global paper 21feb2017-1pm - Duke-Margolis...The United States government (USG) is the world’s...
Transcript of global paper 21feb2017-1pm - Duke-Margolis...The United States government (USG) is the world’s...
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AuthorsGavinYamey,AndreaThoumi,JonathanGonzalez-Smith,CynthiaBinanay,IpchitaBharali,ZeenaJohar,
DavidRidley,NickChapman
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AuthorsGavinYameyisDirectoroftheCenterforPolicyImpactintheDukeGlobalHealthInstitute(DGHI),ProfessorofGlobalHealthandPublicPolicy,andAssociateDirectorofPolicyatDGHI,DukeUniversity.
AndreaThoumiisaManagingAssociateattheDuke-MargolisCenterforHealthPolicy,DukeUniversity.
JonathanGonzalez-SmithisaSeniorResearchAssistantattheDuke-MargolisCenterforHealthPolicy,DukeUniversity.
CynthiaBinanayistheDirectorofOperationsfortheDukeHubert-YearganCenterforGlobalHealthandSeniorProjectLeaderattheDukeClinicalResearchInstitute.
IpchitaBharaliisaPolicyAnalystattheCenterforPolicyImpactinGlobalHealthattheDukeGlobalHealthInstitute.
ZeenaJoharisaResearchFellowwiththeGlobalHealthInnovationCenterandDuke-MargolisCenterforHealthPolicy.
DavidRidleyisanAssociateProfessorofthePracticeandtheFacultyDirectoroftheHealthSectorManagementprogramatDukeUniversity’sFuquaSchoolofBusiness.
NickChapmanistheExecutiveDirectorofPolicyCuresResearch.
AcknowledgementsWethankJenniferKatesattheKaiserFamilyFoundation,MichaelMersonandMarkMcClellanatDukeUniversity,andCourtneyCarson,MarissaChmiola,andMattRobinsonatGHTCfortheirhelpfulcommentsonthefirstdraftofthispaper.
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TableofContentsExecutiveSummary............................................................................................................................viiIntroduction.........................................................................................................................................1Section1.HowWeConductedthisStudy.............................................................................................3
DeskReview..............................................................................................................................................3KeyInformantInterviews.........................................................................................................................3DefiningR&DforGlobalHealth................................................................................................................4
Section2.LevelsandTrendsinUSGFundingforGlobalHealthR&D.....................................................6HowmuchdoestheUSGinvestinglobalhealthproductdevelopment?.................................................6WhatdoestheUSGfund?........................................................................................................................7RecenttrendsinUSGfunding.................................................................................................................10
Section3.USGAgencies:GlobalHealthR&DFunding,Decision-making,andCoordination................11DepartmentofHealthandHumanServices...........................................................................................12
BiomedicalAdvancedResearchandDevelopmentAuthority............................................................13NationalInstitutesofHealth..............................................................................................................15CentersforDiseaseControlandPrevention......................................................................................19USFoodandDrugAdministration(FDA)............................................................................................22
UnitedStatesAgencyforInternationalDevelopment............................................................................24DepartmentofDefense..........................................................................................................................28OfficeofManagementandBudget........................................................................................................31
Overview............................................................................................................................................31FundingDecisions...............................................................................................................................32
Section4.TheAppropriationsandBudgetProcess:InfluenceonGlobalHealthR&D..........................33BudgetFormulation.................................................................................................................................33AppropriationsTimeframe........................................................................................................................33
Section5.CatalystsandBarrierstoUSGSupportforGlobalHealthR&D............................................36CatalyststoUSGagencysupportforglobalhealthR&D........................................................................36
CollaborativeApproacheswithinandbetweenAgenciesandPrograms...........................................36MarketincentivesofferedbytheUSG...............................................................................................38Supportivelegislativechanges...........................................................................................................38Regulatoryincentives.........................................................................................................................39
BarrierstoUSGsupportforglobalhealthR&D......................................................................................39Institutionalsiloes,unwieldysystems,andthedifficultyofcoordination.........................................39Insufficientfunding............................................................................................................................40Under-useofeffectiveagencies.........................................................................................................41Inadequateincentivestructures........................................................................................................42NoclearmechanismtotrackUSGfundingforglobalhealthR&D.....................................................42
Section6.PerspectivesfromIndustry,ProductDevelopmentPartnerships,andFoundations............43PerspectivesfromIndustry.....................................................................................................................43PerspectivesfromNGOs,PDPs,andFoundations..................................................................................46
Section7.Stakeholders’SuggestionsforReformRecommendations..................................................49ConclusionsandRecommendations...................................................................................................54References.........................................................................................................................................59
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FiguresFigure1.USInvestmentinGlobalHealthR&DWithandWithoutEbolaFunding.....................................................viiiFigure2.GuidingFrameworkfortheKeyInformantInterviews...................................................................................4Figure3.GovernmentFundingforGlobalHealthR&D,2015.......................................................................................6Figure4.USGFundingforGlobalHealthR&Din2015byDisease................................................................................7Figure5.USGFundingforGlobalHealthR&Din2015byTypeofResearch................................................................9Figure6.USGDepartments,Agencies,Offices,andInstituteswithaKeyRoleinSupportingGlobalHealthR&D....11Figure7.USGFundingforGlobalHealthR&DbyAgency,2015.................................................................................12Figure8.USGFundingforEbolaandOtherAfricanVHFs,2015.................................................................................13Figure9.NIHFundingin2015forGlobalHealthR&DbyDisease..............................................................................16Figure10.CDCFundingin2015forGlobalHealthR&DbyDisease............................................................................20Figure11.USAIDFundingin2015forGlobalHealthR&DbyDisease........................................................................25Figure12.USGFundingforReproductiveHealthR&DNeedsinLMICs,2015............................................................25Figure13.USGFundingin2015forPDPsthatDevelopProductsforGlobalHealth,byRecipientandAgency.........27Figure14.DoDFundingin2015forGlobalHealthR&DbyDisease............................................................................29Figure15.IllustrativeTimelineofAppropriationsProcess.........................................................................................35
TablesTable1.OverviewofUSGAgencies,Departments,andOffices..................................................................................ixTable2.NewTherapeuticProductsApprovedorRecommendedbyDifferentRegulatoryBodies,byDiseaseCategory,2000-2011...................................................................................................................................2Table3.KeyInformantsInterviewedfortheStudy,bySector.....................................................................................3Table4.USGFundingin2015forGlobalHealthProductDevelopment,byDisease—ShowingPrimaryInvestmentAreasandKeyUSGAgenciesInvolved...........................................................................8Table5.ExamplesofSuccessfulGlobalHealthR&DCoordinationBetweentheNIHandOtherFederalandNon-federalAgencies....................................................................................................................19Table6.ExamplesofSuccessfulGlobalHealthR&DCoordinationBetweentheCDCandOtherFederalandNon-federalAgencies....................................................................................................................22Table7.AppropriationCommitteesandSubcommitteesinthe114thCongressthatOverseeAgenciesInvolvedinGlobalHealthR&D.......................................................................................................34
BoxesBox1.DefinitionofGlobalHealthR&DUsedinOurReport.........................................................................................5
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AbbreviationsAAAS AmericanAssociationfortheAdvancementofScience
ADEPT AutonomousDiagnosticstoEnablePreventionandTherapeutics
AMCs Advancedmarketcommitments
AMR Antimicrobialresistance
AMRH AfricanMedicinesHarmonizationProgram
AU AfricanUnion
BARDA BiomedicalAdvancedResearchandDevelopmentAuthority
BSC BoardofScientificCounsellors
BMGF BillandMelindaGatesFoundation
CARB-X CombatingAntibioticResistantBacteriaBiopharmaceuticalAccelerator
CBRN Chemical,biological,radiologicalandnucleardefense
CDC CentersforDiseaseControlandPrevention
CDRH CenterforDevicesandRadiologicalHealth
CEWG ConsultativeExpertWorkingGrouponResearchandDevelopment
CGH CenterforGlobalHealth
COR-NTD CoalitionforOperationalResearchonNeglectedTropicalDiseases
CRADA CooperativeResearchandDevelopmentAgreement
DAH Developmentassistanceforhealth
DALYs Disability-adjustedlifeyears
DARPA DefenseAdvancedResearchProjectsAgency
DCs Developingcountries
DFID DepartmentforInternationalDevelopment
DNDi DrugsforNeglectedDiseasesinitiative
DoD DepartmentofDefense
DTRA DefensiveThreatReductionAgency
EID Emerginginfectiousdiseases
EMA EuropeanMedicinesAgency
EOP ExecutiveOfficeofthePresident
EU EuropeanUnion
FAR FederalAcquisitionsRegulations
FDA FoodandDrugAdministration
FENSA FrameworkofEngagementwithNon-StateActors
G20 GroupofTwenty
GAO GovernmentAccountabilityOffice
GDP GrossDomesticProduct
G-FINDER GlobalFundingofInnovationforNeglectedDiseases
GHI GlobalHealthInitiative
GHITF GlobalHealthInnovativeTechnologyFund
GHTC GlobalHealthTechnologiesCoalition
GHSA GlobalHealthSecurityAgenda
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GNNTDs GlobalNetworkforNeglectedTropicalDiseases
GPGs Globalpublicgoods
HHS UnitedStatesDepartmentofHealthandHumanServices
IAVI InternationalAIDSVaccineInitiative
IFPMA InternationalFederationofPharmaceuticalManufacturers
IMDRF InternationalMedicalDeviceRegulatorsForum
IP Intellectualproperty
IVCC InnovativeVectorControlConsortium
LICs Low-incomecountries
LMICs Low-andmiddle-incomecountries
MassBio MassachusettsBiotechnologyCouncil
MCM Medicalcountermeasures
MDIC MedicalDeviceInnovationConsortium
MDR-TB Multi-drugresistanttuberculosis
MDSAP Medicaldevicesingleauditprogram
MENA MiddleEastandNorthAmerica
MHS MilitaryHealthSystem
MMV MedicinesforMalariaVenture
MPP MedicinesPatentPool
MSF MédecinsSanFrontières(DoctorswithoutBorders)
NAFTA NorthAmericanFreeTradeAgreement
NAM NationalAcademyofMedicine
NCATS NationalCenterforAdvancingTranslationalSciences
NCE Newchemicalentity
NCEZID NationalCenterforEmergingandZoonoticInfectiousDiseases
NCHHSTP NationalCenterforHIV/AIDS,ViralHepatitis,STD,andTBPrevention
ND Neglecteddisease
NGO Non-governmentalorganization
NIAID NationalInstituteofAllergyandInfectiousDiseases
NIH NationalInstitutesofHealth
NMRC NavalMedicalResearchCenter
NSC NationalSecurityCouncil
NSTC NationalScienceandTechnologyCouncil
NTD Neglectedtropicaldisease
NVPO NationalVaccineProgramOffice
OAR OfficeofAIDSResearch
ODA Officialdevelopmentassistance
OECD-DAC OrganizationforEconomicCooperationandDevelopment-DevelopmentAssistanceCommittee
OGA OfficeofGlobalAffairs
OGAC OfficeoftheU.S.GlobalAIDSCoordinatorandHealthDiplomacy
OMB OfficeofManagementandBudget
OPA OrphanDrugAct
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OSTP OfficeofScienceandTechnologyPolicy
OTA OtherTransactionAuthority
PACCARB PresidentialAdvisoryCouncilonCombatingAntibiotic-ResistantBacteria
PCAST President’sCouncilofAdvisorsonScienceandTechnology
PDP Productdevelopmentpartnership
PDVAC ProductDevelopmentforVaccinesAdvisoryCommittee
PEPFAR USPresident’sEmergencyPlanforAIDSRelief
PHEMCE PublicHealthEmergencyMedicalCountermeasuresEnterprise
PMI President’sMalariaInitiative
PPPs Publicprivatepartnerships
PRV Priorityreviewvoucher
R&D Researchanddevelopment
RFA Requestforapplications
RFP Requestforproposals
RMNCH Reproductive,maternal,newbornandchildhealth
RMO ResourceManagementOffice
SADC SouthAfricanDevelopmentCommunity
SARS Severeacuterespiratorysyndrome
SBIR SmallBusinessInnovationResearch
SDG SustainableDevelopmentGoals
SIB Socialinvestmentbond
TATFAR TransatlanticTaskforceonAntimicrobialResistance
TB Tuberculosis
TOSSD TotalOfficialSupportforSustainableDevelopment
USPTO UnitedStatesPatentandTrademarkOffice
USAID UnitedStatesAgencyforInternationalDevelopment
USG UnitedStatesgovernment
VHF Viralhemorrhagicfever
VICP NationalVaccineInjuryCompensationProgram
VRC VaccineResearchCenter
WHO WorldHealthOrganization
WIPO WorldIntellectualPropertyOrganization
WRAIR WalterReedArmyInstituteofResearch
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ExecutiveSummaryDespiterecentprogressinglobalhealth,poorpopulationsinlow-andmiddle-incomecountries(LMICs)continuetobedisabledordiedisproportionatelyfromneglecteddiseasesandconditionsofpoverty.Whilesomeofthisburdenofdisabilityanddeathcouldbeavertedbyimprovingthedeliveryofexistinghealthtools,newtechnologiestoaddressunmetneedarealsourgentlyneeded.
Amajorbarriertoinvestingintheresearchanddevelopment(R&D)ofnewproductsfordiseasesofpovertyisthelackofsufficientincentives.Thetime,cost,technicalchallenges,andriskoffailureduringproductdevelopmentcreateaformidabledisincentivetoproductdevelopers.Furthermore,existingtechnologiesmaynotaccountforcontextualfactorsinLMICsthatmayhindertheuptakeanduseoftheseinnovations.Asaresult,researchontheregulatoryapprovalsofnewdrugsandvaccinessince1975hasshownthatfewofthesenewproductsareforneglecteddiseasesandconditionsofpoverty.
TheUnitedStatesgovernment(USG)istheworld’slargestfunderofproductdevelopmentforglobalhealth,butasweshowinthisreport,itsfundingforsuchresearchanddevelopment(R&D)isindecline.ThereportaimstoidentifyopportunitiestostrengthenUSG’sroleinsupportingglobalhealthproductdevelopment.ItdoessobyexaminingthelandscapeofUSGfundingforsuchglobalhealthR&D;describingcatalystsandbarrierstoincreasingUSGfundingandcoordinationofglobalhealthR&D;providingperspectivesfrombothUSGandprivateactors(e.g.,industryandfoundations);andproposinginitialideasforreform.Weusetheterm“globalhealthR&D”torefertoproductdevelopmentfornewmedicines,vaccines,diagnostics,andotherhealthtechnologiestotackleaspecificlistofpoverty-relatedandneglecteddiseasesandconditions(adaptedfromtheG-FINDERsurveysproducedbyPolicyCuresResearch).
Webasedourstudyonadeskreviewand36keyinformantinterviewswithseniorrepresentativesfromgovernmentandprivatesector(for-profitandnon-profit)organizations.
LANDSCAPEOFUSGFUNDINGFORGLOBALHEALTHR&D
LevelsandtrendsinUSGfunding
TheUSGistheworld’smostsignificantfunderofglobalhealthR&D,investing$1.7billionin2015—threequartersofallgovernmentfundingworldwide.However,itdirectstwiceasmuchglobalhealthR&Dfundingtobasicandearlystageresearchasitdoestolate-stageproductdevelopment.ThisdiscrepancyresultsfromthefocusoftheNationalInstitutesofHealth(NIH),whichaccountsfor80%ofUSGfunding,onearly-stageresearch.TheonlyUSagencytoinvestmoreinclinicaldevelopmentthanbasicandearlystageresearchistheUnitedStatesAgencyforInternationalDevelopment(USAID),butUSAIDisresponsibleforjustfivepercentofallUSGfundingforglobalhealthR&D.
ThelargestshareofUSGglobalhealthR&Dfundingin2015wenttoHIV/AIDS(45percent),followedbyEbolaandotherAfricanviralhemorrhagicfevers(VHFs,16percent),tuberculosis(TB,13percent),andmalaria(12percent).ThefocusonEbolaandAfricaVHFswaspromptedbyauthorizationofemergencyfundingandleveragingexistingR&Dprograms,allowingtheUSGtorapidlymobilizesignificantR&Dresourcesinresponsetothe2014Ebolaoutbreak.ButthisfundingsurgehidamajordeclineinR&Dfundingforotherneglecteddiseases,whichhasfallensinceitspeakin2009(Figure1).Adjustedforinflation,annualUSGinvestmentinneglecteddiseaseR&Dhasfalleneveryyearbutonesince2009,andisnowmorethanaquarterofabilliondollarsbelowits2009peak(down$263million,orareductionof16percent).
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USGagencies:funding,decision-making,andcoordination
TheUSGinvestsinglobalhealthR&Dacrossmultipleagenciesandprograms,andthereisno“whole-of-government”strategy.Individualagenciesorofficesoperatemostlyautonomously,includingsettingtheirownR&Dpriorities,thoughwedidfindsomeexamplesofsuccessfulcross-agencycollaboration.Table1summarizesouranalysisofthefivelargestfundersofglobalhealthR&D,alongwiththeUSFoodandDrugAdministration(FDA),whichisnotamajorfunderbutwhichhasinfluenceinotherways.TheseagenciesaretheNIH,DepartmentofDefense,BiomedicalAdvancedResearchandDevelopmentAuthority(BARDA),USAID,andCentersforDiseaseControlandPrevention(CDC).
Figure1.USInvestmentinGlobalHealthR&DWithandWithoutEbolaFunding
Source:ChmiolaM,CarsonC,KelleyK,MortonEW,RobinsonM.Achievingaboldvisionforglobalhealth:PolicysolutionstoadvanceglobalhealthR&D.GlobalHealthTechnologiesCoalition;2016.
2014
US$
(mill
ions
)
WITH EBOLA
FUNDING
WITHOUTEBOLA
FUNDING
0
1700
201420132012201120102009200820072006*2005*2004
1300
1400
1500
1600
1650
1550
1450
1350
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Table1.OverviewofUSGAgencies,Departments,andOfficesAgencyoroffice
FundingforglobalhealthR&D,2015
Focusareas Decision-making Examplesofsuccessfulcoordinationcitedbystakeholders
NIH $1.3billion(80%oftotalUSGfunding)
• HIV/AIDS(50%of2015funding),TB(15%),malaria(12%)
• Three-quartersofallocatedfundingwasforearlyandbasicstageresearch
• About90%ofbudgetisforextramuralresearch,awardedviaabottom-upapproachthroughcompetitivepeer-reviewedgrantapplicationprocess
• Someflexibilityinusingintramuralfundsintop-downwaytorespondtoglobalhealthemergencies
• PartnerinPublicHealthEmergencyMedicalCountermeasuresEnterprise(PHEMCE)
• NIH-industrycollaboration:CooperativeR&DAgreements(CRADAs)betweenfederallaboratoriesandnon-federalparties
DoD $123million(7%oftotalUSGfunding)
• EbolaandotherAfricanVHFs(41%of2015funding),malaria,(24%),HIV/AIDS(23%)
• Otherpriorities,e.g.,leishmaniasisanddengue,reflectdiseasethreatsfacingsoldiersoverseas
• Investmentinintramuralinfectiousdiseaseresearchisdrivenbytwostreams:workforcehealthprotection(i.e.needsofmilitarypersonnel)andbiodefenseneeds.TheseoverlapwithneedsofaffectedpopulationsinLMICs(e.g.,denguevaccinedevelopment)
• PartnerinPHEMCEandPresidentialAdvisoryCouncilonCombatingAntibiotic-ResistantBacteria(PACCARB)
• KeymemberofGlobalHealthSecurityAgenda(GHSA)
BARDA $104million(6%oftotalUSGfunding)
• AllfundingwasforEbolaandotherAfricanVHFs(BARDAwasnotamajorfunderofglobalhealthR&Duntilthe2014Ebolaoutbreak)
• Developsmedicalcountermeasures(MCMse.g.,vaccines,therapeutics)againstnaturallyoccurringorintentionalpublichealththreats
• OnlycivilianentitywithsolefocusonlatestageR&Dformedicalproducts
• Fundingdecisionsandbudgetsaredrivenlargelybyits5-yearstrategicplan
• BARDAmodelhasprovidedanattractiveecosystemtoincentivizeindustryintoglobalhealthproductdevelopment;modelinvolvesadvanced(“push”)R&Dfunding;procurementfunds(“pull”incentives)todevelopstockpiles(e.g.,ProjectBioShieldprocurementfund);andtechnicalassistanceandinfrastructuresupport
• ParticipatesinPHEMCE;keyactorinCARB-X(CombatingAntibioticResistantBacteriaBiopharmaceuticalAccelerator),anewpublic-privatepushmechanism
USAID $87million(5%oftotalUSGfunding)
• HIV/AIDS(66%of2015funding),TB(15%),malaria(11%),andreproductivehealthneedsindevelopingcountries(8%)
• USAIDprovidesthreequartersofallUSGfundingforreproductivehealthneedsindevelopingcountries
• SupportsglobalhealthR&DthroughitsCenterforAcceleratingInnovationandImpact;GlobalDevelopmentLab;GrandChallengesprogram;disease-specificprograms
• R&Dfundingdecisionsaremadeatindividualprogramlevel
• Multiple,separatefundingstreamsfordifferentdiseasesorconditions;no-overarchingagency-widestrategy
• PartnerinmultiplePDPs,includingInternationalAIDSVaccineInitiative(IAVI),MedicinesforMalariaVenture,andInnovativeVectorControlConsortium
• GrandChallengesprogram
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Agencyoroffice
FundingforglobalhealthR&D,2015
Focusareas Decision-making Examplesofsuccessfulcoordinationcitedbystakeholders
CDC $18million(1%oftotalUSGfunding)
• TB(48%of2015funding),EbolaandotherAfricanVHFs(45%)
• FundingforR&Dforacorelistof34neglecteddiseaseswashalvedfrom2014to2015,fallingby$9million
• Budgetisheavilyearmarkedandso,unlikeNIH,CDCdoesnothavemuchflexibilityonhowtospenditsbudget
• PartnerinPHEMCE• Inter-agencycollaboration:
CDCworkswithDoDandNIHtoproducemultiplexassays(whichdetectseveralinfectiousagentsinasingleclinicalspecimen)
• InternationalcollaboratorinMeningitisVaccineProjectandInternationalAIDSVaccineInitiative(IAVI)
• LeadagencyforGHSA
FDA Nofunding(buthasfundedglobalhealthR&Dinthepast)
• Significantnon-financialcontributionstoglobalhealthR&D,e.g.,priorityreviewvoucher(PRV)scheme,grantingoforphandrugstatus,foreignpoststoinspectmanufacturingglobally,regulatoryharmonizationefforts
• ObjectiveeligibilitycriterialimitFDAdiscretiononPRVsandorphandrugstatus,butthereissomeflexibility,e.g.,in2015,FDAexpandedvouchereligibilitytoincludeChagasdiseaseandneurocysticercosis
• IssuedBroadAgencyAnnouncementtosolicitcollaborationonR&Dtosupportregulatoryscienceandinnovation
• PartnerinPHEMCE
Appropriationsandbudgetprocess
TheappropriationsprocessiskeytoUSsupportforglobalhealthR&DbecauseitultimatelydeterminestheR&Dfundingenvelopewithinwhichtheindividualagenciesmustoperate.CongressallocatesfundingforfederalglobalhealthR&Dactivitiesthroughanannualappropriationsprocess.Congressionalcommitteestaffersmeetwithexecutiveagencyofficialsandnon-governmentstakeholderstoconsiderhigh-levelbudgets,thenspecificappropriationsforindividualagenciesandprograms.WhileCongressoccasionallydelineatesspecificfundingamountsforglobalhealthR&Dthroughindividualearmarks,itgenerallyfundsdiseaseortechnology-specificaccountsandyieldstoimplementingagencyleaderstodetermineR&Dprioritizationwithinthataccount.Whilethefederalbudgetandappropriationsprocesswedescribebelowisthewaythattheprocessisintendedtooccur,therealityisthatmostyearshavebeenexceptionstothisrule.
TheappropriationsprocessismeanttobeginwhenthePresidentsubmitsanannualbudgettoCongressinFebruaryforthefollowingfiscalyear.TheOfficeofManagementandBudget(OMB)preparesthisbudget,reflectingthePresident’sprioritiesforgovernmentspending.StakeholdersdescribedOMBasthe“centerofgovernment,”workingcloselywithexecutiveagencyofficialsandothers—includingadvocacygroups—duringthebudgetpreparationprocessandthroughouttheyearwhilemonitoringthebudgetimplementation.BecauseOMBstaffisdividedalongagencylines,theofficeischallengedinitsabilitytocomprehensivelycoordinatethefundingofglobalhealthR&DacrossallofUSG.Whenconsideringbudgetrequests,OMBstafffavorprogramsorpoliciesthatdemonstrateclearneedsandtangibleoutcomes,andrelyondataprovidedbyindividualagenciesandadvocatestohelpguidethisdecision-making.ThispreferencecanmakeprioritizationofglobalhealthR&Dspendingdifficult,asR&Drequireslong-terminvestmentsanddoesnotalwaysyieldshort-termresults.Politicalfactors—includingPresidentialinterest,campaignpledges,andcurrentevents—canalsodriveOMB’sfundingdecisions.
CongressreceivesthePresident’sbudget,andbeginsitsowndecision-makingandfundingprioritizationprocess.WhilethisprocessisoftenguidedbythePresident’sbudget,Congressultimatelysetsfundinglevelsindependently,anditcanacceptorrejecttheAdministration’srequests.Inrecentyears,such
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independencehasbeenprevalentinglobalhealthfunding,withCongressrejectingfundingcutsfortuberculosisandnutritionproposedbythePresident,andCongresscuttingfundingtofamilyplanningandreproductivehealthaccountsdespiterequestsforbudgetincreasesinthePresident’sbudget.
CATALYSTSANDBARRIERSTOUSGSUPPORTFORGLOBALHEALTHR&D
Severalcross-cutting,cross-agencythemesemergedfromourstudy,relatedtocatalystsandbarrierstosupportingglobalhealthR&D.withintheUSgovernmentandthroughprivatesectorandNGOpartners.
Catalysts
Ouranalysisfoundfourmaincategoriesofcatalyststoenhanceproductdevelopment:• Cross-agencyinitiativesandprograms.StakeholdersdescribedseveralexamplesofUSGactorscollaboratingeffectivelytoachievegreaterimpactinglobalhealthR&D.Theyarguedthatsuchcross-agencycollaborationcancatalyzeinnovationbysharingofideasandresources(e.g.,laboratoriesorsamples)anditcandriveefficiencythroughcostsavings.TheGrandChallengesmodel,forexample,waspraisedforallowing“organicandproductive”collaborationandprovidingfundingacrossthewholeproductdevelopmentcontinuum.Whenthereisanurgentpublichealthproblemandclearask,thereisastrongermotivationforbreakingdowninstitutionalandinter-agencybarriers;withoutacrisis,collaborationismuchharder.Similarly,thereisatensionbetweentheshort-termgoalofaddressinganemergencyandlong-termobjectiveofcreatingasustainablefundingenvironment.Cross-agencyglobalhealtheffortshavesucceededwhentheyareledbytheAdministrationorthroughsustained,coordinatedeffortsledbyagencies,asseenwiththeGlobalHealthSecurityAgenda(GHSA)ledbyCDC.Theimprimaturofahigh-levelfederaladvisorycouncilwasviewedascriticaltobringingaboutproductivecollaboration,asseenwiththePresidentialAdvisoryCouncilonCombatingAntibiotic-ResistantBacteria(PACCARB),whichaimstoaccelerateproductdevelopmentbystreamliningeffortsatthehighestlevel.
• MarketincentivesofferedbyUSG.ThemarketincentivesprovidedbyBARDAwereseenasasuccessfulmodelforUSGengagementinproductdevelopmentpartnerships(PDPs).TheseincludeBARDA’sintegratedpushandpullmechanisms(fundingfortranslationalR&Dandadvancedmarketcommitments[AMCs]),aswellasitsOtherTransactionAuthority(OTA),whichfacilitatesitsabilitytoestablishlongtermportfoliopartnershipswithindustry.Suchportfoliopartnershipshaveencouragedindustrytostayintheantibioticdevelopmentspace.Thepriorityreviewvoucher(PRV)schemeaimedatincentivizingthedevelopmentofdrugsforaselectedlistofinfectiousandparasiticdiseasesaffectingLMICsisseenbysomeasawelcomeadditiontotherangeofgovernmentincentivemechanismstosupportR&D.However,theimpactofthePRVtodateisunclear.
• Supportivelegislativechanges.TherehavebeenseveralexamplesofCongressbeingpersuadedtoalterlegislationinwaysthatstrengthenUSG’sroleinglobalhealth,includingglobalhealthR&D,suggestingthatadvocacytoCongresscanbeeffective.Forexample,BARDA’sremitwasexpandedtoincludeproductdevelopmentforantimicrobialresistance(AMR),whichallowstheagencytoconsiderworkoutsidethebiodefensespace.
• Regulatoryincentives.FDAhasatitsdisposalarangeofregulatoryincentivesthatcanhelptocatalyzeproductdevelopmentforglobalhealthchallenges.Examplesincludefast-trackandorphandrugdesignations(theseweregranted,alongwithpriorityreview,tothedrugbedaquilinefortreatingmultidrug-resistantTB)andemergencyuseauthorization(grantedforEbolacountermeasures).
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Barrierstoglobalhealthproductdevelopment
Ouranalysisfoundfivemaincategoriesofbarrierstoglobalhealthproductdevelopment:• Institutionalsiloesandunwieldysystemsmakecoordinationdifficult.Despiteexamplesofsuccessfulinter-agencycoordination,agencieslargelyworkinsiloes,hamperedbysystemsbarriers.ThefailureoftheGlobalHealthInitiativeexemplifiesthedifficultiesinaddressingcoordinationacrossagenciesandsuggeststhattryingto“force”acollaborationcanhavetheoppositeeffect,particularlywhentheylackclearleadership,budgetaryauthority,oraunifyingmandatemission.Evenwithinagencies,theremaybedivisionsthatcanimpedeglobalhealthR&D.R&Deffortswithinanagencyareoftendivorcedfromitsdiseasecontrolprogramsandscale-upefforts,amissedopportunityfortestinginnovativeproductsinthefield.JurisdictionaldivisionsbetweenCongressionalappropriationssub-committees,mirroredinOMBoffices,canstovepipeR&Dfundingdecisionsandimpedeinteragencycoordinationandcollaboration.Inaddition,theinabilityofCongresstoenactaregularappropriationsbillbeforethestartofthefiscalyearalsohindersstrategicplanning.
• Afundinggapfortranslationalandproductdevelopment.Amajorchallengetoproductinnovationisthefundinggapforthistypeofresearch.LowlevelsoffundingatCDC,forexample,hassloweddownthedevelopmentofapromisingdiagnosticfortrachoma.BudgetcapsandsequestrationshaveshrunkalreadylimitedglobalhealthR&Dfunding,slowingdownproductdevelopmenteffortsatseveralagencies.Ebolavaccinedevelopmentwasstalled,forexample,asaresultofthesequester.Financingoflater-stageclinicaltrialshasbecomeprohibitivelyexpensive.Nevertheless,somestakeholdersarguedthatjustincreasingfundingalonewillnotaccelerateglobalhealthR&DunlessotherweaknessesinthecomplexR&D“ecosystem”areaddressed.
• Under-useofeffectiveagencies.Thereissignificant,under-usedvalueintheDepartmentofDefense(DoD)overseaslabsforglobalhealthR&D,includingforvaccinedevelopment.StakeholdersarguedthatDoD’smedicalR&Ddoesnotgettherecognitionthatitdeservesandisdwarfedbyhigherprofiledefenseprojects.
• Inadequatemarketincentivestructures.Previousmarketfailureshighlighttheinadequacyofthecurrentincentivestructurestopromoteproductdiscoveryanddevelopmentintheareasofantimicrobialresistance(AMR),emerginginfectiousdiseases,andneglectedtropicaldiseases.Recentoutbreaks(e.g.,Ebola)wereneveranticipatedandtheexistingstructureswerenoteasilyadaptabletomeettheseoutbreaks.TheUSGdoesnothaveR&Dsurgecapacity;suchcapacitywouldneedanewappropriation.
• LackofaclearmechanismtotrackUSGfundingforglobalhealthR&D.Thereisnocommon,standardworkingdefinitionofR&DacrossexecutiveagenciesandnoclearmechanismtotrackR&Dfundingflows.ThisinconsistencypreventsOMBfromadequatelytrackingglobalhealthR&Dacrossmultipleexecutivebranchesandlimitsconversationsaboutcoordinationthatmightotherwisehavebeentriggered.
PERSPECTIVESFROMINDUSTRY,PDPS,NGOS,ANDFOUNDATIONS
InadditiontoUSGstakeholders,wealsointerviewedprivatesectoractors(for-profitandnon-profit)tounderstandtheirexperiencesofpartneringwithUSGonglobalhealthR&D.
IndustrystakeholdersindicatedthattheyareincentivizedtoconductglobalhealthR&DbythepushandpullmechanismsofferedbytheUSG,suchasthePRVandorphandrugdesignation.However,thesearenotthekeydriverintheirdecision-making,inpartbecausetheincentivesonlyaccountforafractionof
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thetotalcostofdevelopingaproduct.TheyexperiencesignificantbarrierstopartneringwithUSG,includingbureaucraticprocesses,complexreportingrequirements,slowFDAapprovalsystems,limitedlevelsoftranslationalfunding,andoveralllackofpoliticalwilltopartner.SeveralindustrystakeholdersengagewithPDPstoleverageexpertiseandfinancingnotavailablewithintheparentcompany.ButsomeindustrystakeholdersinterviewedforthisreportarguedthatthatthereareadvantagestogoingitalonebecauseindustrygoalsarenotalwaysalignedwiththoseofPDPs;theyseetechnologytransferasanequallyviablemodelforproductdevelopmentandaccess.
NGO,PDP,andfoundationstakeholdersalsofacepracticalhurdlescollaboratingwithUSG.Theyhighlightedtwobarriers:thelackofanexplicitprioritysettingprocessforglobalhealthR&Dandtherelativelackoffundingforproductdevelopmentcomparedwithearlystageoroperationalresearch.TheyhadmixedviewsonthePRV,butfeltitwastooearlytojudgeitsimpact,andpositiveviewsontheirexperiencesworkingwithindustry,includinginPDPs,seeingbenefitsfromgreaterUSG-industrycollaboration.NGOswhoworkonadvocacyforincreasedglobalhealthR&DfindtheUSG’slong,complexbudgetandappropriationsprocessamajorbarrier.NGOsandPDPsinterviewedreceivedfundingfromtheBillandMelindaGatesFoundation(BMGF)andtheirR&DprioritizationwasinfluencedbytheFoundation’spriorities.TheyexpressedconcernsabouttheFoundation’srecentshiftinitsfocusawayfromvaccinedevelopmentthroughPDPstowardsindustryplayers.
STAKEHOLDERS’SUGGESTIONSFORREFORM
KeyinformantsgavesixmainsuggestionsonwaystostrengthenUSGsupportforglobalhealthproductdevelopment.1. USGshouldimplementstrategiestosupportleadershipandcollaborationattheAgencylevel—for
example,anewforumorblueribbontaskforcecouldbeestablishedtohelpNIHwithglobalhealthR&Dprioritysetting.USGstakeholdersrecommendeda“ManhattanProject”typeprogramforglobalhealthR&Dtargetedtohelpovercomethechallengeofmaintainingindividualagencymissionwhileworkingcollaboratively.
2. TheUSGshouldinvestinR&DcapacitybuildinginLMICs.SuchinvestmentshouldincludestrengtheningregulatorycapacityinLMICS.
3. TheUSGneedstoincreaseitseffortsoncollaborationandknowledgeexchangewithoutsidepartners,bothdomesticallyandinternationally(especiallywiththeWHO),tohelpinformglobalhealthR&DprioritizationandimproveR&Defficiency.USGshouldmakeuseofopportunitiestobetterengagewithindustryandnongovernmentactors,suchasthroughthecreationofplatformstoshareknowledgeandcreateeconomiesofscale.TherearealsovaluablelessonstolearnfromEurope’ssuccessesincreatinganinfrastructuretofundglobalhealthR&D.
4. TheUSGshouldallocatefundingmorestrategicallytoaddressgapsinproductdevelopment,includingtranslationalsupportforglobalhealthR&D.ThereshouldbeanincreaseinUSGfundingforglobalhealthR&D,especiallyclinicaltrials,whetherthroughprovidingbetterincentivemechanismsorinnovativeandadditionalfinancingmechanisms.StakeholdersweredividedonwhetherUSGshouldparticipateinaninternationalpooledfundforglobalhealthR&D.CreativeandinnovativeapproachestoR&Dfinancingshouldbetried,suchasdevelopingblendedfinancingmechanismstobringtogetherpublic,private,andphilanthropicfunding.
5. TheUSG’spushandpullincentivemechanismsshouldberefinedtoimprovetheirimpact.Forexample,thePRVcouldberedesignedtoincludecommitmentstoregisterthedrugandmakeitavailableandaffordabletopatientsandtreatmentproviders.
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6. ScaledupandmorestrategicadvocacyeffortscouldhelpimproveUSGsupportforglobalhealthR&D.Strategicadvocacyand“goodstorytelling”couldhelptoimprovefundingandprioritizationofglobalhealthR&D.Creativeapproachestoadvocacyareneeded,suchasshowcasingtheeconomicbenefitsofglobalhealthR&D,itspotentialtocreatejobs,anditsroleinmaintainingUSG’sreputationasthegloballeaderinproductdevelopmentandinnovation.Advocacyeffortsshouldincludepushingforregulatoryreviewprocessesforglobalhealthproductstobeharmonizedacrosscountries.TheFDAcanplayanimportantmentoringroleintheharmonizationofregulatoryprocesseswhilealsobuildingin-countryregulatorycapacity.
CONCLUSIONSANDRECOMMENDATIONS
OurstudyfoundthatwhileUSGplaysavitalroleinsupportingglobalhealthproductdevelopment,therearemanywaysinwhichthissupportisbeingweakenedorthreatened.Wedrawninemajorconclusions,eachaccompaniedbyourinitialrecommendations.• Conclusion1:ThereisanongoingstruggletofindthecorrectbalancebetweenUSGagencyautonomyandgreaterinter-agencycoordination.Whilethechallengeofcoordinationhasbeenwelldescribed,the“positiveconsequences”ofthefracturedUSGinfrastructureforglobalhealthR&Dhavereceivedlessattention.Afracturedarchitecturemaywellgeneratemoreinnovationthantryingtohaveallagenciesinlock-step.Recommendations:ThedebateonwhethergreatercoordinationwillimproveR&Disunlikelytobesettledwithoutadeepanalysisofthecurrentinstitutionalarrangementsandthedevelopment,piloting,andevaluationofnewinter-agencycoordinationmechanisms.SuchananalysisshouldalsolearnlessonsfromthesuccessofmechanismssuchasPACCARBandPHEMCE.
• Conclusion2:TheUSGismissingopportunitiestostrengthenitsexternalcollaborationswithotheractorsintheglobalhealthR&Dspace.Inparticular,thereisarealhungerfortheUSGtobecomeamoreseriousparticipantinandfunderofPDPs.Recommendations:USGshouldbecomeamoresignificantparticipantinPDPs.TheNIHshouldconsiderdirectingaportionofitsextramuralfundingtothehighest-impactPDPs.USAIDshouldexpanditsroleinsupportofPDPs,includingdevelopingnewreproductivehealthtechnologies(e.g.,toolsforpost-partumhemorrhage),arolethatwouldbeanaturalfitforUSAID’scoremission.ImprovingUSG’scollaborativeeffortswiththeWHOislowhangingfruitthatcouldhavealargepayoff.
• Conclusion3:ThedecliningUSGfundingforR&D,includingglobalhealthproductdevelopment,isanexistentialthreattotheUSG’simpact,influence,andcredibilitywithintheR&DlandscapeandjeopardizestheUSG’sreputationasagloballeaderininnovation.Itisnoexaggerationtosaythatfallingfundinglevelshavereachedcrisispoint,hamstringingagencyeffortsandsendingasignaltotheworldthattheUSmayberelinquishingitsleadershiprole.Recommendations:Therehasneverbeenamoreimportanttimefortheadvocacycommunitytomakethepublichealth,economic,business,andmoralcaseforUSGsupportforglobalhealthR&D.Giventheearlyindicationsthateconomicandbusinessinterestswilldominatethenewadministration’sapproachtoglobalhealth,thereisatime-criticalneedtodocumentanddemonstratetheextraordinaryreturnstoinvestinginglobalhealthR&D.Forexample,outofeverydollarthatUSGinvestsinglobalhealthR&D,around89centsgoestosupportingjobsintheUS,boostingU.S.researchandtechnologicalcapacity,andprovidingadirectinvestmentintotheUSeconomy.
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• Conclusion4:BARDA’secosystemofpushandpullmechanismsandtheOtherTransactionAuthorityusedbyBARDAandtheDefenseAdvancedResearchProjectsAgencytoestablishlongtermpartnershipswithindustryhavebeensuccessfulincentivemechanisms.BARDA’sintegratedmodelofpushandpullmechanisms,whichrequiressignificantfunding,hasbeeneffectiveinaddressingmarketfailuresforanumberofconditions.TherehasbeenenoughflexibilitytoallowitsmandatetobeexpandedtoincludeAMR,whichmayhaveopenedthedoortofindingwaystoincludeadditionalglobalhealthchallenges.Recommendations:Successfulincentivemechanismsshouldbeexpandedtootherdiseasesandreplicatedbyotheragenciesandoffices.Notallmarketfailureshavethesamecauses,andaBARDA-typemodelusedfordifferentobstaclesmayneedrefinementtomakeitspecifictotheactualchallenge.
• Conclusion5:Betterleveragingofwhatisworkingwellisaprinciplethatcanalsobeappliedwhenitcomestotheunder-useofeffectiveagencies.Inparticular,theDoD’smedicalresearchcapabilitiesareunder-recognizedandunder-used.Recommendations:ThenewAdministrationhaspledgedahugeincreaseindefensespending.Whiletherearecertainlyrisksinthe“securitization”ofglobalhealth(itcanbedangeroustoconflatetheprinciplesofpublichealthwiththoseofnationalsecurity),thisincreasemayrepresentanavenuetoboostUSGsupportforglobalhealthR&DifsomeofitcanbedirectedtoDoD’sglobalhealthresearch.
• Conclusion6:AlthoughtheUSGisgenerallyseenasagiantbureaucracy,ithashadtheforesighttoexpanditsglobalhealthR&Dremit.Legislationhasbeenamendedandagencymandateshavebeenrevisedtoincludeadditionaldiseases.Recommendations:Importantlessonscouldbelearnedfromananalysisofhowtheseshiftshappened—forexample,whowerethekeyactorsinvolvedandwhatweretheleversthatallowedchangetohappen?TheselessonscouldbeappliedtofindotherlegislativechangestostrengthenUSGtosupportforglobalhealthR&D.
• Conclusion7:ThereisnostandarddefinitionofwhatconstitutesglobalhealthR&DuseduniformlyacrossUSGagencies,includingtheOMB.USGneedsacleardefinitionandtypologyofglobalhealthR&D,toallowbettertrackingoffundingflowsandhelpdrivemoreexplicitprioritization.Recommendations:Adefinitionandtypologyshouldbeurgentlydeveloped,whichwouldgoalongwaytoenhancingtheeffortsofresearchers,advocacygroups,andthegovernmentitselftotrackfundinglevels,distributions,andtrends.Thetimingisrightforagreeingonsuchadefinition,giventhatthedonorcommunityiscurrentlyupdatingthewaythatitmeasuresofficialdevelopmentassistancetoincludefundingforglobalpublicgoods,suchasglobalhealthR&D.
• Conclusion8:ThefutureofUSGsupportforglobalhealthR&Dmustincludeatransitiontogreatersupportfordevelopingin-countryR&Dandregulatorycapacity.Thiswouldhelpwithlongertermsustainabilityplans.Recommendations:Inthe2015-2030SustainableDevelopmentGoalsera,anincreasingproportionofUSdevelopmentassistanceforhealththatisdirectedtoindividualcountriesshouldbespentondevelopingdomesticR&Dcapabilities.Fogartywouldbeideallyplacedtoprovideleadershipforsuchastrategy.
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• Conclusion9:AdvocacyforglobalhealthR&Dhasanimpressivehistoryofsuccess—andwillhaveaparticularlyimportantrolewiththenewAdministration.Thereisanurgentneedtocontinuedeveloping,testing,andrefiningadvocacyeffortstoinfluencemajordecisionmakerssuchastheCongress.Recommendations:Buildinganevidencebaseon“whatworks”inmobilizingUSGsupportforglobalhealthR&D—forexample,whetheritisemphasizingthenumberoflivessavedortheboosttotheUSeconomy—hasgainedincreasingimportancegivenhowlittleisknownaboutthenewAdministration’sglobalhealthcommitment.OnestrategytoconsideristofocusonthelinkbetweenadequateinvestmentinR&DasacriticalprecursorfortheUSGtomaintainitspreeminentpositionasaglobalinnovator.
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IntroductionOverthepasttwodecades,globalhealthhasbeentransformedbyincreasedattentionandfunding,ariseinthenumberofglobalhealthorganizations,economicgrowthoflow-andmiddle-incomecountries(LMICs),andtheadventofpowerfulnewhealthtechnologies.Aidforglobalhealthtripledduringthe“goldendecade”ofglobalhealth(2000-2010),fromabout$10billionto$30billionannually,muchofittargetedathighlyeffectiveinfectiousdiseasecontrolinitiatives.1ManynationalgovernmentsinLMICsincreasedtheirfocusonhealthsectorimprovements,oftenthroughincreaseddomestichealthfinancing.2Andnewtechnologiesbecameavailable,includingthedevelopmentandlarge-scaledeploymentofhighlyactiveantiretroviralmedications,long-lastinginsecticide-treatedbednets,andartemisinin-basedcombinationtherapiesformalariatreatment.3
WhiletherehasbeenadramaticdeclineinavertabledeathsinLMICs,poorpopulationsinLMICsstilldiedisproportionatelyfrompotentiallypreventableandtreatablescourgesofpoverty.Thesescourgesincludemeasles,malaria,tuberculosis(TB),diarrhea,andpost-partumbleeding.Forexample,in2012,infectionsandreproductive,maternal,newbornandchildhealth(RMNCH)conditionsinLMICsaccountedfor34percentofdisability-adjustedlifeyears(DALYs)—thenumberof“healthy”yearsthatapersonlostduetoillness—andfor23percentoftotaldeathsworldwide.4Poorpopulationsarealsohit“firstandworst”byoutbreaksofemerginginfections,asseenwiththerecentEbolaoutbreakinWestAfrica.
Whilesomeofthesedeathscouldbeavertedbyimprovingthedeliveryofexistingmedicines,vaccines,andotherhealthtools,newproductstoaddressunmetneedarealsocritical.Appropriatetoolsandtechnologiesmaynotexist,orexistingtoolsmaynotaccountforcontextualfactorsinLMICsthatmaylimittheuptakeoruseoftheseinnovations.Amajorbarriertoinvestingintheresearchanddevelopment(R&D)ofnewproductsfordiseasesofpovertyisthelackofsufficientincentivesandsubsequentmarketfailuretoproducenewtechnologiesforglobalhealthdiseasesandconditions.5-7Thetime,cost,technicalchallenges,andriskoffailureduringproductdevelopmentcreateaformidabledisincentivetoproductdevelopers.Asaresult,researchontheregulatoryapprovalsofnewdrugsandvaccinessince1975hasshownthatfewofthesenewproductsareforneglecteddiseasesofpoverty(Table2).8-11TheindependentresearchgroupPolicyCuresResearchnotesthatthereare145“missing”drugs,vaccines,diagnostics,microbicides,vectorcontrolagents,andtechnologiesthatareneededtoreachthehealthtargetsintheSustainableDevelopmentGoals(SDGs).12
AlthoughtheUnitedStatesgovernment(USG)istheworld’slargestfunderofglobalhealthR&D,thetotalamountrepresentsatinyfractionoftotalUSGexpenditure,anditsfundingforglobalhealthR&Disindecline.TheUSGisamajorfunderofbothglobalhealthprogramsandglobalhealthR&D.From2010-2014,itallocatedanannualaverageofjustunder$10billiontoimproveoverallhealthoutcomesintheworld’spoorestandmostvulnerablepopulations.13In2014,itwasresponsibleforabout45percentofallinternationalfundingforneglecteddiseaseR&D($1.5billionoutofatotalof$3.4billion).14However,thisamountofR&Dfundingisequivalenttolessthan0.01percentoftheU.S.nationalbudgetand,leavingasideEbola,thelevelsofUSGfundingforglobalhealthR&Darefalling.Mostofthefundingisdirectedtowardbasicscienceandearly-stagedevelopmentratherthangettingpromisingproductstomarket,andanumberofcriticallyneededproducts,suchasnewcontraceptivesanddrugstotreatpost-partumbleeding,havereceivedlittleR&Dfunding.7,15
Thisreport,commissionedbytheGlobalHealthTechnologiesCoalition(GHTC),aimstoidentifyopportunitiesforstrengtheningtheUSG’sroleinsupportingglobalhealthproductdevelopment.Itdoessothroughathree-stepapproach:
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• First,itexaminesthecurrentlandscapeofUSGfundingforsuchR&D,includingfundinglevelsandtrends,thecomparativeroleofthedifferentUSGagenciesinsupportingR&Dforglobalhealth,andthedecision-makingprocessesandtimelinesthatinfluencethissupport.
• Second,itdescribesincentivemechanismsandbarrierstoincreasingUSGfundingandcoordinationofglobalhealthR&D.
• Finally,basedonthefindingsfromthefirsttwosteps,itputsforwardaninitialsetofideasonopportunitiesfortheUSGtostrengthenitsroleinthefundingandcoordinationofglobalhealthR&D.Weaimtofurtherdevelopandrefinetheseideasinfutureresearch.
Thereporthassevensections,followedbyourconclusions.InSection1,webrieflydescribethemethodsthatweusedtoconductourstudy,acombinationofadeskreviewandkeyinformantinterviews.InSection2,weprovidenewdataonlevelsandtrendsinUSGfundingforglobalhealthR&D.Section3givesadetailedagency-by-agencyaccountoffunding,decision-making,andcoordination.InSection4,wedescribetheUSG’sappropriationandbudgetprocessandhowtheseinfluencesupportforglobalhealthR&D.Section5presentsoursynthesisofkeycross-cutting,cross-agencyfindingsoncatalystsandbarrierstoUSGagencysupportforglobalhealthR&D.InSection6,webrieflysummarizeperspectivesofkeyinformantsfromoutsidegovernment—specifically,fromindustry,foundations,andproductdevelopmentpartnerships(PDPs)—focusingonhowtheirperspectivesdivergefromthoseoftheUSGkeyinformants.Section7givestherecommendationsofkeyinformantsforreformsthatcouldimprovethewayinwhichtheUSGsupportsglobalhealthR&D.Finally,wepresentourninekeyconclusions—eachaccompaniedbyourrecommendationsonhowUSGcouldstrengthenitsroleinglobalhealthproductdevelopment.
OurchieffocusinthisreportishowUSGissupportingproductdevelopment,ratherthanthedeliveryofneworexistinghealthtechnologies.Werecognizethatresearchondevelopmentanddeliverymustgohandinhandfortechnologiestohaveanimpactinimprovingglobalhealth,andwedotouchonthistopicinourreport.Nevertheless,ourremitwastofocustothewaysinwhichtheUSGisfinancingandcoordinatingproductinnovationforglobalhealth.
Table2.NewTherapeuticProductsApprovedorRecommendedbyDifferentRegulatoryBodies,byDiseaseCategory,2000-2011
NCE
(n=336)OtherNewProduct
(n=420)*VaccineorBiological
(n=94)†Total
(n=850)
NeglectedDiseases
Malaria 3(1%) 9(2%) 0 12(1%)
Tuberculosis 0 7(2%) 0 7(1%)
DiarrhealDiseases 1(<0.5%) 3(1%) 3(3%) 7(1%)‡
NeglectedTropicalDiseases 0 5(1%) 0 5(1%)§
Other 0 1(<0.5%) 5(5%) 6(1%)¶
Subtotal 4(1%) 25(6%) 8(9%) 37(4%)
OtherInfectiousDiseases 35(10%) 48(11%) 66(70%) 149(18%)
AllOtherDiseases 297(88%) 347(83%) 20(21%) 664(78%)
Source:TableoriginallypublishedinPedriqueetal(2013)9NCE:newchemicalentity*Newindication,newformulation,orfixed-dosecombination.†Includesimmunoglobulinsandotherbiologicalproducts.‡Fordiarrhea,cholera,cryptosporidiosis,andgiardiasis.§ForhumanAfricantrypanosomiasis,Chagasdisease,andleishmaniasis.¶ForJapaneseencephalitis,hemorrhagicfevers,andsnakebite.
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Section1.HowWeConductedthisStudyWeconductedadeskreviewofpeer-reviewedandgreyarticlesandcombinedthefindingswiththosefrom36keyinformantinterviewswithstakeholdersfromgovernment,industry,foundations,andPDPs.
DESKREVIEW
WeconductedadeskreviewofrelevantEnglishlanguageliteraturepublishedoverthelast10years.WedevelopedkeysearchtermstoidentifyarticlespublishedinEnglishbetween2006and2016inPubMed,Embase,andEbscoGlobalHealthdatabases;USGdatabases;andgreyliteraturepublishedbyleadingglobalhealthorganizations.Theprojectteamalsoidentifiedadditionalarticlesfrombibliographiesofselected,highlyrelevantarticles.Searchtermsincluded:neglecteddiseases;neglectedtropicaldiseases;globalhealth;individualdiseases,suchasHIV/AIDS,tuberculosis,andmalaria;productordrugdevelopment;researchanddevelopment;financialincentives;globalburden;appropriations;andfunding.Theinitialsearchproducedseveralthousandsofarticles.Weexaminedarticletitlesandabstractsandusedthesetoselectfulltextsofarticlesbasedonrelevancetothisproject.Ourfinalreviewincluded147fulltextarticles.
KEYINFORMANTINTERVIEWS
Weconducted36semi-structuredinterviewswithstakeholdersfromthreesectors—theUSG,industry,andfoundations/PDPs(Table3)—usingoneofthreeinterviewguidesthatwedevelopedforthisstudy(oneforeachsector).Weidentifiedkeyinformantsthroughreferralsandacademicreferences.MostkeyinformantsworkedintheUnitedStates.Interviewsweremostlyone-on-one,althoughwealsoconductedthreegroupinterviews.Severalstakeholdersprovidedinsightsfrommultipleperspectives,havingservedbothinthepublicandprivatesectorsinnumerouscapacities.Figure2showstheguidingframeworkforthesekeyinformantinterviews.
Table3.KeyInformantsInterviewedfortheStudy,bySector
SectorNo.of
Interviews Institutions
USG 22 HHS(includingBARDA),OMB,USAID,NIH,CDC,FDA,State,formerrepresentativeofDoD
FoundationsandPDPs 8 GNNTDs,BMGF,MMV,AAAS,MSF,DNDi,FHI360,TaskForceforGlobalHealth
Industry 6 Anacor,BectonDickinson,NovartisInstituteofTropicalDiseases,Sanofi,Gilead,Janssen
Keytoabbreviationsisfoundonpagesiv-viofthisreport.
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DEFININGR&DFORGLOBALHEALTH
Forthisreport,“globalhealthR&D”referstoproductdevelopmentfornewmedicines,vaccines,diagnostics,andotherhealthtechnologiestotackleaspecificlistofpoverty-relatedandneglecteddiseasesandconditions.Asdescribedbelow,thislistincludesmostlyinfectiousdiseasesandselectedreproductivehealthconditionsthatdisproportionatelyaffectLMICs.Indeterminingwhichdiseasesorconditionstoinclude,particularlyinSection2(onfundinglevelsandtrends),weusedacombinationof:(a)thecorelistof34infectiousdiseasesintheannualGlobalFundingofInnovationforNeglectedDiseases(G-FINDER)reportproducedbythepolicyresearchgroupPolicyCuresResearch,(b)EbolaandotherAfricanviralhemorrhagicfevers(VHFs),and(c)thelistofreproductivehealthconditionsandunmetneedsspecifictodevelopingcountriesthatwereincludedinG-FINDER’s2014ReproductiveHealthReport.16
Figure2.GuidingFrameworkfortheKeyInformantInterviews
FUNDING DECISION MAKING
What is the process?
Where are the gaps?
How can we close the gaps?
Who makes the key decisions?
When are the decisions made?
COORDINATION
Which agencies are involved?
How do they coordinate?
What are the coordina!on
barriers and how can they be addressed?
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Box1summarizestherationalefortheinclusionofthesediseasesinthedefinition.Theterm“neglecteddiseases”inG-FINDERisbroaderthantheWorldHealthOrganization(WHO)definitionof“neglectedtropicaldiseases”—theWHOdefinitionhasjust17diseases.Somediseases,particularlypandemicinfluenzaandZika,arenotincludedintheG-FINDERdefinition,andsotheyarenotincludedinourdataonfundinglevelsandtrends(Section2).However,becausetheUSGhassupportedinnovationeffortstocontrolpandemicinfluenzaandZika,andbothdiseaseswerefrequentlymentionedinkeyinformantinterviews,theyarediscussedinothersectionsofthereport.
Ourreportfocusesonproductdevelopmentratherthanthedeliveryorimplementationoftechnologiesinthefield.Thereportthereforeexcludesfinancingforprogrammaticactivities,suchasthedeliveryofantiretroviralmedicationsorbednetstopreventmalariatransmission.
Box1.DefinitionofGlobalHealthR&DUsedinOurReport
Thisreportusestheterm“globalhealthR&D”torefertoproductdevelopmentforalistofdiseasesandconditionsincludedintheG-FINDERsurveysproducedbyPolicyCuresResearch.AsdescribedbyPolicyCuresResearch,thediseaseorconditionhastomeetthefollowingcriteriatobeincludedinthelist:
“(1)Diseasemorbidityandmortalitydisproportionatelyaffectpeopleindevelopingcountries;AND
(2)Thereisnoexistingproducttotreat/preventthatdisease,ORaproductexistsbutispoorlysuitedfordevelopingcountryuse;AND
(3)ThereisnocommercialmarkettostimulateR&Dbyindustry.”17
ThecoresetcomprisesHIV/AIDS,tuberculosis,andmalaria;diarrhealdiseases;kinetoplastids(leishmaniasis,sleepingsickness,andChagasdisease);wormsandflukes;dengue;bacterialpneumoniaandmeningitis;Salmonellainfections;hepatitisCgenotypes4,5and6;leprosy;trachoma;cryptococcalmeningitis;Buruliulcer;leptospirosis;andrheumaticfever.
Inadditiontothecoresetofdiseases,wehaveincludedEbolaandotherAfricanviralhemorrhagicfevers(VHFs),andthereproductivehealthneedsofdevelopingcountries,asdefinedbyPolicyCuresResearch:post-partumhemorrhage,contraception,syphilis,andothersexuallytransmittedinfections.
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Section2.LevelsandTrendsinUSGFundingforGlobalHealthR&DThissectionsummarizesthemostrecentlyavailable,high-qualitysurveydataonhowmuchtheUSGinvestsinglobalhealthproductdevelopment;whichdiseasesandwhichtypesofresearchreceivethemostfunding;andhowlevelsoffundinghavechangedinrecentyears.ThedataonR&Dfundingforinfectiousneglecteddiseases,includingEbolaandotherAfricanviralhemorrhagicfevers(VHFs),aretakenfromtheG-FINDERsurvey,coveringtheperiod2007-2015.DataonreproductivehealthfundingwerecollectedasasupplementtotheG-FINDERsurvey,andwereonlyavailablefor2013and2015.AnyanalysiscomparingtheUSGwiththerestoftheworld,analysisoftrendsovertime,oranalysisofinvestmentfocusbyproducttypeexcludefundingforreproductivehealthR&D.Furthermore,asnotedinpriorG-FINDERsurveys,fundingisgenerallydifficulttotrackbecauseagencieslackspecificbudgetlineitemsforglobalhealthR&D.
ThroughoutSection2,thefundingdatareferonlytoproductdevelopment.ThedatadonotincludeothertypesofR&D(suchasimplementationoroperationsresearch).
HOWMUCHDOESTHEUSGINVESTINGLOBALHEALTHPRODUCTDEVELOPMENT?
TheUSGisbyfarthemostsignificantfunderofglobalhealthproductdevelopmentglobally.Since2007,ithasinvested$13.9billioninR&Dtodelivernewglobalhealthtechnologies.Thiswasnearly13timesgreaterthanthecontributionofthesecondbiggestgovernmentfunderoverthesameperiod(theUnitedKingdom,with$1.1billion).Itwasalsoclosetohalf(48percent)oftotalglobalfundingfromallsources.
In2015,theUSGinvested$1.7billioninglobalhealthproductdevelopment(Figure1).Ofthisamount,$1.4billion(83percent)wasforneglecteddiseases(asdefinedbythe2016G-FINDERreport),$276million(16percent)wasforEbolaandotherAfricanVHFs,andtheremaining$10million(onepercent)wasforreproductivehealthtechnologiesdesignedtomeettheneedsofLMICs.
TheUSG’s$1.7billioninvestmentrepresentedthree-quarters(74percent)ofallgovernmentfundingworldwidein2015(Figure3).Thenextlargestgovernmentfunderin2015wastheEuropeanCommission,whichprovided$171million.
Figure3.GovernmentFundingforGlobalHealthR&D,2015
Abbreviations:EC:EuropeanCommission,UK:UnitedKingdom,US:UnitedStates.Source:authors’ownanalysisbasedondatafromG-FINDER2016
US74%
EC7%
UK5%
Multilaterals1%
Allothergovernments
13%
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WHATDOESTHEUSGFUND?
TheprimaryfocusforUSGfundingforglobalhealthR&DisHIV/AIDS,reflectingtheunprecedentedchallengethatthisemergingdiseasepresentedandtheneedforever-improvingdrugtreatments(antiretroviraltherapies),diagnostics,andpreventivetechnologies.USGfundingforproductdevelopmentforHIV/AIDSisnowheavilyfocusedonvaccinedevelopmentandbasicresearch.Thediseasehasconsistentlyreceivedaround55percentofUSGneglecteddiseaseR&Dfundingineachofthelastnineyears.HIV/AIDSstillaccountedfor45percentofUSGfundingforallglobalhealthR&Din2015(Figure4),despitethefactthat2015fundinglevelsincludedsignificantnewfundingforEbolaandotherAfricanVHFs.Table4givesasummaryofUSGfundingfor2015bydisease,maintypeofresearch,andkeyagenciesinvolved.
Figure4.USGFundingforGlobalHealthR&Din2015byDisease
Source:authors’ownanalysisbasedondatafromG-FINDER2016*Other:otherneglecteddiseasesandreproductivehealth
HIV/AIDS46%
Malaria12%
Other*12%
Tuberculosis13%
EbolaandotherAfricanviralhemorrhagicfevers(VHFs)
17%
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Table4.USGFundingin2015forGlobalHealthProductDevelopment,byDisease—ShowingPrimaryInvestmentAreasandKeyUSGAgenciesInvolved
DiseaseCategory
Total(millions)2015a
ShareofTotalUSG
R&DSpending(%)2015a
PrimaryInvestment
Area(2015)
Total(millions)2014b
USGFundingas%ofTotalGlobalR&DSpendingfortheSpecificDiseaseor
Conditionb
USGAgenciesFundingProductDevelopment(2015)a,c
NIH DOD USAID CDC BARDA
HIV/AIDS $753.8 45.0% Vaccines $792.8 73.4% X X X X
EbolaandOtherAfricanViralHemorrhagicFevers(VHFs)
$275.5 16.5% Drugs $100.6 60.0% X X X X
TB $217.7 13.0% Basicresearch
$323.2 35.5% X X X
Malaria $194.5 11.6% Basicresearch
$177.9 29.2% X X X
Dengue $46.7 2.8% Basicresearch
$40.5 45.8% X X X X
DiarrhealDiseases(Cholera,Shigella,rotavirus,etc.)
$44.6 2.7% Basicresearch
$180.0 46.4% X X
Kinetoplastids(Chagas,leishmaniasisandhumanAfricatrypanosomiasis)
$38.6 2.3% Basicresearch
$41.6 27.9% X X
HelminthInfections(soil-transmittedhelminths,lymphaticfilariasis,onchocerciasis,schistosomiasis)
$28.4 1.7% Basicresearch
$31.1 32.0% X X
SalmonellaInfections $28.2 1.7% Basicresearch
$30 44.4% X
HepatitisCGenotype4 $4.6 0.3% Vaccines $6.5 16.3% X
Trachoma $4.6 0.3% Vaccines $6.4 93.4% X
Leprosy $4.2 0.3% Basicresearch
$5.6 52.7% X
CryptococcalMeningitis
$3.5 0.2% Drugs 4.1 71.2% X
BacterialPneumonia&Meningitis
$1.2 Less.1% Vaccines $2.1 2.7% X
RheumaticFever $1 less0.1% Vaccines $.5 37% X
Leptospirosis $.3 less0.1% Diagnostics $.3 20.7% X
BuruliUlcer N/A N/A N/A $4.1 NA
aDatafromG-FINDER2016,bDatafromG-FINDER2015,X=fundsR&D(asdefinedbyG-FINDER),cItisimportanttonotethatagenciesalsoinvestedsignificantlyinglobalhealthresearchnotrelatedtothedevelopmentandintroductionofnewhealthtechnologies(suchasprogrameffectivenessevaluationandotherhealthsystemsresearch),whichisoutsidethescopeoftheG-Finderanalysis.Forexample,whileUSAIDdidnotprovideanyproductdevelopmentfundingin2015forEbola/VHFR&D,theagencycontributedtoprogramdeliveryonthegroundandrelatedevaluationresearch.
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ThepresenceofexistingR&DprogramsinEbolaandotherAfricanVHFs—coupledwiththeauthorizationofemergencyfunding—allowedtheUSGtorapidlymobilizesignificantR&Dresourcesinresponsetothe2014WestAfricanEbolaoutbreak.G-FINDERonlystartedtrackinginvestmentinEbolaR&Din2014(andonlyexpandedthiscategorytoincludeotherAfricanVHFsin2015).TheestimatedannualUSGinvestmentinR&DforEbolaandotherAfricanVHFspriorto2014wasonlyaround$5-10millionperyear—representinglessthanonepercentofannualUSGfundingforglobalhealthR&D,oraboutthesameamountitinvestedinleprosyR&D.In2015,theUSGinvested$275millioninEbolaandotherAfricanVHFs,makingVHFsthesecondhighestfundeddiseasecategoryafterHIV/AIDS,aheadofmalariaandTB.
Basicresearchandvaccinedevelopmentcollectivelyaccountedforjustovertwo-thirds(68percent)ofallUSGfundingforglobalhealthR&Din2015,withvaccinedevelopment(41percent)receivingbyfarthelargestshare(Figure5).TheinfluxofVHFfundingin2015didlittletochangethelong-termaveragesinthebreakdownofspending(e.g.,basicresearchcontinuedtoreceivejustoveraquarterofallfunding).ThepictureforVHFsalonewasdifferent:withafocusonrapidlyadvancingexistingcandidatesthroughthepipeline,basicresearchaccountedforjust12percentofallUSGfundingforVHFR&D,whilevaccinesanddrugsaccountedforaroundaquartereach.
Giventhat80percentofUSGfundingforproductdevelopmentgoestotheNIH(seeSection3),itisperhapsnotsurprisingthattheUSGdirectstwiceasmuchfundingtobasicandearlystageresearchthanitdoestolate-stage(clinical)productdevelopment.AsdescribedinSection3,theonlyagencytoinvestmoreinclinicaldevelopmentthanbasicandearlystageresearchisUSAID.However,USAIDfundinghasonlyaminimalimpactontheoverallpicture,giventhatUSAIDisresponsibleforjustfivepercentofallUSGfundingforglobalhealthR&D.
Figure5.USGFundingforGlobalHealthR&Din2015byTypeofResearch
Source:authors’ownanalysisbasedondatafromG-FINDER2016*Other:otherneglecteddiseasesandreproductivehealth
Vaccines41%
Drugs15%
Microbicides8%
Diagnostics4%
Vectorcontrolproducts
1%
Other*4%
Basicresearch27%
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RECENTTRENDSINUSGFUNDING
USGfundingforglobalhealthR&Din2015wasthehighesteverrecorded—butasurgeinfundingforEbolaandotherAfricanVHFshidalargedeclineinfundingforotherneglecteddiseases(thistrendanalysisexcludesinvestmentinreproductivehealthR&D,whichwasonlycollectedfor2013and2015).TwokeyeventshaveshapedUSGfundingforglobalhealthR&Dsince2008:the‘greatrecession’ofthelate2000sandthe2014WestAfricanEbolaoutbreak.StimulusspendingbytheUSGinresponsetothefinancialcrisis—mostnotablyundertheAmericanRecoveryandReinvestmentActof2009—ledtoasharpincreaseinUSGfundingforglobalhealthR&D,whichtotaled$1.65billionin2009.The2014Ebolaoutbreakelicitedasimilarlyrobustresponse,pushingUSG2015fundingforglobalhealthR&Dto$1.66billion(Figure1);thiswasnotonlyitsbiggestannualcontributionsince2009,butalsothelargesteverrecorded.
TherehasbeenaremarkablemobilizationofR&DfundsinresponsetotheEbolathreat.Fromnegligiblelevelspriorto2014,USGfundingforR&DtotackleEbolaandotherAfricanVHFstopped$275millionin2015.ThisamountismorethantheUSGinvestedinanyotherdiseaseexceptHIV/AIDS.However,thesurgeoffundingforEbolaisaone-time,emergencyappropriation,notsustainable,annuallyappropriatedfunds.
Incontrast,USGfundingforglobalhealthproductdevelopmenthasbeenfallingsteadilysinceits2009peak.Adjustedforinflation,annualUSGinvestmentinsuchproductdevelopmenthasfallenineveryyearbutonesince2009(Figure1)andisnowmorethanaquarterofabilliondollarsbelowits2009peak(down$263million,orareductionof16percent).
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Section3.USGAgencies:GlobalHealthR&DFunding,Decision-making,andCoordinationInthissection,wefocusonthoseUSagenciesthatplaythemostimportantroleinglobalhealthR&DaswellastheWhiteHouseOfficeofManagement&Budget(OMB).Wereport2015fundinglevelsforthelargestfundersofglobalhealthR&D.WedescribehowdecisionsonglobalhealthR&Dfundingaremadewithineachagencyandthewaysinwhichagenciescoordinatewitheachother,andwithorganizationsoutsidetheUSG,intheresearchenterprise.Figure6showstheagenciesthatarethemainfocusofdiscussioninourreportandFigure7showstheshareoffundingbyagency.
Figure6.USGDepartments,Agencies,Offices,andInstituteswithaKeyRoleinSupportingGlobalHealthR&D
Abbreviations:BARDA:BiomedicalAdvancedResearchandDevelopmentAuthority,CDC:CentersforDiseaseControlandPrevention,DoD:DepartmentofDefense,FDA:FoodandDrugAdministration,HHS:USDepartmentofHealthandHumanServices,NIAID:NationalInstituteofAllergyandInfectiousDiseases,NIH:NationalInstitutesofHealth,OGA:OfficeofGlobalAffairs,OGAC:OfficeoftheU.S.GlobalAIDSCoordinatorandHealthDiplomacy,PEPFAR:TheUSPresident’sEmergencyPlanforAIDSRelief,PMI:President’sMalariaInitiative,USAID:USAgencyforInternationalDevelopment.Source:adaptedfromafigurebytheGlobalHealthTechnologiesCoalition185
White House
USAID
State
PMI
OGAC
PEPFAR
DoD
OMB in Executive Branch
HHS
OGA
BARDA CDCFDA NIH
NIAID
Congress
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DEPARTMENTOFHEALTHANDHUMANSERVICES
TheprimaryfocusoftheDepartmentofHealthandHumanServices(HHS)istoenhanceandprotectthehealthandwell-beingoftheUSpopulationbutmanyoftheDepartment’scentersandofficesplayasignificantroleinglobalhealthR&D.ThefourmostimportantforglobalhealthR&D,whichwefocusonbelow,aretheBiomedicalAdvancedResearchandDevelopmentAuthority(BARDA),theNationalInstitutesofHealth(NIH),theCentersforDiseaseControlandPrevention(CDC),andtheFoodandDrugAdministration(FDA).HHSalsoleadstheNationalVaccineProgramOffice(NVPO),whichplaysaroleinglobalimmunizationefforts.18TheNVPOencouragescollaborationandcoordinationamongfederalagenciestoreducetheburdenofvaccine-preventabledisease,includingthroughthedevelopment,production,andprocurementofvaccines.19IncollaborationwiththeNationalAcademyofMedicine(NAM),theofficeiscurrentlydevelopingasoftwaretooltohelpprioritizevaccinedevelopmentefforts(theStrategicMulti-AttributeRankingToolforVaccines).20
ThemainofficeoverseeingglobalhealthinHHSistheOfficeofGlobalAffairs(OGA),apolicyandcoordinationofficethatidentifiesoverseaschallengesandopportunities;whileitisnotspecificallymandatedtoengageinresearch,itisengagedinseveralglobalhealthR&Dactivities.21Forexample,ithasfacilitatedproductdevelopmentcollaborationswithChina,India,Mexico,andSouthAfrica;ithasworkedcloselywithWHO’sConsultativeExpertWorkingGrouponResearchandDevelopment:FinancingandCoordination;anditco-chairs,alongwiththeEuropeanUnion(EU),theTrans-AtlanticTaskforceforAntimicrobialResistance,whosemandateincludesdeveloping“strategiesforimprovingthepipelineofnewantimicrobialdrugs.”22,23
Figure7.USGFundingforGlobalHealthR&DbyAgency,2015
Source:authors’ownanalysisbasedondatafromG-FINDER2016
NIH80%
DOD8%
BARDA6%
USAID5%
CDC1%
AllotherUSGfunders<1%
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BiomedicalAdvancedResearchandDevelopmentAuthority
OverviewandFundingLevels
BARDAleadsUSGcivilianR&Donmedicalcountermeasures(MCMs),including“vaccines,therapeutics,diagnostics,andnon-pharmaceuticalcountermeasures,againstabroadarrayof[domestic]publichealththreats,whethernaturalorintentionalinorigin.”24ItwasestablishedunderthePandemicAll-HazardsPreparednessActof2006andishousedinHHS’OfficeoftheAssistantSecretaryforPreparednessandResponse.25ItisheadedbytheOfficeoftheDirector.InFY2016,BARDA’sbudgetforMCMswas$1.3billion,outofwhich$521.7millionwasearmarkedforadvancedR&Dof12high-prioritythreatsidentifiedbytheDepartmentofHomelandSecurity.Thesethreatsincludeanthrax,EbolaandotherVHFs,radiation,andchemicalexposure.26Asdescribedbelow,onlyasmallfractionofthisfundingisrelevanttoglobalhealthR&D.
BARDAdoesnothaveaclearmandatetoengageinR&DforhealthtechnologiestargetingtheneedsofLMICsandthuswasnotamajorplayerinsupportingglobalhealthR&DforconditionsofLMICsuntilthe2014WestAfricanEbolaoutbreak.In2015,itsinvestmentsinEbolaandotherVHFsmadeBARDAthethirdlargestUSGfunderofglobalhealthR&D.Thiswasduetoone-time,emergencyfunding.Withoutsimilarfundinginthefuture,itisunclearwhetherBARDAwillcontinuetoplayaroleinfundingglobalhealthproductdevelopment.In2015,BARDAinvested$104millioninR&DforEbolaandotherAfricanVHFs,providing6percentoftotalUSGfundingforglobalhealthR&D.BARDAwasthereforethethirdlargestfunderofglobalhealthR&DbehindonlyNIHandDoD.AllofBARDA’sglobalhealthR&Dfundingin2015wasforEbolaandotherAfricanVHFs.Figure8showsthecontributionofBARDAtoR&DforEbolaandotherAfricanVHFscomparedwiththatofotherUSGagencies.
StakeholdersdescribedBARDAastheonlycivilianagencyprimarilyfocusedonlatestageR&Dformedicalproducts.27,28Theseproductsareaimedattacklingpandemicinfluenza,emerginginfectiousdiseases(EIDs),andchemical,biological,radiological,andnuclearagents.28
BARDAhelpstoaddressgapsintheUSG’sdevelopmentandprocurementprocessforMCMsandtobridgethe“valleyofdeath”thatseparatescandidatesidentifiedinearlyresearchfrompotentialFDAlicensure/approval.Itdoessobyproviding“funding,technicalsupport,andservicesnecessarytoadvancecandidateproductsthroughthedevelopmentalpipeline.”24ThisworkisundertakenundersevenprogramdivisionsatBARDA:Chemical,Biological,RadiologicalandNuclear(CBRN)
Figure8.USGFundingforEbolaandOtherAfricanVHFs,2015
Source:authors’ownanalysisbasedondatafromG-FINDER2016.Note:USAID(andCDC/DoD)isfundingEbolaR&DthroughtheEbolaGrandChallengeinitiative.However,thisfundingisforinterventionssuchasfieldtreatmentfacilitiesandpersonalprotectiveequipment,whichareoutsidethescopeofouranalysis(ouranalysisfocusesonproductdevelopment:newdrugs,vaccines,anddiagnostics,aswellasbasicresearch).
NIH41%
BARDA38%
DOD18%
CDC3%
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Countermeasures;Influenza;StrategicScienceandTechnology;Manufacturing,Facilities,andEngineering;RegulatoryandQualityAffairs;ClinicalStudies;andModeling.29
GlobalHealthR&DFundingDecisions
BARDA’sinternalbudgetingandbudgetsaredrivenlargelybyits5-yearstrategicplan,firstdevelopedin2007andthenupdatedin2011.TheplanisdraftedinalignmentwiththeprioritiesoftheAdministration,theOfficeoftheAssistantSecretaryforPreparednessandResponse,andBARDAleadership.BARDAischargedbystatutewith“directingandcoordinatingthecountermeasureandproductadvancedresearchanddevelopmentactivities”ofHHS.29
BARDAconsidersseveralguidingprincipleswhenestablishingitsR&Dbudgetarypriorities.Asidefromsupportingthedevelopmentofproductstocombatthe12high-prioritythreatsdiscussedabove,principlesdrivinginvestmentinclude(i)engaginginpublic-privatepartnerships,(ii)supportingthedevelopmentanduseofadjuvantplatformstoenhancecurrentlylicensedproducts,and(iii)prioritizingmultipurposeproducts.Asanexample,BARDAwillsupportthedevelopmentofcandidateantimicrobials,butonlyaslongasprivatesectorpartnerssupportthedevelopmentoftheseproductsforbiodefensethreatagentindications.29
StakeholdersindicatedthatBARDA’sthree-stepmodelforproductdevelopmentisanattractiveecosystemtoincentivizecompaniestodevelopproductsintheabsenceofsignificantcommercialprofit.Thethreecomponentsofthemodelare:• Advanced(“push”)R&Dfundingtohelpproductscross“thevalleyofdeath”oncetheyentertheclinicaltrialsphase,
• Procurementfundsorapromisetopurchaseproducts(“pull”incentives)todevelopstockpiles,and• Technicalassistanceandinfrastructuresupport,whichprovidesaccesstoanimalmodel/clinicalstudynetworks,manufacturingfacilities,andregulatorysupport.
Althoughnotspecifictotheglobalhealthdiseasesandconditionsthatwefocusoninthisreport,withBARDAsupport,23productshavereachedFDAapprovaland18newproductshaveenteredthestrategicnationalstockpile.30,31ThissuccessisseenasbeingduetothecombinationofdirectfundingsupportforR&D,partneringwithindustryonproductdevelopment,andprovidingtechnicalassistance.31
Aninitialten-yearappropriationcommitment,withtheUSGasamonopsonysinglepurchaser,establishedBARDA’sProjectBioShield,aprocurementfund(pullmechanism)forCBRNthreats(e.g.,smallpoxvaccinedevelopment).32ThiscommitmentwasmadethroughtheProjectBioShieldAct,whichauthorizedtheappropriationofupto$5.6billionfromFY2004toFY2013inaspecialreservefund.SubsequentCongressesrescindedortransferred$2.3billion(overone-third)fromthisadvanceappropriation.33Keyinformantsarguedthattherecentshifttoannualappropriationshasweakenedtheproject.
InFY2016,ProjectBioShieldwasallocated$646.4milliontosupportR&DandtoprocuresevennewMCMsagainstCBRNagents,includingEbolavaccines.Anadditional$166.0millionwasallocatedforU.S.andglobaleffortstoplanforandfightpandemicinfluenzaandemerginginfectiousdiseases.26
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GlobalHealthR&DCoordination
BARDAischargedbystatutetocoordinatewithothers;itsroleistopromote“collaborationandcommunicationbetweentheUSGandpartiesinterestedintheadvanceddevelopmentandlicensureofneededmedicalcountermeasures.”29ItworkswithmanufacturersandtheNIH,CDC,FDA,DHS,DoD,andtoalesserextentUSDAandVeteransAffairs,toguidethetransitionbetweenearlypreclinicaldevelopmentthroughlaterstagedevelopment.Forexample:• BARDAhasdevelopedacollaborativerelationshipwithFDAtoenhanceflexibilityandensureregulatoryprocessesrunsmoothlybyworkingwithgroupsontheuniquechallengesofMCMs.
• ItalsoworkswiththeCDCtodevelopconceptsofoperationsandclinicaluseguidelinesandtoensurethattheCDC’sstockpileisreadytoreceiveproducts.
• OneofBARDA’sguidingprinciplesspecificallylaysouttheimportanceofensuringthatitintegratesitsportfoliowiththeDoDtooptimizetheuseofresources.
BARDAhasadoptedanintensiveapproachtoproject,programandportfoliomanagementcalleda“casemanagement”matrixorganizationalstructure.Thestructureensuresthatintra-andinter-agencystakeholdersarekeptinformedaboutprogressandchallengesthroughoutthecourseofproductdevelopment(e.g.,establishingcostandschedulemetricsforeachphaseofdevelopment,allowingUSGstakeholderstobeawareoflong-termbudgetaryimplications).Italsoprovidesanopportunityforcollaboratorstoidentifyandsharebestpracticesandhopefullyintervenewhenthingsarenotgoingwell.
BARDAisonecomponentofabroaderpublichealthcollaborativeeffortledbythePublicHealthEmergencyMedicalCountermeasuresEnterprise(PHEMCE).34PHEMCEbringstogetherleadersfromNIH,DoD,CDC,FDA,theUSDepartmentofVeteransAffairs,andtheUSDepartmentofAgriculturetoovercomebarriersencounteredacrosstheproductdevelopmentcycleforVHFs,pandemicinfluenza,andotherthreats.ItisrunbytheAssistantSecretaryforPreparednessandResponsewithinHHS.
BARDAprovidessupporttotheWHOtoimproveglobalvaccineproductioncapacityin.developingcountries,includingthroughsupportingtrainingcourses.35Itsinitialvaccineproductiontrainingcourseincluded16participantsfromsevencountries(Egypt,Romania,Russia,Serbia,SouthKorea,Thailand,andVietnam).
BARDAisakeyactorinanewpublic-privatepushmechanism,calledCombatingAntibioticResistantBacteriaBiopharmaceuticalAccelerator(CARB-X).BARDA’spartnersaretheNIAID,theWellcomeTrust,theMassachusettsBiotechnologyCouncil(MassBio),andtheCaliforniaLifeSciencesInstitute.CARB-Xisaproductacceleratoraimedattacklingantibioticresistance,focusingonpreclinicaldiscoveryanddevelopmentofnewantimicrobialproducts.36,37Itiscurrentlyworkingtoestablishadiverseportfoliowithmorethan20high-qualityantibacterialproducts.
NationalInstitutesofHealth
OverviewandFundingLevels
ThemissionoftheNIHistoconductscientificresearchtoimprovepopulationhealth.Theagency’smandateistoconductbasicresearch;itisneitheradirectiveagencynoraproductdevelopmentagency.TheNIHreliesonthebestideasofitsscientists—a“bottomup”approachinwhichscientistsdeterminetheresearchratherthanbeingtoldina“topdown”waywhattostudy.Asaresult,NIHscientificprioritiesmaynottranslatetodevelopingproductsforLMICs.TheOfficeoftheDirectorisresponsible
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forpolicysettingforNIHandalsocoordinatesandmanagesthevariousprogramsoftheNIH’s27institutesandcenters.38Togethertheseinstitutesandcenterssupportthefullcontinuumofbiomedicalresearchfrombasicresearch,pre-clinicaltrials,clinicalresearch,post-clinicaltranslationalresearchtoresearchonclinicalandcommunitypractice.39Duringthefinancialyear2016(FY2016),theNIHhadatotalbudgetof$32.3billion,upfrom$30.4billioninFY2015.40
TheNIHisbyfarthelargestcontributortoglobalhealthR&DoutofalltheUSGagencies.Its2015investmentof$1.3billionrepresented80percentofUSGfundingforthatyear.Itspentabout4.3percentofitsoverallbudgetonglobalhealthR&Din2015.TheNIHhasprovided86percentofallrecordedUSGfundingforglobalhealthR&Dsince2007.
Givenitsdominanceasafunder,thediseasefocusoftheNIHlooksverysimilartothatoftheUSGoverall(Figure9).HalfofallNIHglobalhealthR&Dfundingin2015wasforHIV/AIDS($664million,50percent).The“bigthree”diseases(HIV/AIDS,TB,andmalaria)togetheraccountedforthree-quartersofsuchfunding($1.0billion,76percent).Aboutthreequarters(74percent)ofthefundingthatcouldbeallocated(i.e.,allocablefunding,whichexcludesunspecifiedfunding)wasforbasicandearlystageresearch.Thelargestshare(41percentoffunding)wasforvaccinedevelopment,withjust11percentfordrugs,sevenpercentformicrobicides,andfourpercentfordiagnostics.
FundingforEbolaandotherAfricanVHFs($113million)accountedforeightpercentoftotalNIHinvestmentinglobalhealthR&Din2015.WhilethisisarelativelysmallfractionofNIHsupport,theabsoluteamountwaslargeenoughtomakeNIHthemajorfunderofR&DforEbolaandotherVHFsamongalltheUSGagencies,contributing41percentoftheUSGtotal.
NIHfundingforR&Donotherneglecteddiseasesfollowsasimilarpattern:althoughthesediseasesreceiveonlyaminorshareoftotalNIHfunding,theNIHisgenerallyamongthetopglobalfundersformostofthesediseases.Indeed,NIHisthemostsignificantUSGfundingagencyforeveryareaofglobalhealthR&Dexceptreproductivehealthneedsindevelopingcountries.
KeyNIHinstitutesorcentersthatdealwithglobalhealthR&DaretheOfficeofAIDSResearch(OAR),theNationalInstituteofAllergyandInfectiousDiseases(NIAID),theFogartyInternationalCenter,andtheNationalCenterforAdvancingTranslationalSciences(NCATS).
Figure9.NIHFundingin2015forGlobalHealthR&DbyDisease
Source:authors’ownanalysisbasedondatafromG-FINDER2016.NDs:neglecteddiseases,DCs:developingcountries
HIV/AIDS50%
Tuberculosis15%
Malaria12%
EbolaandotherAfricanVHFs
8%
OtherNDs15%
ReproductivehealthneedsofDCs
<1%
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• TheOAR,whichhasrequestedabudgetof$62.25millionforFY2017,coordinatesallaspectsoftheNIH’sdomesticandglobalHIVresearchandproducestheannualtrans-NIHAIDSresearchbudgettogetherwiththeNIHDirector.
• TheNIAIDprovidesscientificleadership,policyguidance,andoveralloperationalandadministrativecoordinationtothevariousextramuralandintermuraldivisionsfocusingonbasicresearchforHIV/AIDS,infectiousdiseasesandallergy,immunology,andtransplantation.41NIAID’sothermandateistoprovidearesearchresponseinanemergency,soitmusthaveflexibledollarsreadilyavailableinordertorespond.Stakeholdersindicatedthereisnoprecisemeanstodetermineexactlyhowmuchfundingisallocatedforflexiblepurposesastherearediversewaystofundurgentneeds.NIH’sintramuralprogramisonemechanismthatallowsforgreateragilityinchangingresearchdirections.InFY2016,NIAIDreceived$4.615billion,orthesecondlargestbudgetofNIHcentersandinstitutes.42
• TheFogartyInternationalCenterbuildsinternationalpartnershipstofacilitatebasic,clinical,andappliedresearchandtraininginglobalhealthbybothUSandinternationalinvestigators.43ItisoneofthemostpoorlyfundedoftheNIHinstitutesorcenters,receivingabudgetofjust$70.11millioninFY2016.44
• ThemissionoftheNCATSistoenhancetranslationalresearchbycatalyzinginnovationsintechnologythatwillimprovethedevelopment,testing,andimplementationofdiagnosticsandtherapeuticsacrossawiderangeofdiseasesandconditions,includingneglecteddiseasesinLICsandMICs.Thecenter’sapproachisknownas“the3Ds”–developingnewapproaches,technologies,resources,andmodels;demonstratingtheirusefulness;anddisseminatingthedata,analysis,andmethodologiestothecommunity.ArecentexampleofanNCATSglobalhealthR&Dprojectwasthescreeningofahugecollectionofapprovedandinvestigationalmalariadrugstoidentifypromisingantimalarialdrugcombinations.Thecenterhadabudgetof$685.41millionforFY2016.45AlthoughNCATShasaprogramontherapeuticsforrareandneglecteddiseases,todatethishasfocusedmuchmoreonrarediseasesintheUSratherthanneglecteddiseasesofLMICs.Overall,theroleofNCATSinglobalhealthR&Dhasbeenmodest.
Nearly90percentofNIHfundingisdedicatedtoextramuralresearchthatfundsotheracademicandresearchinstitutions.ThisprioritizationlimitstheNIH’sroleinproductdevelopmentforglobalhealth,assuchproductdevelopmentismorelikelytohappeninPDPsandindustrythaninacademicsettings.
NIH’sdiversepeer-reviewedgrantandcontractfundingmechanismsareviewedasanorganizationalstrengthbyUSGstakeholders.NIHtypicallyfundsonlyabout17percentoftheproposalsitreceives.ThecurrentDirectorhasstatedthatthefractionofproposalsworthyoffundingiscloserto50percent,meaningthatalotofpotentiallyinnovativeandgroundbreakingideasthatcouldleadtoproductdevelopmentareleftunfunded.46
NIHdoesleverageseveralprograms,includingtheSmallBusinessInnovationResearch(SBIR)programandCooperativeResearchandDevelopmentAgreements(CRADAs),tosupportcommercializationofNIH-fundedproductsandtranslateresearchintonewproducts.7NIHalsoreceivesfundingasanimplementingpartnerofPEPFAR.13
GlobalHealthR&DFundingDecisions
NIH’sfundingallocationsrelyona“bottom-up”approach,wherebythecentersandinstitutesrelyonthesubmissionofcompetitivepeer-reviewedgrantapplicationstogeneratethebestideas,althoughwhennecessary,thereisalsoflexibilitytorespondina“top-down”wayforurgentneeds.Stakeholders
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notedthathistorically,theNIHhasbeenabletopivottoareaswherethereisanurgentneed,aswasthecaseforbioterrorismpreparednessafter9/11andEbola,orwherethereisanopportunityfortransformativeresearch.However,itisgettingincreasinglydifficulttodosowithcurrentfundingtrends.Whenaddressingurgentneeds,stakeholdersdescribedfundingallocationsas“top-down”—callsforapplicationsareissuedafterconsultationwithscientistsandwiththeCouncilofAdvisors,whichgivesoverallinputtotheNIHDirector.47TheNIHAdvisoryCouncilshaveaprominentroleinthebudgetaryprocess.Institutesmayalsoindividuallyadjusttheirfundingallocationsinresponsetowhatotherprivateorgovernmentcounterparts(e.g.,theBill&MelindaGatesFoundation,theUK’sMedicalResearchCouncil)aredoingtoproactivelydevelopunderfundedresearchareas,aswasthecasefordrug-resistantTB.48Additionally,Institutestrytostayattunedtopolicyissuesandhavebeenknowntoshiftfundingpriorities,aswasthecaseforHIV/AIDSresearchinthewakeofpressurefromvocaladvocacygroups.
WhileNIHfundingdecisionsaretypicallyresearchdriven,attimesCongressdoesearmarkfundingforspecificpriorities.Thishasincludedtargetedfundingforearlystage,innovativeproductdevelopmentandpartnershipswithindustry.StakeholdersnotedthattheresearchareasoftheseearmarkshavegenerallybeenbroadandthatNIHearmarkshavehistoricallybeenlimitedinnumber.Largelyscientistshavebeen“leftalonewhenitcomestocongressionalearmarks,”andcandeterminethroughscientificmerithowthefundsshouldbespent.Challengesarisewhencongressionalreportlanguagedoesnotincreasefundingbutisdirectiveaboutprioritiesbecausethatresultsinreducingfundingelsewhere.
TheunderlyingmissionandmandateoftheNIH,anditsfocusonextramuralfunding,arefactorsinwhyfundingisdirectedmostlyatbasicandvaccineresearch.KeyinformantswithintheUSGgaveanumberofexplanationsforwhyonlyasmallproportionofNIHfundingisdirectedtowardstranslationalresearch,including:• ThereisaconsciouseffortonbehalfoftheNIHtodistanceitself—tomaintainanarm’slength—betweentheuseofpublicfundsandanyperceptionofsupportingonespecificaspectoftheprivatesector.Congressmightnotappropriatethefundsifthesewereviewedasbeingforproductdevelopment.
• Fundingbasicresearchwithinacademicinstitutions,seenasthenexusofscientificdiscovery,isamajorthrustofNIHfunding.Theacademicinstitutionsalsoexertstronginfluenceovertheircongressionalrepresentatives.
GlobalHealthR&DCoordination
TheNIHhasavarietyofformalandinformalcollaborationswithinandacrossagenciesandwithexternalpartners;keyinformantsarguedthatstrengtheningtheseexistingarrangementsispreferabletotryingto“force”newcollaborations.Stakeholdersarguedthattryingtopushorforceagenciestocollaboratedoesnotalwaysworkandoftendependsonthepersonalityoftheindividualsinleadershippositions.Theyarguedthattherewerealreadyseveralsuccessfulcollaborationsthatcouldbebuiltupon(Table5).
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Table5.ExamplesofSuccessfulGlobalHealthR&DCoordinationBetweentheNIHandOtherFederalandNon-federalAgenciesTypeofCollaboration Examples
FederalInteragencyCollaboration
• NIAIDhasagovernanceroleinthePublicHealthEmergencyMedicalCountermeasuresEnterprise(PHEMCE),whichcoordinatesfederaleffortstoprepareforchemical,biological,radiologicalandnuclearthreatsandemerginginfectiousdiseases.PHEMCE’seffortsincludesupportingR&DforpandemicinfluenzaandVHFs(e.g.,Ebola,Marburg).
• NIAIDandtheNationalCancerInstitutebothparticipateintheNationalInteragencyConfederationforBiomedicalResearch,abiotechnologyandbiodefensepartnershipacrossUSfederalagencies.
• TheDeputyDirectorforClinicalResearchandSpecialProjectsatNIAIDliaiseswiththeDepartmentofDefenseandHomelandSecurity.ThisworkcomesatthedirectiveoftheNIAIDDirector,oftenasaresultofinteragencyandinterdepartmentalforums.Fundsforspecialprojects,suchasEbola,comefromeitherreservedfundsorsupplementalappropriations.
CollaborationwithFoundations
• MultipleinstitutesmeetwiththeBillandMelindaGatesFoundation(BMGF)informal,highlevelmeetingsatleasttwiceayear,withnumerousphoneinteractionsthroughouttheyeardowntothescientistmanagerlevel.NIAIDhasmanyseatsatthetablebecauseinfectiousdiseasesareahighpriorityforBMGF.Thesemeetingsprovideaforumtodiscussfundingprioritiesandtoavoidduplicationofeffort.
• NIAIDcoordinatesinformallywiththeWellcomeTrustand,toalesserextent,withotherfoundations.
CollaborationwithIndustryandAcademia
• NIHinvestigatorscancollaboratewithindustryandacademicpartnersthroughCRADAs,agreementsbetweenafederallaboratoryandanon-federalpartyforconductingspecifiedR&D.49,50ThepurposeofCRADAsis“tomakeGovernmentfacilities,intellectualproperty,andexpertiseavailableforcollaborativeinteractionstofurtherthedevelopmentofscientificandtechnologicalknowledgeintouseful,marketableproducts.”50
CentersforDiseaseControlandPrevention
OverviewandFundingLevels
TheCDC’smissionistoprotecttheUSfromhealth,safety,andsecuritythreats,bothforeignandwithintheUS.AstheUSG’sfederalpublichealthagency,CDCconductsresearchtodetectandrespondtoemerginghealththreatsanddevelopstechnologiestodetect,prevent,andrespondtodiseases.Italsopromoteshealthyandsafebehaviorsandprovidestrainingtothepublichealthworkforce.51Inthisrole,itmustbeabletogeneratedatatoinformandprovidetechnicalexpertise.TheCDC’sexpertise,especiallyinimplementationscience,helpstoinfluencedecisionsbothwithinandoutsidetheUSG.CDCprovidesguidancefromdataobtainedthroughitssurveillancearmandworkswithpartnerstoidentifywhatproductsareneededandtodevelopinterventions,emphasizingpointofcarediagnostics.Forexample,itisattemptingtocreateeffectivemulti-targetdiagnosticassays,whichsimultaneouslydetectseveralinfectiousagentsinasingleclinicalspecimen,toincreaseefficiency.52CDCisledbytheOfficeoftheDirector.
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CDCprovided$18millioninfundingforglobalhealthR&Din2015(1%ofUSGfunding),almostentirelycomprisedoffundingforTB($9million,48percent)andEbolaandotherAfricanVHFs($8million,45percent)(Figure10).AlthoughtotalCDCfundingforglobalhealthR&Din2015wasessentiallyunchangedfromthepreviousyear,thishidahalvingofitsfundingforneglecteddiseaseR&D(whichfellby$9million),withnewinvestmentinVHFs(upby$9million)takingitsplace.
KeyCDCinstitutesorcentersthatimpactglobalhealthR&DaretheCenterforGlobalHealth(CGH)andtheOfficeofInfectiousDiseases.TheofficehousestheNationalCenterforEmergingandZoonoticInfectiousDiseases(NCEZID)andtheNationalCenterforHIV/AIDS,ViralHepatitis,STD,andTBPrevention(NCHHSTP).• TheCGH’smissionistoprotectandimprovehealthgloballythroughscience,policy,partnership,andevidence-basedpublichealthaction.TheCGHsitswithintheOfficeoftheCDCDirectorandisresponsibleforcoordinatingandprovidingstrategicdirectionacrossCDCglobalhealthworkwhileharmonizingCDCglobalhealthprioritieswithhostcountrypriorities.
• NCEZID,headedbyitsdirector,usesitsepidemiologicandlaboratoryexpertisetotacklebacterial,viral,andfungalpathogensaswellasinfectiousdiseasesofunknownorigin.53Thecenterfocusesonimprovinginfectiousdiseasesurveillance,outbreakresponse,andepidemiology;improvingcorelaboratorycapacity;andacceleratingdevelopmentandapplicationofnoveldiagnosticmethods.
• NCHHSTP,headedbyitsdirector,supportsresearch,surveillance,andcontrolprogramsforitsfocusdiseases.
WhileCDC’s2015globalhealthR&DbudgetwasdominatedbyTBandVHFs,itwasalsofocusedinternationallyoncontrolofneglectedtropicaldiseases(NTDs)andmalaria.StakeholdersdescribedtheCDCasfocusedonachievingtheNTDgoalsdetailedintheLondonDeclarationandWHO’s2020RoadmaponNTDs,andonthemalariagoalsdelineatedinthePMIstrategicplan2015-2020andWHO’sGlobalTechnicalStrategyforMalaria2016-2030.54-56CDCsitsonthepanelsthatdevelopthesedocuments,whichinturnguidelongrangeCDCpriorities.
GlobalHealthR&DFundingDecisions
CDCdesignatesonlyalimitedamountoffundingforR&Dbecauseitsprimarymissionishealthprotectionandnotproductdevelopment.ItprioritizesitsbudgetforR&Dbasedondiseaseburden,severityofdisease,opportunitiesforimpact,perceivedgaps,andtheneedforenhanceddiseasepreventionandcontrol.
Figure10.CDCFundingin2015forGlobalHealthR&DbyDisease
Source:authors’ownanalysisbasedondatafromG-FINDER2016.NDs:neglecteddiseases,DCs:developingcountries
Tuberculosis48%Ebolaandother
AfricanVHFs45%
HIV/AIDS2%
OtherNDs5% Reproductivehealth
needsofDCs0%
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UnliketheNIH,theCDCdoesnothavemuchflexibilityonhowtospenditsbudget.InsteadaverydirectedbudgetlimitsCDC’sabilitytomakeindependentfundingdecisions.
StakeholdersdescribedtheCDCbudgetprocessasbothaformalandinformalprocess—abalancebetweentopdownandbottomup.Inthisprocess,individualprogramexpertsformulateopinionsaboutwherethegapsareandtargetareastheythinkmeritadditionalfunding.
Developingevidenced-basedtargetshasnotbeenimplementedwhenmakingbudgetaryrequests,althoughpublichealthemergencies(e.g.,outbreaks)havebeenusedastriggerstorequestincreasedfunding.Eventhen,“thepienevergrows,”sowhiletheCDCmaywanttotakeonnewefforts,itmeansbalancingthesewhiledownsizingotherpriorities.
GlobalHealthR&DCoordination
OpportunitiesandmutualinterestsdrivethemultipleformalandinformalchannelsforcollaborationattheCDC.OnecoordinationmechanismistheCDCBoardofScientificCounselors(BSC),OfficeofInfectiousDiseases(OID),whichholdsmeetingsatleasttwiceayearsupplementedbyconferencecalls.57TheBSC,OIDincludesex-officiomembersfromtheDoD,theFDA,theNIH,theHHSNationalVaccineProgramOffice,andtheUSDepartmentofAgriculture.Keyinformantsindicatedthattheseagenciestalkregularlyandinterfaceatastrategicagencylevel.Therearealsocollaborationswithstafffromvariousdisease-specificprograms.Forinstance,CDCsitsonseveralFDA,NIAID,andUSAIDAdvisoryCommitteesandreviewpanels,whichdiscussbroadconceptsandfundingdecisionsaboutborderlinegrantapplications.
CDCalsohelpedimplementtheGlobalHealthSecurityAgendaincoordinationwithotherU.S.agenciesandglobalpartners.58Thisagendaisamultinational,multi-sectoralinitiativelaunchedinFebruary,2014to“strengthenboththeglobalcapacityandnations’capacitytoprevent,detect,andrespondtoinfectiousdiseasesthreatswhethernaturallyoccurring,deliberate,oraccidental.”59
CDCparticipatesinNIH’sstrategicplanningprocess,whichconsistsofformallyplanned,quarterlymeetingsindependentofthebudgetarycycle.CDCprioritiesarenotnecessarilydeterminedbasedonwhattheNIHisdoing,buttheyarecoordinatedtocreateacohesiveworkflow.Forexample,theNIHdoesnothavefieldsitesbutfundsstafftoworkatCDCfieldsites,andtheCDCalsohasexpertiseatfieldsitesthatcanbeusedbyNIH.Ingeneral,CDC’sgoalistoallowdifferentUSagenciestomaximizeandleveragetheirstrengthsandtominimizeduplication.Itidentifiescollaborationopportunitiesonacase-by-casebasisandwillleverageprojectsoccurringinotheragencies.Italsocollaborateswithotheragenciesthroughthedevelopmentofcountryworkplansforcross-cuttingprograms,suchasPEPFAR,tohelptargetandimplementprogramgoalsbasedonburdenofdisease.
TheCDCofferstechnicalscientificexpertisethroughcooperativeagreements,settingaside3%ofitsextramuralbudgetforNIH’sSBIRprogramthatprovidesgrantstosmallbiotechnologycompaniesforproductdevelopment.60Companiescanproposetopicstoaccessthesefunds.TheCDChasaTechnologyTransferOfficethatpartnerswithindustry,academia,nonprofitsandotherUSGagenciestotransferitsresearchportfoliointoproductinnovation.Itspecificallysetsasideaportionofitsbudgetforcollaborationswithacademia.61
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CDC’scollaborationonglobalNTDresearchiscoordinatedthroughavarietyofcoordinationvenuesandmechanisms.Theseinclude:• WHOtechnicalexpertmeetings,whichfacilitateoverallglobalcoordinationoftheNTDresearchagenda.
• MeetingsoftheTaskForceforGlobalHealth(whichreceivesfundingfromBMGF).62• TheannualAmericanSocietyofTropicalMedicineandHygienemeeting,whichisanotheropportunityforcollaborativeprioritysettingonNTDresearch
• TheCoalitionforOperationalResearchonNeglectedTropicalDiseases(COR-NTD),supportedbyUSAIDandBMGF.63
StakeholdersindicatedthatresearchprioritizationformalariaoccursinadifferentvenuewithPMI,USAID,andCDC.
Keyinformantsdescribedmanyexamplesofsuccessfulcoordination(Table6)andnotedthatthesuccessoftheseprogramsdependedoncommitment,understanding,andtrust.
Table6.ExamplesofSuccessfulGlobalHealthR&DCoordinationBetweentheCDCandOtherFederalandNon-federalAgenciesTypeofCollaboration Examples
FederalInter-agencyCollaboration
• CDCisworkingwithDoDandNIHtoproducemultiplexassays,whichcansimultaneouslydetectseveralinfectiousagentsinasingleclinicalspecimen,andisevaluatinghowtogetthemtothenextdevelopmentphaseonacase-bycase-basis
• FDAandCDCarecollaboratingonaprojecttocontrolcyclosporiasis,afood-borneparasite,throughgenomesequencingandidentificationofnewspecies64
• CDC,NIH,andBARDAareworkingtogetheronEbolavaccinedevelopment• CDC,NIHandPMIcollaborateonmalariavaccinedevelopment
CollaborationwithProductDevelopmentPartnerships
• CDCwasacollaboratorontheMeningitisVaccineProject,tosupportmeningitisAvaccinedevelopment65
• CDCisacollaboratorontheInternationalAIDSVaccineInitiative
USFoodandDrugAdministration(FDA)
OverviewandFundingLevels
TheFDAistheUSregulatoryauthoritythatensuressafetyofhumanandveterinarydrugs,biologicalproducts,andmedicaldevices.Italsopromotesinnovationstodevelopmoreeffective,safer,andaffordablemedicalproductsandproductsthatwouldhelptackleemergingpublichealththreats.66TheFDAisheadedbytheOfficeoftheCommissioner.FourdirectorateswithinFDAoverseethecorefunctionsoftheagency:MedicalProductsandTobacco,Foods,GlobalRegulatoryOperationsandPolicy,andOperations.67TheFDAbudgetforFY2016is$4.9billion,andtheFY2017requestisfor$5.1billion.68ThekeydirectoratesandcentersthatplayaroleinglobalhealthR&DaretheOfficeofGlobalRegulatoryOperationsandPolicyandthreecenterswithintheMedicalProductsandTobaccodirectorate.TheOfficeofGlobalRegulatoryOperationsandPolicyregulatesproductqualityandsafetyefforts,includingglobalcollaboration,globaldatasharing,developmentandharmonizationofstandards,fieldoperations,compliance,andenforcementactivities.69WithintheOfficeofMedicalProductsandTobacco,threecenters—theCenterforBiologicEvaluationandReview,theCenterforDrugEvaluationandResearch,andtheCenterforDevices,andRadiologicalHealth—areresponsiblefordrug,device,andbiologicresearchandregulationforproductsafety.
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TheFDAdidnotprovideanyfundingforglobalhealthR&Din2015,althoughithasawardedgrantsforglobalhealthR&Dinthepast.AnexampleofitspastfundingisitsCriticalPathInitiative,whichin2010issuedacompetitivecalltofundthedevelopmentofnewTBdrugs,vaccines,anddiagnostics.70,71However,thesizeoftheFDA’sfinancialcontribution(lessthan$5millionbetween2010and2013fortheinitiative)isnotinthesameleagueasthatoftheotherUSGagencies.TheFDAdoesprovideongoingcorefundingtothenon-profit,public-privatepartnershipC-PathInstitute—createdbyFDAundertheauspicesoftheCriticalPATHInitiative—afoundingpartneroftheCriticalPathtoTBDrugRegimens(CPTR)initiative.
TheFDAprovidessignificantnon-financialcontributionstoglobalhealthR&D—suchasthroughthepriorityreviewvoucher(PRV)scheme,whichhasbeenestablishedthroughlegislation,andprovidingtechnicalsupportandcapacitybuildingforregulatoryauthoritiesinLMICs.KeyinformantsdescribedmultiplewaysinwhichtheFDAsupportsglobalhealth,includingR&Dforneglecteddiseases:• ItcanawardaPRVfordevelopmentofdrugsforaselectedlistofinfectiousandparasiticdiseasesaffectingLMICs.Thevoucher,whichcanbesold,grantsthebearerfasterFDAreviewofadifferentdrug(ahighlyprofitable“blockbuster”drug);priorityreviewcanbeworthmorethanahundredmilliondollars.72,73Todate,however,PRVshavebeenawardedtodrugsalreadyavailableinothercountries(suchasartemether/lumefantrine)andtodrugsalreadyatalatestageofdevelopment(suchasbedaquiline).
• Bydesignatingdrugsaseligiblefororphandesignation,FDAmakesthedrugdevelopereligibleformanybenefits,includingtaxcreditsforhalfofallclinicaltrialcosts.Drugs,vaccines,anddiagnosticsqualifyfororphanstatusiftheyareintendedtotreatadiseaseaffectingfewerthan200,000Americancitizens(evenifthediseasehasahighburdenoutsidetheUS)orifthereisnoexpectationofprofitafterR&Dcostshavebeenincurred.Forexample,malariadrugtreatmentswouldqualifyfororphandrugtaxcredits,thoughavaccinemaynot(asmorethan200,000Americancitizenscouldpotentiallybenefit).TheOrphanDrugActreducesdevelopmentcosts,butdoesnoteliminatethosecosts,anddoesnotmaketheproductprofitable.Hence,thisincentivealoneisinsufficientformotivatingdrugdevelopmentbycommercialmanufacturers.Non-pecuniarymotivationoradditionalpushand/orpullmechanismsareneeded.
• FDAapprovalofaproductprovidesasignaltoregulatorsinothercountriesofthequalityofthatproduct,whichcanhaveknock-oneffectsforitsapprovaloutsidetheUS.Forexample,MexicomightgoaheadandapproveanFDA-approvedproductandthenotherLatinAmericancountriesmightapproveproductsthatMexicohasapproved.Inthisway,FDAapprovalcandirectlyandindirectlyinfluenceregulatoryapprovalinothercountries.
• Itinspectsmanufacturingfacilitiesaroundtheworld.In2008,Congressallocatedfundstoestablishforeignpostsinstrategiclocationsaroundtheworld,followingincidentsoftaintedheparinandbabyformula.By2016,FDAhadpostsinBelgium,Chile,China,CostaRica,India,andMexico.
• FDAhasworkedforregulatoryharmonizationthroughbodiessuchastheInternationalMedicalDeviceRegulatorsForum(IMDRF)thatwasledbyFDA’sCenterforDevicesandRadiologicalHealth(CDRH).74TheIMDRFhasimplementedamedicaldevicesingleauditprogram(MDSAP)withFDA,theEuropeanMedicinesAgency(EMA),Brazil,andCanadaworkingtogethertowardasingleauditinordertoavoidredundancy.
• ItfacilitatesknowledgetransfertoproductdevelopmentfirmsinLMICsandtechnicalsupportandcapacitybuildingforregulatoryauthoritiesinthesecountries.
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• ItreviewsantiretroviraldrugsthatareintendedforpurchasebyUSAIDunderPEPFAR.FDAcancertifythequalityofanantiretroviraldrug,evenifitcannotbesoldintheUSduetopatent(orotherexclusivity)protection.IfthedrughaspatentprotectionintheUS,FDAcanissuea“tentative”approvalratherthana“full”approval.Thetentativeapprovalsignifiesthattheproductmeetsallsafety,efficacy,andmanufacturingqualitystandardsformarketingintheUS.UnderPEPFAR,anyimplementingagencycanpurchaseaproductthathaseitheratentativeorfullFDAapproval.75
GlobalHealthR&DFundingDecisions
FDA’sauthoritytograntorphandrugstatusandawardPRVsaimstoincentivizeglobalhealthR&Dfunding;whileobjectiveeligibilitycriterialimitFDAdiscretion,thereissomeflexibility.USGstakeholdersnotedthatoneareaofdiscretionisthattheFDAhastheauthoritytoexpandthelistoftropicaldiseaseseligibleforaPRV.In2015,forexample,theFDAexpandedvouchereligibilitytoincludeChagasdiseaseandneurocysticercosis.76
GlobalHealthR&DCoordination
TheFDAhasanumberofmechanismsthatitcanpotentiallyusetocollaboratewithinternationalandprivatesectorentitiestoimproveglobalhealthR&D.FDA’sCentersofExcellenceinRegulatoryScienceandInnovationfacilitatescollaborationsbetweenFDAandacademicinstitutionsforinnovativeresearchforimprovedregulation.77TheFDAhasissuedBroadAgencyAnnouncementsasacontractmechanismopentoprivatesectorparticipantstocollaborateonregulatoryscienceR&D.78TheMedicalDeviceInnovationConsortium(MDIC)atFDAisapublic-privatepartnershipthatallowsindustry,government,andpatientorganizationstocollaborateonmedicaldeviceandtechnologyresearch.79
UNITEDSTATESAGENCYFORINTERNATIONALDEVELOPMENT
OverviewandFundingLevels
USAIDistheUSG’scivilianforeignaidagencywhosemissionistopartnertoendextremepovertyandpromoteresilient,democraticsocietieswhileadvancingUSsecurityandprosperity.USAIDwascreatedin1961throughthepassagebyCongressoftheForeignAssistanceActof1961.USAIDisheadedbytheOfficeoftheAdministrator.TheAssistantAdministratorforglobalhealthleadstheGlobalHealthBureauatUSAID.80USAIDhadabudgetof$22.3billioninFY2016,ofwhich$2.8billionwasallocatedtoitsglobalhealthprograms.81The2017USAIDbudgetrequestsetsaside$2.9millionforitsglobalhealthprograms.ItisunclearhowmuchoftheglobalhealthbudgetwillbedirectedtoglobalhealthR&D.82
USAIDisthefourth-largestUSGfunderofglobalhealthR&D(afterNIH,DoD,andBARDA).In2015itinvested$87million,orfivepercentofallUSGfunding.However,whileitmaybeasmallerfunderrelativetootheragencies,USAIDistheonlyUSGagencywithaclearglobalhealthanddevelopmentmandateandamandatetoconductR&DfortechnologiestargetingthespecifichealthneedsofpeopleinLMICs.
USAID’sproductdevelopmentforglobalhealthisdirectedalmostexclusivelytothe‘bigthree’neglecteddiseases(HIV/AIDS,TBandmalaria)andthereproductivehealthneedsofdevelopingcountries(Figure11).Allofitsinvestmentin2015wasinthesefourareas,andhistoricallytheseareasaccountformorethan99percentofalltheagency’sglobalhealthR&Dinvestmentssince2007.Two-thirdsofUSAID’s2015funding($58million,66percent)wasforHIV/AIDs,withtheremainingthirddividedbetweenTB($13million,15percent),malaria($9million,11percent),andreproductivehealthtechnologies($7
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million,eightpercent).In2015,USAIDwasbyfarthelargestUSGfunderofreproductivehealthtechnologiesfordevelopingcountries(Figure12).
ItisimportanttonotethatUSAIDalsoinvestssignificantlyinglobalhealthresearchthatisnotrelatedtothedevelopmentandintroductionofnewhealthtechnologies,suchasprogrameffectivenessevaluationandotherhealthsystemsresearch.Suchresearchisoutsidethescopeofouranalysis.Similarly,whilstitdidnotprovideanyproductdevelopmentfundingin2015forproductdevelopmentforEbolaandotherVHFsin2015,theagencywasasignificantcontributortoprogramdeliveryonthegroundandrelatedevaluationresearchduringtherecentWestAfricanEbolaoutbreak.
WithinUSAID,twocentershaveakeyroleencouraginginnovationtoadvanceglobalhealthR&D—theCenterforAcceleratingInnovationandImpactandTheGlobalDevelopmentLab.• TheCenterforAcceleratingInnovationandImpactfocusesondevelopingandscalinguphealthinterventionsthroughabusinessmindedapproach.83Itprovidesseedfinanceforpromotinginnovativetechnologiesandinterventions.Itfocusesonidentifyingstateoftheartpractices,catalyzinginnovationandpartnerships,andscalingforimpact.
• TheGlobalDevelopmentLabwaslaunchedinApril,2014withaviewto“increasetheapplicationofscience,technology,innovation,andpartnershipstoacceleratetheAgency’sdevelopmentimpactinhelpingtoendextremepoverty.”84Thelabactsasacentralhubforinformationoninnovation,anditsworkisorganizedacrossfivemaincenters:DevelopmentResearch,DigitalDevelopment,DevelopmentInnovation,TransformationalPartnerships,andAgencyIntegration.ItisledbyanExecutiveDirector,whooverseesprogramsandmanagementactivities.84ForFY2017,theGlobalDevelopmentLabhasa$170millionbudgetrequestforworkthatincludesglobalhealthR&D.82
Figure11.USAIDFundingin2015forGlobalHealthR&DbyDisease
Source:authors’ownanalysisbasedondatafromG-FINDER2016
HIV/AIDS66%
Tuberculosis15%
Malaria11%
ReproductivehealthneedsofDCs
8%
Figure12.USGFundingforReproductiveHealthR&DNeedsinLMICs,2015
Source:authors’ownanalysisbasedondatafromG-FINDER2016G-FINDER2016
USAID75%
NIH25%
CDC<1%
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USAID’sGrandChallengesforDevelopmentinitiativewaslaunchedin2011totacklesomeofthegreatestinternationaldevelopmentproblemsandtofosterinnovativesolutionsthroughscienceandtechnologypartnerships.Itengagesbothtraditionalandnon-traditionalactors.USAIDhaslaunchedeightgrandchallengestodate,ofwhichthreearedirectlyrelatedtoglobalhealth:FightingEbola;CombatingZikaandFutureThreats;andSavingLivesatBirth.85R&DthroughtheCenterforAcceleratingInnovationandImpact,TheGlobalDevelopmentLab,andtheGrandChallengesprogram,mostUSAIDsupportforglobalhealthR&Doccurswithinitsdisease-specificprograms.Theseincludeprogramsonmalaria,HIV/AIDS,maternalandchildhealth,andneglectedtropicaldiseases.
ThePresident’sMalariaInitiative,ledbyUSAID,ismandatedtoscaleupproveninterventionsandsodoesnotdirectlysupportproductdevelopment,butitdoesfundoperationalresearch,productdevelopmentpartnerships,andbothDoDpartnersandprivatecontractors(e.g.,formalariavaccinedevelopment).StakeholdersdescribedtheinitiativeasaprogrammandatedbytheWhiteHouseandCongresstoreducemalaria-associatedmorbidityandmortalitybysupportingthescale-upofproveninterventionsinspecificcountriesbasedonevidencefromthepast10years.ItsmandaterequiresthatitworkwithotherUSGagencies.WhilePMIdollarsarenotdirectlyinvestedinvaccine,drug,orothertechnologydevelopment,theyareinvestedinoperationalresearchtounderstandhowtoimproveprogrammingandtobuildanevidencebaseonscale-upofoperations.
StakeholdersindicatedthatwhileUSAIDhasastrategyforglobalhealth,theagencydoesnothaveoneunifiedstrategyforpromotingglobalhealthproductdevelopment.However,theyarguedthatthereisagreatdealofsynergyandcoordinationacrossdifferentpartsofUSAIDand,asdescribedbelow(undercoordination),withotherUSGagencies,evennon-traditionalpartnerssuchastheDepartmentofHomelandSecurity.
USAIDpreparesanannualHealth-RelatedResearchandDevelopmentProgressReporttoCongress.86ThisprovidesdetailedinformationonitsR&Dportfolioandhighlightssuccessesfromyeartoyear.Abroader,morecomprehensiveviewofitsR&DisintheFive-YearResearchandDevelopmentStrategyReport.87
StakeholdersthoughtthatitisimportantforUSAIDtomaintainflexibilityinidentifyingtherightframework(e.g.,GrandChallengesorPDPs)toacceleratespecificproductdevelopment.USAIDisthethirdlargestinternationalinvestoringlobalhealthPDPs.88KeyinformantsarguedthatotherUSAID-supportedmodels,suchastheGrandChallengesrelatedtoEbola,Zika,andnewbornsurvivalandworkingdirectlywithinnovatorsinpreparingproductdossiers,havealsobeeneffectiveinpromotingproductdevelopment.FortheEbolaGrandChallenge,USAIDsupportwasdirectedatinterventionssuchaspersonalprotectiveequipment(ratherthanmedicines,vaccines,anddiagnostics).
GlobalHealthR&DFundingDecisions
CongressgenerallydoesnotearmarkfundingforR&DatUSAID.Rather,itfundsprogramsforspecificdiseasesandhealthconditions.DecisionsonhowtoallocatethisfundingforR&Dpurposesarethenmadeattheindividualprogramlevel.StakeholdersindicatedthatteamsdecidehowmuchfundingisallocatedtoR&Dversusimplementationandthereisnoonefromabovechallengingthedecisions.TheexceptionislegacyearmarksforcertaintypesofR&DforHIV/AIDS(e.g.,developmentofmicrobicides
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andHIVvaccinedevelopment).ThishighlightstheimportanceofhavingchampionsforR&Dwithindisease-specificprogramsatUSAID,asexemplifiedbyUSAID’sNTDsProgram.
USGstakeholdersbelievedthattheperceptionthatUSAIDonlyinvestsinimplementationandnottranslationalresearchwasinaccurate;itsportfolioisdiverseacrossthedevelopmentchain.Forexample,ithasmadeinvestmentsinmaternalandchildhealthattheprototypestageandworkedtotakethesethroughtheentireproductdevelopmentcycle.Ratherthanjustbeingagapfiller,USAIDlookstoseeatwhichpointsintheR&Dcycleitcanhavethegreatestaddedvalue.IthasalsosupportedadiversearrayofPDPs(Figure13).
GlobalHealthR&DCoordination
StakeholdersdescribedtheGrandChallengesas“crossagencycollaborationatitsbest.”Theydescribedfourkeystrengthsofthisprogram:• ProjectteamsatstafflevelfromdifferentUSGagencieshavebeenabletobuildeffectiverelationships.
• Itusesastagedfundingapproachacrossthedevelopmentcontinuum:seedgrantsfordevelopingprototypes,transitioningtoscale,tofullydeployingproductsinthefield.
• Itpoolsdifferentexpertisefromdifferentagencies—forexample,theEbolaGrandChallengewasledbyUSAID,butDoDprovidedtechnicalexpertiseonpersonalprotectiveequipmentandtheCDC’sNationalInstituteofOccupationalSafetyandHealthtestedthenewsuitsinitslabs.
• GrandChallengeshavehadacatalyticeffectinraisingfundsfromothersources.Forexample,theSavingLivesatBirthGrandChallengehasbeen“agreatleveragestory”—aninitial$20millioninvestmentsubsequentlyattractedadditional$110millioninfundingfromnumerousinvestors.
TheCenterforAcceleratingInnovationandImpacthasstrongcross-agencysupport.89Ithassuccessfullybuiltbridgesforinter-agencycollaboration,soughtoutexpertiseacrosstheUSG,andworkedtoensurealignmentinordertoavoidduplication.
USAIDisapartnerinmultiplePDPs,includingIAVI,theMedicinesforMalariaVenture(MMV),andtheInnovativeVectorControlConsortium(IVCC).
Figure13.USGFundingin2015forPDPsthatDevelopProductsforGlobalHealth,byRecipientandAgency
Abbreviations:USAID:UnitedStatesAgencyforInternationalDevelopment,NIH:NationalInstitutesofHealth,CONRAD:ContraceptionResearchandDevelopment,IAVI:InternationalAidsVaccineInitiative:InfectiousDiseaseResearchInstitute,IPM:InternationalPartnershipforMicrobicides,IVCC:InnovativeVectorControlConsortium,MMV:MedicinesforMalariaVenture,TBAlliance:TuberculosisAlliance.Source:authors’ownanalysisbasedondatafromG-FINDER2016.Note:G-FINDERdataforPATHincludesfundingfortheMalariaVaccineInitiative(MVI),TechnologySolutions,VaccineDevelopment,VaccineAccessandDeliveryandWomanCareGlobal
0
10
20
30
40
50
60
USAID NIH
USD($Millions)
CONRAD
IAVI
IDRI
IPM
IVCC
MMV
PATH
TBAlliance
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• USAIDhassupportedIAVIsince2001;itssupportisaimedatacceleratingthedevelopmentandclinicaltestingofnewvaccinecandidates,strengtheningresearchcapacityinLMICs,andstrengthening“theglobalenvironmentforAIDSvaccinedevelopmentandfutureaccess.”90
• PMIsupportsMMVandtheIVCC,helpingtocreatenewmalariavaccineandinsecticidecandidatesandallowingPMItobealong-termbeneficiaryoftheinnovationsproduced,givingitaccesstolower-pricepointsfortheseproducts.ThetechnicalstaffatPMIworkdirectlywithbothofthesePDPs,andPMIparticipatesattheboardlevelofboth.PMIcollaborateswithMMVindevelopingmalariaeradicationstrategiesandproductaccessinitiatives,andinreviewingdrugsinthepipelineandchallengesandsolutionsforaddressingregulatoryhurdles.ItalsohasanagreementwithMMVtopurchasepromisingproductsforcountryoperations.PMI’sroleintheIVCCistohelptestnewinsecticidesandidentifywhichnewtoolswouldbebeneficialformalariacontrol.ThePDPsfacilitateregulatoryapprovalsforPMIprogramsataninternationalandcountry-specificlevel.
AnotherexampleofUSAID’sinter-agencycoordinationistheInteragencyAdvisoryGroup,withrepresentativesfromUSAID,CDC,DoD,DepartmentofState,theNationalSecurityCouncil,andOMB,thatoverseesPMI.Thegroupmeetsatmultiplelevels,includingatechnicalworkinggrouptoformulatestrategyandbudgetaryreviewmeetings,anditapprovesPMI’scountryMalariaOperationalPlans.PMIcanonlyaddcountriesiffundingincreases.Whileinvestmentsindeliveringonthismandatehaveincreased,USGinvestmentsinmalariaresearchhaveremainedstable.Withinthisfixedresourceenvelopefordevelopingvaccines,drugs,andinsecticides,PMIworksinpartnershipwithotherUSGagenciestoadvisethemoninvestments(e.g.,givingago/no-gosignal).
StakeholdersarguedthattherewasagreatdealofsynergyandcoordinationbetweendifferentpartsofUSAIDandbetweenUSAIDandotherUSGagencies.USAIDseesoneofitsimportantrolesasbuildingbridgeswithinteragencycolleagues,seekingoutexpertisefromacrossUSG,ensuringalignment,andavoidingduplicationofefforts.
DEPARTMENTOFDEFENSE
OverviewandFundingLevels
ThemissionoftheDepartmentofDefense(DoD),establishedin1789,istoprovidethemilitaryforcesneededtodeterwarandtoprotectthesecurityoftheUS.91HeadquarteredatthePentagon,itisledbytheOfficeoftheSecretaryofDefense,whoalsoservesastheprincipaldefensepolicyadvisortothePresident.92TheMilitaryHealthSystem(MHS),headedbytheAssistantSecretaryforDefenseforHealthAffairsisresponsibleforservingUSArmy,NavyandAirforcepersonnelworldwide.93TheMHSisengagedinhealthcaredelivery,medicaleducation,publichealth,privatesectorpartnershipsandhealthR&D.ItalsohousestheDefenseHealthAgency,whichexecutestheDefenseHealthProgram—thisprogramsupportsthedeliveryofhealthservicestoUSdefensepersonnel,healthinformationtechnology,andR&D.94ThepurposeoftheDoD’sengagementinglobalhealthR&DistoprotectthehealthofarmedforcesandpreventbiologicalthreatstotheUSpopulation.Whileitdoesnothaveaspecificmandateforglobalhealth,DoDresearchmayincludeneglecteddiseases,suchasmalaria.
TheDoDinvested$123millioninglobalhealthR&Din2015(sevenpercentofUSGfunding).ThismadeitthesecondlargestUSGagencyfunderaftertheNIH.
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EbolaandotherAfricanVHFsaccountedforthelargestshareofDoDfundingin2015($51million,41percent;Figure14).ThisamountmeansthatDoDwasthethird-largestfunderofVHFR&DofalltheUSGagencies,behindNIHandBARDA.Malaria($29million,24percent)andHIV/AIDS($28million,23percent)accountedformostoftheremainder.
AfterNIH,DoDhasthesecondmostdiverseportfolioofglobalhealthR&Dinvestments.Inadditiontoitsthreefocusdiseases,otherDoDprioritiesincludeddiarrhealdiseases,leishmaniasis,anddengue,reflectingthekeyinfectiousdiseasesthreatsfacingitssoldiersoverseas.
AlthoughDoDactivitiesareaimedatprotectingmilitarypersonnelandbiologicalthreatreductiontheancillaryoutcomeoftheDoD’sinvestmentinglobalhealthistechnologythatcantreatandpreventawiderangeofdiseases.95Over60percentoftheDoD’sglobalhealthfundingisusedtofunddiscoveryandpreclinicalstageR&D.7
TheDoDhasnodepartment-widepolicyorstrategyguidingitsglobalhealthR&Defforts;theseeffortsarelargelycarriedoutbytheWalterReedArmyInstituteofResearch(WRAIR),theNavalMedicalResearchCenter(NMRC),theDefenseAdvancedResearchProjectsAgency(DARPA)andDoD’soverseaslabs.96
• TheWRAIRwasfoundedin1893astheArmyMedicalSchoolandistheDoD’slargestbiomedicallaboratory.97ItsworkmainlysupportsresearchandtechnologytodevelopanddeliverlifesavingproductstoensurethecombateffectivenessoftheUSwarfighter.TheinstitutehousestwoCentersofExcellence:MilitaryPsychiatryandNeuroscienceResearch,andInfectiousDiseaseResearch.TheInfectiousDiseaseResearchCenter,whichworksonthedevelopmentofvaccinesanddrugsforthepreventionandtreatmentofinfectiousdiseases,hasresearchprogramsinbacterialdiseases,entomology,HIV,malaria,preventivemedicine,translationalmedicine(thisbranchhousestheClinicalTrialCenterwhichconductsPhaseI,II,andIIIhumanclinicaltrials),veterinaryservices,andviraldiseases.97-99
• TheNMRCfocusesitsresearchontraditionalbattlefieldmedicalproblemsandnaturaloccurringinfectiousdiseases,aswellasonnon-conventionalhealthproblemsrelatedtothermobaricblast,biologicalagents,andradiation.100ItsInfectiousDiseasesDirectorateconductsresearchonsignificantthreatstodeployedsailors,marines,soldiers,andairmenandhasfourresearchdivisions—malaria,entericdiseases,viralandrickettsialdiseases,andwoundinfections.Thedirectorateoperateswithanannualresearchbudgetof$10million.101
• DARPAwasfoundedin1957andmakesinvestmentsinbreakthroughtechnologiesfornationalsecurity.Itworksasaninnovationecosystemwithavarietyofacademicsandcorporateandgovernmentpartners.Ithassixtechnicalofficestoworkonbreakthroughtechnologies—officesfor
Figure14.DoDFundingin2015forGlobalHealthR&DbyDisease
Source:authors’ownanalysisbasedondatafromG-FINDER2016
EbolaandotherAfricanVHFs
41%
Malaria24%
HIV/AIDS23%
OtherNDs12%
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biologicaltechnologies,defensesciences,informationinnovation,microsystemstechnology,strategictechnology,andtacticaltechnology.TheBiologicalTechnologiesOfficeworksonneurotechnology,thehuman-machineinterface,humanperformance,infectiousdiseases,andsyntheticbiologyprogramsandservesasaplatformfortechnologists,researchers,start-upsandindustry.UnderitsProphecyproject,DARPAisdevelopingasimple,hand-held,battery-operatedpoint-of-carediagnosticdevicetorapidlyidentifyarangeofinfectiousdiseases.DARPA’sADEPTprogram(AutonomousDiagnosticstoEnablePreventionandTherapeutics)developsdiagnostics,vaccines,newdrugdeliverymethods,andantibodies.DARPAhasabudgetof$2.87billioninFY2016andhasrequestedabudgetof$2.97billionforFY2017.102,103
GlobalHealthR&DFundingDecisions
TheDoDhasalargeamountofdiscretionovertheuseofmostofitsfunding.However,CongressdoesprovidespecificappropriationsforitsHIV/AIDSpreventionprogram(e.g.,$8millionin2012).104,105
StakeholdersdescribedtheDoDfundingprocessforR&Dasrequirements-driven.Requirementsarehighlybureaucratic,definedprocessesestablishedinternally,sometimesattheservicelevel(e.g.,navy,army,airforce)oratahigherlevel,withinputfromvariousstakeholders(e.g.,Africacommand,medicalcommand).Requirementsmustspecify:wherethetechnologygapis;whatisneededandwhy;howitfitsintoDoD’sstrategy;andanestimateofthepricetag.ThisprocessisthesameforallrequestsacrosstheentireDoDspectrum,whetherforthelatestmilitaryairfighterorforthedevelopmentofanewvaccine.
TherequirementsdocumentultimatelyformsthebasisforfundingrequeststhatgointotheNationalDefenseAuthorizationActpassedeachyearthatspecifiestheDoD’sbudgetandexpenditures.106Ifaprogramisnotincludedintherequirementsdocument,itwillbedifficult,thoughnotimpossible,fortheDoDtostartfundingsomethingnew.Forinstance,afterearlyworkontheZikavaccinelookedpositive,publicpressandpressurefromexpertshelpedtobreakthroughthenormalgridlocktomovethingsforward.
DoD’sintramuralinvestmentinitsinfectiousdiseasesresearchandbiologicalthreatreductionprogramsisdrivenbytheneedsofmilitarypersonnel,buttheseneeds(e.g.,vaccinesformalariaanddengue)areoftenthesameasthoseaffectingpopulationsinLMICs.ThisoverlapprovidesacompellingreasonforseniorleadersfromotherUSGagenciesandfromoutsideUSG(acrossvarioussectorsandorganizations)tocollaboratewithDoDinglobalhealthR&D.TheUSGandbroaderglobalhealthcommunitycoulddomoretoleverageDoD’smodestinvestmentinglobalhealthR&D.107
GlobalHealthR&DCoordination
DoDparticipatesinabroadarrayofinter-agencycollaborativepartnerships.Forexample,itisamemberoftheOfficeofAIDSResearchAdvisoryCouncil,whichprovidesadvicetotheDirectoroftheNIH’sOfficeofAIDSResearch;amemberofthePresidentialAdvisoryCouncilonCombatingAntibiotic-ResistantBacteria(PACCARB),andPHEMCE,anditcollaboratedwithUSAIDandCDContheEbolaGrandChallenge.
ItisalsoparticipatesintheGlobalHealthSecurityAgendaaspartoftheUSengagement.
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OFFICEOFMANAGEMENTANDBUDGET
Overview
ThemissionoftheOMBistoassisttheWhiteHouseinenactingthePresident’svisionacrosstheExecutiveBranch.OMBachievesthisthroughtwocorefunctions:(1)preparingthefederalbudgettoreflectthePresident’spriorities,and(2)managingexecutiveagenciesinimplementingfederalprograms.OMBalsocoordinatesfederalregulationsandoverseestheAdministration’sprocurement,financialmanagement,information,andregulatorypolicies.108
Duetoitsextensivescope,stakeholdersdescribedOMBasthe“centerofgovernment.”AllregulationsandbudgetsofexecutivebranchagenciesaresubjecttoOMB’slens,givingOMBavantagepointofthefederalgovernmentthatfeworganizations,ifany,have.OMBalsoreportsdirectlytothePresidentaspartoftheExecutiveOfficeofthePresident(EOP).109,110Assuch,althoughCongresshastheultimatepower,OMBhassignificantinfluenceoveragencieswhileenactingthePresident’spolicyandbudgetarypriorities.
OMBworkscloselywithexecutiveagencyofficialsandothers(includingadvocacygroups),duringthebudgetpreparationprocessandthroughouttheyearwhilemonitoringthebudgetimplementation.OMBmeetswithagencyofficialsandstringentlyreviewstheirbudgetfundingrequestsfromSeptembertoFebruaryandwithadvocacygroupsbetweenJulyandAugust.111WhileOMBusesthisprocesstocommunicatethePresident’spreferences,italsoseesthisprocessasanopenconversationwithexecutiveagencies,enablingpolicyprioritiestopercolatebothdownfromtheAdministrationandupfromtheagencies.StakeholdershavecharacterizedthisinteractionbetweenOMBandagencyofficialsasbothcontentiousandcollaborative,dependingonthelevelofpolicydisagreementbetweenthetwoorganizations.
OMB’sexpansivescopelimitsitsabilitytocomprehensivelycoordinateacrossagencies.Thislimitationisreflectedinitsorganizationalstructure,wheresupportiveoffices—knownasResourceManagementOffices(RMOs)—aredividedintofivegroupsbysubjectmatter.Forexample,theNationalSecurityProgramsRMOoverseesUSAID,StateDepartment,andtheDoDandtheHealthProgramsRMOoverseesNIH,FDA,CDC,andHHS.StakeholdersalsonotedthatOMBfocuseslessonminutedetailsandnuancedissues.GlobalhealthR&Dprogramsarereviewedbydifferentoffices,andtendtoreceivelessattentionthanotherpriorities.110
AcrossOMB’sverticalhierarchy,staffcan“shifttheneedle”ininfluencingbudgetrequests.OMBhasaclearlydefined,butrelativelyflat,verticalhierarchy,givingjuniorstaffaccesstoseniorleadership.112OMBstaff,knownasProgramExaminers,arethefocalpointinOMB,servingasliaisonstoagencies.TheyplayacriticalroleinOMB,reviewing,monitoring,andevaluatingprogramsandrecommendingprogrammaticfunding.DeputyAssociateDirectorsandProgramAssociateDirectorsaretheseniortiersofleadershipwithineachRMOandhavesignificantleewayininfluencingbudgetaryrequests.
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TheOfficeofScienceandTechnologyPolicy(OSTP)andtheNationalSecurityCouncil(NSC)aretwoentitieswithintheEOPthatwereconsideredtobeextremelyinfluentialonglobalhealthpolicyintheObamaAdministration;however,givenrecentdeparturesandvacanciesattheleadershipleveloftheseoffices,theirimportancemaydiminishandOMBmaybecomeincreasinglypowerful.• TheOSTPadvisestheEOPontheeffectsofscienceandtechnologyonnationalandinternationalaffairs.Keyinformantscitedthe2015WhiteHouseplan,guidedbyOSTP,theNationalPlanforCombatingAntibioticResistantBacteria,asamodelforhowtheAdministrationcoulddriveglobalhealthR&Dcollaborationacrossagencies.113
• TheNSCsupportsthePresidentonnationalsecurityandforeignpolicyissues,includingontheGHSA.114,115
FundingDecisions
Whenconsideringbudgetrequests,OMBstafffavorprogramsorpoliciesthatdemonstrateclearneedsandtangibleoutcomes.Forglobalhealthprograms,assessmentmayincludefactorssuchasdiseaseburdenandimpactanalysis.ThisprioritizationapproachhasapotentialbiastowardsR&Dproductswithanimmediatehigh-impact,undercuttingR&Dproductswithlongerdevelopmentperiods.Asaresult,certainglobalhealthareasareneglectedpartlybecauseitishardertomeasuretheireffectiveness.StakeholderscitedthisasapotentialcauseforHIVbudgetflat-liningandthesuccessofmalariafunding.
Inadditiontoprogramperformancedata,factorssuchaspoliticalconcernsdriveOMB’sfundingdecisions.OMBdoesnotdirectlyengageinmonitoringandevaluationofindividualprograms,butwillratherrelyondataprovidedtothembyUSGagenciesandadvocates.AndwhilestakeholdersindicatedthatOMBstrivestostayabovethepoliticalfray,staffconsiderthepoliticalrealitiesofaprogramorbudgetrequest.WithaCongresswaryofincreasedspending,agencyproposalamountstendtobeinlinewithpreviousyears.OMBwillconsiderappropriationsandreportlanguagetocraftpoliciesandgaugeCongressionalappetite.OMBmakesanexceptioniftheAdministrationfeelsstronglyaboutanissue.
AlthoughOMBdesignedthereviewprocesstobeimpartialandsystematic,keyinformantsstatedthatfundingdecisionsaresusceptibletothepersonaldiscretionofindividuals,particularlyasthosedecisionsmoveupthechainofcommand.112Stakeholdersparticularlynotedthatoutcomesaremorelikelytobesuccessfulwhenindividualagencydirectorscoordinatetheirbudgetrequestsandoveralllobbyingeffortsinsteadofadoptingapiecemealapproach.OMBemployeesmustusetheirjudgmenttointerprethowtoimplementthePresident’spolicies.112Additionally,theymayhaveapersonalpreferenceforspecificprograms.Theextentandfrequencyofsuchpreferentialbehaviorisnotclearlyorwidelyunderstood.
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Section4.TheAppropriationsandBudgetProcess:InfluenceonGlobalHealthR&DInthissection,westepbackfromexaminingindividualUSGagenciesandfocusonprocesses“higherup”—specifically,theoverarchingappropriationsandbudgetprocessthatultimatelydeterminestheglobalhealthR&Dfundingenvelopewithinwhichagenciesmustoperate.
Notethattheprocessbelowappliessolelytodiscretionaryspending,whichmustbereviewedannuallybyCongress.Discretionaryspendingisapproximately35percentto39percentoftotalfederalspendingandencompassesthemajorityofglobalhealthR&Dprograms.116Mandatoryspending,whichincludestheDoD,isnotsubjecttoannualreviewandisleft“ongoing.”
BUDGETFORMULATION
ThefederalfundingprocessbeginswhenthePresidentsubmitsanannualbudgetrequesttoCongressinFebruaryforthefollowingfiscalyear(Figure15),inaccordancewiththeCongressionalBudgetActof1974.117Theproposalreflectstheadministration’sfederalprioritiesandprovidesdetailedbudgetrecommendationsperfederalprogram.Thepresident’sbudgetisnotlegallybindingonCongress,butsimplyreflectsthePresident’srecommendedspendinglevelsforprograms.Notably,CongressandtheExecutiveBranchdonotalwaysadheretothetraditionalbudgetandappropriationsschedule.Intheseinstances,Congresshasextendedthedeadlinestatutorilyorinformally.118
FederalagenciesandOMBworktogethertodevelopthebudgetrequest.Beginninginearlyfall,agenciessubmittheirbudgetrequeststoOMB.Overthenextseveralmonths,OMBreviewstheproposalswhileagenciesjustifytheirrequests.AgenciescanacceptorappealOMB’sdecision.111OMBthendevelopsthefinalbudgetproposalandsubmitsittoCongress.119,120
APPROPRIATIONSTIMEFRAME
InresponsetothePresident’sbudget,Congressadoptsanannualbudgetresolution,draftedandfinalizedbytheSenateBudgetandHouseWaysandMeansCommitteesthatsetsspendingceilingsforthefollowingfiscalyear(knownasa“302aallocation”).Underregularorder,abudgetshouldbeadoptedbyApril15th,althoughCongressmayenactseparatemotionstowaivethisrequirementandhasnotmetthedateinrecentsessions.116,118Thebudgetresolutiondoesnotappropriatefunding,butrathersetstoplevelfundingceilingsforspecificaccountsandactivitiestoguidetheworkofCongressionalappropriators.Importantly,theCongressionalbudgetdoesnotneedtomirrorthePresident’srequest—andoftenitreflectsdifferentprioritiesandpoliticalideology.
Afterthebudgetresolutionispassed,theAppropriationsCommitteesineachchamberdividesthebudgettargetamongthe12AppropriationSubcommittees,formingonetoplinesub-budgetpersubcommittee(knownas“302ballocation”).BothChambersconsiderappropriationbillsseparatelyand,asofmorerecently,concurrently.116Afundingbillispassedforeachsubcommittee,whichmeansthatunderregularorder,Congresspasses12appropriationsbills,whichmustbereconciledbeforetheentireappropriationsprocessiscomplete.Table7givesanoverviewofcommitteesandsubcommitteesinthe114thCongressthatoverseeagenciesinvolvedinglobalhealthR&D.120
Duringthistime,subcommitteestaketestimonyfromagencyofficialstohearspendingjustifications.116Congressionalcommitteestaffersmeetwithexecutiveagencyofficialsandnon-governmentstakeholderstoconsiderannualappropriationsforagenciesandprograms.AlthoughCongressoccasionallydelineatesfunding
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amountsforR&D,keyinformantsstatedthatCongressgenerallyfundsprogramsatahigherlevelandyieldstoagencyleaderstodetermineR&Dprioritieswithinthosespendinglines.Forexample,the2011DepartmentofDefenseandFull-YearContinuingAppropriationsActprovided$2.5billiontoUSAIDforglobalhealthprogramswithoutspecifyinghowmuchUSAIDshouldspendoneachactivity.121,122Inresponse,agenciesoftendeveloptheirownhealthstrategies,suchasUSAID’sGlobalHealthStrategicFramework.
InMayandJune,appropriationbillsareusuallysubmittedtotheHouseandSenatefloorforconsiderationbytheentirechamber.SincethefiscalyearbeginsinOctober,littletimeremainsfortheHouseandSenatetoresolveanydifferences.Congresshasnotenactedaregularappropriationsbillbeforethestartofthefiscalyearsince2009.123Whenappropriationslegislationisnotpassedbythestartofthefiscalyear,Congresstypicallyenacts“continuingappropriations”tomaintaintemporaryfundingatpreviousyear’slevelsuntilregularbillsareenacted.Ascontinuingappropriationsarefrequentlypassedinajointresolutiontheyaremorecommonlyreferredtoas“continuingresolutions.”116IfCongresshasnotpassedanappropriationsmeasureoracontinuingresolutionbythedeadline,affectedagencieslackbudgetaryauthorityandmustceasenonessentialactivities.119
AppropriationmeasuresareonecomponentofCongressionalfundingmeasures.Theothercomponent,knownas“authorizationmeasures”,“establish(es),continue(s),ormodif(ies)agenciesorprograms.”116WhileCongressusuallypassesappropriationsbillsforeachfiscalyear,authorizationbillsarepassedlessfrequently,sinceCongresscanauthorizeanagencyorprogramformultipleyears(e.g.,thePEPFARStewardshipandOversightActof2013authorizedPEPFARthrough2018).124WhileauthorizationlegislationpresentsanopportunitytoinfluenceglobalhealthR&D,manyprogramslackactiveauthorization,includingNIH(amountingto$31billionin2016).In2016,lawmakersappropriatedapproximately$310billionfor“unauthorized”programs.125
Inadditiontodirectlyfundingoramendingprograms,Congresscanprioritizeglobalhealthissues,andestablishtargetsforglobalhealthR&D,throughavarietyofothervehicles.Theseincludeholdinghearings,reviewinglegislatively-mandatedreportstoCongress,issuingCongressionalreports,approvingtreaties,orconfirmingpresidentialappointeestofederalagencies.122
Memberscanalsoformcaucuses—alsoknownascoalitionsorstudygroups—tofocusonaspecificlegislativetopic.Caucuseshavenojurisdictionoverauthorizationsorappropriations,butservetobringattentiontoanissue.Currentcaucusesrelatedtoneglecteddiseasesinclude:theCongressionalGlobalHealthCaucus,theCongressionalHIV/AIDSCaucus,theTuberculosisEliminationCaucus,theCongressionalCaucusonMalariaandNeglectedTropicalDiseases,andtheSenateCaucusonMalariaandNeglectedTropicalDiseases.126
Table7.AppropriationCommitteesandSubcommitteesinthe114thCongressthatOverseeAgenciesInvolvedinGlobalHealthR&D
AppropriationCommittees Function Subcommittees FunctionofSubcommittees
SenateCommitteeonAppropriations/HouseCommitteeonAppropriations
Appropriatefundsforallagencies
SenateLabor,HealthandHumanServices(LHHS)/HouseLabor,HealthandHumanServices(LHHS)
AppropriatesfundsforHHSandrelatedagencieswiththeexceptionofFDA
SenateStateandForeignOperations(SFOPS)/HouseStateandForeignOperations(SFOPS)
AppropriatesfundsfortheStateDepartmentandUSAID
SenateDefense/HouseDefense AppropriatesfundsfortheDepartmentofDefense
SenateAgricultureRuralDevelopment,FoodandDrugAdministration(Ag-FDA)/HouseAgricultureRuralDevelopment,FoodandDrugAdministration(Ag-FDA)
AppropriatesfundsforFDA
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Figure15.IllustrativeTimelineofAppropriationsProcess.Note:Tablereferstoconventionalbudgetprocess,butactualbudgetprocesscandiffer.
Pre-Appropriation Formulation Phase Congressional Phase
October
November
December
January
February
March
April
May
June
July
August
September
Authorizinglegislation is
introduced byHouse or Senate
during any point ofthe year. Becauseauthorization notlegally mandated,
numerous programsare increasinglyfunded without
active authorization.OMB Director sends budget
guidance (based on previous FY;stipulates any reductions) to
Agency or Department Directors
OMB and Agencies collaborate onbudget.
Agencies submit budget to OMBfor next FY
OMBreviewsbudgets Agencies submit
budget data fromprevious FY to OMB;
OMB submits budget toPresident
Agencies can appeal decisions anddiscuss with OMB/President
October 1: FY starts; OMB appropriatesfunding to Agencies
September 10 (or 30 days after bill isappropriated): OMB approves appropriations
request
August 21 (or 10 days after bill isappropriated): Agency submits appropriation
request to OMB
By July 15: President submits a revision of thebudget based on programmaticadjustments or
economic changes
By June 30: House AppropriationsCommittee appropriation bills (reviewed by
relevant subcommittee) are passed asRegular Supplemental, or Continuing
appropriations
House Appropriations Committee introducesappropriation bills; Senate considersHouse
appropriations as they are passed
By April 15: House/Senate BudgetCommittees pass (or not pass) Budget
Resolution
Subcommittees begin to hold hearings onappropriationrequests (following Committees: House - Energy &Commerce andForeign Affairs; Senate - ForeignRelations and Health,Education, Labor & Pensions)
By 1st Monday of February: President sendsBudget for the United States Government to
Congress (request for funding)
CBO develops new estimate of the President'sbudget based on economic outlook
Agencies submit Budget Justifications(reviewed by OMB) to send to Congressional
Committees
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Section5.CatalystsandBarrierstoUSGSupportforGlobalHealthR&DUptothispointinthereport,wehavechieflyfocusedonindividualagencies.Thisisappropriateasitreflectsthefactthatthereisno“whole-of-government”strategyforglobalhealthR&D,andthereisagreatdealofagencyautonomyforsuchresearchactivities.
Nevertheless,webelieveitisvaluabletotryanddraw“cross-cutting”lessonsforUSGsupportforglobalhealthR&Dfromacrossallagencies.Inthissection,wedescribethecross-cutting,cross-agencythemesthatemergedwhenweanalyzedthecollectiveresultsoftheliteratureandallkeyinformantinterviews.Wehavedividedthesethemesinto(a)catalysts(enablingfactors)and(b)barrierstosupportingglobalhealthR&D.
CATALYSTSTOUSGAGENCYSUPPORTFORGLOBALHEALTHR&D
Ouranalysisfoundfourmaincategoriesofcatalysts:collaborativeapproacheswithinandbetweenagenciesandprograms;marketincentivesofferedbyUSGagencies;supportivelegislativechanges;andregulatoryincentives.
CollaborativeApproacheswithinandbetweenAgenciesandPrograms
Disease-specificeffortssuchasPEPFARandOfficeoftheUSGlobalAIDSCoordinator(OGAC)leveragemultipleactorstoachievegreaterimpact.ThecombinedforcesoftheUSDepartmentoftheTreasury,theUSDepartmentofLabor,thePeaceCorps,HHS,DoD,USAID,CDC,andtheministriesofhealthanddefenseinimplementingcountriesresultedinmovingthenumberoftreatedindividualsfromzeroto10millioninarecordperiodoftime.StakeholdersarguedthatthelevelofsynergyandnetworkingshownbyPEPFARandOGAChave,unfortunately,notbeenreplicatedbyotherpartsoftheUSGforotherdiseasesorforbroaderresearchefforts.Butthesuccessshowsthatcross-agencyUSGcollaborationcanbedoneeffectively.
SeveralNIHvaccineresearchfundinginitiatives,suchastheVaccineResearchCenter(VRC),haveusedsuccessfulcollaborativeapproachestoaddresscriticalhealthcareneeds.127KeyinformantsarguedthattheVRCisagreatexampleofevaluatingneedsandtryingallpossibleavenuestodevelopamodelwiththebestchanceofsuccess.TheVRCwaslaunchedduringtheClintonAdministration,whenPresidentClintonaskedtheNIHandNIAIDdirectorsaboutthebarrierstoHIVvaccinedevelopment(theyexplainedthehighriskoffailureandthelimitedmarketincentivesasanimpedimentforindustryengagement).ThroughtheVRC,theUSGtakesontheriskofbasicdiscovery,candidatevaccinedevelopment,testlotsproduction,andearlystagetrials.USGthenlicensestheseproductstoindustry.Stakeholderscontendthatsinceinception,over50productshavegonefromdiscoveryintohumanclinicaltrials,includingtheSARS,pandemicflu,andEbolavaccines.Othertransformative,collaborativeNIHfundinginitiativesincludetheCenterforHIV/AIDSVaccineImmunology,theHIV/AIDSClinicalTrialsNetwork,andtheAIDSClinicalTrialsGroup.128-130
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TheGrandChallengesmodelallowsfor“organicandproductive”collaboration.TheGrandChallenge’sstagedfundingapproachwaswidelypraisedbystakeholdersasamodelforfacilitatingcollaboration.Aspreviouslynoted,GrandChallengesprovidesfundingacrossthedevelopmentcontinuum,fromseedgrantstoproductdeployment.Collaborationsareimportantinthisapproachbecausenotallagencieshavethenecessaryexpertiserequiredtobringaproducttomarket.However,theGrandChallengesmodelcannotbeusedtoadvancedrugsandvaccinesthroughlatestagedevelopment.Theonlytechnologiesthatitcanfeasiblytakethroughtomarketarediagnosticsanddevicesthatrequireonlysmallamountsoffunding.
Urgentpublichealthproblemsandaclearaskarestrongmotivationforbreakingdowninstitutionalandinter-agencybarriers;withoutacrisis,collaborationismuchharder.StakeholderspointedtotheFightingEbolaGrandChallenge,aresponsetotheWestAfricanEbolaoutbreak,asaprogramthatenabledprojectteamsatthestaffleveltobuildrelationshipsandgaintrust.Arepeatedthemeemergingfromourstudyisthatthiskindof“natural”trust-buildingcanbemoreeffectivethanforcedcollaboration,whichcanbackfirebybecomingpolitical.IntervieweesbelievedthattheresponsestotherequestforproposalsforthisGrandChallengecameinrapidlybecausetheproposalwasforaspecificrequest(“opportunitiestoco-create,co-design,co-invest,andcollaborateinthedevelopment,testing,andscalingofpracticalandcost-effectiveinnovationsthatcanhelphealthcareworkersonthefrontlinesprovidebettercareandstopthespreadofEbola”).131WhilecriseshavebeencatalyststoUSGsupportforglobalhealthproductdevelopment,theyalsodemonstratethecleartensionbetweentheshort-termgoalofaddressinganemergencyandthelonger-termobjectiveofcreatingasustainablefundingenvironment.CrisesallowtheUSGtobedirective,toquicklybuildconsensusonwhattheissuesareandwhoisgoingtotacklethem,andtoissueveryclearcallsforproposals.Incontrast,undernon-crisis“businessasusual”conditions,whenthecallsforproposalsarevague(e.g.,“thesearethediseasesweareinterestedinbroadly”),notonlyisitmoredifficulttogetagencybuy-in,butprivateindustrystaysonthesidelinesbecausethereisnoclarityaboutproductlinesandprofitmargins.
Cross-agencyglobalhealtheffortshavesucceededwhentheyareledeitherbytheWhiteHouseorthroughsustained,coordinatedeffortsledbyexecutiveagencies,asseenwiththeGHSAledbyCDC.132StakeholdersdescribedthisagendaasoneofthemostexcitingareasCDChasbeeninvolvedwithforacceleratingproductdevelopmentforglobalhealthchallenges.Theagendaaimstobuildcapacityincountriestorespondtothreats;whilestakeholdersdescribedcapacitybuildingasbeing“lessdramaticthantreatingnewbornsformalaria,”theythoughtthatithadmuchmorelong-termpotentialtodogood.
Theimprimaturofahighlevelfederaladvisorycounciliscriticaltobringaboutproductivecollaboration,asseenwithPACCARB,whichaimstoaccelerateproductdevelopmentbystreamliningeffortsatthehighestlevel.Announcedin2015,PACCARBisahighlevelfederaladvisorycommitteethatincludesliaisonsfromkeygovernmentagencies(includingDoD,FDA,CDCandNIH),academia,andindustry,withamandatetodeveloprecommendationstoHHSonhowto“de-stovepipe”concurrenteffortsandreduceduplication.132PACCARBwaschargedbyHHSleadershiptospecificallyconsiderwhatincentivesmightberequiredtospurdevelopment,deployment,utilization,anduptakeofdrugs,vaccines,anddiagnostics.OneresultoftheinitiativewasthatCDCandDoDlearnedthattheywereworkingonasimilarprojectandthattheDoDhad36thousandwell-characterizedsamplesthattheCDCcouldalsouse.TheNationalVaccineAdvisoryCommitteewashighlightedasanotherexampleofahighleveladvisorycouncil.133
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Additionalhigh-levelentitiesthatcansupportcollaborationincludetheOfficeofScienceandTechnologyPolicy(OSTP)andtheNationalScienceandTechnologyCouncil(NSTC).AlthoughUSAIDhasrecentlyundergoneareorganization,theOSTPandtheNSTCwerebothdescribedaseffectiveentitiesforbringingcollaborativegroupstogetherfordiscretepurposes.115,134Establishedbycongressin1976,OSTPisauthorizedtoleadinteragencyeffortsondevelopingandimplementingscienceandtechnologypolicyandtoworkwithallsectors(particularlytheprivatesector,stateandlocalgovernments,andthescienceandhighereducationcommunities)andothercountriestowardthisend.BecausetheOSTPhasconveningpowerandisabletosetupworkinggroupsandchartersforoperation,itwasveryeffectiveduringtheEbolaGrandChallenge,settingaclearresearchagendafortheresponse.StakeholdersbelievedthatusingtheOSTPwouldbeunwieldyforanoverallglobalhealthstrategy,butthatitcouldbeveryeffectivefordiscretepurposes.
MarketincentivesofferedbytheUSG
BARDA’sintegratedpushandpullmechanisms,aswellasitsOtherTransactionAuthority(OTA)thatallowsittoestablishlongtermportfoliopartnershipswithindustry,isseenasamodelforUSGengagementwithPDPs.ThroughOTA(firstgrantedtoDARPAin1989),BARDAcanestablishcommercialrelationshipswithprivatesectorpartners,exemptfromfederalacquisitionsregulations(FAR).135,136Onesuchrelationshipistheproductportfoliopartnership,whichpoolsfundsforclinicaldevelopmentandcreatesajointoversightcommitteecomprisedofBARDAandpharmaceuticalrepresentativestosharedecisionmakingforanentireportfolioofproductsoverthelongterm.Beforetheseportfoliopartnershipswereestablished,itcouldtakeupto18monthstosetupacontractforasingleproduct.Ifthatproductfailed,thecontractingworkwaswasted.Theportfoliopartnershipremovedbarriersthatwouldhavediscouragedpharmaceuticaldevelopersfrommanufacturingcertainproducts.Forexample,shortlyafterAstraZenecadisbandeditsanti-infectivesdivision,afive-yearportfoliopartnershipwithBARDAinvolvingfederalcommitmentsofupto$220millionpersuadedthecompanybackintotheantibioticR&Dspace.137
AnotherUSGmarketincentive,thePRVprovidedbytheFDA,isseenbysomeasawelcomeadditiontotherangeofincentivemechanisms,eventhoughitsimpacttodateisnotclear.Underthe2007lawthatestablishedthePRV,adeveloperofatreatmentforaneglectedorrarepediatricdiseasereceivesavoucherforpriorityreviewfromtheFDAtobeusedwithaproductofitschoiceorsoldtoanotherdeveloper.KeyinformantsarguedthatthePRV,whichwasconceptualizedatDukeUniversity,hashadsomesuccessincreatinganincentivemechanismforneglecteddiseaseR&D.Sinceitsintroduction,vouchershavebeenawardedforseveralneglectedinfectiousdiseases,includingmalaria,TB,leishmaniasis,andcholera.138Buttheoverallimpactremainsunclear,assomeproductsmayhavebeendevelopedevenintheabsenceofthevoucherscheme.
TheGrandChallengesmodelalsoactsasamarketincentive.Thecontestsencourageinnovatorsfromoutsidegovernmenttoinvestindevelopingnewtechnologiesforspecificchallenges.
Supportivelegislativechanges
AnimportantfindinginourstudyisthatthereareexamplesofCongressenactinglegislationinwaysthatstrengthenUSG’sroleinglobalhealth,includingglobalhealthR&D.CongressplaysanimportantroleinstrengtheningtheUSG’sroleinglobalhealth,includingglobalhealthR&D.ExamplesoflegislativechangestoenhanceUSeffortsinglobalhealthR&DdemonstratetheimportantroleofadvocacytoCongress.
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Examplesofsuchamendmentsinclude:• CongressbroadeningCDC’smandateafterCDCstaffarticulatedaneedtoprotectAmericansglobally.
• AfterthelaunchofPEPFAR,theWhiteHouseestablishedaspecialprocessforFDAtoapprovegenericHIVdrugsexclusivelyforuseoverseas.ThiswasthefirsttimeanFDAprocesswascreatedtomeetthisobjective.FDA’sworkwithPEPFARhasbeenevenmoreeffectivethanexpected,havingapprovedmorethan180therapies,includingpediatricformulations.75
• LegislationestablishingtheNationalVaccineInjuryCompensationProgram(VICP),whichprovidedvaccinecompaniesprotectionagainstinjury,andasimilarprogram,theCountermeasuresInjuryCompensationProgramrelatedtopandemicfluvaccinesandotherMCMs.139,140
TherehasbeenprecedentforvaluableexpansionofaUSGagency’smissioninsupportofglobalhealthR&D.Forinstance,CongressandtheexecutivebranchextendedBARDA’sremittoincludeAMR.
Regulatoryincentives
FDAhasatitsdisposalarangeofregulatoryincentivesthatcanhelptocatalyzeproductdevelopmentforglobalhealthchallenges.Twoexamplesthatweregivenbykeyinformantsare:
• FDAapprovedbedaquilinefortreatmentofmulti-drug-resistantTBattheendof2012,eventhoughinthephaseIItrialmorepatientsinthetreatmentgroupdiedthanintheplacebogroup.141FDAdeterminedthatthebenefitsofthedrugoutweighedtherisks(the10-yearmortalityfromthediseaseis70percent).FDAapprovedthedrugunderitsacceleratedapprovalprogram,which“allowstheagencytoapproveadrugtotreataseriousdiseasebasedonclinicaldatashowingthatthedrughasaneffectonasurrogateendpointthatisreasonablylikelytopredictaclinicalbenefittopatients.”142Italsograntedthedrugfasttrackdesignation,priorityreviewandorphan-productdesignation.
• TheEmergencyUseAuthorizationauthority,whichwasaneffectiveplatformwithinFDAforfasttrackingdiagnostictestingforZikaandEbola.143
BARRIERSTOUSGSUPPORTFORGLOBALHEALTHR&D
Ouranalysisfoundfivemaincategoriesofbarriers:theinstitutionalsiloesandunwieldysystemsthatmakecoordinationdifficult;insufficientfundingandlackofaglobalhealthchampion;under-useofeffectiveagencies;inadequateincentivestructures;andalackofaclearmechanismacrossandwithinUSGagenciestotrackUSGfundingforglobalhealthR&D.
Institutionalsiloes,unwieldysystems,andthedifficultyofcoordination
Thoughtherehavebeensomeexamplesofsuccessfulinter-agencycoordinationinglobalhealthR&D,agencieslargelyworkinsiloes,hamperedbysystemicbarriers.Twoexamplescitedbystakeholdersare:• TheNIHprocessisdisconnectedfromtheFDAapprovalprocess,inpartduetoconcernsaboutconflictofinterest.
• USGstakeholdersreportedthattheunwieldycontractingprocesskeepsagenciesapart.IftheDoDweretogotoNIHtoinvitekeyresearchersovertoWRAIRtoworkonpromisingdatacomingoutofitsbiomedicalresearchlabs,thereisnoeasycontractingmechanismtomovethatforward.Itwouldbealengthyprocesstogetacontractorinteragencyagreementinplace—withtheresultthatagenciesjuststicktothemselves.
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ThefailureoftheGlobalHealthInitiative(GHI)exemplifiesthedifficultiesinaddressingcoordinationacrossagenciesandsuggeststhattryingto“force”acollaborationcanhaveunintendedconsequences.GHIbeganin2009asanattempttointegrateprogramsandconsolidateseparatefundingstreams.AnOperationsCommitteemadeupofofficialsfromUSAID,CDC,andtheStateDepartmentoversawGHI,withguidancefromOMBandtheNSC.144By2012,theleadershipofGHIwasexpectedtotransitiontoUSAIDfromtheStateDepartment’sOGAC,contingentonUSAIDcompletingmanagementbenchmarks.145UltimatelyGHIneverliveduptoitsgrandvision.146Stakeholdersattributethistoavarietyofreasons:• GHIhadnoclearstatutorydecision-makingauthorityorleadershipstructure.• Therewerenoseparateappropriationstoachieveitsobjectives.• AlthoughGHIwastaskedwithcoordinatingacrossparticipatingagencies,PEPFAR—about70percentofGHI’sbudget—continuedtobehousedwiththeStateDepartment’sOGAC,separatefromGHI.
• Therewerereportsofinteragencydiscord,withagenciesunwillingtoacceptUSAIDleadershipofGHI.147StakeholdersstressedthedifficultyinfindinganappropriateunifyingglobalhealthchampionbutsuggestedtheAdministrationshouldplaceleadershipofglobalhealthwithonepersonorentity.Thispersonshouldkeepeveryone’seyeonthetarget.ThishappenedtosomeextentwithEbola,butthatenergyhasfadedaway.
• GHI’sscopewastoobroad,ittriedtodotoomuch(includingR&D,programimplementation,policyanddiplomacy),andtheconceptitselfwastoovast,leadingtonoclearunderstandingofitspurpose.Insteadoftakingonsomethingsohuge,itwouldhavebeenbettertoagreeonareasthatpeoplewereinvestinginandseeingifthesecouldbebettercoordinated.
• FundingintendedforGHIendedupbeingsiphonedofftoothermorehighprofileprograms.148• ManyUSGstakeholderscitedthefailureofGHItogaintractionasacasestudyinhow“forced”attemptstoimprovecoordinationcanbackfire.148Somewerevocalopponentstooftheconceptofa“wholeofgovernment”approachandforcedcollaborationfromabove,emphasizingthatglobalhealthisnotmonolithic,ishardtocharacterize,andrespectiveagencieswithintheUSGhavetheirownspecificgoals,objectives,andmandates.
Withinandbetweenagencies,USGstakeholdersindicatedtheremaybestructuraldivisionsthatcanimpedeglobalhealthR&D.Forexample:• R&Deffortswithinanagencyareoftendivorcedfromitsdiseasecontrolprogramsandscale-upefforts—amissedopportunityfortestinginnovativeproductsinthefield.
• JurisdictionaldivisionsinCongressionalappropriationsandbetweenOMBofficescanstovepipeR&Dfundingdecisionsandimpedecoordination.Whilethereareinstancesofcommunicationacrossoffices,givenresourceconstraints,itisprimarilylimitedtoavoidingredundantworkratherthanfosteringagency-wideinitiatives.
Insufficientfunding
Amajorchallengetoglobalhealthproductinnovationisthefundinggapforthistypeofresearch.LowlevelsoffundingatCDC,forexample,havesloweddownthedevelopmentofapromisingdiagnosticfortrachomathattestsbacteriallevelsinsteadofrequiringaneyeexamination.BudgetcutsandsequestrationshaveshrunkalreadylimitedglobalhealthR&Dfunding,slowingdownproductdevelopmenteffortsatseveralagencies.149Forexample,Ebolavaccinedevelopmentwasstalledasa
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resultofthesequester.150OneanalysisoffundinglevelsforEbolaresearchconcluded:“clearly,budgetcutsareleadingtoreduceddollarsforfindinganEbolavaccine.”150
ThevariousinstitutesatNIHhavereachedthelimitofwhattheycanallocateandhavebeenforcedtotakefundsfromotherareastodealwithemergencies.TheunpredictabilityofcompetitivegrantfundinghasalsomadeitdifficultfortheNIHtofocusonlongtermgoals.Stakeholdersfearsthattightbudgetswillallowothercountries’scientificinnovationtooutpaceUSinnovation.
FundingforglobalhealthR&DislikelytobefurtherjeopardizedbythelackofanidentifiablechampiontodrivetheUSG’sglobalhealthagenda;thedifficultygainingsupportforsomethingnotdirectlyimpactingtheUSpopulation;andpartisandivisionsinCongress.PartisanshipinCongresshasresultedinapoliticalclimatewhereevenessentiallegislationhastroublepassing.Thisisparticularlyevidentingovernmentfunding.Overthelastdecade,ithasresortedtolast-minutemeasuressuchascontinuingresolutionsinsteadoffollowingtheconventionalappropriationsprocess.Politicalgridlockhindersanagency’sabilitytoachievealong-termbudgetaryoutlook.Stakeholderscitedtheabsenceofalong-termappropriationsframeworkascreatingchaos.
Financingoflater-stageclinicaltrials,criticaltotranslatingresearchintoproducts,hasbecomeprohibitivelyexpensive.Newthinkingisneededonhowglobalhealthresearchcanbedoneinmorefrugalandefficientways.Oneofthebiggestmissedopportunitiesarelessonsthatcouldbelearnedfromfailed,unpublishedclinicaltrials.
Anotherresultofinadequatefunding,arguedseveralkeyinformants,isthatUSGdoesnothavesufficientR&Dsurgecapacity.Suchcapacitywouldneedanewappropriation.SomestakeholdersarguedthatjustincreasingfundingwillnotaccelerateglobalhealthR&DunlessotherweaknessesinthecomplexR&D“ecosystem”areaddressed.Thesekeyinformantsarguedthat(a)thereisatendencytooversimplifytheproblembyassumingthatmoremoneyisthesolution,and(b)therewillneedtobebetterincentivemechanismsandmorediverseandrobustfundingvehiclestostrengthenUSsupportforglobalhealthR&D.SomeUSGstakeholdersviewthecurrentconversationoverglobalhealthfundinglevelsaslessimportantthanhowtobetterdirectexistingfundstodrivethemarketforproductdevelopment.
Under-useofeffectiveagencies
TheDoD’sglobalhealthR&Dcapacityisbeingunder-used—amajormissedopportunity.Keyinformantsarguedthatthereissignificant,under-usedvalueinDoDoverseaslabsforglobalhealthR&D,includingforvaccinedevelopment.ThereisaperceptionwithintheUSGthatwhenyouneedvaccinedevelopment,youmustgototheNIHbecausethatiswherethescientificexpertsareandtheNIHhasabigbudget.YetNIH’scorecompetencyisnotproductdevelopment.TheDoD’scapabilitiesarebeingoverlooked—aquarterofvaccinesapprovedbytheFDAinthelastcenturyhavebeendevelopedwithDoDparticipation.151
StakeholdersarguedthatDoD’smedicalR&Ddoesnotgettherecognitionthatitdeserves,andisdwarfedbyhigherprofiledefenseprojects.ThecoremissionofDoD—theprovisionofthemilitaryforcesneededtodeterwarandtoprotectUSsecurity—hasnodirectlinktoglobalhealthresearch,andsome(thoughnotall)membersofCongressbelievesthedepartmentshouldstayfocusedonitscoredefenseresponsibilitiesratherthanextendingitself.Seniormedicalmilitaryleadershipismorefocusedontreatmentneedsandthecrisisoftheday,suchasaccesstomedicalcareforveterans,traumaticbraininjury,andpost-traumaticstressdisorderandsuicide,ratherthanR&D.Additionally,whileDoDpolicyandbudgetinghaveawell-oiledmachinetosecureadditionalfundingfromappropriatorsand
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committeestafffordefenseprojects,thatkindofmachinedoesnotexistonthemedicalside.Andwhileglobalhealthchallengeshaverecentlybeenframedthroughasecuritylens,asseenwiththeGHSA,globalhealthisstillseenas“lowpolitics”withinthenationalsecurityworldcomparedwithotherthreats.Asaresult,globalhealthresearchexpertsmaynotcommandasmuchattentionfromseniorleadershipasnationalsecurityexperts.
Historically,WRAIR,whichpredatedtheNIH,wastheplacetogointhefederalgovernmentfortranslationalmedicalresearch,whetheritwasforthefirstfluvaccine,meningococcalvaccine,acurefortyphoid,typhustherapyinrefugeesafterWWII,andmore.152ButasHHSandNIHgrew,thecontributionofWRAIRanditsresearchworkgoteclipsed.
Inadequateincentivestructures
TherewaswidespreadagreementamongkeyinformantsthatthecurrentincentivemechanismsforglobalhealthR&Dareinadequate;newermechanismsareneededthatwouldprovidelarger,morereliable,longer-termfinancing.OngoingmarketfailureshighlighttheinadequacyofthecurrentincentivestructurestopromoteproductinnovationanddiscoveryintheareasofAMR,EIDs,andNTDs.Inaddition,itisdifficulttopredictintheabstractwhatwillbeneededinthefuture.Forinstance,recentoutbreakssuchasEbolaandZikawereneveranticipatedandtheexistingstructureswerenoteasilyadaptabletomeettheseoutbreaks.
NoclearmechanismtotrackUSGfundingforglobalhealthR&D
Thereisnocommon,standardworkingdefinitionofR&DacrosstheexecutiveagenciesandnoclearmechanismtotrackR&Dfundingflows(e.g.,therearenoclearbudgetlinesforglobalhealthR&D).ThisinconsistencypreventsOMBfromadequatelytrackingglobalhealthR&Dacrossmultipleexecutivebranchesandlimitsconversationsaboutcoordinationthatmightotherwisehavebeentriggered.
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Section6.PerspectivesfromIndustry,ProductDevelopmentPartnerships,andFoundationsInthissectionwebrieflysummarizeperspectivesoftwogroupsofkeyinformantsfromoutsidegovernment—onegroupcomprisingseniorrepresentativesfromsixcompaniesthatconductglobalhealthR&D,andtheothermadeupofseniorrepresentativesfromeightNGOs,PDPs,andfoundations(Table3).Toavoidrepetitionandredundancy,wefocusonwaysinwhichtheirperspectivesweredistinctfromthoseoftheUSGkeyinformants.Oneaimofthissectionistoexplorewhatitislikeforprivatesectoractors(bothfor-profitandnon-profit)topartnerwiththeUSGonglobalhealthR&D.
PERSPECTIVESFROMINDUSTRY
Industrystakeholdersindicatedasignificantcommitmenttodevelopinginnovationstoaddresstheunmetneedsofvulnerablepopulations,basedonsocialresponsibilityandthevisionoftheirleadership,despitethechallengespresentedbythelimitedreturnoninvestment.Whentheirscientistsidentifiedinnovativeopportunitieswithintheirlibraryofassets,theyfeltanobligationtomakethemwidelyavailabletobothdevelopedanddevelopingcountries.Insomecases,commitmentand,consequently,fundingweresusceptibletochangesinleadership.Whenpossible,companiestrytoinvestinproductsthathavemulti-marketpotentialtoaddresssimilarneedsinbothlowandhigherincomepopulations,improvingexpectedreturns.Somecompanieshaveestablishedinstitutesdedicatedtononprofitmissions,orhavelookedatspinningoutaportionoftheirportfoliointoafoundationtoeliminateinvestorconcernsaboutreturnoninvestment.
Despitethiscommitment,industryscientistsfacesignificantpressuretocreateacostneutraldevelopmentenvironmentbysecuringfundingfromnontraditionalsources.Whileitishelpfulforcompaniestoestablishinternalring-fencedbudgetstopreventglobalhealthprojectsfromhavingtocompeteinternallyagainstothermoreprofitablemainstreamprojects,theystillrelyonexternalfundsforglobalhealthR&D.Fundingopportunitiescancomefrompartnershipswithotherpharmaceuticalcompanies,academia,foundations,USG,WHO,orPDPs.Somecompaniesareexploringinnovativefinancingsources,suchas:• Socialimpactbonds:socialinvestorstakeontherisk,whichislinkedtothesuccessfuldevelopmentofaproduct(successmetricsarepre-defined);ifthemetricsareachieved,investorsarepaidapremiumbyguarantorssuchasBMGF.
• Venturephilanthropyfunds:inthismechanism,returnsarebasedonthehealthvaluecreated(e.g.,DALYsaverted)ratherthanbeinglinkedtoaspecificproduct’sdevelopment.
Industrystakeholdersdescribedfundingand“go/no-go”decisionsascomplexprocessescontingentupon(a)innovativescientificopportunityandimpact,(b)burdenofdiseaseandunmetmedicalneed,and(c)marketconditions,suchasthedistributionnetwork,thepurchasingpowerofthepatientand/orgovernment,theregulatorylandscape,andthereturnoninvestment.Industrystakeholdersthoughttheindustrywaswellpositionedtoaddressmostoftheseissues,butwasstrugglingtoovercomethebarriersofhighriskinvestmentintheabsenceofadequatemarketreturn.
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Pushandpullmechanisms—includingthoseofferedbytheUSG,suchasresearchfunding(push)thePRV(pull),andorphandrugdesignation(pushandpull)—areimportanttoindustrybutnotthekeydriverintheirdecision-making,inpartbecausetheincentivesonlyaccountforafractionofthetotalcostofdevelopingaproduct.IndustrystakeholdersviewthePRVandorphandrugdesignationaspartofthesolution,butnotthewholesolution.Given(a)investmentdecisionsforproductdevelopmenthaveatleastaten-yeartimehorizon,(b)theattritionofsuccessfulmolecules,and(c)diminishedvalueofmoneyovertime,thePRVisseenasbeinginsufficienttoencourageearlystageinvestmentallbyitself.Industryindicatedthereisahugeneedforseedfunding,suchasthatprovidedbytheWellcomeTrust,oradvancedmarketcommitments,suchasthoseprovidedbytheUSGforbiodefenseprojects,tojumpstartearlydiscoveryworkattheoutset.
Industrystakeholdersalsosuggestedthatmarketincentivesarenotasreadilyavailablefordiagnosticsastheywereforvaccinesanddrugs.However,thisperceptionislikelytobeduetolowawarenessofsuchincentivesamongtheindustrykeyinformants;therearemoreprizesfordiagnosticdevelopmentthantherearefordevelopingdrugsandvaccines,andtherearealsomajordiagnosticprocurementprograms(e.g.,throughtheGlobalFund,UNITAID,thePresident’sMalariaInitiative,andtheClintonHealthAccessInitiative)thathelptocreateadefactomarketincentive.
Criticalfactorsconsideredearlyonbyindustrykeyinformantswhenmakinginvestmentdecisionsareknowingthedownstreamplansformarketing,whowillpurchasetheproduct,andhowitwillbedistributed.Thesekeyinformantsnotedthatifthereisnotsometypeofcommitmentbyfundingagencies,foundations,orlocalgovernmentstoprocuretheproducts,thentheeffortjustgoestowaste,discouragingfutureinvestment.
IndustrystakeholdersexperiencesignificantbarrierstopartneringwithUSG.Theseincludebureaucraticprocesses,complexreportingrequirements,slowFDAapprovalsystems,limitedlevelsoftranslationalfunding,andoveralllackofpoliticalwilltopartner.Ofthese,thetwomostimportantare:• TheFDAapprovalsystem.SomestakeholdersavoidseekingFDAapprovalforproductsintendedforuseoutsidetheUS,thoughothersbelievethereissignificantvalueingoingthroughthestringentFDAapprovalprocessasitassureshighmedicalstandardstodifferentregulatorybodiesworldwideandsoexpeditesapprovalintoothermarkets.SomebelieveFDAlackstherequisiteexpertiseforneglecteddiseasesubmissionsandareinclinednottopursueFDAapprovaliftheproductisonlyintendedtobeusedinjustafewcountries.StakeholdersviewedtheEuropeanMedicinesAgencyapprovalprocessasbettersuitedtoglobalhealthneedsand,ifsecured,asameanstoexpediteapprovalbytheFDA.WhilesomeindustrykeyinformantsarguedthattheWHOprequalificationprocessisrelativelyeasyandflexible,otherscommentedthatitwasgettingmorecumbersomeandnotaneasywayout.DevicecompaniesweremorelikelytoseekCEMarkcertification,anindicationthataproductmeetsallofthesafetyrequirementsoftheEuropeanUnion,asitwasconsideredmuchsimplerthantheFDAapprovalprocess.153
• LowlevelsoftranslationalfundingfromtheUSG.Theamountsoffundingonthetablefortranslationalresearcharerarelyatthelevelneededtoincentivizeindustry.Or,asonekeyinformantputit:“thepaylinesareworsethaneverandthefundingisminiscule—theNIHspreadsthestuffsothinyoucan’teventastethepeanutbutter.”OneindividualindicatedthattheDefenseThreatReductionAgencyprovidedaflexiblefundingmechanismthatprovided“real”moneyfordrugdiscovery(e.g.,againstbiologicalthreats),butitwouldneedtobeexpandedbeyondbiodefensetohavearealimpactonglobalhealthR&D.154StakeholdersthoughttheUSGcouldtransformitselftobearealplayeringlobalhealthinnovationbychangingitsmodelcompletely,toapproachinnovationinthewaythattheDepartmentofEnergydidduringtheearlydaysofthe
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Obamaadministrationtoadvancerenewableenergytechnology.Aspartofthe2009AmericanRecoveryandReinvestmentAct,largemarketincentives(loan,guarantees,advancedmarketcommitments)wereofferedforthedevelopmentof“neworsignificantlyimprovedtechnologies.”155TheincentiveswerecoupledwithtechnicalsupportfromexpertsintheDepartmentofEnergytohelpnewtechnologiesovercomethebarrierstocommercialization(the“valleyofdeath”).Hundredsofsubmissionswerereceivedduringthewindowfornewapplications.Thereisevidencethattheprogramhelpedtobringdownthecostofelectricityproducebywindturbines,boostvehiclefuelefficiencystandards,andexpandsolarenergyproduction.
IndustryengageswithPDPsandPPPstoleverageexpertiseandfinancingnotavailablewithintheparentcompany.Partnershipstypicallyevolveaftertheparentcompanyhasdonesomepreliminarydiscoveryworkeitherinternallyorinpartnershipwithacademiaandhasgeneratedsufficientdatatoallowthemtodevelopacredibleproposalforfunding.PDPsenablesmallercompaniestodevelopnewskillsincross-sectorcollaborationsthattheycanapplyinfastgrowingmarketssuchasIndiaandChina.OthercompaniesengagedirectlywithUSmilitaryhospitalssotheycandoanimaltestingoreventuallypurchasemedicationsforstockpiles.
Despitethebenefitsofcollaboration,somestakeholdersconsiderpartnershipstobemoredifficulttomanagethangoingitalonebecausegoalsarenotalwaysaligned.Onecriticismwasthatacademicpartnersweremoreinterestedinrapidlypublishingwhileindustrywasmorecautiousaboutwhentheywoulddiscloseinformationandgiveuptheirintellectualproperty(IP).Manystakeholdersbelievedtheircompaniesalreadyhadend-to-endcapabilitiesandsupportingfunctionssuchasregulatory,finance,legal,toxicology,manufacturing,anddistributionteamsthatcouldfacilitateproductdeliveryandregistration,whichislostwhentheworkisshiftedoutsideoftheparentcompany.
Someindustrystakeholdersfavoredtechnologytransferasanequallyviablemodelforproductdevelopment.TheywerewillingtowaivetheirIPrightstopre-qualifiedpartnersalmostimmediatelyuponFDAapproval,transferringthetechnologytogenericmanufacturerswiththerighttoproduceandsellproducts.TominimizeabuseoftheIP,companiesnegotiatedaprice-ceilingagreementupfronttoensurethatthepriceofaproductstayedwithintheaffordablerangeforaconsumer.OneintervieweecommentedthatIndiangenericmanufacturerswerethebestathighvolume,lowmarginproduction.Andeventhoughtheparentcompanyrecoupedasmallroyaltyfromsales,theyindicatedtheywerenotmakingmuchmoneyinthesegeographies.
R&Dneedstobecoupledwithimprovedmodelstoexpandaccesstoinnovations;thesemodels,arguedindustrykeyinformants,needtoincludelocalgovernmentengagementandincreasingdomesticcommitmenttohealthfinancing.GreaterleadershipfromtheUSG,andfromWHOandothermultilateralorganizations,topersuadelocalgovernmentstomoreactivelyparticipateinadvancedmarketcommitmentsandovercomingregulatoryhurdlescouldbeinstrumentalinsecuringindustry’songoingR&Defforts.OneexamplegivenwashepatitisC,whichnowhascurative—butveryexpensive—drugtreatments(called“directactingantivirals”).156Onekeyinformantarguedthatmiddle-incomecountrieswillneedtocontributedomesticfinancingtoscaleuphepatitisCcontrolprograms.
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Industrystakeholdershighlightednovelaccessmodelsthatworktoovercometheconfluenceoflogisticalbarriersthatimpedemarketaccess.Stakeholderssuggestedthefollowingexamples:(a)providingmicrocreditsandloansformedicationprocurement,(b)technologytransfertogenericmanufacturers,and(c)healthworkereducationandtrainingtoaddresschallengesofweakhealthsystems.Twoprogramswerecitedasexamplesofsuchnewmodels:• TheMedicinesPatentPool(MPP),whichaimstoincreasetheaccessibilityofquality-assuredgenericproductsinLMICs.157Onecompanynotedthatbyplacingitsantiretroviraldruginthepool,itwasabletosellthedrugin112countries.SofartheMPPhassignedagreementswithsevenpatentholdersfor12ARVsandforonehepatitisCdirect-actingantiviral.
• PatentsforHumanity,avoluntaryprizecompetitionrunbytheUnitedStatesPatentandTrademarkOffice,whichprovidesacertificateforexpeditedprocessingofpatentsworkingonhumanitarianproducts.158TheprizecompetitionisbasedonthePRVprogram,butislesscommerciallyvaluablebecauseprioritizedexaminationcanbepurchasedattheUSPTOforjustthousandsofdollars.
Stakeholdersalsoindicatedtheimportanceofharmonizationinitiatives,suchastheworkoftheInternationalFederationofPharmaceuticalManufacturers(IFPMA)topromoteregulatoryharmonization.159BMGFhasalsospearheadedaCEOForumonregulatoryharmonization,particularlyfortheSouthAfricanDevelopmentCommunity(SADC)whereeconomicagreementsarealreadyinplace;theforumiscalledtheAfricanMedicinesHarmonizationProgram(AMRH).160-161ItishopedthattherecouldbeaNAFTA-typeagreementfordrugsthatwouldallowforeasieraccessacrosstheentireAfricanUnion,notjustlimitedtoSADC.
PERSPECTIVESFROMNGOS,PDPS,ANDFOUNDATIONS
KeyinformantsfromNGOs,PDPs,andFoundationssharedindustry’sviewthattherearepracticalhurdlespreventingcollaborationwithUSG.Itcanbechallenging,theyargued,toworkwiththeUSG’spiecemealprograms,disease-specificapproach,andagency-centeredR&Dactivities.Keyinformantsco-fundR&DbasedoncommongoalswiththeUSagencies,buttheprocessismessy,withmultiplebilateralMOUswithvariousUSagencies,orwiththesameagency,onvariousdiseases.“Walkingthepathofsplitcollaborations”hasbeenchallengingandfinanciallyinefficient,andleadstoduplicationofefforts.
StakeholdersfromthissectorfeelthattheUSG’sfundingforglobalhealthR&Disbeinghinderedbythelackofanexplicitprioritysettingprocess.Withoutsuchaprocess,congressionalandUSdiplomaticprioritieslargelydeterminetheseinvestments,intermsofprioritycountriesanddiseasesaswellasbudgetallocations.USAIDprioritizescountriesofstrategicimportanceandUSmilitarypresenceisanotherdeterminantofwhichdiseasesandregionsareprioritized—anapproachthatcanworkagainstfundingforR&Dforcertaindiseasesorcountries.Withineachgovernmentagency,R&DprioritiesareinfluencedgreatlybyreportsfromtheNationalAcademiesaswellasbyadvisoryboardsandtaskforcecommittees.Assuch,influencingprioritizationwouldmeanpenetratingthebureaucracytoreachvariousactorsintheseagencyadvisorypanelsaswellasadministrativeandexecutiveoffices.AgencieslikethePresident’sCouncilofAdvisorsonScienceandTechnology(PCAST)are“heavyweights”intermsoftheirexpertiseandinfluenceonprioritysetting;thegrowingfocusonAMRisaresultofthegreatpushonthischallengefromPCAST.162
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NGOswhoworkonadvocacyforincreasedglobalhealthR&DfindtheUSG’slong,complexbudgetandappropriationsprocessamajorbarrier.Therigidityofthesystemandthelengthoftheprocessmakeitraretoseeanimmediateimpactofanyadvocacyefforts.BudgetaryincreasesmaynotguaranteeadditionalR&DfundingbecauseoftheinterlinkageofthevariousagencybudgetsandbecausetherearenotdirectR&Dfundinglines.Forexample,iffundingisincreasedundertheLabor,Education,HHSfundingbill,theincrementmaynotnecessarilyaccruetoNIH,becausemorefundsforNIHmeanslesselsewhere.Informantsalsocomplainedaboutthenon-transparent“backroomdeals”thatfundcertainofficessuchasBARDA.
WhilethereissignificantUSGfundingforglobalhealthtranslationalresearch,keyinformantsarguedthatthereremainsanimbalance,giventhatUSGfundingforglobalhealthR&Disconcentratedattwoendsofthespectrum—upstreambasicscienceanddownstreamoperationalresearch.StakeholdersarguedthatwithNIHfocusedmostlyonbasicscienceandearlyclinicaltrials,andUSAIDfocusedonimplementationandoperationalresearch,thereisanongoinggapinthefundingoftranslationalanddiagnosticsresearchandproductdevelopmentplatformsthatarekeytodevelopingdrugs,vaccinesandtechnologies.Academicinstitutions,amajorrecipientofNIH’sextramuralfunding,havelimitedopportunitiesforsecuringadditionalfundingfortranslationalresearch.ThevoidinproductdevelopmentfundingisreflectedintherelativelackofUSGfundingforPDPscomparedwithfundingfromEuropeangovernments.Forexample,14percentofMMV’stotalfunding(receivedorpledged,from1999-2020)hascomefromUKDFID,andonlyfourpercentfromUSagencieslikeUSAIDandNIH.163MostofMMV’sfunding(60percent)hascomefromBMGF,thedominantUSfunderofPDPs.KeyinformantsarguedthatEuropehasamorereliablesupportandfundingsystemforPDPsandunderstandsthePDPmodelbetter.
KeyinformantshadmixedviewsonthePRV,butfeltitwastooearlytojudgeitsimpactanditspotentialmaynotyethavebeenreached.TheypraisedtheFDAforplayingacrucialroleinpopularizingthisincentiveandtryingtobringmorepartnersandresourcestoneglecteddiseaseR&D.SincethePRVisacommercialinstrument,informationonwhichproductsarebeingdevelopedliveswithinthecompaniesthemselvesandmaynotbepubliclyavailable—whichmakesithardforpeopleseethefullimpactofthePRVondrugdevelopment.Nevertheless,severalkeyinformantspointedoutthatPRVshavehadonlyashorttrackrecordofsuccessandcanhaveunintendedconsequences.ExpandingPRVstoomuchwouldmakethemlessvaluableonthemarket.ThereisalsosomeconcernthatthePRVschemedoesnotguaranteeaccesstoproducts,especiallybythepopulationswhoneeditthemost.
StakeholdershadpositiveviewsontheirexperiencesworkingwithindustryandgenerallysawbenefitsfromgreaterUSG-industrycollaboration.Whilesomeworkwithindustryonearlystageresearch,techtransfers,knowledgesharing,anddrugandvaccinedevelopment,othersconcentratemoreonthedeliverysidetoensureaccessandaffordabilityofmedicines.Oneexamplecitedwasthepublic-privateWIPORe:Searchconsortium,whichprovidesaccesstoIP,includingpharmaceuticalcompounds,technologies,know-how,anddataforglobalhealthR&D.164,165Bytheendof2014,theinitiativehadfacilitated70researchagreementsbetweenconsortiummembers.Mostkeyinformantsarguedthatwhilecriticismofindustryissometimeswarrantedforitsgenuineprofit-mongeringpractices,constantattacksonthesectorcouldovershadowitseffortstodevelopdrugsandvaccinesandtoaidtechnologytransfers.
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BMGFisaninfluentialfunderofglobalhealthR&D,andmostNGOsandPDPsinterviewedreceivedfundingfromthefoundation.TheresultisthatR&DprioritizationwithintheseorganizationsisgreatlyinfluencedbytheprioritiesofBMGF.Thisinfluencecanhavebenefits,arguedthekeyinformants,aslongastheprioritieshelpinmakingadvancementsinafieldwhereinvestmentsarehighlyrisky.However,concernswerealsoexpressedaboutBMGF’schangingpriorities,theseriousnessofitscommitmenttofundingPDPs,andtherecentshiftinitsfocusawayfromvaccinedevelopmentthroughPDPstowardsindustryplayers.ThisshiftmayhaveresultedfromthehighrisksandcostsinvolvedinfundingtranslationalresearchandvaccinedevelopmentandtheFoundation’sexperiencewiththeRTS,SmalariaandTBvaccines,whichprovedtobequiteexpensive($200millionwasprovidedbyBMGFforRTS,S).166SomekeyinformantsbelievedthatpartofthisshiftmaybeduethefactthattheGlobalHealthDivisionisnowledbysomeonewhocamefromindustry,whichmayhaveresultedinmoregrantsshiftingtowardsindustryandawayfromPDPs.WhiletheWHO’sProductDevelopmentforVaccinesAdvisoryCommittee(PDVAC)couldcreatemomentumtosupportPDPs,keyinformantsstatedthatitisreceivingsomepushbackfromBMGF.167
ImprovingtheUSG’spoorcoordinationwiththeWHOwouldbehelpfultotheUSG’sglobalhealthR&Defforts.SomekeyinformantsarguedthattheUSdoesnotrecognizethesignificanceandreputationenjoyedbytheWHOindevelopingcountriesinAsiaandAfrica.DuetothelackofcoordinationwiththeWHO,USGprocessesdifferfromtheWHO’sprocesses,creatingunnecessaryandtimeconsumingbureaucratichurdles.
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Section7.Stakeholders’SuggestionsforReformRecommendationsInthissection,wesummarizethesixmainsuggestionsgivenbykeyinformantsforreformsthatcouldimprovethewayinwhichtheUSGsupportsglobalhealthR&D.
1.TheUSGshouldimplementstrategiestosupportleadershipandcollaborationattheAgencylevel
USGstakeholdersrecommendeda“Manhattanproject”typeprogramforglobalhealthR&Dtargetedtoleaders(notnecessarilyattheSecretarylevel)toimprovekeycompetenciesinUSGagenciesandovercomethechallengeofmaintainingindividualagencymissionwhileworkingcollaboratively.ThisapproachwasoneofthereasonsforthesuccessofPEPFAR,witheachgroupmakingcompromisestoincreaseimpact.USGstakeholdersemphasizedthatseniorleadersshoulddriveandtakeresponsibilityforsuchaninitiative,otherwiseprogresswillbeincremental.SomeUSGstakeholdersarguedthatleadershipneedstocomefromtheWhiteHouseorCongress,otherwiseitwillbedifficulttobringallrelevantagenciestothetable,thoughothersworriedthatthiskindofforced,“top-down”collaborationwouldbeamistake.USGstakeholdersnotedthatCongressortheWhiteHouseshouldprovidenewresources,clearlydefinedgoals,andbudgetaryauthorityforthiskindof“ManhattanProject”typeprogram.
USGstakeholdersexpressedaneedformorejointstakeholdermeetingstoensurealignmentofprioritiestoexpediteproductdevelopmentandtofacilitatehand-offstoavoidgapsinthedevelopmentcycle(theynotedthatcancerhasdonemoreofthisthanotherdiseaseareas).KeyinformantsfromUSGbelievethatmanyofthechallengesarepracticalproblemsrelatedtoaccess,financing,anddeliveryoftheproductsthatare“interventionready.”Theycautionedagainstdevelopingaprescriptiveframework,notingtheimportanceofdiversityandflexibility.Non-USGactorsalsonotedthatgreaterflexibilityoffundingwouldimprovetheinvestmentenvironmentandpromotethefreeexchangeofideas.OneUSGstakeholdersuggestedthatanoutsidepartneroradvocacygroupcouldplayaconveningrole.
TheUSGshouldcreateataxonomyofglobalhealthR&DandclearlydefineR&Dtobettertrackresourceallocations,whichwouldallowOMBtobettertrackresourcesacrosstheboard.OSTPwasmentionedasthegroupmostlikelytoengageinthistypeofeffort.SuchtrackingcouldalsohelptoaligndifferentresearchactivitiesacrossUSGagencies;avoidduplicativeefforts;increasecosteffectiveness;andpotentiallydriveamoreintegrated,streamlinedapproachintargetingfunding.WhileUSGreportingmechanismsarecumbersome,stakeholderswerequicktopointoutthattheagenciesareanswerabletoCongressandtaxpayerstomakesurethatpublicfundsareusedwisely,soreportingrequirementsareessential.Butstreamliningreportingrequirementscouldbeahelpfulinnovation.
AnewforumorblueribbontaskforceintheNIHcouldbeestablishedtohelpwithglobalhealthR&Dprioritysetting.Thistaskforcecouldincorporatelessonsfromothersectors,suchasfromPCASTortheAmericanEnergyInnovationCouncil.168
2.TheUSGshouldinvestinR&DcapacitybuildinginLMICs
USGstakeholdersbelievethatmorefundingshouldbeinvestedindevelopingforeigninvestigatorexpertise,researchcapacitywithinLMICcountries,andregulatorysciencesothatsolutionsbecomesustainable.OneavenuetoachievethiswouldbetoproperlyfundtheFogartyCentertosupportin-countrycapacitybuilding.TheWorldBankandtheNationalAcademyofMedicinecouldbetwokeypartnersforthiswork,astheyarewellpositionedtoforecastwherethemostsignificanthealthproblemswillunfold.TheUSScienceEnvoyProgramisadvocatingforin-countryR&Dcapacitybuilding,andthisadvocacyshouldbematchedwithUSGfunding.Forexample,theprogramisadvocatingfor
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vaccineR&DcapacitybuildingintheMiddleEastandNorthAfrica(MENA)regionandtheestablishmentofavaccineresearchinstituteinSaudiArabia,butfundswillcomefromMENAgovernmentinvestmentsandnottheUS.169Bolsteringlocalnationalregulatorysystemstoattractmanufacturingcapacityandcreateinfrastructuretoensurethesafetyandqualityofproductscouldalsohelpsustaininvestmentforkeyprograms,suchasPEPFAR.
3.TheUSGshouldstepupitseffortsoncollaborationandknowledgeexchangewithoutsidepartners,bothdomesticallyandinternationally,tohelpinformglobalhealthR&DprioritizationandimproveR&Defficiency
TheUSGshouldworkmorecloselywiththeWHO,whichiswellplacedtoleadtheprioritizationofglobalhealthR&Dandtosupportregulatorysystemsaroundtheworld.AstheWHOcommandsinternationalrespectinthefield,USGshouldcollaboratemorecloselywiththeorganizationtodevelopnewR&Dstrategies,guidelines,regulations,andoperationaltools.Forexample,theUSGcoulddevelopapartnershipwiththeWHOtostrengthentheWHOGlobalObservatoryonHealthResearchandDevelopmentortoharmonizeregulationacrosstheWHOandFDA.170Non-USGactorsalsonotedthattheEuropeangovernmentssupporttheWHO,whichisgenerallyunderstaffedandunderfunded,bysecondinggovernmentpersonneltotheorganization.Thisbuildsworkingrelationshipsandhelpsalignprioritiesinthecountryoforigin.
IndustrystakeholdersrecommendgreatercollaborativeleadershipfromtwoUSGpartners—BMGFandWHO—asawaytostimulatemorerapidinnovation.Prioritiesshouldbeestablishedbaseduponanunbiasedoutlook,drivenbyscienceandneed,andnotbyoverarchingpoliticalandeconomicparameters.SpeedisoftheessencetomaximizeR&Dimpactandwithoutsynergisticoversightoftheentireglobalhealthportfolio,therewillbecontinueddevelopmentdelaysandwastedexpenditureonproductsoflimiteduse.
TheUSGshouldbetterengagewithindustryandnongovernmentactorstoshareknowledgeandcreateeconomiesofscale.Toincreaseinteractionwithindustry,theUSGcanusePDPsthatspecializeinsuchinteraction.OneexamplegivenofsuchaplatformwastheAnacor/MMVcollaboration,asuccessfuldrugdevelopmentpartnershipformalaria.171Anothervaluableknowledgeplatformwouldbeaglobalrepositoryofdataonnegativetrials.Thesinglelargest“blackhole,”saidtheindustrykeyinformants,isnothavingaccesstodataandinformationontrialsacrosstheindustrythatwerenegative.Significantlessonscanpotentiallybedrawnfromsuchnegativetrials,whichwouldbevaluablewhensimilarproductsarebeingdeveloped.Thislackoftransparencyoftenleadstoduplicationofcost-intensivetrials.Creatingarepositoryofthisinformationthatwouldbeavailableeitherinthepublicdomainoraccessiblewithcertainpermissionscouldsignificantlybenefitearly-stageR&D.
TherearevaluablelessonsfortheUSGtolearnfromEurope’ssuccessesincreatinganinfrastructuretofundglobalhealthR&D.Forexample,keyinformantsarguedthatEuropeangovernmentsaremorewillingtofundPDPsandhavemechanismstodosoviaforeignministries.TheUSGcouldadoptasimilarmechanismtoprovidefundingthroughforeignassistanceorganizations(suchasPMIorPEPFAR).TherewaswidespreadsupportamongkeyinformantsfortheUSGtostepupitsfundingforPDPs,includingPDPshousedinUSuniversities.Onekeyinformant,whoworksinaPDPhousedatauniversity,arguedthathousingPDPsinacademicinstitutionshasseveraladvantages—forexample,itcansavecostssincelabsarealreadyinplace,thePDPbenefitsfromhavingacademicfacultydeeplyengaged,anduniversitieshaveindependencefromoutsideagendasandpriorities.AnotherexamplethatkeyinformantscitedofasuccessfulEuropeanapproachistheEMA’sdevelopmentofArticle58inpartnershipwiththeWHO,allowingEMAtoofferascientificopiniononproductsthatwillnotbeused
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intheEuropeanmarket.172,173Sinceitsintroductionin2004,sevenmedicalproductshavereceivedapositivescientificopinion,whichincludeantimalarial,hepatitisandpostpartumhemorrhagedrugs.174Article58offersapotentiallessonforUSG:itcouldbevaluabletoexpandtheremitoftheexistingFDAinitiativeonprovidingtentativeapprovalforHIVdrugsforusebyPEPFARtoincludeadditionalglobalhealthdiseasesandconditions.
4.TheUSGshouldallocatefundingmorestrategicallytoaddressgapsinproductdevelopment
AllstakeholdersbelievedthatthereshouldbeanincreaseinUSGfundingforglobalhealthR&D,includingprovidingbetterincentivemechanismsorinnovativeandadditionalfinancingmechanisms.Fundingshouldstrategicallyaddressthegapsinproductdevelopment,especiallyconductingclinicaltrialsandinmanufacturing,andshouldbettersupporthigh-impact,breakthroughtechnologies.ThisstrategiceffortcouldbeguidedbytheOfficeofGlobalAffairsinHHS,theWHO,andWHO’sexpertadvisorygroups.Non-USGactorssuggestedthatthefederalgovernmentcouldincreaseitssupportforindustryresearchdirectly,notingtheSBIRhasmainlybenefittedsmallplayersandthatthegovernmenthasexperimentedwiththismodeltodevelopcleanenergytechnologies.175,176
OMBisinfavorofsettingevidenced-basedtargetsforR&Dfundinganddisease-specificprioritiesinthebudgetingprocess,butotherUSGagenciesareconcernedthattargetswouldbeharmful.Forexample,targetsmightunderestimatethespendingthatisalreadythereandinadvertentlyreduceR&Dfunding.GiventheannualUSbudgetcycle,itwouldbedifficulttoplanandtoproscriptivelyimplementabudgetwithR&Dtargets.USGstakeholdersoutsideOMBarguedthatmoreflexibilityandclearerprioritizationwouldbebetterthanearmarkingfunds.TheyalsocitedconcernabouttoomuchtransparencyinR&Dallocationsbecauseitcreatesaneasytargetforpeoplewhowanttostrikeoutcertaininvestments(e.g.,forreproductivehealth).TargetsmayalsobiasfundingtowardsR&Dproductswithanimmediateimpact,undercuttingR&Dproductswithlongerdevelopmentperiods.
SomestakeholdersbothinsideandoutsidetheUSGbelievethatthegovernmentshouldparticipateinaninternationalpooledfundforglobalhealthR&D,butmanygovernmentstakeholdersarestronglyopposedtothisproposal.TheWHO’sConsultativeExpertWorkingGroupandmanyglobalhealthadvocateshavecalledforeachcountrytocontributeatleast0.01%ofitsgrossdomesticproduct(GDP)toglobalhealthR&D,with20-50%ofthefundinggoingtoapooledfund.177SomekeyinformantsbelievethatasustainableandconstantfundingstreamsuchasthisoneisnecessarytoachievelongtermgoalsandrecommendedthattheG7establishthefundtobemanagedbyapublic-privatestakeholderboardaccountableforaportfolioofproducts.178ThisstreamliningandexplicitdecisionmakingmechanismcouldhelpinstrengtheningthevaluechainofglobalhealthR&Dfromearlystageclinicaltrialstocountrylevelimplementation.WhileproductdevelopmentisnotakeyWHOstrength,theyargued,theWHOcouldserveasthearbiterandfacilitatorforsettingR&Dpriorities.ButmanyotherstakeholdersstronglyopposedtheideaofUSGsupportingsuchapooledfund.AsthelargestfunderofglobalhealthR&D,theyargued,theUSGhaslittleinterestinrelinquishingitsauthoritytoagroupthatmayhavepoorlydefinedobjectives.USGspendingisbasedonmandatesandauthoritieswithinitslaw;itisnotpossibletosuspendcurrentlawanddivertfundingfromdesignatedareastoafundoverwhichUSGhasnocontrol.Inaddition,whilethesestakeholdersrecognizedthatthereareinefficienciesanddisconnectsinbringingproductstomarket,therehavebeenmanypositiveresultsinrecentyears.TheydidnotacceptthenotionthatglobalhealthR&Dlackedfundingorthatfundingwasallocatedinappropriatelyandfeltthatthesenotionswerenotbasedonsoundevidence.
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CreativeandinnovativeapproachestoR&Dfinancingshouldbetried.Suggestedexampleswere:• ExplorewaysinwhichUSGcouldsupportEuropeaninstitutionsthatareconductingglobalhealthR&D,andEuropeangovernmentscouldsupportUSinstitutionsconductingthistypeofresearch;
• Supportblendedfinancingmechanismstobringtogetherpublic,private,andphilanthropicfunding;• Createanewfund,supportedbytheG20countries,modeledonJapan’sGlobalHealthInnovativeTechnologyFund,whichbringsJapaneseandnon-Japaneseorganizationstogethertospurinnovation.179
5.TheUSG’spushandpullincentivemechanismsshouldberefinedtoimprovetheirimpact
Refiningexistingmechanismscouldimprovetheoddsofnewproductsreachingpatientswhoneedthemthemost.Forexample,thePRVcouldberedesignedtoincludecommitmentstoregisterthedrugandmakeitavailableandaffordabletopatientsandtreatmentproviders.Anotherstakeholdersuggestedcommissioningofrequestsforapplications(RFAs)andrequestsforproposals(RFPs)targeteddirectlyatPDPs,notingthatwhiletheWIPORe:Searchconsortiumhasbeenapositiveaddition,itwillnotsustainindustryengagement.TherewaswidespreadinterestandexcitementaboutBARDA’srecentlaunchofCARB-X,whichisseenasapotentiallyimportantPPParrangementtoincentivizeanti-bacterialdrugdevelopment.180
IndustryactorsbelievethattheUSG,WHO,andotherorganizationsshouldbemorecreativeindevelopingmodelsandincentivesthataresubstantialenoughtokeeptheprivatesectorengagedinthefaceofhighriskandlimitedmarketreturn.AcademicpartnersandsmallstartupcompaniesbenefitthemostfromNIHfundingandwhiletheymaybevaluablepartners,theyoftenhaveasteeplearningcurveandmayneverbesuccessfulingettingproductstomarket.CurrentmarketincentivessuchasthePRVarehelpful,butthereneedstobefarmorefundingavailablethroughoutthedevelopmentcontinuum.TheBARDAandDARPAmodelsarebothframeworksthatshouldbeexpandedbeyondbiodefense.
6.ScaledupandmorestrategicadvocacyeffortscouldhelpimproveUSGsupportforglobalhealthR&D
Strategicadvocacyand“goodstorytelling”couldhelptoimprovefundingandprioritizationofglobalhealthR&D.Stakeholdersindicatedthatwhileitcangetroutineforadvocacygroupstopushtheirmessagesoutonanongoingbasis,theyshouldbe“primed”withcriticalfactsandgoodsuccessstoriesthatcancapitalizeonsituationaleventstopropelpolicyinitiativesforward.BuildingrelationshipswiththeNIH,OMB,agencyheads,andexpertcommitteememberscanbecrucialinbuildingsupportbeforemajordecisionsaremadeonadvocacyefforts.Linkingpeopleworkingonglobalhealthissues,whetherindustryorNGOs,withlegislatorsisalsoimportantforimpactfuladvocacy.AdvocacygroupscanhelptoboostR&Dfunding.Forexample,NIHfundingdoubledovertheperiodFY1998toFY2003from$13.7billionto$27.1billion,inpartthroughNIHDirectorHaroldVarmus’seffortstoengageoutsideadvocacygroupstoinfluenceCongressaswellasindividualinstitutionalleaderspushingformorefunding.181RotaryandBMGFhavesuccessfullylobbiedforsupplementalfundingforpolio.
Creativeapproachestoadvocacyareneeded,suchasshowcasingtheeconomicbenefitsofglobalhealthR&Danditspotentialtocreatejobs.TheseapproachescouldpotentiallyhelpgeneratemoreinterestthantalkingaboutglobalhealthR&Ditself.MMVadoptedasimilarapproachinwhichitsresearchersshowedthatfundsinvestedbytheUKandAustraliaintothePDPwerebeingreinvestedbackintheirowncountriesintermsofpublications,PhDstudentenrollment,andgrants.Thisframingisacounter-argumenttothenotionthatdevelopmentaid—acommonsourceoffundingforPDPs—justgoesintoablackbox.
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Influencingkeylegislation,suchastheEndNeglectedTropicalDiseasesAct(BillHR1797),whichiscurrentlystalledinCongress,isalsoimportant.Thisactaimsto“extendtheUSAID’sNTDProgramtotargetmorediseasesandbetterintegrateprograms,directtheUSDepartmentofHealthandHumanServicestoresearchtheimpactofNTDsintheUSandrequireUSpolicymakerstoadvocateforincreasedNTDseffortsamonginternationalinstitutionssuchastheWorldBankandUnitedNations.ThebillwillalsocreateoneormoreNTDcentersofexcellenceandestablishapanelonintestinalworminfectionstoencourageincreasedR&Dfortoolstodiagnose,prevent,treatandcontrolNTDs.”182,183LikethePRV,theprovisionsofthisbillcouldbeinstrumentalinsupportingglobalhealthR&D.AnotherlegislativeexampleistheGlobalDevelopmentLabActof2016(HR3924),whichpassedtheHouseinSeptember,2016.184ThisActestablisheskeydutiesfortheLabrelatedtotheapplicationofinnovationtoaddressingextremepoverty;thediscovery,testing,andscalingofdevelopmentinnovations;forgingpartnershipsacrosssectors;using“innovation-drivencompetitionstoexpandthenumberanddiversityofsolutionstochallengesofdevelopment”;and“supportingUSAIDmissionsandbureausinapplyingscience,technology,innovation,andpartnershipapproachestodecision-making,obtainmentandprogramdesignaccordingtothelegislation.”
Advocacyeffortsshouldincludepushingforregulatoryreviewprocessesforglobalhealthproductstobeharmonizedacrosscountries,especiallyattheregionallevel,tofacilitateclinicaldevelopmentandmaximizetheimpactofinvestments.Auniformtechnicaldossieracrossregions,forexample,wouldallowforeasieroperationsofpharmaceuticalcompanies.Streamliningregulationsshouldbecomplementedwithfasttrackapprovalswhereappropriate,basedonarisktobenefitratioapproach.Stringentapprovalisstillnecessary,but,asshownbytheFDA’sapprovalofbedaquilineforMDR-TB,ifaconditionhasahighmortalityrate,thisshouldbefactoredintothereviewprocess.
ManystakeholdersbelievethatFDAcanplayanimportantmentoringroleintheharmonizationofregulatoryprocesseswhilealsobuildingcapacitybyprovidingtrainingonregulatoryprocessestoothercountries.Thisglobalcoordinationcouldhelpinestablishingamoreglobalregulatoryframeworkandinfindingtherightregulatorybalance.Developingthisframeworkandfindingthisbalancecouldbeachievedthroughinformationsharingandbringingtogetherregulatorsfrommultiplecountriesandagencies,includingtheWHO,aswasseeninthecaseoftheEbolaclinicaltrials.SomestakeholderssuggestedthatifmorefundingbecomesavailableforglobalhealthR&D,staffingshouldberampedupattheFDAtodealwiththetime-consumingprocesses.
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ConclusionsandRecommendationsOurreviewoftheliteraturecombinedwithinterviewswithadiversearrayofstakeholdersacrossthepublicandprivatesectorshasshownthattheUSGclearlyplaysavitalroleinsupportingglobalhealthR&D.ItsoutsizeimpactandinfluenceisreflectedinthefactthatitisbyfarthemostsignificantfunderofglobalhealthR&Dglobally,especiallyamonggovernmentfunders.ThisdominanceinfundingiscoupledwithmanyotherspheresofinfluenceupontheglobalhealthR&Dlandscape.Theseincludeitsinnovativemechanismstorapidlymarshalattentionandresourcestowardsproductdevelopmentintacklingglobalcrises(asseenwiththeEbolaandZikaGrandChallengesandBARDA’ssupportofEbolaandZikacountermeasures)anditsworld-renownedresearchandtechnicalagenciesthathelpfuelglobalhealthinnovation,includingNIHandCDC.
Nevertheless,ourstudyhasalsohighlightedseveralareasofconcernandwaysinwhichtheUSG’sroleinglobalhealthR&Disbeingweakenedoreventhreatened.Theseincludefundinglevelsthatareindecline,under-useofpotentiallyimportantagencies,anongoingcorechallengeinimprovingcommunication,collaboration,andalignmentwithinandbetweendifferentagencies,andmissedopportunitiestobetterengagewiththeWHOandotherinternationalactors.
WeendourreportbydrawingninemainconclusionsrelatedtowaysinwhichUSGsupportforglobalhealthR&Dcouldbestrengthened.Wehavelinkedeachoftheseconclusionswithourrecommendationsonpolicyproposals,solutions,ornextsteps.
Conclusion1:ThereisanongoingstruggletofindthecorrectbalancebetweenUSGagencyautonomyandgreaterinter-agencycoordination
Coordinationisoftenassociatedwithcentralizedcontrol,thoughitcansimplymeanmoreinformationsharing.Thechallengeofcoordinationhasbeenanongoingconcern,ashighlighted,forexample,byGHTC’sseventhannualpolicyreportpublishedinApril,2016,whichnotedthat“USeffortscanbehamperedbythefracturednatureoftheUShealthR&Dinfrastructure.”185Weheardmanycasestudiesfromstakeholdersofthenegativeconsequencesofthisfracturing—frommicrobialsamplesnotbeingsharedacrossagenciestothenear-impossibilityofsettingupcontractualrelationshipsthatwouldallowinvestigatorsatdifferentagenciestoworkonasharedproject.
The“positiveconsequences”ofthefracturedUSGinfrastructureforglobalhealthR&Dhasreceivedlessattention.ItisclearfromourstudythatseveralhighlevelUSGstakeholders,includingthosewhoareinvestigatorsthemselves,believepassionatelythatthereisgreatvalueinlettingagenciesoperateautonomously.Differentagencieshavetheirownmandatesandmissions,theiruniqueexpertise,andtheirownwaysofdoingbusiness.“Lettingamillionflowersbloom”inthiswaymaywellbeanapproachthatgeneratesmoreinnovativeideasthantryingtohaveallagenciesinlock-step.
Recommendations:InformingthedebateonhowbesttofacilitatecoordinationtobetterleverageUSGfundingandbuildefficiencieswillrequirecarefulanalysisoftheproblemsandrobustevidenceonwhichsolutionswillworkbest.ThefailureoftheGHItogaintractionshowsthelimitsofattemptingtoforceinter-agencycollaboration.ButisthereabettermechanismforimprovingthearchitecturalarrangementswithintheUSGtoavoidduplicativeeffortsandmaximizesynergies?Answeringthisquestioncouldhaveprofoundbenefits,butwillrequirein-depthanalysisofthecurrentarrangementsandthedevelopment,piloting,andevaluationofnewinter-agencycoordinationmechanisms.SuchananalysisshouldalsolearnlessonsfromthesuccessofmechanismssuchasPACCARBandPHEMCE.
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Conclusion2:TheUSGismissingopportunitiestostrengthenitscollaborationwithotheractorsintheglobalhealthR&Dspace
Industry,NGOs,foundations,andPDPswanttheUSGtostepupitscollaborationswiththem.AnimportantconclusionfromourstudyisthatthereseemstobearealhungerfortheUSGtobecomeamuchmoreseriousparticipantinandfunderofpublic-privatePDPs.Thiswouldrequireashiftinthinking—itmightmean,forexample,thattheNIHmodelofsendingnearlyallresearchdollarstoacademiawouldevolvetooneinwhichaportionoffundinggoesinsteadtothehighest-impactPDPs.OneofthedisconnectsinUSGsupportforglobalhealthR&D,whichisseeninotherdonorcountries,isthatfundingisdominatedbyitsbiomedicalscienceagency(NIH)ratherthanitsdevelopmentagency(USAID).Thismattersbecausesciencefundinganddevelopmentagencyfundinghavedifferentpriorities,asshownbyourstudy.AsMaryMoran,ExecutiveDirectorofPolicyCures,hasargued,“sciencefundingisshapedbybiomedicalresearchparadigmsratherthanglobalhealthparadigms”anditisoften“investigatordriven,ratherthanbeinglinkedtodevelopmentprioritiesandstrategies—forinstance,whilenewtoolsforpost-partumhaemorrhage(PPH)areadevelopmentpriority,theyreceiveverylittlesciencefunding.”12
Recommendations:WhileweacknowledgethatNIH’sbasicscience,investigator-driven,anduniversity-dominatedfundingapproachhasbeenanextraordinaryengineofdiscovery,webelievethereisscopeforNIHtosupportmoredownstreamtranslationalresearchwithoutstrayingtoofarfromitscoremandate.IncreasedUSGfundingtoPDPswouldbothincreaseopportunitiestocollaboratewithabroadarrayofglobalhealthR&Dactorsfromthepublic,private,andphilanthropicsectorsandwouldprovidemoresupportfortranslationalandlate-stageproductdevelopment.USAIDcouldplayanexpandedroleinsupportofPDPs,includingdevelopingnewreproductivehealthtechnologies,suchastoolsforPPH.TherolewouldbeanaturalfitforUSAID’scoremission.RobertClay,USAID’sdeputyassistantadministratorintheBureauforGlobalHealth,coinedtheterm“boldendgames”inglobalhealth,referringtooutcomessuchasanAIDS-freegenerationandanendtoavertablechildmortality.186Theseoutcomeswillonlybepossiblewiththedevelopmentofnewhealthtechnologies,andsoitwouldmakesenseforUSAIDtomatchits“boldendgames”rhetoricwithscaledupsupportforproductdevelopment.187IfsupportfromfoundationsforPDPsisatriskofdeclininginthefuture,assuggestedbyourstudy,webelieveUSGshouldpositionitselftofillthisvoid.
ImprovingUSG’scollaborativeeffortswiththeWHOislowhangingfruitthatcouldhavealargepayoff.OurstudysuggestedthatthereisafrostinessintheUSG-WHOrelationship,whichhasunfortunateconsequences.DespiteWHO’sweaknesses,whichwereonfulldisplayatthestartoftheWestAfricanEbolaoutbreak,theorganizationisstillthemostimportantglobalbodyforsettingnormsandstandardsinglobalhealth.TheUSG’sglobalhealthR&Defforts,includingitsin-countrytrialsandotherstudies,couldbefacilitatedbycloserworkingwiththeWHO.
Conclusion3:ThedecliningUSGfundingforR&D,includingglobalhealthR&D,isanexistentialthreattotheUSG’simpact,influence,andcredibilitywithintheR&DlandscapeandjeopardizestheUSG’sreputationasagloballeaderininnovation
ItisnoexaggerationtosaythatthefallingR&DfundinglevelsrepresentanexistentialcrisisinUSsupportforinnovationwritbroad,hamstringingagencyefforts,andsendingasignaltotheworldthattheUSmayberelinquishingitsleadershiprole.The2015surgeinfundingforR&DforEbolaandotherAfricanVHFsgivesafalselyreassuringpicture—infact,thesurgehidadeclineinoverallfundingforglobalhealthR&DotherthanEbolaandotherVHF.Thisdeclineisalreadybeingfeltattheagencylevel,particularlyattheCDC,andthereisevidencethatitisslowingdowninnovationacrossthespectrumof
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neglecteddiseasesandconditions.Asonestakeholdernoted,thereisalimittoone’sabilityto“robPetertopayPaul.”TheUSGhasshownthatitcanmobilizeR&Dfundsfortime-boundemergencies,butthisislittleconsolationwhenitcomestothelackofsustainedfundingneededtotackle“non-emerging”conditionsofpovertythatprimarilyaffectpopulationsoutsideoftheUS—suchasAfricansleepingsickness,Chagasdisease,andMDR-TB.
Recommendations:Therehasneverbeenamoreimportanttimefortheadvocacycommunitytomakethepublichealth,economic,business,andmoralcaseforUSGsupportforglobalhealthR&D.ThisisparticularlytruegiventhattheincomingAdministrationhasnotmadeanyclearpronouncementsaboutitscommitmenttoglobalhealthfunding.ADecember19,2016analysisbytheNewYorkTimesoftheglobalhealthpositionsofthenewAdministrationnotedthat“advocatesforthepoor,healthexpertsandgovernmentofficialsadmitthattheyhavenoideawhatdirectiontheincomingTrumpadministrationisgoingtotake.”188TheanalysissuggestedthattheTrumpadministrationwillpursuean“Americafirst”approachtoglobalhealth.Giventheearlyindicationsthateconomicandbusinessinterestswilldominate,thereisatime-criticalneedtodocumentanddemonstratetothenewadministrationtheextraordinaryreturnstoinvestinginglobalhealthR&D.Forexample,aforthcominganalysisbyGHTCandPolicyCuresResearchestimatesthatoutofeverydollarthatUSGinvestsinglobalhealthR&D,around89centsgoestosupportingU.S.-basedresearchersandproductdevelopersandbuilding,improvingU.S.researchandtechnologicalcapacity,andprovidingadirectinvestmentintotheUSeconomy.189AnanalysisbyPolicyCuresandDSW,aninternationalhealthNGO,foundthateveryEuroinvestedbyEuropeangovernmentsintoR&Dforpoverty-relatedneglecteddiseasesandconditionsbroughtanadditional1.47EurosininvestmentfromoutsideintoEurope.190
Conclusion4:BARDA’secosystemofpushandpullmechanismsandtheOtherTransactionAuthorityusedbyBARDAandDARPAtoestablishlongtermpartnershipswithindustryhavebeensuccessfulincentivemechanisms
BARDA’sintegratedmodelofpushandpullmechanisms,whichrequiressignificantfunding,hasbeeneffectiveinaddressingmarketfailuresforanumberofconditions.TherehasbeenenoughflexibilitytoallowitsmandatetobeexpandedtoincludeAMR,whichmayhaveopenedthedoortofindingwaystoincludeadditionalglobalhealthchallenges.OurstudyhassuggestedthatlongtermportfoliopartnershipsestablishedthroughOTAhasbeena“gamechanger,”forexampleinincentivizingcompaniestodevelopantimicrobials.WhileitwouldbehardtomakethecasethatthePRVhashadasimilareffect,webelieveitismuchtooearlytowriteitoff.Outsideofthisstudy,companieshavetoldusthatthePRVisthereasonthattheyenteredtheneglecteddiseasespace.AtapresentationgivenatDukeUniversityin2013,forexample,EugeneSeymour,CEOofNanoViricidesdiscussedhowthePRVhadincentivizedhiscompanytostartworkingondengue.44
Recommendations:Thesesuccessfulincentivemechanismsshouldbeexpandedtootherdiseasesandreplicatedbyotheragenciesandoffices.Notallmarketfailureshavethesamecauses,andaBARDA-typemodelusedfordifferentobstaclesmayneedrefinementtomakeitspecifictotheactualchallenge.Forexample,whileincentivizingmoleculediscoverymaybeoneobstacle,incentivizingmanufacturingofsufficientquantitiesofvaccineatanaffordablepricemaybeaverydifferentone.
Conclusion5:Betterleveragingofwhatisworkingwellisaprinciplethatcanalsobeappliedwhenitcomestotheunder-useofeffectiveagencies
Animportantfindingofourstudyisthattherearesomekeyresources,suchastheDoD’smedicalresearchcapabilities,thatareunder-recognizedandunder-used.TheDoD’soverseaslabshavegreatlyunder-usedpotentialforglobalhealthR&D,includingforvaccinedevelopment.
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Recommendations:ThenewAdministrationhaspledgedahugeincreaseindefensespending,perhapsbyasmuchas$500billion.191Whiletherearecertainlyrisksinthe“securitization”ofglobalhealth(e.g.,itcanbedangeroustoconflatetheprinciplesofpublichealthwiththoseofnationalsecurity),thisincreasemayrepresentanavenuetoboostUSGsupportforglobalhealthR&DifsomeofitcanbedirectedtoDoD’sglobalhealthresearch.
Conclusion6:AlthoughtheUSGisgenerallyseenasabehemoth—agiant,inflexiblebureaucracy—ithastheabilitytoexpanditsglobalhealthR&Dremit
Wefoundanencouragingnumberofexamplesoflegislativeandbureaucraticflexibility.LegislationhasbeenadoptedtobroadenUSG’sroleinglobalhealthR&D.Agencymandateshavebeenrevisedtoincludeadditionaldiseasesorconditions.
Recommendations:Importantlessonscouldbelearnedfromananalysisofhowtheseshiftshappened—forexample,whowerethekeyactorsinvolvedandwhatweretheleversthatallowedchangetohappened?TheselessonscouldpotentiallybeappliedtofindothervaluablewaysfortheUSGtosupportadditionalR&Defforts.Togiveoneexample,theremaybearoutebywhichPHEMCEcouldtakeonadditionalglobalhealthconditionsordiseases.
Conclusion7:ThereisnostandarddefinitionofwhatconstitutesglobalhealthR&DuseduniformlyacrossUSGagencies,includingOMB.
USGneedsacleardefinitionofwhatconstitutesglobalhealthR&D,whichwillallowbettertrackingoffundingflowsandhelpdrivemoreexplicitprioritization
Recommendations:Adefinitionandtypologyshouldbeurgentlydeveloped,whichwouldgoalongwaytoenhancingtheeffortsofresearchers,advocacygroups,andthegovernmentitselftotrackfundinglevels,distributions,andtrends.Thisinitselfcouldhaveknock-onbenefits,includinghelpingtoalignR&DacrossagenciesandeventodrivethekindofexplicitR&Dprioritizationprocessthatmanystakeholderscalledfor.Thetimingisrightforagreeingonsuchadefinition,giventhattheOrganizationforEconomicCooperationandDevelopment-DevelopmentAssistanceCommittee(OECD-DAC),aforumof29donors,has(a)recognizedtheincreasingimportanceofdonorsupportforglobalpublicgoods(GPGs)suchasglobalhealthR&D,and(b)startedaprocesstodevelopimprovedandmorecomprehensivemeasuresofofficialdevelopmentassistance(ODA)thatincludefundingforsuchGPGs.192Aspartofthisprocess,OECDiscurrentlyworkingonanewstatisticalmeasure,theTotalOfficialSupportforSustainableDevelopment(TOSSD),whichaimstoenhanceinternationalaccountabilitybyincreasingtransparencyandrigorinreportingondevelopmentfinancebeyondODA.193TOSSDislikelytoincludefundingforGPGs,includingglobalhealthR&D,makingitimportantthatUSGinvestmentsinsuchresearchcanbeproperlycaptured.
Conclusion8:ThefutureofUSGsupportforglobalhealthR&Dmustincludeatransitiontogreatersupportfordevelopingin-countryR&Dandregulatorycapacity
Totacklefutureglobalhealthchallenges,developmentassistanceforhealth—includingfromUSG—mustincludeincreasingsupportforin-countryR&D.TheCommissiononInvestinginHealthmadethecasethattheentireworld,andparticularlyhigh-povertyregions,isleftvulnerablebytheunder-fundingofproductdevelopmentforglobalhealth,includingforpandemicpreparednessandtacklingAMR.192
Recommendations:IntheSDGsera,anincreasingproportionofDAHthatisdirectedtoindividualcountriesshouldbespentondevelopingdomesticR&Dcapabilities.Fogartywouldbeideallyplacedtoprovideleadershipforsuchastrategy.
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Conclusion9:AdvocacyforglobalhealthR&Dhasanimpressivehistoryofsuccessandwillhaveaparticularlyimportantroleintheyearsahead.
Thereisanurgentneedtocontinuedeveloping,testing,andrefiningadvocacyeffortstoinfluencemajordecisionmakerssuchastheCongress.Advocacyeffortshavebeencrucialinpushingforwardimportantlegislationandpastglobalhealthinitiatives.
Recommendations:Buildinganevidencebaseon“whatworks”inmobilizingUSGsupportforglobalhealthR&D—forexample,whetheritisemphasizingthenumberoflivessavedortheboosttotheUSeconomy—hasgainedincreasingimportancegivenhowlittleisknownaboutthenextAdministration’sglobalhealthcommitment.OnestrategytoconsideristofocusonthelinkbetweenadequateinvestmentinR&DasacriticalprecursorfortheUSGtomaintainitspreeminentpositionasaglobalinnovator.
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