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Pathway to Patients Charting the Dynamics of the Global TB Drug Market

COMPENDIUM OF FINDINGS MAy 2007

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Compendium |page�

may2007

PathwaytoPatientsChartingtheDynamicsoftheGlobalTBDrugMarket

Compendium of findings may2007

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page�| TBallianCe

paThwayTopaTienTs

TableofContents

1. Preface ....................................................................................................... 4 1.1 IntroductiontotheProject. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

1.2 Methodology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2. GlobalProcurementServicesAgencies(PSAs). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.1 GlobalTBDrugFacility:BackgroundandRole. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.1.1 Customers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.1.2ProcurementAgentSelectionProcess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.1.3SupplierPre-QualificationandSelectionProcess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.1.4Pricing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.1.5Suppliers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.1.6 QualityControl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.1.7 TransportProcess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.2 GreenLightCommittee:BackgroundandRole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.1Customers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.2 ProcurementAgentSelectionProcess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.3 Suppliers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.4 Pricing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.5 TransportPathway. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2.2.6QualityControl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1

2.3 ConvergenceoftheGlobalTBDrugFacilityandtheGreenLightCommittee. . . . . . . . . . . . . . . . . . . 1 1

2.4 OtherGlobalPSAs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

3. CountryCaseStudies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.1 TBControlintheContextofNationalHealthcareSystems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

3.1.1 HighBurdenCountries(HBCs). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

3.1.2HighIncomeCountries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

3.2 OverviewofKeyTrendsImpactingTBFundingandTreatmentinHBCs. . . . . . . . . . . . . . . . . . . . . . . . .14

3.3 HBCNationalTBControlPrograms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

3.3.1 Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

3.3.2Financing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

3.3.3Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.4 TreatmentofTBPatients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.4.1HBCs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.4.2HighIncomeCountries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

3.4.3UseofFixed-DoseCombinationsinTreatmentRegimens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

3.4.4 ServiceProvision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

3.5 PublicSector:ReferralPathwayandSettingsofCare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

3.5.1 HBCs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17

3.5.2HighIncomeCountries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

3.5.3PaymentforDrugsandServices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

3.6 PrivateSector:ReferralPathwayandSettingsofCare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

3.6.1 RoleofPublic-PrivateMixProgramsinTBTreatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

3.6.2 PaymentforDrugsandServicesinthePrivateSector . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

3.7 MDR-TBControl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

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4. ProcurementandDistributionofTBDrugsinHighBurdenCountries. . . . 20 4.1 FinancingforFirst-lineTBDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

4.1.1FinancingforSecond-lineTBDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21

4.2 PublicDrugProcurement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21

4.2.1PublicTenderProcess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21

4.2.2DemandForecasting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

4.2.3 DistributionPathways. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

4.3 PrivateDrugProcurement:First-andSecond-lineDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

5. ProcurementandDistributionofTBDrugsinHighIncomeCountries.....25 5.1 FinancingofTBDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

5.2 ProcurementofTBDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

5.3 FlowofDrugs.............................................................................................25

6. CostofTreatmentofTBinBothHighBurdenandHighIncomeCountries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26

6.1 PricesofTBDrugRegimens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

6.2 PublicandPrivatePricing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

7. ValueEstimatesForFirst-andSecond-LineTBDrugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28 7.1 OverviewofMethodology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28

7.2 Country-by-CountryEstimates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

7.3 GlobalEstimates..........................................................................................32

8. AdditionalConsiderations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

9. PredictingFutureMarketDynamics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

10. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

11. Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 11.1 PartialListofAcronyms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

11.2 ListofManufacturers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38

11.3 PricesofDrugsforSelectCountriesandPurchasers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

11.4 InterviewLists. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41

12.Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

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1.Preface

MorethanacenturyafterthediscoveryofMycobacteriumtuberculosis(M.tb),thebacillusthatcausestuberculosis(TB),andahalf-centuryafterthediscoveryofantibioticstotreatthedisease,TBissecondonlytoHIVastheleadinginfectiouskillerofadultsworldwide.

TBkillssomeoneevery20seconds—about4,400peopleeveryday,orapproximately1.6millionin2005alone,accordingtothelatestestimatesfromtheWorldHealthOrganization(WHO).1Itaccountsformoredeathsamongwomenthanallothercausesofmaternalmortalitycombined2andistheleadinginfectiouscauseofdeathamongpeoplewithHIV/AIDS.3

TheWHOestimatesthatonethirdoftheworld’spopulationisinfectedwithM.tb,whichcausesTB,withthegreatestburdenrelativetopopulationconcentratedinthedevelopingworld,withhighincidenceofinfectioninsub-SaharanAfrica,AsiaandSouthAmerica,asshowninFigure1.Further-more,today’sTBepidemicisfuelledbyasurgeinHIV-M.tbco-infectionandcompoundedbythegrowingemergenceofdrugresistantstrains.

Apartfromitsdevastatinghealthconsequences,theeconomicimpactofthediseaseisstaggering,makingTBasignificantcontributortoworldpoverty.TBisestimatedtoabsorbUS$12billionfromtheincomesoftheworld’spoorestcommunities.Insomecountries,lossofproductivityattributabletoTBisintheorderoffourtosevenpercentofgrossdomesticproduct.4

1 Global tuberculosis control: surveillance, planning, financing. WHO report 2007. Geneva, World Health Organization.2 Connolly M, Nunn P. Women and tuberculosis. World Health Stat Q. 1996;49:115-119.3 Frequently Asked Questions About TB and HIV. World Health Organization. http://www.who.int/tb/hiv/faq/en/. Accessed 2/27/07.4 HIV/AIDS, Tuberculosis and Malaria: The Status and Impact of the Three Diseases. The Global Fund to Fight AIDS, Tuberculosis

and Malaria, 2005.

Figure 1. Estimated Global TB Incidence (2005)

Source: Global tuberculosis control: surveillance, planning, financing. WHO report 2007. Geneva, World Health Organization.

l No Estimate

l 0-24

l 25-49l 50-99l 100-299l 300 or more

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ThecurrentTBdrugregimen,aproductofthebestscientificadvancesofthe1960s,worksforactive,drug-susceptibleTB—aslongaspatientscompletethesix-tonine-monthtreatment.However,today’sfour-drugcombination,takenideallyunderdirectobservationbyahealthcareworkerorcommu-nitymember,isburdensomeforpatientsandcareprovidersalikeanddespitetheenormousadvancesinprovisionofservicesoverthepastfewyears,manypatientsdonotorcannotcompletetreatment.

Thepooradherenceandimproperadministrationofexistingantibioticshaveledtotheemergenceofmulti-andextensivelydrugresistantTBstrains,knownasMDR-TBandXDR-TB,respectively.Further,theglobalHIV/AIDSpandemicisfuellinganincreaseinTB,resultinginadramaticriseinthenumberofco-infectedindividuals.Anestimatedone-thirdofthe40millionpeoplelivingwithHIV/AIDSworldwideareco-infectedwithTB.PeoplewithHIVareupto50timesmorelikelytodevelopTBinagivenyearthanHIV-negativepeople,andTBisoneoftheleadingcausesofdeathinHIV-infectedpeople,particularlyinlowincomecountries.5Insub-SaharanAfrica,upto80percentoftuberculosispatientsarealsoHIVinfected.6Unfortunately,thecurrentTBdrugregimenisnotcompatiblewithcertaincommonantiretroviraltherapiesusedtotreatHIV/AIDS.

Criticaltofightingthisancientdiseaseisthedevelopment—andsubsequentadoption—ofaffordable,new,fasterandsimplerdrugregimens.Afteralmosthalfacenturyofvirtualinactivity,TBdrugdevelopmenthasresurged.Bolsteredbynewscientificinformationonthebacillus,transforminginternationalfundingfromphilanthropicsectorsandgovernmentdonors,andtheappearanceofinnovativebusinessmodelsdesignedtobreachthedrugdevelopmentgap,thecurrentglobalTBdrugpipelineisthelargestinhistory.

ExperiencehasdemonstratedthatattritionratesareveryhighindrugdevelopmentanditisexpectedthatTBdrugswillbenoexception.However,thestrengthoftheportfoliounderscoresthefactthatevenmorenewTBdrugcandidatesandnoveldrugregimensarelikelytobeforthcomingwithinthenextfivetotenyears.

Experiencehasalsodemonstratedthattheuptakeofinnovationisaprocessthatrequiresunderstanding

ofmarketforces,distributionchannels,purchasingpowerandmyriadotherconsiderations.ThepromisingnewTBcureswillbeineffectiveandtheresurgentmovementforTBdrugdevelopmentwillhavefailedifthenewtreatmentsdonotreachpatients.

In2006,theGlobalAllianceforTBDrugDevelopment(TBAlliance)commissionedPathway to Patients: Charting the Dynamics of the Global TB Drug Market.Thestudyisthefirstcomprehensiveanalysisofhowtoday’sTBdrugsreachpatientsonaglobalscale.Itincludesanassessmentoftenstrategicallyselectedcountries—Brazil,China,France,India,Indonesia,Japan,thePhilippines,SouthAfrica,theUKandtheUS—aswellasanappraisaloftoday’sworldwideTBdrugmarketvalue.

ThiscompendiumisadigestofinformationgatheredfromPathway to Patientsanddetailsthepricing,purchasing,procurementanddistributionmechanismsforfirst-andsecond-lineTBtreatmentsinthesecountries.Inaddition,thestudyupdatestheoriginalglobaldrugmarketassessmentcarriedoutbytheTBAlliancein2001inThe Economics of TB Drug Development .7

TheresearchforPathway to PatientswasconductedinpartnershipwithIMSHealth,Inc.,aglobalstrate-gicconsultinggroupfocusedonthepharmaceuticalandhealthcareindustries.TheprojectwasfinancedbyagrantfromtheNetherlandsMinistryofForeignAffairs’DepartmentofDevelopmentCooperation(DGIS)andwiththesupportoftheBill&MelindaGatesFoundation.Anabridgedoverviewofthesefindingsandaseparatemethodologydocumentareavailableonlineatwww.tballiance.org.

1.1 Introduction to the Project

Ofthetencountriesstudied,sixwerechosenfromamongthe22identifiedbytheWHOashighburdencountries(HBCs):Brazil,China,India,Indonesia,thePhilippines,andSouthAfrica.Together,thesecountriescarryapproximately50percentoftheworld’sTBburden.8Theprojectalsoencompassedfourhighincomecountries,France,Japan,theUKandUS.Althoughthelatterhavealowburdenofdisease,theyrepresentasignificantvalueoftheTBmarketbecauseofhighercostoftreatment.Thesecountriesareofparticularinteresttodrug

5 Frequently Asked Questions About TB and HIV. World Health Organization. http://www.who.int/tb/hiv/faq/en/. Accessed 2/27/07.6 Reid A, Scano F, Getahun H, et. al. Towards universal access to HIV prevention, treatment, care, and support: the role of tuberculosis/HIV

collaboration. Lancet 2006 ; 6: 483-495.7 The Economics of TB Drug Development. Global Alliance for TB Drug Development. October, 2001.8 Global tuberculosis control: surveillance, planning, financing. WHO report 2007. Geneva, World Health Organization.

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manufacturersbecausetheyaccountfor61percentofthetotalglobalmarketforallpharmaceuticals.9Moreover,theywerechosenbecausetheyreflectdifferentgeographies,differentpricinganddifferenthealthsystemsstructures.

Forthestudy,researchonIndonesiaandJapanwaslimitedtodeterminingmarketvalueanddidnotexamineprocurementanddistribution.

1.2 Methodology10

Themethodologyusedinthestudyallowedforbothqualitativeandquantitativeanalyses.Qualita-tivecharacterizationoftheTBmarketincludedmappingtheflowofTBmedicinesfromthesuppliertothepatient,theselectionprocessforsuppliers,andtheroleofpublicandprivatepayersforfirst-andsecond-lineTBmedicines.Qualitativeanalysisalsoincludedthefollowingsteps:

1.Primaryresearchwasconductedthroughface-to-faceinterviewswithglobalandcountrystakehold-ersbytelephoneandinperson,includingstaffattheWHO,theStopTBPartnership,andnationalandlocalstafffromTBcontrolprogramsofthecountriesstudied

2.SecondarydatawerecollectedfromanumberofpubliclyavailablesourcesaccessedthroughsearchenginesanddirectlyfromtheWHOwebsite

3.Additionaldataandreportswerecollectedfromindividualstakeholdersfollowingdiscussions

Quantitativecharacterizationofthefirst-andsecond-linepublicTBdrugmarketsfocusedonmeasuringtheactualvalue(definedasmarketvalue)inthepublicandprivatesectors.Datawerecollectedfromseveralsecondarysources:

1.IMSHealthdatabasesprovidedinformationonvalueandunitssoldintheprivatemarketinallcountrieswhereaprivateTBmarketexists(China,India,Japan,thePhilippinesandtheUS)andthepublicmarketinsomecountries(France,SouthAfrica,theUKandtheUS)

2.Globalorganizationsprovideddataoncostsandsupplyofproductsbothgloballyandatthecountrylevel

3.ProductsuppliersprovideddataoncostsandsalesofTBproductssold

4.NationalTBcontrolprogramsinthecountriesstudiedprovideddataonthenumberofpatientstreatedinthepublicsector,fundingfordrugprocurement,andcostsperproductandregimeninthepublicsector

Fortheprivatefirst-andsecond-linemarkets,IMSHealthdatabaseswereusedwhereavailable(e.g.India)toestimatevalue.Valueestimatesarebasedontheactualvalueofdrugssoldintheprivatemarketplace.Recognizingthatmanysecond-linedrugsareusedforindicationsotherthanTB,prescriptiondatawereusedtoadjustthosefiguressothattheymorecloselyreflectedthevalueofsecond-linedrugsusedforTBspecifically.First-linedrugvaluefigureswereleftunadjustedbecausetheprescriptiondataindicatedthatonlyamarginalfractionofthosedrugsinthecountriesstudiedwerebeingusedforindicationsotherthanTB.

Estimatesofpatientvolumeintheprivatesectorcouldnotbeobtainedforeitherfirst-orsecond-linedrugsbecausepatientadherenceandtreatmentpractices,aswellasrecordkeeping,variedgreatlybetweenandwithincountries.Therefore,patientvolumesareonlyprovidedforpublic-sectorprograms.

Thepublic-sectordrugbudgetfiguresandthepricepertreatmentregimenestimatesdescribedinthisreportmaydifferslightlyfromthosereportedinthe2006WHOreportGlobal Tuberculosis: Surveillance, Planning, and Financing.ThisisbecauseresearchfortheWHOreportandforPathway to Patientsweregatheredatdifferenttimes.FiguresreportedtotheWHOmayhavebeenbasedonprojectionsfor2005,whereastheresearchinthisstudywasprimarilybasedonactualexpendituresfor2005.Moreover,where2005datawerenotavailableforthisreport,researchersreliedon2004datainstead.11Becausethefiguresaregatheredusingthesamemethodologyfromyeartoyear,thecombinationofdatafromconsecutiveyearswasdeterminedtobeappropriate.

ItshouldalsobenotedthatthestudydidnotseektorevieworaddressthequalityofTBtreatmentorthequalityofprocurementanddistributioninanyofthecountriesstudied.

9 IMS Knowledge Link. http://www.imsknowledgelink.com.10 For full information about the specific methodology used to determine the market estimates for each country and the global estimates, including

individual drug cost figures and a list of the countries included in the global extrapolation, a separate methodology document is available online at www.tballiance.org.

11 Discussions with Kathryn Floyd, WHO, October 2006.

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2.GlobalProcurementServicesAgencies

Anumberoforganizationsknownasprocurementservicesagencies(PSAs)existatthegloballeveltoassistcountriesand/ororganizationsinsupplyingdrugstotheirrespectiveTBprograms.TheseincludeagenciesthatarededicatedspecificallytoTBdrugprocurement,suchastheStopTBPartnership’sGlobalTBDrugFacility(GDF)andGreenLightCommittee(GLC),orthosethatprocurearangeofproducts,suchasCrownAgentsortheIDAFoundation.Insomecountriesnon-governmentorganizations(NGOs)alsoprocureTBdrugs,eitherfortheirownprogramsorforthegeographicregioninwhichtheyoperate.Pathway to PatientsfocusedontwoofthePSAsengagedinprocurementinHBCs:TheGDFandtheGLC.12

2.1 Global TB Drug Facility: Background and Role

HousedattheWHOheadquartersinGeneva,SwitzerlandandmanagedbytheStopTBPartner-shipSecretariat,theGDFwasinitiatedin2001inresponsetothedifficultiesexperiencedbycountriesinfindingandfundingstableTBdrugsupplies.Itsstatedmissionis“toexpandaccessto,andavailabilityof,high-qualityTBdrugstofacilitateDOTSexpansion.”13

TheGDFseekstodirectlyaddressseveralproblemscountriesmayfaceintheprocurementofTBmedication,includinglackoffinancialresources,inefficientprocurementmechanisms,poorqualityassurancesystemsandinadequatein-countrymanagementandmonitoring.Forcountriesthatlacktheresourcestofunddrugprocurement,theGDFoffersin-kindgrantservices.Forcountriesthatcanaffordtopurchasedrugs,theGDFalsooffersdirectprocurementservices.Forallcountries,itofferspre-qualificationservicestoensureadequatequalitycontrolmechanismsandprovidesin-countrymonitoringandtechnicalsupporttoimproveandmaintainhigh-qualitydrugsupply,management,anddistributionprocesses.

Asdescribedinthissection,orderingTBmedicinesthroughtheGDFisamulti-stepprocess.ThepurchasermustapproachtheGDFwithrequestsfor

TBdrugs.TheGDFthenconfirmstheeligibilityofthepurchaserandforwardstheordertoaselectedprocurementagent.Theprocurementagentplacestheorderwithsuppliersthathavewonaninterna-tionalcompetitivebid.Finally,themajorityofordersareforwardedtotheprimarysuppliernamedinthebidand,ifnecessary,asecondarysupplierisusedtoprovideadditionalvolumes.

2.1.1 CustomersGDFcustomersfallintooneoftwocategories,purchasersorgrantees.

Purchasers (mostoftenhealthministries)obtaindrugsfromtheGDFthroughdirectprocurement.Incountrieswherethenationalgovernmentdoesnotplayacentralroleinprocurement,stateorprovincialhealthministriesorNGOssuchasPartnersinHealth(PIH)orMédecinsSansFrontières(MSF)mayserveasprimarypurchasers.

CountriesseekingtoprocuredrugsthroughtheGDF’sdirectprocurementprocessmustfirstbeapproved.Eligiblecountriesororganizationsinclude:

• CountriesthatimplementWHO-recommendedDOTSstrategyin90percentormoreofthepopulation

• NGOsthatsupportDOTSstrategyinthesecountries

• CountriesorNGOsapprovedbytheGDFforTBdruggrants

• CountriesorNGOsapprovedforagrantforTBcontrolbytheGlobalFundtoFightAIDS,TuberculosisandMalaria(GFATM)

• Organizations,donorsandtechnicalagenciessupportingthesecountriesorNGOs14

ThevaluetoclientsoftheGDF’sdirectprocure-mentservicesvariesdependingonthecapabilitiesandneedsofeachcountry.Forthemostpart,theGDF’svaluepropositionismeasuredinitsabilitytoassistcountriesthatdonothavesufficient,reliablequalitycontrol,and/orefficientinternalpurchasingorproductioncapabilities.Forsomecountries,priceandpackagingarealsoviewedasanattribute.

12 In early 2006, the GDF announced that it would converge with the GLC. Procurement functions of the GDF and GLC already have been combined. Plans to combine their application, review, monitoring, and evaluation functions are currently underway. For more information about the GDF/GLC convergence, see section 2.3 of this report.

13 Stop TB Partnership. http://www.stoptb.org/gdf/whatis/what_is.asp. Accessed 2/28/07.14 As per “Global Drug Facility: An Introduction”. Available in PDF format:

www.stoptb.org/gdf/documents/FS%20GDF%20An%20Introduction_June06.pdf.

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GranteesincludecountriesthatlackfinancialresourcestoprocureTBmedicinesandinsteadreceivein-kindgrantsintheformoffreedrugs.Granteesreceivingdrugsmustmeetalleligibilityrequirementsfordirectprocurementaswellasthefollowingcriteria:

• Annualpercapitagrossnationalincome(GNI)underUS$3,000

• AnationalplanandbudgetallocationforDOTSexpansiontomeetglobalTBcontroltargets

• TechnicalguidelinesdemonstratingcommitmenttomeetglobalTBcontroltargets

• CompletionofanannualreportonDOTSperformance(WHOTBcollectionform)

• MusthavereceivedarecentexternalnationalTBprogramreview15

AsshowninFigure2,theGDFsuppliesfirst-lineTBdrugsto13ofthe22WHO-designatedhighburdencountries.However,ofthecountriesforwhichprocurementwasstudied,onlyIndiaandthePhilippinescurrentlyusetheGDF,andevenforthesecountries,first-linedrugsarealsosourcedthroughpublictenderprocesses.

2.1.2 Procurement Agent Selection ProcessTheGDFdoesnotprocureTBmedicinesonitsown.Instead,itservesasascreenerandbrokerbetweensuppliersandpurchasers.ItfirstidentifiesagenciesandorganizationsbestsuitedtoperformtheTBdrugprocurementanddistributionfunction.

Afterformingcontractualrelationshipswiththeseorganizations,theGDFseekstomatcheligiblecountrieswiththem.Indoingso,itfacilitatesaccesstoanuninterruptedsupplyofconcessionally-priced,high-qualityTBdrugs.

Figure3ontheoppositepagedescribestheprocessthroughwhichtheGDFselectsaprocurementagent.Theprocurementagentthenbecomesresponsibleforsub-contractingotherpartnersforqualitycontrolandfreight-forwardingfunctions.

SincetheinceptionoftheGDF,itsprimaryprocure-mentagenthasbeentheInter-AgencyProcurementServicesoftheUnitedNationsDevelopmentProgramme(UNDP-IAPSO).In2006,theservicewasre-bidandtheGermanAgencyforTechnicalCooperation(GTZ)wasselectedasthenewprocure-mentagent,contractedforaperiodoftwoyears.

2.1.3 Supplier Pre-Qualification and Selection Process InordertobeeligibletosupplydrugstotheGDF,suppliersmustbeassessedbytheWHO.ManufacturingsitesmustcomplywiththeWHO’sGoodManufacturingPractices(GMP)standards.TheymustthenmeetWHO/PSM16pre-qualificationrequirements.17Theselectionprocessforapprovedsuppliersisthencarriedoutbytheprocurementagentthroughanannualinternationalcompetitivebiddingprocess.

Typically,theprocurementagentselectstwosuppli-ersforeachproduct—aprimaryandasecondarysource.Theprimarysupplierisusuallyawarded65percentoftheannualsupplyandthesecondary,35percent.Pricesofferedbythesecondarysupplieraretypicallyhigher.TheawardperiodforeachproductistypicallyoneyearandisspecifiedinaLongTermAgreement(LTA).

2.1.4 PricingAnumberoffactorscancausethecostofGDF-sourcedtreatmentstofluctuate.Priceshaveincreasedinrecentyears,inpartbecausetheyarenotguaranteedorstabilizedduringthecompetitivebiddingprocess.18Also,thecostofgoodsofsomerawmaterialsrequiredtomanufactureTBdrugshasincreased.Furthermore,astheGDFincreasesthenumberofcountriesitserves,itexhauststhesupplyfromprimarysuppliers.Itmustthenrelyonthe

15 Stop TB Partnership Global Drug Facility: www.stoptb.org/gdf/applying/application_documents.asp.16 Medicines Policy and Standards (PSM).17 The specific prequalification standards for TB drugs are determined by the Procurement, Quality and Sourcing Project: Access to Anti-

Tuberculosis Drugs of Acceptable Quality (TB Prequalification Project). This project was initiated in 2002 by the WHO Department of Medicine and Policy Standards: Quality Assurance and Safety of Medicines (PSM/QSM) to facilitate access to anti-TB drugs of acceptable quality through the assessment of products and manufacturers for adherence with WHO-recommended standards.

18 Stakeholder discussions with GDF, UNDP-IAPSO, 2006; information also available online in PDF format: www.stoptb.org/gdf/documents/GDFFactBrief_April2005.pdf

* Do not purchase TB drugs or receive grants of drugs through the GDF

1. India

2. China*

3. Indonesia

4. Nigeria

5. Bangladesh

6. Pakistan

7. Ethiopia*

8. South Africa*

9. Phillipines

10. Kenya

11. DR Congo

12. Russian Federation*

13. Vietnam*

14. Tanzania

15. Brazil*

16. Uganda

17. Thailand*

18. Mozambique

19. Zimbabwe*

20. Myanmar

21. Afganistan

22. Cambodia*

Figure 2. WHO 22 High Burden Countries Based on GDF Supply

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secondarysupplier,thusincreasingtheaveragepriceofthestandardfirst-lineregimen.

2.1.5 SuppliersInresponsetoincreasesinpricesanddecreasesinavailablesupply,theGDFissuedanewtenderforadditionalmanufacturersinMarch,2005.Theresultwasanincreaseinsuppliersfromthreecompaniestofour:Lupin,Cadila,Svizera,andStrides-Sandoz.19

2.1.6 Quality Control Beforeproductsareshippedtothepurchaser,ordersmustmeetspecificqualitycontrolstandardsdeterminedbytheGDF.Thequalitycontrolprocessincludespre-shipmentinspection(PSI)andlabora-torybatchtestingoftheproduct.Bothstepsaresub-contractedbytheprocurementagent.TheGDFappointsaqualitycontrolagentwhoisresponsibleforensuringthatanordermeetsGDFstandards.Thebatchtestisconductedbyasub-contractedqualitycontrollaboratory.

Beforeanorderisshipped,suppliersarerequiredtonotifyadesignatedagentthattheorderisready.ThesuppliermustthensubmitasampleoftheproducttotheGDFforqualitycontrol.Alocalagentissenttothesupplierfacilitytoevaluateproductpackagingandlabelingandreporttheresultstothequalitycontrolagent.Asampleofeachproductbatchisthensenttoalaboratoryfortesting.Thelaboratoryalsoreportsitsresultstothequalitycontrolagent.

OnceitisconfirmedthatanordermeetsalloftheGDF’sspecifications,thequalitycontrolagentnotifiestheprocurementagenttoreleasetheshipmenttoafreightforwarder.20

2.1.7 Transport ProcessOncethequalityoftheorderhasbeenassessed,afreightforwarderthathasbeencontractedbytheprocurementagentisnotifiedthattheorderisreadyforshipment.Thefreightforwarderpicksuptheorderfromthesupplierfacilityand,ifallproductsinthecountry’sorderarebeingsourcedfromonemanufacturer,theorderistransporteddirectlytothepurchaser.Iftheyarebeingsourcedfrommultiplemanufacturers,allproductsaretransportedtoaconsolidationpointwhereordersareassembledpriortobeingsenttothepurchaser.Oncetheorderhasbeentransported,thedistributionofdrugsbecomestheresponsibilityofthepurchaser.

Thequalitycontrolandtransportationprocessesarethesamewhentherecipientisagrantee.However,underthedirect-procurementmechanism,purchasershavetheoptionofspecifyingwheretheywouldliketheirordersshipped,andarebilledforthisservice.Conversely,whentheGDFisprocessingagrant,theorderisshippedtothecountry’sportofentryonly.Onceordershavebeenreceived,theGDFusuallyconductsafollow-upassessmentwithinfourtosixmonthstoensurethedrugsarebeingusedappropriately.

Figure 3: GDF Procurement Agent Selection Process

GDF invites expressions of interest

GDF issues an invitation for expressions of interest from potential procurement agents

Candidates submit preliminary application

Procurement agents outline the following:

• Experience in pharmaceutical procurement

• Experience in issuing international competitive bids

• Ability to maintain an Internet-based data collection and processing system

• Ability to manage buffer stock

GDF issues request for proposals/bids

Procurement agents who meet the minimum requirements are then asked to submit proposals to the GDF

Selection of Procurement Agent

GDF selects the procurement agent based on its capabilities and mark-up

19 Tender procedures and criteria can be found online in PDF format: www.stoptb.org/gdf/assets/documents/GDFFactBrief_April2005.pdf20 Stakeholder discussions with GDF, UNDP-IAPSO, 2006.

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2.2 Green Light Committee: Background and Role

Asnotedintheintroduction,casesofdrugresistantTBarebecomingincreasinglycommonacrosstheglobe.Becausethecostoftreatingthesepatientsisabarriertoreceivingcare,astrategyknownasDOTS-PluswaslaunchedbytheWHOin1998.Aspartofthisstrategy,theGLCwasformedin2000toservesasaglobalsupplierofsecond-linedrugstotreatMDR-TB.TheGLCmeetssixtimesayeartoassessapplicationsfromDOTS-Pluspilotprograms,determinesifaprogramisincompliancewiththeGuidelinesforEstablishingDOTS-PlusPilotProjectsfortheManagementofMDR-TB,andprovidesaccesstoaffordablypricedsecond-lineTBdrugstoapprovedprograms.2122

2.2.1 CustomersTheGLCacceptsapplicantsfromanyprogram,agencyororganizationthatfulfillsseveralcriteria.23Theymust:

•EnsurethattheDOTSstrategyisinplaceandisfunctioningwell

•Securegovernmentcommitmentandadequatefunding

• Developacoordinatedprojectmanagementplan• Demonstratethattheyhaveadequate

laboratoryresources• Devisearationaltreatmentstrategy•Developanadequateinformation

managementsystem•Confirmthatthedrugsrequestedareregistered

inthecountryoftheproject•Developadrugmanagementplanincluding

transportation,registration,customsprocedures,storage,distribution,monitoringandreporting

Eachapplicationmustbecompletedwiththefollowinginformation:

•Location•Sizeofpatientcohort•Anticipatedstartdateanddurationofprogram• Timescheduleforinclusionofpatientsduring

thepilotproject•Listofallorganizationsinvolved• JustificationoftheneedforaDOTS-Plus

pilotproject

Projectsmustalsofacilitateasitevisituponrequest.

Eachprogramisapprovedforasetnumberofpatients.Oncetheprogramhasmetitsquota,itmustreapplyforexpansion.Through2005,programsrepresentingapproximately9,000patientsworldwidewereapprovedbytheGLC.MorethanhalfofthosepatientswereinPerualone.24

2.2.2 Procurement Agent Selection ProcessTheprimaryprocurementagentservingtheGLCtodayistheIDAFoundation(IDA)25,whichhandlesdrugprocurement,qualitycontrol,andtransportation.IDA’sprimaryresponsibilityistoen-sureahigh-qualityandaffordablesupplyofsecond-linedrugsisavailablebynegotiatingpricesdirectlywithsuppliersfromalistofeligiblemanufacturersanddrugsthathavebeenassessedbytheWHOand/orGLC.IDAplaysakeyroleinqualitycontrolbyassessingpotentialmanufacturersandconduct-ingitsownqualitycontrolofprocureddrugs.Inaddition,IDAstandardizespacking,labelingandproductinformationspecificationsforgenericdrugs.Finally,IDAisresponsiblefortransportingdrugstopurchasers’portsofentryorairports.

2.2.3 Suppliers Becausemanysecond-linedrugsarepatent-protectedorareproducedbyalimitednumberofqualifiedsuppliers,neithertheGLCnorIDAcurrentlyusebidstoprocureitsdrugs.Instead,IDAapproachesmanufacturerswhoproducesecond-lineTBdrugsandformsagreementsdirectlywiththemforreducedpriceproducts.Duringitsinteractionswithpotentialsuppliers,IDAattemptstonegotiatethelowestpricepossibleforgenericdrugsor,inthecaseofbrandeddrugs,aconcessionalpricethatisaffordabletoitscustomers.ThemanufacturermayormaynotspecifyamaximumvolumeofreducedpricedrugsthatitwillprovidetotheGLC.

2.2.4 PricingTable1ontheoppositepagedescribesthepricesofsecond-lineTBdrugsofferedthroughtheGLCin2006,aswellasthecompaniesthatmanufacturethem.

2.2.5 Transport PathwayThefirststepofGLCprocurementisanapplicationprocessthatallpotentialpurchasersmustundergo.

21 Rajesh Gupta et al., Increasing transparency in partnerships for health – Introducing the Green Light Committee, Tropical Medicine and International Health, 2002; Stakeholder interviews, 2006.

22 As noted previously, the GLC recently converged with the GDF. Drugs procured on behalf of projects approved by the GLC will now be supplied through the the GDF procurement mechanism.

23 “Instructions for Applying to the Green Light Committee for Access to 2nd line Anti-tuberculosis Drugs”, 2002. whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.369_eng.pdf

24 Data provided by the GLC, 2006.25 GLC’s most recent tender process was held in 2006. IDA, which already was serving as procurement agent, won that bid as well and new

contract is currently being finalized.

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DOTS-PluspilotprojectsarerequiredtosubmitapplicationstotheGLC,whichreviewsthemanddecideswhethertograntaccesstoitsprice-negoti-atedsecond-lineTBdrugs.IftheGLCapprovestheapplication,anapprovalletterisissuedtotheapplicantoutliningthenumberofpatientsforwhomtheprogramhasbeenapproved.OnceGLCapprovalhasbeengranted,pilotprojectsarepermittedtoworkthroughIDA.PilotprojectsthensubmitorderstoIDA,andtheagentworkswithitsnetworkofsupplierstofillorders.Onceasupplierhasfilledanorder,drugsaresenttoanIDAwarehouse.

2.2.6 Quality Control Asnotedearlier,IDAconductsqualitycontrolassessmentstoensureproductsmeetGLCstandards.AfteranorderisplacedandbeforetheproductistransportedtoanIDAwarehouse,IDAevaluatesproductpackagingandlabelingandtestsbatchesofitsproductorders.Theproductisthenreleasedfortransport,andafreightforwardercontractedbyIDAprocessestheshipment.Ordersaresentdirectlytoacountry’sportofentry—mostcommonlyamajorairport.Oncetheorderreachesthatlocation,the

distributionofthedrugsbecomestheresponsibilityoftheprojectcoordinators.

2.3 Convergence of the Global TB Drug Facility and the Green Light Committee

In2006,theStopTBPartnershipmadeadecisiontocombinetheprocurementresponsibilitiesoftheGDFandGLC.27Underthisnewmodel,theGLCwillcontinuetoreviewapplicationsandgrantaccesstoitsnegotiatedratesforsecond-lineTBdrugs,andtheGDFwilltakeresponsibilityfortheselectionofsecond-linedrugprocurementagents.Thesameprocessesandpoliciesusedforfirst-linedrugsundertheGDFwillbefollowedfortheprocurementofsecond-linedrugs.IDAwillcontinueprocurementonbehalfofDOTS-PlusprojectsthathavealreadybeenapprovedbytheGLC,andanewprocurementagentwillpurchasedrugsonbehalfofallotherDOTS-Plusprojects.Movingforward,theGDFwillconductabid-and-tenderprocessforsecond-linedrugsthathavemultiplemanufacturers,andwillnegotiatedirectlywithmanufacturersofdrugsthatareproducedbyonlyonecompany.

Table 1. Prices of Second-Line Drugs Through the GLC26

UNITS PRICE (US$) SUPPLIER

Capreomycin, 1 gram powder for injection 1 vial $ 3.21 Eli Lilly

Cycloserine, 250 mg 100 cap $ 14.12 Eli Lilly

Cycloserine, 250 mg 100 cap bl $ 50.96 Macleods Daman Plant

Ethionamide, 250 mg 100 tab $ 10.21 Macleods Daman Plant

Amikacin 500 mg/2mL injection 100 amp $ 23.15 Gland Pharma Ltd. Pally Factory

Kanamycin, 1 gram powder for injection 50 vls $ 18.58 Panpharma

Ciprofloxacin, 250 mg 100 tab bl $ 2.12 Micro Labs Ltd. (Brown & Burke)

Ciprofloxacin, 500 mg 100 tab $ 3.81 Micro Labs Ltd. (Brown & Burke)

Ciprofloxacin, 500 mg 100 tab bl $ 3.80 Micro Labs Ltd. (Brown & Burke)

Ofloxacin, 200 mg 100 tab $ 3.49 Micro Labs Ltd. (Brown & Burke)

PAS acid sachet eq. to 4 gram aminosalicylic acid 30 sac $ 48.18 Jacobus Pharma Company Inc.

Prothionamide, 250 mg 100 tab $ 13.03 Fatol Arzneimitel

PAS sodium granules 60% (p-aminosalicylate sodium) 100 g $ 9.74 Macleods Daman Plant

Ofloxacin, 200 mg 60 tab $ 2.74 Macleods Daman Plant

26 Data provided by IDA, 2006.27 Discussions with GDF, GLC and procurement agents, 2006.

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2.4 Other Global PSAs

InadditiontotheGDFandGLC,thereareanumberofPSAsthatplayaroleinglobalTBdrugprocurement.Forexample,whileIDAprocuressecond-linedrugsfortheGLConly,italsoprocuressomefirst-line.RoyalCrownAgentsisaPSAthatprocuresTBdrugsonbehalfofthestateofAndhraPradeshinIndiaandplayssomeroleinvariousregionsaroundtheworld.TheUnitedNationsChildren’sFund(UNICEF)hasaPSAdivisionthatprocurespediatricformulationsofTBmedicines.

Additionally,regionalprocurementmechanismsexistthatservetheCaribbeanandPersianGulf.ThismethodofprocurementisdemonstratedbythePanAmericanHealthOrganization(PAHO),whichwasonceresponsibleforthebiddingprocessformanu-facturersinBrazil.Finally,whiletheydonotplayasignificantroleinthecountriesincludedinthisstudy,anumberofNGOssuchasMSFfrequentlyprocureTBdrugsfortheirownprogramsand/ortheregionsinwhichtheyoperate.

3.CountryCaseStudies

Asnotedintheintroduction,atotaloftenstrategically-selectedcountrieswereincludedintheresearchforPathway to Patients.In-depthqualitativeanalysisofnationalandglobalprocurementanddistributionsystemsineightofthesecountrieswasconductedtoprovidethebasisforunderstandingthemarketdynamics.ResearchonIndonesiaandJapanwaslimitedtodeterminingmarketvalue.ThissectionprovidesanoverviewoftheroleofnationalhealthcaresystemsincontrollingTBinthefivehighburdenandthreehighincomecountriesstudiedforin-depthqualitativeanalysis.

Table2providesthepopulation,TBburden,andTBcasenotificationstatisticsforthetencountriesstudied.

3.1 TB Control in the Context of National Healthcare Systems

Allcountriesstudiedhaveanational,publicly-financedhealthcareprogramthroughwhichaportionoforalldrugsandmedicalservicesareprovidedfreeofchargetoatleastasegmentofindividualsandoftentoallcitizens.TBcontrolisoneofseveralcomponentsofthesenationalhealthcaresystems,andpatientsmaychoosetogotoapublicfacilityfortreatment.

28 As noted, Japan and Indonesia were included in the market sizing exercise, only. In depth analysis of procurement and distribution were not performed.

Table 2. Key Statistics for Focus Countries

PROJECTED TB PREVALENCE POPULATION NEW TB CASES (TOTAL) (TOTAL) TB CASE NOTIFICATION (TOTAL)

Brazil 184 million 109,672 141,115 86,881

China 1.3 billion 1,324,633 2,892,422 790,603

France 60 million 7,411 5,901 5,004

India 1.1 billion 1,824,395 3,394,040 1,136,506

Indonesia 220 million 539,189 605,759 210,229

Japan28 128 million 37,814 50,394 29,736

Philippines 82 million 239,459 378,094 130,530

South Africa 47 million 339,078 316,260 264,183

UK 59 million 7,101 5,497 7,039

US 295 million 13,877 14,517 14,517

Note: All data are 2004 numbers, as noted in WHO surveillance report released in 2006.

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Theactualstructureofeachcountry’snationalhealthcaresystemdiffersinmanyways,includingwhichpatientshaveaccess,howpatientsenterthepublicsector,wherepatientsaretreatedandbywhom,whatdrugsandproceduresareprovidedinthepublicsector,andwhatcostspatientsincurinthepublicsystem.

Forexample,inBrazilallpatientshaveaccesstofreehealthcareacrossmultiplefacilities.Thismayincludelargepublichospitals,outpatientclinics,orevenprivatehospitalsthathavecontractswiththenationalpublichealthinsuranceprogram.Inthesefacilities,inpatientproceduresandpharmaceuticalsareprovidedforfree.Medicationforsomeoutpa-tienttreatmentiscovered,includingdrugsfortheoutpatienttreatmentofTB,HIVanddiabetes.

InSouthAfrica,clinicvisitsforthetreatmentofTBandsomeotherconditionsarefreeforallpatients,buthospitalstaysarebilledaccordingtoapatient’sincomelevel.Individualswhoareunabletopayforsuchservicesreceivecarefreeofcharge.

IntheUS,thereisnoseparateorcentralizedfundingforthetreatmentofeitherdrugsusceptibleorMDR-TB.Rather,TBtreatmentsarefundedbybothpublicandprivatepayers(e.g.Medicare,Medicaid,privatehealthinsurance.)Fortheuninsured,fundingmaybeprovidedthrougheitherthefederal,stateorlocalhealthsystemsorthroughpatientassistanceprogramssponsoredbypharmaceuticalcompanieswhomanufacturethedrugs.

Inaddition,treatmentandcarefornationalhealthpriorities(includingHIVandTB)areprovidedtopatientsthroughthepublicsectoratfederal-,state-,andcity-runhealthclinics.

3.1.1 High Burden CountriesManysimilaritiesanddifferencesexistacrossTBcontrolprogramsinHBCs,includingfunctionoftheprogram,structureoftheprogramanddivisionofresponsibilities,andsourceoffundingforTBcontrol.

AllHBCsstudiedhavenationalTBcontrolprogramswithintheirbroaderhealthcaresystems.TheseprogramsareresponsiblefordefiningTBcontrolstrategiesandpolicies.

Inhighburdencountries,TBcontrolistypicallyadministeredbyadedicateddepartmentwithintheMinistryofHealth(MOH)orequivalentagency,

althoughthestructureandreportingflowvariessignificantlybycountry.29Insomecountries,thenationalTBcontrolprogrammayreportdirectlytotheMOH,asisthecaseinBrazilandIndia.InothercountriestheTBcontrolprogramreportstoacommunicable-diseasesorinfectious-diseasesbranchofthehealthcareprogram.Forexample,inthePhilippines,TBcontrolispartofthecommunicable-diseasesdepartment,whichreportstothehealthministry.InSouthAfrica,theTBcontrolprogramfallsundertheTB,HIV/AIDSandSexuallyTransmittedInfectionsDepartment,whichisasubgroupoftheStrategicHealthPrograms,undertheMOH.InChina,thenationalTBcontrolprogramfallsdirectlyundertheChineseCenterforDiseaseControlandPreventionandreportstotheOfficeofTBAdministrationundertheMOH’sDepartmentofDiseaseControl.

3.1.2 High Income CountriesInthehighincomecountriesstudied,TBincidenceisrelativelylow.Forexample,in2004therewere6,242newcasesofTBinFrance30and6,837intheUK.31In2005intheUS,14,095casesofTBweredocumentedbytheUSCentersforDiseaseControlandPrevention(CDC).32

Inthesecountries,TBdiseasedisproportion-atelyaffectsspecificpopulations—particularlylowincomeandimmigrantcommunitiesinurbanareas.Forexample,intheUK,accordingtotheHealthProtectionAgency(HPA),in2004almost50percentoftheTBburdenwasconcentratedinLondon,andmostinfectedpatientswereimmigrantsfromSouthAsia.SimilartrendsexistinFrance,whereprevalenceishighestinPariswherethereisaconcentrationofhighriskgroups,includingimmigrantsfromendemiccountriesandpeoplelivinginpoverty.

InbothoftheEuropeancountriesstudied,TBcontrolisanintegratedfunctionofthepublichealth-caresystem.Forexample,intheUKtheNationalHealthService(NHS)providesuniversalcoveragetoallcitizens.Thereisnostand-aloneTBcontrolprogramintheUK.Instead,thecommunicable-diseasesbranchofthehealthministryisresponsibleforoverseeingthesurveillance,prevention,andcontrolofTB,aswellasotherinfectiousdiseases,includingCreutzfield-Jacobsdisease,diphtheria,hepatitis,flu,rubella,andpolio.InFrance,theDirectionsDépartementalesdesAffairesSanitairesetSociales(DDASS)—partoftheDepartmentof

29 Discussions with health ministries and national TB control programs in each country, 2006.30 Superior Council for Public Hygiene Guidelines; Bulletin Epidemiologique Hebdomadaire.31 Health Protection Agency; Office of National Statistics. www.hpa.org.uk/infections/topics_az/tb/menu.htm32 Trends in Tuberculosis – United States, 2005. MMWR. 2006;55(11):305-308. US Centers for Disease Control and Prevention (CDC)

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HealthandSocialAffairs—actsasadefactoTBcontrolprogramandisresponsibleforsurveillanceandmonitoringofTBcases.IntheUS,TBcontrolispartoftheNationalCenterforHIV,STD,andTBPrevention,whichisaunitoftheCoordinatingCentersofInfectiousDiseaseswithintheCDC.

BecauseTBisconsideredapublichealththreat,additionalmeasuresexistinallcountriestoensurethatphysicianordrugcostsarenotabarriertotreatmentandthatallpatientshaveaccesstoTBmedicines.InFranceandtheUK,allpatientsmayreceiveTBtreatmentforfreeregardlessofimmigra-tionstatus.PaymentfordrugsandtreatmentismorecomplicatedintheUS,however.WhileitistheresponsibilityofeachstatetoprovidetreatmenttoeveryTBpatientregardlessofabilitytopay,onlypatientswithoutinsurancecoverageorwhocannotaffordtopayforphysicianofficeordrugco-paymentsareeligibleforassistance.Paymentassistanceisdeterminedusingaslidingscalebasedonapatient’sincome.Hospitalstypicallyreferpatientswhocannotaffordtreatmenttostatehealthdepartmentsorassisttheminapplyingforemer-gencyMedicaidcoverage,ifpotentiallyeligible.

3.2 Overview of Key Trends Impacting TB Funding and Treatment in HBCs

SeveralemergingtrendsmayaffecthowTBtreat-mentisfunded.First,somecountrieshavesignificantprivate-sectoractivityinthetreatmentofTB.Inthesecases,governmentsaremakingaclearefforttoshifttreatmentfromtheprivatetothepublicsectorsothattheycanincreasecontrolandmonitoringofpatientsandensureappropriateandsuccessfuldiag-nosis,tracking,andadherencetoTBtreatment(see Section 3.4.4).Second,asMDR-TBbecomesmoreprevalentanddiagnosismoreaccessible,countriesarebeginningtoincludetreatmentofdrugresistanceintheirnationalTBcontrolprograms.Currently,BrazilandSouthAfricaprovidesecond-linedrugs,andChina,IndiaandthePhilippineshaverecentlypilotedorwillbegintopilotsecond-linetreatmentprogramswithinthenextyear.33

3.3 HBC National TB Control Programs

3.3.1 FunctionInallHBCsstudied,nationalTBcontrolprogramswereestablishedtoprovideacentralorganizationtohelpcontrolTBthroughthepublicsector.Althoughthereareslightdifferencesbetweeneachcountry’s

program,theoverarchinggoalistoeffectivelytreat,monitor,andultimatelyeliminateTB.Fromanorganizationalstandpoint,thesenationalTBcontrolprogramstypicallyinclude:

•National,regional,orlocalbudgetlinesallocatedtoTBcontrol

•Establishedtreatmentguidelines•Mechanismsofmonitoringandevaluation•Drugprocurementanddistributionmechanisms•Treatmentimplementation,training,and

logisticalsupport

3.3.2 Financing InBrazil,China,IndiaandthePhilippines,financingandresource-allocationdecisionsforTBcontrolaresetatthenationallevelbyoneormoreindividualdepartments,includingacentralfinancingdepart-ment,MOH,and/ornationalTBcontrolprogram.

Additionally,inmanycountries(includingChinaandthePhilippines)thenationalTBcontrolprogramissupplementedbyregional(stateorprovincial)andlocalormunicipalresources,thoughthisisgenerallynotamandatedrequirement.Forexample,inthePhilippines,localgovernmentunitsareexpectedtosupplementnationalgovern-mentfundsbyprocuringsomeTBdrugs,providingresourcesforraisingawareness,andtrainingpharmacistsandphysicians.However,aspecificfundingthresholdisnotmandatedbythenationalgovernmentasaprerequisite.Instead,itisuptothelocalgovernmenttodeterminewhatpartofthebudgettoallocatetoTBcontrolversusotherhealthcare,education,orsocialinitiatives.

AsimilarmodelexistsinBrazil.Althoughfundingforthepublicsectorisgenerallydecentralized,BrazilianstatesandmunicipalitiesarenotrequiredtoallocatespecificfundingforTBcontrol.However,theydofrequentlyprovidefundstosupplementprograms.Forexample,officialsmaychoosetoimplementDOTSinmunicipalpublichospitalsorprovidefinancialincentivestopatientswhoadheretotheDOTSprogram.

InChina,localfundingismoreregulated.Theleveloffundingprovidedbythenationalgovern-mentisdeterminedbyaprovince’swealth,andallprovincesareexpectedtocontributeadditionalfunds.Withrespecttodrugprocurementspecifically,wealthierprovincesareexpectedtoprocuredrugsontheirown.

33 Stakeholder discussions with national TB control programs.

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InSouthAfrica,thefinancingofTBcontroldiffersfromthatoftheotherHBCsincludedinthisstudy.Thenationalgovernmentallocatesan“equitableshareofresources”forprimaryhealthcaretoeachprovince,andtheprovinceisresponsiblefordetermininghowmuchofthisfundingisallocatedtoTBcontrolandhowthismoneyisused.

3.3.3 Structure IntheHBCsstudied,TBcontrolinthepublicsectoristypicallyadministeredthroughaverticallystructuredprogram,withresponsibilitiesdefinedatnational,stateorprovincial,andlocalormunicipallevels.34Figure4providesanoverviewoftherespon-sibilitiestypicallyassociatedwitheachsuchlevel.

3.4 Treatment of TB Patients

Thissectiondescribestypicalpatienttreatmentregimensinboththehighburdenandhighincomecountries.Amongtheissuesdiscussedaretheuseoffixed-dosecombinations(FDCs);theroleofpublicandprivatesectorsinserviceprovision,includingtypicalreferralpathways;andpublic-privatemix(PPM)programsinTBcontrol.

3.4.1 HBCsIneachoftheHBCsstudied,therearenationaldiagnosisandtreatmentguidelinesinplacetoinformtheclassificationandtreatmentofTBpatientsby

physiciansinthepublicsector.InIndiaandthePhil-ippines,wheremanypatientsreceivetreatmentintheprivatesector,prescribingpracticesvarywidely.35

Ingeneral,activeTBpatientsarecategorizedbasedontheirsputumtestresults,symptoms,andothercriteria,includingwhethertheirinfectionisextra-pulmonaryorpulmonaryandwhethertheyhavebeenpreviouslytreated.Thefirst-linetreatmentregimentypicallylastssixmonths,withanintensi-fiedtwo-monthphaseoftreatmentwithafour-doseregimenofrifampicin(RorRIF),isoniazid(HorINH),pyrazinamide(Z),andethambutol(E),andacontinuationphaseoftreatmentwithrifampicinandisoniazid.Insomecountriesstreptomycin(S)isalsoprescribedforre-treatmentcases.

Forexample,inIndia,first-lineTBpatientsarecategorizedasfollows:

• Category I:Newsmear-positive;seriouslyillsmear-negative;seriouslyillextra-pulmonary

• Category II:Previouslytreatedsmear-positive(relapse,failure,treatmentafterdefault)

• Category III:Newsmear-negative;andextra-pulmonary,notseriouslyill

Therearesomevariationsinnationalguidelinesandprotocolsfortreatment.OnekeyexampleisthedifferenceinregimensusedtotreatCategoryIandIIIpatients.Insomecountries,suchasIndia,

Figure 4. National TB Control Program Responsibilities

LEVEL OF NTP DESCRIPTION OF RESPONSIBILITIES

National • Defining the policy and strategy of the country’s TB control efforts • Allocating funding across TB control activities • Coordinating national level activities such as drug procurement • Overseeing regional TB control programs

Provincial/State • Implementing the TB program within a specific geographic region, which may Cinclude planning, training physicians and healthcare workers, supervising facilities, and monitoring program effectiveness • Prioritizing activities Cwithin a specific geographic region Cand allocating additional funds to carry out many of the implementation activities (e.g., training, public awareness programs, DOTS incentives programs for patients and physicians) • Tracking drug supply needs and reporting to national level • Aggregating TB/ MDR-TB patient case reporting and reporting to national level registry • Monitoring local level implementation activities within specific geographic regions

Local Office • Implementing on a local level, including public awareness, training, delivering e.g., city or drugs and equipment to facilities metropolitan area • Focusing on direct healthcare delivery, including diagnosing and treating patients

34 Stakeholder discussions with national, provincial/state and municipal/county level TB program administrators.35 NTP, pharmacist and physician discussions in India and the Philippines; discussions with PhilTIPS in the Philippines, 2006.

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ethambutolmaynotbeusedforCategoryIIIpatientsasitisforCategoryIpatients,whereasinothercountries,suchasthePhilippinesandSouthAfrica,thesameregimenisusedforCategoryIandIIIpatients.InBrazil,ethambutolisnotapartoftheregimenforanynewTBpatients,whethersmear-positiveorsmear-negative,andisonlyprescribedforpreviouslytreatedsmear-positivepatients.

Variationalsoexistsbycountryindosingandadministration.InBrazil,ChinaandIndia,nationalguidelinesfollowthethree-times-weeklyorevery-other-dayapproach.InthePhilippinesandSouthAfrica,once-dailyregimensareused.

3.4.2 High Income CountriesInhighincomecountries,bothactiveandlatentTBpatientsareroutinelytreated.InFrance,theUKandtheUS,thefour-doseregimenofisoniazid,rifampicin,pyrazinamideandethambutol(HRZE)isusedintheintensivephaseandacombinationofrifampicinandisoniazidisadministeredinthecontinuationphase.Thesedrugsareoftenadminis-teredinfixed-dosecombinations(FDCs),whicharepopularinFranceandtheUKwheretheycompriseapproximately50percentand40percent,respec-tively,ofthevolumeoffirst-linedrugsbyunit.36

InbothEuropeancountriesstudied,patientswithlatentTBaremostcommonlytreatedwitharegimenofrifampicinandisoniazidforthreemonths37orsixmonthswithisoniazidalone.38IntheUS,thesepatientsaretreateddailywithisoniazidforninemonths.39

3.4.3 Use of Fixed-Dose Combinations in Treatment RegimensViewsandpracticesregardingtheuseofFDCsintreatmentdifferwidelybycountry.ThegovernmentsofBrazil,thePhilippines,andSouthAfricaactivelyprocureFDCsandincludethemasakeycomponentoftheirpublic-sectorTBprograms.PerceptionsaroundtheadvantagesofusingFDCsincludeeaseofadministration,easeofstockmanagement,andanincreaseinadherence.40Conversely,neitherChinanorIndiausesFDCsinthepublicsector—althoughtheyareadministeredintheIndianprivatesector.Similarly,FDCsarenotcommonlyusedintheUS,largelybecausephysiciansvaluetheirabilitytotitrateeachseparateagent.

3.4.4 Service Provision Allcountriesstudiedhaveapublicsectorinwhichpatientscanreceivediagnosticandtreatmentservices.InBrazilandSouthAfrica,mostTBtreatmentisprovidedbythegovernment.Insomecountries,TBcarecanbeobtainedthroughtheprivatesectorandPPMfacilities.

InBrazilandSouthAfrica,mostTBtreatmentisprovidedbythegovernment.Incontrast,inIndiaandthePhilippines,despitesignificantpublicsectorprograms,manypatientsprefertoseekdiagnosisandtreatmentintheprivatesectorforreasonsthatincludeperceivedqualityofcareandmaintenanceofanonymity.

PrivatesectorpracticesinTBposeanumberofchallengestothepublicsectorprogram.Forexample,patientsenteringtheprivatesectormaynotbereportedintotheNationalTBprogrammakingitdifficulttoestimatetheTBburdenandtracksuccessindiagnosingandtreatingpatients.Also,physicianregimensdifferfromnationalguidelinesandinmanyinstanceslesseffortisplacedontreatmentadherence.Toaddressqualityofcareintheprivatesector,IndiaandthePhilippineshavepilotedPPMprogramsinanefforttoreachmorepeoplewithappropriatetreatmentandhelpprovideanincentivetotheprivatesectortoadheretothenationallyapprovedregimen.Underthismodel,physicianswhosuspectapatientofhavingTBorinitiallydiagnoseapatientwithTBcanreferthepatienttothepublicsectorforfurtherdiagnosisandfreetreatment,ormaycontinuetotreatthepatienthimorherself,withdrugsprovidedatnocostorsubsidizedbythegovernment.(The PPM model is described in greater detail in Section3.6.1).

3.5 Public Sector: Referral Pathway and Settings of Care

Thissectiondetailsthegeneralreferralpathwayofapatientinthepublicsectoranddescribesspecificsettingsofcareforthehighburdenandhighincomecountriesstudied.Overall,therearethreemajorsectorsinwhichTBcareisadministered:thepublicsector,theprivate(forprofit)sector,andthroughNGOs.Inthecountriesstudied,NGOswerenotasignificantserviceproviderandthereforearenotcoveredindepthinthisreport.

36 IMS MIDAS data for 2005.37 France guidelines from Superior Council for Public Hygiene Guidelines; U.K. guidelines from National Institute for Health and Clinical

Excellence, British Thoracic Society.38 U.K. only guidelines from National Institute for Health and Clinical Excellence, British Thoracic Society.39 CDC Targeted TB Testing and Treatment of Latent TB Infection. Available online in PDF format at www.cdc.gov/mmwr/PDF/rr/rr4906.pdf40 Discussions with NTP and physicians in Brazil, the Philippines and South Africa, 2006.

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3.5.1 HBCsGenerally,patientsenterthepublicsysteminoneoftwoways:ByvisitingapublichealthcareworkerandbeingreferredtoaTBspecialistorfacility,orbyvisitingaprivatephysicianandbeingreferredtothepublichealthcaresystem.

InmanyHBCs,patientssuspectedofhavingTBarereferredtoapublicoutpatientsettingfordiagnosisandtreatment.PatientswithTBaresubsequentlymanagedintheoutpatientsettingforthedurationoftreatment.IntherarecasethatapatienthasMDR-TB,HIVoranotherseriousconcomitantdisease,theymaybereferredtoaspecialcenteroradmittedtoahospital.FollowingaredescriptionsofpublicsectorreferralpathwaysandcaresettingsineachofthefiveHBCsstudied,followedbythethreehighincomecountriesstudied:

Brazil

InBrazil,patientswilltypicallypresentinapublichospitalambulatorysettingintheircommunity,andwillbereferredtothepulmonologydepartmentatthathospitalforsputumtesting.Oncediagnosed,patientswillbemanagedinthehospitaloutpatientdepartment.IfthefacilityhasbeendesignatedasaDOTShospitalbythemunicipal-orstate-levelauthorities,thepatientwillbeaskedtoreturndailyfortreatment.IfthefacilityisnotDOTS-designated,thepatienttypicallycomesinonaregularbasiseitheronceaweekoronceamonthforthenextsup-plyofpills.Patientswhoprefertoreceivetreatmentatafamilyhealthprogramintheircommunityorbyavisitinghealthcareworkermaychoosetodosoifsuchservicesareavailableintheirmunicipality.

China

InChina,patientstypicallypresentatacountyortownshiphospitalortoavillagehealthcareworker.PatientssuspectedofhavingTBarereferredtoaTBtreatmentdispensary—alocalChineseCDCunitorTBpreventioninstitute,forfreediagnosis,treatmentandmonitoring.Atthecountyortownshiphospitallevel,healthcareworkersmayconductX-raysandCTscans.Somefacilitiesmayhavecapabilitiestoconductsputummicroscopytestingaswell.Insuchcases,patientsarerequiredtopayaconsultationfeeinadditiontofeesforconductingX-rayandsputumtesting.OnceapatienthasbeendiagnosedwithTB,thefacilitywillrecordthepatientintoanInternet-basedreportingsystemandreferthepatienttothedispensary,wherethepatientisreportedagain.This

mayresultinduplicativecounting.Patientstypi-callyreturntotheCDCunitonceaweekoreverytwoweeksfortreatmentandmonitoring.InsomeruralareaspatientslivefarfromtheTBdispensary,avillageclinicphysicianwillreceivethemedicinesfromtheTBdispensaryandadministerdirectlytothepatientonceeveryonetotwoweeks.Theyareusuallypaidamonitoringfeetoperformthisservice.

india

InIndia,patientscanpresenttoanypublichealthfacility.IfapatientissuspectedofhavingTB,heorsheisreferredtooneofthemanydesignatedmicroscopycenterslocatedthroughoutthecountry.Oncediagnosed,anIDcardisfilledoutforthepatient,aTBhealthcareworkerconductsaninitialvisitwiththepatienttoinformhimorherofthetreatmentregimen,andthepatientisreferredbacktohisorheroriginalsiteofpresentationtobegintreatment.Ifthepatientlivesfarfromthistreatmentsite,theTBhealthcareworkerattemptstolocateaDOTSsitethatisclosertothepatient’sresidence.AvariationinthisreferralpathwayisthroughthePPMmodel,whichisviewedbygovernmentofficialsasanimportantwaytoleverageprivate-sectorcapacity.Throughthismodel,patientspresenttoprivateclinicsand/orhospitalsand,ifsuspectedofhavingTB,arereferredtopublic-sectormicroscopycenters.Afterdiagnosis,patientsmayopteithertoreceiveprivatelyfundedtreatment,astheywouldfromanyotherprivate-sectorphysician,orreceivefreedrugtreatmentthroughtheRevisedNationalTBControlProgram(RNTCP)underthesupervisionoftheirprivate-sectorphysician.Thisprogramhasbeenincreasingrapidlyinscope,althoughitstillinvolvesasmallfractionofprivate-sectorpractitioners.

PhiliPPines

InthePhilippines,patientsmayinitiallypresentatapublicorprivatehospitalorclinic.PatientsareusuallydiagnosedfirstbyX-rayandthenfollowingasputumtest,dependingonthefacility’scapabilitiesandresources.Inthepublicsetting,patientswhoarediagnosedsmear-positivearemanagedataDOTSclinicthatmaybelocatedatalargepublichospital,abarangay(ruralhealthunit),orevenaPPMclinicataprivatehospital.Thosepatientspreferringtobetreatedintheprivatesectoratnon-PPMsitesmaydoso,thoughtheyincurthecostofdrugsaswellasphysicianvisits.

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south afriCa

AlthoughsomevariationexistswithinSouthAfrica,generalTBcontrolisamandateofthepublicsector,andprivate-sectorphysiciansarerequiredtoinformpatientsthattheycanreceivefreecareinpublicfacilities.Patientsmaythenchoosetoreceivecareintheprivatesectorattheirowncostorpresenttothepublicsector.Patientsinthepublicsectormostfrequentlypresenttoprimaryhealthcareclinics.IfsuspectedofhavingTB,patientsaregivenasputumsmeartestandtheresultsaresenttoamicroscopylabforconfirmation.IfdrugresistantTBisnotsuspectedandsymptomsarenottoosevere,thepatientbeginsDOTStreatmentattheclinic,inthecommunityunderthesupervisionofavolunteerDOTSsupporter,orinsomecases,athisorherworkplace.Inexceptionalcircumstances,suchasifthepatientismigrantormusttravelextremelylongdistancestohealthcarefacilities,heorshemaybeallowedtoself-administertreatment.

PatientswithseveresymptomsorthosewhoaresuspectedofhavingMDR-TBarereferredtospecialistcentersormajorhospitals,wheretheyundergoadrugsusceptibilitytest(DST)andaretreatedasaninpatientuntiltheyarenolongercontagious.Whereservicesareavailable,patientswhoareco-infectedwithHIVandTBarereferredtoaspecialHIVtreatmentsite,wheretheyreceivecarefromaspeciallytrainedhealthcareworker.

3.5.2 High Income Countries

franCe

InFrance,patientspresentmostcommonlyintheemergencyroomandalsotoageneralpractitioner.Inbothcases,theyarereferredtoahospitalforachestX-ray.IfapatientissuspectedofhavingTBaftertheX-ray,heorsheisreferredtoaspecialistforsputumtestingandsubsequenttreatment.

uK

PatientsintheUKpresenttoageneralpractitionerortheemergencyroomandarereferredtothehospitaloutpatientsettingfordiagnosisbyachestX-ray.PatientswhoaresuspectedofhavingTBaftertheinitialX-rayarereferredtoahospitalspecialistineitherthepublicorprivatesetting,dependingontheirpreference.Thatspecialistconfirmsdiagnosisthroughtheresultofasputumtestandsubsequentlymanagestreatment.ThegovernmentalsohasamandatoryscreeningpolicyforimmigrantsfromcountriesinwhichTBisendemicandwhoplanto

stayinthecountryformorethansixmonths.TheseindividualsmusthaveachestX-raywhentheyenterthecountry.

us

Similarly,patientsintheUStypicallypresentintheemergencyroomortotheirgeneralpractitionerandarereferredtoaspecialistforsputumanddrug-sensitivitytesting.ImmigrantsenteringthecountryarerequiredtoreceiveTBtestingpriortoobtainingavisaandanysuspectedcasesareimmediatelyreferredtothelocalhealthdepartmentuponentry.ThosewithlatentTBarerequiredtoundergoninemonthsofprophylactictherapywithisoniazid.

3.5.3 Payment for Drugs and Services InallHBCsstudied,TBdrugtreatmentinthepublicsectorisfreeofcharge.However,asprevi-ouslynoted,somepatientsmayincurfeesbeforebeingreferredtospecificfacilitiesfordiagnosisandtreatment.Forexample,inChina,patientsseekingdiagnosisinacountyhospitalorspecializedhospitalmaypayconsultationanddiagnosticfeesfortheadministrationofX-raysandsputumtests.OncetheyarereferredtoaTBdispensarydesignatedbytheChineseCDC,diagnosticproceduresandtreatmentarefree.InSouthAfrica,patientsreceiv-inginpatienttreatmentforTBwiththefinancialresourcestopayfortreatmentareaskedtopayaportionofthecosts,basedontheirincomelevel.

IntheUK,patientsinapublichospitalwillnotpayanythingiftreatmentisadministeredinaninpatientsetting.Inthehospitaloutpatientsettingorinaretailpharmacy,patientspaythestandardprescriptioncharge—£6.65(US$13)atthewritingofthisreport.InFrance,TBisclassifiedasanaffection de longue durée (ALD)andisthereforeexemptfromallconsultationfees,hospitalchargesanddrugco-payments,irrespectiveofsector.Alltreatmentanddrugsarealways100percentcoveredbysocialsecurityandarefreeofcharge.IntheUS,patientswhodonothaveinsuranceorcannotaffordco-paymentsarereferredtoapublicclinicandreceivetreatmentfreeofcharge.

3.6 Private Sector: Referral Pathway and Settings of Care

Basedonsalesfiguresandinformationfromprimaryandsecondarysources,asignificantportionofthepopulationinIndiaandthePhilippinesusesprivatehealthcarefacilitiesandsystemsforTBtreatment.

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Inothercountries,private-sectorhealthcaremaybesignificant,butnotforthetreatmentofTB.41InthecaseofTB,patientsmaypresenttoanynumberoffacilitiesandmostlikelywillbediagnosedandtreatedonanoutpatientbasis.Asoutpatients,theywillreceiveprescriptionsfordrugtreatmentwhichtheymustself-administer.RegulationinHBCpri-vatesectorsislimited,andtreatmentpracticesvaryconsiderablyfromphysiciantophysician.Itisnotuncommonforpatientstoself-medicate,especiallyinareaswhereTBinfectioncarriesasocialstigma.

Thereasonsthatpatientsmaychoosetopayfortreatmentwhenfreetreatmentisavailablevarycon-siderably.Twoofthemostcommonlycitedreasonsarethatsomepatientsperceiveprivatetreatmentasbeingfasterandbetterandthatprivatetreatmentismorediscrete.

3.6.1 Role of Public-Private Mix Programs in TB TreatmentInIndiaandthePhilippinessignificantprivatemarketsforTBtreatmentexist.TheWHOpilotedthePPMmodelto:

• Increaseadherencebyensuringthatcostisnotanissueandbyrequiringthattreatmentisobserved

• Facilitatetheflowofpatientsbetweenthetwosectorsinorderto1)ensurethatpatientsdiagnosedwithTBarereportedintothenationalregistriesfortrackingandmonitoringpurposes;and2)facilitateproperdiagnosisandtreatmentbasedonthetreatmentguidelinesetinthatcountry,includingimplementationofdirectlyobservationaltherapy

APPMprogramwaslaunchedinIndiain1995inanefforttoextendthecapacityoftheRevisedNationalTBControlProgram(RNTCP)aswellasitsscopeofinfluenceintheprivatesector.Itwasinitiallypilotedin14citiesandwillsoonberolledoutnationwide.Throughtheprogram,patientsmayinitiallyconsultwithaprivateproviderandstillbeeligibleforfree,directly-observedtreatment.PatientswhoinitiallyvisitaprivatepractitionerhavetheoptionofbeingdiagnosedbytheirprivatephysicianorimmediatelybeingreferredtotheRNTCPfordiagnosis.Ifdiagnosedintheprivatesector,patientsmayremaininprivatecareormovetothepublicsector.ThoseunabletoaffordprivatetreatmentaregivenareferralformandsenttotheRNTCPfortreatment.Thosewhoprefertobetreatedintheprivatesectormaydo

so,howeverphysicianscanchoosewhetherornottowaivetheconsultationfee.

APPMprogramwaslaunchedinthePhilippinesin1993toaddressavarietyofchallengesthatexistedintheprivatesector.Private-sectorphysicianshadalackofknowledgeregardingTBcontrolchallengesanddevelopmentofdrug-resistance.Physiciansfrequentlyusedmanydifferenttreatments,oftennotfollowingtheregimensrecommendedbythenationalTBcontrolprogram.Furthermore,physiciansdidnotfollowupwithpatientsonaregularbasistoensureadherence.UnderthecurrentPPMmodel,aPPMfacilitycontractswithprivatephysiciansinthearea.PrivatephysiciansaffiliatedwiththePPMareaskedtoreferTBpatientstoapublichealthcenterunitwhentheyaresuspectedofhaving—orarediagnosedwith—TB.IfthediagnosisforTBisconfirmed,thepatientremainsinthepublicsectorfortreatmentbutmaychoosetoalsoreturntotheprivatesectorforperiodicfollow-upvisitsduringtreatment.

3.6.2 Payment for Drugs and Services in the Private SectorAsnotedpreviously,asizeableprivatemarketforfirst-lineTBmedicinesexistsinIndia,thePhilip-pinesandtheUS.Intheprivatesector,patientsareresponsibleforpayingforconsultationanddiagnos-ticfeesatthephysician’sofficeorhospitalandareresponsibleforthecostofdrugsatthepharmacy.Asanexceptiontothis,patientswhoarecoveredbyprivateorpublichealthinsurancemaynotincurallfeesassociatedwithTBtreatment.ForexampleintheUS,manypatientshaveprivateinsuranceandthuspayanofficeco-paymentandadrugco-pay-mentratherthanthefullcostofservicesanddrugs.However,thecostvariesbecausethereisamixofpublicandprivateinsurancecoverage.

3.7 MDR-TB Control

BrazilandSouthAfricacurrentlyhavenationalpublic-sectorprogramsfortreatmentofMDR-TBandutilizedomesticfundingandin-countryprocurementmechanisms.ChinaandIndiaplantoimplementand/orexpandDOTS-Pluspilotprojectsasearlyas2007.Meanwhile,patientswhoneedtoreceivetreatmentforMDR-TBmustdosointheprivatesectorattheirownexpense.ThePhilippinesreceivesfundingfortreatmentofMDR-TBthroughGFATMgrantsanddrugsthroughtheGLC.In

41 In China, village doctors may provide TB care but they receive a payment from the government to do so and drugs are free to patients.

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2005,treatmentwasprovidedfor250patientsandthecountryisnowintheprocessofexpandingtreatmentforupto2,500MDR-TBpatients(seesection4.1.1).42

MDR-TBpatientstypicallystarttoflowintonationalTBcontrolprogramsmuchastheywouldforregularTB.However,oncetheyarediagnosedwithMDR-TB,theyarereferredtoaspecializedsitethatmayormaynotfunctionexclusivelyforthetreatmentofTB.InSouthAfrica,patientsareusuallysenttoaspecialistatadistrictorregionalfacility,andinthePhilippines,patientsaresenttoeitherMakatiMedicalCenterinManilaoranothertertiarycarecenterfortreatment.Brazil’sMDR-TBpatientsaresenttospecializedTBreferencecenters.

ThetreatmentofMDR-TBisaregularfeatureofTBcontrolinhighincomecountries,and—likethe

treatmentofdrug-susceptibleTB—isfullyinte-gratedintothegeneralhealthcaresystem.InFranceandtheUK,thetreatmentofsuchpatientsisprimar-ily,ifnotexclusively,publicallyfunded.IntheUSthefundingofMDR-TBtreatmentdependsonthepatient’sinsurancecoverageandwhetherheorsheiseligibletoreceiveassistancefromthegovernment.Inthethreehighincomecountriesstudied,theprimarydifferencebetweenthetreatmentofdrug-susceptibleandMDR-TBpatientsisinthesettingofcare.InFranceandtheUK,patientsgenerallyreceivetreat-mentonaninpatientbasisatahospitaluntiltheyarenolongerconsideredcontagiousandarehealthyenoughtofinishtreatmentontheirown.IntheUS,patientsmayalsobetreatedonaninpatientbasisatanyhospital,ortheymayalsobereferredtooneoftheTB“CentersofExcellence”fundedbytheCDC.

4.ProcurementandDistributionofTBDrugsinHighBurdenCountries

Thissectionfocusesonthefinancingoffirst-andsecond-linedrugsaswellasthepublictenderingprocess,akeyprocurementmechanismintheHBCsstudied.DiscussionofthepublicsectorincludesthedemandforecastingprocessanddistributionpathwaysofTBdrugs.Finally,thissectionprovidesanoverviewofprocurementintheprivatesectorsofIndiaandthePhilappines,thetwoHBCsevaluatedinPathway to PatientsinwhichtheprivatesectorplaysalargeroleinTBcontrol.

4.1 Financing for First-line TB Drugs

InallHBCsstudied,thepurchaseofTBdrugsisatleastpartiallyfundedbythenationalgovern-ment(seeFigure5).InBrazil,allfundingfordrugpurchasescomesfromthenationaltreasury.InIndia,

donorfundsfromGFATM,theUKDepartmentforInternationalDevelopment(DFID),theUSAgencyforInternationalDevelopment(USAID),andotheragenciesarepaidtothecentralTBdivisionandcombinedwithdomesticfunding,aswellasWorldBankloans,topayforTBdrugs.

InChina,themajorityoffundingcomesfromthenationalgovernment.However,thegovernmentsofwealthierprovinces—mostlylocatedonthecoast—arealsoresponsibleforprovidingfundingfordrugssuppliedintheirlocalities.

InthePhilippines,nationalandregionallevelsofgovernmentsharethecostofdrugpurchases.ThenationalgovernmenthascommittedtopurchasingCategoryIandIIpatientkitsfortheentireTB

Figure 5. Level of Centralization of Drug Funding in the Public Sector, HBCs

Centralized

42 Discussions with national TB control officials in each country.

DecentralizedMix of Centralized and

Decentralizaed

India, Brazil China Philippines South Africa

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controlprogramandlocalgovernmentsgenerallyfunddrugpurchasesforCategoryIIIpatients.

InSouthAfrica,provincialgovernmentsholdprimaryhealthcarebudgets,aportionofwhichareallocatedtodrugpurchasesforthepublicsector.Althoughdrugsaretenderedatthenationallevel,theactualamountthatissetasideforTBdrugpurchaseisdeterminedattheprovinciallevel.

4.1.1 Financing for Second-line TB DrugsSystemsthatsupportsecond-lineTBdrugfinancingareintheirinfancyinmanycountries.However,astheincidenceofMDR-andXDR-TBbecomesagrowingconcern,anefforthasemergedtoincludesecond-linecoverageaspartofnationalTBcontrolprograms.Atthewritingofthisreport,onlyBrazilandSouthAfricahadestablishedfundingforsecond-linemedicinesundertheirnationalTBcontrolprograms.Theremainingcountriesstudiedhaveonlyrecentlybegunpilotprogramsorhaveplanstoinitiatethemoverthenextyear.

InIndia,theRNTCPhasbegunapilotprogramtoincludesecond-linedrugs.Theprogram,whichfundedtreatmentfor100patientsfor2006,43isexpectedtogrowrapidly—althoughfundingsourcesareintheprocessofbeingconfirmed.

ThePhilippineshasreceivedGFATMfundingforitspilotMDR-TBprogram.In2005,theGFATMRound2grantprovidedfundstotreat250patientsthroughtheGLC.Another2,500patientsareexpectedtobetreatedbetween2007and2011withfundsprovidedintheGFATMRound5grant.

FundsfromaGFATMRound5grantwillallowChinatolaunchtwopilotprogramstotreatap-proximately4,000patients,withplanstoexpandthenumberofprojectstoinclude115countiesinsixprovincesby2011.

4.2 Public Drug Procurement

4.2.1 Public Tender ProcessTable3illustratesthemodesofprocurementinthepublicsectorforeachHBCincludedinthestudy.

MostofthepublicmarketsintheHBCsstudiedprocuredrugsthroughabidandtenderprocess.Forsecond-lineproducts,theremayalsobeadirectnegotiationbetweenthegovernmentsandsuppliers.ThenationalTBcontrolprogram(orarelatedagencywithinthegovernment)determinestheapproximatevolumeofdrugsthatareneededbythepublicsectorfortheperiodofthetendercontract,requestsbidsfromdrugmanufacturersandselectssupplierswhoagreetoprovidedrugsforapresetperiodoftime,atapricedeterminedinthebiddingprocess.WiththeexceptionofSouthAfrica,44allten-dercontractsintheHBCsstudiedarebidannually.

Althoughtendersareopentobothnationalandinternationalsuppliers,nearlyallofthecountriesincludedinthestudyprefertosourcetheirdrugsfromlocally-basedcompanieswhenpossible.Onlytwoofthecountriesstudied,IndiaandthePhilip-pines,usetheGDF.InIndia,theGDFsuppliesapproximatelyhalfofthedrugsusedbythepublicsectorandinthePhilippines,theGDFsuppliesalltreatmentsforsmearpositiveandre-treatmentcases.

Moreover,withtheexceptionofChina,tendersinthefiveHBCsstudiedareadministeredatanationallevel,evenifthefinancingfordrugscomesfromprovincialbudgets.InChinathetenderingsystemissplitbetweenthenationalandtheprovinciallevels,dependingontheoriginoffunds.IftheChinesegovernmentorexternalfundersareprovidingtheresources,thetenderisadministeredbythenationalgovernment.Whenprovincesareprovidingthefunding,tendersareissuedbytheprovincialhealthministry.

Inmostcases,beforeadrugmanufacturercanparticipateinabidandtenderprocess,itmustbepre-qualifiedormeetanumberofcriteriasetbythetenderadministrator.Onecommonlyusedcriterioniswhetheramanufacturerislocaltothecountryissuingthetender.Mostofthecountriesstudiedpreferredtosourcetheirdrugsfromlocalcompanieswhenpossible.ProcuringdrugsdirectlyfromlocalsuppliersoftenoffersnationalTBcontrolprogramsandgovernmentsthebenefitoflowerprices,asisthecaseinChinaandIndia.

Table 3. Procurement Mechanisms in HBCs

PUBLIC COUNTRy TENDER45 GDF GLC

Brazil46 l

China l

India l l

Philippines l l l

South Africa l

43 The program is administered in the states of Gujarat and Maharashtra with the first cohort scheduled to begin in early 2007. The LRS Institute in Delhi also has had a small self-funded program with approximately 150 patients.

44 South Africa bids on a bi-annual basis. 45 For some second-line drugs, procurement is done through direct negotiation with suppliers rather than through a tender process.46 In 2005 due to internal manufacturing problems, Brazilian national suppliers were unable to meet the total demand for first-line TB drugs,

and were assisted by PAHO. Generally, Brazil produces 100 percent of its national drug supply.

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However,procuringdrugslocallydoesnotalwaysresultincost-savings.ThepubliclysanctionedTBtreatmentregimensinothercountriesstudied,notablyBrazil,thePhilippinesandSouthAfrica,actuallycostmorethansimilarregimensofferedontheglobalmarketorthroughtheGDF.Thecitedrationaleforprocuringdrugsatthesehigherpriceswasadesiretosupportlocalindustryaswellasensurethequalityandsafetyofproducts.SomeoftheHBCsstudiedhaveturnedtointernationalcompetitivebidsortheGDFfortheirdrugprocurementneedswhenqualityorsufficientvolumescouldnotbeassuredbylocalsuppliers,orbecauseofdonorpreference.

Whilesomeelementsofthepre-qualificationofsuppliersweresimilaramongtheHBCsstudied,othercriteriausedinmanufacturerpre-qualificationvariedwidely.Forexample,inIndia,potentialsuppliersmusthaveWHO-GMPcertification,meetaminimumthresholdofannualrevenues,anddemonstratepriorexperienceinmanufacturinglargequantitiesofTBdrugs.47InChina,manufactur-ersmustbecertifiedbytheStateFoodandDrugAdministrationbeforetheycansubmitbidsinthepublictender.InBrazil,theinvitationforbidsinthepublictenderisissuedonlytostateandmilitarylaboratories.

4.2.2 Demand ForecastingEnsuringacontinuoussupplyofdrugsforpatientsisanimportantaspectofTBcontrol.EachoftheHBCsstudiedhasdevelopeddifferentstrategiestoensurethatsufficientsupplieswillbeonhandforpatientsevenintheeventofmanufacturingdelaysoremergencies.ThesestrategiestypicallyrequireanassessmentoftherateofTBdrugutilization,antici-pationofneedsfortheupcomingtenderperiod,andthemaintenanceofa“bufferstock”ateachlevelofthesupplychain.Thisdemandforecastingisusuallyconductedatthelevelatwhichthetenderisbeingadministered.

DemandforecastingisusuallyperformedbyapersonordivisionwithinthenationalTBcontrolprogram,asisthecaseinBrazil.48Everyyear,theBrazilianMinistryofHealthforecaststheneedsoftheprogramforthefollowingyearusingfiguresfromstatereportsthatarebasedonprojectionsbyeachmunicipality.Theministrythenaugmentsthesefigureswithabufferstockof25percent.Similarly,inChina,forecastingisconductedbytheStatistics

andSurveillanceOfficewithintheNationalCenterforTBControlandPrevention.TheTBpreventioninstitutesatthecounty,prefectureandprovinciallev-elsreportthesupplyanddistributionofdrugs—aswellasthenumberofnewpatientsdetected—tothenationalgovernment,whichusesthosefigurestoforecastthedemandfortheentireprogramandallocationsofdrugsforeachprovince.InIndia,forecastingisconductedbytheCentralTBDivisionandtheMinistryofHealthandFamilyWelfarewiththeassistanceofaprivateagencycalledStrategicAlliance.AlllevelsoftheTBcontrolprogramarerequiredtosubmitstandardizedreportsthatindicatepatientnumbers,inventorylevels,anddrug-utiliza-tionrates.Thesereportsfeedintotheforecastingprocess,whichdeterminesthedrugsupplyneedsoftheprogramatnational,regional,andlocallevels.

InSouthAfrica,bycontrast,forecastingisnotperformedbyapersonoragencydedicatedsolelytoTBcontrol.49BecauseTBcontrolinSouthAfricaisintegratedintothegeneralprimarycaresystem,adivisionwithintheMinistryofHealthcalledPhar-maceuticalPlanningandPolicyforecastsdemandfornearlyalldrugsusedinthepublichealthcaresystem.Thisdivisionalsonegotiatessuppliesofcertainsecond-lineTBdrugswhosevolumesdonotwarrantapublictender.Usinghistoricalutilizationreportsfromprovincialgovernmentdepots,thisagencydeterminestheannualneedfortheentirehealthcaresystemandinsertsthesefiguresintothepublictender.However,theactualorderingofthedrugsduringthetendercontractperiodisperformedbytheprovincialdepotsthatserveasthefirstpointofdelivery.Oncethepriceissetbythenationaltender,theresponsibilityforprocurementfallsattheprovincialdepotlevel,whichisresponsibleforcontactingmanufacturerstoplaceordersandprovidingpayment.

InthePhilippines,trackingpatientsandforecastingsupplyaredonethroughabottom-upapproach.Localhealthsitesreporttoruralhealthunits,whichreporttotheprovincialandregionallevels.Dataarecollectedatthenationallevel,analyzedattheDOH,andusedforfundingallocation,futureplanningandpolicydevelopment.

4.2.3 Distribution PathwaysPublicdistributionsystemsfordrugswithinthecountriesstudiedarequitediverse.However,qualityassurancewasidentifiedasachallengefacedbyall

47 As noted in Section 2.1.3 GMP refers to Good Manufacturing Practices. Additional information available on the WHO website at www.who.int/medi-cines/areas/quality_safety/quality_assurance/gmp/en/index.html.

48 Stakeholder discussions with Brazil MOH and NTP, 2006.49 Stakeholder discussions with South Africa MOH and NTP, 2006.

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programs.Accordingly,eachcountryhasaseriesofcheckpointstotestthequalityofdrugordersbeforetheyarereleasedtootherpartsofthesupplychain.

Inthecountriesstudied,qualitytestingisusuallyfirstconductedattheproductionsite.Onceanorderhasbeenmanufacturedandisreadyfordeliv-ery,theagencythathasplacedtheorderisnotified.Asampleofthebatchissenttoalaboratory—eitheragovernmentlaboratoryoraprivatelaboratorythathasbeencontractedbythegovernment—andistestedbeforetheorderisshipped.Iftheresultsofthebatchtestindicatethattheorderisnotofsufficientquality,follow-uptestsareconductedtoconfirmtheresultsoftheinitialtest.Duringthistime,theorderisheldatthemanufacturingsite.Ifnegativeresultsareconfirmed,anorderisfrozenandmanufacturersarerequiredtoreplacetheproduct.Iftheresultsofasecondarybatchtestaresatisfactory,theorderisreleasedfordistributionanddeliveredtoaninitialpointofdelivery—usuallyagovernmentdepot—wherethefinalpackagingofdrugsisconductedifnecessary.Anadditionalbatchtestmaybeconductedatthislevelbeforetheorderisshipped,eithertootherdepotsorthevarioushealthcarefacilitieswhereproductsaredistributed.

TBdrugspurchasedbythepublicsectortendtoflowthroughaseriesofpublicdepotsorwarehousesbeforereachingthefacilitiesthatadministerthemtopatients.Thefrequencywithwhichdrugordersaresubmittedandshippedvariesbycountry.Thecountriesstudiedfollowoneoftwomodelsofdistri-bution:thepushsystemorthepullsystem.Figure6representshowdrugsareorderedanddistributedinthepublicsectorthoughthepushandpullsystems.

Underthepushsystem,drugsareorderedbyonecentralagencyordivisionandthen“pushed”ordeliveredatregularintervalstootherpartsofthesupplychain.ThispushsystemisfoundinmostprovincesinChina.TBmedicinesflowtofacilitiesatpre-specifiedsupplylevelsandarriveatfacilitiesatregularintervals,typicallyfourtimesayear.

InthePhilippines,drugstotreatCategoryIandIIpatientsflowthroughapushsystemandaredeliveredtwiceayeartoaportofentry,withsuppliessenttoregionalwarehousesoneitheramonthlyorquarterlybasis.Second-linedrugsarealsoorderedonanintermittentbasisbytheTropicalDiseaseFoundationfordistributioninitsfacility.

Underthepullsystem,theflowofdrugsisdrivenprimarilybyordersfromdepotsand/orfacilitiesfurtheralongthesupplychain.CountriesoperatingonsuchamodelincludeBrazil,thePhilippines(forCategoryIIIdrugs)andSouthAfrica.Throughthissystem,bulksuppliesofdrugsareorderedbyandheldinregionaldepotsuntiltheyarerequestedbyfacilities.Ordersmayvarywidelyinsizeandfrequency,dependingontheneedsofthefacilityordepot.

Indiahasahybridsystemthroughwhichthecentralunitprocuresdrugsanddeterminesannualrequire-mentsforthecountryasawhole.Theamountsuppliedtostatesanddistrictsisdeterminedbasedonmonitoringofdrugstocks.

4.3 Private Drug Procurement: First- and Second-line Drugs

InBrazil,ChinaandSouthAfrica,thedistributionofTBdrugsinprivatefacilitiesorpharmaciesiseitherdiscouragedorprohibitedforqualitycontrolreasons.

InIndiaandthePhilippinestreatmentintheprivatesectorisutilizedbyabroadersegmentofthepopulation.Inthesecountries,theprivatesectorplaysasignificantroleintheprocurementanddistributionofTBdrugs.

Figure 6. Flow of Drugs Through the Public Pull vs. Push Systems in High Burden Countries

Push-Through Public Sector Channels

SuPPLIERS

HEALTHCARE FACILITIES

PATIENT

GOVERNMENT DEPOTS

Pull-Through Public Sector Channels

SuPPLIERS

HEALTHCARE FACILITIES

PATIENT

GOVERNMENT DEPOTS

Flow of Drugs:

Flow of ordering Flow of drugs

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Theflowofdrugsintheprivatesectorisquitedifferentfromthatofthepublicsector.InIndia,forexample,treatmentintheprivatesectorisnotfreeofcharge,thoughpricesarerelativelylowandoftencontrolled.Patientsintheprivatesectoraremorelikelytoreceiveaprescriptionsorareadvisedtopur-chasecertainTBdrugsratherthanbeadministeredmedicationinafacility.Ifthisisthecase,apatientmustobtaindrugsfromaretailpharmacy,wheretheyarepaidforeitherout-of-pocketorthroughfundsfromaninsuranceplan,ifthepatienthasone.AsinIndia,inthePhilippines,patientsmayapproachapharmacydirectlyandpurchaseTBmedicineswithoutaprescription.Patientsmayalsovisitadoctorwhoprovidesaninitialsupplyofmedica-tionandaprescriptiontoobtaindrugsfromaretailpharmacy,wheretheyarepaidforout-of-pocket.

Anotherdifferencebetweentheprivateandpublicsectorsisinthedecentralizationofdistribution.Forexample,intheprivatesectorsinIndiaandthePhilippines,manufacturersoftenselltheirproductstoseveralwholesalerswhoresellthosedrugstothemanyretailersthroughoutthecountry.Mostprocurementanddistributionisperformedeitherbylargeandcomplexnetworksofmassivepharmacychainsorby“mom-and-pop”pharmaciesthatservespecificregions.

AnothersignificantdifferencebetweentheprivateandpublicsectorsinIndiaandthePhilippinesisthemannerinwhichdrugsarepricedandprocured.Ratherthanusingabidandtenderprocessforpricesetting,manufacturerssetapriceatthelaunchandnegotiatevolumediscountsorrebatesonanindivid-ualclientbasis.Wholesalersordistributorspurchasedrugsfrommanufacturersatan“ex-manufacturing”price.Theythenselltheirdrugstoretailpharmaciesorfacilitiesatamarked-upprice.ThesefacilitiessubsequentlyselldrugstopatientsataCmargin.Asanexample,Figure7describeshowdrugsmostcommonlyflowfrommanufacturertopatientinIndia’sprivatesector.

Althoughthestructureofprivate-sectorprocure-mentanddistributionwasfairlysimilaramongthecountriesstudied,thenumberof“middle-men”whoprocessdrugorders,andthepricemark-upstheseintermediariescharge,varywidely.Private-sectorpricesandmark-upsinIndiaandSouthAfricaarehighlyregulated,althoughadditionalmarginsmaysometimesbenegotiatedthroughvolumediscountsandrebates.Figure7describestheprivatesectorpricemark-upstructureinIndiaandtheaveragemark-upateachstageofthedrug-flowprocess.Inothercountries,notablyChina,themark-upstruc-tureissounpredictablethatitwouldbemisleadingtostatedefinitenumbers.

Figure 7. India Private-Sector Mark-up Structure

*Bears the risk-burden of procurement

First Point of Sale: Manufacturers work with a series of wholesalers who sell drugs at the ex-manufacturing price to private secondary stockists (distributors) or directly to certain healthcare facilities.

Secondary Stockist Sale: Stockists sell drugs to retail pharmacies, clinics, etc., at a marked-up price that has been predetermined (usually 8%).

Retail Sale: Retail pharmacies and/or providers then sell drugs to patients–again at a marked-up price that has been predetermined (usually 16%). This price to the patient is known as the maximum retail price (MRP).

PRIVATE CLINICS/HOSPITALS*

MANuFACTuRERS

WHOLESALERS

STOCKISTS*

PATIENT

NGOS/ CORPORATE-RUN

FACILITIES*

RETAIL PHARMACIES*

Drug Flow:

Private Sector Channels

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5.ProcurementandDistributionofTBDrugsinHighIncomeCountries

5.1 Financing of TB Drugs

AsnotedinSection3.1.2,TBcontrolinthehighincomecountriesstudiedisnotaseparateprogrambutratheranextensionoftheexistinghealthcaresystem.FinancingofTBdrugtreatmentfollowsthesamefinancingpatternsasthatofotherdrugs.

5.2 Procurement of TB Drugs

WhileprocurementofTBdrugsinthepublicsectorsoftheHBCsstudiedismostlycentralized,itisdecentralizedinthepublicsectorsofhighincomemarkets.Insomecases,drugsarepricedthroughapublictendersystem.Forexample,intheUK,anyordersvaluedatorabove£100,000(US$197,000)mustbepricedthoughpublictenderbytheprimarycaretrusts.50InFrance,eachindi-vidualhospitalnegotiatespriceandordersuppliesdirectlywiththewholesaler.TheonlyexceptiontothisisforhospitalbuyinggroupsinLyonandParis,thetwolargestcities,whichmayusepurchasingcollectivestonegotiatevolumediscounts.However,mostfrequently,thepricesofdrugsaredirectlynegotiatedbyfunders(e.g.,privateinsuranceplans

intheUS)and/orwholesalersthatsupplyhealthcarefacilitiesandretailpharmacies.

ThedistributionofTBdrugsinhighincomecountriesoperatesalmostentirelybythepullsystem.51ThisislikelybecausethevolumeofTBdrugsneededissmallandtheprocurementanddistributionsystemsareoftendecentralized.Inthesemarkets,thevolumeandfrequencyofdrugordersaredeterminedonareal-timebasisandbufferstocksarekeptatsmalllevels,ifatall.Furthermore,thepullsystemiseasilysupportedbytheinfrastructuresinhighincomemarkets.Facilitiesandretailpharmaciesoftenhaveelectronicstockmaintenanceprogramsthatprovidealertswhennewproductsneedtobeordered.Thesmallsizeofordersandtheeaseoftransportationallowfacilitiesandretailpharmaciestoquicklyreplenishtheirstocks,ifnecessary.

5.3 Flow of Drugs

ThedistributionofdrugsinhighincomecountriesalsodifferssignificantlyfromthatinHBCs.UnliketheHBCsstudied,whichmaintaincompletely

Drug Flow:

Figure 8. Comparison of Typical Drug Flow in High Income Countries

MANuFACTuRERS

WHOLESALERS/DISTRIBuTORS

PATIENT

HEALTHCAREFACILITIES

RETAIL PHARMACIES

MANuFACTuRERS

CENTRALIZED WAREHOuSE

PATIENT

HOSPITALPHARMACIES

Private Sector Channels

Public Hospitals (Buying Group)

50 Primary care trusts are responsible for setting healthcare budgets for all NHS Hospital Trusts and general practitioners (GPs) in their area and allocating resources across settings.

51 In the US, some states also use a push system, with the state providing free supply and distribution of drugs to regional or local health units.

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separatedistributionroutesforthepublicandprivatesectors,TBdrugsinthehighincomemarketsstudiedflowthroughoverlappingdistributionroutes,regardlessofhowthedrugsarefunded.Ratherthanpassingthroughaseriesofgovernmentdepots,TBdrugsinthehighincomemarketsflowthroughthesamechannelsasanyotherlegalmedicines—frommanufacturerstowholesalers,tofacilitiesorretailpharmacies,andfinallytopatients.Insomecases,

drugsmayflowthroughacentralizedwarehousethatservesaregionorpurchasinggroup.Forexample,inPariscertainhospitalretailpharmaciesarepermittedtoconsolidatetheirorders.Figure8onthepreviouspageprovidesacomparisonofthetypicalflowofTBdrugsthroughcentralizedwarehousesvs.wholesalersinhighincomecountries.

6.CostofTreatmentofTBinBothHighBurdenandHighIncomeCountries

6.1 Prices of TB Drug Regimens

TBdrugpricesinthepublicsectorcanvarysignifi-cantlybycountrybasedonsupplysourcesusedandtheprocessthroughwhichdrugsareprocured.IntheHBCsstudied,andinsomecasesFranceandtheUK,procurementofdrugsinthepublicsectorisadministeredthroughapublicbiddingprocessinwhichmanufacturersbidtosupplyTBmedicines.Priceisthusdeterminedaspartofthebiddingprocess.Inothercountries,pricesmaybenegotiatedbyeachfacility,eitherwithwholesalersordirectlywithmanufacturers.

Pricesalsovarybecausesupplysourcesdifferbycountry.Forinstance,inChinaandSouthAfrica,localmanufacturersareutilizedasaresultofthebiddingprocess.InBrazil,rawmaterialsareprocuredthroughabiddingprocessanddrugsareproducedbystatelaboratories.InthePhilippines,theNTPprocuresfromtheGDFandpricesareestablishedduringtheGDF/manufacturerbiddingprocess.AdditionaldrugsupplyinthePhilippinesisprocuredbylocalgovernmentunitsfromlocalandmultina-tionalmanufacturers,throughwhichdrugpricesaresignificantlyhigher.InIndia,theNTPprocuresfromacombinationoflocalsuppliersandtheGDF.Ex-amplesofhowpricesforvariousTBdrugregimenscanvarybetweenthecountriesstudiedareillustratedinTables4and5onthefollowingpage.

6.2 Public and Private Pricing

Pricesofdrugsalsodiffersignificantlybetweentheprivateandpublicsectorsinbothburdenandhighincomecountries.IntheHBCsstudiedthathavesizeablepublicandprivateTBsectors(i.e.,IndiaandthePhilippines),drugprocurementintheprivatesectorismoreexpensivethaninthepublicsector.Thisislikelyduetosupplysources—forexample,whetherdrugsareprocuredfromtheGDF,fromlocalmanufacturers,orfrommultinationaldrugmanufacturers.Differencesindrugprocure-mentcostsbetweenthepublicandprivatesectorsalsostemfromthevaryingprocurementprocesses.Theseincludenationalbidding,localbidding,ordirectnegotiationswithmanufacturers.Moreover,pricemark-upsoccurregularlyalongthesupplychaininprivate-sectors.

Tables6and7onthefollowingpageprovideexamplesofthecostsofvariousTBdrugregimensinthepublicvs.privatesectorsinIndiaandPhilip-pines.InthePhilippines,pricesdifferbecausethepublicsectorisabletoutilizetheGDFandobtaindirectsupplyatalownegotiatedprice.Privatesectordrugprocurementoperatesthroughthetraditionalpharmaceuticalpathwayandfacesadditionalmark-upsthatoccuralongthesupplychain.

InthepublicsectorinIndia,drugsareprocuredthroughtwomajorpathways,theRNTCPandthenon-RNTCP.TheRNTCPutilizestheGDFforabout50percentofpatients.Fortheotherhalf,theRNTCPobtainsdrugsthroughacentrally-adminis-teredbidandtenderprocesstochoosemanufacturersanddrivedowncosts.Thefewpublicfacilitiesthat

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52 Prices refer to cost of full drug treatment regimen. 53 Prices refer to cost of full drug treatment regimen.

Table 5. National TB Control Programs Public Sector Prices in Studied High-Income Countries53

ACTIVE SOURCE

France $270.92 Local and Multi-national manufacturers

UK $489.83 Local and Multi-national manufacturers

USA $409.79 Local and Multi-national manufacturers

Table 4. Select Public-Sector Prices in HBCs52

CATEGORy I CATEGORy II CATEGORy III SOURCE

Brazil $41 $69 $62 Drugs traditionally produced internally (Scheme 1) (Scheme 1R) (Scheme 2) through state, military or national laboratories.

China $8-17 $14-27 $8-11 Sourced from national manufacturers. Procured through competitive bidding process. Prices differ based on bid (central, JICA or WB funds).

India $10 $18 $8 GDF (loose drugs)

Philippines $18 $33 $18 Categories I and III procured by the national TB program from GDF (patient kits and FDCs); Category II procured from local government units and patients from local manufacturers.

South Africa $47 $127 $47 Sourced from multinational manufacturers with production facilities in South Africa (Sanofi-aventis and Sandoz).

Note: In South Africa, smear negative and extrapulmonary are treated as Category I.

Table 6. Private vs. Public Costs of a Full Course Treatment in the Philippines (Drugs Only)

TREATMENT COST OF DRUGS IN COST OF THERAPy CATEGORy THE PRIVATE SECTOR ($) USING GDF PRODUCTS ($)

Philippines Category I $135.36 $17.89

Category II $315.84 $32.50

Category III $135.36 $17.89

Table 7. Private vs Public Cost of Full Course of Category I Treatment in India (Drugs Only)

Note: All amounts in US$.

TREATMENT COST OF DRUGS IN COST OF THERAPy CATEGORy THE PRIVATE SECTOR ($) USING GDF PRODUCTS ($)

India Category I $135.36 $17.89

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Figure 9. Prices in the uS Across Different Settings54

0% 20% 40% 60% 80% 100%

Patient Assistance Programs

340B

Federal Supply Schedule Service

Wholesale Acquisition Cost (WAC)-Market Price

Average Wholesale Price (AWP)

20%

46%

50%

57%

100%

Veterans Affairs Price

Discount

Market Price

54 States, and the 340B Drug Pricing Program, 2006 edition. Average Wholesale Price (AWP) defines the list price published in RedBook, currently used only as a reference to negotiate discounts. Wholesaler Acquisition Cost (WAC) is typically at 20 percent below AWP; usually referred to as the market price. Federal Supply Schedule Price, VA Price, and 340B are all set discounted prices calculated based on Medicaid best price available for all federally covered entities.

arenotprocuringtheirdrugsthroughtheRNTCPnegotiatedirectlywithmanufacturerstoobtainthelowestpricepossible,orthroughabidandtenderprocesssimilartothatusedbytheRNTCP.Privatemarketdrugsarepurchasedthroughwholesalers,stockistsandretailersandfacehighmark-upsateachlevel.

PricesforTBdrugsintheUS—theonlyhighincomecountrystudiedwithasizableprivateTBmarket—differbasedonwhetherpayersareprivateinsurancecompaniesorapubliclyadministered

programsuchasMedicaid.Intheprivatesector,manufacturerssetalistpriceandinsuranceplansnegotiatewithmanufacturersforrebates.However,inthepublicsectorpricesarepartiallysetbythefederalgovernment.Thegovernment’spricelevelisrequiredtobesetatorbelowthebestpriceofferedtocommercialplanswhichistypicallyatorbelowtheWholesaleAcquisitionCost(WAC)price,andmanufacturersbidatthatpriceorlessforgovernmentbusiness.Asaresult,pricesdifferacrossdifferentsettings,asshowninFigure9.

7.ValueEstimatesForFirst-andSecond-LineTBDrugs

AkeyobjectiveofPathway to Patientswastocollectsufficientdatatoprojectaglobalestimateofthemarketforfirst-lineTBdrugs,basedonthevalueoftheTBdrugmarketineachofthecountriesstudied.

Thissectiondescribesthefirst-andsecond-lineTBdrugmarketvalueestimatescalculatedforeachofthetencountriesstudiedandonaglobalaggregatelevel.Abriefdescriptionofthemethodologyusedtodetermineboththecountryandglobalestimatesisprovided,aswellasinformationoneachhighburdenandhighincomecountry.Valueestimatesforfirst-andsecond-linedrugmarketsareprovidedbycountryand,whereavailable,patientvolumenumbersarealsoincluded.Finally,basedonanextrapolation,thestudyestimatestheglobalmarket

valueforfirst-lineTBdrugs.BecauseMDR-TBpatientregimensvarysignificantly,itwasimpossibletoquantifytreatedMDR-TBpatientsandestimateaglobalmarketvalueforsecond-lineTBdrugs.

7.1 Overview of Methodology

ThemethodologyusedtodeterminethevalueoftheTBdrugmarketineachcountryincludedinPathway to Patientsvariedaccordingtothedataavailable.Thevalueofthepublicmarketswasinmostcasessourceddirectlyfromdiscussionswithstakeholders—usuallygovernmentofficialsorkeyfunders—orfromfinancialreportsissuedbyNTPs.ForSouthAfrica,figuresforthepublicsectorweresourcedfromthetwosupplierschosenthroughthegovernmenttender.Whenreliablepatientfiguresand

0% 20% 40% 60% 80% 100%

Patient Assistance Programs

340B

Federal Supply Schedule Service

Wholesale Acquisition Cost (WAC)-Market Price

Average Wholesale Price (AWP)

20%

46%

50%

57%

100%

Veterans Affairs Price

Discount

Market Price

0% 20% 40% 60% 80% 100%

Patient Assistance Programs

340B

Federal Supply Schedule Service

Wholesale Acquisition Cost (WAC)-Market Price

Average Wholesale Price (AWP)

20%

46%

50%

57%

100%

Veterans Affairs Price

Discount

Market Price

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drugpriceswereavailable,abottom-upcalculationwasconductedtovalidatetop-linefigures.

Private-sectorfiguresweresourcedfromIMSHealthdatabasesandsegmentedbyproductintothefirst-andsecond-linemarket.Becauseprelimi-naryanalysisoffirst-lineprescriptiondataindicatedthatalmostallfirst-linedrugsforTBwereusedexclusivelyforTBtreatment,figuresforthesedrugswereleftunadjusted.However,prescriptiondata—availableformostcountriesinthestudy—wereusedtoadjustsecond-linefigures.55ThepercentageofprescriptionswrittenforTBforeachdrugwasmultipliedbythetop-linesalesfigureforthedrugtocalculatethesecond-lineTBdrugmarketvalue.

Formoreinformationaboutthespecificmethodol-ogyusedtodeterminethemarketestimatesforeachcountryandtheglobalestimates,includingindividualdrugcostfiguresandalistofthecountriesincludedintheglobalextrapolation,aseparatemethodologydocumentisavailableonlineatwww.tballiance.org.

7.2 Country-by-Country Estimates

Forthetencountriesstudied,publicandprivatesectorvaluedataforfirst-andsecond-linedrugsweredeterminedusingIMSandprogramdata(seeTable8).First-linevalueisdefinedasthetotalvalueofthefirst-lineregimen(rifampicin,isoniazid,ethambutol,andpyrazinamide).Volumeisdefinedbythenumberofpatients,ratherthanunits,sinceregimensmayvarybycountryandactualadherencemaydifferaswell.

Estimatingpatientvolumeintheprivatesectorisextremelychallengingbecausetreatmentregimensofferedmayvarysignificantlyandactualadherenceisunknown.Therefore,estimatesonprivate-sectorvolumewerenotconsideredreliableenoughtoincludeinthisreport.

However,thetotalvalueofthesecond-linemarketinthepublicandprivatesectorsinthecountriesstudiedwascalculated.Intheinstanceswherevolumedataarecollectedforsecond-linepatientsinthepublicsector(e.g.,BrazilandthePhilip-pines),volumecalculationsweredevelopedforthesecond-linemarket.Fortheprivatesector,volumewasnotcalculatedbecauseofsignificantvariationintreatmentregimensandadherence.Suchvariationrenderedestimatestoouncertaintoyieldaconfident

Table 8. First- and Second-Line Market Values in Each Country Studied

* China first-line private market sales could not entirely be extricated from public sales, so exact figures are not available at this time.** Some of India’s public-sector facilities may procure second-line drugs directly, but figures for such sales were not available.

Interviews suggest that such purchases are unusual.*** Figure does not include Category III drugs, which are procured primarily by Local Government Units.

The estimated value of Category III drugs is US$908,865.

Note: All figures in US$. NA = not available

FIRST-LINE PUBLIC FIRST-LINE PRIVATE SECOND-LINE PUBLIC SECOND-LINE PRIVATE

Brazil $4.9 million NA $5.0 million NA

China $20 million Unknown* NA $25 million

India $24.25 million $61.2 million Unknown** $8.4 million

Indonesia $5.75 million $8.96 million NA $2.7 million

Philippines*** $2.16 million $28.9 million $58,600 $13,100

South Africa $18.31 million $940,000 $1.71 million $850,000

France $3.6 million NA $4.0 million NA

Japan $11.3 million NA $1.99 million NA

UK $4 million NA $4.5 million NA

US $16.2 million $4.01 million

55 Not available for China or the Philippines.

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globalsecond-linevalueprojection.FollowingareTBdrugmarketvalueestimatesforthetencountriesstudied(SeeFigure10).

Brazil

TheBrazilianTBdrugmarketisvaluedatapproxi-matelyUS$10million,allofwhichisaccountedforinthepublicsector.Thevalueofthetotalmarketisnearlyevenlysplitbetweenfirst-linedrugs(US$4.9million)andsecond-linedrugs(US$5million).However,duetothemuchhighercostofsecond-linetreatment,thefirst-linemarketismuchlargerintermsofpatientvolume.Thereareapproximately115,000first-lineTBdrugrecipientsinBrazilandonly5,000patientswhoreceivesecond-linedrugs.

China

Thecombinedfirst-andsecond-lineTBdrugmarketinChinaisvaluedatUS$45million.Thefirst-linemarketispredominantlyapublicmarket.

Public-sectorreportsfrom2005indicatethat789,189patientsweretreatedandapproximatelyUS$20millionwasspentonfirst-linedrugs.Thetotalvalueforfirst-linedrugsprocuredthroughnationaltenderswasapproximatelyUS$10.8million.AnadditionalUS$8.9millionaccountsfordrugsfundedlocally.Thisincludesexpendituresbyboththeprivateandpublicsectors,thoughresearchindicatesthatthemajorityof“locallyprocured”drugsarefinancedbythepublicsector.

Unlikethefirst-linemarket,thesecond-linemarketinChinaisexclusivelyprivate.ItsvalueisapproximatelyUS$25million.

india

ThetotalTBdrugmarketinIndiaisvaluedatapproximatelyUS$94million,about74percentofwhichisrepresentedintheprivatesector.India’smarketispredominantlyfirst-line,valued

Figure 10. First- and Second-line TB Drug Market Value by Country

l First-line Drug (Public Market) l First-line Drug (Private Market) l Second-line Drug (Public Market) l Second-line Drug (Private Market)

(USD millions)

$0 $10 $20 $30 $40 $50 $60 $70 $80 $90 $100

Brazil

China*

India

Indonesia

Phillipines

South Africa

France

Japan

UK

US*

4.9 5.0

20.0 25.0

5.75 8.96 2.7

2.16 0.0130.05928.9

24.25 61.2 8.4

11.3 2.0

18.3 1.7

3.6 4.0

4.0 4.5

16.2 4.0

0.94 0.85

high Burden

high inCome

(USD millions)

$0 $10 $20 $30 $40 $50 $60 $70 $80 $90 $100

Brazil

China*

India

Indonesia

Phillipines

South Africa

France

Japan

UK

US*

4.9 5.0

20.0 25.0

5.75 8.96 2.7

2.16 0.0130.05928.9

24.25 61.2 8.4

11.3 2.0

18.3 1.7

3.6 4.0

4.0 4.5

16.2 4.0

0.94 0.85

* Although exact figures are unknown, the majority of first-line treatment is financed by the public sector. In the US, this is also true for second-line treatments.

(USD millions)

$0 $10 $20 $30 $40 $50 $60 $70 $80 $90 $100

Brazil

China*

India

Indonesia

Phillipines

South Africa

France

Japan

UK

US*

4.9 5.0

20.0 25.0

5.75 8.96 2.7

2.16 0.0130.05928.9

24.25 61.2 8.4

11.3 2.0

18.3 1.7

3.6 4.0

4.0 4.5

16.2 4.0

0.94 0.85

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atUS$85.45million,withbothpublicandprivatepayers.Payersrepresentingthepublicsector,whichinitiatestreatmentin1.5millionpatientsperyear,purchaseapproximatelyUS$24.3millioninTBdrugs.Theprivatesector,whosepatientnumberscannotbeestimatedwithaccuracy,accountsfortheremainingUS$61.2million.

AsisthecaseinChina,thesecond-linemarketinIndiaisfoundonlyintheprivatesector,thoughspendingbythepublicsectorinthisareawillbegintoincreaseinthenextthreetofiveyearsasDOTS-Pluspilotprojectsareimplemented.Thesecond-linemarketiscurrentlyvaluedatUS$8.4million.

indonesia

ThetotalIndonesianTBdrugmarketisvaluedatUS$17.4million,abouttwothirdsofwhichisspentintheprivatesector(US$11.7million),andathirdofwhichisspentinthepublicsector(US$5.75million).AsinotherHBCs,first-linedrugsaccountformostofthemarket,withsalesfiguresatapproximatelyUS$14.7million,or85percentofthetotal.Thefirst-linemarketissplit61percentand39percentbetweentheprivateandpublicsectors,respectively.

Indonesia’spublicprogramdoesnotdistributesecond-linedrugsatthistime.Thesecond-linemarketisentirelyprivateandhasanestimatedvalueofUS$2.7million.

PhiliPPines

AsinIndia,thevalueoftheTBdrugmarketinthePhilippinesispredominantlyprivate.Thevalueofthecombinedfirst-andsecond-linemarketisapproximatelyUS$31.13million,93percentofwhichisaccountedforintheprivatesector.Thefirst-linemarket,valuedatUS$31.1million,isalmostentirelyprivate.Thepublicsector,inwhichabout135,000patientsaretreatedperyear,accountsforUS$2.16millionperyear.ThisfiguredoesnotincludeCategoryIIIdrugs,whichareprocuredprimarilyviapublictenderbyLocalGovernmentUnits(LGUS).TheestimatedvalueofCategoryIIIdrugsisUS$908,865.Thesecond-linemarket,whichaccountsforlessthanUS$100,000peryear,isdominatedbypublic-sectorexpenditures(approximatelyUS$58,600).Presently,theprivatesectoronlyspendsapproximatelyUS$13,100peryearonsecond-linedrugs.However,treatmentofMDR-TBisexpectedtogrowoverthenextfiveyears.

south afriCa

ThevalueoftheSouthAfricanTBdrugmarketisestimatedatapproximatelyUS$21.8million,nearlyallofwhichisspentinthepublicsectoronfirst-linedrugs.OftheUS$19.25millionfirst-linemarketinSouthAfrica,almost95percent(US$18.31million),ispurchasedinthepublicsector.Proportionally,theprivatesectorplaysalargerroleinthesecond-linemarket,representingaboutonethird,orUS$850,000,oftheUS$2.56millionmarket.

high inCome marKets

SalesandpatientfiguresforthehighincomemarketsstudiedinPathway to PatientsweremoreeasilyaccessedthandataforHBCs.However,pricingoftreatmentregimenswasdifficulttoascertain,whichmadeitdifficulttovalidatethroughbottom-upcalculations.

Ofthehighincomecountriesstudied,JapanhadthehighestincidenceofTBinfection.In2004,therewereapproximately30,000newlyregisteredcasesandthepercentageofpatientswithMDR-TBwaslessthanonepercent.ThevalueoftheJapanesedrugmarket,whichisentirelypublic,isestimatedatUS$13.3million,withUS$11.3millionrepresentingthefirst-linemarket.

TheFrenchandBritishTBdrugmarketsarealsoentirelypublicandarevaluedatapproximatelyUS$7.6millionandUS$8.5million,respectively.ThemarketvalueinFranceissplitbetweenfirst-linetreatment(US$3.6million)andsecond-linetreatment(US$4million).AsinFrance,thetotalBritishTBdrugmarketissplitbetweenfirst-linetreatment(US$4million)andsecond-linetreatment(US$4.5million).

TheUSreportedapproximately14,000newcasesofTBin2005,lessthanonepercentofwhichwereMDR-TB.ThetotalUSmarketvalueforTBdrugsisapproximatelyUS$20.21million,82percentofwhichisrepresentedbyfirst-linetreatment(US$16.2million)withtheremainingUS$4.01millionrepresentingsecond-linetreatment.

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7.3 Global Estimates

First-line treatmentAsnotedearlier,thesixhighburdencountriesstudiedrepresentapproximately60percentofTBdiseaseinthe22highburdencountriesandalltencountriesstudiedaccountforapproximately50percentofthetotalglobalTBburden.

Researcherswereabletoextrapolatethefirst-everestimateoftheglobalmarketbasedonoriginalresearchbyusingthedataofthecountriesstudiedtoyieldthefollowingprojectionsonaworldwidescale:

1)Alowendestimate,basedonDOTSnotificationrates(actualnumberofcasesreportedeachyear)andarangeofactualandaveragepriceperpatientregimencosts,suggeststhatthevalueoftheglobalfirst-linemarketisbetweenUS$261M–316M.

2)Ahighendestimate,basedontheWHO’sglobalincidencefigures(totalprojectednumberofnewcases)andarangeofactualandaveragepriceperpatientregimencosts,suggeststhatthevalueoftheglobalfirst-linemarketisbetweenUS$310M–418M.

Assumingthatcurrentcasenotificationratesdonotalwaysreflectthefullnumberofpatientsbeingtreated,andthatincidenceratesreflecttheabsolutemaximumnumberofpatientsthatcanbetreated,

theoverlapofthetworangesistheclosestestimateoftheactualfirst-linemarket,indicatingthatthetotalvalueoftheglobalmarketforfirst-lineTBdrugsisapproximatelyUS$315M(seeFigure11).

Second-line TreatmentThestudyfoundthatanumberoffactorspreventmakingasimilar,globalestimateofthesecond-lineTBdrugmarket.AccordingtotheStopTBPartnership’sGlobalPlantoStopTB2006-2015,lessthantwopercentofestimatedculturepositiveMDR-TBpatientsaretreatedappropriately.CasesofMDR-TBarenotconsistentlyreported,particularlyiftheyarenottreatedinthepublicsector.Thereareanumberofpotentialtreatmentsincludedinsecond-lineregimens,andthereisvarianceinprescribingpractices,lengthofregimenaswellasadherencerates.Similarly,costsalsovarydramaticallyacrosscountriesandthereisnorealistic“averagecost”forsecond-lineregimens.Therefore,researchersfeltitisinappropriatetoapplythemethodologyusedtoprojectthefirst-lineglobalestimatetoasecond-lineworldwideestimate.

However,lookingonlyatthetencountriesstudied,theresearchfoundthattheestimatedvalueofthesecond-lineTBdrugmarketinthosecountriesisapproximatelyUS$54M.

Figure 11. Global Estimate Ranges of First-Line TB Drug Market

(US

D m

illio

ns)

250

300

350

400

450

Low End Range High End Range Estimated Actual Market Value

US$261M

OverlapUS$310M–316M

US$418M

Low end range defined based on case notification approach; High end range based on incidence.

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8.AdditionalConsiderations

Pathway to Patientsprovidesin-depthinsightintoissuesthataffectthedynamicsoftoday’sTBdrugmarket.Thesefindingshelpmapfactorsthatwillhavedirectandindirectimpactonmarketdynamicsbetweennowandthetimenoveldrugregimensareapprovedandreadyforintroductionintotheglobalmarketplace.However,thisanalysisalsosuggeststheneedforadditionalresearchorexplanation.

Quality of TB services, programs and processesAsmentionedintheintroduction,thisresearchdidnotrevieworaddressthequalityofTBservicesortheprocurementanddistributioninthecountriesstudied.Instead,itsoughtonlytodescribethem.Issuesrelatedtothedegreetowhichthosesystemsfunctioneffectively—suchaswhetherthequalityofcareiseffective,whetherpatientsarereceivingDOTS,whetherdemandforecastingisaccurate,orwhetheradequatelevelsofbufferstocksarealwaysonhand—werenotaddressed.

TB control programs in decentralized systems ThecharacterizationoftheTBcontrolprogramsofhighlydecentralizedhealthcaresystems,suchasthosefoundinChinaandSouthAfrica,wouldbenefitfromadditionalstudy.Inthosecountries,theimplementationofTBcontrolvarieswidelyfromprovincetoprovinceandamorerobustanalysisofeachprogram,includingaregion-by-regionstudy,wasnotpossiblewithinthetimeconstraintsofthisproject.Futurestudiesofsuchprogramsshouldincludeacomprehensiveregionalanalysistoensurethatthenuancesoflocalvariationarecaptured.

Data discrepancies regarding value and volume estimates Inmostcases,thedifferentdatasourcesfromwhichfigureswerepulledeithercorroboratedwithoneanotherorcouldbecheckedwithanalternativecalculation.However,inafewinstances,suchasinChina,stakeholderdiscussionsyieldednumbersthatdidnotalign,and/orresearcherswereunabletotriangulateontheactualfiguresthroughabottom-upcalculation.Asystematicauditofeachofthesourcesusedwouldhelptofurtherrefineestimatesinfuturemarketsizingattempts.

Market segmentation of private-sector data Thesegmentationofprivate-sectordataintofirst-lineandsecond-linemarketsalsoposedachallenge.Inmostcountries,IMSHealthprivate-sectordatabasesareaggregatedbyproductandnotindication,sothefirst-linemarketincludesdrugsthatareusedinsecond-linetreatmentandviceversa.Therefore,availableprescriptiondatadidnotalwaysallowresearcherstodistinguishbetweenthefirst-andsec-ond-lineuseofanygivendrug.Improvedabilitytoallocateeachdrug’ssalesandvolumetoitsrespectiveusemightchangethecharacterizationofthemarket.

Lack of estimates for private-sector patient volumeEstimatingthepatientvolumeintheprivatesectorwasnotpossible.Thereasonsstemmedfromvariationsintreatmentregimens,lackofinformationaboutadherence,andlackofdataavailableregardingflowofpatientsbetweenprivateandpublicsectors.AsurveyofprescribingpracticesandadherenceinHBCswithasignificantprivatesectorwouldallowforthedevelopmentofarelativelyreliablevolumeestimateforeachcountry.

Inherent imprecision in extrapolatingFinally,whilethemarketestimatesofthecountriesincludedinthescopeoftheresearchprovidedthebasisforextrapolationtoothercountries,itisclearthatsuchcomparisonsarenotaperfectproxy.Forinstance,Russia’sgroupingintotheHBCswasbasedonitsTBincidence,butthepricesofitsTBdrugsaresignificantlyhigherthaninotherHBCs.The“restofworld”extrapolationalsohasadegreeofuncertainty.Drugpricesforcountriesinthe“restofworld”categorywerealsodeterminedbasedoninformationfromHBCsstudied.Thus,morespecificpricingandutilizationinformationfromthesecountrieswouldallowforamoreexactestimate.

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9.PredictingFutureMarketDynamics

UnderstandingthestructureoftheTBdrugmarket,includingprocurementanddistributionsystemsinhighburdencountries,isessentialforplanningtheintroductionofnewTBdrugregimens.

Potential Market ChangesThisstudyprovidesin-depthinsightsintoissuesthataffectthedynamicsoftheTBdrugmarkettodayandhelpsmapfactorsthatwillhavedirectandindirectimpactonthesedynamicsbetweennowandthetimenoveldrugregimensareapprovedandreadyforintroductionintotheglobalmarketplace.TheanalysisalsosuggeststheneedforadditionalresearchintoanumberofevolvingfactorsthatmayaltertheflowofTBdrugs,highlightingthatabetterunderstandingofallofthisclosertothenewproductsroll-outwouldfacilitateadoptionofandaccesstonewTBdrugswhentheybecomeavailable.

TheGlobalPlancallsforexpanded,equitableaccessforalltoqualityTBdiagnosisandtreatmentby2015.Therefore,effortsundertakenoverthenextdecadetoachievetheGlobalPlan,includingtheintroductionofnewtoolstodiagnose,treatandpreventthedisease,alongwithpolicyandfundingconsiderations,areexpectedtoincreasesignificantlythenumberofpatientsbeingtreatedforTB.

New DiagnosticsNew,fasterandmorereliablediagnostictoolsforTBareinthepipeline,andshouldbegintoenterthemarketoverthenextseveralyears.TheGlobalPlancallsforpointofcarediagnosticsby2010thatwillallowrapid,sensitiveandinexpensivedetectionofactiveTB.Twoyearslater,StopTBenvisionsadiagnostictoolboxthatwillaccuratelyidentifypeoplewithlatentTBinfectionandthoseathighriskofprogressiontodisease.Newdiagnostics,oncedeveloped,shouldleadtoincreasesincasefindingthatwillresultinanincreaseindemandfortreatment.

New DrugsThegoaloftheGlobalPlanistohaveanewshort(one–twomonths)TBregimen(s)by2015.Anumberoftrialsarecurrentlyunderwaythatcould,by2010,potentiallyshortentheregimentothree–fourmonths.Shortenedtreatmentwithnoveldrugsoffersthepotentialtoenhancepatientadherence,decrease

defaultrates,curtailcoststothehealthcaresystemandpatients,andsubstantiallyimproveoutcomesforthoseinfected,especiallyforpatientsco-infectedwithHIVandTB.Ifrealized,theseadvantagesareexpectedtoincreasetheneedanddemandfornewTBdrugs.

TheexpansionofdrugresistantTBworldwideisaf-fectingmarketdynamics.ThisisexpectedtoincreasebecausecountriesarebeginningtoincludetreatmentofMDR-TBandXDR-TBaspartoftheirnationalTBcontrolprograms.Expandingthecoverageofdrug-resistantTBwillincreasethemarketdemandforsecond-linedrugs.

Patientaccesstonoveltherapieswillrequirenationalandinternationaladoptionofnewtreatmentsandextensive“retooling”ofTBprogramstoaccommo-datechangesintheregimen.Anumberofelements,includingcost,availabilityandeaseofadministra-tionwillhaveadirectimpactonadoptionofnewtherapies.Fullyunderstandingtheseandotherfactorswillbecriticalforimplementationofnewshorterregimensworldwide.

New VaccineWhilenumerousfactorsleadtothepotentialofincreasednumbersofpatientsbeingtreated,resultinginlargerdemandforTBdrugs,otherscouldleadtoalonger-termdecreaseinmarketdemand.Specifically,theGlobalPlancallsforanew,safe,effectiveandaffordablevaccinetobeavailableby2015.Thecurrentvaccineis85yearsold,worksonlyinchildren,andisnotalwayseffective.Anewpreventivevaccinethatworkstoprotectallagegroupshasthepotential,ifwidelyadoptedandused,toprovideapositiveimpactonTBcontroland,inthelong-term,asignificantreductioninthenumberofthoserequiringtreatment.

ItwillbeimportanttounderstandthepotentialeffectsofasuccessfulvaccineonTBdrugdemandandthemarket.Furtherstudyofthisinterfacewillbepossiblewhenmoreisknownabouttheprofileofanewvaccine.

Policy InfluencesPolicychangeshavethepotentialtoincreasethenumberofpatientstreated,therebyaffectingthemarketdynamicsandhighlightingtheneedfor

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closemonitoringofthesechangesintheyearsahead.AnexampleisChina’srecentdecisiontoincludetreatmentofsmearnegativepatientsasapartofitsnationalTBcontrolprogram,whichaddspatientsandincreasestheamountofdrugsneededbythepublicprogram.Similarly,theexpansionofpublicsectorfundingfortreatmentofdrugresistantTBinmarketslikeIndia,ChinaandthePhilippines,albeitslow,willincreasethenumberofpatientsreceivingsecond-linedrugsand,overtime,willchangethevaluedynamicsofthatmarket.

Inthepast15years,publicsectorTBprogramshavedramaticallyexpandedinmanyhighburdencountries.Inthosecountrieswithlargeprivatesectormarkets,likeIndiaandthePhilippines,thereisaslowtrendofpatientsmovingfromprivatetopublicsectortreatment,largelyduetogovernmentimplementationofWHO-recommended“public-privatemix”programs.Thiscouldresultinadecreaseinthevalueoftheprivatemarket,butanincreaseinvalueofthepublictendermarket.

Funding InfluencesWithwidespreadcommitmenttotheGlobalPlanandtheintroductionofnewfinancingmechanismsandcommitmentsbytheUN,G8,anddonorandhighburdencountries,itisexpectedthatTBcontrolprogramswillcontinuetoexpandandstrengthenoverthenexttenyears.However,theextenttowhichthedrugmarketrespondstothisexpansionwilldependonanumberofvariables.

Inthecountriesstudied,mostfundingusedforTBdrugs,whetherfromthepublicorprivatesectors,comesfromdomesticsources.Somehighburdencountries,however,aredependentonexternaldonorfundingtoenhancetheirnationalcommitment,especiallyforsecond-linedrugsandpediatricTBmedication.Newfundingschemes,suchastheGlobalFundforAIDS,TBandMalaria(GFATM)andUNITAID,aninternationaldruganddiagnos-ticspurchasefacility,mayofferincreasedaccesstosecond-lineTBmedicationsovertime.Thus,markets—especiallyforsecond-linedrugs—willcontinuetobesusceptibletotrendsandchangesinfunding.

�0.Conclusions

Pathway to PatientsstudiedtheTBdrugmarketplaceintencountries,providingacomprehensiveunder-standingofcountry-specificdataandananalysisofprocurementanddistributionsystemsineightofthesecountriesandatthegloballevel.Thestudypointstothevariabilityofthemarketdynamicsamongthecountriesstudied,thecomplexitiesoftheissuesfaced,andthefragmentednatureofthemarket.

The MarketThestudy’scurrentglobalestimateforfirst-lineTBdrugsisapproximatelyUS$315Mperyear,includ-inghighincomecountrysales.Thisprojectionisconsistentwiththatofferedinthe2001studyThe Economics of TB Drug Development56which,usingadifferentmethodology,estimatedthefirst-linemarketin2001atapproximatelyUS$350M.

Whilethetotalmarketestimateisnotinconsider-able,theTBmarketplaceishighlyfragmentedbecauseitissharedbymorethanfourdrugsandamultiplicityofsuppliers.Thisfragmentationisnotlikelytochange.First,successfultreatmentof

TBwillmostlikelyrequireacombinationtherapy.Second,asthestudysuggests,domesticdrugproductionfacilitiesmaybeintegraltomarketentryfornewTBdrugsinmostcountriesstudiedandlikelyinothers.

Atpresent,thereisalsoalimitedcommercialmarketforsecond-lineTBdrugs.WhiletheMDRandXDR-TBmarketshaverevenue-generatingpotential,currentaccessinmostcountriesisprimarilyrestrictedtotheprivatesector,withpricesthatseverelylimitaccessformostpatientswithdrugresistantTB.Tappingthismarketwouldrequireasignificantexpansionofpublicsectortreatmentprograms,aswellasgovernment-ordonor-sponsoredpurchaseandprocurement.

Inthehighincomecountriesstudied,thetotalTBmarketisrelativelysmall,withpricingandprocure-mentfollowingthesamepricingsystemsasotherpharmaceuticals.France,Japan,theUKandtheUScombined—accountingfor61percentofthetotalglobalpharmaceuticalmarket57—purchaselessthanUS$50MworthofTBdrugs.

56 Executive Summary for The Economics of TB Drug Development. Global Alliance for TB Drug Development. October, 2001.57 IMS Knowledge Link. http://www.imsknowledgelink.com.

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Lessons Learned from High Burden CountriesThestudysuggeststhatcarefulplanningwillbeneededtoacceleratetheadoptionofanynewTBdrugregimeninthehighburdencountries.ResearchconfirmsthepreferenceofmanycountriestopurchaseTBdrugsdirectlyfromlocalsuppliersandnotfromtheglobalmarketplace.AlthoughtheGDFservicesanumberofcountries,especiallythosethatlacklocalmanufacturersorqualityassurancecapacity,mostpurchasersforthepublicsectormarketsstudiedshowastrongpreferenceforprocurementfromdomesticmanufacturers.Itwillbeessentialtoresearchthisissuefurther,includingotherhighburdencountries,beforedevelopingroll-outplansfornewTBdrugs.

Thestudyalsosuggeststhatthelaunchofanynewdrugregimenwillrequireaphasedroll-outinhighburdencountries.Drugapprovalbyregulatoryauthoritiesisonlythefirststeptowardadoption.ThenationalTBprogrammustthendecideifitwillincludethenewtherapyaspartofthetreatmentregimen.Thus,accesstopublicsectormarketswillrequireanunderstandingoftheprocessesbywhichnewregimensareadoptedbynationalTBprogramsaswellasthepublictendersystemsandtheirrequirements.

Evenafteradoption,nationalroll-outleadingtoactualpatientaccesswilltaketimebecausecountrieswillneedtounderstandtheimpactofanewregimenonservicedeliveryandexistingsupply.Also,bufferstocksofexistingmedicationsmustbeexhaustedfromboththeGDFandnationalstores.Planningforappropriateproductionwillrequireanunderstandingofhowlongitwouldtakepost-approvalforhighburdencountriestoimplementachangeintherapy.Collaborationwithdiseasecontrolprogramsanddonoragencieswhichhaveworkedonsupplychainissuesinotherareas,suchasmalariaandHIV,wouldbehelpfulinsuchplanning.

Lessons Learned from High Income CountriesTBisdetectedthroughoutthehighincomecountriesstudied,althoughmostdiagnosedandtreatedcasesareconcentratedinthemajorcities.Intheseeconomies,anumberofmedicalspecialtiesandsubspecialtiestreatTB,withphysiciansdecidingwhichtreatmentregimenstouse.Combinedwithotherfactors,thisdynamicsuggeststhatnewTBdrugsandregimenswillrequireanawarenessbuildingcampaignand/orsubstantialmarketingeffortstoreachthesedoctors.

Summary ObservationsAlthoughthisstudyfoundsomesimilaritiesacrossmarkets,thecriticalfindingwiththesupplychainforTBdrugswasthevariabilitybycountry.Therehasbeenarecentcallforaglobal“infomediary”togatherandorganizemarketdataforlowandmiddleincomecountries,acrossdiseaseareas,andactasanintermediarybetweenthosewhosupplytheinformation,suchasnationalTBcontrolprograms,andthosewhowanttheinformationtoassistsupplierswithdemandforecasting,reducedelaysandensureconsistentsupply.58Thisresearchsuggeststhataglobal“infomediary”couldbeextremelyhelpfultothedevelopmentandroll-outofnewTBdrugs,byprovidingefficientandcost-effectiveinformationsharing.

Thisstudyprovidesuniqueinsightintothecomplexityoftoday’sglobalTBmarket.Justasresearchanddevelopmentintonewcompoundsrequiresmanystagesbeforeadrugisreadyforregulatoryapprovalanduse,preparingtheworldforrapiduniversaladoptionanduseofnewTBtreatmentswillrequiretheunderstandingofmarketdynamics,perceivedbenefitsofthenewregimens,manufacturingandsupplychainissues,operationalchangesnecessitatedbynewtherapies,donorpolicies,priceelasticityofdemandandotherattributesthatwouldjustifythechangeintreatmentregimen.

Giventhemarketintricaciesrevealedinthisresearch,itissafetoconcludethatprovidingtheproperpath-wayforanewgenerationoffasterandeasier-to-useTBdrugstoreachthepatientwillrequireatargetedandinformedcountry-levelandglobalstrategy.

58 Center for Global Development, Global Health Policy Research Network. Consultation Report of the Global Health Forecasting Working Group. February, 2007.

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11.Appendices

11.1 Partial List of Acronyms

APHA AmericanPublicHealthAssociation

ARVs antiretrovirals

AWP averagewholesaleprice

BMGF Bill&MelindaGatesFoundation

CDC U.S.CentersforDiseaseControlandPrevention

ChinaCDC ChineseCenterforDiseaseControl andPrevention

CIDA CanadianInternationalDevelopmentAgency

DFID U.K.DepartmentforInternationalDevelopment

DGIS Directorate-GeneralforInternationalCooperation(oftheNetherlandsMinis-tryofForeignAffairs)

DOH DepartmentofHealth

DOTS directlyobservedtherapy,shortcourse

EMB ethambutol

EU EuropeanUnion

FDC fixed-dosecombination

GDF GlobalDrugFacility

GFATM GlobalFundtoFightAIDS,TBandMalaria

GLC GreenLightCommittee

HBC highburdencountry

HR isoniazid,rifampicin

HRE isoniazid,rifampicin,ethambutol

HRZE isoniazid,rifampicin,pyrazinamide,ethambutol

IAPSO Inter-AgencyProcurementServicesOrganization

IBEF IndiaBrandEquityFoundation

IDA InternationalDispensaryAssociation

INH isoniazid

JICA JapanInternationalCooperationAgency

JSI JohnSnowInternational

KNCV RoyalNetherlandsChemicalSociety

MDR-TB multi-drugresistanttuberculosis

MRC MedicalResearchCouncil

MRP maximumretailprice

MSH ManagementSciencesforHealth

NCTB NationalTBControlProgram(China)

NDTI NationalDiseaseandTherapeuticIndex

NGO non-governmentalorganization

NPA IMSHealth’sNational PrescriptionAudit

NSP IMSHealth’sNationalSalesPerspective

NTP nationalTBcontrolprogram

OPPI OrganisationofPharmaceuticalProducersofIndia

PAHO PanAmericanHealthOrganization

PDI PharmacyDOTSInitiative

PhilCAT PhilippinesCoalitionAgainstTuberculosis

PhilTIPS PhilippinesTBInitiativesinthePrivateSector

PIH PartnersInHealth

PPM public-privatemixprograms

PZA pyrazinamide

RIF rifampicin

RNTCP RevisedNationalTBControlProgram(India)

TAC TreatmentActionCampaign

TB tuberculosis

ICD-10 InternationalClassificationofDiseases

UNICEF UnitedNationsChildren’sFund

UNDP UnitedNations DevelopmentProgramme

USAID U.S.AgencyforInternationalDevelopment

WAC wholesaleracquisitioncost

WB WorldBank

WHO WorldHealthOrganization

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11.2 List of Manufacturers (By Country)

BrazilThemajorityofdrugsareproducedbyNationalandStateLaboratories

National:• Farmanguinhos(underFiocruz)

Military:• Army(LQFEX)• AirForce(LQFAE)• Navy(LFM)

State:• FURP(SaoPaulo)• Iquego(Goias)• LAFEPE(Pernambuco)• Nuplan(RioGrandedeNorte)

ChinaManufacturersawardednationaltender:• ShenyangHongqiLuoshanSanjiu• GuoyaoGuorui

Hospitalscanprocurefromanyapprovedmanufacturer.

FranceManufacturersoffirst-linedrugs:• Ethambutol(GenoPharm;SERP;GSK)• Isoniazid(Laphal)• Pyrazinamide(Sanofi-aventis)• Rifampicin(Sandoz;Sanofi-aventis)• Rifampicin+isoniazid(Sanofi-aventis)• Rifampicin+isoniazid+pyrazinamide

(Sanofi-aventis)

Manufacturersofsecond-linedrugs:• Ciprofloxacin(Sandoz)• Clavulanicacid(Sandoz)• Levofloxacin(Sanofi-aventis)• Ofloxacin(Sanofi-aventis,Sandoz)

India• CadilaPharma• ConceptPharma• Lupin• Macleods• OverseasHealthcare• Sandoz-Novartis• ShreyaLifeScience• ThemisMedicare• Wockhardt

Japan• Cycloserine(MeijiMeuiseka)• Ebutol(KakenSeiyaku)• Ethambutol(SandozJapan)• Iscotin(Daiichiseiyaku)• Pyramide(Sankyo)• Rifampicin(SandozJapan,NiproPharma)• Rifandin(Daiichiseiyaku)• Rimactane(NovartisPharmaJapan)• StreptomycinSulfmei(Meuiseka)• Tubermin(Meuiseka)

Philippines• Biomedis• DuncanPharmPhil• Medichem• Natrapharm• PascualLabs• PatriotPharma• PediatricaLab• Sandoz• TerramedicInc.• UnitedAmerican• Westmont• Wyeth

South AfricaManufacturersawardednationaltenders:• Sandoz• Sanofi-aventis

Manufacturersofsecond-linedrugs:• Be-tabsPharmaceuticals• BiotechLaboratories*• BizshelfPharmaceuticals• CapsPharmaceuticals*• PfizerLaboratories*• Sandoz• Sanofi-aventis• InternationalSuppliers

* Suppliers of streptomycin, which is also used in first-line treatment of relapse patients

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11.3 Prices of Drugs for Select Countries and Purchasers

China

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 1.57 3 3 0.62 3 4 86 $ 10.79

CAT II HRZE HRE 1.57 3 3 1.14 3 6 139 $ 17.33

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 2.10 3 2 0.82 3 4 81 $ 10.13

CAT II HRZE HRE 2.10 3 2 1.52 3 6 138 $ 17.26

CAT III HRZ HR 1.25 3 2 0.82 3 4 66 $ 8.65

Price per regimen for centrally financed drugs (2005)

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 2.10 3 3 0.82 3 4 115 $ 14.37

CAT II HRZE HRE 2.10 3 3 1.52 3 6 185 $ 23.13

CAT III HRZ HR 1.25 3 3 0.82 3 4 84 $ 10.55

COST PER REGIMEN (ASSUMING 3 MONTHS INTENSIFIED PHASE)

Price per regimen for JICA funded centrally procured drugs (2005)

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 1.57 3 2 0.62 3 4 67 $ 8.41

CAT II HRZE HRE 1.57 3 2 1.14 3 6 120 $ 14.94

COST PER REGIMEN (ASSUMING 3 MONTHS INTENSIFIED PHASE)

Price per regimen for DFID/WB funded centrally procured drugs (2005)

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 2.44 3 2 0.93 3 4 103 $ 12.88

CAT II HRZE HRE 2.44 3 2 1.76 3 6 185 $ 23.12

INTENSIFIED CONTINUATION

PER PER UNIT # PER # OF UNIT # PER # OF TOTAL TOTAL REGIMEN RMB WEEK MONTH RMB WEEK MONTH COST RMB COST USD

CAT I HRZE HR 2.44 3 3 0.93 3 4 133 $ 16.56

CAT II HRZE HRE 2.44 3 3 1.76 3 6 215 $ 26.82

COST PER REGIMEN (ASSUMING 3 MONTHS INTENSIFIED PHASE)

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Philippines

FIRST LINE DRUGS

The cost of First- and Second-Line TB drugs in the private sector

SECOND LINE DRUGS

DRUG MANUFACTURER DOSE COST PER PILL

Myrin P Wyeth HRZE $ 0.23

Myrin Wyeth HRE 0.18

Tritab Unilab HRE 0.20

Quadtab Unilab HRZE 0.18

Ciprofloxacin Local 300 mg $ 0.34 -1.50

Clarithromycin Local 300 mg 1.88

South Africa

Sandoz private-sector prices (uS$)

Sanofi-aventis private-sector prices (uS$)

SANDOZ TRADE NAME PACK SIZE SEP PRICES (VAT ExCLUDED) SEP PRICES (VAT INCLUDED)

Rimactane 150 100 $ 16.50 $ 18.81

Rimactane 300 Vials 1 17.29 19.71

Rimactane 450 100 29.03 33.09

Rimactane 600 100 54.15 61.73

Rimactazid 150/75 60 7.00 7.98

Rimactazid 300/150 40 6.20 7.07

Rimactazid 60/30 40 5.27 6.00

Rimactazid Paed 60/60 80 11.92 13.59

120 17.88 20.38

Rimcure Paed 3-FDC 80 15.93 18.16

120 23.90 27.24

500 99.57 113.51

Rimstar 4-FDC 40 4.60 5.24

60 6.90 7.87

80 9.20 10.49

100 11.50 13.11

500 57.50 65.55

Sandoz Ethambutol HCl 400 100 12.67 14.44

Sandoz Pyrazinamide 500 100 14.72 16.78

SANOFI-AVENTIS TRADE NAME PACK SIZE SEP PRICES (VAT ExCLUDED) SEP PRICES (VAT INCLUDED)

Rifafour e-275 40 $ 4.43 $ 5.05

60 6.64 7.57

80 8.86 10.10

100 11.65 13.29

500 55.35 63.10

Rifinah 300 mg 40 5.83 6.65

Rifater Junior 40 7.00 7.98

40 5.78 6.58

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11.4 Interview Lists

GLOBAL STAKEHOLDERS

Marcos Espinal ExecutiveSecretary,StopTBPartnershipSecretariat

Peter Evans Consultant,IndependentconsultanttoGDF

Kathryn FloydActingHeadofTBMonitoringandEvaluation,WHO

Christina FoleyTBAdvisor,CIDA

Ernesto JaramilloMDR-TBWorkingGroupSecretariat,WHO/GLC

Fabienne JoubertonProcurementOfficer(second-line),GDF/GLC

Kathryn Kempton DirectorofDrugProcurement,PIH

Marieke Korsten AreaManager,IDA

Robert Matiru ManagerofOperations,Procurement,GDF/GLC

Elisabetta Molari Procurement,SupplyPolicy&ManagementTeamLeader,GFATM

Poul MullerAccountManager,ProcurementServicesHealthCommodities,UNDP-IAPSO

Sue PerezDonorCountryProjectManager,GlobalTBCampaign,ResultsInternational

Ralph RackPharmaceuticalandLogisticsAdvisor,JohnSnowInc.(JSI)

Jim Rankin Director,CentreforPharmaceuticalManagement,ManagementSciencesforHealth

Mario RaviglioneDirector,StopTBDepartment,WHO

Doris RouseDirector,GlobalHealth,RTIInternational

Jereon van GorkomSeniorConsultant,KNCV

Hilary VaughanSeniorHealthAdvisor,RoyalCrownAgents

Hugo VrakkingProcurementAdvisor,GDF/GLC

Diana WeilSeniorPublicHealthSpecialist,StopTBDepartment,WHO

BRAZIL

Miguel Aiub Hijjar Director,NationalReferenceLab(HelioFraga)

Paulo Alburquerque Physician,PoliclinicaAmaralPeixoto

Joao Batista Oliveira MOHconsultanttoFarmanguinhosFarmanguinhos

Solange CavalacanteRiodeJaneiroMunicipalTBProgram

Joseney dos SantosNationalTBProgramManager,NationalTBProgram

Betina Durovni MunicipalTBProgramManager,RiodeJaneiroMunicipalTBProgram

Paiva Edilson StateTBProgramManager,MinasGeraisStateTBProgram

Fernando Fiuza Mello DirectorandPhysician,InstitutoClementeFerreiraTBReferenceCenter,SãoPauloTBReferenceCenter

Lisia FreitasStateTBProgramManager,RiodeJaneiroStateTBProgram

Vera Galesi StateTBProgramManager,SaoPauloStateTBProgram

Germano Gerhardt-Filho DirectorandformerPNCT,ProgramManagerFundaçãoAtaulfodePaiva-R.J.

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Gustavo Bastos, Luis MSH/practicingphysician

Joel Keravec Director,MSH/RPMPlus

Naomi Komatsu MunicipalTBProgramManager,SaoPauloMunicipalTBProgram

Afranio Kritski DirectorofAcademicTBProgram, UniversidadeFederaldoRiodeJaneiro

Ana Regina Physician,CentroMunicipaldeSaúdePíndarodeCarvalhoRodrigues(DOTS)

Jorge Rocha Practicingphysician,MSH/RPMPlus

Dr. Rosangela StateTBProgramManager, BahiaStateTBProgram

Waldir Silva MOH,NationalTBProgram

Andrea Sousa de Ataide Pharmacyservices,MOH/NationalTBProgram

Marcio Thome DirectorofLogisticsandSupply, BEMFAM(NGO)

EzioTavora dos Santos Filho GrupoPelaVidda

Marilene Vinhas Pharmacistatwarehouse,BEMFAM(NGO)

CHINA

Yanbing ChenAssistantofGuangdongCDCDirector,GuangdongCDC

Sun Chenguang DirectorofShanghaiChangningDistrictCDC,ShanghaiCDC

Daniel Chin MedicalOfficer,StopTBDepartment,WHO

Vimal Dias MSHProject-RPMPlus,ManagementSciencesforHealth

Xiao Fan Physician&DirectorofInternalMedicine,GuangzhouThoracicHospital

Lin Fen HainanCDCDirector,HainanCDC

Cornelia M. Hennig MedicalOfficer,StopTBDepartment,WHO

Dr. Li PhysicianatHainanCDC,HainanDongChuangCountyCDC

Hongdi LiDoctorinCharge,ManagerofTBPreventionSection,ShanghaiChangningCDC

Jianjun LiuDirector,NCTB,ChinaCDC

Jian Mei DirectorofTBPreventionDepartment,ShanghaiCDC

Shen MeiAssociateDirectorofTBPreventionDepartment,ShanghaiCDC

Vice General ManagerFirst-LineSupplier

Sales and Marketing DirectorSecond-LineSupplier

Vice General Manager NationalDistributor

Tao Tao DirectorofPharmacy,GuangzhouThoracicHospital

Lin Wang AssociateResearcher,Director,Dept.forHealthPromotion,Director,Dept.ofDrugandFacilityResources,NCTB,ChinaCDC

Ni Wang DepartmentofDrugandFacilityResources,NCTB,ChinaCDC

Xiaomei Wang ProgramOfficer,GFATMChinaTBProgram

Zhao Wang FormerDirector,ChinaCDC

Compendium |page��

may2007

Ying Xu DirectorofPharmacy,GuangdongPanyuCountyChronicDiseasesHospital

Fu Yu Director,TBClinicalCenter;President,BeijingThoracicTumorandTBHospital

Qiang Zhang SurgeonandDeputyDirector,GuangzhouThoracicHospital

Shuo Zhang HealthOperationsOfficer,HumanDevelopmentSector,WorldBank

Xi Zhang ManagerofPharmacy,BeijingThoracicTumorandTBHospital

Yu Wen Zhang PhysicianatHainanCDC,HainanDongChuangCountyCDC

FRANCE

PharmacistChiefPharmacist,Hospital

Specialist Pulmonologist,Hospital

INDIA

Two DirectorsRKMissionClinicandGTBChestClinic

Three PPM Providers

Rajiv Alex Sandoz GeneralManager,GlobalTBBusinessandExports

Dr. ChauduryStateTBOfficerforMaharashtra,StateTBDivision

LS Chauhan DeputyDirectorGeneral(TB),CentralTBDivision

Mandar Deo MarketingManager,GlobalTB,Sandoz

Vijay K. Dhiman PPMCoordinator,Delhi,WHO-RNTCPDepartment

Ritu GuptaAdditionalGeneralManager,RITES

Rajesh KabuVicePresident,SalesandMarketing,Macleods

Ritu Khushu ProjectLeader,CentralTBDivision-StrategicAlliance

Alok Malik Sr.GeneralManager,Marketing,Macleods

Jayanti Patel Chairman,ManagingDirector, MaheshwarDistributorsPrivateLtd.

RK Pradham Representative,DrugControllerOffice

Suvanand Sahu NationalProfessionalOfficer,TB,WHO-RNTCPDepartment

VS Salhotra ChiefMedicalOfficer,CentralTBDivision

Vinay SapteManagingDirector,ManeeshPharma-Svizera

Pradeep Saxena ChiefMedicalOfficer,CentralTBDivision

Tariq ShahMedicalOfficer,CentralTBDivision

Preetish ToraskarGeneralManager,SalesandMarketing,Lupin

RP VashistStateTBOfficerforDelhi,StateTBDivision

D. Fraser WaresMedicalOfficer,WHO-RNTCPDepartment

INDONESIA

Andy Barraclough PrincipalProgramAssociate,ManagementSciencesforHealth

Petra Heitkamp StopTBPartnership

Jan Voskens SeniorConsultant,KNCV

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JAPAN

Hajime Inoue Director,MinistryofHealth,LaborandWelfare–InternationalAffairsDivision

PharmacistHospital

PHILIPPINES

Asuncion Anden Director,DOHCenterforHealthDevelopment,MetroManila

Michael Arabit Pharmacist,MakatiMedicalCenter

Eduardo Banzon VicePresident,HealthFinancePolicy&ServicesSectorandOIC,BenefitsDevelopmentOffice,PhilHealth

Victoria Basa-Dalay ChairmanTBResearchUnit,DeLaSalleUniversity(PrivateDOTSProgram)

Jubert Benedicto Chairman,PhilCAT

Marilou Costello HealthSystemsAdvisor,PhilTIPS

Ruben Escarda PhysicianandDepartmentChairmanofInternalMedicine,VisayaCommunityMedicalCenter(PrivateHospital)

Nereza S. Javier ProvincialCoordinatorforTBProgram,ProvincialTBProgram,Cavite

Dory C. Loquias ProvincialCoordinatorforTBProgram,ProvincialTBProgram,Cebu

Amelia Medina RegionalCoordinatorforTBProgram,NationalCapitalRegion(MetroManila),DOHRegionalOffice,MetroManila

Jose Hesron D. Morfe PhysicianandDOTSProgramManager,PhilTIPS;UniversityofStThomasHospital(PrivateDOTSProgram)

DOTS Nurse Coordinator UniversityofStThomasHospital(PrivateDOTSProgram)

Individual DOTS-PlusCommitteeofStopTB

Pharmacy ManagerPhilippinesGeneralHospital

Pharmacist; Purchasing ManagerNationalPharmacyChain(PDI)

Marketing Coordinator; General ManagerSupplier

Marilyn Noval-Gorra PolicyandFinanceAdvisor,PhilTIPS

Erlinda Pascual President,DrugstoresAssociationofthePhilippines

Earl Stanley Perez Comptroller-MerchandizingDivision,WatsonsPersonalCareStores

Fulgencia Ricero RHP,DOH,BatangasCity

Leticia Rivera ProvincialCoordinatorforTBProgram,ProvincialTBProgram,BatangasCity

Marilyn Tiu PurchasingManager,MedExpress

Thelma Tupasi PresidentofTDF,ChairmanofDOTS-PlusCommittee,TropicalDiseaseFoundation(TDF),MakatiMedicalCenter

Rosalind VianzonNationalTBProgramManager,DOH,OfficeofInfectiousDiseases

Sergio Villahermosa SupplyOfficer,ProvincialTBProgram,Cebu

Andre Daniel Villanueva PharmacyDOTSInitiative-ProgramManager,PhilTIPS

John Wong SpecialistforDrugManagementandFinance,PhilTIPS;AsianDevelopmentBankHealthSectorDevelopmentProgram

Charles Y. Yu SeniorAdvisor,PhilTIPS

Compendium |page��

may2007

SOUTH AFRICA

Shabir Banoo SeniorProgramAssociate,MSH

Alan Beattie NationalSalesManager(PublicSector),AspenPharmacare

Gavin Churchyard CEO,AurumInstitute

Elaine Cross HeadofTBSupplies,Sandoz

Virginia de Azeveda Sub-districtNTPDirector(Kylitscha),Sub-districtTBControlProgram(Kylitscha)

Deon Du Plessis MedicalDirector,Netcare

Bernard Fourie ResearchAssociate/ClinicalTrialsAdvisortotheMRC;ChiefScientificOfficer/Director,SouthAfricanOperationsofMEND,MedicalResearchCouncil(MRC)

Ria Grant Director,TBCareAssociation

John Heinrich CEO,SANTA

Mandisa Hela DirectorofPharmacyServices,PharmacyPlanningandPolicy

James Kruger DistrictNTPDirector(Boland,Overberg),DistrictTBControlProgram(BolandOverberg)

Liezel Channing PharmacistARVProgram,ProvincialTBControlProgram,WestCape

M. Makhetha TBProgramCoordinator/NPO–TB,WHO

Ethel Makoena Chairman,SANTA

Reuben Mawela DistrictSalesManager,TB Sanofi-aventis

Penny Mkalipe MedicalOfficer,ESKOM

Tumi Molongoana SeniorProgramAssociate,MSH

Sipho Mthathi GeneralSecretary,TreatmentActionCampaign(TAC)

Lindiwe Mvusi NTPDirector,NationalTBControlProgram

Ann Preller ProvincialNTPCoordinator,ProvincialTBControlProgram,NorthWest

Jean-Pierre Sallet RegionalTechnicalAdvisor,MSH

Mandisa Swartz ProvincialNTPCoordinator,AssistantDirector,TBControl,ProvincialTBControlProgram,WestCape

UK

Pharmacist ChiefPharmacist,Hospital

Pharmacist Ownerofasmallchainofretailpharmacies,Retail

SpecialistConsultantinRespiratoryDiseases,Hospital

US

Muhammad Anwar Pulmonologist,St.Joseph’sHospital

Kenneth Castro MedicalDirector,DivisionofTuberculosisElimination,U.S.CDC

MikeEhren Pharmacist,FloridaStateHealthDept.,BrowardCountyTuberculosisControlClinic

Sonal S. Munsiff MedicalOfficer,BureauofTuberculosisControl,U.S.CDC,NYCDepartmentofHealthandMentalHygiene

MaryAnn O’Brien Pharmacist,QuincyMedicalCenter

Lee Reichman ExecutiveDirector,NewJerseyMedicalSchool,NationalTuberculosisCenter

Susan Spieldenner PublicHealthAdvisor,TBControlBranch–CaliforniaDepartmentofHealthServices

Charles Wallace ProgramManager,TBControlBranch–TexasDepartmentofStateHealthServices

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12.Acknowledgements

TheTBAlliancewouldliketoacknowledgethemanypeoplewhosetime,effortandenthusiasm,madethisunprecedentedresearchprojectpossible.

Weareverygratefultoourprojectadvisors:MonaAshiya,SarahEwart,JordanLewis,MariekeKorsten,RobertMatiru,JimRankinandDorisRouse,andthemembersofourresearchteam:NinaSchwalbeandHeatherIgnatiusfromtheTBAlliance,andAlyseForellina,AlexisGeaneotes,MichelleLee,LaurenDiCola,TarekRaafat,andClareWalkerfromIMSHealth.

ThePathway to PatientsresearchteamwouldliketoacknowledgethecontinuoussupportofTBAllianceofficersMariaFreire,MelSpigelman,KarenWright,AlHinmanandBradleyJensen;theresearch&developmentteam’sAnnGinsberg,ZhenkunMa,ChristovanNiekerk,andKhisiMdluli;andthecommunicationsandpolicyteams’CuylerMayer,DerekAmbrosino,StephanieSeidel,andAsmitaBarvefortheirreview,writingandpublicationsupport.

TheTBAlliancewouldalsoliketothankthefollowingfortheircontribution:KenCastro,LSChauhan,DanielChin,GavinChurchyard,KatherineFloyd,PetraHeitkampp,MandisaHela,JeffHoover,MichaelHowley,HajimeInoue,FabienneJouberton,JoelKeravec,HannahKettler,AfranioKritski,ElisabettaMolari,SonalMunsiff,LindiweMvusi,Pierre-YvesNorval,AntonioRuffinoNetto,IkushiOnozaki,NitinPatel,SuvanandSahu,VSSalhotra,ThelmaTupasi,RosalindG.Vianzon,JanVosken,DianaWeil,FraserWares,WangXiaomei,andCharlesYu.

Finally,thisprojectwouldnothavebeenpossiblewithoutthegenerousfinancialsupportofTheNetherlandsMinistryofForeignAffairs’DepartmentofDevelopmentCooperation(DGIS)andtheBill&MelindaGatesFoundation.

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About the Global Alliance for TB Drug Development

The Global Alliance for TB Drug Development (TB Alliance) is a not-for-profit, product

development partnership accelerating the discovery and/or development of new TB

drugs that will shorten treatment, be effective against susceptible and resistant strains,

be compatible with antiretroviral therapies for those HIV-TB patients currently on such

therapies, and improve treatment of latent infection.

Working with public and private partners worldwide, the TB Alliance is leading the

development of the most comprehensive portfolio of TB drug candidates in history,

and is committed to ensuring that approved new regimens are affordable, accessible

and adopted.

The TB Alliance operates with the support of the Bill & Melinda Gates Foundation,

Irish Aid, the Netherlands Ministry of Foreign Affairs (DGIS), the United Kingdom

Department for International Development (DFID), and the United States Agency for

International Development (USAID).

For more information on TB drug development and the TB Alliance, please visit

www.tballiance.org.

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80 Broad Street

31St Floor

New York, NY 10004

USa

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Fax: +1 212 227 7541

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