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REVIEWInnovativepayerengagementstrategies:willtheconvergenceleadtobettervaluecreationinpersonalizedmedicineIldarAkhmetov1&RostyslavV.
Bubnov2,3Publishedonline:13February2017#TheAuthor(s)2017.
ThisarticleispublishedwithopenaccessatSpringerlink.
comAbstractBackgroundAsreimbursementauthoritiesaregaininggreaterpowertoinfluencetheprescriptionbehaviorofphysicians,itremainscriticalforlifesciencecompaniesfocusingonper-sonalizedmedicinetodevelop"tailor-made"payerengage-mentstrategiestosecurereimbursementandassuretimelypatientaccesstotheirinnovativeproducts.
Dependingonthetypesofsuchengagement,pharmaceuticalanddiagnosticcompaniesmaybenefitbyobtainingaccesstomedicalandpharmacyclaimsdata,gettinginvaluableupfrontinputsonevidencerequirementsandclinicaltrialdesign,andstrength-eningtrustbypayers,thereforeavoidinguncertaintieswithregardstopricing,reimbursement,andresearchanddevelop-mentreinvestment.
Thisarticleaimstostudytheevolvingtrendofpartneringamongtwointerdependent,yetconfronting,stakeholdergroups—payersandproducers—aswellastoidentifythemostpromisingpayerengagementstrat-egiesbasedoncocreationofvalueintroducedbylifesciencecompaniesinthepastfewyears.
Weanalyzedtherecentcasestudiesfromboththerapeuticanddiagnosticrealmsconsid-eredasthe"bestpractices"inpayerengagement.
Thelast5yearswereabreakoutperiodfordealsbetweenlifesciencecompaniesandreimbursementauthoritiesintheareaofper-sonalizedmedicinewithanumberoffelicitouscollaborativepracticesestablishedalready,andmanymoreyettoemerge.
Wesuggestthattherearemanywaysforproducersandpayerstocollaboratethroughouttheproductlifecycle—fromdataexchangeandscientificcounselingtoresearchcollaborationaimedatreducinghealthcarecosts,addressingadherenceis-sues,anddiminishingrisksassociatedwithfuturelaunches.
ConclusionsThepresentedcasestudiesprovideclearinsightsonhowsuccessfulpersonalizedmedicinecompaniescustom-izetheirstate-of-the-artpayerengagementstrategiestoensurecloserproximitywithpayersandestablishlonger-termtrust-basedrelationships.
KeywordsPredictivepreventivepersonalizedmedicine.
Payerengagementstrategy.
Valuecreation.
Marketaccess.
ReimbursementBackgroundTheemergenceofcomparativeeffectivenessresearchandtheshiftofthehealthcareindustrytowardnoveloutcome-basedpaymentmodelshaveputdiagnosticandpharmaceuticalcom-paniesinalessconvenient,yetpropitious,positioninperson-alized(andso-calledprecision)medicine.
Ononehand,theneedtoprovideconvincingevidenceforthesuperiorityoftherapeutic,diagnostic,ordrugdeliverysolutionsovertheexistingalternativeshasescalateddevelopmentalcostsandcreatedadditionalmarketaccesscomplexities.
Ontheotherhand,companiesthatareabletojustifythevalueoftheirproductsbydemonstratingameasurabledifferentiationvis-à-viscompetitorshavealuxurytoenjoyhighpremiumsandgainuniquecompetitiveadvantagetoalargeextentdueto*RostyslavV.
Bubnovrostbubnov@gmail.
comIldarAkhmetovildar.
export@gmail.
com1StrategicMarketIntelligenceDepartment,Unicorn,P.
O.
Box91,Zhytomyr10020,Ukraine2ClinicalHospital"Pheophania"ofStateAffairsDepartment,ZabolotnyStr.
,21,Kyiv03680,Ukraine3ZabolotnyInstituteofMicrobiologyandVirology,NationalAcademyofSciencesofUkraine,ZabolotnyStr.
,154,Kyiv03680,UkraineEPMAJournal(2017)8:5–15DOI10.
1007/s13167-017-0078-6moreextensivereimbursementandwiderstakeholderacceptance.
Consideringheterogeneityofstakeholderneeds,diversityoftoolstoquantifyvalueofproducts,andbreadthofpossibleclinicalandnonclinicalevidence,itremainscriticalforinno-vativecompanieswithfocusonpersonalizedmedicinetopart-nerwithinstitutionalcustomers,particularlypayers,tocreatethealignedincentivesandsupportthenecessarycapabilitiestomakevalue-baseddealswork.
Dependingonthetypesofsuchcollaboration,lifesciencecompaniesmaybenefitbyobtainingaccesstomedicalandpharmacyclaimsdata,gettinginvaluableupfrontinputsonevidencerequirementsandclinicaltrialdesign,andstrengtheningtrustbypayers,there-foreavoidinguncertaintieswithregardstopricingandreimbursement.
Therecentsurveyconductedamong75managedcareex-ecutivesintheUSAshowedthatpartneringbetweenpayersandbiopharmabecomesaprevailingwindintheindustrywithmorethan70%ofrespondentsrecognizingvalueintheearlystagecollaboration[1].
Notwithstandingthatpayersrecognizethevitalityofpharmadatapresentedupfront,only31%ofthepayersclaimtotakepartinphaseIIIclinicaltrials,andlessthanaquarterinvolveintheearlierphasetesting.
Thereasonsforsuchdiscrepancyaremultifold:lackoftrustinmanufac-turers,pharma'sunderestimationoftheimportanceofearlystakeholderengagement,andevenmoresotheinabilityoftheindustrytonavigatethetwotopmostpayerchallenges—complianceandcostcontainment.
Theaforementionedsignifiesthatthereisacleargapinthewaytheindustryandpayersinteract,makingitexceedinglydifficultforbothpartiestorealizethefullpotentialoftheirconvergence.
However,italsoimpliesthetremendousoppor-tunitiesforpharmaceuticalanddiagnosticcompaniesfocusingonprecisionmedicinetoaddressthisgapbydesigningandimplementingmoresophisticatedprecompetitiveprogramsinvolvingpayersinthematureandfast-growingmarkets.
Thispaperaimstostudytheevolvingtrendforpartneringamongthetwointerdependent,yetconfronting,stakeholdergroups—payersandproducers—aswellastoidentifythemostpromisingpayerengagementstrategiesbasedoncocreationofvalueintroducedbycompanieswithfocusonpersonalizedmedicineinthepastfewyears.
ThegrowinginfluenceofpayersandinnovationcrisisThedramaticspikeinhealthcarecostsovertimehasputanenormouspressureonpayerstotoughenthereimbursementcriteriaforpharmaceuticalanddiagnosticproductsinthede-velopedandemergingmarkets.
Exertinggreaterinfluenceontheglobalhealthcareecosystem,payers(governments,phar-macybenefitsmanagers,publicandprivateinsuranceplans,andmanagedcareorganizations)havesetupanunspokenrulethatobtainingFDA,EMA,orCEapprovalnolongerprovidesthelifesciencecompanieswithaprivilegetochargepremiumpricesandsecurereimbursement.
Today,reimbursementauthoritiesaredemandingaddition-alevidencethatgoesfarbeyondthecustomarysafetyandefficacydata,incorporatingrelativecost-effectivenessandbudgetimpactanalysesintheirformularydecisions.
Asaresult,innovativecompaniescontinuesufferingfromintensedrop-offsinpositivedecisionsfornewproductreimbursement.
Thus,outof102cancerdrugindicationsappraisedbytheNationalInstituteforHealthandCareExcellence(NICE)be-tween2007and2014,only47(46%)werefullyorpartiallyrecommendedforNHScommissioning[2].
SimilarnumberswereobservedinGermanyintheperiodof2011–2014,whereInstituteforQualityandEfficiencyinHealthCare(IQWIG)determinedthat50%oftheassessednewdrugsoffered"noadditionalbenefit"vis-à-viscomparators[3].
Moreover,sub-stantialprivateandpublicreimbursementrejectionswereev-idencedamongmoleculardiagnosticandtherapeuticcompa-niesintheUSAandAustraliaparticularlyduetotheinabilitytojustifyvalue-for-money[4,5].
Recognizingthegrowinginfluenceofpayersandaccount-ingforthedirectcorrelationofinsurancepremiumswiththeescalatingmedicinalcosts,largemedicalsocieties,suchasAmericanSocietyofClinicalOncology(ASCO)andAmericanHeartAssociation(AHA),arenowconsideringonincorporatingcostsor"financialtoxicity"asanotherimpor-tantperspectiveintheguidelines[6,7].
Theriseinhealthcareexpenditurehasalsocreatedmuchanxietyamidphysiciansinthecountrieswhereretirementbenefitorotherfinancialincen-tivesareaffectedbyoverprescribing[8].
Withpressurefrompublicandprivatepayers,thecost-sensitiveprescribersbe-comelessandlessinfluentialintheirclinicaldecisionsoftengivingpreferencestocheaperandlesseffectiveoptionsoverhighlyeffectivetherapeuticsanddiagnosticsthatarenotcov-eredbyhealthplans.
Forexample,intheNetherlands,75%ofthetotaldrugs(includingHerceptin)inabout1/3oftheDutchhospitalswereuncoveredbythehealthcareinsuranceinthemid-2000s,leadingtounequalaccesstohighlyeffectiveandcostlymedicines[9].
Anditisonlythe7-yearHerculeaneffortofthetwopatientadvocacygroups—theDutchBreastCancerAssociationandtheDutchFederationofCancerPatientOrganizations—thatchangedthestatusquoofHerceptin,eventhoughthefinalimpactonthecostcontrolandreim-bursementproceduresintheNetherlandswerestillnotachieved.
Whiletheeconomicexpediencyandethicsassociatedwithpayer-guidedhealthcareprovisionarenotthatstraightforwardandarealwayssubjecttolengthydebates,itisquiteobviousandparticularlycriticalthatasignificantundervaluationof6EPMAJournal(2017)8:5–15diagnosticsandtherapeuticsbymeansofseverepricingandreimbursementrestrictionsleadstoanunderincentivizedin-novation.
AccordingtoThomsonReutersandDeloittejointsurvey,thecostofbringinganewmedicinefromdiscoverytolaunchhasescalatedfromUSD1.
1billionin2010toUSD1.
3billionin2013(+18%).
Moreover,theburdenoflatestagefailureswasestimatedtodeprivethetop12pharmacompa-niesofUSD243billionin2010–2013[10].
Asinnovativecompaniesprioritizetheirportfoliosbasedoncommercialexpectations,healthinsurancereimbursementlevelsarethekeyeconomicsignalsforinnovatorstodeter-minewhetherthelikelymarketforanewdiagnosticorthera-peuticwillbelargeenoughtosubstantiatecostlyinvestments.
Hence,bearinghighmarginalcostsandgettinglowincentivesfrompayers,today,profit-driveninnovativecompaniesbe-comemorerigidinrevisingtheirpipelineassetsintermsofreimbursementattractiveness,frequentlylimitingpatientac-cesstohigh-qualityproductsforfearofacoveragefiasco.
Thus,intheearly2000s,severallargepharmaceuticalcom-panieshaveabandonedantibioticsresearchandinvestmentprioritizingdrugsinotherclasses,suchascancerandheartdisease.
Thisresultedinthefactthatresistancetoexistingmedicinescontinuedtoincrease,whilethenumberofnewantibioticsreceivingFDAapprovaldeclined[11,12].
In2014,theproblemwasaddressedbythePresident'sCouncilofAdvisorsonScienceandTechnologythatassembledmis-cellaneousstakeholderstocreatenewalignedincentivesfacil-itatingresearchanddevelopment(R&D)inantibiotics[13].
Allofthesesuggestthatthecurrentapproachtohealthcarecoverageisimbalancedand,inlightofthegrowinginfluenceofpayers,itiscrucialtorevisetheway"innovation"isdefinedandvaluated,outliningunambiguousincentivesforthelifesciencecompaniestocontinuereinvestingintoR&D.
"Perasperaadastra"—innovativepayerengagementstrategiesInthepastseveralyears,thelifesciencecompanieshavebeenresponsivetothenewpayerrolebymeansofexpandingtheirmarketaccessandregionalsalesteamstotargetthespecificreimbursementaccounts,collectingmoredataonpayer"painpoints"anddecision-makingprocesses,customizingcoreval-uedossierstothelocalpayerneeds,andallocatingsubstantialfundsonlocalizedreal-worldevidencestudies.
Althoughim-portant,thesestrategiesprovidecompanieswithonlyincre-mentalbenefits,anddonotallowthenecessaryproximitywithreimbursementauthorities.
Hence,toachievesuchprox-imity,companiesshouldhavemoreopendialoguesandtightercollaborationwithpayersbasedontrustandcocreationofvalue(Fig.
1).
Reimbursementauthorities,uncertainofwhatmanufac-turershaveintheirpipelines,generallyappreciateearlydialogueswiththelifesciencecompaniestobemoreinformedaboutimpendinglaunchesandtheassociatedadditionalbud-getloads.
Inresponse,companiesareabletoaddresstheirquestionsandcreatemoreclarityonwhattheycandotomakethepipelineandmarketedtherapeuticsmoreattractivefromapayerperspective.
Yet,despiteofmarketaccessandcommer-cialteamscreatingamyriadofbrilliantideasonhowtopart-nerwithreimbursementauthorities,therearealwaysethicalandregulatoryconstraintsaboutgoingbeyondtheconven-tionalunitprice-basedrelationshipsandco-pays.
Oneoftheprimeconcernsofthehealthcarestakeholdersregardingtheindustry–payerpartnershipsistransparency.
ToaddressthisissueandtoharmonizeearlydialoguesbetweenHTAagenciesandtheproducersofhealthtechnolo-gies,recently,therehasbeenlaunchedanewinitiativeinEuropecalled"ShapingEuropeanEarlyDialogue"(SEED)[14].
Thispilotconsortium,ledbytheFrenchHauteAutoritédeSanté(HAS)andfinancedbytheEuropeanCommission(EC),iscurrentlycovering10projects(7fortherapeuticsand3formedicaldevices),whichwillfacilitatethedevelopmentofmethodologicalguidelinesontheearlystagepayer–producerinteraction.
Anumberoflegislativeactsincentivizingindustry–payerconvergencehavealsoappearedatanationallevel.
Forexam-ple,intheUK,theHealthandSocialCareActof2012hasintroducedaframeworktoencouragecollaborationbetweentheNationalHealthServiceandlifesciencecompaniesaimedatfacilitatinginnovationandhealthcaredelivery[15].
Theearlydialoguesbetweenmanufacturerandreimburse-mentauthoritiesareparticularlyimportantinlightoftheexistinginconsistenciesintheway"innovation"isdefinedbybothparties.
Itfrequentlyoccursthatproducersconsider"me-too"medicinesasinnovativebecauseoftheirdistinctmanufacturingprocessanddifferencesinthemechanismofactionvis-à-visthestandardofcare.
Onthecontrary,reim-bursementauthoritiespaymoreattentiontotheoverallcom-parativeeffectofatherapeuticversustheassociatedcosts,andlittlearetheyinterestedinthesurrogateendpointsortechno-logicalpeculiaritiesofaninnovativeproduct.
AccordingtoBach(2009),pricesofthemajorityofanti-cancertherapeuticsareescalatingwithgreatervelocitythanthehealthbenefitsassociatedwiththem,makingeachtreat-mentprogresslesscost-effectivethanthepreviousone[16].
Havingnoultimatewaytoassessthetruevalueofinnovation,payersareguidedbyasimpleprinciplethatinnovationwith-outastrongdifferentiationshouldnotbeincludedintheirdrugformularies,whileauniquetherapeuticordiagnosticsolutionwithgreaterrelativeeffectivenesstargetingahighunmetneedismorelikelytoseethereimbursementgreenlight.
Yet,theborderlinebetween"strong"and"weak"differen-tiationvariesgreatlybetweenHTAandreimbursementau-thorities,makingitliterallyimpossibletoadequatelyquantifyinnovation.
Forexample,therecentstudyconductedbyEPMAJournal(2017)8:5–157Droescheletal.
showedthatofthe20identicaloncologytherapiesevaluatedbyFrenchandEnglishHTAbodies,17havebeenrecommendedbyHAS,andonly4receivedposi-tivedecisionsbyNICE[17].
AssuggestedbyFig.
1,apartfromearlydialogueswithcompanies,payersrecognizesubstantialvalueinalmostallkindsofresearchinitiativesrelatedtocostmitigation—fromparticipationinreal-worldevidencestudiestoengagementinacomparativeeffectivenessresearch.
Forexample,in2009–2011,MedcoHealthSolutions(acquiredbyExpressScripts)haslaunchedalargehead-to-headstudyofPlavix(clopidogrel)andEffient(prasugrel)stretchingoutover2yearstoidentifythestrataofheartpatients,whowerenotabletometabolizeclopidogrelandrequiredtobeswitchedtoprasugrelbasedontheirgeneticmakeup[18].
Thus,beingabletodirectpatientstolessexpensivegenericversionsofclopidogrel,thepharmacybenefitmanageracquiredmoreconfidencethatithadachievedcomparablecareatasignifi-cantlyreducedcost.
Alongthesamelines,in2011AstraZenecahassignedanagreementwithWellPoint'sHealthCoretoestablisha4-yearevidenceofdevelopmentpartnershipgeneratingreal-worlddataviaprospectiveandretrospectiveobserva-tionalstudiesonthemosteffectiveandeconomicaltreat-mentsinchronicandotherdiseases[19].
Asapartofthisdeal,companiesweretoanalyzeelectronicmedicalre-cords,reviewclaimsinformation,andconductpatientsurveys.
PayerengagementstrategiesPayerconsultationsAdvisoryboardmeetingsPayersurvey/interviewsOnlinediscussionsGroupworkshopsFormalconsultationsIn-personVirtualForumsFeedbackformsRisksharingagreementsOutcomesbasedschemeEvidencebasedschemeFinanciallybasedschemePrice-volumeagreementsRebates/DiscountsUtilizationcapsPay-for-performanceOutcomesguaranteeDiseasemanagementschemesCoveragewithevidencedevelopmentExpertisebasedpartnershipsJointevidencegenerationMedicationadherenceprojectsRealworldevidenceComparativeeffectivenessTelemedicineE-pillsM-healthPatientfinancialincentivesUser-friendlydeliverydevicesBetterhealthcaredeliveryPatient/providereducationRetrospectivedataanalysisMedicalclaimsdataPharmacyclaimsdataLaboratoryclaimsdataFig.
1Examplesofinnovativepayerengagementstrategiesinpersonalizedmedicine8EPMAJournal(2017)8:5–15Anotherattractiveareaforlifesciencecompaniestocol-laboratewithreimbursementauthoritiesispoormedicationadherence,whichisperhapsthehottestissuefacedbypayersthesedaysalongwithcostcontainment.
Hence,byleveraginginnovativepatient-centeredsolutions(e.
g.
,financialincen-tives,telemedicine,e-pills,m-health,user-friendlydrugdeliv-erydevices,andimprovinghealthcaredelivery)companiesareabletowintrustandcreategreatervalueforpayers.
TheMerck–CignacollaborationonJanuviaandJanumetisoneofthesuccessfulindustry–payerpartnershipexamplesresultingin87%improvedpatientadherencetotherapy,inwhichMerckintroducedlargediscountstopatientswhofollowedthemedicationregimeasprescribed,andCignaloweredco-paylevelsforadheringpatients[8].
AnothercaseofWellDoc'sBlueStaralsoperfectlyillustrateshowamobile-integratedtherapycoupledwithelectronichealthrecordsen-ablesadultswithtype2diabetestoachievestatisticallysig-nificantimprovementsinHbA1clevel,enhancepatientsatis-factionandwinreimbursement[20,21].
Establishingrisk-sharingagreements(also,"manageden-tryagreements,""patientaccessschemes,""RSAs,""MEAs,"and"PAS")isanotherbroadlyutilizedapproachtoengagewithpayers,forsucharrangementsofferthepotentialforear-lieraccesstonewtherapeuticsanddiagnosticsbylinkingre-imbursementlevelstoreal-worldperformanceoruseofaproduct.
RSAsaimatsharingfinancialrisksduetouncertaintyrelatedtotheintroductionofnewtechnologies[22].
TherearethreemajorgroupsofRSAs[23]:1)Financiallybasedschemesdefineproducer'scontribu-tionstothecostofatherapeuticordiagnosticbasedonfinancialthresholds,andnotlinkingcoveragetohealthoutcomes(e.
g.
,price–volumeagreements,rebates,dis-counts,andutilizationcaps);2)Outcome-basedschemesareperformance-basedagree-ments,inwhichhealth-relatedqualityoflifepredeter-minespricingandreimbursementlevels(e.
g.
,pay-for-performance,outcomesguarantee,anddiseasemanage-mentschemes);3)Evidence-basedschemes(also,"coveragewithevidencedevelopment"or"CED")areacategoryofindustry–pay-erdeals,inwhichacompanyisgrantedtemporaryreim-bursementinexchangeforgenerationofsupplementaryreal-worldevidencewiththesubsequentrevisionofcov-erageconditionsbasedonthecollectedevidence.
AccordingtoFerrarioandKanavos,Belgium,England,Sweden,andtheNetherlandshad133activeRSAsasof2012,withEnglishpayersgivingpreferencestodiscountsandfreedoses;DutchprioritizingCED;SwedesconsideringCED,monitoringutilizationandcompliancewithrestrictionsviaobservationalstudies;andBelgiansequallyusingalloftheaforementionedpractices[24].
TheutilizationofRSAsisalsogainingmomentumintheAsia-Pacificregionwith98schemesobservedinAustralia,5inNewZealandand3inSouthKorea[23].
Theemergenceofsuchinnovativeap-proachestomarketaccessisanimperativemilestoneinfor-mulatingnewgenerationpayer–produceragreementsbasedonopendialogue,cooperation,andmulti-stakeholdervaluecreation.
Amongotherpremisesfortheindustryandpayerstocol-laborateisthefactthatreimbursementauthoritiesareunder-staffed,budget-constrainedandboggeddownintheirroutine,oftenunderperformingintheareasofdiseasemanagement,dataanalysis,aswellaspatientandprovidereducation[25].
Hence,therearetremendousopportunitiesforthesestake-holderstopartnerfillingtheaforementionedgapsonaccountofadisease-specificexpertiseandresources.
Forinstance,lastyear,NovoNordiskhaslaunchedanini-tiativecalledcitieschangingdiabetes,whereitpartneredwithanumberoflargeprivateinsurers,likeUnitedHealthcare,BlueCrossBlueShield,Aetna,andCigna,totackletheprob-lemofurbandiabetesintheUSA,analyzingkeyfactorsthatdrivetheglobalpandemicandutilizingthatknowledgetoshapereal-worldsolutions[26].
Likewise,in2011,PfizerteamedupwithHumanatobringtogetherdataandscientificinformationtocreateabettercomprehensionofpatientneedsanddrugeffectiveness[27].
Tosumup,therearenumerousopportunitiesforproducersandreimbursementauthoritiestocollaboratebasedontheunmetpayerneeds,includingthenecessitytoreducehealthcarecosts,pooradherence,highuncertaintyandrisksassociatedwithfuturelaunches,andlackofspecificexpertiseandresources.
Successfullifesciencecompaniesthatareabletocustomizetheirstate-of-the-artpayerengagementstrategiestotheseneedsmayachievecloserproximitywithpayersandestablishlonger-termtrust-basedrelationships.
CasestudiesThelast5yearswereabreakoutperiodfordealsbetweenlifesciencecompaniesandreimbursementauthoritiesintheareaofpersonalizedmedicinewithanumberoffelicitouscollabo-rativepracticesestablishedalready,andmanymoreyettoemerge.
Belowareseveralcasestudiesfromboththerapeuticanddiagnosticrealms,consideredasthe"bestpractices"inpayerengagement:"Roche–SwissRe"collaborationinChinaRocheisaglobalhealthcarecompanydevelopinginnovativetherapeuticanddiagnosticproductsintheareaswithunmetmedicalneeds.
Asof2014,threeoutoftenbest-sellingblock-bustermedicinesinoncologyweredevelopedandcommer-cializedbyRoche[28].
EPMAJournal(2017)8:5–159In2010,thecompanylinedupwithSwissRetostrengthenitspresenceintheChinesemarketbyintroducingrisk-sharingdealstolocalinsurers.
SincedirectcommerceofforeignretailinsurancewasprohibitedbylawinChina,RocheandSwissRecameupwitharevolutionaryideatostartsellingreinsur-ance,andthusconvincingChineseinsurerstooffercoverageforhigh-qualitycancertherapeutics.
Asapartofthiscollabo-ration,RocheprovidesSwissReandlocalinsurerswithmar-ketingsupportandstatisticaldataondifferenttypesofcancer,whileSwissReprovidesChineseinsurancecompanieswithreinsuranceandtechnicalsupportontheproductdesignandpricing[29].
Withinjust2years,theRoche–SwissRecollaborationinChinaallowedthelocalinsurancepolicyholders,includingCPICLife,toachievetheirfirstmilestone—sellinginsuranceto6millioncustomers—thusfacilitatingaccessofalargenumberofcancerpatientstoinnovativetreatments,liketrastuzumab[30,31].
"VitrOmics–CZ–CPCT"partnershipintheNetherlandsVitrOmicsHealthcareHoldingisanorganizationspecializedinpersonalizedmedicinefocusingonthedevelopmentofdi-agnosticproductstomeasurekinaseandnuclearreceptorac-tivities,basedonthePamChipplatformcreatedbyitsdaughtercompanyPamGene.
Intheearly2012,thecompanylaunchedaprivate–publiccollaborativeinitiativeengagingwiththeDutchhealthinsur-anceproviderCZandtheCentreforPersonalizedCancerTreatmentwiththegoaltoaddresstheproblemofovertreat-mentinbreastcancer,providingmuchmoreselectivetherapytoastratifiedsubpopulationofpatientsthanstipulatedbytheusualclinicalpractice[32].
Asaresult,thetriadwasawardedavalue-basedhealthcareprizeunderthepatronageofanhonorarychairmanMichaelE.
Porter,establishingabenchmarkfor"goodpractice"inindus-try–payerpartnershipsbasedoncocreationofvalueandtrust.
Thisinitiativehasalsopreparedthegroundfortwosubse-quenttrialsinlungandesophagealcancer.
"EliLilly–Humana"initiativeintheUSAEliLillyisaglobalbiopharmaceuticalcompanywithprimaryfocusonnoncommunicablechronicdiseasesandnearlyacen-turyofexperienceindiabetesresearch.
In2013,thecompanyannouncedjointresearchcollabora-tionwithalargehealthcareinsurancecompany,Humana,inordertoconductaretrospectiveanalysisofmedical,pharma-cy,andlaboratoryclaimsdatawiththeprimaryobjective—toidentifymodifiablecharacteristicsofdiabeticpatientsassoci-atedwithincreasedhealthcarecosts,aswellastostudyther-apeuticinterventionsaffectingpatients'adherenceandout-comes[33].
ThisdatawillenableEliLillydesignmoretargetedthera-peuticinterventionsanddiseasemanagementprogramsinthefuture,andassistHumanainaddressingadherenceandcostissuesindiabetes.
Similarresearchinitiativeswerealsointro-ducedbyPfizer,Merck,AstraZeneca,andothercompanies,tightlycollaboratingwithleadinghealthinsuranceproviders[27].
"MolecularMD–Medco"partnershipintheUSAMolecularMDisamanufacturerofmoleculardiagnostictestsforoncologyapplications,includingaqRT-PCRassaytomea-sureBCR-ABLlevelspriortoinitiationofchronicmyeloidleukemia(CML)therapy.
ThePhiladelphiachromosome(BCR-ABL)isfoundin95%ofCMLpatientsandiscurrentlyconsideredtobetheprimarycauseofthedisease[34,35].
In2011,theUSleadingpharmacybenefitmanagerMedcoHealthSolutionshaslaunchedaprogramtitled"DNADirectbyMedco"incollaborationwithMolecularMDtoidentifypatientseligiblefortreatment,therebyreducingcostsfortreatingpatientsthatarenotresponsive[35].
Thiscollaborativepatient-centeredinitiativeledtoasignif-icantreductioninhealthcarecostsforMedco,increasedmar-ketshareandrevenuesofMolecularMD,improveddecision-makingofphysicians,andenhancedthequalityofcareofpatients.
ApartfromtheCMLprogram,Medcohasalsosignedpartnershipswithotherlifesciencecompaniestoiden-tifypatientseligibleforwarfarin,clopidogrel,tamoxifen,abacavir,andmaraviroc.
"NuoTherapeutics–CMS"risk-sharingdealintheUSANuoTherapeuticsisabiomedicalcompanydevelopingandcommercializingindividualizedregenerativewound-healingtherapies.
Thecompany'sflagshipproductisAurix,anau-tologoushematogelusedtotreatdiabeticfoot,pressure,andvenouslegulcers.
In2010,facinganationalnoncoveragedeterminationonblood-derivedproductsforchronicnonhealingwounds,NuoTherapeuticshasinitiatedadialoguewiththeCentersforMedicare&MedicaidServices(CMS)onhowtoabolishthisnationalmandateforAurix,consideringtherobustsafetyandeffectivenessprofileofitsproduct[36].
In2011,theman-dateforAurixwasremoved,yettheCMSconcludedthatalthoughpromising,theprovideddatawasnotsufficienttovalidatetheproduct'sgeneralizabilitytotheMedicarepopu-lation,hence,additionalreal-worldevidencewouldhavebeenrequiredforAurixtobeincludedinthepositivereimburse-mentlist.
In2014–2015,aftertheapprovalofprotocolsforlaunchingthethreeprospectiverandomizedeffectivenesstri-als,thepositiveCEDdecisionwasgrantedtoNuoTherapeutics[37].
10EPMAJournal(2017)8:5–15GlobalpricingpoliciesCurrently,weobservethedebateonglobalpricingpoliciesinparticulartodevelopessentialmedicinesandensureitsafford-abilityandavailabilityinthelongertermforaconsistentsup-plyindevelopingcountries,likeantiretrovirals,artemisinincombinationtherapies,drug-resistanttuberculosismedicines,liposomalamphotericinB(forvisceralleishmaniasis),andpneumococcalvaccines,andtopromotepoliciesthat"de-link"thefinancingofR&Dfromthepriceofmedicines[38].
Theroleofinternationalalliances,not-for-profitenter-prises,isconstantlyincreasing,e.
g.
,thecontributionofGlobalAllianceforTuberculosisDrugDevelopment(TBAlliance)toapublic–privatepartnership,thatdrawsupontheresourcesofbothprivateandpublicinstitutionstohelpaddressthisurgenthealthneedaimstostopthespreadoftuberculosisbydevelopingnew,faster-acting,andaffordabletuberculosisdrugs[39].
TheGlobalFund[40]workstosup-portprogramsofprevention,treatment,andcareforAIDS,tuberculosis,andmalariaandtostrengthenhealthsystems.
Eligiblecountriescanreceiveanupfrontallocation,whichprovidesimprovedpredictabilityoffunding.
Startingfromthecountry'snationalstrategicplan,stakeholdersparticipateinanongoingandinclusivecountrydialogue.
Theseveralexamplesoftheso-called"philanthrocapitalism"thatincludeprivateinitiatives/effortsofBillandMelindaGates[41]andChanZuckerbergInitiative(CZI)[42]demonstratefairsuccessandmightbecomemoreimportantplayertohelpfightingchallenginginequalitiesinhealthcarefundinginthefuture.
Horizon2020andpersonalizinghealthandcareDuringthefirst4yearsofHorizon2020(workprogramsfor2014/2015and2016/2017),theEUresearchfundingprogramHorizon2020(2014–2020)andinparticulartheCommission'sproposalforhealth,demographicchange,andwellbeingchallenge[43]willinvestmorethan2billionincallsforproposalsoractionsconsideredasaninvestmentinbetterhealthforall,aimstosupportthedevelopmentofnew,safer,andmoreeffectiveinterventionstotestanddemonstratenewmodelsandtoolsforhealthandcaredeliveryandalsocontributestothesustainabilityofhealthandcaresystems[43,44].
GrantingschemesoftheEuropeanCommission,likethelargestpublic–privateinitiativeinnovativemedicinesinitia-tive(IMI)[45]withatotalbudgetof130millionaimingtospeedupthedevelopmentofbetterandsafermedicinesforpatientsaddressestherapyanddiagnosticdevelopmentchal-lengestodevelopnovelsolutionsforunmetmarketneeds.
Thus,relevantHorizon2020callslike"Thedevelopmentofnewmethodsandmeasuresforimprovedeconomicevalu-ationandefficiencymeasuresinthehealthsector"focusoneconomicmodeldevelopment[46];EUfundingforprecommercialprocurement(PCP)andpublicprocurementofinnovativesolutions(PPI)projectsareavailableacrossthedifferent2016–2017Horizon2020workprograms[47]over-comingbarriersinprecompetitivepublicprocurementsofin-novativesolutionsinparticularfromSMEs.
Thiscasestudysignifiestheimportanceofearlydialogueswithpayers.
Yet,italsodemonstratesthatalthoughNuoTherapeuticswasrewardedforitspersistenceandcollabora-tiveapproachtoCMS,muchtimeandfinancialresourcescouldhavebeensaved,shouldthecompanyestablishthedi-aloguewiththereimbursementauthorityearlierinthedevel-opmentalphase.
ConclusionsReimbursementauthorities,substantiallyfreefromregulatoryconstraintsanddrivenbytheescalatinghealthcareexpendi-tures,aregaininggreaterpowertoimpacttheprescriptionbehaviorofphysicians.
Althoughthepayers'attemptstocon-tainhealthcarecostsmayhaveapositiveeconomiceffectfromanationalhealthserviceperspective,itmayalsohaveaneg-ativeclinicalaffectfromanindividualpatientperspective,duetorestrictedcoverageofeffectivepremium-pricedproducts(directimpact),aswellasviaunderincentivizationofinnova-tion(indirectimpact).
Inthepastseveralyears,thelifesciencecompanieshavebeenresponsivetothenewpayerrolebyredesigningsalesandmarketaccessteams,adjustingandlocalizingtheirclinicalandpharmacoeconomicstudiesinaccordancewiththeidenti-fiedpayerrequirements,aswellasconductingmoreresearchonpayerneeds.
Consideringthatthesestrategiesprovidepharmaceuticalanddiagnosticcompanieswithonlyincre-mentalbenefits,producersareadvisedtohavemoreopendialogueswithpayersupfrontandtoestablishtightercollab-orativeinitiativeswithreimbursementauthoritiesbasedontrustandcocreationofvalue.
Therearemanywaysforproducersandpayerstocollabo-ratethroughouttheproductlifecycle—fromdataexchangeandscientificcounselingtoresearchcollaborationaimedatreducinghealthcarecosts,addressingadherenceissues,anddiminishingrisksassociatedwithfuturelaunches.
Successfullifesciencecompaniesthatareabletodesigntheirstate-of-the-artpayerengagementstrategiesaroundpayerneedsmayachievecloserproximitywiththesestakeholdersandestablishlonger-termtrust-basedrelationships.
Gazingintothefuture,scenariosinwhichpayersinvestintothelifesciencecompaniestodevelop"tailor-made"ther-apeuticordiagnosticproductsseemnottobethatfaroff,althoughtheethicalandlegalconcernsassociatedwithsuchpracticesarealsolikelytoemerge.
Moreover,weanticipateagreaternumberofearlydialogueinitiativesbetweenlifesci-encecompaniesandpublicpayers(notonlyprivatepayers)toEPMAJournal(2017)8:5–1511ariseattheregional,nationalandinternationallevels.
Withtheemergenceofpan-Europeanprograms,likeSEED,itisalsoexpectedthatearlydialogueswithpayerswillbecomemoretransparentandsystemized,whichwillleadtopromptermarketaccessofnewtherapeuticanddiagnosticproducts.
Theseandothertopicsaresubjecttoourfuturescientificresearch.
OutlookandexpertrecommendationsCurrentpaperconformwiththePPPMobjectivessummarizedintheEPMAWhitePaper2012[48]tosupportpersonalizedmedicinetobewidelyadoptedinclinicalsettoyieldsafer,moreeffective,andlessexpensivemedicalinterventions[39]andprovidestakeholderswithevidenceofitsclinical,cost-effectiveness,andfinancialviability.
Personalizedmedicineraiseinvestors'interestandexpectationsanddesireswhopro-videtherequiredcapital.
Ultimately,thebigpharmaceuticalindustryhasbeenditheringtoreceiveapersonalizedmedicineapproachasitwasexpectedthatpatientstratificationwouldpromptdrasticallydiminishedmarketsizes[48,49].
However,thereisevidencethatpersonalizedmedicine,basedonbio-markers,maydemonstratesuperioreffectivenessthatwarrantshigherpricing.
Manynewpersonalizedmedicinescanbeex-pectedtobecost-effectivebecauseoftheincreasedclinicaleffect,eveniftheyhavepremiumprices.
Ontheotherhand,inmanycountries,tolinkreimbursementtocost-effectivenessviacleardialoguebetweenthecommercialandscientificgroupsbecomeacommonpracticeensuringa"rightculture"forpromotingtruth-seekingratherthanprogression-seekingbehavior[50]fordifferentiatedandreimbursablemedicine,includingimportantelements,likemarketopportunity,scien-tificunderstandingandunmetmedicalneeds,evaluatingrisk,andprobabilityoftechnicalandregulatorysuccess.
Therecentmassiveresourcesdevotedtogenome-sequencingstudiespar-adoxicallyprovidedverylittlenewevidence.
However,abet-terstrategyforidentifyingnewtreatmentoptionsmaybetodevelopmethodsforanalyzingthesignalingnetworksthatunderliediseasedevelopment,progression,andtherapeutic[51–53].
NationalandinternationalgrantingstrategiesinPPPMareconstantlydiscussedbyEuropeaninitiative,suchasEPMA[54],pilotprogramstosupportprospectivehealthcarehavealreadybeenset.
Sinceitsverybeginning,EPMAissystematicallyworkingontheeconomyofPPPM[4,44,48,52,54–58].
Potentialproblems/limitationsofimplementationpersonal-izedmedicineapproach,whichstillfacesanuncertainfuture,sincebeingaddressingpreventionratherthantargetedtherapy,ismoreexpensivethanexistingsuccessfulpreventiveinter-ventions[59–61].
Personalizedmedicineaffectingthecostsofmedicalcarealtersthefutureoftheentirehealthcaresystemandhassuggestedthatmedicalcarecostswillbereducedinthefuture.
Anotherchallengeforimplementingpersonalizedmedicineinlow-andmiddle-incomecountries(LMICs)[60]isthelackofawarenessofneedsforpersonalizedmedicineamongthegeneralpopulation,loweducationallevel(overallliteracyratesformanyLMICslessthan67%),howeverthisstatementmightbeisstereotyped—e.
g.
,UkraineisformallyLMIC,butdemonstrateratherhigheducationallevelofpopulation.
Wesuggestthefurtherstudiesonthefollowingpoints:&thedevelopmentofnewmethodsandmeasuresforim-provedeconomicevaluationandefficiencymeasuresinthehealthsectortogainadvancesinincreasingvalue,promotehealth-seekingbehaviors;&strategicplanningforreimbursement,theoutputofnewproductsonthemarketandpatientaccesstoinnovationsonallstages—developmentpredictivemarkersforpa-tientsstratification,personalizedtreatments,andpreven-tionandbeyond;&avoidoverusingunnecessaryclinicaldiagnostic,screen-ing,andtherapeuticalinterventionsthatlacksufficientev-idenceonefficacyandsafetyviavalue-guidedapproach;&developmulticriteriamodelsforvaluingmedicines[62];&toorganizerelevantclinicaltrialstosearchtheevidence,comparativeeffectivenessresearch(CER)usingpopula-tion-based,retrospectivedatacaninformassessmentsofpersonalizedmedicine,includingimplementationofN-of-1trials[63];&thedevelopmenteducationalprogramsincompliancewithexpertsinmedicalfieldsconsiderethicalissuestobalanceinvolvementofbigpharmacologycompanies&adaptationofNationalmedicallegislation;politicalsup-portwilllikewisebeexpectedtohelpforaccomplishingnormalrepaymentamongstsuppliersandpayers,sothatforthcomingconsiderationcansatisfyitsguaranteeofbe-ingthecost-effectivemedicalmodeltoimprovenationalhealthsystems;&adherethemedicallegislationindevelopingcountriestomeetrequirementsofnovelandeffectivemodels;&toinvolvesmallcompanieswhichhavehigherR&Dpro-ductivitycomparedwithlargercompanies[64];&todevelopapplicablebusinessmodelsforLMICsforre-ductioninhealthdisparitiesbetweenresource-richcoun-triesandLMICs;&furtherresearchisneededtodevelopthemodelstoboostthereimbursementpolicyforeffectivenonpharmacologicalapproaches,likephysicaltherapy,painmanagement,musculoskeletalultrasound-guidedinterventions[65,66],treatmentsviaprobiotics,personalizeddiets[67],andregenerativemedicine,whichrecentlydemonstratedhighlevelofefficacyandsafety[68];&considerethicalissues,security,andprivacyofmedicalandfinancialinformation[56];12EPMAJournal(2017)8:5–15&implementationofpersonalizedapproachshouldbedonesmoothlyviadevelopmentaccessiblehealthcareandNationalmedicaleconomyandupdatedlegislationforin-clusive,innovativeandreflectivesocieties[69].
AHA,AmericanHeartAssociation;ASCO,AmericanSocietyofClinicalOncology;CE,ConformitéEuropéenne;CED,CoveragewithEvidenceDevelopment;CMS,CentersforMedicare&MedicaidServices;EC,EuropeanCommission;EMA,EuropeanMedicinesAgency;FDA,FoodandDrugAdministration;HAS,HauteAutoritédeSanté;HTA,healthtechnologyassessment;IQWIG,InstituteforQualityandEfficiencyinHealthCare;NHS,NationalHealthService;NICE,NationalInstituteforHealthandCareExcellence;RSA,risk-sharingagreements;SEED,ShapingEuropeanEarlyDialogue;LMIC,low-andmiddle-incomecountries.
AcknowledgementsWeacknowledgetheEPMAJournaleditorialteamandBioMedCentralteamfortheopportunitytopublishthiswork.
Authors'contributionsIAsuggestedtheideaofthestudy,preparedthefirstdraftofmanuscript,didtheliteratureanalysis,andreviewedthecasestudies.
RVBdidtheworkonthesecondmanuscriptdraft,formu-latedfutureoutlooks,andthePPPMconcept.
Bothauthorsreadandapprovedthefinalmanuscript.
CompliancewithethicalstandardsAuthor'sinformationIAisaMarketAccessConsultantatUnicorninZhytomyr,Ukraine.
RVB,M.
D.
,Ph.
D.
isamedicaldoctorintheClinicalHospital"Pheophania"oftheStateAffairsDepartment,researcherintheInterferonDepartmentofZabolotny,InstituteofMicrobiologyandVirology,NationalAcademyofSciencesofUkraine,andnationalrepre-sentativeoftheEuropeanAssociationforPredictive,Preventive,andPersonalizedMedicine(EPMA)inUkraine.
EthicsapprovalandconsenttoparticipateNotapplicableConsentforpublicationNotapplicableAvailabilityofdataandmaterialNotapplicableCompetinginterestsAuthorsdeclarethattheyhavenocompetinginterests.
FundingAuthorsdidnotreceivefundingtopreparecurrentarticle.
OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.
0InternationalLicense(http://creativecommons.
org/licenses/by/4.
0/),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedyougiveappro-priatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicense,andindicateifchangesweremade.
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