global paper 21feb2017-1pmcenterforpolicyimpact.org/wp-content/uploads/sites/18... · health tools,...

AuthorsGavinYamey,AndreaThoumi,JonathanGonzalez-Smith,CynthiaBinanay,IpchitaBharali,ZeenaJohar,

DavidRidley,NickChapman

StrengtheningtheUnitedStatesGovernment’sRoleinProductDevelopmentforGlobalHealth

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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)


$41.6 27.9% X X

HelminthInfections(soil-transmittedhelminths,lymphaticfilariasis,onchocerciasis,schistosomiasis)


$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.


9

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


ThemissionoftheNIHistoconductscientificresearchtoimprovepopulationhealth.Theagency’smandateistoconductbasicresearch;itisneitheradirectiveagencynoraproductdevelopmentagency.TheNIHreliesonthebestideasofitsscientists—a“bottomup”approachinwhichscientistsdeterminetheresearchratherthanbeingtoldina“topdown”waywhattostudy.Asaresult,NIHscientificprioritiesmaynottranslatetodevelopingproductsforLMICs.TheOfficeoftheDirectorisresponsible


16

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%


17

• 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


NIH’sfundingallocationsrelyona“bottom-up”approach,wherebythecentersandinstitutesrelyonthesubmissionofcompetitivepeer-reviewedgrantapplicationstogeneratethebestideas,althoughwhennecessary,thereisalsoflexibilitytorespondina“top-down”wayforurgentneeds.Stakeholders


18

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.


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


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.


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.


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)


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


FDA’sauthoritytograntorphandrugstatusandawardPRVsaimstoincentivizeglobalhealthR&Dfunding;whileobjectiveeligibilitycriterialimitFDAdiscretion,thereissomeflexibility.USGstakeholdersnotedthatoneareaofdiscretionisthattheFDAhastheauthoritytoexpandthelistoftropicaldiseaseseligibleforaPRV.In2015,forexample,theFDAexpandedvouchereligibilitytoincludeChagasdiseaseandneurocysticercosis.76


TheFDAhasanumberofmechanismsthatitcanpotentiallyusetocollaboratewithinternationalandprivatesectorentitiestoimproveglobalhealthR&D.FDA’sCentersofExcellenceinRegulatoryScienceandInnovationfacilitatescollaborationsbetweenFDAandacademicinstitutionsforinnovativeresearchforimprovedregulation.77TheFDAhasissuedBroadAgencyAnnouncementsasacontractmechanismopentoprivatesectorparticipantstocollaborateonregulatoryscienceR&D.78TheMedicalDeviceInnovationConsortium(MDIC)atFDAisapublic-privatepartnershipthatallowsindustry,government,andpatientorganizationstocollaborateonmedicaldeviceandtechnologyresearch.79

UNITEDSTATESAGENCYFORINTERNATIONALDEVELOPMENT


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


25

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


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).


CongressgenerallydoesnotearmarkfundingforR&DatUSAID.Rather,itfundsprogramsforspecificdiseasesandhealthconditions.DecisionsonhowtoallocatethisfundingforR&Dpurposesarethenmadeattheindividualprogramlevel.StakeholdersindicatedthatteamsdecidehowmuchfundingisallocatedtoR&Dversusimplementationandthereisnoonefromabovechallengingthedecisions.TheexceptionislegacyearmarksforcertaintypesofR&DforHIV/AIDS(e.g.,developmentofmicrobicides


27

andHIVvaccinedevelopment).ThishighlightstheimportanceofhavingchampionsforR&Dwithindisease-specificprogramsatUSAID,asexemplifiedbyUSAID’sNTDsProgram.

USGstakeholdersbelievedthattheperceptionthatUSAIDonlyinvestsinimplementationandnottranslationalresearchwasinaccurate;itsportfolioisdiverseacrossthedevelopmentchain.Forexample,ithasmadeinvestmentsinmaternalandchildhealthattheprototypestageandworkedtotakethesethroughtheentireproductdevelopmentcycle.Ratherthanjustbeingagapfiller,USAIDlookstoseeatwhichpointsintheR&Dcycleitcanhavethegreatestaddedvalue.IthasalsosupportedadiversearrayofPDPs(Figure13).


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


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


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


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


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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References1. UnitedNationsInternationalChildren’sFund.Levels&TrendsinChildMortality.

http://www.childmortality.org/files_v20/download/igme%20report%202015%20child%20mortality%20final.pdf.PublishedSeptember2015.AccessedJanuary20,2017.

2. JamisonDT,SummersLH,AlleyneG,etal.Globalhealth2035:aworldconvergingwithinageneration.Lancet.2013;382(9908):1898-1955.doi:10.1016/S0140-6736(13)62105-4

3. MurrayCJ,OrtbladKF,GuinovartC,etal.Global,regional,andnationalincidenceandmortalityforHIV,tuberculosis,andmalariaduring1990-2013:asystematicanalysisfortheGlobalBurdenofDiseaseStudy2013.Lancet.2014;384(9947):1005-1070.doi:10.1016/S0140-6736(14)60844-8

4. WorldHealthOrganization.GlobalHealthEstimates(GHE).http://www.who.int/healthinfo/global_burden_disease/en/.AccessedFebruary16,2017.

5. HouwelingT,Karim-KosH,KulicM,etal.Socioeconomicinequalitiesinneglectedtropicaldiseases:asystematicreview.PLoSNeglectedTropicalDiseases.2016;12(10(5)):e0004546.doi:10.1371/journal.pntd.0004546

6. FenwickA.Theglobalburdenofneglectedtropicaldiseases.PublicHealth.2012;126:233-236.doi:10.1016/j.puhe.2011.11.015

7. PolicyCures.SavingLivesandCreatingImpact:WhyInvestinginGlobalHealthResearchWorks.http://www.policycures.org/downloads/Saving%20lives%20and%20creating%20impact.pdf.Published2012.AccessedDecember7,2016.

8. TrouillerP,OlliaroP,TorreeleE,OrbinskiJ,LaingR,FordN.Drugdevelopmentforneglecteddiseases:adeficientmarketandapublic-healthpolicyfailure.TheLancet.2002;360(9337):2188–2194.doi:10.1016/S0140-6736(02)09096-7

9. PedriqueB,Strub-WourgaftN,SomeC,etal.Thedrugandvaccinelandscapeforneglecteddiseases(2000-11):asystematicassessment.LancetGlobalHealth.2013;1(6):e371-e379.doi:10.1016/S2214-109X(13)70078-0

10. CohenJ,DibnerMS,WilsonA.DevelopmentofandAccesstoProductsforNeglectedDiseases.PLoS2010;5(5).doi:10.1371/journal.pone.0010610

11. CohenJ,SturgeonG,CohenA.Measuringprogressinneglecteddiseasedrugdevelopment.ClinTher.2014;36(7):1037-1042.doi:10.1016/j.clinthera.2014.05.004

12. MoranM.TheGrandConvergence:ClosingtheDividebetweenPublicHealthFundingandGlobalHealthNeeds.PLoSBiol.2016;14(3).doi:10.1371/journal.pbio.1002439

13. WexlerA,ValentineA,KatesJ.TheU.S.GlobalHealthBudget:AnalysisofAppropriationsforFiscalYear2016.KaiserFamilyFoundation.http://kff.org/global-health-policy/issue-brief/the-u-s-global-health-budget-analysis-of-appropriations-for-fiscal-year-2016/.PublishedJanuary,202016.AccessedDecember5,2016.

14. MoranM,ChapmanN,Abela-OversteegenL,etal.NeglectedDiseaseResearchandDevelopment:TheEbolaEffect.PolicyCures.http://policycures.org/downloads/Y8%20GFINDER%20full%20report%20web.pdf.Published2015.AccessedJanuary17,2017.

15. MoranM,GuzmanJ,ChapmanN,etal.ReproductiveHealth:R&DfortheDevelopingWorld.PolicyCures.http://www.policycures.org/downloads/RH%20full%20report.pdf.Published2014.AccessedFebruary16,2017.


60

16. MoranM,ChapmanN,Abela-OversteegenL,etal.NeglectedDiseaseResearchandDevelopment:TheEbolaEffect.PolicyCures.http://policycures.org/downloads/Y8%20GFINDER%20full%20report%20web.pdf.Published2015.AccessedFebruary16,2017.

17. G-FINDERPublicSearchToolFAQ.PolicyCureswebsite.http://gfinder.policycures.org/PublicSearchTool/faq.Published2014.AccessedAugust23,2016.

18. EnhancingtheWorkoftheDepartmentofHealthandHumanServicesNationalVaccinePrograminGlobalImmunization:RecommendationsoftheNationalVaccineAdvisoryCommittee:ApprovedbytheNationalVaccineAdvisoryCommitteeonSeptember12,2013.PublicHealthReports.2014;129(Suppl3):12-85.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121882/.AccessedFebruary16,2017.

19. 2010NationalVaccinePlan.U.S.DepartmentofHealthandHumanServiceswebsite.https://www.hhs.gov/sites/default/files/nvpo/vacc_plan/2010-Plan/nationalvaccineplan.pdf.Published2010.AccessedFebruary16,2017.

20. SMARTVaccines:StrategicMulti-AttributeRankingToolforVaccines.TheNationalAcademisPresswebsite.https://www.nap.edu/smartvaccines/.AccessedNovember29,2016.

21. OfficeofGlobalAffairs.AIDSwebsite.https://www.aids.gov/federal-resources/federal-agencies/hhs/office-of-global-affairs/index.html.UpdatedJune19,2012.AccessedOctober3,2016.

22. ConsultativeExpertWorkingGrouponResearchandDevelopment:FinancingandCoordination.WorldHealthOrganizationwebsite.http://www.who.int/phi/cewg/en/.UpdatedMay16,2016.AccessedOctober5,2016.

23. TransantlanticTaskForceonAntimicrobialResistance(TATFAR).CentersforDiseaseControlandPreventionwebsite.http://www.cdc.gov/drugresistance/tatfar/.UpdatedJune24,2016.AccessedOctober5,2016.

24. BARDA’SVision,Mission,andValues.PublicHealthEmergencywebsite.http://www.phe.gov/about/barda/stratplan/Pages/barda-vision-mission-and-values.aspx.UpdatedFebruary16,2017.AccessedFebruary16,2017.

25. DivisionofChemical,Biological,RadiologicalandNuclearMedicalCountermeasures.PublicHealthEmergencywebsite.http://www.phe.gov/about/barda/Pages/cbrn.aspx.UpdatedSeptember12,2014.AccessedFebruary16,2017.

26. U.S.DepartmentofHealthandHumanServicesAssistantSecretaryforPreparednessandResponse.FY2016BudgetinBrief:AnOverviewofASPR’sBudgetRequestandStrategicPriorities.http://www.phe.gov/about/ofpa/Documents/bib-2016.pdf.PublishedAugust,2015.Accessed27October,2016.

27. U.S.DepartmentofHealthandHumanServices.BiomedicalAdvancedResearchandDevelopmentAuthority.2016;http://www.phe.gov/about/BARDA/Pages/default.aspx.AccessedSeptember26,2016.

28. U.S.DepartmentofHealthandHumanServices.BARDAStrategicPlan2011-2016.https://www.phe.gov/about/barda/Documents/barda-strategic-plan.pdf.PublishedOctober4,2011.AccessedFebruary16,2017.

29. BARDAStrategicPlan2011–2016:Introduction.PublicHealthEmergencywebsite.http://www.phe.gov/about/barda/stratplan/Pages/introduction.aspx.UpdatedAugust19,2013.Accessed27October,2016.

30. HHSenhancesnation’shealthpreparednessforradiologicalthreats[newsrelease].U.S.DepartmentofHealthandHumanServiceswebsite.https://www.hhs.gov/about/news/2016/10/06/hhs-enhances-nation-s-health-preparedness-radiological-threats.html.PublishedOctober6,2016.AccessedOctober12,2016.


61

31. RobinsonRA.WrittenStatementtotheU.S.SenateCommitteeonHealth,Education,Labor,andPensions.BARDA’sRoleinMedicalandPublicHealthPreparednessandResponse.http://www.help.senate.gov/imo/media/doc/Robinson2.pdf.PublishedFebruary26,2015.AccessedFebruary16,2017.

32. ProjectBioShield.MedicalCountermeasureswebsite.https://www.medicalcountermeasures.gov/barda/cbrn/project-bioshield-overview/.UpdatedOctober18,2016.AccessedFebruary16,2017.

33. GottronF.TheProjectBioShieldAct:Issuesforthe112thCongress.R42349.U.S.CongressionalResearchService.https://fas.org/sgp/crs/terror/R42349.pdf.PublishedOctober12,2012.AccessedDecember20,2016.

34. PHEMCEMissionComponents.PublicHealthEmergencywebsite.http://www.phe.gov/Preparedness/mcm/phemce/Pages/mission.aspx.UpdatedFebruary27,2015.AccessedOctober5,2016.

35. TarbetEB,DorwardJT,DayCW,RashidKA.VaccineproductiontrainingtodeveloptheworkforceofforeigninstitutionssupportedbytheBARDAinfluenzavaccinecapacitybuildingprogram.Vaccine.2013;31(12):1646-1649.doi:10.1016/j.vaccine.2012.06.041

36. XcceratingGlobalAntibacterialInnovation.CARB-Xwebsite.http://www.carb-x.org.AccessedOctober12,2016.

37. CARB-X:CombatingAntibioticResistantBacteriaBiopharmaceuticalAccelerator.PublicHealthEmergencywebsite.http://www.phe.gov/about/barda/CARB-X/Pages/default.aspx.UpdatedJuly28,2016.AccessedOctober27,2016.

38. NIHOrganization.NationalInstitutesofHealthwebsite.https://www.nih.gov/about-nih/what-we-do/nih-almanac/nih-organization.UpdatedOctober25,2016.AccessedNovember16,2016

39. NationalInstitutesofHealth.BiennialReportoftheDirector,FiscalYears2012&2013.https://report.nih.gov/pdf/NIH_Biennial_Report_2012.pdf.Published2012.AccessedFebruary17,2017.

40. NationalInstitutesofHealth.CongressionalJustificationoftheNIHFiscalYear2017BudgetRequest.https://officeofbudget.od.nih.gov/pdfs/FY17/31-Overview.pdf.AccessedNovember16,2016.

41. NIAIDRoleinResearch.NationalInstituteofAllergyandInfectiousDiseaseswebsite.https://www.niaid.nih.gov/research/role.AccessedNovember16,2016.

42. HHSFY2016BudgetinBrief.U.S.DepartmentofHealthandHumanServiceswebsite.http://www.hhs.gov/about/budget/budget-in-brief/nih/index.html.PublishedFebruary2,2015.AccessedNovember29,2016.

43. OurMissionandVision.FogartyInternationalCenterwebsite.https://www.fic.nih.gov/About/Pages/mission-vision.aspx.AccessedNovember16,2016.

44. CongressionalJustificationforFiscalYear2017.FogartyInternationalCenterwebsite.https://www.fic.nih.gov/About/Budget/Pages/2017.aspx#orgchart.AccessedNovember16,2016.

45. NationalCenterforAdvancingTranslationalSciences.FY2017BudgetRequest.https://ncats.nih.gov/files/FY17-justification.pdf.AccessedNovember16,2016.

46. ReardonS,TollefsonJ.Obama’stopscientisttalksshrinkingbudgets,DonaldTrump,andhisbiggestregret.Nature.2016;535:15-16.doi:10.1038/535015a.PublishedJuly6,2016.AccessedNovember10,2016.


62

47. AdvisoryCommitteetotheDirector.NationalInstitutesofHealthwebsite.http://acd.od.nih.gov/.UpdatedDecember28,2016.AccessedFebruary17,2017.

48. SizemoreCF,SchleifAC,BernsteinJB,HeilmanCA.Theroleofbiomedicalresearchinglobaltuberculosiscontrol:gapsandchallenges:AperspectivefromtheUSNationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth.EmergingMicrobes&Infections.2012;1(7):e9-.doi:10.1038/emi.2012.21

49. AbouttheNICBR.NationalInteragencyConfederationforBiologicalResearchwebsite.http://www.nicbr.mil/.UpdatedNovember30,2016.AccessedFebruary14,2017.

50. CRADASOverview.NationalInstitutesofHealth,OfficeofTechnologyTransferwebsite.https://www.ott.nih.gov/cradas.AccessedOctober14,2016.

51. Mission,RoleandPledge.CentersforDiseaseControlandPreventionwebsite.http://www.cdc.gov/about/organization/mission.htm#.UpdatedApril14,2014.AccessedNovember16,2016.

52. CentersforDiseaseControlandPrevention.CDCGlobalHealthStrategy2012-2015.http://www.cdc.gov/globalhealth/strategy/pdf/cdc-globalhealthstrategy.pdf.PublishedJune29,2012.AccessedSeptember26,2016.

53. NationalCenterforEmergingandZoonoticInfectiousDiseases.NCEZIDStrategicPlan2012–2017.CS234429-A.https://www.cdc.gov/ncezid/pdf/strategicplan_ncezid.pdf.AccessedFebruary17,2017.

54. UnitingtoCombatNeglectedTropicalDiseases.LondonDeclarationonNeglectedTropicalDiseases.http://unitingtocombatntds.org/sites/default/files/resource_file/london_declaration_on_ntds.pdf.Published2014.AccessedFebruary17,2017.

55. U.S.AgencyforInternationalDevelopment.President’sMalariaInitiativeStrategy2015–2020.https://www.pmi.gov/docs/default-source/default-document-library/pmi-reports/pmi_strategy_2015-2020.pdf.PublishedApril,2015.AccessedDecember1,2016.

56. WorldHealthOrganization.GlobalTechnicalStrategyforMalaria2016–2030.http://apps.who.int/iris/bitstream/10665/176712/1/9789241564991_eng.pdf?ua=1.Published2015.AccessedOctober20,2016.

57. BoardofScientificCounselors,OID.CentersforDiseaseControlandPreventionwebsite.http://www.cdc.gov/oid/bsc.html.UpdatedJune13,2016.AccessedSeptember26,2016.

58. GlobalHealth-CDCandtheGlobalHealthSecurityAgenda.CentersforDiseaseControlandPreventionwebsite.https://www.cdc.gov/globalhealth/security/.UpdatedFebruary11,2016.AccessedOctober7,2016.

59. AboutGlobalHealthSecurityAgenda.GlobalHealthSecurityAgendawebsite.https://www.ghsagenda.org/about.Accessed16November,2016.

60. SmallBusinessInnovationResearch.NationalInstitutesofHealth,SmallBusinessInnovationResearchwebsite.https://sbir.nih.gov/.AccessedSeptember26,2016.

61. OfficeoftheAssociateDirectorforScience:TechnologyTransferOffice.CentersforDiseaseControlandPreventionwebsite.http://www.cdc.gov/od/science/technology/techtransfer/.UpdatedOctober14,2016.AccessedFebruary17,2017.

62. TheTaskForceforGlobalHealth.TheTaskForceforGlobalHealthwebsite.http://www.taskforce.org/.AccessedSeptember8,2016.


63

63. 2015COR-NTDMeeting.NeglectedTropicalDiseasesSupportCenterwebsite.http://www.ntdsupport.org/news/2015-cor-ntd-meeting.PublishedJuly30,2015.AccessedSeptember26,2016.

64. QvarnstromY,Wei-PridgeonY,LiW,etal.DraftGenomeSequencesfromCyclosporacayetanensisOocystsPurifiedfromaHumanStoolSample.GenomeAnnouncements.2015;3(6):e01324–01315.doi:10.1128/genomeA.01324-15

65. DevelopingameningococcalAconjugatevaccine.MeningitisVaccineProject.http://www.meningvax.org/developing-conjugate-vaccine.php.AccessedNovember15,2016.

66. WhatWeDo.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/AboutFDA/WhatWeDo/default.htm.UpdatedOctober24,2016.AccessedOctober27,2016.

67. FDAOrganization.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/AboutFDA/CentersOffices/default.htm.UpdatedSeptember9,2015.AccessedOctober27,2016.

68. U.S.FoodandDrugAdministration.JustificationofEstimatesforAppropriationsCommitteesFiscalYear2017.http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/BudgetReports/UCM485237.pdf.AccessedFebruary17,2017.

69. OfficeofGlobalRegulatoryOperationsandPolicy.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/default.htm.UpdatedJanuary24,2017.AccessedFebruary17,2017.

70. FDAawardsnearly$3millionforTBresearch[newsrelease].U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm228250.htm.PublishedOctober4,2010.AccessedOctober5,2016.

71. CriticalPath2010Update:Q’sandA’s.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ucm204289.htm.UpdatedApril7,2011.AccessedAugust1,2016.

72. RidleyDB,GrabowskiHG,MoeJL.DevelopingDrugsForDevelopingCountries.HealthAff(Millwood).2006;25(2):313-324.doi:10.1377/hlthaff.25.2.313

73. RidleyDB,RégnierSA.TheCommercialMarketForPriorityReviewVouchers.HealthAff(Millwood).2016;35(5):776-783.doi:10.1377/hlthaff.2015.1314

74. InternationalMedicalDeviceRegulatorsForum.InternationalMedicalDeviceRegulatorsForumwebsite.http://www.imdrf.org/.AccessedOctober12,2016.

75. ApprovedandTentativelyApprovedAntiretroviralsinAssociationwiththePresident’sEmergencyPlan.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/InternationalPrograms/PEPFAR/ucm119231.htm.UpdatedJanuary18,2017.AccessedFebruary17,2017.

76. DesignatingAdditionstotheCurrentListofTropicalDiseasesintheFederalFood,Drug,andCosmeticAct.Finalorder.FedRegist.2015;80(161):50559-50564.

77. AdministrationUSFaD.CentersofExcellenceinRegulatoryScienceandInnovation.http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm301667.htm.Accessed27October,2016.


64

78. U.S.FoodandDrugAdministration.FoodandDrugAdministrationBroadAgencyAnnouncementfortheAdvancedResearchandDevelopmentofRegulatoryScience.FDABAA-16-00122.https://www.fbo.gov/index?s=opportunity&mode=form&tab=core&id=f526e63aa7e70f2c79f1ada43e7147ef&_cview=0.PublishedFebruary23,2016.Accessed27October,2016.

79. AboutMDIC.MedicalDeviceInnovationConsortiumwebsite.http://mdic.org/about-us/.Accessed27October,2016.

80. BureauforGlobalHealth.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/who-we-are/organization/bureaus/bureau-global-health.UpdatedSeptember26,2016.AccessedNovember18,2016.

81. U.S.AgencyforInternationalDevelopment.FY2016DevelopmentandHumanitarianAssistanceBudgetFactsheet.https://www.usaid.gov/sites/default/files/documents/1869/FY2016DevelopmentBudget_FactSheet.pdf.Accessed27October,2016.

82. U.S.DepartmentofState.CongressionalBudgetJustification:DepartmentofState,ForeignOperations,andRelatedProgramsFiscalYear2017.https://www.usaid.gov/sites/default/files/documents/9276/252179.pdf.PublishedFebruary9,2016.Accessed27October,2016.

83. CenterforAcceleratingInnovationandImpact.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/cii.UpdatedJanuary12,2017.AccessedFebruary17,2017.

84. U.S.GlobalDevelopmentLab.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/who-we-are/organization/bureaus/us-global-development-lab.UpdatedJanuary19,2017.AccessedFebruary17,2017.

85. GrandChallengesforDevelopment.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/grandchallenges.UpdatedOctober27,2016.AccessedOctober27,2016.

86. U.S.AgencyforInternationalDevelopment,BureauforGlobalHealth.USAIDHealth-RelatedResearchandDevelopmentProgressReport.https://www.usaid.gov/sites/default/files/documents/1864/Health-Research-Report-2016-508_0.pdf.Published2015.AccessedOctober6,2016.

87. U.S.AgencyforInternationalDevelopment.ReportToCongress:Health-RelatedResearchandDevelopmentStrategy2011–2015.http://pdf.usaid.gov/pdf_docs/pdacw525.pdf.PublishedDecember,2012.AccessedOctober27,2016.

88. GlobalFundingofInnovationforNeglectedDiseases.Sydney,Australia:PolicyCuresResearch;2015.https://gfinder.policycures.org/PublicSearchTool/.AccessedOctober11,2016.

89. CenterforAcceleratingInnovationandImpact.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/cii.UpdatedJanuary12,2017.AccessedFebruary17,2017.

90. USAIDHIVVaccineResearchandDevelopment.U.S.AgencyforInternationalDevelopmentwebsite.https://www.usaid.gov/what-we-do/global-health/hiv-and-aids/technical-areas/hiv-vaccine-research-development.UpdatedFerbruary23,2016.Accessed27October,2016.

91. AbouttheDepartmentofDefense.U.S.DepartmentofDefensewebsite.http://www.defense.gov/About-DoD.UpdatedJanuar27,2017.AccessedFebruary17,2017.

92. AshtonB.Carter,FormerSecretaryofDefense.U.S.DepartmentofDefensewebsite.http://www.defense.gov/About-DoD/Biographies/Biography-View/Article/602689/ashton-b-carter.AccessedFebruary17,2017.


65

93. AbouttheMilitaryHealthSystem.MilitaryHealthSystemwebsite.http://www.health.mil/About-MHS.AccessedNovember16,2016.

94. DefenseHealthAgency.MilitaryHealthSystemwebsite.http://www.health.mil/About-MHS/Defense-Health-Agency.AccessedNovember16,2016.

95. GlobalHealthTechnologiesCoalition.Fromideatoimpact:HowtheUSgovernmentcanimprovecoordinationofglobalhealthresearchanddevelopment.http://www.ghtcoalition.org/pdf/From-idea-to-impact-how-the-US-government-can-improve-coordination-of-global-health-research-and-development.pdf.PublishedNovember,2014.AccessedSeptember10,2016.

96. MichaudJ,MossK,KatesJ.U.S.GlobalHealthPolicy:TheU.S.DepartmentofDefenseandGlobalHealth.KaiserFamilyFoundation.http://kff.org/global-health-policy/report/the-u-s-department-of-defense-global/.PublishedSeptember29,2012.AccessedNovember16,2016.

97. Mission.WalterReedArmyInstituteofResearchwebsite.http://www.wrair.army.mil/AboutWRAIR.aspx.UpdatedFebruary17,2017.AccessedFebruary17,2017.

98. TranslationalMedicine.WalterReedArmyInstituteofResearchwebsite.http://www.wrair.army.mil/ReAndDevelop_InfectDisRe_TranslationalMed.aspx.UpdatedFebruary17,2017.AccessedFebruary17,2017.

99. WRAIRResearchandDevelopment.WalterReedArmyInstituteofResearchwebsite.http://www.wrair.army.mil/WRAIRResearchAndDevelopment.aspx.UpdatedFebruary17,2017.AccessedFebruary17,2017.

100. NavalMedicalResearchCenter.NavalMedicalResearchandDevelopmentwebsite.http://www.med.navy.mil/sites/nmrc/NMRC/Pages/NMRC.aspx.AccessedFebruary17,2017.

101. InfectiousDiseases.NavalMedicalResearchandDevelopmentwebsite.http://www.med.navy.mil/sites/nmrc/NMRC/NMRC_Offices/Pages/IDD.aspx.AccessedFebruary17,2017.

102. Prophecy(PathogenDefeat).DefenseAdvancedResearchProjectsAgencywebsite.http://www.darpa.mil/program/prophecy-pathogen-defeat.AccessedOctober27,2016.

103. PrabhakarA.StatementtoU.S.SenateSubcommitteeonEmergingThreatsandCapabilitiesArmedServicesCommittee.StrategyandImplementationoftheDepartmentofDefense’sTechnologyOffsetsInitiativeinReviewoftheDefenseAuthorizationRequestforFiscalYear2017andtheFutureYearsDefenseProgram.http://www.darpa.mil/attachments/DARPA2016SASCTestimony4-1-2016.pdf.PublishedApril12,2016.AccessedOctober27,2016.

104. Salaam-BlytherT.U.S.GlobalHealthAssistance:BackgroundandIssuesforthe113thCongress.R43115.U.S.CongressionalResearchService.https://fas.org/sgp/crs/row/R43115.pdf.PublishedJune21,2013.AccessedNovember16,2016.

105. SerafinoN.TheDepartmentofDefenseRoleinForeignAssistance:Background,MajorIssues,andOptionsforCongress.RL34639.U.S.CongressionalResearchService.https://fas.org/sgp/crs/natsec/RL34639.pdf.PublishedDecember9,2008.AccessedNovember16,2016.

106. NationalDefenseAuthorizationAct.U.S.HouseCommitteeonArmedServiceswebsite.https://armedservices.house.gov/hearings-and-legislation/ndaa-national-defense-authorization-act.AccessedOctober12,2016.


66

107. U.S.DepartmentofDefense,UnderSecretaryofDefense(Comptroller).DefenseHealthProgram:FiscalYear(FY)2017BudgetEstimates.http://comptroller.defense.gov/Portals/45/Documents/defbudget/FY2017/budget_justification/pdfs/09_Defense_Health_Program/DHP_PB17_Vol_I-II.pdf.PublishedFebruary,2016.AccessedOctober13,2016.

108. TheMissionandStructureoftheOfficeofManagementandBudget.TheOfficeofManagementandBudgetwebsite.https://www.whitehouse.gov/omb/organization_mission.AccessedOctober8,2016.

109. ExecutiveOfficeofthePresident.TheWhiteHouseAdministrationwebsite.https://www.whitehouse.gov/administration/eop.AccessedOctober8,2016.

110. TheOfficeofManagementandBudget.TheOfficeofManagementandBudgetStrategicPlan.https://www.whitehouse.gov/sites/default/files/omb/organization/omb-strategic-plan.pdf.Published2014.AccessedOctober8,2016.

111. HourihanM.TheFederalBudgetProcess101.AmericanAssociationfortheAdvancementofScience.https://www.aaas.org/news/federal-budget-process-101.UpdatedFebruary2,2016.AccessedOctober8,2016.

112. PasachoffE.ThePresident’sBudgetasaSourceofAgencyPolicyControl.TheYaleLawJournal.2016;125(8):2182-2555.http://www.yalelawjournal.org/article/the-presidents-budget-as-a-source-of-agency-policy-control.AccessedNovember16,2016.

113. TheWhiteHouseAdministration.NationalActionPlanforCombatingAntibiotic-ResistantBacteria.https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf.PublishedMarch,2015.AccessedFebruary10,2017.

114. TheNationalSecurityCouncil.TheWhiteHouseAdministrationwebsite.https://www.whitehouse.gov/administration/eop/nsc.AccessedOctober8,2016.

115. TheOfficeofScienceandTechnologyPolicy.TheWhiteHouseAdministrationwebsite.https://www.whitehouse.gov/administration/eop/ostp/about.AccessedOctober8,2016.

116. SaturnoJV,HeniffB,LynchMS.TheCongressionalAppropriationsProcess:AnIntroduction.R42388.U.S.CongressionalResearchService.https://fas.org/sgp/crs/misc/R42388.pdf.PublishedNovember30,2016.AccessedDecember16,2016.

117. “FiscalYear,”31U.S.Code,§1102.U.S.GovernmentPublishingOffice.https://www.gpo.gov/fdsys/pkg/USCODE-2012-title31/pdf/USCODE-2012-title31-subtitleII-chap11-sec1104.pdf.AccessedNovember20,2016.

118. ChristensenMD.ThePresident’sBudget:OverviewofStructureandTimingofSubmissiontoCongress.R43163.U.S.CongressionalResearchService.https://fas.org/sgp/crs/misc/R43163.pdf.PublishedJuly25,2013.AccessedNovember16,2016.

119. StreeterS.TheCongressionalAppropriationsProcess:AnIntroduction.97-684.U.S.CongressionalResearchService.https://www.merkley.senate.gov/imo/media/doc/appropriations.pdf.PublishedDecember2,2008.AccessedNovember16,2016.

120. HeniffB.OverviewoftheAuthorizationAppropriationsProcess.RS20371.U.S.CongressionalResearchService.http://www.aacn.nche.edu/downloads/sgl/Overview_of_the_Authorization-Appropriations_Process.pdf.PublishedNovember29,2010.AccessedNovember16,2016.


67

121. KatesJ,FischerJ,LiefE.TheU.S.Government’sGlobalHealthPoliceandArchitecture:Structure,Programs,andFunding.KaiserFamilyFoundation.https://kaiserfamilyfoundation.files.wordpress.com/2013/01/7881.pdf.PublishedApril,2009.AccessedNovember10,2016.

122. MossK,KatesJ.TheU.S.CongressandGlobalHealth:APrimer.KaiserFamilyFoundation.http://files.kff.org/attachment/report-the-u-s-congress-and-global-health-a-primer.PublishedJanuary15,2016.AccessedAugust15,2016.

123. RitzB.CanCongressDeliverAppropriationsBillsOnTime?BipartisanPolicyCenterwebsite.http://bipartisanpolicy.org/blog/can-congress-deliver-appropriations-bills-on-time/.PublishedMay16,2016.AccessedFebruary10,2017.

124. PEPFARStewardshipandOversightActof2013(enacted).S.1545.113thCongress.https://www.govtrack.us/congress/bills/113/s1545.AccessedFebruary17,2017.

125. CongressionalBudgetOffice.UnauthorizedAppropriationsandExpiringAuthorizations.51131.https://www.cbo.gov/sites/default/files/114th-congress-2015-2016/reports/51131-uaea-appropriations2.pdf.PublishedJanuary15,2016.AccessedNovember16,2016.

126. SalamRA.USAIDGlobalHealthPrograms:FY2001-FY2012Request.RS22913.U.S.CongressionalResearchService.http://pdf.usaid.gov/pdf_docs/pcaac428.pdf.PublishedJune30,2011.AccessedNovember20,2016.

127. VaccineResearchCenter.NationalInstituteofAllergyandInfectiousDiseaseswebsite.https://www.niaid.nih.gov/about/vrc.UpdatedJune3,2016.AccessedOctober12,2016.

128. HIV/AIDSClinicalTrialsNetworks.NationalInstituteofAllergyandInfectiousDiseaseswebsite.https://www.niaid.nih.gov/research/hivaids-clinical-trials-networks.UpdatedJuly15,2016.AccessedSeptember23,2016.

129. CHAVI-ID.TheDukeCenterforHIV/AIDSVaccineImmunologyandImmunogenDiscoverywebsite.https://chavi-id-duke.org/.AccessedOctober12,2016.

130. HistoryoftheACTG:StaffReflectonNetwork’sMilestones.AidsClinicalTrialsGroupwebsite.https://actgnetwork.org/History.AccessedOctober12,2016.

131. U.S.AgencyforInternationalDevelopment.USAIDDevelopmentInnovationAcceleratorBroadAgencyAnnouncementforFightingEbola:AGrandChallengeforDevelopment.BAA-EBOLA-2014.http://pdf.usaid.gov/pdf_docs/PBAAB273.pdf.AccessedNovember16,2016.

132. PresidentialAdvisoryCouncilonCombatingAntibiotic-ResistantBacteria.OfficeoftheAssistantSecretaryforHealthwebsite.http://www.hhs.gov/ash/advisory-committees/paccarb/about-paccarb/index.html.UpdatedSeptember15,2015.AccessedOctober8,2016.

133. NationalVaccineAdvisoryCommittee.U.S.DepartmentofHealthandHumanServices,NationalVaccineProgramOfficewebsite.https://www.hhs.gov/nvpo/nvac/.UpdatedAugust18,2015.AccessedOctober12,2016.

134. NationalScienceandTechnologyCouncil.TheWhiteHouseAdministrationwebsite.https://www.whitehouse.gov/administration/eop/ostp/nstc.AccessedOctober7,2016.

135. OtherTransactionsforAdvancedResearch.PublicHealthEmergencywebsite.http://www.phe.gov/about/amcg/otar/pages/default.aspx.UpdatedDecember7,2015.AccessedOctober12,2016.


68

136. FederalAcquisitionRegulation.U.S.GeneralServicesAdministration,Acquisitionwebsite.https://www.acquisition.gov/?q=browsefar.UpdatedJanuary19,2017.AccessedFebruary12,2017.

137. CarrollJ.Inspiredby$220MinBARDAfunding,AstraZenecastepsupantibioticsR&D.FierceBiotech.http://www.fiercebiotech.com/r-d/inspired-by-220m-barda-funding-astrazeneca-steps-up-antibiotics-r-d.PublishedSeptember17,2015.AccessedNovember21,2016.

138. PriorityReviewVoucher.PriorityReviewVoucherwebsite.http://priorityreviewvoucher.org/.AccessedOctober13,2016.

139. NationalVaccineInjuryCompensationProgram.U.SDepartmentofHealthandHumanServices,HosueResourcesandServicesAdministrationwebsite.https://www.hrsa.gov/vaccinecompensation/.UpdatedFebruary,2016.AccessedOctober12,2016.

140. CountermeasuresInjuryCompensationProgram.MorbidityandMortalityWeeklyReport.http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5925a5.htm.59(25);780.PublishedJuly2,2010.AccessedNovember21,2017.

141. CoxE,LaessigK.FDAApprovalofBedaquiline—TheBenefit–RiskBalanceforDrug-ResistantTuberculosis.NEnglJMed.2014;371(8):689-691.doi:10.1056/NEJMp1314385

142. FDANewsRelease.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm.PublishedDecember31,2012.AccessedDecember27,2016.

143. EmergencyUseAuthorization.U.S.FoodandDrugAdministrationwebsite.http://www.fda.gov/EmergencyPreparedness/Counterterrorism/ucm182568.htm.PublishedJanuary26,2017.AccessedFebruary18,2017.

144. TheKaiserFamilyFoundation.TheU.S.GlobalHealthInitiative.https://kaiserfamilyfoundation.files.wordpress.com/2013/01/8116.pdf.PublishedDecember,2011.AccessedNovember20,2016.

145. U.S.DepartmentofState.LeadingThroughCivilianPower:TheFirstQuadrennialDiplomacyandDevelopmentReview.https://www.state.gov/documents/organization/153108.pdf.Published2010.AccessedDecember20,2016.

146. ShahR,GoosbyE,FriedenT,QuamL.OfficialsChartNextStepsforU.S.GlobalHealthInitiative.GlobalHealthInitiativeOfficialBlog.http://iipdigital.usembassy.gov/st/english/article/2012/07/201207058538.html.PublishedJuly3,2012.AccessedDecember20,2016.

147. OommanN,SilvermanR.GHIMid-TermReviewandaWayForward:AReportoftheRethinkingU.S.ForeignAssistanceProgram.CenterforGlobalDevelopment.https://www.cgdev.org/sites/default/files/1425914_file_NO_RS_GHI_FINAL_0.pdf.PublishedJanuary30,2012.AccessedFebruary18,2017.

148. U.S.GovernmentGlobalHealthInitiative.TheUnitedStatesGovernmentGlobalHealthInitiativeStrategy.http://www.pepfar.gov/documents/organization/136504.pdf.AccessedOctober12,2016.

149. BudgetControlActof2011(enacted).S.365.112thCongress.https://www.congress.gov/bill/112th-congress/senate-bill/365.AccessedNovember20,2016.

150. SandersK.StephanieCutter:Ebolavaccineresearchwascutinhalf,andmorecutsarecoming.PunditFact.http://www.politifact.com/punditfact/statements/2014/oct/24/stephanie-cutter/stephanie-cutter-ebola-vaccine-research-was-cut-ha/.PublishedOctober24,2014.AccessedDecember27,2016.


69

151. HistoryandAchievements.MilitaryInfectiousDiseasesResearchProgramwebsite.https://midrp.amedd.army.mil/info/HAchieve.jsp.AccessedNovember22,2016.

152. CollinsC.WalterReedArmyInstituteofResearch:ABriefHistory.DefenseMediaNetwork.http://www.defensemedianetwork.com/stories/walter-reed-army-institute-of-research-a-brief-history/.PublishedApril28,2014.AccessedJanuary12,2017.

153. CEmarking.EuropeanCommissionwebsite.https://ec.europa.eu/growth/single-market/ce-marking_en.UpdatedOctober13,2016.AccessedOctober13,2016.

154. DefenseThreatReductionAgency.DefenseThreatReductionAgencywebsite.http://www.dtra.mil/.AccessedOctober13,2016.

155. BielloD.ObamaHasDoneMoreforCleanEnergyThanYouThink.ScientificAmerican.https://www.scientificamerican.com/article/obama-has-done-more-for-clean-energy-than-you-think/.PublishedSeptemerb8,2015.AccessedDecembe27,2016.

156. WapnerJ.WeNowHavetheCureforHepatitisC,butCanWeAffordIt?ScientificAmerican.https://www.scientificamerican.com/article/we-now-have-the-cure-for-hepatitis-c-but-can-we-afford-it/.PublishedSeptember1,2014.AccessedDecember27,2016.

157. MedicinesPatentPool.MedicinesPatentPoolwebsite.http://www.medicinespatentpool.org/.AccessedOctober12,2016.

158. USPTOPatentsforHumanity.UnitedStatesPatentandTrademarkOfficewebsite.http://patentsforhumanity.devpost.com/.AccessedOctober12,2016.

159. InternationalFederationofPharmaceuticalManufacturers&Associations.InternationalFederationofPharmaceuticalManufacturers&Associationswebsite.http://www.ifpma.org/.AccessedOctober13,2016.

160. SouthAfricanDevelopmentCommunity.SouthernAfricanDevelopmentCommunitywebsite.http://www.sadc.int/.AccessedOctober13,2016.

161. AfricanMedicinesRegulatoryHarmonisation.NewPartnershipforAfrica’sDevelopmentwebsite.http://www.nepad.org/content/african-medicines-regulatory-harmonisation-armh-programs.AccessedOctober13,2016.

162. President’sCouncilofAdvisorsonScienceandTechnology.TheWhiteHouseAdministrationwebsite.https://www.whitehouse.gov/administration/eop/ostp/pcast.AccessedOctober13,2016.

163. MedicinesforMalariaVenture.AnnualReport2015.http://www.mmv.org/sites/default/files/uploads/docs/publications/MMV_Annual_Report_2015.pdf.AccessedNovember30,2016.

164. WorldIntellectualPropertyOrganization.WIPORe:SearchSharingInnovationintheFightAgainstNeglectedTropicalDiseases.http://www.wipo.int/export/sites/www/research/docs/guiding_principles.pdf.PublishedJune8,2011.AccessedNovember28,2016.

165. RamamoorthiR,GraefKM,DentJ.WIPORe:Search:Acceleratinganthelminticdevelopmentthroughcross-sectorpartnerships.InternationalJournalforParasitology:DrugsandDrugResistance.2014;4(3):220-225.doi:10.1016/j.ijpddr.2014.09.002.

166. MalariaVaccineInitiative.FrequentlyAskedQuestions.http://www.malariavaccine.org/files/MVI-GSK-FAQ-FINAL-web.pdf.AccessedNovember27,2016.


70

167. ProductDevelopmentforVaccinesAdvisoryCommittee:Meetings,termsofreferenceandcomposition.WorldHealthOrganizationwebsite.http://www.who.int/immunization/research/committees/pdvac/en/.AccessedNovember27,2016.

168. OurMission.AmericanEnergyInnovationCouncilwebsite.http://americanenergyinnovation.org/our-mission/.AccessedOctober12,2016.

169. AnnouncementofU.S.ScienceEnvoys.U.S.DepartmentofStatewebsite.http://www.state.gov/r/pa/prs/ps/2014/12/234682.htm.AccessedOctober20,2016.

170. WorldHealthOrganization.GlobalObservatoryonHealthResearchandDevelopment.http://www.who.int/research-observatory/onepager_20160607.pdf?ua=1.AcessedOctober12,2016.

171. AnacorPharmaceuticalsandMMVsignagreementtopursuepromisingcompoundformalaria(pressrelease).MedicinesforMalariaVenture.http://www.mmv.org/newsroom/press-releases/anacor-pharmaceuticals-and-mmv-sign-agreement-pursue-promising-compound.PublishedMarch18,2011.AccessedOctober12,2016.

172. Article58applications:Regulatoryandproceduralguidance.EuropeanMedicinesAgencywebsite.http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000157.jsp.AccessedOctober12,2016.

173. EuropeanMedicinesAgency,CommitteeforMedicinalProductsforHumanUse.GuidelineonproceduralaspectsregardingaCHMPscientificopinioninthecontextofcooperationwiththeWorldHealthOrganisation(WHO)fortheevaluationofmedicinalproductsintendedexclusivelyformarketsoutsidethecommunity.http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003883.pdfPublishedNovember17,2005.AccessedJanuary20,2017.

174. BrennanZ.Article58:HowEMAHelpsIncreaseAccesstoDrugsinLow-andMiddle-IncomeCountries.RegualtoryAffairsProfessionalsSociety.http://www.raps.org/Regulatory-Focus/News/2016/04/26/24825/Article-58-How-EMA-Helps-Increase-Access-to-Drugs-in-Low--and-Middle-Income-Countries/#sthash.llKcKmfi.dpuf.PublishedApril26,2016.AccessedOctober12,2016.

175. TheWhiteHouseAdministration.ObamaAdministrationAnnouncesMoreThan$4BillioninPrivateSectorCommitmentsandExecutiveActionstoScaleupInvestmentinCleanEnergyInnovation(pressrelease).https://www.whitehouse.gov/the-press-office/2015/06/16/fact-sheet-obama-administration-announces-more-4-billion-private-sector.PublishedJune16,2015.AccessedOctober12,2016.

176. TheWhiteHouseAdministration.PresidentObamaAnnouncesNewInvestmentstoCombatClimateChangeandAssistRemoteAlaskanCommunities(pressrelease).https://www.whitehouse.gov/the-press-office/2015/09/02/fact-sheet-president-obama-announces-new-investments-combat-climate.PublishedSeptember2,2015.AccessedOctober12,2016.

177. WorldHealthOrganization.ResearchandDevelopmenttoMeetHealthNeedsinDevelopingCountries:StrengtheningGlobalFinancingandCoordination.http://www.who.int/phi/CEWG_Report_5_April_2012.pdf.PublishedApril5,2012.AccessedOctober12,2016.

178. LaubZ.TheGroupofEight(G8)IndustrializedNations.CouncilonForeignRelations.http://www.cfr.org/international-organizations-and-alliances/group-eight-g8-industrialized-nations/p10647.UpdatedMarch3,2014.AccessedOctober12,2016.

179. FoundingPrinciples.GlobalHealthInnovationTechnologyFundwebsite.https://www.ghitfund.org/hww/principles.AccessedOctober12,2016.

180. Scope.CARB-X.website.http://www.carb-x.org/scope.AccessedOctober12,2016.


71

181. JohnsonJA.BriefHistoryofNIHFunding:FactSheet.R43341.U.S.CongressionalResearchService.https://fas.org/sgp/crs/misc/R43341.pdf.PublishedDecember23,2013.AccessedNovember27,2016.

182. EndNeglectedTropicalDiseasesAct(introduced).H.R.1979.114thCongress.https://www.congress.gov/bill/114th-congress/house-bill/1797.AccessedJanuary20,2017.

183. GundersonD.BreakingNowonCapitolHill:IntroducingtheEndNeglectedTropicalDiseasesAct.END7.http://endtheneglect.org/2014/06/breaking-now-on-capitol-hill-introducing-the-end-neglected-tropical-diseases-act/.PublishedJune13,2014.AccessedOctober14,2016.

184. GlobalDevelopmentLabActof2016(introduced).H.R.3924.114thCongress.https://www.congress.gov/bill/114th-congress/house-bill/3924.AccessedSeptember20,2016.

185. ChmiolaM,CarsonC,KelleyK,MortonEW,RobinsonM.Achievingaboldvisionforglobalhealth:PolicysolutionstoadvanceglobalhealthR&D.GlobalHealthTechnologiesCoalition.http://www.ghtcoalition.org/pdf/Achieving-a-bold-vision-for-global-health-Policy-solutions-to-advance-global-health-R-D.pdf.Published2016.AccessedNovember30,2016.

186. ChristophM.Imagining“BoldEndgames”InGlobalHealth.InterAction.https://www.interaction.org/blog/imagining-%E2%80%9Cbold-endgames%E2%80%9D-global-health.PublishedApril12,2013.AccessedNovember22,2016.

187. YameyG,MorelC.InvestinginHealthInnovation:ACornerstonetoAchievingGlobalHealthConvergence.PLoSBiol.2016;14(3):e1002389.doi:10.1371/journal.pbio.1002389

188. McNeil,DG.TrumpAdministrationPutstheU.S.ataCrossroadforGlobalHealthAid.NewYorkTimes.http://www.nytimes.com/2016/12/19/health/donald-trump-foreign-aid-global-health.html.PublishedDecember19,2016.AccessedDecember27,2016.

189. GlobalHealthTechnologiesCoalition.MakingthecaseforUSGovernmentinvestmentinpoverty-relatedneglecteddiseaseresearchanddevelopment.March2017(inpress).

190. WalshE.WhyinvestinR&DforHIV,TBandMalaria?Becauseit’sgoodforglobalhealth,andgoodforEurope.DeutscheStiftungWeltbevoelkerung.http://www.dsw.org/en/2014/09/invest-for-hiv-tb-malaria-good-for-global-health-good-for-europe/.PublishedSeptember4,2014.AccessedDecember27,2016.

191. TieferC.PresidentTrumpIsLikelyToBoostU.S.MilitarySpendingBy$500BillionTo$1Trillion.Forbes.http://www.forbes.com/sites/charlestiefer/2016/11/09/president-trump-is-likely-to-boost-u-s-military-spending-by-500-billion-to-1-trillion/#10000a1c4108.PublishedNovember9,2016.AccessedNovember22,2016.

192. JamisonDT,SummersLH,AlleyneG,etal.Globalhealth2035:aworldconvergingwithinageneration.TheLancet.2013;382(9908):1898-1955.doi:10.1016/S0140-6736(13)62105-4

193. Whatistotalofficialsupportforsustainabledevelopment(TOSSD)?OrganisationforEconomicCo-operationandDevelopment.http://www.oecd.org/dac/financing-sustainable-development/tossd.htm.AccessedNovember20,2016.