1149Holmiumyaglaser Enucleation Oftheprostatefor the Treatment Ofbenign Prostatichyperplasia

Public Summary Document

1149HolmiumYAGLaser Enucleation oftheProstatefor the treatment ofBenign ProstaticHyperplasia

Applicant:MD Solutions PtyLtd

Dateof MSAC Meeting:29-30November 2012

1.Purpose of application

In May2012, theDepartment ofHealth and Ageingreceived an application from MD Solutions PtyLtdrequestingMedical Benefits Schedule (MBS)listingofholmium: YAG laser enucleation oftheprostate (HoLEP)with orwithout tissuemorcellation forthe treatment ofbenign prostatichyperplasia(BPH).

HoLEPis arelativelynew surgical treatment option formen with BPH inwhom surgeryis indicated.Lightfrom holmium: YAG lasers – which contain acrystal ofyttrium, aluminium and garnet(YAG), dopedwith holmium – has adefined wavelength whichcan beused to produceuniqueeffects on targeted tissue.In this instance, theselasers serve as aprecise cuttinginstrument forthedissection ofprostaticlobes into anumberofsections. Dissected lobes arethen pushed into thebladder, wheretheycan becut into smallerpieces and removed–usingamorcellator.

This treatment is not currentlyin widespread usein Australia.It is known howeverthat the procedureis availableinsomeprivatehospitals through patient self-insurance arrangements. It has beenclaimed that this new procedure, ifmorewidelyavailable, mayconfersome advantages over existing surgical options formenwith BPH.It isclaimed it mayreducethe numberofpost-operativecomplications and reducethe risk ofbleedingin somemen. This would makeit amoresuitable alternativeforthosemen with cardiovasculardiseaseorthose who areelderlyand infirm. Moreover, it is claimed that this procedurecould in some instances beperformedas daysurgery.

BPH is anon-malignantovergrowth oftheprostategland which can ariseas a result of physiological dysfunction or anatomical obstruction oftheurinarytract (ora combination of these), and typicallyinvolves threefactors:

•A histological changeof hyperplasiawithin thegland

•Clinicallydeterminedenlargement oftheprostategland

•The clinical syndromeoflowerurinarytract symptoms (LUTS).

Clinical BPH is verycommon in the ageingmanand is most often associated with various

LUTSwhichcancauseurinaryobstruction orirritation. Moderateto severesymptoms are

recognisedas significantlyimpactingon qualityoflife. The first-linemanagement formen with BPH includes avarietyofpharmaceuticals, includingalpha receptorblockers, 5-alpha reductaseinhibitors and anti-cholinergicdrugs. However, thesepharmaceuticals haveboth high failure and high discontinuation rates (thelatterdueto sideeffects), and theBPH symptoms in themajorityofmenwill progress.Manyofthesemenwill eventuallyundergo second-linesurgical treatments.Inaddition, somemen maynot opt forinitial medical management.

2.Background

Othersurgical interventions forBPH havebeen assessed byMSACin thepast. Theseinclude Transurethral NeedleAblation (TUNA)forbenignprostatichyperplasia(MSACreport 1014, MBSitem 37201) and high-energyTransurethralMicrowaveThermotherapy(TUMT) (MBS37230) forbenign prostatichyperplasia (MSACreport 1076). VisualLaserAblation ofthe Prostate (VLAP) (MBSitem 37207)has also beenincluded on theMBSsinceJuly1995 (which pre-dates theMSAC).

3.Prerequisites to implementation of any funding advice

Twelveholmium: YAG lasers are currentlyTGA-registeredand listed on theAustralian RegisterofTherapeuticGoods (ARTG). Threetissuemorcellators arealso TGA-registered and listed on theARTG.

4.Proposal for public funding

HoLEPis proposedas analternativeproceduretoTransurethral resection oftheprostate (TURP) formen with moderatelysized prostates (estimated to beless than80–100g).HoLEP is furtherproposedas analternativeto open prostatectomyin men with largerprostates (estimated to bemorethan 80–100g).

5.Consumer Impact Statement

Public comment was sought duringthedevelopment ofthe final DAP. This public comment was incorporated into thefinal DAPas aresult ofPASCdeliberation on 13–14 April 2011.

6.Proposed intervention’s place in clinical management

Therearetwogroups ofmen forwhom asurgicalintervention forthetreatment ofBPHwould beindicated. These are:

•Men with moderate-sizedprostates (estimated at less than 80–100g)– in this group, TURPwould be considered thegold standard surgical treatment. Othersurgical options are currentlyavailable forthis group, includingVLAP, TUNA orTUMT.

•Men with largeprostatesizes (estimated at greaterthan 80–100g)– in this group, OP would be considered thegold standard. Otheralternatives that areconsidered appropriateand currentlyavailableincludeatwo-stageTURPprocedureor VLAP.

It was proposed in theapplication that HoLEP(whereit is available) couldbeused as an alternativeto existingsurgical procedures in eachofthegroups listed above.

Figure1: Proposedmanagementusing HoLEP

7.Other options for MSAC consideration

Therearetwo distinct patient cohorts and consideration wasgiven as to whethertwo distinct items wererequiredgiven the cost differential in the comparators. ESCresolved that asingle item number forboth cohorts was appropriategiven the relativelysmall cohort forOPand the fact that it is adiminishingservice.

PASCin its deliberations, removed laservaporisation as a comparativetreatment as the proposed medical serviceis atypeoflaservaporisation.

8.Comparator to the proposed intervention

TURPMBSitem number37203, is considered thegold standard forthetreatment ofbladder obstruction formen withmoderateprostatesizes, estimated to besmallerthan 80–100g.OP

MBSitem number37200(ortwo-stageTURP), is considered thegold standard in men with largerprostates, estimated at greaterthan 80–100g.

Therewere12,673 MBSclaims forTURPprocedures in the financialyear2010–2011. A much smallernumberofclaims duringthesametimeperiod wererecordedforOP(141), TUNA (too small to report), transurethral microwavetherapy(TUMT) (43) and VLAP(938).

Although anumberofsurgical options areavailable formen with moderate-sized prostates (less than 80–100g), onlyTURPwas consideredasuitable comparatorforHoLEPin this evaluation. Formen with largerprostates (greaterthan 80–100g), OPwas the comparatorthat was used forassessingthe evidence forHoLEP.

Thenewersurgical interventions forBPH (that is, TUNA, TUMT and VLAP)werenot considered suitablecomparators becausetheyhavelowerutilisation rates and represent smaller costs to theMBSrelativeto thegold standards. Furthermore, if approved, HoLEP would be expected to replacetheseprocedures incentres whereit would be available.

TURPand OParein-hospital procedures only. Theyareboth listed on theMBS. TheMBSitem descriptors forTURPare:

TheMBSitem descriptorforOPis:

9.Comparative safety

Ninesystematic reviewsand HTAs that comparedHoLEPwith TURPand/orOPmet the inclusion criteria. Fourofthesesystematic reviewsand HTAs compared HoLEPwith TURP and five compared HoLEPwith TURPand OP. Thesystematic review ofLourenco etal (2008), updated with 2 new otherstudies (Eltabeyet al 2010 &Mavuduruet al 2009), to compareTURPand HoLEPwas chosen forupdatingin this assessment. TheAustralian and NewZealand Horizon ScanningNetwork (ANZHSN)2010 review ofthecurrent stateof development oflaserprostatectomywas chosen forupdatingin thecomparison ofHoLEP with OP.

Themain results ofHoLEPto TURPstudies areillustrated bythebelow table:

Safety outcomes: HoLEPin comparison withTURP Outcome / Studies
(n) / Patients
HoLEP
/TURP(n) / HoLEP (total events) / TURP (total events) / Estimate ofeffect / Range (95% CI)* / I2(%) / p-value
Blood transfusion rate / 7 / 348/342 / 1 / 13 / RR0.27 / 0.09–
0.85 / 0 / 0.02
Urethral stricture / 7 / 322/309 / 14 / 23 / RR0.65 / 0.33-
1.27 / 0 / 0.21
Incontinence / 6 / 306/296 / 7 / 8 / RR0.84 / 0.31–
2.28 / 0 / 0.97
Acuteurinary retention / 5 / 293/287 / 15 / 21 / RR0.71 / 0.38–
1.32 / 8 / 0.28
Urinarytract infection / 2 / 91/89 / 5 / 5 / RR0.98 / 0.31–
3.09 / 37 / 0.97

HoLEPappears to be assafe as TURPacross therangeofoutcomes assessed. Therewould appearto bestatisticallysignificantadvantages overTURPin relation to blood transfusion rates post procedure.Urethral stricturerates, dysuria, and mortalityall slightlyfavourHoLEP but the evidencefrom thesystematicreviewand two additional RCTs suggested that differences in therates ofthese adverse events arenot statisticallysignificant. However, there is no in evidenceofdifferencein safetyfor erectiledysfunction, TURsyndrome (hypernatremiadueto theirrigation solution used duringtheprocedure),capsularperforation and incontinencewith HoLEPcompared to TURP. Although, as aresult ofthewide confidenceintervals forsomeoftheoutcomes, caution was exercised with interpretation of this information.

Main results ofHoLEPto OPstudies areillustrated bythebelow table:

Outcome / Studies
(n) / Patients
HoLEP
/OP(n) / HoLEP
(total events) / OP
(total events) / Estimate
ofeffect
(RR) / Range
(95% CI)* / I2
(%) / p-value
Blood transfusion
rates / 2 / 101/99 / 2 / 15 / 0.19 / 0.05–
0.73 / 0 / p=0.02
Urethral
stricture / 2 / 101/88 / 5 / 4 / 1.07 / 0.30–
3.87 / 0 / p=0.91
Incontinence / 2 / 97/99 / 7 / 9 / 0.79 / 0.31–
2.04 / 0 / p=0.

HoLEPalsoappears to be as safe as OP across therangeofoutcomes assessed, although this information was analysed from fewerstudies andwith asmallernumberofpatients.Ina

meta-analysis ofthetwostudies, patients allocated to HoLEPwereless likelyto haveablood transfusion than those allocated to TURP. Othercomplications, such as incontinence and stricture, were comparablebetween thegroups.

10.Comparative effectiveness

The evidencebase forthe comparison ofHoLEPand OPcomprised oftworandomised controlled trials with 100 patients in total in each arm. Results from thesetrials areconsistent, and probably generalisableto theAustralian population.

TURPas thecomparator

HoLEPappeared to be aseffective, ormore effective, than TURPacrossarangeof effectiveness outcomes.Theseincluded peak flow (Qmax), symptom scores and PVR(Post Void Residual).Itwas noted that caution should be exercised in theinterpretation ofsomeof these findingsgivenwide confidenceintervals and significant heterogeneityacross the studies. Qualityoflifedifferencesand differencesbetween thetwo interventions in respect of treatment failure/re-treatment rates werenot significant. Thetablebelow indicates that

HoLEPtakes slightlylonger, but thereis ashorterhospital stay.

Outcome / Studies
(n) / Patients
HoLEP
/TURP (n) / HoLEP (mean) / TURP (mean) / Estimate ofeffect (MD) / Range (95% CI)* / I2(%) / p-value
Durationof operation (min) / 6 / 331/336 / 70 / 54.6 / 15.8 / 8.7–
21.5 / 72 / p0.001
Durationof
catheterisation
(hours) / 6 / 285/282 / 31.1 / 53.4 / 22.4 / 28.2–
16.6 / 80 / p0.001
Durationof hospital stay(days) / 5 / 281/276 / 1.9 / 3.0 / 1.1 / 1.26–
0.89 / 28 / p0.001

OPas thecomparator

HoLEPappeared to be aseffective as OP across arangeofeffectiveness outcomes, albeit with asmallerbodyof evidence. Theseincluded Qmax, symptom scoresand PVR. No evidenceofsuperiorityforHoLEP(orOP)was demonstrated.

A HoLEPproceduretakes longertocompletethanaTURPprocedure, but is associated with astatisticallysignificantlyshorterhospital stay. Catheterisation times are also shorter. Surgeonexperiencewasoften not noted in thestudies and so it was difficult to ascertain whetherthese results would reflectcurrent operativetimes.

HoLEPappeared to be aseffective as OP, based on the evidence from twoRCTs, across a rangeofeffectiveness outcomes. TheseincludedQmax, symptom scores and PVRs. No evidenceofsuperiorityforHoLEP(orOP)was demonstrated fromeitherofthestudies.It was not possibleto adequatelyaddress,from thedata available, thedifferences between the interventions with respect to qualityoflifeortreatment failure/re-treatment rates. A HoLEP proceduremaytakelongerto completethanan OPprocedure, but maybeassociated with a shorterhospital stayandshorter catheterisation times. Thesedatashould howeverbe interpreted with caution.

11.Economic evaluation

The reviewed literature’sfocus was not adirect comparison ofHoLEP against TURPorOP, and used overseas costs and inputs. As a result acost utilityanalysis was undertaken that examined the costs and benefits ofanumberofsurgical treatment strategies forBPH that included eitherHoLEP and/orTURPformen with prostatesizes ofless than 80-100gor HoLEPand/orOPformen with largerprostates.

A Markov model was developed, allowingpatients to transition through health overatime horizon of fiveyears.Individual cyclelengths weresixmonths with half-cycle correction employed toaccount forthe continuous natureoftransition probabilities within acycle. Fiveyears waschosen based on the availabilityofclinical effectiveness dataused in the

meta-analysis.Inaccordancewith theDAP, patients who failed an initial HoLEPprocedure could be re-treated with eitherHoLEPorTURP. Patients who failed aTURPprocedure would be re-treatedwith TURP.In theOPcomparison, patients who failedan initial HoLEP could be re-treated with eitherHoLEPorOP. Therewas no treatment alternativeto a failed OP.

Themodel included health states of: initial treatment (with orwithout adverse events); well; long-term side effects; treatment failure;repeat treatment (with orwithoutadverseevents); treatment forurethral stricture; and death (all-causemortality). Thetransition through these health states was determined from theresult oftheliteraturereview and meta-analysis. The adverseevents datawasderived from studies which presented worse-casescenarioanalysis. Theutilityvalues were as previouslyestimated byKok et al 2002, such that theutility associated with urethral stricturewas thesame as that forlong-term incontinence.

TURPas thecomparator

Costs ofTURPand OPprocedures weretaken from theprivatehospital weighted AR-DRG costs (with orwithout complications). Costs forHoLEPprocedures werederived based on theTURPMBSusagedata.

In both economic evaluations, HoLEPtreatment was demonstrated to beassociated with lower averageper-patienttreatment costs than treatment options includingeitherTURPor OP, with equivalent ornear equivalent effectiveness. This lower cost wasdriven bythe reduced length ofstayrequired forHoLEPtreatment, as well as reducedrates of adverse events, long-term incontinenceand treatment failure.

In thebasecaseanalysis, therewasamarginal increaseineffectiveness forTURP(with repeat TURPupon failure)of0.008 QALYs. This was considered to be anartefact ofthe calculation ofpatient progression through themodel, and thetwo treatments could be consideredequallyeffective. Theincremental cost-effectivenessratio ofHoLEP(with HoLEPupon failure)was modelled to be$179,725 saved perQALY lost overTURP(with TURPupon failure). This result was driven bythemarginal differencein effectiveness between thetreatment options. Overall, HoLEPtreatment was associatedwith lower average per-patientcosts with near equivalenteffectiveness.

OPas thecomparator

Thetreatment pathwayemploying HoLEPfollowed byasecond HoLEPupon initial treatment failurewas found to havealower averageper-patient cost thanOP. The reduction of cost was primarilydriven bya reducedcost oftreatment as aresult ofHoLEPrequiring a reduced length ofstay(LOS)than OP. HoLEPtreatment pathways weremarginallymore effectivethan those employingOPwith amarginal increaseof~0.006 QALYs compared to

OPtreatment alone. HoLEPtreatment (with eitherHoLEPorOPupon treatment failure)

dominated OPtreatmentin that theywerelesscostlyand moreeffective.

Theinputs used in the economic evaluation assessingthetreatment ofBPH in men with an expected prostatesize80-100gusingeitherHoLEPorOPwas based upon datapublished in two clinical trials with 200 patients in total. Thus, whilst the evidence at hand suggested that HoLEPis acost-effectivetreatment option forBPH compared toOP, some caution should be exercised in drawingfirm conclusions from theassessment.

Sensitivity analyses

Treatment pathways thatincluded HoLEPremained cost-effective against eitherTURPorOP across arangeofvariables tested in sensitivityanalysis. TURP(with TURPfor re-treatment) was more cost-effectivethan HoLEPin onescenario only. This was with anincreased cost of HoLEPassociated with alongerlength ofstaycoupled with thehighest confidenceinterval relative risk ofHoLEPre-treatment for failure.This resulted in theICERbeingmostsensitiveto changes in the relativerisk of experiencingstrictures.

Economicmodellingto assess the costs and effects ofvarious treatment options forBPH was undertaken. Theeconomic evaluations showed that HoLEPtreatment was associated with lower averageper-patienttreatment costs than treatment options includingeitherTURPor OP, with verysimilareffectiveness. This lowercost was driven bythereduced length ofstay required forHoLEPtreatment, as well as reducedrates of adverseevents, long-term incontinence and treatment failure.

As the results forHoLEPcompared with OP arebased on arelativelysmall numberoftrials with small numbers ofpatients, the comparativecost-effectiveness ofHoLEPtreatment compared with OPwas investigated using awiderangeofvalues in thesensitivityanalyses. HoLEPtreatment wasconsistentlyfound to be associated with alower averageper-patient treatment cost, and superior effectiveness.For example, when the costs associated with a

LOSforHoLEPwere adjusted upwards from two to threedays, HoLEPtreatment remained a more cost-effectivestrategy. As such, the availabilityofmoredata could be anticipated to reducethis uncertaintyratherthan altertheoutcomeofthe assessment.

HoLEPappeared to beacost-effectivealternativeto eitherTURPorOPin thesurgical management ofmenwith BPH. This was primarilydueto reduced costs associated with the procedure, in turn driven byreduced lengths ofstayin hospital and reducedcomplications. Scenarios that would reducethe cost-effectiveness oftheprocedurewouldincludeincreased lengths ofhospital stayorincreased rates ofre-operations required forthere-treating BPH.

A numberofpotential MBSfeeswerelisted in theDAP. Themaximum ofthese fees was used in thebasecasewhich included apremium of20% fortrainingto providetheservice. This premium fortrainingwas requested bytheapplicant and included in themodellingbut it is not applicable for fundingunderMedicarepolicyand thereforehas to beremoved from the final proposed fees.It should benoted anyreduction in the feefrom base casewhich hadthe

20%premium and morcellation rendered thetreatment more cost-effective.

The capital outlayoftheequipment and additional trainingrequired will influencetheuptake oftheprocedureand alsotheatrebanding for consumables.

12.Financial/budgetary impacts

HoLEPis proposedas areplacement for existingtreatments and theimpact on service volumes would benegligible. Therewould bealearning curveto develop skills in the

procedure. Therefore, it is likelythat uptakeoftheprocedure followingpositivelistingwould initiallybeslow, and increasegraduallyovertime.Estimates ofuptakeoftheprocedureover a fiveyearperiod in theevent ofapositivelisting ranged from 1%ofthetotal numberof TURPprocedures that areperformed annuallybyyear1 andrisingto 10% by year5.

Table41:Projected numbers ofMBSclaims from2013-2017 ineventofpositive MBS

listing

2012 / 2013 / 2014 / 2015 / 2016 / 2017
Year1 / Year2 / Year3 / Year4 / Year5
TURPprocedures / 12500 / 12375 / 12125 / 11875 / 11500 / 11250
OPprocedures / 150 / 142 / 142 / 142 / 142 / 142
HoLEPprocedures replacingTURP / 0 / 125 / 375 / 625 / 1000 / 1250
HoLEPprocedures replacingOP / 0 / 8 / 8 / 8 / 8 / 8
TotalHoLEP
procedures / 0 / 133 / 383 / 633 / 1008 / 1258
Totalnumberof BPH
procedures / 12650 / 12650 / 12650 / 12650 / 12650 / 12650

(Amended)Table42:Projectedtotalcosts to the MBSovera fiveyear period:listing ofHoLEPwithmorcellation

Itemfee / 2012 / 2013 / 2014 / 2015 / 2016 / 2017
Year1 / Year2 / Year3 / Year4 / Year5
TURPprocedures / 12500 / 12375 / 12125 / 11875 / 11500 / 11250
OPprocedures / 150 / 142 / 142 / 142 / 142 / 142
TotalHoLEPprocedures / 0 / 133 / 383 / 633 / 1008 / 1258
TURPMBSfees / $1,002.65 / $12,533,125 / $12,407,794 / $12,157,131 / $11,906,469 / $11,530,475 / $11,279,813
OPMBSfees / $977.80 / $146,670 / $138,848 / $138,848 / $138,848 / $138,848 / $138,848
HoLEPMBSfees(withor withoutmorcellation) / $1,423.18 / $- / $189,283 / $545,078 / $900,873 / $1,434,565 / $1,790,360
HoLEPMBSfees(with
morcellationless20%
premium) / $1,222.70 / $- / $162,619 / $468,294 / $773,969 / $1,232,482 / $1,538,157
TotalMBSfeesforBPH
proceduresover5years
(HoLEPfee$1423.18) / $12,679,795 / $12,735,924 / $12,841,057 / $12,946,189 / $13,103,888 / $13,209,021
TotalMBSfeesBPH
procedures(HoLEPfee
$1222.70) / $- / $12,709,260 / $12,764,273 / $12,819,285 / $12,901,804 / $12,956,817
Additionalcosts/yearwith
HoLEPlisting(HoLEPfee
$1423.18) / $- / $56,129 / $161,262 / $266,394 / $424,093 / $529,226
Additionalcosts/yearwith
HoLEPlisting(HoLEPfee
$1222.70) / $- / $29,465 / $84,478 / $139,490 / $222,009 / $277,022
Totaladditionalcostto
Government(75%) HoLEPfee$1423.18 / $- / $42,097 / $120,946 / $199,796 / $318,070 / $396,919
Totaladditionalcostto
Government(75%) HoLEPfee$1222.70 / $- / $22,099 / $63,358 / $104,618 / $166,507 / $207,766

1

Based on theprojectionsoutlined, it is estimated that the additional annualcost to theMBSin

2015 as a result ofpositivelistingofthis procedure as pertheproposed descriptorwould be$199,796. This would riseto $396,919 by year5.These costs reflect onlythe75%benefit for theitem and it is expected that anyadditional costs would beout-of-pocket.

Therefore, iflisted, HoLEPwould have an additional direct cost to theMBSon an annual basis as a result oftheincreased fee fortheitem. The cost offsets thatarisefrom reduced length ofstayand reduced complications would accrueto hospitals, to health insurers and to patients.

13.Key issues for MSAC from ESC

Main issues around theproposed eligiblepopulation forpublic fundingand/ortheproposedmain comparator

ESCwas unsureiftherewas anyadvantagespecifyingtheindication forHoLEPas moderate to severeBPH in thedescriptorgiven that thereis unlikelyto beleakagetoeithermild BPH patients or anyotherpatients ifthis specification is not included. Howevergood practiceis to haveadescriptorthat is specificto thepopulationwhich ESChas examined.

ESCagreed that HoLEPwill beused primarilyasa replacement for existingtherapies for moderate-to-severeBPH patients and is not expectingit will increasetheoverall pool or prevalenceofpatients beingtreated forBPH.

Main issues around theevidence andconclusionsforsafety?

ESCagreed the comparative evidence forsafetyofHoLEPto eitherTURPorOPwould indicatethat HoLEPwasas safeas orsaferthan the current comparators.

ESCnoted that therewasno trial data fortwo stageTURPcompared to HoLEP. Thesafety issues fortwo stageTURPdo not appearto besignificantlydifferent fromthose associated with asingleTURPbut thereareno datato support ordenythis position.

Main issues around theevidence andconclusionsfor clinical effectiveness?

ESCnoted that Botherscores weresuggested in thein DAPas ameans ofassessing effectiveness but werenot ableto beprovided in the report dueto the absenceof anystudies usingthem as aprimarymeasureofeffectiveness.

ESCagreed the evidencefor clinical effectivenessofHoLEPcompared with eitherTURPor OPwould indicatethat, given themarginal differences in QALYs in eithercomparsion, HoLEPcould be considered as having equivalenteffectiveness, subject to the caveat that thereis ahigh degreeoftheheterogeneitybetweenstudies and small numbers ofstudies availableto support this position.

Other important clinicalissuesand areasofclinical uncertainty?

ESCdid not considerin thesecond population that open prostatectomywasthemost likely clinical treatment to beused at present,as indicated bytheMBSusagedata. As a result of this ESCfelt HoLEPwasmorelikelyto beused asasubstitute forTURP, especiallyas the numberofpractitioners performingOPis diminishing.

Main economicissuesand areasofuncertainty?

ESCfelt thenegativeutility gain forHoLEPcauses it to appearto beinferior ratherthan non- inferiorin terms ofeffectiveness. This is dueto interpretation ofthedatagiven forthesafety outcomes. Howeverwhen lookingat theeffectiveness scores (Qmax,IPSS/AUA, PVRand QALY)ofHoLEPcompared to TURPit shows that HoLEPhas much better6 and 12 month mean health outcomes.

ESCalso questioned thevalidityofsomeoftheutilityweights used: for example, usingthe sameutilityweight forurethral strictureand longterm incontinenceseems inappropriateas strictureis usuallytreatablewhileincontinenceisalongterm complication.

ESCalso noted that thehospitalisation costs avoided byHoLEPdueto lowerbleedinghave not been factored into theMarkov model and subsequent effectiveness modelling. ESCwas also concerned to usethat AR-DRG has been usedforHoLEPcompared toMBSforOPand TURPwhich means therehas been two differentsources forthe costs, which mayhaveled to an errorin interpretation of relative risk.

ESCfelt theMarkov model was fundamentallyflawed dueto theuncertaintyas to theorigin oftheutilityweights, thetransitions through thehealth states, theuseofnon-comparable cost data, the exclusion oftheavoided hospital costs, and theinclusion ofatrainingpremium in thesuggested Schedulefee. FurtherESCquestioned the consistencyoftheresults ofthe incremental QALYsgained from themodel whencompared with theconclusions ofthe clinical evaluation and the relativerisks included in themodel and asked the assessmentgroup to verifythemodel(Attachedas Errata).

ESC’s judgment is that these flawsarelikelyto haveimpartedaveryconservativebias against HoLEPto the analysis.

ESCnoted that without the claimed premium fortrainingthen therewould beasmall increasein MBSoutlays. However, savings elsewherein thehealth caresystem, primarily dueto thedecreasein hospital costs through reducedLOSand/orreducedbleedingimpacts, will likelymorethan offset these additional MBSoutlays.

ESCsuggests that theuptake from TURPand OPto HoLEPmaybe fasterthan predicted but this will be affected bythe co-payments requested.

Anyotherimportant areas ofuncertainty(e.g. budget impact, translation ofclinical evidenceinto the economic evaluation, linkagebetweenaninvestigativeintervention and asubsequenttherapeuticintervention and outcomes?

ESCdiscussed theissueofhaving oneMBSitem forHoLEPwith orwithout morcellation compared with two itemsand differential Schedule feesforHoLEPwith and without morcellation. Whilemorcellation increases the cost ofHoLEPand thereforeprovides a justification forhavingtwo items, ESCwas concerned that this approachmayprovidea financial incentiveto providemorcellation in circumstances whereit might not otherwisebe deemed necessary. ESCtherefore considers that asingleMBSitem with aSchedule fee reflecting a “weightedaverage” cost ofperformingHoLEPwith orwithoutmorcellation may bepreferable. This accords with the applicant’s request foroneMBSitem forHoLEP.