ContentslistsavailableatScienceDirect
Health
policy
journalhomepage:www.elsevier.com/locate/healthpol
Establishing
a
national
HTA
program
for
medical
devices
in
Italy:
Overhauling
a
fragmented
system
to
ensure
value
and
equal
access
to
new
medical
technologies
Rosanna
Tarricone
a ,b ,∗,
Fabio
Amatucci
b,
Patrizio
Armeni
b,
Helen
Banks
b,
Ludovica
Borsoi
b,
Giuditta
Callea
b,
Oriana
Ciani
b,
Francesco
Costa
b,
Carlo
Federici
b,
Aleksandra
Torbica
a ,b,
Marcella
Marletta
ca Department of Social and Political Science, Bocconi University, Via Roentgen 1, 20136 Milan (Italy)
b Centre for Research on Health and Social Care Management (CERGAS), SDA Bocconi School of Management, Via Sarfatti 10, 20136 Milan (Italy) c Drugs and Medical Devices, Ministry of Health, Via Ribotta 5, 00144 Rome (Italy)
a
r
t
i
c
l
e
i
n
f
o
Article history: Received 5 January 2020 Revised 10 February 2021 Accepted 10 March 2021 Available online xxx Keywords: HTA Medical devices Governance Italy Procurement Coveragea
b
s
t
r
a
c
t
Differingcontextshavegreatly influencedHTAdevelopment invariouscountries,withconsiderable ef-fortrecentlymadebyinternationalHTAnetworks(e.g.,EUnetHTA)andtheEuropeanUnion(EU)tomake HTAamorecoherent,equal,andefficientprocess.Medicaldevices(MDs)presentparticularchallengesfor HTAbecauseoffrequent,rapidinnovation,outcomesinfluencedbyend-usercompetence,dynamic pric-ingandoftenlow-qualityscientificevidence.Ourobjectiveistodescribethedevelopment,structureand governanceofaNationalHTAProgramforMDs(PNHTADM)inItaly,ahighlyparticipatory, stakeholder-engaged,evidence-basedprocesstoreformafragmentedsystemofappraisalandapproval.Basedlargely onEUnetHTAmethods,theresultingprocessdelineatesastandardizedsystemforproposingMDsbyany stakeholders,accreditingHTAproducers,settingcriteriaforprioritizationandappraisals,andinnovatively linkingrecommendationswithcoverage,reimbursementandprocurementofMDs.Expectedbenefits in-cludereduceddisparitiesinpricingandreimbursementpoliciesandimprovedaccesstonewtechnologies across21regionalhealthcaresystemsinItaly’sdecentralized,universalsystem,completewithprovisions torequireadditionalevidence collectionand centrally monitordiffusion.Thoughdevised forItaly,the design,resourcesandunderlyinganalysisprovideaframeworkforothernationsseekingtoconsolidate HTAinitiatives,particularlyinlightofnewEUregulation.
© 2021PublishedbyElsevierB.V.
1. Introduction
HealthTechnologyAssessment(HTA)hasevolvedovertimeasa consolidated evidence-basedapproachto assessthemedical, eco-nomic, ethicalandsocialaspects ofhealthtechnologies. Diffusion of HTAhasbeenrapidandwidespread sinceits firstapplications in the United States (US) in the 1970s [1–3] , sweeping through Europe and by now well-entrenched in Asia, South America and Africa [2 ,4–9 ]. While some early adopters of HTA (notably, the UnitedKingdomandSweden)establishedcentralizedprocesses,in mostcountriestheprocesshasevolvedovertimeinafragmented manner, whereHTA may be carried out in different government agenciesandindependententities,atvariouslevels,including
na-∗Corresponding author at: Department of Social and political Science, Bocconi
University, Via Roentgen 1, 20136 Milan (Italy).
E-mail address: rosanna.tarricone@unibocconi.it (R. Tarricone).
tional,regional, andeven hospital [2 ,4–9 ]. The scope ofHTA has also expandedconsiderably, fromassessments of themost costly technologiesandmedicines ina fewcountries, toincludethe full gamutofdrugs,medicaldevices(MDs),surgicalprocedures, diag-nostics,publichealthandevendiseasemanagementprogramsand counselling,practicedonaworldwidescale[1 ,2 ].
EffortstobuildconsensusonHTAmethodologyandreduce re-dundancy led to the establishment of international networks to help standardizeHTA processes,particularlyinEurope wherethe EuropeanNetworkforHealthTechnology Assessment(EUnetHTA), with30countriesandover80organizations,isthebestexampleof (voluntary)collaborationonHTAbymemberstates[10] .Toolssuch as the HTA Core Model®, developed through EUnetHTA, provide thebasisforstandardizedapplicationsofHTA[11] .However, dupli-cationandconflictingrecommendationshavebeennoted[12 ,13 ].A recentanalysisofHTAprocessesandreimbursementinEuropefor newdrugs (i.e. innovative cancerdrugs) found considerable
vari-https://doi.org/10.1016/j.healthpol.2021.03.003 0168-8510/© 2021 Published by Elsevier B.V.
Please citethisarticleas:R.Tarricone, F.Amatucci,P.Armeni etal., EstablishinganationalHTA programformedicaldevicesinItaly: Overhaulingafragmentedsystemtoensurevalueandequalaccesstonewmedicaltechnologies,Healthpolicy,https://doi.org/10.1016/j.
ation amongnations andeven evidence of market approvals be-foreHTAreportswerecompleted[14] .Asformedicaldevices,HTA agencies seldomdifferentiateintermsofmethods betweendrugs andMDs,butoftendevelopdedicatedtracksandprocessestodeal with the evaluation of this type of health technologies [15 ,16 ]. A continuingproblem withprice differentiationamong countries [17] – and within countries[18–20] – for the same devices has also underlined the need for transparency in price negotiations and abetter understanding ofhow bargainingability, centralized purchasingandsharing ofHTAatdifferentlevelscan combatthe problem.
Thus, as a resultof ex-post evaluations, stakeholder consulta-tionsandimpactassessments,theEuropeanCommission(EC) pre-pared a proposal in 2018 for a Regulation of the European Par-liament (EP) and ofthe Councilon HTA, aimed atimprovingthe functioning of the internal market and overall health protection [21] .JustastheECisstrivingtomakeHTAamorecoherent,equal, andefficientprocess acrossmemberstates,so hasthe Italian Na-tionalHealthSystem(SSN– SistemaSanitarioNazionale)through its Ministryof Health(MoH)beentrying to achievesimilar goals on asmallerscale.Considerable harmonizationandcentralization ofHTAatthenationallevelhasoccurredinordertoreduce ineffi-cienciesatthelocallevel,culminatingwiththemostrecent initia-tiveforMDs[18] .
The objectiveof thispaperis toprovide a comprehensive de-scription of the process undertaken in Italy to create a national HTA program for MDs. The main goal of the program is to en-sureeffectivestewardshipandguaranteeequalaccesstoinnovative technologiesinallpartsofthenation,notwithstandingthe decen-tralizednatureoftheItalianSSN.Theprocessisnotableforits in-clusive,bottom-upmethodology,transparencyand comprehensive-nessasastructuredsystem,fromcoveragetoprocurementand re-imbursement, the resultofan exhaustiveandevidence-based se-ries ofactivities that can provide a blueprint - andtimesavers -for other nations seekingto similarly ordera fragmented system of HTA [5] . Italy represents a compelling example ofHTA within a universal coverage health system, where policy,regulation and funding distribution is setnationally, but21 regional healthcare systems are responsible for health care planning, budgeting and delivery,carriedoutthrough anetworkoflocalhealthauthorities (LHAs)withineachregion[22] .
The framework for the program’s development refers to the conceptofopportunitycostandeconomicrationality,thatis,tothe assumptionthatintimesofscarcity,resourcesneedtobeallocated efficiently between competing ends to maximize health produc-tion [23] and, toacertain extent,tothemorerecentvalue-based [24] conceptthat evaluatesthe introductionof innovationsby con-sideringthewholespectrumofpatientcarepathways.TheItalian caseseems also toconfirm ahigher predispositionby Beveridge-type healthcare systems – such as the SSN - to adopteconomic evaluationanalysisandHTAapproachestogoverntechnological in-novationaccess[25] .
2. HistoricaloverviewofHTAdevelopmentinItaly
The diffusionofHTAin Italyhasfolloweda patternsimilarto othernationswithadecentralizedhealthsystem,characterizedby earlyapplicationsofHTAinlimitedgeographicareas(usuallya re-gion,LHA,hospitalorresearchinstitute)forsingletechnologiesto assess efficacyandinformcoverageandreimbursement decisions [5 ,18 ,26 ]. As inother nations,the proliferation of HTA initiatives led to efforts to consolidate activities andpromote the diffusion and sharing ofHTA on a wider scale.The first efforts at coordi-nating HTA centrally in Italy stemmed from the 2006–2008 Na-tionalHealthPlan,whentheNationalAgencyforRegional Health-care Services(AGENAS)wasinstitutedandbeganproviding
train-ing andsupportto the regionsin developingHTA [5 ,26 ].Though thiscertainlyhadan impacton thediffusionofHTA inItaly,and spawned an Italian network for HTA (RIHTA), the regional focus ofHTA activity remained[5 ,18 ,26 ] until 2015, when the Stability LawestablishedtheNationalProgramforHTAforMDs(PNHTADM) (Table 1 ).
3. WhyanHTAprogramjustformedicaldevices?
The reasons behind the Italian MoH’s development of an HTA program specifically for MDs are threefold. First, the Italian Medicines Agency (AIFA – Agenzia Italiana del Farmaco) in Italy centrally conducts HTA for drugs and additionally regulates and negotiatespricingfor marketaccess andoversees post-marketing surveillance[18] .TheMoH,withinitsGeneralDirectoratefor Med-icalDevicesandDrugs,regulatesMDs,providingoversight;market, adverse effects andclinical trialsurveillance; consumption moni-toringforpubliclyfundedpurchases,andHTA[27] .TheMoHalso maintainsapubliclyaccessibledatabaseofallCE-markedMDsfor marketingonnationalterritoryaswellasannualreportsonpublic expenditureforMDs.
Second,amongtechnologiessubjecttoHTA,MDswarrant par-ticularattention [28–30] .MDs differ fromother health technolo-giesinseveralrespects:“(i)they oftenchangerapidly;(ii)clinical outcomes oftendepend on the training, competence and experi-enceoftheend-user; (iii)pricingistypically moredynamicthan that of pharmaceuticals; and(iv) costs oftencomprise both pro-curement costs (including theassociated infrastructure) and run-ning costs (including maintenance and consumables)” [28] . Over time, concerns emerged regarding theadequacy of available HTA methodsto meetthechallengesposedby thespecial characteris-ticsofMDs[15 ,29–33 ].AnEU-fundedproject,“MedtecHTA” (2013– 2015),investigatedthe differencesbetweenMDs and pharmaceu-ticalsto assess theneed fora differentHTA framework forMDs. Final recommendations concluded that the methods for HTA for pharmaceuticalscannotbeadaptedtoMDstoutcourtbut,instead, should consider MDs ascomplex interventions; i.e., they require theestablishmentofhighqualityregistries,shouldconsideran it-erativeapproachto evaluationovertime,recognize andallowfor theparticular characteristicsofvarious MDs,anduseappropriate approaches for confounder adjustment in comparative effective-nessstudies[30 ,31 ].
Third, unlike prescription drugs, clinical evidence regarding safety and clinical effectiveness to support HTA for MDs can be lacking or of low quality, even for high-risk medical technolo-gies; thus, various recommendations have been proposed to ad-dressthiscriticalissueinHTAforMDs[33–35] .Recommendations coverinparticulartheneedtofollowinternationalguidelines(e.g., EUnetHTA) in conductingHTA, toaddress specific gaps regarding product lifespan, organizational impact [36] , learning curve and potential bias instudydesigns other thanrandomized controlled trials, as well as requiring increased collection of data for pre-marketing approvalandpost-marketing surveillance,usingrobust statistical methods, and conducting risk analysis using validated toolsandstandards.Centralizedoversightandpoolingofskillsand resourcesinconductingHTAweredeemedessentialtoimplement theprocessesrequiredtomeetsuchrecommendations.
4. MainfeaturesofthenationalHTAprogramformedical devices(PNHTADM)
4.1. Governanceandmethodology
In2015, theStability Law[37] established aSteering Commit-tee (Cabinadi Regia) to address HTAactivity forMDs. Composed ofrepresentatives fromgovernment entities (Fig. 2 ), the Steering
Table 1
Development of the National HTA Program for Medical Devices (PNHTADM) in Italy. 1980 HTA begins at the NIH for big tickets technologies
1990s HTA expands as an uncoordinated, experimental, hospital-based approach
2000 Emilia-Romagna, Veneto and Friuli-Venezia -Giulia regions establish their own HTA programs 2006 The National Health Plan sets HTA as a national priority
2007 AGENAS is instituted
2010 RIHTA is established. Campania and Lombardia regions launch their own HTA programs 2012 Calabria, Liguria, Puglia and Sicilia regions launch their own HTA programs
2014 The National Health Plan recommends governing access of MDs based on value generated 2015 Stability Law institutes the PNHTADM
2016 Stability Law sets the governance of the PNHTADM and establishes the Steering Committee (SC). MoH creates 3 working groups (WG) to support the SC and activates WG#2
2017 MoH and Regions sign off the PNHTADM “Strategy Document” 2018 WG#2 concludes its work
2019 MoH establishes the PNHTADM Governance, Method and Process
Abbreviations: HTA – Health Technology Assessment, MDs – Medical devices, ISS - Istituto Superiore di Sanità (Na- tional Institute of Health), AGENAS - Agenzia Nazionale per i Servizi Sanitari Regionali (National Agency for Regional Healthcare Services), RiHTA - Italian network for HTA, MoH – Ministry of Health.
Fig. 1. Governance and Methodology of the Italian National Program of HTA for Medical Devices (PNHTADM).
Committee(SC)launchedthePNHTADMtopromotetheuseofHTA tools andthe principles of safety, clinical andcost-effectiveness, andsocialequityinasystemofsharedevaluationofmedical tech-nologies. Recognizing the importance of transparency and inclu-siveness,theSCsoughtadvicefroma“BoardofInnovation” (Tavolo diInnovazione)tocollaborateonprogramdevelopment,comprised of stakeholders including academia, patients, private and public health care organizations, professional associations, and the MD industry association. Three main work groupsand five sub-work groups, composed ofmembers of the SC andthe Board of Inno-vation, were created to address the main objectives of the Pro-gram (Fig. 2 ).The four-year process ofdevelopingthe PNHTADM wascompletedin2019 (Fig. 1 ),defining recommendations, meth-odsandmonitoringofthenationalprogram.
CommonmethodologywasusedindefiningthefinalPNHTADM structure and documents, based on focus groups or surveys to identifykeyelementsandissues,followedbysystematicliterature reviews, interviews,in-depthanalysisofselectedinternational ex-amples, andsubsequent focus groupsand internal discussionsto formulaterecommendations.Therecommendationsofthefive sub-workgroupswerefinallydiscussedbytheSCandconsolidatedinto the official document publishedon the MoH website,with addi-tional reportsfromeach work andsub-workgroup, clearly delin-eating the methods,results,references andassociateddocuments [38] .ThefinalstructureandprocessesthatmakeupthePNHTAMD aredefinedbelow.
5. TheprocessandstructureoftheItaliannationalHTA programformedicaldevices(PNHTADM)
Fig. 2 illustrates the processes and structures involved in the PNHTADM, from proposal (signal out) of a technology for HTA throughtheprioritization,assessment,appraisal,decisionand ap-peal processes, completewith policy recommendations regarding coverageinthenationally-definedguaranteedhealthbasket(LEA), indicationsregardingprocurementandreimbursementpoliciesand howthe technologywill be delivered throughoutthe21 regional healthsystems.
5.1. Proposalsandprioritization
Anytechnologiescanbeproposedforassessment,rangingfrom emergent(i.e.,not yetCE-marked) toobsolete (i.e.,disinvestment intechnologiestobedisplacedbyotheravailableoptionswith su-periorsafety,clinicalorcost-effectivenessprofiles).Anonline sys-temfor proposingtechnologies forassessment,developed by the PNHTADM,allowsoneormorestakeholderstouploadtherequest onthesystem,startingtheprocess(Fig. 2 ).
Proposalsfor technology assessments can be uploaded atany time,buteverysixmonthsthey areevaluated bytheSC inorder to decide which will be selected. In order to avoid duplications, MDsthathaverecentlybeenassessedbyotheragencies-asfound forexampleintheEUnetHTAPlannedandOngoingProjects(POP) Database[39] -areexcludedandthosethatremainareprioritized
Fig. 2. The process of the Italian National HTA Program for Medical Devices (PNHTADM)
Abbreviations: AC – Appraisal Commission, AGENAS - Agenzia Nazionale per i Servizi Sanitari Regionali (National Agency for Regional Healthcare Services), ET – Evaluation Team, EUNetHTA – European Network for Health Technology Assessment, HCP – health care providers, HTA – Health Technology Assessment, LEA – Livelli essenziali di assistenza (nationally guaranteed health basket), MDs – medical devices, MoH – Ministry of Health, SC – Steering Committee, SSN – Sistema Sanitario Nazionale (Italian National Health System).
accordingtospecific criteria(Fig. 2 ).Seven criteriahavebeen en-visaged to prioritize MDsforfurther assessmentandmainly per-tain to the relevant domains of conventional HTA processes (e.g. economic, social, organizational, ethical impacts, epidemiological relevanceanduncertaintyinclinicalevidence).
5.2. Assessments
While akey goalofthePNHTADM istoeliminate redundancy in HTA inthe Italian SSN, italso aims to exploit theknowledge, experience andexpertiseaccumulatedby pastandpresentItalian HTA producers.Therefore,theSC willaccredit “collaborating cen-tres”, public orprivate institutions (mainlyregions andacademic centres) that meet certain criteria, to collaborate on assessments forthePNHTADM.Oncetechnologieshavebeenprioritizedfor as-sessment, the SC decides whichare to be assignedto collaborat-ingcentresortocentralgovernmentalagenciessuchasAGENASor theItalianNationalInstituteofHealth(IstitutoSuperiorediSanità – ISS).Favoringfulltransparencyandinclusiveness,thePNHTADM assessment process is clearly delineated, starting from a written protocolsubjecttoexternalreview tothepublicationofthe eval-uation results,opentopublicconsultationfor60days.Forthe se-lected technologies, the evaluationteam identifies the scope (re-search question) inthe studyprotocolusing thePICO framework (Population,Intervention,Comparison,Outcome).
AssessmentdomainsarebasedonthelatestversionoftheHTA CoreModel®[11] ,plusaspectsrelatedtoSSNcoveragedecisionsat thenationalorlocallevel(decisionalcontext)(Fig. 2 ).Foreach do-main,asynthesisispresentedofthescientificevidenceandits rel-ativequality resultingfromthecomparative analysis.Where nec-essary, theEvaluationTeam (ET) maycollectprimary evidenceto address areas where the literature provides insufficient informa-tion. Where HTA reports produced at the international level are proposed, a tested methodology forsuch adaptationswas
devel-oped, based on internationaland national resources, namely the “HTA network reflectionpaper – Reuse ofjoint work in national HTA activities” from the EC [40] , the EUnetHTA HTA Adaptation Toolkit[41] ,andtwomanualsproduced byAGENAS, “HTAReport Adaptation:methodologydocument”[42] andthe“AGENAS Proce-duralManual”[43] .Animportantpreliminaryphaseofthe adapta-tionprocess involvesanalysingtheinformationneeds forthe ref-erencecontext,orassessing theadaptabilityofthereport forthe national health care system. A particularly usefulinstrument for suchadaptabilityanalysisistheSpeedySiftingsection ofthe EU-netHTAAdaptation Toolkit,whichprovides a rapidscreeningtool of 8questions to apply beforegoing on to the main partof the toolkit[41] .Accordingtoqualityandquantityofevidence,urgency andtimeconstraints,theEvaluationTeam(ET)deliversaFullHTA, arapidoradaptiveHTAoraHorizonScanning(Fig. 2 )
5.3. Appraisal
A statedaspiration ofthe process design wasto allow stake-holderstoevaluate,pointby point,thereasoningandinformation supporting thevalidity ofthefinal appraisaldecision, even ifnot incompleteagreement.AppointedmembersoftheAppraisal Com-mission(AC)shouldberepresentativeoftheclinical,economic, or-ganizationalandhealthandsocialserviceareasappropriatetothe technologyunderassessment(Fig. 2 ).AllmembersoftheACmust signstatementsdeclaringthe absenceofpotential conflictsof in-terest.
BasedontheHTAreport,theappraisalprocesscallsfortheAC toevaluateandprovidearulingforeachdeterminantofthe eval-uation criteria(Need,Added ClinicalValue,Sustainability, Accept-ability, Implementabilityand Feasibility, Error! Reference source notfound.3):eitherfully,partiallyornotsatisfied.Fourdifferent recommendationscan emerge out ofthe appraisalprocess:i) re-jected;ii)recommended;iii)recommendedforresearch purposes
only; andiv) recommended provided that additional evidence is generated
5.4. Finaldecisionandappeal
TheSCevaluatestheACrecommendationsandcomestoafinal decisionregardingapproval.Allofthedocumentationispublished ontheMoHandAGENASwebsitesforpublicconsultation, includ-ingaformalappealprocess.Publicconsultationlasts30days. 5.5. ImpactofHTArecommendations
A uniqueandimportantcharacteristic ofthePNHTADM isthe desiretotietheoutcomeoftheHTAassessmentandappraisal pro-cesstothemostfundamentalprocessesinhealthpolicy decision-making: coverage, procurement and reimbursement. In fact, the recommendationsoftheSCareexpressedinrelationtofour funda-mentalcomponentsoftheItalianSSN:theguaranteedhealth bas-ket (EssentialLevelsofAssistance,orLEA),thenationalfee struc-tureforpubliclyfundedhealthcare,thehealthcareservices deliv-erythroughRegionalHealthAuthorities,andtheprocurement pro-cessinvolvedinthepurchaseofMDs(Fig. 2 ).
The NationalLEACommissionoftheMoH determines cover-age policies as they relate to the guaranteed health basket. HTA reports for health and biomedical technologies inform decisions onupdating theLEAandprovideguidanceregarding appropriate-ness and the conditions under which the benefits will be pub-licly funded. MDs that have received a positive recommendation from theSC, aswell asthose healthcareservices andprocedures containingnewly approved devices(e.g.new mini-invasive surgi-cal procedures),needtobediscussedwithin theLEACommission inorder toeitherupgradeorincludethem ifnot presentalready in the health basket. The Permanent Tariff Commission of the MoHthenupdatesthefeestructureforallservicesandprocedures that employ MDs that havebeen incorporated into the LEA.The fee structurewouldcorrespondtothevalue generatedbytheMD incorporatedintotheprocedure.
While the national government is responsible for national health policy,theLEAandthefee system, aswell aslevying and distributingtaxestofundhealthcare,theRegionalHealth Author-ities are responsible for planning and delivering (through LHAs) healthcaretotheir residentsbasedonneeds andavailable funds. Each region mayalsodetermine an ad hoc systemforregulating procedures involvingMDs ormedicines, especiallywhenthey are particularly expensiveorinnovative. The distributionsystem may take theformofahub&spoke,asystemofcentersofexcellence, setting aminimum numberofprocedures for approvinga center for a particular procedure.In this way,the regions interpret and incorporatethecoverage decisionsforthe approvedMDsintothe healthcaredeliverysystemandcanuseHTAreportstoinformthe resourceallocationprocesswithintheirjurisdiction.
The PNHTADM hasalsomadeprovisionsfortheProcurement processesinvolvedinthepurchaseofMDs.HTAreportsforMDs approved for purchase through the PNHTADM are to be used in procurementasthemostrecentandauthoritativesynthesisofthe safetyandclinicalandcost-effectivenessoftheMDinquestion,so to turn thecurrent, mainly price-basedpurchasingsystem intoa value-basedprocurementapproach.
6. Discussion
TheproposedreformofthesystemofHTAforMDsinItaly de-scribedherein illustrateshowtheMoHhasinterpretedand incor-poratedrecommendations basedoninternationalHTAbodies and studies of criticalissues andrelevant aspects of MDs,within the conceptual frameworks of economic rationality and value-based
healthcare [23 ,24 ]. The effortsmade so far by public institutions and a large plethora of stakeholders also show that the times are mature to endorse a more transparent, objective and ratio-nalprocesstogovernequitableaccesstotechnologicalinnovations inhealthcare, whichis alsolikely tobe the onlyway forwardto keeptheSSNabreastofthemostcost-effectivetechnologieswhile maintaining its universalistic architecture and free-of-charge fea-tureatthepointofconsumption.
TheuniquechallengespresentedbyMDsincomparisonto pre-scriptiondrugsforHTA[28–30 ,32 ]wasa maindriverofthepush to create a dedicated, national program. As one ofthe latest EU countriestopromoteaformal,officialHTAprogram,Italyhas how-everhad theadvantage to benefit froma numberof recommen-dations from international initiatives, professionals and associa-tions (e.g. MedtecHTA, EUnetHTA) [30 ,31 ,33 ] to inform the pro-cess and incorporate into the Program. Moreover, the entire de-velopmentprocess ofthePNHTADM hasbeenconductedthrough amixedmethodapproachthathasincorporatedexpertpanels, fo-cusgroups,systematicliteraturereviewsandcase-studiesanalysis which,all in all, makethe Italian HTAprogram solidly evidence-based.
The Program’s centralized process forproposing MDs for HTA alsoallowsforsettingprioritiesandaddressinginacomprehensive mannerthedearthofqualitysafetyandeffectivenessevidencefor MDsoftencitedintheliterature[16 ,31 ,32 ,34 ].Theparties propos-ingtheMDsencompassallrelevantstakeholders,frompatientsto manufacturers, hospitals, clinicians and professional associations, providingthatthoseclosesttothetechnologyprovidethe prelim-inaryinformationregardingtheriskleveloftheMD,theproposed use and novelty of the device, supporting evidence, related care pathways,andwhetheritsubstitutes currenttechnology.The on-linesystemallowsvariousstakeholderstostartandfollowthe pro-cessandcheck on progress.All ofthese measures help tocreate a system that is accountable not only to government needs and decision-making– apotential drawback ofa universal healthcare system[25] – but also thoseof other stakeholders.The monitor-ingprocessalsoallowsforcollectingevidenceaftertheMDis ap-proved,whichcancontinuetoinformreimbursementandpricing practices [44] . Besides theprovision of data,informationand ev-idence,theactive participationofstakeholdersintheformulation ofthe mostrelevant areasofthe program (Fig. 2 ) islikely to be thebestpredictorofendorsementofthePNHTADMbyallrelevant parties.
Theexpectedbenefitsforthe21regionalhealthsystemsinItaly includepurgingredundancywhileimprovingaccesstoinnovative technologiesin a contemporaneous manner, eliminating differing timeframesforapprovalforpurchaseatthe regionallevels,while aidingcentralized,regionalpurchasingunitsinevaluatingthe tech-nical aspects ofthe MDs. Italso addressesdisparitiesin regional resourcesandabilitiestoconductHTAthathadbeenlongobserved andhelps to approach the national process for HTA achieved by AIFAforprescriptiondrugs[5 ,18 ,26 ].
This standardization is expectedto also reduce MD price dif-ferentiation through increased transparency and a greater abil-ity for centralized purchasing bodies to negotiate based on the addedvalue generatedby the newdevice ratherthanacquisition prices [17–20] . Clinicians will find HTA an objective tool to sup-porttheirrequestsforintroducinginnovativeMDsinroutine prac-tice,andRegionalHealthAuthorities, together withLHAs, can or-ganizethe delivery ofnew services orprocedures coherentwith the regional/local context based upon the final synthesis of evi-dencestemmingfromtheSCrecommendations(e.g.,epidemiology, organizationalimpact). Patients will eventually findnodifference inaccessingmodern technologiesacross territories,thusreducing patient mobility andall relatedcosts. Finally,manufacturers will benefitfromthecentralizedPNHTADM approvalprocessthat will
allow them to streamline regulatory andmarket access activities for new technologies, erasing the need to negotiate with single regions oreven LHAs,especially asthese practices relate to evi-dence andsafetyrequirements forhigher-risk MDs, a process al-readystartedinanticipationofthenewmedicaldeviceregulation (MDR)((EU)2017/745)[45] .
7. Futuredirections
Since 2019 the PNHTADM has remained an orphan program. Theoneelementthatdidnotfindagreementwaswhoshouldfund the program. Although several options were proposed (e.g., pub-licly funded through Ministries of Health or Finance, co-funding between government andindustry) none reached full consensus, and the subsequent successionof MoH leadershipand, more re-cently, theCovid-19 pandemic haveshelved theprocess of intro-duction andimplementation ofthe PNHTADM inthe SSN. Inthe meantime, technological innovationsdo continueto enter health-care markets, and regional disparitiesdo continue to emerge. In thisdecisionalvacuum,someregionshavestartedtakingtheirown initiative asit happened last June 2020when theVeneto Region instituted a regional Technical Table for MDs andLHA Units for evaluatingrequestsforpurchasingnewMDs.IfthePNHTADMdoes not take off,the regions – aswell asother stakeholders– might lose trustandgobackto theirregionalprograms. However,there are(atleast)twoupcomingopportunitiesforthelaunchofthe PN-HTADM:theproposedEURegulationonHTAandtheNext Gener-ationEU.
Since the vote of the EP in 2018, the EU’s proposed Regula-tion onHTA hasgonethrough severalamendments,asrequested by the EP, andthe position of the European Council is expected in2021.The Regulationwillfurtherharmonizeandcentralizethe comparativeclinicalassessmentofdrugsandMDs(mainlyclassIIb andIII)withtheaimofreducing disparitiesacrossMemberStates andalleviatingtheir evaluationburdenthat would,instead,focus onnon-clinical domainsofHTA.ThePNHTADM alreadyaddresses adoptingandadaptinginternationalHTAagencyassessments,and the EU Regulation on HTA wouldtherefore fit nicely in the Ital-ian program,whichcould investits firstenergies in contextualiz-ing. More importantly, once EU Regulation haspassed, it will be fundamentalthateach MemberStatebe prepared,structured and organizedtoreceive andprocess theEU clinicalassessments.The PNHTADMiscomplete,andItalywouldfinditselfreadywhenthe timewillcome.
TheNextGenerationEUisthemostgenerousfinancialaidthat the EChas allocatedto MemberStateshit by theCOVID-19 pan-demic. Out of 750 billion Euro, Italy will receive almost a third (209billionEuro),andalthoughthepercentageallocatedto health-careisstillundecided,itwillundoubtedlybeauniqueopportunity tousepartofthesefundstoinvestinthefutureoftheSSN. Tech-nologicalinnovationisclearlyanimportantdriverofimprovement inhealthoutcomesandmustbe fostered,but– atthesametime - access must be governed to keep the entiresystem financially sustainable.Withitsconceptualframeworkrootedineconomic ra-tionality andvalue-based healthcare,thePNHTADMrepresentsan importantstepinshapingthefutureoftheSSNor,better,to safe-guardthecurrentfeaturesofuniversalism,equityandsolidarityfor thefuture.
8. Conclusions
Althoughunique inmanyaspects, webelievetheItalian expe-rience can serve as an example of how HTAcan be governed at thenationallevelinordertofacethechallengesposedby univer-salcoverageinhighlydecentralizedsystems.Notonlythefinal re-sult,butalsotheprocessesthathavebeenputinplacetogenerate
consensus amonga numberofstakeholdersmake theItalian PN-HTADManimportantmodelthatcouldprovideimportantinsights to other jurisdictions faced withsimilar challenges. Compared to otherinternationalHTAprograms,thePNHTADMpresents distinc-tivecharacteristics.The methodology,thegovernance andthe en-tireprocesshavebeenspecificallydevelopedforMDsandnot me-diated through pharmaceuticals. Although there are other coun-tries that have developed ad-hoc MD-based HTA programs (e.g., the Netherlands,France, Austria, UK),the PNHTADM is grounded ina comprehensivestudyof themost up-to-datemethodological approaches developed by international organizationsand consor-tiainthefieldofHTAforMDs.ThePNHTADMishighly participa-torysince all stakeholdershavebeen includedin all steps ofthe process.Afewcountriescanclaimahighlevelofstakeholder par-ticipation(e.g.,UK),butnonecan boastsuchwide-spread partic-ipationfroma large plethora ofstakeholdersinthe developmen-tal phase ofthe Program.Third, the PNHTADM is unique in that itrises toall ofthemostrelevanthealthpoliciesofthe SSN(i.e., coverage,procurementandreimbursement),thussettingthetrend towardsavalue-basedhealthcareapproach.
Recent changes in the Italian government - and the Covid-19 pandemic - havetemporarily slowedthe PNHTADM implementa-tionprocess.However,weareconfidentthattherepeated empha-sisonHTAinthegovernment’s“PlanforHealth(PattoperlaSalute) 2020–2021”,meansthat thecentral governmentandregional au-thoritieswillembracethissingularachievementingoverning tech-nologicalinnovation,inshort,demonstratingthatdelivering mod-ern, cost-effectiveandvalue-based care to all patientsinneed is possible,eveninaresource-constrained,publicly-funded,universal caresystem.
Funding
ThisworkwassupportedbytheDirectorateGeneralDrugsand MedicalDevicesoftheItalianMinistryofHealth.
DeclarationofCompetingInterest None.
Acknowledgments
The work group “Methods, Training and Education” coor-dinated by Marina Cerbo and Laura Velardi for AGENAS in-cludes:ToninoAceti,ValentinaAlbano,AnnaMariaVincenza Ami-cosante,Davide Archi,Luciana Ballini, Giuseppe Banfi, Maria Bar-bato, Paolo Barbieri, Francesca Bassotto, Guido Beccagutti, Gian-piero Benetti, Stefano Bergamasco, Alessia Biondi, Placido Bra-manti, Pietro Calamea, Mauro Caliani, Carla Cambiano, Laura Camoni, Paolo Campanella, Antonino Cartabellotta, Paolo Cas-soli, Silvana Castaldi, Francesco Cattel, Anna Cavazzana, Emilio Chiarolla, Americo Cicchetti, Irene Colangelo, Paolo Colletti, Sil-via Coretti, Filippo Emanuele David, Ottavio Davini, Pietro Der-rico,FrancescoCosimoFaggiano, MariaErnestinaFaggiano,Valeria Fava,Carlo Favaretti,AlessandraFiore,GaddoFlego,Ornella Fouil-louze,FrancescoGabbrielli,GiuliaGaravaglia,AntonellaGarna, Va-leria Glorioso, Giuseppe Grandi, Giovanni Guarrera, Zineb Guen-nouna, Lorenzo Leogrande, Maria Grazia Leone, Michela Liberti, AlessandraLoScalzo,AlbertoLombardi,LoredanaLuzzi, Velio Ma-cellari, Francesco Macrì, Enrico Magliano, Marco Marchetti, Clau-dio Marinai, Pierluigi Marini, Luigi Mazzei, Francesco Mennini, Luca Merlino, Andrea Messori, Rosapaola Metastasio, Adele Mist-iconi Consorti, Francesca Moccia, Marco Montorsi, Angelo Rossi Mori,MariaEugeniaMorreale,SabrinaNardi,NicolaNatale,Fausto Nicolini, Giandomenico Nollo, Marino Nonis, Marcello Pani, Vito
Paragò,Francesca Patarnello,Nicolò Pestelli,Kyriakoula Petropula-cos,NicolaPinelli,LucaPirisi,PieraPolidori,Gian Ludovico Rapac-cini,Matteo Ritrovato,PaoloRoazzi,GiancarmineRusso,Francesca Sabusco, Francesco Scarpa, Stefano Schieppati, Giovanna Scroc-caro, Alessandro Sorrone, Marco Stramba-Badiale, Lorenzo Terra-nova,IlariaToffanello, MicheleTringali,SabrinaTrippoli,IreneLuz Urbina, Marina Urpis, Roberto Verna, FrancoVimercati, Maria Vi-tale,FrancescoZavattaro.
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