientsactualdosinghistory.The
proportionofpatientswhodeviatedfromtheirprescribedmedicationregimenrangedfrom
5%to80%(thefgureof5%camefromastudyonPOAGpatients).30%ofpatientsfor
whomtimololwasprescribeddeviatedfromtheirtreatmentregimen.
Tsai(2006)undertookaliteraturereviewofarticlespublishedonMedlineduringthe18
monthstoOctober2005andfoundthatnon-adherence(extentofdisagreementbetween
theprescribedmedicalregimenandactualpatientpractice)tomedicinalregimensin
patientswithglaucomavariedfrom24%to59%.
Reardonetal,(2004)examinedpatientpersistenceusingrecordsfromamanagedcare
databaseintheUS.PatientshadinitiatedmonotherapybetweenJuly1996andJune2002
withbetaxolol,bimatoprost,brimonidine,dorzolamide,latanoprost,timolol,ortravoprost.
Thenumberofpatientsincludedintheanalysiswas28,741.Discontinuationwasdefned
asnofurtherindexdrug(monotherapydrug)refll90days(ifdispensedonebottle)or180
days(ifdispensedtwobottles)afterthelastprescriptionfll.Persistencewasdefnedasthe
numberofdaysfromdispensedatetodiscontinuationdateorchangeofmedicationdate
(whicheverisearlier).Latanoprostwasthereferencegroupagainstwhichdiscontinuation
dateswerecompared.At12months,33%ofpatientswerepersistingwithlatanoprost
(hadnotdiscontinued);and19%ofthosetreatedwithotherocularhypotensiveshad
notdiscontinued.Thedifferencebetweenlatanoprostandotheragentswassignifcant
(p<0.001).Inthepopulation(28,741patientsonmonotherapy),thethreemostfrequently
prescribeddrugsweretimolol(43%),latanoprost(33%)andbrimonidine(18%).Relatively
fewpatientswereprescribedeithertravoprostorbimatoprost(1%ofpatientsforeach).
5. Treatment
Ongoing adherence
with daily glaucoma
drops is a major
problem.
Centre for Eye Research Australia
39 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
Meta-analysisisnotusefulinsynthesisingtheresultsofthesestudiesbecauseofthedifferences
indefnitionsandmethodsofmeasurement.However,compliance rates of 75% seem a
reasonable assumption, with persistence rates of 33% for latanoprost and 19% for other
medications at 12 months(basedonReardonetal,2004).Themedicationcostestimates
usedinthemodellingarecalculatedbasedonthecostsofdispensedmedicationsforPOAGin
Australia,andsoimplicitlyincludepersistence.
5.2: LASLk 1kLA1MLN1
ThosewhoseIOPisnotcontrolledonmedicationareconsideredforlasertherapy.Twotypesof
lasertherapyareavailable,forthereductionofIOP,butvaryinusagedependingonthestatein
whichglaucomahasprogressed.
Lasertrabeculoplastyisthemainformoftreatment.
LaserdiodecyclophotocoagulationisrarelyusedinPOAGandnotthereforeincludedin
modelling.
LASER TRABECULOPLASTY
Lasertrabeculoplastyaimsto improve outfow through the trabecular meshwork. Itisusually
performedundertopicalanesthesia.Therearetwotypesoftrabeculoplasty.Argon Laser
Trabeculoplasty (ALT)wasdevelopedseveraldecadesago.Itwasfollowedmorerecently
bythedevelopmentofSelective Laser Trabeculoplasty (SLT). Whilethereissomeevidence
thattherearefewersideeffectswithSLT(LatinaanddeLeon2005),thisremainsunprovenin
arandomisedclinicaltrialsetting.Forthepurposesofthisstudy,theeffcacyofALTandSLT
areconsideredthesame.StudieshaveshownequivalencyofSLTtoALTinpatientsinwhom
maximalmedicaltherapyhasbeenunsuccessful(McIlraithetal,2006,Juzychetal,2004and
Damjietal,2006).
Thelaseriseitherappliedtoallofthetrabecularmeshworkatonce(360degrees)ortojusthalf
(180degrees).Thereisnoconsensusaboutwhichapproachispreferable,butwhere180degree
laserisundertakenfrstandglaucomaremainsuncontrolled,afurther180degreetreatmentwill
beconductedonthepreviouslyuntreatedsegmentofthetrabecularmeshwork.
Thepressureloweringeffectoflaserdiminishesovertime(Feldmanetal,1991).Repeatlaser
(anyALTofthetrabecularmeshworkafteracomplete360degreeALT(Feldmanetal,1991))
iscontroversial.RepeatALThasamarkedlyreducedeffectcomparedwithinitiallaser
11
andis
associatedwithanincreaseintheriskofanadverseriseinIOP.
DatafromtheMedicareBeneftsSchedule(MBS)forlasertrabeculoplastyarepresentedin
Figure5.2.ThedataareforMBSitemnumber42782(defnedaseachtreatmenttooneeyetoa
maximumoffourtreatmentstothateyeinatwoyearsperiod)
12
.TheMBSfeeforitemnumber
42782fromthe1November2006ScheduleisA$398.65.
11
Forexample,Feldmanetal,(1991)concludedthatrepeatALTwasnotgenerallyeffectiveforthelongtermcontrolof
OAG.Intheirstudy,repeatALTwassuccessfulin21%ofeyesatoneyear,and5%ofeyesat48months.Richteretal,
(1987)foundthatIOPcontrolwassuccessfulin33%ofeyesoneyearafterrepeatALTandinonly14%ofeyesafter1.75
years.Bothstudiesdefnedsuccessasa3mmHgorgreaterdecreaseinIOPtolessthan22mmHgandnofurthersurgical
intervention.
12
MBSitemnumber42783(Lasertrabeculoplastyeachtreatmentto1eyewhereitcanbedemonstratedthata5thor
subsequenttreatmenttothateye(includinganytreatmentstowhichitem42782applies)isindicatedina2yearperiod)
isextremelyrarelyusedoneprocedurerecordedagainstthisitemnumberin2002,threeproceduresrecordedin2003
andnegativeoneprocedurein2005.Otherwisezeroproceduresfortherestoftheperiodbetween1994and2006.
Laser trabeculoplasty
aims to improve
outfow through the
trabecular meshwork.
40
Tunne l Vi s i on
Centre for Eye Research Australia
TheMedicaredatainFigure5.2includeonlyprocedurescoveredbyMedicareie.theyexclude
proceduresundertakenonpublicpatients(bothadmittedandnon-admitted)inpublichospitals
(fundedbythehospital)andproceduresoncompensablepatients(forexample,fundedby
workerscompensationorganisations).
13
However,ingeneral,trabeculoplastiesareundertaken
atadoctorspracticeandadmittedpatienthospitalproceduresrepresentanexception.Hence,
forthemodelling,theMedicaredataareassumedtoadequatelyrepresentthenumberof
trabeculoplastyproceduresundertakeninAustralia.
ThenumberofMBSproceduresfellfrom16,809in1996,to6,201in2003,beforeincreasing
againto11,113in2006.Thisprobablyrefectstosomeextentgreateruseofprostaglandin
analogueswhichreplacedordelayedtrabeculoplastyprocedures.Itmayalsorefectthe
increaseduseofSLToverALT.
Itisestimatedthathalfthepeoplethatreceiveatrabeculoplastyprocedurehavetwo180
degreetreatmentswhiletheremaininghalfreceiveone(personalcommunication,Professor
JonathanCrowston15thMay2007).Thecostsoftrabeculoplastyhavebeenadjustedupwards
by1.5inthemodelaccordingly(seeSection6.3.2).
fIGURE 5.2: MBS TRABECULOPLASTY PROCEDURES, 1994-2005
Source:MedicareAustraliastatistics,MBSitemnumber42782(Lasertrabeculoplasty-eachtreatmentto1eye,
toamaximumof4treatmentstothateyeina2yearperiod).
13
TheAustralianHealthCareAgreementsspecifythataneligiblepatientpresentingatapublichospitaloutpatient
departmentwillbetreatedfreeofchargeasapublicpatientunless:(a)thereisathirdpartypaymentarrangementwith
thehospitalorQueenslandtopayforsuchservices;or(b)thepatienthasbeenreferredtoanamedmedicalspecialist
whoisexercisingarightofprivatepracticeandthepatientchoosestobetreatedasaprivatepatient.AustralianHealth
CareAgreementbetweentheCommonwealthofAustraliaandtheStateofQueensland,2003-08,http://www.health.qld.
gov.au/publications/aust_hlth_care_agreement/Queensland.pdfaccessed7May2007.
5. Treatment
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
u
m
b
e
r
o
f
p
r
o
c
e
d
u
r
e
s
Centre for Eye Research Australia
41 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
LASER DIODE CYCLOPhOTOCOAGULATION
Cyclodiodelaserlightisdirectedtopassthroughthesurfaceoftheeyeandbehindtheiristo
affecttheciliarybodyinorderto reduce the production of aqueous humourandtherefore
decreasetheIOPwithintheeye.Thistechniqueisusedforrefractorycasesthatdontrespond
toconventionaltreatment.Notmanyoftheseproceduresareundertakeneachyear.Forthe
fnancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,respectively,137
and145cyclodestructiveproceduresforintractableglaucomawereperformed(itemnumbers
42770and42771).TheseproceduresarerarelyusedforPOAGandsonotincludedinthemodel.
5.3: CONVLN1IONAL SUkGLkY {1kA8LCULLC1OMY)
If medical and laser therapies fail, surgery is performed. Trabeculectomyisperformedunder
localorgeneralanaesthesiaandcreatesanalternativepathwayfortheoutfowofaqueous
humour.Atinyportionofthetrabecularmeshworkorsurroundingtissueisremoved,anda
smallfapinsertedtoproduceapassagewayfromtheanteriorchamberoftheeyetoapocket
betweentheconjunctivaandsclera.Asmallblister(flteringbleb)isformedundertheupperlid,
calledatrabeculectomybleb.
fIGURE 5.3: TRABECULECTOMY
14
Insomecases,scartissuedevelopsandpreventsthe
operationfromworking.Incasesthoughttobeat
increasedriskofscarformation,thesurgeonmaygive
thepatientantifbrotics-drugstoinhibitscaringsuchas
5-fuoracil or MMC to reduce scarring andimprovethe
outcomesofsurgery.
Aswithtrabeculoplasty,itisdiffculttoestimatethe
totalnumberofproceduresundertakenforPOAG
eachyear.Medicaredatadonotincludeprocedures
undertakenonpublicpatientsinpublichospitals
(admittedornon-admitted).Hospitaldataincludebothpublicandprivateadmittedpatients
arethereforethemorereliableinthecaseoftrabeculectomy.
ThetotalnumberoftrabeculectomyproceduresforpeoplewithPOAGduringtheperiodof
200405hasbeensourcedfromtheAustralianInstituteofHealthandWelfare(AIHW)asa
specialdatarequest.
ThetotalnumberofproceduresforICD-10-codesH401andH409(whichrelatetopatients
withPOAGandUnspecifedGlaucoma)havebeenincludedinthemodelling.Fortheperiod
200405,1,683trabeculectomyprocedureswereperformed.Ofthese,583procedureswere
performedinapublichospitalwhile1,060wereperformedinaprivatehospital.
14
InternationalGlaucomaAssociationwebsite,accessed10thMay2007
http://www.glaucoma-association.com/nqcontent.cfm?a_id=382&=fromcfc&tt=article&lang=en&site_id=176
5. Treatment
42
Tunne l Vi s i on
Centre for Eye Research Australia
Somepatientshavemorethanonetrabeculectomy.Itisnotpossibletodeterminetheextent
ofrepeatsurgeryfromtheAIHWdata.TheMBSdatasuggestthataround1,435trabeculectomy
procedureswereundertakenin2004-05,with212repeatoperationsinthesameyear(Table
5.4)andwhile1302flteringoperationswereundertakenin2005-06,therewerealso230
repeatoperations.Repeattrabeculectomieswerealsohighercost(Table5.4).Thecostsof
trabeculectomyinthemodelhavebeenadjustedupwardsaccordinglybasedonthesefguresby
summingthetwoyearstofndthatrepeatsmadeup16%offlteringoperationsandcost25%
morewhichsuggeststhecostoftrabeculectomiesneedstobeadjustedupwardsbyaround20%
(seeSection6.3.2).
TABLE 5.4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
(Anaes.)Meanstheserviceattractsananaesthetic.(Assist.)Medicarebeneftsarepayableunderitem51300for
assistancerenderedatanyoperationidentifedbythewordAssist.forwhichthefeedoesnotexceedthefeethreshold
specifedintheitemdescriptor,orataseriesorcombinationofoperationsidentifedbythewordAssist.forwhichthe
aggregateSchedulefeethresholdspecifedintheitemdescriptorhasnotbeenexceeded.
Source:MedicareAustraliastatistics,FeesbasedonMBS1November2006.
AtimeserieswasnotavailablefromtheAIHW,butMedicaredatasuggestthatthenumber
ofinitialMBStrabeculectomyprocedures(item42746)hasfallenfrom3,996in1996to
1,246in2006(Figure5.4).Thisprobablyresultsfromthefowoneffectoftheintroduction
ofprostaglandinanalogueeyedrops(discussedearlier),whichhaveimprovedIOPcontroland
delayedtheneedfordownstreamtreatments.
fIGURE 5.4: MBS TOTAL Of TRABECULECTOMY PROCEDURES, 1994-2005
Source:MedicareAustraliastatistics,MBSitemnos.42746(Filteringoperationforglaucoma)and42749
(Filteringoperationforglaucoma,wherepreviousflteringoperationhasbeenperformed).
Decreasing rates of
surgery refect better
medical treatment.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
38
trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the
same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there
were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).
The costs of trabeculectomy in the model have been adjusted upwards accordingly based on
these figures by summing the two years to find that repeats made up 16% of filtering
operations and cost 25% more which suggests the cost of trabeculectomies needs to be
adjusted upwards by around 20% (see Section 6.3.2).
TABLE 5-4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total
2004-05 559 337 234 110 118 57 20 0 1,435
2005-06 513 311 232 81 117 36 9 3 1,302
2004-05 77 62 36 17 10 4 5 1 212
2005-06 77 62 49 17 17 6 1 1 230
42749
Filtering operation for glaucoma, where
previous filtering operation has been
performed (Anaes.) (Assist.)
1056.55
42746
Filtering operation for glaucoma (Anaes.)
(Assist.)
843.85
(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 for
assistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee
threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."
for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.
Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.
A time series was not available from the AIHW, but Medicare data suggest that the number of
initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in
2006 (Figure 5-4). This probably results from the flow on effect of the introduction of
prostaglandin analogue eye drops (discussed earlier), which have improved IOP control and
delayed the need for downstream treatments.
FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005
0
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
u
m
b
e
r
o
f
p
r
o
c
e
d
u
r
e
s
42746 42749
Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering
operation for glaucoma, where previous filtering operation has been performed).
Economic impact of primary open angle glaucoma Commercial-in-Confidence
38
trabeculectomy procedures were undertaken in 2004-05, with 212 repeat operations in the
same year (Table 5-4) and while 1302 filtering operations were undertaken in 2005-06, there
were also 230 repeat operations. Repeat trabeculectomies were also higher cost (Table 5-4).
The costs of trabeculectomy in the model have been adjusted upwards accordingly based on
these figures by summing the two years to find that repeats made up 16% of filtering
operations and cost 25% more which suggests the cost of trabeculectomies needs to be
adjusted upwards by around 20% (see Section 6.3.2).
TABLE 5-4: TRABECULECTOMY MBS SERVICES PROCESSED BY JURISDICTION BY YEAR
Item No. Description Fee ($) Year NSW VIC QLD SA WA Tas ACT NT Total
2004-05 559 337 234 110 118 57 20 0 1,435
2005-06 513 311 232 81 117 36 9 3 1,302
2004-05 77 62 36 17 10 4 5 1 212
2005-06 77 62 49 17 17 6 1 1 230
42749
Filtering operation for glaucoma, where
previous filtering operation has been
performed (Anaes.) (Assist.)
1056.55
42746
Filtering operation for glaucoma (Anaes.)
(Assist.)
843.85
(Anaes.) Means the service attracts an anaesthetic. (Assist.) Medicare benefits are payable under item 51300 for
assistance rendered at any operation identified by the word "Assist." for which the fee does not exceed the fee
threshold specified in the item descriptor, or at a series or combination of operations identified by the word "Assist."
for which the aggregate Schedule fee threshold specified in the item descriptor has not been exceeded.
Source: Medicare Australia statistics, Fees based on MBS 1 November 2006.
A time series was not available from the AIHW, but Medicare data suggest that the number of
initial MBS trabeculectomy procedures (item 42746) has fallen from 3,996 in 1996 to 1,246 in
2006 (Figure 5-4). This probably results from the flow on effect of the introduction of
prostaglandin analogue eye drops (discussed earlier), which have improved IOP control and
delayed the need for downstream treatments.
FIGURE 5-4: MBS TOTAL OF TRABECULECTOMY PROCEDURES, 1994-2005
0
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
N
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42746 42749
Source: Medicare Australia statistics, MBS item nos. 42746 (Filtering operation for glaucoma) and 42749 (Filtering
operation for glaucoma, where previous filtering operation has been performed).
5. Treatment
Centre for Eye Research Australia
43 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
DRAINAGE IMPLANTS
Inpatientsforwhomtrabeculectomyislikelytofailbecauseofinfammationorscarring,
adrainagedeviceisimplanted(calledaglaucomadrainagedevice)tocreateadrainagepathway.
Variousdevicesexist(eg.Moltenovalves).DrainageimplantsarerarelyusedinPOAG,butare
morecommonlyusedinsecondaryglaucoma.
DatafromtheAIHWhospitalmorbiditydatabasefor2004-05suggestthat136aqueous
shuntinsertion
15
procedureswererecordedforglaucoma.
Forthefnancialyears2004-05and2005-06,MedicareAustraliadatasuggestthat,
respectively,57and70Moltenovalveinsertionswereperformed(itemnumber42752).
TheseproceduresarerelativelyexpensivetheMBSfeeforthe1November2006was
$1,182.75.
Sincetheyarerelativelyrareinprimaryopenangleglaucomapatients,theseproceduresarenot
includedinthemodel.
5.4: kLVALLNCL LS1IMA1LS IOk LACH 1kLA1MLN1 GkOU
Asnotedearlier,oncediagnosedwithPOAG,patientsgenerallyfollowastandardtreatment
protocol.Theprotocolisindependentoftheseverityofthediseasestageatdiagnosis.Patients
usuallycommencewithmedicationswhethertheyhaveseverediseaseorearlystagedisease.
Initially,DismodIIwasusedtomodeltheprogressionfromonetreatmentphasetothenext,
byusingthetotalnumberofpeoplenewlydiagnosedwithPOAGin2005astheincidencerate
forthemedicationtreatmentphase,thetotalnumberoftrabeculoplastyproceduresasthe
indicatoroftreatmentfailureforthemedicationgroup,andthetotalnumberoftrabeculectomy
proceduresasanindicatoroftreatmentfailureforthetrabeculoplastygroup(theoverallRR
ofmortalityof1.18theweightedaverageRRofmortalityfromallprevalentseveritygroups
wasappliedinthemodellingforeachtreatmentphase).
Inthecaseoftrabeculoplasty,thetotalnumberofMBSproceduresneededtobescaleddown
torefectfrst-timeprocedures.Asnotedearlier,itisestimatedthathalfofthepeopleinthe
trabeculoplastytreatmentphasereceivetwo180degreetreatmentswhiletheotherhalfreceive
one.Thetotalnumberoftrabeculoplastyprocedureswasscaleddownby1.5accordingly.
DismodIIwasalsoinitiallyusedtomodeltheremainingtreatmentphases(Table5.5)toensure
thatthefowthrougheachphasewasinternallyvalidandrefectedthenumberofprocedures
occurringinpractice.
However,thesemodelledrateswerenotconsistentwiththeliteratureonfailureratesfor
lasertherapyandsurgery.Inparticular,anumberofstudiesoutlinedinTable5.7andTable5.8
suggestedfailureratesforlaserandsurgerywereoftheorderof50%(withfailuredefnedas
thepatientrequiringfurthertreatment).failure rates applied in the model are therefore:
50% per year for laser trabeculoplasty (consistent with Weinand and Althen 2006); and
50 % for trabeculectomy. While this is a very conservative estimate higher than
the literature sensitivity analysis shows that it makes little difference to the results.
Sensitivity analysis is presented in Section 9.3.3
15
ICD10AMcode42752.
44
Tunne l Vi s i on
Centre for Eye Research Australia
TABLE 5.5: INCIDENCE AND TREATMENT fAILURE RATE fOR EACh STAGE Of TREATMENT
fROM DISMOD II.
Age Group Incidence of Medication Medication Trabeculoplasty Trabeculectomy
(% of population in each failure rates (% of failure rates failure rates
age group) those on medication
40-44 0.02 4.3% 3.2% 2.0%
45-49 0.05 4.3% 3.2% 2.0%
50-54 0.07 4.3% 3.2% 2.0%
55-59 0.10 4.3% 3.2% 2.0%
60-64 0.12 4.3% 3.2% 2.0%
65-69 0.14 4.3% 3.2% 2.0%
70-74 0.17 4.3% 3.2% 2.0%
75-79 0.22 4.3% 3.2% 2.0%
80-84 0.26 4.3% 3.2% 2.0%
85-89 0.32 4.3% 3.2% 2.0%
90+ 0.35 4.3% 3.2% 2.0%
5.5: 1kLA1MLN1 LIIICACY
ForthereasonsoutlinedearlierinSection4.5,manyofthestudiesoftreatmenteffcacy
(ie.theimpactoftreatmentcomparedwithalternativesincludingnotreatment)arediffcultto
applytoacosteffectivenessstudybecauseprogressionisnotdefnedconsistentlyandbecause
ofthenatureoftheendpointsselected.Themajorclinicaltrialsoftreatmenteffcacyare
outlinedinBox4.
8ox 4: Ma|or c|inica| tria|s of g|aucoma treatment efficacy
TheOcular hypertension Treatment Study (OhTS) intheUSAexaminedpatientswho,
atentrytothetrial,hadOHT,butnoevidenceofglaucomatousdamage.Enrolmentended
in1996.1,636participantswererandomisedeithertoobservation,ortoreceivetreatment
withcommerciallyavailabletopicalhypotensivemedicationsusedsinglyorincombination.
TheaimoftreatmentwastoachieveatargetIOPof24mmHgorlessandaminimum
20%reductioninIOP.ProgressionwasdefnedaseitherthedevelopmentofaVFdefector
deteriorationintheopticdisc.
TheEuropean Glaucoma Prevention Study (EGPS) enrolled1,081patientsbetween1997
and1999inBelgium,Germany,ItalyandPortugal.ParticipantshadOHT,butnormalVF
andopticdisc.Patientswererandomisedtotreatmentwithdorzolamide(topicalcarbonic
anhydraseinhibitor)oraplacebo.Participantsandinvestigatorswerebothmasked.Theaim
wastoreduceIOP,buttheprotocoldidnotspecifyatargetIOPreduction.Endpointswere
changesinVFand/ortheopticdisc.
AtentryintheCollaborative Normal Tension Glaucoma Study (CNTGS),145patients
fromspecialtycentresintheUSAhadnormalIOP,butopticdiscabnormalitiesandVF
defects.Participantswererandomlyassignedtotreatmentornotreatment.Progression
wasbasedonachangeintheVForachangeintheopticnerveappearance.Inthetreatment
group,theaimwastoreduceeyepressureby30%in6monthsusingeyedrops,laserand/
orflteringsurgery.
5. Treatment
Centre for Eye Research Australia
45 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
TheEarly Manifest Glaucoma Trial (EMGT)wasconductedinSweden,andincluded255
participantsscreenedbetween1992and1997.Atentry,patientswerenewlydiagnosed
withVFdefects,butwerepreviouslyuntreated.PatientswithadvancedVFdefectswere
excludedfromentry.Participantswererandomisedtoeither360olasertreatment(ALT)
plusbetaxololhydrochloride(topicalbetablocker)ornoinitialtreatment.Theaimwasto
evaluatetheeffectofimmediatetreatmentcomparedwithnoinitialtreatmentorlater
treatment.ProgressionwasbasedonnewVFdefectoropticdiscdeteriorationorboth.
TheCollaborative Initial Glaucoma Treatment Study (CIGTS)wasconductedinthe
USA.Enrolmenttookplacebetween1993and1997.607patientswithnewlydiagnosed
glaucoma,withlimitedornopriortreatment,IOPof20mmHgorgreaterandevidence
ofopticnervedamageand/orVFLinoneorbotheyeswereenrolled.Participantswere
randomisedtoinitialtrabeculectomy(withorwithout5-fuorouacil)ortopicalmedication
(topicalbeta-blocker,followedbyanalternatesingletopicaltherapeuticagent,dual
topicaltherapy,tripletopicaltherapy,analternatecombinationoftripletopicaltherapy
andoptionaladditionaltopicalandororalmedications).Furthertreatment,ifconsidered
necessary,followedstandardtreatmentpatterns(variouscombinationsofALT,medications
andtrabeculectomy).ProgressionwasbasedonchangesinVF.
TheGlaucoma Laser Trial (GLT)andtheGlaucoma Laser Trial follow Up (GLTfU) Study
wereconductedintheUSA.TheGLT(271participants)endedin1989,butaproportionof
GLTpatients(203participants)werethenobservedaspartoftheGLTFUfrom1990to1993.
ParticipantsintheGLTwerenewlydiagnosedwithPOAGandhadanIOPofatleast22mm
Hgineacheyeplusoneof:aVFdefect,orcertainOHTandcuptodiscratiocharacteristics.
OneeyeofeachpatientwasrandomisedtoALTandtheothereyetotimolol.Endpoints
wereVFandIOP.
TheAdvanced Glaucoma Intervention Study (AGIS)conductedintheUSAfocusedon
thosewhosediseasewasnolongercontrolledbymedication.Between1988and1992,
591patientswereenrolled.Atentry,patientshadconsistentlyelevatedIOP,opticdiscrim
deteriorationandaVFdefectscorebasedontheAGISgradingsystemofbetween1and
16
16
.Patientsweregivenadifferentsequenceofinterventionsineacheyeinoneeye,
thesequencewasALT,trabeculectomy,trabeculectomy;intheothereye,thesequencewas
trabeculectomy,ALT,trabeculectomy.ThegoalwastoreduceIOPtolessthan18mmHg.
TheprimaryoutcomevariableintheAGISwastheaveragepercentofeyeswithadecrease
ofvision(eitherVForVA).
Otherstudiesfocussinginparticularontheeffcacyoflasertreatmentandtrabeculectomy
administeredtopatientsfollowingfailureofmaximumtolerablemedicationtocontrol
thediseasegenerallyfocusontheimpactoftreatmentonIOPandtheneedforadditional
intervention.VeryfewmeasuretheeffectoftreatmentonVF.Thestudieshavedifferent
endpointsanddefneprogressiondifferently.Somearenotbasedonintenttotreat.Some
examplesofstudiesoftheeffcacyoftrabeculoplastyareoutlinedinTable5.7andexamples
ofstudiesoftheeffcacyoftrabeculectomyareoutlinedinTable5.8.
16
AGISVFdefectscoresrangefrom0(nodefect)to20(advancedglaucoma).Iftheeyehasinsuffcientvisionfora
patienttocountfngersat30cm,theVFdefectscoreisrecordedas20.
46
Tunne l Vi s i on
Centre for Eye Research Australia
Inordertosynthesisetheimpactoftreatmentonprogression,Weinrebetal,(2004)usedthe
resultsfromtheOHTSandtheEMGTastheonlytrialswhichcomparedtreatmentwithno
treatment.Asnotedearlier,theEGPS(2005)resultswerenotavailableatthetimeWeinreb
etal,(2004)wasreleased.Inanycase,theEGPS(summarisedinBox4)facedcertaindesign
problemsandsoisnotusedherefortheimpactoftreatmentontheriskofdevelopingPOAG
17
.
Weinrebetal,(2004:464)combinedtheimpactoftreatmentonconversionratesfromOHTto
glaucomafromtheOHTSwithresultsfromtheEMGTontheimpactoftreatmentontheriskof
progressionofdisease.
TheOHTS(summarisedinBox4)foundthatafter60months,thosewhowerenot
receivingtreatmentweremorethantwiceaslikelytodevelopPOAGthanthoseontopical
medicationswhohadtheirIOPreducedby20%,ie.thecumulativeprobabilityofdeveloping
POAGwas4.4%inthemedicationgroupand9.5%intheobservationgroup(hazardratioof
0.4,witha95%CIof0.27to0.59).Thedifferenceinprogressionrateswas46%(4.4/9.5).
TheEMGT(summarisedinBox4)showedthatearlyinitialtreatmentwith360
o
ALTplus
betablockereyedropsdelayedprogressioncomparedwithnotreatment.Themediantime
toprogressionwas48monthsinthecontrolgroupand66monthsinthetreatmentgroup
(althoughtimetoprogressionvariedgreatly).At48months,49%ofcontrolshadprogressed
comparedwith30%inthetreatmentgroup(Heijletal,2002).Leskeetal,(2003)foundthat
after6years,53%ofpatientsprogressed.Inmultivariateregressionanalysis,progressionrisk
washalvedbytreatment(HR=0.5,witha95%CIof0.35to0.71).
Thus,Weinrebetal,(2004)estimatedthattreatment reduced the risk of progression from
OhT to blindness by 77%(ie.progressionratesintreatedpatientsare46%x50%=23%that
ofprogressionratesinuntreatedpatients).Progressionfromglaucomatoblindnessintreated
patientsisassumedtobe50%ofthatinuntreatedpatients.Ratesofprogressionintreated
patientsbasedonWeinrebetal,(2004)arepresentedinTable5.6.
TABLE 5.6: PROGRESSION RATES (CUMULATIVE PROBABILITY)
IN TREATED PATIENTS (15 YEAR PERIOD)
Start point Unilateral blindness Bilateral Blindness
OHT 0.3%to2.4%(Weinrebetal,2004) 0.7%(Hattenhaueretal,1998)
Glaucoma 20.25%(Hattenhaueretal,1998) 8.25%(Hattenhaueretal,1998)
17
IntheEGPS,therewasnostatisticallysignifcantdifferencebetweenmedicaltherapyandplaceboinreducingthe
incidenceofPOAG,althoughtheactivelytreatedarmhadameanIOPreductionrangingbetweenapproximately15%to
22%throughoutthe5yearsofthetrial.TheresultsaremostlyexplainedbyaclinicallysignifcantplaceboeffectonIOP
ofapproximately9%to19%,whichincreasedduringthestudy.
5. Treatment
Centre for Eye Research Australia
47 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
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(
n
=
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=
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)
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s
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d
1
8
%
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a
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n
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4
.
6
%
(
4
/
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(
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t
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n
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e
:
1
.
1
%
(
1
/
8
9
)
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3
.
4
%
(
3
/
8
9
)
6
.
7
%
(
6
/
8
9
)
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n
d
9
%
(
8
/
8
9
)
.
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h
r
e
e
a
n
d
f
v
e
y
e
a
r
s
w
e
r
e
:
6
8
%
,
4
6
%
a
n
d
3
2
%
b
y
c
r
i
t
e
r
i
o
n
(
1
)
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n
d
5
8
%
,
3
8
%
a
n
d
3
1
%
b
y
c
r
i
t
e
r
i
o
n
(
2
)
.
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q
u
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l
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n
t
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s
u
c
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e
s
s
r
a
t
e
s
w
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r
e
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0
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n
d
3
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b
y
c
r
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t
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o
n
(
1
)
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n
d
4
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2
3
%
a
n
d
1
3
%
b
y
c
r
i
t
e
r
i
o
n
(
2
)
.
48
Tunne l Vi s i on
Centre for Eye Research Australia
T
A
B
L
E
5
.
7
:
S
T
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5
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3
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d
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6
4
%
a
f
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d
4
2
%
a
f
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y
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a
r
s
.
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f
p
a
t
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e
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c
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f
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p
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b
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s
s
f
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a
t
t
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y
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a
r
s
w
a
s
6
5
%
.
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p
a
e
t
h
a
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a
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z
(
1
9
9
2
)
R
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50
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5.6: SIDL LIILC1S
5.6.1: MEDICATIONS
Topicalanti-glaucomamedications can result in an array of side effects,rangingfrom
minorimpactssuchaseye-lashelongationanddarkeningoftheiristomajorimpactssuchas
cardiovascularevents(Table5.9).
TABLE 5.9: MEDICATION SIDE EffECTS
Medication Side effect
Prostaglandinanalogues(prostamides) Browndiscolouringoftheiris,lengtheninganddarkeningof
eyelashes,ocularirritationandredness,macularoedemaor
iritisinsusceptiblepatients.
badrenergicblockers Ocularirritationanddryeyes.Contraindicatedinpatients
withbradycardia,heartblock,heartfailure,asthmaor
obstructiveairwaydisease.Canhavesubstantial
cardiovascularandrespiratoryside-effects,especially
intheelderly.
Alpha(a)2adrenergicagonists Redeyeandocularirritation,centralnervoussystem
effectsandrespiratoryarrestinyoungchildren,allergic
conjunctivitis,sedation,cautionadvisedinpatientswith
cerebralorcoronaryinsuffciency,Raynaudsdisease,
posturalhypotension(dizzyspells),hepatic(liverfailure)
orrenalimpairment.
Carbonicanhydraseinhibitors Topicalformshavefewsideeffects,howeveroralforms
maycausetransientmyopia,nausea,diarrhoea,lossof
appetiteandtaste,parasthesiae,lassitude,renalstones
andhaematologicalproblems.
Cholinergicagonists Substantialocularside-effectsincludingblurringofvision
duetothesmallpupilandinducedmyopia,ciliaryspasm
leadingtoheadachesespeciallyinyoungerpatients.
Cataractsandiris-lensadhesionsinthelong-term.
Prostaglandinandb-blockersarethemostfrequentlyusedantiglaucomamedicationsinAustralia.
Thesideeffectprofleforprostaglandinmedicationsisrelativelyminor.Topical
prostaglandinsarerapidlybrokendowninthebloodstreamasaresult,systemicsideeffects
arerare.Ocularsideeffectscanincludeconjunctivalhyperemia,increasedirispigmentation
andpigmentationoftheperiocularskinaswellaslengtheningoftheeyelashes.Because
theyarerare,nosideeffectsforprostaglandinsareincludedinthemodelling.
Moresignifcantsideeffectsarepossibleforpatientstakingb-blockers.Twotypesoftopical
b-blockersarecommerciallyavailable,nonselective(timolol,levobunolol,metipranololand
carteolol)andcardioselective(betaxolol),(BrooksandGillies,1992).TheIOPloweringability
ofthenonselectiveb-blockersisgreaterthanthecardioselectivebblockers,providinga
greatertreatmenteffcacy,althoughthesideeffectproflemaybemoresignifcantinthe
nonselectivebblockermedicationgroup.Thesesideeffectsinclude:stinging,achingor
rednessintheeyesafterusingdrops;dryeyesandforeignbodysensation(thefeelingofa
foreignbodyintheeye);bradycardia(slowheartbeat);spasmsofthetubesleadingto
5. Treatment
Prostaglandin
analogues are the
most frequently
used anti glaucoma
medications in
Australia.
Centre for Eye Research Australia
51 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
thelungs(bronchospasmorasthma);heartfailureduetothebuildupoffuid;depression;
confusion;fatigue,dizzinessandinabilitytotolerateexercise;and/orreducedlibido.
Bronchospasmcanexacerbateasthmaandchronicobstructivepulmonarydisease(COPD)
whilebradycardiacanexacerbatecongestiveheartfailure
19
.Prolongeduseoftopical
b-blockershasalsobeenlinkedtodepression,moodalterations,memoryloss,hallucinations,
decreasedlibidoaswellasimpotence.
Themostsignifcantsideeffect(whichhasbeenincludedinthedynamicmodelling)
associatedwithbblockersisCOPD.Apopulationbasedcohortstudyconductedinthe
UK,examiningwhethertopicalbblockersareassociatedwithexcessrespiratorydiseasein
elderlypatientsnotconsideredtobeatexcessrisk(Kirwanetal,2002)showedahigherrisk
ofrespiratorydiseasethanwouldnormallybeexpected.Ahazardratiousedinthemodel
of2.29(95%CI1.71to3.07)wasproducedforpeopletreatedwithbblockerstoreceivea
frst-timemedicaltreatmentforreversibleairwaysobstruction,althoughthisriskceasesto
besignifcantafterthefrstyearoftreatmentwithtopicalbblockers.TheriskofCOPDfora
personnotbeingtreatedwithtopicalbblockersisassumedtobeequaltotheprevalenceof
COPDinthegeneralpopulation.
TABLE 5.10: RISK Of COPD (% Of POPULATION), 2001
Age Males females Persons
0-4 0.00 0.00 0.00
5-14 0.00 0.00 0.00
15-24 0.05 0.01 0.03
25-34 0.44 0.22 0.33
35-44 1.15 0.57 0.86
45-54 2.61 1.06 1.84
55-64 5.71 2.08 3.92
65-74 10.42 3.61 6.91
75-84 14.22 5.26 9.01
85+ 16.01 6.37 9.35
AllAges 2.51 1.09 1.80
Source:AIHWspecialrequest.
ThecostofCOPDperpersonisbasedonAIHWdata,indexedto2005dollars(Table5.11).
19
www.agingeye.net/glaucoma/glaucomadrugtreatment.php
5. Treatment
52
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TABLE 5.11: hEALTh SYSTEM COST Of COPD ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 255,006 476,620 304,254
15-24 2,893 13,717 5,167
25-34 88 527 233
35-44 291 978 522
45-54 373 962 543
55-64 858 1,843 1,117
65-74 1,427 2,717 1,775
75-84 1,904 2,524 2,115
85+ 2,010 2,224 2,111
AllAges 1,191 2,085 1,465
Source:AIHWspecialrequest.
5.6.2: LASER TREATMENT
Anumberofstudiesnotethatthesideeffectsoflaserincludeformationofperipheralanterior
synechiae(LatinaanddeLeon,2005;GLTandGLTFU),uveitis(Nagaretal,2005)andtransient
IOPspikes(LatinaanddeLeon,2005).Theseareexcludedfromthemodellingasforthe
mostparttheydonotaffectqualityoflife.Othermoreserioussideeffects,suchasretinal
detachment,arealsoexcludedfromthemodellingbecausetheyoccuratsuchalowrate.
5.6.3: SURGERY
Thecomplicationsoftrabeculectomyincludecataractandanincreasedriskofeyeinfection.
Cataractisthemostsevereandcostlyofthese(becauseofthenumberinvolved)andthushas
beenincludedinthemodelling.
Trabeculectomyisaninvasiveprocedurethathasaknownassociationwiththedevelopment
ofcataractsfollowingsurgery.Lichteretal,2001(CIGTS)foundthatinitialsurgicaltreatment
resultedinthedevelopmentofmorecataractsrequiringremovalthaninitialmedicaltreatment.
Kaplan-Meierestimatesshowedthatbythreeyearsaftertreatmentinitiation,theprobabilityof
cataractextractionwas11.6%(standarderror,1.9%)inthesurgicalgroupversus2.7%(standard
error,1.0%)inthemedicalgroup.Thedifferencewassignifcant(p=0.0001).Cataracts
occurredinapproximately20%to35%ofpatientsfollowingfrsttimetrabeculectomyover20
monthsto10years(Table5.12).Theoccurrenceofcataractfollowingtrabeculectomypresents
asasignifcantsideeffectthatresultsdirectlyfromglaucomatreatment,withanassociated
morbidityfromVAlossaswellascostsfromsubsequentcataractsurgery.
Other more serious
side effects, such as
retinal detachment,
are also excluded
from the modelling
because they occur at
such a low rate.
5. Treatment
Centre for Eye Research Australia
53 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
5. Treatment
TABLE 5.12: TRABECULECTOMY SIDE-EffECTS
Source Incidence of Cataract following Trabeculectomy Timeframe
Edmundsetal, Cataractsdevelopedin20.2%ofeyesfollowingsurgery. *Cross-sectional
1999 survey
Parcetal,2001 Probabilityofcataractsurgeryatfveyears(aftersurgery) 5,10and
was15%andattenyearswas37%.Nostatistical 20years
differencebetweenpatientsandtherestofthecohort
at20years.
Fontanaetal, Cataractextractionoccurredin35%ofeyesfollowing 36months
2006 trabeculectomy.
AGIS TheRRofcataractfollowingfrsttrabeculectomywas 10years
1.78.WhencomplicationsoccurredinsurgerytheRR=
2.04andwhentheydidnotoccurRR=1.47.
Ehrnroothetal, Cataractsurgerywascompletedin35%ofeyes 3.5years
2002 followingtrabeculectomyduringthefollowupperiod
(mean3.5years).
Ehrnroothetal, Cataractsurgerywascompletedin34.8%ofeyes. 3.5years
2005
OBrartetal, Cataractformationwassimilarbetweenthe 20months
2004 trabeculectomyandviscocanalostomygroups.
*Edmundsetal,1999isacrosssectionalsurveyoftrabeculectomypatientsintheNationalHealthServiceintheUK.
Notimeframewasprovidedinthissurveybetweentrabeculectomyandcataractoccurrence
ThemajorityofstudiesshowninTable5.12measuretheincidencerateofcataractdevelopment
orsurgeryfollowingafrsttimetrabeculectomy.Thesemeasuresdonottakeintoaccountthe
rateofcataractdevelopmentorsurgeryinpeopleofanidenticaldemography.Ifanincident
rateofbetween20%and35%fromthesestudieswereusedtheincreasedmorbidityandhealth
systemcostwouldbeoverestimated.
TheAGISstudyontheotherhandmeasuredtheRRofcataractfollowingtrabeculectomy.
People that undergo a frst time trabeculectomy procedure have a 78% increased chance
of developing a cataract (RR=1.78)accordingtoAGIS.Thisincreasedriskisappliedinthe
modeltopeoplethathaveundergoneatrabeculectomyprocedure,withtheriskofcataractfora
personthathasnotundergonethisprocedureassumedtobeequaltotheprevalenceofcataract
inthegeneralpopulation.
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Centre for Eye Research Australia
5. Treatment
TABLE 5.13: PREVALENCE Of CATARACT (% Of POPULATION)
Age Persons
40-44 0.0000
45-49 0.0000
50-54 0.0000
55-59 0.0844
60-64 0.0107
65-69 0.1620
70-74 0.7254
75-79 2.3713
80-84 5.4910
85-89 8.7109
90+ 15.1689
Source:MVIP&BMESspecialdatarequest.
ThecostofcataractsperpersonisbasedonAIHWdata,indexedto2005dollars.
TABLE 5.14: hEALTh SYSTEM COST Of CATARACT ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 0 0 0
15-24 0 0 0
25-34 0 0 0
35-44 70 71 73
45-54 107 113 110
55-64 118 112 115
65-74 171 178 176
75-84 206 219 215
85+ 210 132 152
AllAges 178 177 178
Source:AIHWspecialrequest.
5.6.4: SUMMARY Of SIDE EffECTS INCLUDED IN ThE MODELLING
Insummary,twosideeffectshavebeenincludedinthemodellingforglaucoma.Theseare:
cataract,RRof1.78followingtrabeculectomy;and,
COPD,RRof2.29followinguseofab-blockertopicaleyemedication.
Healthsystemcostsforthesesideeffectshavebeenincludedintotheperpersontreatment
costsofmedicationandtrabeculectomy.Themodelallocatesthesecostsbyincreasingthebase
costoftreatmenttoincorporatethetotalexpectedhealthsystemcostsofthesesideeffects.
Centre for Eye Research Australia
55 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 5. Treatment
The calculation of disease costs over time is discussed in this section, including:
the impact of glaucoma on a patients quality of life (wellbeing);
the health system costs of glaucoma; and
the indirect costs of glaucoma (including the impact on employment, the need for informal
and paid formal care, the impact on the paid employment of informal carers, aids and
equipment, and the economic costs of welfare payments).
However, rst, discount rates are discussed, as the model is dynamic and calculates the
economic impact of glaucoma in net present value terms over time (2005 to 2025).
6.1: DISCOUNT RATES
Choosing an appropriate discount rate for present valuations in cost analysis is a subject
of some debate, and can vary depending on which future income or cost stream is being
considered. There is a substantial body of literature, which often provides conicting advice, on
the appropriate mechanism by which costs should be discounted over time, properly taking into
account risks, ination, positive time preference and expected productivity gains.
The absolute minimum option that one can adopt in discounting future income and costs is
to set future values in current day dollar terms on the basis of a risk free assessment about the
future (that is, assume the future ows are similar to the certain ows attaching to a long term
Government bond).
Wages should be assumed to grow in dollar terms according to best estimates for ination and
productivity growth. In selecting discount rates for this project, we have thus settled upon the
following as the preferred approach.
Positive time preference: We use the long term nominal bond rate of 5.8% pa (from recent
history) as the parameter for this aspect of the discount rate. (If there were no positive time
preference, people would be indifferent between having something now or a long way off in
the future, so this applies to all ows of goods and services.)
General Ination: The Reserve Bank has a clear mandate to pursue a monetary policy that
delivers 2 to 3% ination over the course of the economic cycle. This is a realistic longer run
goal and we therefore endorse the assumption of 2.5% pa for this variable. (It is important
to allow for ination in order to derive a real (rather than nominal) rate.)
Productivity growth: The Commonwealth Governments Intergenerational report assumed
productivity growth of 1.7% in the decade to 2010 and 1.75% thereafter. We suggest
1.75% for the purposes of this analysis.
Health Ination: Health cost ination from 2005 onwards is assumed to be 3.2%, based on
estimates of increases in health expenditure from the AIHW estimates that health ination
in the eight years to 2004-05 has been around 3.2% per annum (AIHW 2006). This rate is
partially general price ination and partially productivity growth. To be on the conservative
side, productivity growth in the health sector is assumed to be equal to general
productivity growth.
6. Disease Costs
Glaucoma has
signicant social and
economic costs.
56
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Centre for Eye Research Australia
Therearethendifferent discount rates that should be applied:
Todiscountincomestreamsoffutureearnings,thediscountrateis:
5.8-2.5-1.75=1.55%
Todiscounthealthcosts,thediscountrateis:
5.8-(3.2-1.75)-1.75=2.6%
Todiscountotherfuturestreams(healthylife)thediscountrateis:
5.82.5=3.3%
Whiletheremaybesensibledebateaboutwhetherhealthservices(orothercostswithahigh
labourcomponentintheircosts)shouldalsodeductproductivitygrowthfromtheirdiscount
rate,wearguethatthesecostsgrowinrealtermsovertimesignifcantlyasaresultofother
factorssuchasnewtechnologiesandimprovedquality,andwecouldreasonablyexpectthisto
continueinthefuture.
6.2: 1HL COS1 1O QUALI1Y OI LIIL AND wLLL8LING
6.2.1: DISEASE WEIGhTS
Asnotedabove,the impact of treatment on a patients health and quality of life is of
primary importanceinmodellingtheeconomicimpactofdisease.Inthisstudy,eachstage
intheprocessofvisionlossneedstobematchedwithautilityweight(apatientsmeasureof
hisorherqualityoflife)refectingthelossofqualityoflifeexperiencedatthatpointinthe
progressionofthedisease.ThisisverydiffcultforPOAGbecause:
changesinIOPdonoteasilytranslateintoahealthbeneftforpatients(Kobeltetal,2006,
Hymanetal,2005,Jampeletal,2002andMillsetal,2001);and
thereisnoagreeddiseasestagingsystembasedonvisionloss(seeSection4.5).
Thevariousvisiongradingsystemscannotbeeasilytranslatedintoaquantifableimpact
onqualityoflife.
Thereisagrowingliteraturethatattemptstomeasuretheimpactofglaucomaonqualityof
life,althoughthelackofaconsistentdiseasestagingsystemremainsaproblemindrawing
conclusionsfromthesestudies.Theliteraturesuggeststhatduringtheearlystagesofdisease,
glaucomahaslittleimpact,withquality of life deteriorating over time, particularly in the
later stages of the disease. Someexamplesareasfollows.
20
1) Kobeltetal,(2006)undertookacrosssectionalpilotstudytotestwhetherutilitiesfor
differentlevelsofVFdefectcouldbeassessedusingageneralquestionnairesuchasthe
EQ5D.UtilityweightsdevelopedusingtimetradeoffunderlietheEQ5D.InSweden,199
patientswithOHTorPOAGweregroupedaccordingtosixstagesofvisionlossbasedonVF
defectsintheworsteye.ThediseasestageswereadaptedfromtheHAPscalefromno
defect(OHT)toendstagediseasewhereVFmeasurementwasdiffcultornolongerpossible.
Theauthorsfoundthatutilitywasstronglycorrelatedwithoverallvision,andpatients
withsevereglaucomatousdamagehavesignifcantlylowerutility.However,whileutility
decreasedwithincreasingglaucomatousdamage,thedifferencebetweenthestageswasnot
statisticallysignifcantwhencontrollingforco-morbidity.When17outlierswereremoved,
utilityscoresforpatientswithsevereglaucomatousdamageweresignifcantlyworse.
Patientsinstage5hadameanutilityof0.71(autilitylossof0.29),comparedto
6. Disease Costs
20
Foranexplanationofthelinearratingscale,standardgamble,timetrade-off,persontrade-offandEQ-5D,
seeMathersetal,(1999:10).
Centre for Eye Research Australia
57 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
0.88instage1andameanof0.84(autilitylossof0.16)instages2.4.Thesamplesizewas
smallandthenumberofpatientswithmoderatetoseverebilateralvisionlosswaslimited,
however,theresultswereconsistentwithotherstudies(Kobeltetal,2006).
2) Jampeletal,(2002)examinedhow191glaucomapatientsand46glaucomasuspects
ratingoftheirvisioncorrelatedwithEstermanbinocularVFtestingandothervisualfunction
tests.Theyfoundthatutilityvaluesthatpatientsassigntotheirvisiondonotcorrelatewell
withEstermanresultsandsuggestedthiswasbecause,there may not be a close relationship
between visual function and patient perception of that function, especially when the vision loss
is mild ... Perhaps early visual feld loss really does not affect patient assessment of their vision
and in fact is more of an all or none phenomenon with patients only noticing marked visual feld
loss. (Ontheotherhand,appropriatetestsmaynothavebeendeveloped.)Alinearrating
scaleandtimetradeoffwereusedtogaugethepreferencesofpatientswithglaucomafor
visualstates.Basedonthelinearratingscale,glaucomapatientsratedtheirvisionas0.72
andsuspectsratedtheirvisionas0.71(ona0to1scale).Blindglaucomapatients(witha
VAnobetterthancountingfngersinthebettereyeandwhohadbeenblindfor10years)
ratedtheirvisualstateas0.54.Glaucomapatientsandsuspectsassignedavalueof0.38and
0.34respectivelytototalblindness.Timetradeoffresultswerelessinformativeasfewwere
willingtogiveuptimeforimprovedvision.
3) AUKstudy(Brownetal,2001)usedatimetradeoffandastandardgambletomeasure
utilityassociatedwithblindnessfrom65patientswithvariousvisiondiseasesincluding
glaucoma,cataract,agerelatedmaculardegeneration(AMD)anddiabeticretinopathy.
Autilityvalueof1.0indicatesastateofperfecthealthwhereasautilityvalueof0indicates
death.Participantsweregroupedaccordingtovariousmeasuresofblindnessasfollows:
b) totallyblind:15patientswithnolightperceptioninatleastoneeyeandwhowereasked
toassumeascenarioofnolightperceptioninthesecondeyeaswell;
c) somelightperception:17patientswithlightperceptiontocountingfngersinthebetter
seeingeye;
d) justoverthelineforlegalblindness:33patientswith20/200-20/400visioninthebetter
seeingeye.
Thetimetradeoffresultssuggestedutilityvaluesforeachgroupof(a)0.26QALYs(95%CI0.19
to0.33);(b)0.47QALYs(95%CI0.33to0.61);and(c)0.65QALYs(95%CI0.58to0.72).
Thus patients with no light perception in one eye who were presented with the same
scenario in the second eye as well were willing to trade almost 3 out of every 4 years of
remaining life in return for perfect vision in each eye. Thosewithlightperceptiontocounting
fngerswouldtradeapprox1of2remainingyearsandthosewith20/200-20/400wouldtrade
approx1of3remainingyears.
Thestandardgambleutilityresultsweresubstantiallyhigher:(a)0.32(95%CI0.2to0.44);(b)
0.60(95%CI0.46to0.74);and(c)0.80(95%CI0.73to0.87).However,theauthorssuggested
thestandardgambleresultsoverestimateriskaversionbecauseparticipantshavediffculty
understandingthisapproach.
Notably,inblindpatients,utilityimprovedovertimesuggestingadaptationtoblindness(there
weresignifcantdifferencesbetweenthoseblindforlessthanoneyearandthoseblindformore
thanoneyear)andtheworsethevisioninthebettereye,thelowertheutility.Brownetal,
(2001)concludedthat:
6. Disease Costs
Vision loss has a very
signifcant impact
on the quality of life
that is highly valued.
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There is a wide range of utility values associated with legal blindness the preservation of even
small amounts of vision in patients with legal blindness is critically important to their wellbeing
and functioning in life. (Brown et al, 2001:327)
AIHw wLIGH1S
The choice of disease weights is very important.Iftheutility(QALY)weightsassociated
withvisionlossaretooloworthedisabilityweights(DisabilityAdjustedLifeYears-DALYs)are
toohigh,theresultswilloverestimatethecosteffectivenessofinterventions(andviceversa).
Previousmodelsinthisseries(seetheBackgroundSection1ofthisreport)appliedthe
disabilityweightsusedbytheAIHWintheirlossofwellbeingstudy(Mathersetal,1999,Table
6.1).Theseweightsaredrawnfroma Dutch study that used a person trade off methodto
estimateweightsfor53diseases,includingtheestimationofweightsfor175diseasestages,
sequelaeandseveritylevels(citedinMathersetal,1999:11).TheDutchweightsarebasedon
diseasestagesdefnedasfollows(Mathersetal,1999:159):
Milddisease:Somediffcultywithnewspaper,nodiffcultyrecognisingfacesat4m;
Moderatedisease:Greatdiffcultynewspaper,somediffcultyrecognisingfacesat4m;and
Severedisease:Unabletoreadnewspaperorrecognisefacesat4m.
WhileitisdiffculttorelatethesedefnitionstostagesofVFLinthestudiesoutlinedabove,
andspecifcallytoadiseasesuchasglaucomawhichinitiallyaffectsmid-peripheralVF,the
AIHWweightsarenotinconsistentwiththepreviousliteraturereviewnotingthattheAIHW
weightsrefectdisabilityweights(DALYs)ratherthanutilityweights(QALYs).
ManypatientswithOHTortheclinicalsignsofglaucomadonotexperiencevisionlossfor
severalyears.Thusthereisnolossofutilityduringearlystagediseaseandthedisability
weightis0.0.
TheAIHW(Dutch)weightformoderatediseaseliesbelowthelowestweightforsevere
diseasefoundintheliteraturereview(0.17comparedwith0.26).However,ifglaucoma
reallyonlyaffectsqualityoflifeinthelatterstagesofdisease,thenthedisabilityweightsfor
mildandmoderatediseasemightbetoohigh.
LegalblindnessinAustraliaisdefnedasVAof<6/60inthebettereyewithcorrection
(spectacles)oraVFoflessthan10degreesorboth(CERA2004:11).Totalblindnessrefersto
peoplewhoareunabletoseelight.TheseareencompassedintheAIHWweightforsevere
diseasewhichis0.43(comparedwiththerangeofestimatesof0.26tomorethan0.6inthe
studiesoutlinedabove).
The AIhW disease weights will be used here. Theyaredrawnfromastudyofanumberof
diseasesandcomparisonwithotherdiseasesandinterventionsisimportantforbudget/resource
allocationdecisions.Inaddition,itisalsopreferabletouseweightsfromthesamestudysothat
thesamemethodologyhasbeenusedandthesetofweightsisinternallyconsistent.TheAIHW
weightsarealsoconsistentwiththepreviousmodelsdevelopedbyCERAandsoallowforeasy
comparisonsacrossthese.
BasicAIHWweightsareonlyforthediseaseanddonottakeintoaccountco-morbidities.
Glaucomaisassociatedwithbothaccidentalfallsanddepression.Accidentalfallsand
depressionarediscussedbelowinSections6.3.4and6.3.5.Thediseaseweightsarenotadditive
addingtheweightsforapersonwithsevereglaucomaandseveredepressionresultsina
weightgreaterthan1whichisnotintuitivelypossible.
Many patients with
OhT or the clinical
signs of glaucoma do
not experience vision
loss for several years.
6. Disease Costs
Centre for Eye Research Australia
59 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Consequently,thefollowingformulaeareused:
whereWisthedisabilityweight,
VI
denotestheseverityofvisualimpairment(EDS,Mild,
ModerateorSevere),
DEP
denotesdepressionand
FALL
denotesafall.TheAIHWweighting
foraccidentalfallsis0.141andfordepressionis0.223basedon20%ofglaucomasuffers
experiencingmilddepressionwithaweightingof0.140and5%ofglaucomasuffers
experiencingmoderatetosevererdepressionwithaweightingof0.555(seeSection6.3.5for
theevidencebasisforcomorbiddepression)(seeMathersetal,1999,forthederivationofthe
respectivedisabilityweights).
TABLE 6.1: AIhW DISABILITY WEIGhTINGS
EDS Mild Moderate Severe
Glaucomaonly 0.000 0.020 0.170 0.430
Glaucomaandaccidentalfalls 0.141 0.158 0.287 0.510
Glaucomaanddepression 0.223 0.239 0.335 0.557
Glaucoma,accidentalfallsanddepression 0.333 0.346 0.446 0.620
CLkA wLIGH1S
CERAweightsarealsoavailableforusewithinthemodel.Thesearenotcorrelatedwithseverity
ofdiseasebasedonafndingfromresearchduringthedevelopmentoftheVisQoL,thetool
toderivevision-relatedutilities.Therewasnosignifcantdifferencebetweenmild,moderate
andseverevisionloss.TheCERAQALYweightforvisualimpairmentof0.83(utilitylossor
DALYof0.17)appliestoalllevelsofvisualimpairmentandisconsistentwithresultsfromthe
VIPsuggestingthat,withcancer,blindnessisthemostfearedhealthcondition.Noadditional
adjustmentforfallsanddepressionaremadeifCERAweightsareused.Itshouldbenotedthat
usingthesamedisabilityweightforalllevelsofseverityofglaucomareducesthebeneftsof
slowingprogressionofglaucoma.
6.2.2: PLACING A DOLLAR VALUE ON ThE LOSS Of WELLBEING
LossofwellbeingisestimatedusingDALYsandapplyingthelowerboundVSLof$3.7millionto
yieldthe estimated value of a life year of $162,561 (CERA, 2004).
DEP VI VI DEP VI
W W W W ! " + = ) 1 (
,
FALL VI VI FALL VI
W W W W ! " + = ) 1 (
,
FALL DEP VI DEP VI FALL DEP VI
W W W W ! " + = ) 1 (
, , , ,
6. Disease Costs
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6.3: HLAL1H SYS1LM COS1S
Thehealthsystemcostsofglaucomaarecategorisedanddiscussedinthissectionasfollows:
thecostofmonitoringanindividualwithglaucoma(notincludingtreatmentcosts);
thecostsoftreatmentforPOAG;
theincreasedlikelihoodofbeingadmittedtoanagedcarefacilityandtheassociatedcosts;
thecostsassociatedwithanincreasedlikelihoodoffallsandhipfractures;and
thecostsassociatedwithanincreasedlikelihoodofdepression.
DataonthehealthsystemcostsofPOAGarefromaspecialrequestfromtheAIHW.
Themostrecentdataforexpenditurebydiseaseareforthefnancialyear2000-01andhave
beenfactoredupforhealthinfation.Basedonestimatesofincreasesinhealthexpenditure
fromtheAIHW,healthinfationinthelasteightyearsto2004-05hasbeenaround3.2%per
annum(AIHW2006).
TheAIHWincludeonly87.5%(AIHW2005)oftotalrecurrenthealthexpenditureintheir
estimatesofexpenditurebydiseaseandinjury,referredtoasallocatedhealthexpenditure.
Theunallocatedremainderincludescapitalexpenditures,expenditureoncommunity
health(excludingmentalhealth),publichealthprograms(exceptcancerscreening),health
administrationandhealthaidsandappliancesthecodingfortheseareasofexpendituredoes
notallowallocationbydiseasecategory.Toensurecomprehensiveness,theseaspectsofhealth
systemcostshavebeenincorporatedbymultiplyingtheAIHWallocatedexpenditureestimates
by1.143(=1/0.875).Factoringuptheallocatedexpenditureinthiswaymeansthatcareneeds
tobetakentoavoiddoublecounting.Forexample,manyaidsandappliancecostsareprovided
bycommunityprograms(ratherthangovernmentprograms),andarenotincorporatedinthe
AIHWexpenditure.
Theproportionofhealthcostsbornebythegovernment(68.2%)andtheindividual(19.0%)is
basedonAIHW(2006:30).
TABLE 6.2: hEALTh COSTS BY WhO BEARS ThE COST, 2004-05
federal State/Territory Private health Individuals Other Total
Government Government Insurance
% 45.6% 22.6% 6.5% 19.0% 6.3% 100.0%
Source:AIHW(2006:30).
6.3.1: ThE COST Of MONITORING AN INDIVIDUAL WITh GLAUCOMA
Thecostofmonitoringanindividualwithglaucomain2005notincludingmedical,laser
andsurgicaltreatmentsis$649perpersonperyear.Thiswascalculatedbyadjustingthetotal
healthcostsforglaucoma($148.3min2000-01)inthefollowingways:
adjustforthechangeinthepopulationbetween2000-01and2005;
includeunallocatedhealthexpenditure(factoredupby1.143);
indexspendingto$2005(healthinfationof2.6%pa);and
removeexpenditureontreatment(medication,laserandsurgery)andagedcare;
dividebythenumberofpeoplereceivingtreatmentin2005.
6. Disease Costs
Overall, individuals
still pay 19% of
health costs.
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61 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
6.3.2: COST Of TREATMENT
Medication
ThecostestimateswerederivedusingdatafromtheDepartmentofHealthandAgeingweb
publicationAustralian Statistics on Medicines 2005,andAustralianMedicareBeneftsSchedule
fees.Thetotalcostofanti-glaucomamedicationsfor2005isinTable6.3,andisdividedby
thetotalnumberofpeoplereceivingmedicationin2005(ie.thenumberofpeoplewith
diagnosedPOAGin2005estimatedinthedynamicmodel)toderivethecostofmedication
perpersonperannum.
TABLE 6.3: COST Of MEDICATION PER PERSON PER ANNUM
TotalCostofAnti-glaucomaMedications $99,694,643
TotalNo.ofPeopleonMedication 103,820
CostofMedicationperPerson $960
Source:AustralianStatisticsonMedicines2005andAccessEconomicsEconomicModeloftheImpactofPrimaryOpen
AngleGlaucoma.
Thecostofthesideeffectsofmedicationswereaddedtothecostofmedicationsperperson.
TheORofCOPDfollowingtheuseofatopicalbeta-blockerappliedtotheaverageriskof
COPDinTable510is2.29andthecostofCOPDperpersonisinTable5.11.Thetotalcostof
medicationwithsideeffectsincludedbyageandgenderisinTable7.1.
Trabeculoplasty
Thecostofatrabeculoplastyisappliedinthemodelonceatthepointwhenapatient
transitionsintothelasertreatmentphase.To account for people that have more than one
trabeculoplasty procedure, the cost calculated inTable6.4is infated by 1.5 in the modelling
calculations (see Section 5.2). Thecostofthisprocedureisbasedonthetreatmentfeeinthe
MBSforthetreatmentaswellasthecostoftheanaesthesiaservice(Table6.5).Basedonclinical
adviceforthisreport,thecostofanassistanthasnotbeenincluded.
TABLE 6.4: TOTAL COST Of TRABECULOPLASTY PER TREATMENT
MBS Code Description Cost
42782 LaserTrabeculoplastyeachtreatmentto1eye,toamaximum $398.65
of4treatmentstothateyeina2yearperiod(Anaes.)(Assist.)
20140 Initiationofmanagementofanaesthesiaforproceduresoneyes, $84.25
notbeingaservicetowhichanotheriteminthisgroupapplies
(5basicunits)
Total $482.90
Source:MBSBook,1November2006
Medication costs on
average: $960.80
per person per year.
Trabeculoplasty costs
on average $482.90.
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6. Disease Costs
Trabeculectomy
Aswithtrabeculoplasty,thecostofatrabeculectomyisappliedinthemodelonce,whenthe
personmovesintothesurgerytreatmentphase.To account for people that have a second
trabeculectomy procedure, the total cost of surgery in Table6.6is scaled up by 1.2 to
$4,122.50.
Thecostofthisprocedureisbasedontheaveragediagnosisrelatedgroup(DRG)costfor
trabeculectomy,weightedforpublicandprivatehospitals,fromtheNationalHospitalCostData
Collection.ThecodethatrelatestotrabeculectomyproceduresisDRGC15AGlaucomaand
ComplexCataractProcedures.Thetotalcostsofprivatehospitaltrabeculectomyproceduresare
inTable6.5.
TABLE 6.5: TOTAL COST Of TRABECULECTOMY PER TREATMENT
Total Cost No. of Procedures Weighted Average
PrivateHospital $3,027 656 0.3993
PrivateFreeStandingHospital $3,027 404 0.2459
PublicHospital $4,178 583 0.3548
$3,435.42
Source:PersonalCommunication(MarcFoley,EarandEyeHospital);NationalHospitalCostDataCollectionRound9
PublicHospitalCostsandAIHWspecialdatarequest
6.3.3: AGED CARE
Visual impairment compounds the presence of other disabling conditions,leadingtoan
increasedlikelihoodofutilisinginstitutionalisedagedcare.UsingBMESdata,Wangetal,(2003)
foundaRRofpermanentnursinghomeadmissionafteradjustingfornon-cognitivefactors
thatpredictednursinghomeplacementforpeoplewithbestcorrectedvisualimpairment
(6/12)agedover40years,of1.8(95%CI1.12.9).InthismodelforpeoplewithEDStheRR
ofbeinginanagedcarefacilityisassumedtobeunity,whileforMild,ModerateandSevere
visualimpairmenttheRRofbeinginanagedcarefacilityisbasedonalinearadjustment,with
moderatevisualimpairmentasthemidpoint:
1.4formild;
1.8formoderate;and
2.2forseverevisualimpairment.
TheRRisappliedtothegeneralpopulationofbeinginanagedcarefacility,andtheaveragecost
peryearof$52,800,fromtheAccessEconomicsAgedCareDynamicCohortModel.
6. Disease Costs
Depression occurs
three times more
commonly in those
with vision loss.
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67 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
TABLE 6.12: DEPRESSION AND VISION LOSS
Source finding
Brodyetal,2003 33%depressed
Karisson,1998 Lessthan10%depressed
Kleinschmidt,1995 22%mildly;4%moderatelytoseverelydepressed
Rovneretal,1997 39%-70%depressiondependingonmeasurementscaleused
Wahl,1994 43%ofblind,29%ofvisuallyimpaireddepressed
Robbinsetal,1988 Meanscoreof10.3(10+indicatesdepression)
Vuetal,2005 OR6.28forhealthandemotionalproblems;OR4.7fornotfulloflife
Wilsonetal,2002 Nodifferenceindepressivestate
ChenandHe2005 Measuresformildanxietyandmoderatesevereanxietywereallhigherfor
bothacuteangleclosureglaucomaandchronicangleclosureglaucomathan
thenationalnorm.
Forthemodelbasecase,people with glaucoma have an OR of depression which is
approximately 3.5. Theriskofhavingdepressionforapersonwithoutglaucomaisassumedto
beequaltotheprevalenceofdepressioninthegeneralpopulation.Thecostofdepressionper
personisalsobasedonAIHW2000-01data,indexedto2005dollars(Table6.14).
TABLE 6.13: RISK Of DEPRESSION (% Of POPULATION), 2001
Age Males females Persons
0-4 0.00 0.00 0.00
5-14 0.02 0.01 0.01
15-24 0.95 1.02 0.99
25-34 3.29 4.45 3.87
35-44 4.38 5.95 5.17
45-54 4.35 6.32 5.33
55-64 3.82 5.72 4.76
65-74 2.77 3.97 3.39
75-84 1.93 2.37 2.19
85+ 1.34 1.45 1.41
AllAges 2.53 3.52 3.03
Source:AIHW,specialrequest.
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TABLE 6.14: hEALTh SYSTEM COST Of DEPRESSION ($ PER PERSON), 2005
Age Males females Persons
0-4 0 0 0
5-14 18,544 75,852 36,831
15-24 2,793 5,659 4,250
25-34 1,555 2,296 1,983
35-44 1,346 1,831 1,627
45-54 1,634 1,870 1,774
55-64 1,799 2,167 2,017
65-74 2,657 3,610 3,233
75-84 5,872 9,304 8,033
85+ 17,672 12,551 14,052
AllAges 1,915 2,632 2,334
Source:AIHW,specialrequest.
6.4: INDIkLC1 COS1S
Theindirectcostsofglaucomacanincludeareducedlikelihoodofemployment,theneedfor
formalaswellasinformalpersonalcare(andtheassociatedimpactontheemploymentof
informalcarers),aidsandequipment,andtheeconomiccostsofwelfarepayments.Manyofthese
indirect costs are related to the level of visual impairment rather than glaucoma per se,and
arethereforesimilartotheindirectcostsassociatedwithothereyediseasessuchasAMD.
EMPLOYMENT
Glaucomaoverwhelminglyaffectstheelderlysoveryfewpeoplewithseverevisualimpairment
arelikelytobeemployed.Forthepurposesofmodelling,peoplewithEDSareassumedtohave
anORofbeingemployedofunity,whileforMild,ModerateandSeverevisualimpairmentthe
ORofbeingemployedisbasedonalinearadjustmentoftheORcontainedinCERA(2004:66),
withmoderatevisualimpairmentasthemidpoint:
0.75formild;
0.5formoderate;and
0.25forseverevisualimpairment.
TheRRsareappliedtothegeneralemploymentratesbyagefromABS(2005)andtheAverage
WeeklyEarnings(AWE)ratesfromABS(2004),indexedto2005dollars.
OThER INDIRECT COSTS
Otherindirectcostsperperson(suchastheimpact on employment of informal carers, formal
care costs, aids and modifcations, and other indirect costs)wereextractedfromtheMVIP
databaseforthosepeoplewithVAloss(indirectcostsforpeoplewithoutvisualimpairmentare
assumedtobenil).DuetohighSDsinthedata,themeanindirectcostsacrossalllevelsofvisual
impairmentwereused,insteadofindirectcostsbymild,moderateandseverevisualimpairment.
6. Disease Costs
Glaucoma
overwhelmingly
affects the elderly
- fewer people
with severe visual
impairment are likely
to be employed.
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69 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
6. Disease Costs
Informalcareandsupportissplitbetweencostsandlostproductivityofthecarerbasedon
theratiocontainedinCERA(2004:75).TheproportionofMedicines,productsandequipment
thatareaidsandmodifcationsisbasedonthesplitusedinCERA(2004:70-72).Carer
productivitycostswereindexedto2005accordingtoAWEovertime,whiletheremaining
indirectcostswereindexedtohealthinfation.
TABLE 6.15: INDIRECT COSTS ($ PER ANNUM), 2005
Cost
FormalCare 439
LostProductivityofCarer 1,544
AidsandModifcations 337
OtherExpenses 630
Sources:MVIP,CERA(2004).
6.5: DLADwLIGH1 LOSSLS
Thefollowingparameterswereusedtoestimatelost taxes and additional welfare payments
fromglaucoma,whichinturnunderlietheestimationofdeadweightlossestotheeconomy.
Averagepersonalincometaxrateof21.20%andaverageindirecttaxrateof15.51%,based
onAccessEconomicsMacroeconomicmodel(AEM).
Thelevelofdisabilitysupportperannumof$10,340.20($397.70x26fromwww.
centrelink.gov.auin2005),isindexedtotheAWEandisreceivedbyallindividualswithVA
worsethan6/60whoareaged15to65(afterthisageitislikelytheywouldreceivethe
agedpensionregardlessoftheirVA)
21
.
Therateofdeadweightlossis0.275per$1oftaxrevenueraised,basedonProductivity
Commission(2003),plus0.0125per$1oftaxrevenueraisedforAustralianTaxationOffce
(ATO)administration,andisappliedtohealthsystemcostsincurredbythegovernment,lost
taxesandwelfarepayments.
21
Ifapersononthedisabilitypensionisemployed,then(dependingonthelevelofincomeandhoursofemployment)
theamountreceivedmaybeadjustedslightlydownwards.However,givenglaucomamainlyaffectsolderpeople,and
thosethatreceivethepensionarepermanentlyblind,thenumberofpeopleemployedwouldbelowandanyslight
adjustmentsdownwardswouldmakenegligibleimpactontheresults(especiallysinceweonlyincludethedeadweight
lossofthegovernmentexpenditureratherthantheexpenditureitself).
Indirect costs of
vision loss are often
overlooked.
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This section summarises the parameters used in the model.
Modelled prevalence rates are in Table 7.1.
Initial severity of visual impairment splits are in Table 7.2.
Modelled treatment assumptions are in Table 7.3.
The costs of treatment including the expected health system costs of side-effects and
adverse events are in Table 7.4. There is also a cost of monitoring those who are diagnosed
with POAG at $649 per patient per year.
The Sections explaining the other parameters used within the model are listed in Table 7.5.
TABLE 7.1: PREVALENCE OF OHT AND POAG
OHT POAG
Age Males Females Males Females
0-4 0% 0% 0.0% 0.0%
5-9 0% 0% 0.0% 0.0%
10-14 0% 0% 0.0% 0.0%
15-19 0% 0% 0.0% 0.0%
20-24 0% 0% 0.0% 0.0%
25-29 0% 0% 0.0% 0.0%
30-34 0.00% 0.00% 0.00% 0.0%
35-39 0.02% 0.02% 0.00% 0.00%
40-44 0.08% 0.08% 0.07% 0.07%
45-49 0.15% 0.15% 0.14% 0.14%
50-54 0.23% 0.23% 0.60% 0.60%
55-59 0.30% 0.30% 0.94% 0.94%
60-64 0.35% 0.35% 2.29% 2.29%
65-69 0.39% 0.39% 3.46% 3.46%
70-74 0.44% 0.44% 5.51% 5.51%
75-79 0.49% 0.49% 5.78% 5.78%
80-84 0.49% 0.49% 6.74% 6.74%
85-89 0.49% 0.49% 9.66% 9.66%
90+ 0.49% 0.49% 20.66% 20.66%
Source: BMES and MVIP data
7. Summary of Model Parameters
71 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 7. Summary of Model Parameters
TABLE 7.2: SEVERITY OF VISUAL IMPAIRMENT INITIAL PROPORTIONAL SPLIT
Age EDS Mild Moderate Severe
0-4 0% 0% 0% 0%
5-9 0% 0% 0% 0%
10-14 0% 0% 0% 0%
15-19 0% 0% 0% 0%
20-24 0% 0% 0% 0%
25-29 0% 0% 0% 0%
30-34 0% 0% 0% 0%
35-39 0% 0% 0% 0%
40-44 100.0% 0.0% 0.0% 0.0%
45-49 100.0% 0.0% 0.0% 0.0%
50-54 100.0% 0.0% 0.0% 0.0%
55-59 100.0% 0.0% 0.0% 0.0%
60-64 95.1% 0.2% 1.7% 2.9%
65-69 94.3% 0.4% 2.8% 2.6%
70-74 92.5% 0.5% 3.7% 3.3%
75-79 88.6% 1.2% 8.4% 1.8%
80-84 84.4% 1.7% 11.5% 2.5%
85-89 78.0% 2.2% 15.1% 4.8%
90+ 70.6% 1.1% 7.7% 20.6%
Source: BMES and MVIP data
TABLE 7.3: MODELLED TREATMENT ASSUMPTIONS
Treatment efcacy Compliance Treatment Incidence
(reduction in and failure rates
progression of
visual impairment)
Medication 50% Inherent in the data See Table 5.5
and calculation (total
costs of medications for
POAG in 2005 divided by
prevalence of diagnosed POAG)
Trabeculoplasty 50% 100% 50% of patients
fail each year
Trabeculectomy 50%
#
100% 50% of patients
fail each year
#
Based on equivalence between medication and trabeculectomy demonstrated in CIGTS.
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7. Summary of Model Parameters
TABLE 7.4: MODELLED TREATMENT COSTS $ 2005
(INCLUDING SIDE-EFFECTS AND ADVERSE EVENTS)
Medication (a) Trabeculoplasty (b) Trabeculectomy (c)
Male Female Male Female
40-44 964.58 967.45 724.35 4122.50 4122.50
45-49 972.82 973.42 724.35 4122.50 4122.50
50-54 972.82 973.42 724.35 4122.50 4122.50
55-59 1023.46 1009.71 724.35 4122.58 4122.58
60-64 1023.46 1009.71 724.35 4122.51 4122.51
65-69 1152.08 1086.79 724.35 4122.72 4122.73
70-74 1152.08 1086.79 724.35 4123.47 4123.51
75-79 1309.53 1131.53 724.35 4126.31 4126.55
80-84 1309.53 1131.53 724.35 4131.33 4131.88
85-89 1375.39 1143.02 724.35 4136.77 4131.47
90+ 1375.39 1143.02 724.35 4147.35 4138.12
Calculation of these estimates is explained in Section 6.3.2. a) Cost of anti-glaucoma medications plus the costs of
the risk of COPD. b) Cost of trabeculoplasty adjusted upwards by 1.5 to account for people who have a second laser
treatment. c) Trabeculectomy adjusted upwards by 1.2 to account for people who have a second trabeculectomy and
also adjusted upwards in the older age groups to account for the increasing risk of cataract surgery as a side effect.
TABLE 7.5: OTHER MODELLED VARIABLES
Item Reference
Disability weights Table 6.1, page 59
Health System Costs Page 60
Aged Care Table 6.6, page 63
Accidental Falls Table 6.9, Table 6.10 and Table 6.11, pages 65 to 66
Depression Table 6.13 and Table 6.14, pages 67 to 68
Employment Page 66
Other Indirect Costs Table 6.15, page 69
Deadweight losses Page 69
Other indirect costs include formal care, lost productivity of carers, aids and modications and other expenses.
73 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
8. The Model
The model was built in Microsoft Ofce Excel 2003 which ensures portability. The model can
be navigated by clicking on the relevant button on the Main Menu (see Figure 8.1) or by clicking
on the sheet tabs at the bottom of the window. In order to access and view the sheets with the
parameters and the models workings, click the Show/Hide Parameter Sheets button.
Prevalence rates are assumed to be the number of people with the disease at the start of the
year. During the year people are treated, progress, or die, with the impacts of these pathways on
prevalence rates occurring at the start of the following year (see Figure 8.3 for a diagram of the
models logical structure).
To select scenarios, click on the User Options sheet button (see Figure 8.2). To view output, click
the Cost-effectiveness Analysis, PopChart, CostChart or CE-PlaneChart buttons.
FIGURE 8.1: MAIN MENU
Cost effectiveness analysis can be conducted comparing various scenarios with the base case.
To set the base case, tick the No new intervention (Standard treatment) box on the
Options sheet.
Three treatment phases are modelled, consistent with the current treatment regimen:
medication, laser (trabeculoplasty) and surgery (trabeculectomy). The order in which these
treatments is applied can be switched in the Select intervention and Select intervention
detail windows on the options sheet.
74
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8. The Model
fIGURE 8.2: OPTIONS ShEET
Cost effectiveness
analysis can be
conducted by running
various scenarios of
current treatment
and comparing with
the base case.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
72
FIGURE 8-2: OPTIONS SHEET
Centre for Eye Research Australia
75 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
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76
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Centre for Eye Research Australia
The model has been adapted so that users can test the economic impact of changes to current
treatment patterns. The scenarios are as follows:
the base case (No new intervention (standard treatment));
an increase in the rate at which POAG is diagnosed (to 70%, 80% or 90%);
a change in the treatment protocol (using laser trabeculoplasty as the primary treatment
instead of medication, with medication becoming the second treatment phase and surgery
the third phase);
research to delay progression (by 50% or 75%); and
combination scenarios an increase in the rate at which POAG is diagnosed from 50% to
80% together with:
- A change in the treatment protocol; or
- The introduction of a new treatment to delay progression by a further 50%.
9.1: THE BASE CASE
The base case scenario can be set to either the current situation (no new intervention/standard
treatment) or an other intervention which can be chosen using the Select intervention and
Select intervention detail from the Options sheet.
9.1.1: TO RUN A BASE CASE
To select the current situation (No new intervention (Standard treatment)) as the base case
for comparison:
tick the No new intervention (Standard treatment) box on the Options sheet (note: it will
take a little while to reset all the parameters to reect the current situation).
Select frequency every year.
click the Set as Base Case button.
In brief, the base case parameters are: a POAG diagnosis rate of 50%, treatment regimen of
medication rst, followed by laser and then nally by surgery, and an impact of treatment
(treatment efcacy) of a 50% reduction in the progression of visual impairment. The previous
chapters explain the base case in more detail.
If you wish to chose another scenario as the base case (for example, increased diagnosis rates),
you must rst un-tick the No new intervention (Standard treatment) box. Then choose an
intervention from the Select Intervention box and the Select Intervention Detail box.
Then click the Set as Base Case button.
9.1.2: RESULTS
If current standard treatments continue for the next 20 years, and no new intervention scenarios
are applied:
the prevalence of OHT in Australia will increase from 26,000 people in 2005, to 41,000
people in 2025;
the prevalence of POAG in Australia will increase over the same period from 208,000
people to 379,000; and
9. Intervention Scenarios
77 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here
the prevalence of visual impairment from POAG in Australia is expected to grow from
24,000 people in 2005 to 52,000 people in 2025 (Table 9.1).
The prevalence estimates here vary somewhat from those in Clear Insight, (CERA 2004) that
used age and gender specic prevalence rates from the MVIP and BMES, with visual impairment
based on loss of VA. This analysis also uses data from the combined MVIP/BMES data set,
but for persons rather than by gender, and measuring visual impairment measured using a
combination of VA and VF.
Figure 9.1 shows a steady increase in the prevalence of POAG from 2005 and 2025, driven by an
ageing population.
TABLE 9.1: PREVALENCE OF OHT AND POAG, BASE CASE (NUMBER OF PEOPLE)
2005 2025
OHT 25,986 40,004
POAG
Early stage 183,530 326,659
Mild stage 1,872 3,667
Moderate stage 12,914 26,047
Severe stage 9,312 22,613
POAG (all stages) 207,628 378,985
Visual Impairment from POAG 24,098 52,327
Prevalence (Total OHT & POAG) 233,614 419,989
Source: Access Economics/CERA dynamic model
FIGURE 9.1: PREVALENCE OHT AND POAG, BASE CASE
The health system costs of glaucoma in 2005 were $355 million and the total annual cost of
glaucoma in 2005 was $1.9 billion. In real dollar terms, these costs are expected to increase to
$784 million and $4.3 billion respectively by 2025 (Table 9.2). The net present value of DALYs
and other costs of POAG are depicted in Table 9.3.
The total cost of
glaucoma will
increase in 2005 to
$1.92 billion, and
$4.3 billion in 2025.
9. Intervention Scenarios
Prevalence (diagnosed and undiagnosed)
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TABLE 9.2: COSTS OF POAG, 2005 AND 2025, BASE CASE
2005 2025
DALYs 6,940 15,592
YLD 6,678 15,184
YLL 262 408
Burden of Disease Costs ($) 1,043,713,812 2,325,613,694
Health System Costs ($) 355,121,086 783,978,738
Comorbid Health Costs ($) 166,419,635 423,192,582
Treatment Costs ($) 188,701,450 360,786,156
Productivity Costs ($) 60,406,596 130,614,278
Other Indirect Costs ($) 109,422,685 240,987,552
Total Costs ($) 1,923,785,265 4,265,173,000
TABLE 9.3: BASE CASE (STANDARD TREATMENT) NET PRESENT VALUE OF DALYS AND COSTS
Net present value 2005 to 2025
DALYs 155,150
Burden of Disease Costs ($ million) 23,896
Health System Costs ($ million) 8,759
Comorbid Health Costs ($million) 4,505
Treatment Costs ($million) 4,254
Productivity Costs ($ million) 1,665
Other Indirect Costs ($million) 2,695
Total Costs ($million) 37,015
The value of the burden of disease due to POAG over time is depicted in Figure 9.2.
FIGURE 9.2: VALUE OF BURDEN OF DISEASE DUE TO POAG ($M), BASE CASE
Sensitivity analysis zero prevalence and incidence of OHT among those aged 80 and over
9. Intervention Scenarios
Over half the costs
of glaucoma relate to
loss of well being.
0
500
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1,500
2,000
2,500
2005 2010 2015 2020 2025
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Burden of Disease Costs
Centre for Eye Research Australia
79 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.1.3: SENSITIVITY ANALYSIS ZERO PREVALENCE AND INCIDENCE Of OhT AMONG
ThOSE AGED 80 AND OVER
Asnotedearlier,prevalencedataweresmoothedinpartbecauseofthesmallsamplesizesinthe
originaldataset.UnsmoothedoriginaldatashowedzeroprevalenceratesforOHTamongthose
aged80yearsorover.Theimpactofusingsmoothedratherthanoriginaldataispresentedin
Table9.4andTable9.5.ThetotalcostsofPOAGareslightlylower(Table9.5).
TABLE 9.4: COMPARISON Of PREVALENCE Of OhT AND POAG WITh ORIGINAL AND
SMOOThED DATA
Original OhT prevalence Smoothed OhT
data (Zero OhT prevalence prevalence data
and incidence for those
aged 80 years or over)
2005 2025 2005 2025
reva|ence OH1 and OAG 227,827 406,840 233,614 419,989
PrevOHT 23,684 36,340 25,986 41,004
PrevearlystagePOAG 180,149 318,477 183,530 326,659
PrevMildPOAG 1,826 3,550 1,872 3,667
PrevModeratePOAG 12,871 25,918 12,914 26,047
PrevSeverePOAG 9,297 22,555 9,312 22,613
TABLE 9.5: NET PRESENT VALUE Of DALYS AND COSTS, SENSITIVITY ANALYSIS ON OhT
PREVALENCE AND INCIDENCE fOR ThOSE AGED 80+ YEARS
Net present value Net present value
2005 to 2025 2005 to 2025
Zero OhT prevalence and Smoothed data
incidence for those aged
80 years or over
DALYs 154,656 155,150
BurdenofDiseaseCosts($million) 23,836 23,896
HealthSystemCosts($million) 8,636 8,759
ComorbidHealthCosts($million) 4,474 4,505
TreatmentCosts($million) 4,162 4,254
ProductivityCosts($million) 1,660 1,665
OtherIndirectCosts($million) 2,666 2,695
TotalCosts($million) 36,798 37,015
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9.2: IMkOVLD DIAGNOSIS kA1L
Morethan50%ofthoseindevelopedcountrieswithglaucomaareunawaretheyhavethe
disease(Quigley,1996).Inapopulationbasedstudy(theMVIP),Wensoretal,(1998)found
that50%ofthosewithdefnitePOAGhadnotbeendiagnosedpreviously,andWongetal,
(2004)examinedthepresenceofundiagnosedOAGinpeoplewhohadvisitedaneyecare
providerinthepreviousyearusingVisualImpairmentProjectdatafromMelbourneandrural
communitiesinVictoria.Theyfoundthat81%ofpossiblecases,72%ofprobablecasesand
59%ofdefnitecasesofOAGwerepreviouslyundiagnosed.Ofthe115participantswith
probableordefniteOAG,72(63%)werepreviouslyundiagnosed.Oftheseundiagnosed
probableanddefnitecases,35(49%)hadvisitedaneyecareproviderwithintheprevious12
monthperiod.The35undiagnosedpatientswerecomparedwith43diagnosedpatientswho
hadvisitedanoptometristorophthalmologistorbothintheprevious12months.Thetype
ofeyeprofessionalseen,andthepresenceofVFdefectsweretheonlystatisticallysignifcant
variablesbetweenthediagnosedandundiagnosedglaucomagroups.
DiagnosisratesforPOAGcouldbeimprovedby:
1) atthecurrentdiagnosisthreshold,enhancingthequalityofcarebyensuring
ophthalmologistsincludetheappropriateVFtestswhenexaminingpatientseyes;
2) carefulexaminationoftheopticdiscinallpatientsregardlessofIOP;and
3) improvingthefocusonfamilyhistorysincepeoplewithafamilyhistoryofglaucoma
haveahigherchanceofdevelopingPOAG.
Underthebasecasescenario,50%ofpeoplewithPOAGarediagnosedandtreated.Underthis
scenario,theimpactofincreasingtheproportionofpeoplediagnosedwithPOAGto(i)70%,
(ii)80%and(iii)90%canbeassessed.Nocostshavebeenaddedtothemodeltoallowfor
educationofclinicians.
Underthisscenariotheonlyparameterthatisvariedistherateatwhichpeoplearediagnosed.
Thecostsandbeneftsthatresultfromthisanalysisrefectmorepeoplereceivingtreatmentto
slowprogressionofPOAG.
9.2.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
TicktheNonewIntervention(Standardtreatment)boxandclickontheSetasBaseCase
buttontoensurethecurrentsituationisthecomparator.
Un-ticktheNonewIntervention(Standardtreatment)boxandmakesurethatthe
FrequencyEveryYearboxisticked.
OntheOptionssheet,chooseImprovedDiagnosisRateintheSelectInterventionbox
andDiagnosisRate70%,orDiagnosisRate80%,orDiagnosisRate90%intheSelect
InterventionDetailbox.
ThenclicktheSetasScenario1button,torunthenewscenario.
AsecondscenariocanbeevaluatedbyreselectingfromtheSelectInterventionandSelect
InterventionDetailwindows.ThenclicktheSetasScenario2button,torunthenew
scenario.
ClickCompareScenarios(CEA).
9. Intervention Scenarios
At present,
50% of people
with POAG are
undiagnosed.
Centre for Eye Research Australia
81 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.2.2: RESULTS
Inthebasecase,50%ofpeoplewithPOAGarediagnosed.Theresultsofincreasingtherateof
diagnosisarepresentedinTable96.Theestimatesinthetablerefectthenetpresentvalueof
costsandbeneftsovertheentireperiod(2005to2025).Incomparisonwiththebasecase,the
increaseddiagnosisratereducesthetotalnumberofDALYs(Table96)asmorepeoplereceive
benefcialtreatment,however,thismeansthattreatmentcostsrise.Productivitycostsand
comorbidhealthcostsarelessthanforthebasecasebecauseagreaterproportionofpeople
receivetreatmentwhichslowdiseaseprogressionallowingthemtospendmoretimein
employment,andtoavoidcomorbidconditionssuchasdepression,fallsandfracturesassociated
withthelaterstagesofglaucoma.
TABLE 9.6: MODEL RESULTS INCREASED DIAGNOSIS RATE, NET PRESENT VALUE 2005 TO 2025
Net Present Values, Base Case
2005 to 2025 (Standard Diagnosis rate Diagnosis rate Diagnosis rate
treatment) 70% 80% 90%
DALYs 155,150 146,141 142,248 138,702
BurdenofDiseaseCosts($m) 23,896 22,249 21,529 20,866
HealthSystemCosts($m) 8,759 10,091 10,747 11,400
ComorbidHealthCosts($m) 4,505 4,403 4,354 4,307
TreatmentCosts($m) 4,254 5,687 6,393 7,093
ProductivityCosts($m) 1,665 1,514 1,443 1,373
OtherIndirectCosts($m) 2,695 2,894 2,993 3,092
TotalCosts($m) 37,015 36,748 36,711 36,731
CL ratio: keturn on $1 spent{a) $1.19 $1.14 $1.10
$/DALY avoided{b) $153,144 $159,908 $166,948
(a)CEratioisthechangeintotaldiseasecostsdividedbythechangeintreatmentcosts.(b)$/DALYavoidedisthe
changeinhealthsystem,productivityandotherindirectcostsdividedbythedifferenceinDALYs.
Figure9.3showstheoutcomeofadiagnosisrateof70%and90%.Inthebasecase,DALYsrise
to15,600in2025(Table9.2).Withimproveddiagnosis,theburdenofdiseaseislowerin2025
thaninthebasecase14,300DALYs(70%diagnosed)and13,200DALYs(90%)diagnosedin
2025(Figure9.3).However,withhigherdiagnosisrates,treatmentcostsarealsohigherthanin
thebasecase(Figure9.4).
82
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Centre for Eye Research Australia
9. Intervention Scenarios
fIGURE 9.3: IMPACT Of INCREASED DIAGNOSIS RATES ON DALYS(A)
fIGURE 9.4: IMPACTS Of INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
TherelativecosteffectivenessofeachscenarioisdepictedinFigure9.5.Thebasecaseis
representedattheorigin.EffectivenessismeasuredasthetotalnumberofDALYsavoidedand
costsaretotalcosts(excludingthevalueoftheburdenofdisease).
Atzeroadditionalcosts(ie.noadditionalcostsofeducatingcliniciansinordertoimprove
diagnosisrates),improveddiagnosisratesfrom50%to70%,80%and90%,are cost
effective at between $153,000 and $167,000 per DALY avoided.
Ifeducatingclinicianswerecostly,thesescenarioswouldbecomelesscosteffective.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
80
diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are
also higher than in the base case (Figure 9-4).
FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is
represented at the origin. Effectiveness is measured as the total number of DALYs avoided
and costs are total costs (excluding the value of the burden of disease).
At zero additional costs (ie. no additional costs of educating clinicians in order to improve
diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are cost
effective at between $153,000 and $167,000 per DALY avoided.
If educating clinicians were costly, these scenarios would become less cost effective.
Economic impact of primary open angle glaucoma Commercial-in-Confidence
80
diagnosed in 2025 (Figure 9-3). However, with higher diagnosis rates, treatment costs are
also higher than in the base case (Figure 9-4).
FIGURE 9-3: IMPACT OF INCREASED DIAGNOSIS RATES ON DALYS(A)
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
FIGURE 9-4: IMPACTS OF INCREASED DIAGNOSIS RATES ON TREATMENT COSTS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 70%
Diagnosis rate 90%
The relative cost effectiveness of each scenario is depicted in Figure 9-5. The base case is
represented at the origin. Effectiveness is measured as the total number of DALYs avoided
and costs are total costs (excluding the value of the burden of disease).
At zero additional costs (ie. no additional costs of educating clinicians in order to improve
diagnosis rates), improved diagnosis rates from 50% to 70%, 80% and 90%, are cost
effective at between $153,000 and $167,000 per DALY avoided.
If educating clinicians were costly, these scenarios would become less cost effective.
Increasing the
diagnosis rate to
80% would cost
$160,000/DALY.
Centre for Eye Research Australia
83 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
fIGURE 9.5: COST EffECTIVENESS PLANE INCREASE DIAGNOSIS RATE(A)
(a)EffectivenessmeasuredasDALYsavoided.Costsrefecthealthsystem,productivityandotherindirectcosts.
(CosteffectivenessismeasuredasthecostperDALYavoided.Thevalueoftheburdenofdiseaseisexcludedfrom
thecostestimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).
9.3: CHANGL IN 1HL 1kLA1MLN1 kO1OCOL {kIMAkY LASLk)
Asnotedabove,inbrief,thebasecaseparametersare:aPOAGdiagnosisrateof50%,
treatmentregimenofmedicationfrst,followedbylaserandthenfnallybysurgery,failure
ratesformedicationof4.3%ofpatientsperannum,50%forlasertrabeculoplastyand50%
fortrabeculectomy,andanoverallimpactoftreatmentonvision(treatmenteffcacy)ofa
50%reductionintheprogressionofvisualimpairment.UnderthisscenarioChangeinthe
treatmentprotocollaserreplacestopicalmedicationasfrstlinetherapyfrom2005onwards
sothatpatientsbegintreatmentwithalasertrabeculoplasty,thenfollowwithmedicationand
fnallytrabeculectomy.
Treatmentcost-savingsarepossiblefromthisscenario,asmedicationisnolongerrequired
incombinationwithlasertreatment.Underthebasecase,ontheotherhand,wherelaseris
secondlinetherapy,itiscombinedwithmedication.
TheGLT(whichcomparedtwo180degreeALTtreatmentswithtimolol)showedthatALTwasat
leastaseffcaciousasmedicationasaninitialtreatmentforglaucoma(GlaucomaLaserTrialResearch
Group,1995).However,ALTwasnotcommonlyadoptedasaprimarytreatmentbecauseofconcern
aboutsideeffectsandthereducedeffcacyofrepeatALTtreatments.Inaddition,atthetimeofthe
GLT,prostaglandinswerenotinuseastopicalmedicationsforglaucoma(asMcIlraithetal,(2006)
noted).Evidencefortheeffectivenessoflasertreatmentsasaprimarytherapyinclude:
TheEMGT,arandomisedclinicaltrialcomparingALTandmedicationwithnotreatment,
foundthat,whenadjustedforcensoringandothercovariates,progressionriskwashalvedby
treatment.After6years,theHRwas0.5(95%CI0.35to0.71).
Nagaretal,2005,whoconductedarandomisedprospectivestudycomparing360degree
selectivelasertherapy(SLT)with0.005%latanoprostatnight,foundnodifferencesinmean
VFdefectsbetweengroupsafter12months.
McIlraithetal,2006,inanon-randomisedpilotstudyof100eyesnewlydiagnosedPOAG
andOHTin61patients,andcomparing180degreeSLTwithlatanoprost,foundthatthetwo
treatmentswereequallyeffcaciousinreducingIOPinover12months.
Commercial-in-Confidence Economic impact of primary open angle glaucoma
81
FIGURE 9-5: COST EFFECTIVENESS PLANE INCREASE DIAGNOSIS RATE(A)
Diagnosis rate 70%
Diagnosis rate 90%
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
9.3 CHANGE IN THE TREATMENT PROTOCOL (PRIMARY
LASER)
As noted above, in brief, the base case parameters are: a POAG diagnosis rate of 50%,
treatment regimen of medication first, followed by laser and then finally by surgery, failure
rates for medication of 4.3% of patients per annum, 50% for laser trabeculoplasty and 50% for
trabeculectomy, and an overall impact of treatment on vision (treatment efficacy) of a 50%
reduction in the progression of visual impairment. Under this scenario Change in the
treatment protocol laser replaces topical medication as first line therapy from 2005
onwards so that patients begin treatment with a laser trabeculoplasty, then follow with
medication and finally trabeculectomy.
Treatment cost-savings are possible from this scenario, as medication is no longer required in
combination with laser treatment. Under the base case, on the other hand, where laser is
second line therapy, it is combined with medication.
The GLT (which compared two 180 degree ALT treatments with timolol) showed that ALT was
at least as efficacious as medication as an initial treatment for glaucoma (Glaucoma Laser
Trial Research Group, 1995). However, ALT was not commonly adopted as a primary
treatment because of concern about side effects and the reduced efficacy of repeat ALT
treatments. In addition, at the time of the GLT, prostaglandins were not in use as topical
medications for glaucoma (as McIlraith et al, (2006) noted). Evidence for the effectiveness of
laser treatments as a primary therapy include:
The EMGT, a randomised clinical trial comparing ALT and medication with no treatment,
found that, when adjusted for censoring and other covariates, progression risk was
halved by treatment. After 6 years, the HR was 0.5 (95% CI 0.35 to 0.71).
Nagar et al, 2005, who conducted a randomised prospective study comparing 360
degree selective laser therapy (SLT) with 0.005% latanoprost at night, found no
differences in mean VF defects between groups after 12 months.
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9. Intervention Scenarios
Sanflippo(1999)citedresearchsuggestingALTwasmoreeffcaciousthatpilocarpine.Two
yearsuccessrateswhenassessingIOPwere63%and44%fortheALTandpilocarpinegroups
respectively.ItwasfoundthatALTgaveasignifcantlybetterpreservationoftheVFthan
pilocarpine.ThroughregressionanalysisthetimelefttoblindnessfortheALTgroupwas31years
andforthepilocarpine-treatedgroup,12years(assumingalineardecay)(SanflippoP,1999).
9.3.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clickthescenarioresetbuttons.
TicktheNonewintervention(Standardtreatment)box
Selectfrequencyeveryyear
clickontheSetasBaseCasebutton(sothatstandardtreatmentisthecomparator).
Un-ticktheNonewintervention(Standardtreatment)box.
MakesurethattheFrequencyEveryYearboxisticked.
OntheOptionssheets,chooseChangeTreatmentProtocolintheSelectInterventionbox
andPrimarylasertrabeculoplastyintheSelectInterventionDetailbox.Thenclickthe
SetasScenario1button,torunthenewscenario.
ClickCompareScenarios(CEA).
9.3.2: RESULTS
TheresultsarepresentedinTable9.7.Thechangeintreatmentprotocoliscost-saving
(consistentwiththehypothesisabove).Thereislittleimpactontheresultsifthecostoflaseris
tripledorincreasesfvefoldtoaccountforthecostofsideeffects(assumingthesecanbefxed
relativelyquicklysothereisnoimpactonthepatientsqualityoflife)(Table9.7).
Figure9.6showsthatthecost-savingsassociatedwiththenewprotocolincreaseovertimeas
morepeoplearediagnosedandtreatedforPOAGbecauseofpopulationageing.Theburdenof
diseaseisdepictedinFigure9.7.
TABLE 9.7: MODEL RESULTS PROTOCOL ChANGE TRABECULOPLASTY AS PRIMARY TREATMENT
Net Present Standard Primary Standard Primary Standard Primary
Values Laser treatment treatment Laser treatment Laser
($724) ($2,173) ($3,622)
DALYs 155,150 155,974 155,150 155,974 155,150 155,974
BurdenofDisease 23,896 24,095 23,877 24,070 23,858 24,046
Costs($m)
HealthSystem 8,759 8,392 8,865 8,548 8,971 8,703
Costs($m)
ComorbidHealth 4,505 4,519 4,505 4,519 4,505 4,519
Costs($m)
TreatmentCosts($m) 4,254 3,873 4,360 4,029 4,465 4,184
ProductivityCosts($m) 1,665 1,671 1,665 1,671 1,665 1,671
OtherIndirectCosts($m) 2,695 2,628 2,715 2,658 2,736 2,689
TotalCosts($m) 37,015 36,787 37,122 36,948 37,230 37,109
CL ratio: keturn on $0.40 $0.47 $0.57
$1 spent{a) Cost- Cost- Cost-
$/DALY avoided Saving Saving Saving
(a)Defnedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspentontreatment.
Centre for Eye Research Australia
85 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
fIGURE 9.6: COST-SAVINGS RESULTING fROM A PROTOCOL ChANGE(A)
(a)Lasercosting$724pertreatment.
fIGURE 9.7: BURDEN Of DISEASE
Economic impact of primary open angle glaucoma Commercial-in-Confidence
84
FIGURE 9-7 BURDEN OF DISEASE
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Primary laser trabeculoplasty
Scenario 2
9.3.3 SENSITIVITY ANALYSIS THE IMPACT OF THE CONSERVATIVE
APPROACH TO SURGERY FAILURE RATES
Taking a conservative approach to the surgery failure rate doesnt substantively affect the
results because treatment efficacy is measured according to whether a patient is treated or not
rather than the particular treatment the patient receives. In other words, all treated patients
(no matter what order they receive treatments) experience a reduction in progression of visual
impairment by 50% compared with people who have undiagnosed POAG. Taking a
conservative approach to the surgery failure rate means that more patients progress more
quickly to medications bringing forward the costs of medications for those patients and
leading to higher health system cost estimates (Table 9-8) . Repeat surgery may also be
performed. Based on MBS data surgery is performed at a rate of 1.2 and costs have been
factored accordingly.
Commercial-in-Confidence Economic impact of primary open angle glaucoma
83
TABLE 9-7: MODEL RESULTS PROTOCOL CHANGE TRABECULOPLASTY AS PRIMARY
TREATMENT
Net Present
Values
Standard
treatment
Primary
Laser
($724)
Standard
treatment
Primary
Laser
($2,173)
Standard
treatment
Primary
Laser
($3,622)
DALYs 155,150 155,974 155,150 155,974 155,150 155,974
Burden of
Disease
Costs ($m) 23,896 24,095 23,877 24,070 23,858 24,046
Health
System
Costs ($m) 8,759 8,392 8,865 8,548 8,971 8,703
Comorbid
Health Costs
($m) 4,505 4,519 4,505 4,519 4,505 4,519
Treatment
Costs ($m) 4,254 3,873 4,360 4,029 4,465 4,184
Productivity
Costs ($m) 1,665 1,671 1,665 1,671 1,665 1,671
Other Indirect
Costs ($m) 2,695 2,628 2,715 2,658 2,736 2,689
Total Costs
($m) 37,015 36,787 37,122 36,948 37,230 37,109
CE ratio:
Return on $1
spent(a) $0.40 $0.47 $0.57
$/DALY
avoided
Cost-
Saving
Cost-
Saving
Cost-
Saving
(a) Defined as the difference in indirect costs between primary laser and the base case for every additional dollar
spent on treatment.
FIGURE 9-6: COST-SAVINGS RESULTING FROM A PROTOCOL CHANGE(A)
Treatment Costs
0
50,000,000
100,000,000
150,000,000
200,000,000
250,000,000
300,000,000
350,000,000
400,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Primary laser trabeculoplasty
Scenario 2
(a) Laser costing $724 per treatment.
Laser trabeculoplasty
actually saves money
when used as the
initial treatment.
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9. Intervention Scenarios
9.3.3: SENSITIVITY ANALYSIS ThE IMPACT Of ThE CONSERVATIVE APPROACh
TO SURGERY fAILURE RATES
Takingaconservativeapproachtothesurgeryfailureratedoesntsubstantivelyaffectthe
resultsbecausetreatmenteffcacyismeasuredaccordingtowhetherapatientistreatedornot
ratherthantheparticulartreatmentthepatientreceives.Inotherwords,alltreatedpatients
(nomatterwhatordertheyreceivetreatments)experienceareductioninprogressionofvisual
impairmentby50%comparedwithpeoplewhohaveundiagnosedPOAG.Takingaconservative
approachtothesurgeryfailureratemeansthatmorepatientsprogressmorequicklyto
medicationsbringingforwardthecostsofmedicationsforthosepatientsandleadingto
higherhealthsystemcostestimates(Table9.8).Repeatsurgerymayalsobeperformed.Based
onMBSdatasurgeryisperformedatarateof1.2andcostshavebeenfactoredaccordingly.
TABLE 9.8: SENSITIVITY ANALYSIS A CONSERVATIVE APPROACh TO SURGERY
fAILURE RATES
Net Present Standard Primary Laser Standard Primary Laser
Values treatment ($724) treatment ($724)
Laser failure rate 50%, Laser failure rate 50%,
surgery failure rate 50% surgery failure rate 10%
DALYs 155,150 155,974 155,150 155,974
BurdenofDiseaseCosts($m) 23,896 24,095 23,950 24,144
HealthSystemCosts($m) 8,759 8,392 8,468 8,128
ComorbidHealthCosts($m) 4,505 4,519 4,505 4,519
TreatmentCosts($m) 4,254 3,873 3,963 3,609
ProductivityCosts($m) 1,665 1,671 1,665 1,671
OtherIndirectCosts($m) 2,695 2,628 2,638 2,576
TotalCosts($m) 37,015 36,787 36,721 36,520
CL ratio: keturn on $1 spent{a) $0.40 $0.43
$/DALY avoided Cost-Saving Cost-Saving
(a)Defnedasthedifferenceinindirectcostsbetweenprimarylaserandthebasecaseforeveryadditionaldollarspent
ontreatment.
Centre for Eye Research Australia
87 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
9.4: kLSLAkCH AND DLVLLOMLN1
Thisscenariolooksatthepossiblereturnsfromnewtreatmentsthatmightbedevelopedto
furtherslowtheprogressionofPOAG.Onepossibleexamplecurrentlyunderinvestigation
mightbeneuroprotectionwiththedrugMemantine(anNMDA
22
-receptorantagonistcurrently
usedforAlzheimersdisease).MemantineiscurrentlyinphaseIIItrialsforglaucomaandatthe
timeofwritingtreatmenteffcacyresultswerenotavailable.
Themodelallowsfortwopossiblenewtreatmenteffcacyoptionsthenewtherapyreduces
theprogressionofglaucomabyafurther50%or75%overandabovethereductionin
progressionfromcurrenttreatments.Itisassumedthatthehypotheticaltreatmentisgiven
toeachpersonbeingtreatedforPOAG,regardlessoftheirtreatmentstage.The new therapy
is taken continuously over the patients remaining life. Thetreatmentisaddedtocurrent
treatmentsratherthansubstitutingforthem.Inthismodel,theannualcostperpersonforthis
treatmenthasbeensetat$1,000regardlessofeffcacy.
9.4.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clicktheresetbuttons.
OntheOptionssheets,chooseResearchandDevelopmentintheSelectInterventionbox
andR&DReducesProgression(50%),orR&DReducesProgression(75%).
TicktheNonewIntervention(StandardTreatment)boxandclickontheSetasBaseCase
buttontosetthecurrentsituationasthebasecomparator.
Un-ticktheNonewIntervention(StandardTreatment)boxandmakesurethatthe
FrequencyEveryYearboxisticked.ThenclicktheSetasScenario1button,torunthe
newscenario.
ClickCompareScenarios(CEA).
9.4.2: RESULTS
Theresultsofintroducingtwonewtherapiesthatreduceprogressionby50%andby75%over
thebasecasearepresentedinTable9.8.Comparedwiththebasecase,thenetpresentvalue
ofDALYs,productivitycostsandcomorbidcostsarelower.Theresultsrefectthebenefts
ofdelayingprogression,allowingpeopletoremaininwork,andexperiencefewercomorbid
conditionsthatareassociatedwiththelaterstagesofglaucoma.ThedeclineinDALYsovertime
associatedwithdelayingprogressionby50%and75%overthebasecaseisdepictedinFigure9.8.
22
N-methyl-D-aspartate
The impact of new
treatments to reduce
progression was
examined.
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9. Intervention Scenarios
Treatments with
annual costs over
$5000 are expensive
but cost effective.
fIGURE 9.8: DECLINE IN DALYS fROM NEW EffICACIOUS TREATMENT
Healthsystemcostsontheotherhandarehigherwiththenewtreatmentbecausethe
treatmentisaddedtocurrentlyavailabletherapies(Figure9.9).
fIGURE 9.9: TREATMENT COSTS WITh NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR
Overall,costeffectivenessdependsonthecostperpersonperannumofthenewtreatment
(Table9.8).Attreatmentcostsof$1,000perpersonperannum,newtreatmentsarecostsaving.
However,ifthenewtreatmentsthatdelayprogressionby50%overthebasecasecostmore
than$5,000perpersonperannum,theywouldbecomerelativelyexpensive(costeffectiveness
ratiosofbeyond$60,000perDALYavoided).
Economic impact of primary open angle glaucoma Commercial-in-Confidence
86
Tick the No new Intervention (Standard Treatment) box and click on the Set as Base
Case button to set the current situation as the base comparator.
Un-tick the No new Intervention (Standard Treatment) box and make sure that the
Frequency Every Year box is ticked. Then click the Set as Scenario 1 button, to run
the new scenario.
Click Compare Scenarios (CEA).
9.4.2 RESULTS
The results of introducing two new therapies that reduce progression by 50% and by 75% over
the base case are presented in Table 9-9. Compared with the base case, the net present
value of DALYs, productivity costs and comorbid costs are lower. The results reflect the
benefits of delaying progression, allowing people to remain in work, and experience fewer
comorbid conditions that are associated with the later stages of glaucoma. The decline in
DALYs over time associated with delaying progression by 50% and 75% over the base case is
depicted in Figure 9-8.
FIGURE 9-8: DECLINE IN DALYS FROM NEW EFFICACIOUS TREATMENT
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
R&D reduces progression 50%
R&D reduces progression 75%
Health system costs on the other hand are higher with the new treatment because the
treatment is added to currently available therapies (Figure 9-9).
Commercial-in-Confidence Economic impact of primary open angle glaucoma
87
FIGURE 9-9 TREATMENT COSTS WITH NEW TREATMENTS COSTING $1000 PER PERSON PER YEAR
Treatment Costs
0
50,000,000
100,000,000
150,000,000
200,000,000
250,000,000
300,000,000
350,000,000
400,000,000
450,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
R&D reduces progression 50%
R&D reduces progression 75%
Overall, cost effectiveness depends on the cost per person per annum of the new treatment
(Table 9-9). At treatment costs of $1,000 per person per annum, new treatments are cost
saving. However, if the new treatments that delay progression by 50% over the base case
cost more than $5,000 per person per annum, they would become relatively expensive (cost
effectiveness ratios of beyond $60,000 per DALY avoided).
Centre for Eye Research Australia
89 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
TABLE 9.9: MODEL RESULTS RESEARCh AND DEVELOPMENT ShOWING ThE IMPACT Of
NEW TREATMENT TO REDUCE PROGRESSION BY 50% AND 75%
Cost of new $1,000 per person $5,000 per person $10,000 per person
treatment per annum per annum per annum
Net resent 8ase 50% 75% 50% 75% 50% 75%
Va|ues Case
DALYs 155,150 134,793 125,718 134,793 25,718 134,793 125,718
Burdenof
DiseaseCosts
($m) 23,896 20,660 19,240 20,510 19,091 20,324 18,905
HealthSystem 8,759 8,843 8,773 9,793 9,729 10,980 10,924
Costs($m)
Comorbid 4,505 4,319 4,227 4,319 4,227 4,319 4,227
Health
Costs($m)
Treatment 4,254 4,524 4,545 5,474 5,501 6,661 6,697
Costs($m)
Productivity 1,665 1,428 1,317 1,428 1,317 1,428 1,317
Costs($m)
OtherIndirect 2,695 2,623 2,575 2,808 2,762 3,040 2,995
Costs($m)
TotalCosts($m) 37,015 33,553 31,905 34,539 32,899 35,772 34,141
CL ratio: keturn $13.82 $18.55 $3.03 $4.30 $1.52 $2.18
on $1 spent
$/DALY avoided Cost- Cost- $44,670 $23,380 $114,386 $71,914
Saving Saving
9.5: COM8INA1IONS
Thissectionexaminestheimpactofcombiningtheinterventionswemodel.Twoscenariosare
availablehere.Bothinvolveanincreaseinthediagnosisrateforglaucomafrom50%to80%,
togetherwitheither:
theadditionofanewtherapythatdelaysprogressionbyafurther50%;or
achangeinthetreatmentprotocolsothatlaserbecomesthefrstlinetherapyinsteadof
medication.
9.5.1: TO RUN ThIS INTERVENTION ThROUGh ThE MODEL
Toensureyoustartwithablankpage,ontheOptionssheet,clicktheresetbuttons.
OntheOptionssheets,choose5.CombinedscenariosintheInterventionFocusboxand
5.1Scenario1.2and4.1,or5.1Scenario1.2and3.1intheInterventionDetailbox.
TicktheNoIntervention(CurrentSituation)boxandclickontheSetasBaseCasebutton
tosetthecurrentsituationasthebasecomparator.
Un-ticktheNoIntervention(CurrentSituation)boxandmakesurethattheFrequency
EveryYearboxisticked.ThenclicktheSetasScenario1button,torunthenewscenario.
AsecondscenariocanbeevaluatedbyreselectingfromtheInterventionsFocusboxaswellas
theInterventionsDetailbox.ThenclicktheSetasScenario2button,torunthenewscenarios.
ClickCompareScenarios(CEA).
The combined effects
of better diagnosis
and laser frst, or
better diagnosis and a
new treatment were
examined.
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9. Intervention Scenarios
Economic impact of primary open angle glaucoma Commercial-in-Confidence
90
FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Treatment costs increase over time (driven by an ageing population and an increase in the
proportion of people with POAG who are diagnosed from 50% in the base case to 80% in each
of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown in
Figure 9-12.
FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
9.5.2: RESULTS
TheresultsofthecombinedscenariosarerefectedinTable9.10.Bothscenariosreducethe
totalDALYscomparedwiththebasecase(Table9.10).
TABLE 9.10: MODEL RESULTS COMBINED SCENARIOS
Net Present Base Case Diagnosis rate Diagnosis rate
Values standard 80% and 80% and
treatment R&D reduces primary laser
progression 50% trabeculoplasty
DALYs 155,150 121,220 149,999
BurdenofDiseaseCosts($m) 23,896 18,184 21,752
HealthSystemCosts($m) 8,759 10,921 10,156
ComorbidHealthCosts($m) 4,505 4,132 4,367
TreatmentCosts($m) 4,254 6,789 5,789
ProductivityCosts($m) 1,665 1,133 1,448
OtherIndirectCosts($m) 2,695 2,918 2,882
TotalCosts($m) 37,015 33,157 36,237
CL ratio: keturn on $1 spent $2.52 $1.51
$/DALY avoided $54,607 $112,411
TheimprovementstototalDALYsincreaseoverthedurationofthemodel(Figure9.10)withthe
increasedbeneftfromthefrstScenariobecomingmoreprominentovertime.
fIGURE 9.10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
Treatmentcostsincreaseovertime(drivenbyanageingpopulationandanincreaseinthe
proportionofpeoplewithPOAGwhoarediagnosedfrom50%inthebasecaseto80%ineach
ofthecombinedscenarios)(Figure9.11).Thepatternoftotalcostsovertimeareshownin
Figure9.12.
Treatment costs
increase over time
because of an ageing
population and
an increase in the
proportion of people
with POAG who are
diagnosed from 50%
in the base case to
80% in each of the
combined scenarios.
Centre for Eye Research Australia
91 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
9. Intervention Scenarios
Thecosteffectiveness(relativetothebasecase)ofthetwoscenariosisshowninFigure9.13.
Thebasecaseisrepresentedattheorigin.
fIGURE 9.13: COST EffECTIVENESS PLANE, COMBINED SCENARIOS(A)
(a)EffectivenessmeasuredasDALYsavoided.Costsrefecthealthsystem,productivityandotherindirectcosts.(Cost
effectivenessismeasuredasthecostperDALYavoided.Thevalueoftheburdenofdiseaseisexcludedfromthecost
estimateinthenumeratorsincethisisrepresentedbyDALYsavoidedinthedenominator).
Combining better
diagnosis rates with
a hypothetical new
therapy to further
reduce progression is
more cost effective
than combining
better diagnosis
rates with primary
trabeculoplasty.
fIGURE 9.11: TREATMENT COSTS, COMBINED INTERVENTIONS
fIGURE 9.12: TOTAL COSTS, COMBINED SCENARIOS
Economic impact of primary open angle glaucoma Commercial-in-Confidence
90
FIGURE 9-10: REDUCTION IN DALYS, COMBINED INTERVENTIONS
DALYs
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Treatment costs increase over time (driven by an ageing population and an increase in the
proportion of people with POAG who are diagnosed from 50% in the base case to 80% in each
of the combined scenarios) (Figure 9-11). The pattern of total costs over time are shown in
Figure 9-12.
FIGURE 9-11: TREATMENT COSTS, COMBINED INTERVENTIONS
Treatment Costs
0
100,000,000
200,000,000
300,000,000
400,000,000
500,000,000
600,000,000
700,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
Commercial-in-Confidence Economic impact of primary open angle glaucoma
91
FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS
Total Costs
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
3,500,000,000
4,000,000,000
4,500,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.
The base case is represented at the origin.
FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and
primary laser trabeculoplasty
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
Commercial-in-Confidence Economic impact of primary open angle glaucoma
91
FIGURE 9-12: TOTAL COSTS, COMBINED SCENARIOS
Total Costs
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
3,000,000,000
3,500,000,000
4,000,000,000
4,500,000,000
2005 2010 2015 2020 2025
Base Case (Standard treatment)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and primary
laser trabeculoplasty
The cost effectiveness (relative to the base case) of the two scenarios is shown in Figure 9-13.
The base case is represented at the origin.
FIGURE 9-13: COST EFFECTIVENESS PLANE, COMBINED SCENARIOS(A)
Diagnosis rate 80% and R&D
reduces progression 50%
Diagnosis rate 80% and
primary laser trabeculoplasty
0
500,000,000
1,000,000,000
1,500,000,000
2,000,000,000
2,500,000,000
0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000
Effectiveness
C
o
s
t
s
(a) Effectiveness measured as DALYs avoided. Costs reflect health system, productivity and other indirect costs.
(Cost effectiveness is measured as the cost per DALY avoided. The value of the burden of disease is excluded
from the cost estimate in the numerator since this is represented by DALYs avoided in the denominator).
92
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
Falls and Hip Fractures
Section 6.3.4 presents the results of a meta analysis of literature that examined the increased
likelihood of an accidental fall and hip fracture with a visual impairment as well as specic VFL
or glaucoma impairment. The list of articles used in the meta-analysis is presented in Table 10.4,
Table 6.7 and Table 6.8. From those lists, studies that reported the risks of an accidental fall or
hip fracture as an OR were excluded, due to their technical incompatibility with RR (as well as a
lack of data to accurately convert the ORs into RRs).
Meta-analysis refers to the statistical analysis of analyses, where the results of multiple trials are
combined to estimate an overall effect size. A number of studies have been published examining
the impact that visual impairment has on the risk of an accidental fall and/or hip fracture. The
results of these studies have been combined to estimate an overall RR of an accidental fall for
people that have a visual impairment.
10.1: FIXED-EFFECTS VERSUS RANDOM-EFFECTS
An inverse variance methodology has been used to weight the study trials for both the xed
effects and random effects models
23
. The results of which are presented in Table 10.1.
TABLE 10.1: FIXED EFFECTS AND RANDOM EFFECTS, META-ANALYSIS RESULTS
Accidental Falls Hip Fractures
Visual Impairment VFL / Glaucoma
No. of Studies 13 6 9
Weighting Method, Inverse variance Inverse variance Inverse variance
FE RE Inverse variance +
Inverse variance +
Inverse variance +
Fixed Effects 1.33 (1.24 1.43) 2.52 (1.92 3.30) 1.43 (1.25 1.64)
(95% CI)
Random Effects 2.05 (1.54 2.71) 3.18 (1.82 5.55) 1.46 (1.24 1.73)
(95% CI)
The studies that specically examined VFL/Glaucoma are a subset of the visual impairment
group of studies. Overall the RR of an accidental fall was higher for people with glaucoma
(or VFL) than people with any type of visual impairment and the RR of an accidental fall is
higher than the RR of a hip fracture.
For all three groups, the RR of an accidental fall is greater in the random effects model than the
xed effects model. This indicates that heterogeneity exists between the combined studies.
The presence of heterogeneity is not unexpected as the studies incorporated into the meta-
analysis include different denitions, measures and severity criteria for visual impairment.
10.2: HETEROGENEITY
Heterogeneity between studies can be problematic when using a xed effects model (which
assumes that the studies used to determine the treatment effect have the same criteria). In this
instance the studies use a variety of different visual impairment, severity and other criteria and
it is not unexpected that (as seen in Table 10.1) heterogeneity exists. Table 10.2 displays a series
of statistical tests that estimate the presence of heterogeneity within the meta-analysis.
23
An inverse variance plus tau weighting method has been used for the random effects model.
93 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
Main heading to go here 10. Appendix 1: Meta-Analysis -
Falls and Hip Fractures
TABLE 10.2: HETEROGENEITY WITHIN THE COMBINED STUDIES
Accidental Falls Hip Fractures
Visual Impairment VFL / Glaucoma
Fixed Effects
Q-statistic 55.11 17.44 9.66
p-value (two-tailed) <0.0001 0.0037 0.2894
H-statistic (95% CI) 2.14 (1.65 2.78) 1.87 (1.23 2.85) 1.10 (1.00 1.57)
I
2
-statistic (95% CI) 78.22% 71.33% 17.22%
(63.23% - 87.10%) (33.42% - 87.66%) (0.00% - 59.21%)
Random Effects
2
-statistic 0.1630 0.3191 0.0110
Q statistic: is the main analysis of heterogeneity and tests whether the assumption that all
of the effect sizes are estimating the same population is reasonable. The test statistic has a
chi-square distribution with k-1 degrees of freedom. If the test is rejected, the distribution
of effect sizes is assumed to be heterogeneous.
H-statistic: describes the relative excess in Q over its degrees of freedom. When
considering a regression of a standardised treatment effect on the standard error, the slope
of an unweighted least squares regression line corresponds with the xed effect pooled
value. The H statistic is the residual SD from this regression. A low H statistic means high
consistency among study results.
I
2
-statistic: describes the percentage of total variation across studies that cannot be
attributed to chance or sampling error and varies between 0% and 100%. In the case of
consistent study results, the I2 is 0 or very low. P-values and CIs can be used to describe the
compatibility of the data-based statistic with a null-hypothesis.
2
-statistic: is an estimate of the between study variance. The -value is used in the
random effects model as an addition to the inverse variance study weight.
The statistical tests for heterogeneity presented in Table 10.2 indicate that heterogeneity
is present in the results of the accidental falls studies, however heterogeneity for studies
examining the relationship between visual impairment and falls is small.
The random effects methodology of meta-analysis has been used to control for this inter study
heterogeneity, for each interest group. The results are presented in the following section.
10.3: FOREST PLOTS
Figure 10.1, Figure 10.2 and Figure 10.3 display the forest plots of each study group using a
random effects meta-analysis methodology. The effect size of each trial is represented by the
red square with a black line indicating the 95% CI. The size of the red square for each trial
indicates the relative weight applied to each study result (using an inverse variance plus tau)
weighting methodology. This gives studies with lower standard errors higher weights, as results
with more accurate estimations are assumed to provide better estimations of the true effect
size. The overall effect size is displayed at the bottom of the gure as a grey diamond with a
horizontal line providing the 95% CI.
94
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
falls and hip fractures
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95 The Economic Impact of Primary Open Angle Glaucoma - A Dynamic Economic Model
10. Appendix 1: Meta-Analysis -
falls and hip fractures
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96
Tunne l Vi s i on
Centre for Eye Research Australia
10. Appendix 1: Meta-Analysis -
falls and hip fractures
10.4: U8LICA1ION 8IAS
Publicationbiaspresentsasauniqueproblemformeta-analyses.Whiletheinclusionand
exclusionofstudiescanimpartsomecontroloverpublicationbias,thepotentialforitsexistence
isstillpresentwithstudiesshowinganeffectmorelikelytobepublishedthanstudiesthatshow
noeffectatall.Tosomeextentpublicationbiaswillalwaysbepresentwithinameta-analysis,
theproblemisthentoestimatehowlargeandwhateffecttheproblemhasontheresult.
TABLE 10.3: MEASURES Of PUBLICATION BIAS
Accidental falls hip fracture
Visual Impairment VfL / Glaucoma
Model RandomEffects RandomEffects RandomEffects
WeightingMethod IV+
IV+
IV+