Cost-effectiveness analysis of a surveillance program to prevent hip dislocation in children with cerebral palsy

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Original Article

Cost-effectiveness analysis of a surveillance program to prevent hip dislocation in children with cerebral palsy

Laura Vallejo-Torres

^a^,^b^,^c^,∗

, Amado Rivero-Santana

^a^,^c^,^d

, Carlos Martin-Saborido

^f

, David Epstein

^g

, Lilisbeth Perestelo-Pérez

^c,d,h

, Carmen Luisa Castellano-Fuentes

^a

, Antonio Escobar-Martínez

^c,i

, Pedro Serrano-Aguilar

^c^,^d^,^h

aFundaciónCanariadeInvestigaciónSanitaria(FUNCANIS),IslasCanarias,Espa˜na

bDepartamentodeMétodosCuantitativosenEconomíayGestión,UniversidaddeLasPalmasdeGranCanaria,IslasCanarias,Espa˜na

cReddeInvestigaciónenServiciosdeSaludenEnfermedadesCrónicas(REDISSEC),Madrid,Espa˜na

dCentrodeInvestigaciónBiomédicadeCanarias(CIBICAN),IslasCanarias,Espa˜na

fUnidaddeEvaluacióndeTecnologías,UniversidadFranciscodeVitoria,Madrid,Espa˜na

gDepartamentodeEconomíaAplicada,UniversidaddeGranada,Granada,Espa˜na

hServiciodeEvaluacióndelServicioCanariodelaSalud(SESCS),IslasCanarias,Espa˜na

iUnidaddeInvestigación,HospitalUniversitarioBasurto,Bilbao,Espa˜na

a r t i c l e i n f o

Articlehistory:

Received21November2018 Accepted3May2019

Availableonline15September2019

Keywords:

Cost-beneﬁtanalysis Hipdislocation Cerebralpalsy

a b s t r a c t

Objective:Inthisstudyweconductedaneconomicevaluationofasurveillanceprogrammetoprevent hipdislocationinchildrenwithcerebralpalsy.

Method:Wedevelopedamodelthatcomparedcostsandhealthoutcomesofchildrenwithcerebralpalsy withandwithoutasurveillanceprogramme.Informationfromanumberofsourceswascombinedinto adecisionanalyticalmodel,primarilybasedondatafromacomparativestudywitha20-yearfollow-up.

EffectivenesswasmeasuredusingQuality-AdjustedLifeYears(QALYs).Theanalysistooktheperspec- tiveoftheSpanishNationalHealthService.Weundertookextensivesensitivityanalysesincludinga probabilisticsensitivityanalysis.

Results: ThesurveillanceprogrammeledtohigherQALYsandhigherhealthcarecosts,withanesti- matedincrementalcostperQALYgainedof12,282D.Theresultswererobusttomodelassumptions.

Theprobabilitythattheprogrammewascost-effectivewasestimatedtobeover80%atthethresholdof 25.000D/QALYrecommendedinSpain.

Conclusion:Thisstudyindicatesthatsurveillanceprogrammestopreventhipdislocationinchildrenwith cerebralpalsyarelikelytobecost-effective.

Análisisdecoste-utilidaddeunprogramadevigilanciaparaprevenirla luxacióndecaderaenni ˜nosyni ˜nasconparálisiscerebral

Palabrasclave:

Análisiscoste-beneﬁcio Luxacióndecadera Parálisiscerebral

re s um e n

Objetivo:Enesteestudioserealizaunaevaluacióneconómicadeunprogramadevigilanciaparaprevenir laluxacióndecaderaenni ˜nosyni ˜nasconparálisiscerebral.

Método: Sedesarrollóunmodeloquecomparóloscostesylosresultadosensaluddeni ñosyni ñas conparálisiscerebralincluidasynoincluidasenunprogramadevigilancia.Secombinólainformación provenientedediversasfuentesenunmodeloanalíticodedecisión,principalmentebasadoendatosde unestudiocomparativocon20a ñosdeseguimiento.Laefectividadsemidióempleandolosa ñosdevida ajustadosporcalidad(AVAC).ElanálisistomólaperspectivadelSistemaNacionaldeSaluddeEspa ña.

Serealizóunextensoanálisisdesensibilidad,incluyendounanálisisdesensibilidadprobabilístico.

Resultados:ElprogramadevigilanciaestuvoasociadoamásAVACymayorescostessanitarios,conun costeincrementalporAVACganadoestimadoen12.282D.Losresultadosfueronrobustosalossupuestos delmodelo.Laprobabilidaddequeelprogramafueracoste-efectivoseestimóenunvalorporencima del80%paraelumbralde25.000DporAVACrecomendadoenEspa ˜na.

Conclusión:Esteestudioindicaqueesprobablequelosprogramasdevigilanciaparaprevenirlaluxación decaderaenni ˜nosyni ˜nasconparálisiscerebralseancoste-efectivos.

∗ Correspondingauthor.

E-mailaddress:[email protected](L.Vallejo-Torres).

https://doi.org/10.1016/j.gaceta.2019.05.005

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Introduction

Cerebralpalsyhasanincidenceofapproximatelytwoper1000 livebirthsanditisconsideredthemostcommoncauseofphysical disabilityinchildrenindevelopedcountries.¹Acommonbutoften preventablecomplicationinchildrenwithcerebralpalsyisthedis- locationofthehip,usuallyattributedtospasticityandcontracture ofthehipadductorsandﬂexorsaswellasthemedialhamstrings.² Between 15-20% of children with cerebral palsy develop this condition.³

Atfirst,childrenwithcerebralpalsymightexperienceasymp- tomaticsubluxationordisplacementofthehipthatcanprogress intopainful dislocation,contributing todifficultieswithsitting, standing,walking,dressing,andperinealhygiene.⁴Inmostcases childrenwithidentified displacementwillneedsurgery topre- ventdislocation.⁵Treatmentsforhipdisplacementinchildrenwith cerebralpalsyarelessinvasiveandmoresuccessfulinhipswithless hipdegenerativechangeandlessdisplacement.⁶Duetothesilent natureofearlystages of thedevelopmentof hipdisplacement, screeningorsurveillanceprogramsmaypermitearlydetectionand treatment.

Surveillanceprogramsinvolvethemonitoringofchildrenwith cerebralpalsyuntiltheyreachskeletal maturitybasedonstan- dardizedclinicalevaluationsand radiologicalexaminations.Hip displacementisoftenevaluatedusingtheReimerindexormigra- tionpercentage (MP)⁷,with mostauthorsclassifying hipswith a MP>30% as displaced, and hips withan MP>90%to 100% as dislocated.² The potentialofsurveillance toreducehipdisloca- tiondependsontheappropriateplanningofearlytreatmentonce displacementisdetected.Surgicaltreatmentstopreventdisloca- tionincludeadductor–psoastenotomyandvarusosteotomyofthe proximalfemur.Salvagesurgery(e.g.femoralheadresection)is usuallyperformed,ifthechildisﬁttoundergosurgery,whenthe hiphasreacheddislocation.⁸

Salvage surgery Dislocation

Revision surgery No salvage surgery

No dislocation

No revision surgery No salvage surgery

No dislocation

No salvage surgery

Cerebral palsy No dislocation

No surveillance

programme #Same as above Surveillance

programme

Preventive surgery

No preventive surgery

Figure1.Decisiontree.Decisionnoderepresentedbysquaresandchancenodebycircles.

Somecountriesandregionshaveestablishedsurveillancepro- grams,achievingareduction intherateofhipdislocation.^3,9–14 Well-applied surveillanceprograms have therefore beenconsi- deredeffectiveandpractical.⁶However,nopreviousstudyhaspro- videdevidenceonthecost-effectivenessofthisintervention.

Theaimofthisstudyistodeterminethecost-effectivenessofa surveillanceprogramtopreventdislocationofthehipinchildren withcerebralpalsyinSpain.

Method Modeloverview

InthisanalysiswecomparedthecostsandQuality-AdjustedLife Years(QALYs)ofchildren withcerebralpalsywithandwithout asurveillance programtopreventhipdislocation.The perspec- tivewasof theSpanish NationalHealth System,¹⁵ witha time horizonof18years,coincidingapproximatelywiththefollow-up durationofavailabledata.Weapplieda3%discountratetofuture costsandQALYs.^15,16ThepaperfollowstheCHEERSStatementfor economicevaluations.¹⁷

Thisis,toourknowledge,theﬁrstcost-effectivenessevaluation ofasurveillanceprogram topreventhipdislocationin children withcerebralpalsy. The analysiswas thusbased on a denovo decisionanalytical model.Similartopreviouscost-effectiveness analysesofrelated interventions,suchasscreeningof develop- mental dysplasiaof thehip,^18–20 themodel tooktheformof a decisiontree(Fig.1).A decisiontreeisappropriate inthis case becausethedatadidnotindicateacomplexpatternofrecurring- remittinghealthconditions.However,toaccountforthetimingof preventivesurgery,dislocationorsalvagesurgery,costsandQALYs associatedwitheachpathwaywerecomputedonayearlybasisand summedupforthedurationofthetimehorizonwithappropriate discounting.

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Based on this model, mean cost and mean QALYs and the incrementalcost-utilityratio (ICUR)underboth strategieswere computed. TheICUR representsthe additional cost requiredto achieveoneadditionalQALY,¹⁶whichisthencomparedwiththe decision makers’willingness topaythresholdin orderto draw conclusions aboutthe cost-effectiveness of the intervention. In Spainacost-effectivenessthresholdof20,000-25,000D perQALY hasbeenrecommended.²¹

Modelinputparameters

1)Effectivenessofthesurveillanceprogram

A systematic review was performedto identifystudies that estimated the effectiveness of a screening program to prevent hipdislocationin children/adolescents(0to18 yearsold) with cerebral palsy. Methodological quality of the included studies wasassessedwiththeScottishIntercollegiateGuidelinesNetwork (SIGN)criteria²²(seeonlinesupplementaryAppendixI).Themeth- odsandresultsofthesystematicreviewaredescribedindetailin onlinesupplementaryAppendixII.

Threearticles(reportingontwostudies)wereincludedinthe ﬁnalanalysis.Thesetwostudieswereretrospectiveanalysesofthe effectivenessofthesameprogram:theCerebralPalsyFollow-Up Program(CPUP),initiatedinsouthernSwedenin1994.Hägglund etal.,^3,9 in2005and2014,reportedresultsat 10and20 years, respectively,comparingacohortofchildrenbornbetween1992- 1997(study group 1)and between 1998-2007(study group2) includedintheCPUP,toahistoricalcontrolgroupofchildrenborn in1990-1991notincludedintheprogram.Elkamiletal.,¹⁰in2011, comparedasubsampleoftheCPUPtoasampleofchildrenrecruited overthesameperiodandwiththesameGMFCS(GrossMotorFunc- tionClassiﬁcationSystem)levelsinNorwegianregionswhowere notinasurveillanceprogram.Noneofthestudiesreporteddataon painorhealth-relatedqualityoflife.

Theoverlapoftheinterventionsamplesintheincludedstudies precludedameta-analysisoftheirresults.Thecost-utilitymodel waspopulatedbasedondatafromHägglund etal.,⁹ whichpro- videdthelongestfollow-upandcomparedtwogroupsofchildren fromthesameregion.Themethodologicalqualityof thisstudy was evaluated as acceptable, the highest possible quality for retrospectivestudies accordingto theSIGN criteria (seeonline supplementaryAppendixI).

Inthisstudy,childrenincludedinthecontrolandintervention groupswerenotborninthesameperiod.Asaresult,attheend offollow-upchildreninthecontrolgroup(aged22-23yearsby then)havebeenatriskofdevelopingdislocation(deﬁnedinthe studyasMP=100%)for farlongerthanchildrenincludedinthe interventiongroup2(aged6-15yearsatfollow-up).Therefore,we comparedinformationonlyfromchildrenincludedinintervention group1(aged16to21atfollow-up)withthoseincludedinthe controlgroup,sincetheyhadasimilarfollow-updurationthatwas longenoughtodetectmostcasesofhipdislocation.Nineof103 childrendevelopeddislocationofthehipinthecontrolgroup(8of thembetween3and6yearsofage,andoneatage16),whiletwoout of210childrenfromstudygroup1includedintheCPUPprogram sufferedfromadislocatedhip(relativerisk=0.1090; 95%conﬁ- denceinterval[CI]:0.2-0.49).Informationontheprobabilitiesof undergoingpreventiveprimary,revisionandsalvagesurgerywere alsocomputedbycomparingchildrenfromstudygroup1withthe historicalcontrolcohort.ThesearepresentedinTable1.

2)Resourceuseandunitcosts

The intervention under analysis is the CPUP surveillance program,^3,9 which includeda standardized physiotherapist and

occupationaltherapistvisittwiceayearuntiltheageofsixyears, andonceayearthereafter.Inclusionintheprogramwasfromiden- tiﬁcationofapossiblecerebralpalsydiagnosis,i.e.,frombirthon mostpatients,untiltheyreachedskeletalmaturity.Radiological examinationsintheCPUPprogramarebased,since2007,onthe GMFCS,withchildreninlevelInotexaminedradiologically(ifthey have normal pain-freerange ofmovement),children in level II examinedattwoandsixyearsofage,andchildreninlevelIII-V examinedannually.⁹GMFCSiscurrentlythemostwidelyapplied scale for motor functionclassiﬁcation in patientswithcerebral palsy.²³We assumethateachradiologicalexaminationinvolves avisitwithanorthopeadicspecialistdoctor.Inordertocompute themeancostoftheprogramweconsideredthepercentageofchil- drenineachGMFCScategoryasreportedinHägglundetal.,⁹and showninTable1.ThisdistributionbyGMFCSwasverysimilarto thatreportedinapreviousstudyconductedinaSpanishregion.²⁴ IntheCPUP,decisionsregardingpreventivesurgeryweremade locally,andthemostcommontypesofpreventivesurgeriesper- formedconsistedofadductor–psoastenotomy²⁵andvarusfemoral osteotomy.²⁶ Theproportionsofsurgerytypesare presentedin Table1,alongsidewiththemeanageofchildrenwhenundergoing preventive,revisionandsalvagesurgery.

Informationontheuseofnon-surgicaltreatmentstopreventhip dislocation,suchasappropriatelying,sittingandstandingposi- tionsandtheuseoforthoses,isnotprovidedinHägglundetal.⁹ Weassumetherearenotdifferencesacrossgroupsintheprovision ofthisusualcare,andthereforethesecostsarenotincludedinthe analysis.Furthermore,noinformationwasprovidedinthisstudyon thefollow-uprequiredforchildrenaftersurgeryorwhodeveloped dislocationbutcouldnotundergoasurgicalprocedure.Inouranal- ysisweassumed,basedonclinicalexpertise,anadditionalannual visittothephysiotherapistandanadditionalradiologicalexamina- tioninvolvinganorthopaedicsurgeonvisitinthesechildren.The impactofthisassumptionwastestedinsensitivityanalyses.

Unitcostsdata(Table1)weretakenfromthemeanvaluesofthe mostup-to-date(2013to2018)Spanishregionaltariffs(seeonline supplementaryAppendixIIIforreferences).

3)Lifeexpectancyandhealth-relatedqualityoflife(HRQoL)

InordertocalculatetheQALYsassociatedtoeachstrategy,we combinedinformationonlife-expectancyaswellasonHRQoL,the latterexpressedintermsofQALYweights.

Weestimatedmortalityratesforpatientswithcerebralpalsy until18yearsofagebasedondatafromHägglundetal.⁹ There isnoevidenceofdifferencesinmortalityforchildrenunderand notunderasurveillanceprogram,andneitherthereisevidence thathipdislocationhasanimpactonlifeexpectancyinpatients withcerebralpalsy.Therefore,weappliedthesamemortalityrates (representedassurvivalcurvesinonlinesupplementaryAppendix IV)forallchildreninouranalysis.

Severalstudieshaveshownthathipdisplacement/dislocation is signiﬁcantlyassociated witha lowerHRQoLin children with cerebralpalsy.^27–30However,thesestudieshaveusedameasureof HRQoLnotsuitableforthecomputationofQALYsweights(e.g.the ChildHealthIndexofLifewithDisabilities).QALYmeasurement in paediatric populations is very challenging.³¹ One study by Carrolland Downs³² calculated QALYweights for awide range ofhealthproblemsinthepaediatricpopulation.Theyconsidered mild, moderate andsevere symptomsfor each health problem, includingcerebralpalsy.Inourbasecaseanalysis,weappliedthe reportedutilitiesforchildrenwithmildcerebralpalsytochildren withcerebralpalsynotsuffering fromhipdislocation,andthat estimatedforchildrenwithmoderatecerebralpalsytochildren withcerebralpalsywithhipdislocation(Table1).Weexploredthe impactofthis assumptioninsensitivityanalyses,andestimated

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Table1 Datainputs.

Relativerisk Mean(95%CI) Prob.distrib. Ref.

Dislocationundersurveillanceprogram 0.10899(0.02-0.49) Lognormal 9

Probabilities Mean(SD) Prob.distrib. Ref.

Non-surveillanceprogram

Primarypreventivesurgery 0.1165(0.0315) Beta 9

Revisionsurgeryafterpreventivesurgery 0.5833(0.1367) Beta

Dislocation 0.0874(0.0277) Beta

Salvagesurgeryafterdislocation 0.4444(0.1571) Beta

Surveillanceprogram

Primarypreventivesurgery 0.1512(0.0223) Beta 9

Revisionsurgeryafterpreventivesurgery 0.4359(0.0784) Beta

Salvagesurgeryafterdislocation 0.4444(0.1571) Beta

Proportionoftypeofpreventivesurgery

Tenotomy(vs.osteotomy)inprimarypreventivesurgery 0.6117(0.0478) Beta 9

Tenotomy(vs.osteotomy)inrevisionpreventivesurgery 0.0652(0.0360) Beta

ProportionofchildrenineachgroupoftheGMFCS

GMFCSI 0.4312(0.01791) Dirichlet 9

GMFCSII 0.1665(0.01347) Dirichlet

GMFCSIII 0.1048(0.01108) Dirichlet

GMFCSIV 0.1442(0.01270) Dirichlet

GMFCSV 0.1533(0.01303) Dirichlet

Unitcosts

X-ray 21.12D

(11.38D)

Gamma Seeonline

supplementary AppendixIII

Physiotherapistvisit 25.84D(18.17D) Gamma

Occupationaltherapyvisit 20.17D(7.29D) Gamma

Orthopedicspecialistdoctorvisit 91.19D(28.58D) Gamma

Adductor–psoastenotomy 1,912.1D(1,405.93D) Gamma

Femoralosteotomy 2,185.4D(1,018.68D) Gamma

Femoralresection 3,253.4D(948.07D) Gamma

QALYweights

Cerebralpalsywithouthipdislocation(Mildcerebralpalsy) 0.8700(0.2000) Beta 32

Cerebralpalsywithhipdislocation(Moderatecerebralpalsy) 0.7600(0.2300) Beta

Disutilityduetosurgery(1-year) 0.1000(0.1000) Beta Assumption

Otherparameters Mean[min;max] Prob.distrib. Ref.

Ageatprimarypreventivesurgery 5[3;8] Uniform 9

Ageatrevisionsurgery 8[4;12] Uniform

Ageatsalvagesurgery 13[7;20] Uniform

Ageatdislocation 5[3;8] Uniform

CI:conﬁdenceinterval;GMFCS:GrossMotorFunctionClassiﬁcationSystem;Prob.distrib.:probabilitydistribution;QALY:qualityadjustedlifeyears;SD:standarddeviation.

Note:AmoredetaileddescriptionoftheparameterssummarizedinTable1isprovidedinonlinesupplementaryAppendixV.

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Table2

Resultsforthebasecaseanalysis.

Surveillanceprogram Mean(95%CI)

Non-surveillanceprogram Mean(95%CI)

Incrementaldifference Mean(95%CI)

ICUR Mean(95%CI)

Costs 1569D (917-2470D) 613D (258-1151D) 956D (394-1708D) 12,282D/QALY(3013-60,707D)

QALYs 11.994 (3.832-13.8450) 11.916 (3726-13.780) 0.0778 (0.028-0.131)

ICUR:incrementalcost-utilityratio;QALY:quality-adjustedlifeyears.

0 € 5,000 € 10,000 € 15,000 € 20,000 € 25,000 € 30,000 € Time horizon

Risk of dislocation without program Cost of program Disutility associated with dislocation Probability of preventive surgery with program Age at dislocation Probability of preventive surgery without program Discount rate RR of dislocation with program Percentage of children in GMFCS I Probability of resection surgery after dislocation Follow-up after surgical intervention or dislocation Cost of undergoing preventive primary surgery Cost of undergoing resection surgery Age at salvage surgery Cost of follow up after preventive surgery Age at revision prevention surgery Cost of follow up after resection surgery Cost of follow up of dislocation without surgery Disutility associated with surgical intervention Age at primary prevention surgery

ICER

Figure2.One-waysensitivityanalyses.

thechangeinutilityrequiredfortheprogramtobecost-effective.

Weassumedthatthemeanageofchildrendevelopingdislocation was5yearsofage.^3,9Furthermore,toallowforthefactthatunder- goingasurgicalproceduremighthaveashort-termdetrimental impactonHRQoL,weappliedadisutilityassociatedtoanysurgical procedureequivalentto0.1QALYsforone-yearaftersurgery.The impactofthisassumptionisalsoanalyzedinsensitivityanalyses.

Sensitivityanalysis

Dataparameterswereincreasedtodoubleandreducedbyhalf thebase-casevalueinone-waydeterministicsensitivityanalyses.

Widerrangeswereappliedtotheassumptionsincludedintheanal- yses:thenumberoffollow-upvisitsaftersurgerywasvariedfrom nofollow-uptomonthly(base-case:annualvisits);thedisutility associatedtoanysurgicalprocedureforaone-yearaftersurgery wasvariedfrom0.05to0.5(base-case:0.1);thetimehorizonof thestudywasvariedfrom10to100years(base-case:18years) anddiscountratevariedfrom1%to5%(base-case:3%).Inaddi- tion,weundertookathresholdanalysisthatcomputedthevalue requiredonthechangeinQALYweightsafterdislocationforthe interventiontobeconsideredcost-effective.

Wealsoconductedaprobabilisticsensitivityanalysistocharac- terizethejointuncertaintyinthemodelusing1,000simulationsin aMonteCarlosimulation.Theresultsoftheprobabilisticsensitivity analysisarepresentedintermsofacost-effectivenessplaneand

cost-effectivenessacceptabilitycurves,whichindicatetheproba- bilitythataninterventioniscost-effectivefordifferentvaluesof thewillingnesstopayforaQALY.Probabilitydistributionsforeach parameterareshowninTable1.

Results

Thecost-utilityresultsofthebasecaseanalysisarepresentedin Table2.Themeancostperchildincludedintheprogramis1569D (95%CI:917-2470D)andthemeancostperchildnotincludedin theprogramis613D (95%CI:258-1151D).ThemeanQALYsfor childrenincludedandnotincludedintheprogramare11.99(95%

CI:3.83-13.85)and11.92(95%CI:3.73-13.78)QALYs,respectively, foran18-yeartimehorizon.TheICURoftheprogramisestimatedas 12,282D/QALY(95%CI:3014-60,708D),andthereforeconsiderably lowerthanthethresholdofupto25,000/QALYrecommendedin Spain.²¹

Theresultswererobusttoone-waysensitivityanalyses(Fig.2).

TheICURvaluesestimatedunderthesensitivityanalyseswerein everyinstanceunder25,000D/QALY,withtheexceptionofwhen thetimehorizonisreducedto10yearsandwhentheunderlying riskofdislocationwithoutaprogramisassumedtobehalfthevalue ofthebase-case.Othervariablesfoundtohavealargeimpactonthe ICURwerethecostoftheprogram,theprobabilityofundergoing preventivesurgery,andthedisutilityassociatedwithdislocation.

Withregardstothelatter,ouranalysissuggestedthatthescreening

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1,000 € 500 € 0 € 500 € 1,000 € 1,500 € 2,000 € 2,500 € 3,000 €

Costs

-0.1 -0.05 0 0.05 0.1 0.15 0.2

Threshold of 25,000€/QALY Simulations Mean

QALYs

Figure3.Cost-effectivenessplane.

0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

0 € 5,000 € 10,000 € 15,000 € 20,000 € 25,000 € 30,000 € 35,000 € 40,000 €

Probability of being cost-effective

Threshold value

Surveillance program Non-surveillance program

Figure4.Cost-effectivenessacceptabilitycurves.

programwouldbecost-effectivewhenthedifferenceintheutility weightbetweenchildrenwithcerebralpalsywithandwithouthip dislocationis0.06orgreater(thebase-casedifferenceinthemodel is0.11).

Figures 3 and 4 shows thecost-effectiveness plane and the cost-effectiveness acceptability curves. At a threshold value of D25,000/QALY,theprobabilitythatthesurveillancestrategyisthe mostcost-effectiveoptionapproaches90%inthebasecaseanalysis.

Discussion

Thisstudyprovidestheﬁrstcost-utilityevaluationofasurveil- lanceprogramtopreventhipdislocationinchildrenwithcerebral palsy.

Theanalysiswasbasedonthebestavailableevidence,which islimitedtoapopulation-basedretrospectiveobservationalstudy implementedinsouthernSweden.Thisstudyshowedacceptable

internal validity (seeonline supplementary Appendix I).Exter- nalvaliditymight becompromisedduetopotentialdifferences betweencountriesintheorganizationalrequirementstoimple- menttheprogramandthequalityofservicesprovidedin usual care.Therefore,boththeunderlyingdislocationrateundernon- surveillanceandtheeffectivenessofasurveillanceprogrammight bedifferentin othercontexts.Unfortunately, there arenodata ontheunderlyingdislocationrateinchildrenwithcerebralpalsy inSpain,butsimilarlytothecontrolgroupincludedinHägglund etal.,⁹currentclinicalguidelinesforchildrenwithcerebralpalsy inSpaindonotincluderoutinesurveillanceforhipdislocation,but onlyrecommendconsideringannualradiologicalexaminationsin severecases.³³Therefore,therateofdislocationinSpainisunlikely tobelowerthanthatreportedinHägglundetal.⁹ Infact,stud- iesfromothercountries,suchasinaNorwegiannon-surveillance cohortwitha 15years offollow up,¹⁰have reportedadisloca- tionratelargerthanthatinthecontrolgroupinHägglundetal.⁹

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(8.7%vs.15.1%).Dislocationratesundersurveillanceprogramsin othercountrieshavealsobeingfoundtobelargertothatobserved intheinterventiongroupofHägglundetal.⁹Weidentiﬁedthree non-comparativestudiesofsurveillanceprogramsinNorway³⁴and Australia.^14,35TheresultsofConnellyetal.¹⁴andTerjesenetal.³⁴ arenotdirectlycomparabletothoseofHägglundetal.,⁹sincethey deﬁneddislocationasMP>90%insteadof100%,andindeedthey reportedmuchhigherdislocationrateswithshorterfollowup(6.8%

and4%,respectively,vs.1.0%).Wynteretal.³⁵publishedanabstract reportingtenyearsoffollowupofthelargestcohortstudiedtodate (n=2278);theydidnotdeﬁnedislocation,althoughinaprevious5- yearreportitwasdeﬁnedas100%ofMP.¹³Theobserveddislocation rateinWynteretal.³⁵(1.8%)wassimilarbutslightlylargerthanthat ofHägglundetal.⁹(1.0%);althoughmorethanhalfofcasesofdis- locationwereobservedattheinitialentrytotheprogram.Another threattoexternalvaliditycouldbethetechnicalevolutionofther- apeuticpreventiveandreconstructiveprocedures,sincetheCPUP programinSwedenstartedmorethan20yearsago.However,treat- mentmodalitieshavenotfundamentallychanged,assuggestedby recentpublishedsystematicreviewsabouttreatmentsoptions.⁸

Thecost-utilityanalysishasaseriesoflimitations. First,and relatedtothepreviouspoint,theanalysisisbasedondatafromthe studyimplementedinSwedenand,therefore,someinputparam- eters might notcorrespond totheepidemiological context and clinicalpracticein Spain.Nevertheless,theextensivesensitivity analysesconductedaroundthesemodelparametersshowedthe results were generally robust to variations in these values.

Thevalidityofanymodeldependsonaseriesofassumptions.In ourmodel,theseassumptionsincludetheintensityoffollow-up aftersurgeryorwhendislocationisnotsurgicallymanageable,as wellasthedisutilityassociatedwithsurgicalinterventions.Inevery caseresultswerefoundnottobesensitivetotheseassumptions.

Finally,possiblythemainmethodologicalchallengeinundertak- ingcost-utilityanalysesinpaediatricpopulationspertainstothe estimationofQALYweights.Weexploredthechangerequiredin theQALYweightofchildrenwithcerebralpalsywithadislocated hipfortheinterventiontobeconsideredcost-effective,whichwas estimatedin0.06.Thisvalueissigniﬁcantlylowerthanthebase- lineassumption.Theresultsofpreviouspapersthathaveshown a signiﬁcantassociationof hipdislocationwitha lower HRQoL inchildrenwithcerebralpalsy,^27–30indicatethattheprogramis cost-effectiveeven when usingconservativeassumptionsabout HRQoL.

Theresultsofthisstudysuggestthatasurveillanceprogramto preventhipdislocationinchildrenwithcerebralpalsyislikelytobe acost-effectiveuseofhealthcareresourcesoftheSpanishNational HealthSystem.However,thereisaneedforfurtherresearch,inpar- ticularaboutepidemiologicaldataontheincidenceofdislocation inchildrenwithcerebralpalsy,theimpactofdislocationonquality oflife,aswellasonthecomparativeeffectivenessofsurveillance andotherpreventativetreatmentsoptions.

Editorincharge

MiguelÁngelNegrínHernández.

Transparencydeclaration

Thecorrespondingauthoronbehalfoftheotherauthorsguar- antee the accuracy, transparency and honestyof the data and informationcontainedinthestudy,thatnorelevantinformation hasbeenomittedandthatalldiscrepanciesbetweenauthorshave beenadequatelyresolvedanddescribed.

Whatisknownaboutthetopic?

Dislocationofthehipisacommonbutoftenpreventable complicationinchildrenwithcerebralpalsy.Surveillancepro- gramsforearlydetectionhavebeenshowntobeeffectiveand practical,butnopreviousstudyhasprovidedevidenceonthe cost-effectivenessofthisintervention.

Whatdoesthisstudyaddtotheliterature?

We provide the ﬁrst cost-effectiveness evaluation of a surveillanceprogramtopreventhipdislocationinchildrenwith cerebralpalsy.Ourstudyindicates thattheseprogramsare likely tobe cost-effective.This informationaims tosupport decisionmakingintheSpanishNationalHealthService,but theseresultsmightbeofrelevanceinothersettings.

Authorshipcontributions

L.Vallejo-Torres,A.Rivero-SantanaandL.Perestelo-Pérezcon- ceived the study, and P. Serrano-Aguilar oversaw its conduct.

A.Rivero-Santana,L.Perestelo-PérezandP.Serrano-Aguilarcon- ductedthesystematicreviewofeffectiveness.C.Martin-Saborido, C.L.Castellano-FuentesandA.Escobar-Martínezcontributedtothe design of the modeland tothedata collection ofthe parame- tersrequiredtopopulatethecost-effectivenessmodel,including epidemiological data, resource use, unit costs and utilities.

L.Vallejo-Torres,A.Rivero-SantanaandD.Epsteinledthemodel design,analyzedthedataandinterpretedtheresults.L.Vallejo- Torresdraftedthemanuscript,andallauthorseditedandrevised themanuscript,andapprovedtheﬁnalmanuscript.

Funding

Thisworkwasundertakenintheframeworkofactivitiesrunby theNetworkofHealthTechnologyAssessmentAgencies,fundedby theMinistryofHealth,SocialServicesandEqualityinSpain.

Conﬂictsofinterest None.

Acknowledgements

TheauthorswouldliketothankCarlosGonzálezRodríguezfor hissupportintheliteraturereview.

AppendixA. Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound,in theonlineversion,atdoi:10.1016/j.gaceta.2019.05.005

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