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MDR-TBELIMINATION:WHATWILLITCOST?
Emily A. Kendall, MD Assistant Professor, Infectious Diseases,
Johns Hopkins University School of Medicine
48th Union World Conference on Lung Health, Guadalajara, Mexico, 14 October, 2017
OUTLINE
TrendsanddriversofMDR-TBepidemics
Whatinterventionswilleliminationrequire?
Atwhatprice?
Aretheyworththecost?
Drivers of MDR TB epidemics: What we know ◦ Acquisi(on:Treatmentofdrug-suscep(bleTBseedsMDRepidemics1,2◦ Transmission:TransmiAedMDRexceedsnewresistanceacquisi(on3,4,5
◦ Under-diagnosis:Failuretodiagnoseandtreatprolongstransmission◦ Ineffec(vetreatment:Prolongstransmissionandpromotes2nd-lineresistance◦ Recentspread:KnownMDRTBcontactsathighrisk6,7
1. MenziesPlosMed20092. RockwoodJID20173. YangLancetID2016
4. KendallLancetRespirMed20155. WHOGlobalReport2016no(fica(ons6. GrandjeanPlosMed2015
7. Prajapa(PedsIntChildHealth2015
…SuggesAng a mulA-faceted approach ◦ Treatmentofdrug-suscep(bleTBseedsMDRepidemicsàBeAerDS-TBcontrolmayhelp◦ Transmissionexceedsnewresistanceacquisi(onàMustinterruptMDR-TBtransmission
◦ FailuretodiagnoseandtreatprolongstransmissionàXpertscale-up,casefinding◦ Ineffec(vetreatmentprolongstransmissionandpromotessecond-linedrugresistanceàSecond-lineDST,op(mizedregimens,treatmentmonitoring,beAerregimens
◦ Recenttransmissionpredominates;knownMDRTBcontactsathighriskàContacttracing,second-linepreven(vetherapy,biomarkersforprogression
As for DS-TB, mulAple strategies needed
ExampleofprojectedimpactofmoreMDR-TBtreatmentandamore-effec(veregimen,SoutheastAsia:
(Repeatedly,modelinganalyseslikethisoneshowthatmoreandbeAerMDRtreatmentcanhavealargeimpact,buts(llwon’tgetustoelimina(ononitsown.)
Kendalletal,LancetRespirMed2017
MDR-TB requires a mulA-faceted approach ◦ Treatmentofdrug-suscep(bleTBseedsMDRepidemicsàBeAerDS-TBcontrolmayhelp◦ Transmissionexceedsnewresistanceacquisi(onàMustinterruptMDR-TBtransmission
◦ FailuretodiagnoseandtreatprolongstransmissionàXpertscale-up,casefinding◦ Ineffec(vetreatmentprolongstransmissionandpromotessecond-linedrugresistanceàSecond-lineDST,op(mizedregimens,treatmentmonitoring,beAerregimens
◦ Recenttransmissionpredominates;knownMDRTBcontactsathighriskàContacttracing,second-linepreven(vetherapy,biomarkersforprogression
Most-efficientcombina/onswilldependonlocalepidemiology&economics.
ProhibiAve costs of MDR-TB control? RifampinDST:◦ GeneXpertIVmachine:$17,000,◦ $10perXpertMTB/RIFcartridge1
MDR-TBtreatmentcourse,LIC:◦ median$3,3002
Second-lineDST:◦ $100?(volumeandassay-dependent,laboratoryintensive)3
Contactinves(ga(ons:◦ ~$10-100percontactscreened4
Resultofcostsandcomplexity:under-u/liza/on◦ 24%rifampinDSTcoverage,fornewTBdiagnoses2◦ 23%MDR/RRno(fica(on,perincidentMDR/RRTBcases2
◦ 36%second-lineDSTcoverage,forMDR/RRTBdiagnoses2
◦ ??screening,forMDRTBcontacts(7%ofunder-5[DS]TBcontactsreceivepreven(vetherapy)2
Budgets,30TBHBCs
DS MDR/RR
No(fica(ons,30TBHBCs
DS MDR/RR
1. FINDnego(atedpricing2. WHOGlobalReport20163. VassallPLOSMed2011
4. YadavAJTMH2014,SteffenPLOSOne2013,A(fSpringerplus2012,MandalakasThorax2013
Two perspecAves on acceptable cost, illustrated for a novel RR-TB regimen:
Fixedper-pa(entcosts
Regimen-anddura(on-dependentmanagement
costs
Drugcosts
Otherfixedcosts
1.Affordabilityperspec/ve,e.g.atwhatpricewouldbeEerdrugs/regimensbebudget-neutral?
Shorterregimenreducesmanagementcosts,freesresourcesfordrugs
Fixedper-pa(entcosts
Reducedmanagement
costs
Increaseinavailabledrugbudget
Otherfixedcosts
Oneyear Oneyear
$0
$2,000
$4,000
$6,000
$8,000
$10,000
$12,000
$14,000
$16,000
$18,000
DRC India SouthAfrica Russia
$980 $1,579$2,700
$4,745
$1,754$2,940
$14,591$16,242
Budget-neutralregimenprice,pertreatmentcourse
Currentaverageregimencost,2015standardofcare(reference)Novel6moMDRregimen;~50%lowerdelivery&monitoringcosts
Fixedper-pa(entcosts
Regimen-anddura(on-dependentmanagementcosts
Drugcosts
Otherfixedcosts Otherfixedcosts
Per-pa(entcostsdecreasewithdecliningincidence
Managementcost
sdecreasewith
dura(on
anddeclinefurt
herover(me
Time
Furtherincreasein
poten(aldrugspending
Increaseinavailabledrugbudget
ShorterandbeAerregimenalsoreducesincidenceandimproveshealthoutcomes
2.Costeffec/venessperspec/ve:• Over(me,beAerregimensreducenumberofpa(entsrequiringtreatment.• Reduc(onsinmorbidityandmortalityalsohavevalue.
Addi(onalvalueofimprovedhealthoutcomes
Time
$300/DALYaverted(120,1040)
Exampleofepidemiologicprojec(on:
…withmortalityandprevalenceprojec(onsthatwecantranslateintoDALYsaverted:
Actualepidemiologicprojec(onsusedforthisanalysisarebasedonKendalletal,PLOSMed2017
*InPeruandPhilippines,perFitzpatrickandFloydPharmcoeconomics2012,convertedto2015USD
Fixedper-pa(entcosts
Regimen-anddura(on-dependentmanagementcosts
Drugcosts
Otherfixedcosts Otherfixedcosts
Per-pa(entcostsdecreasewithdecliningincidence
Managementcost
sdecreasewith
dura(on
anddeclinefurt
herover(me
Time
Furtherincreasein
poten(aldrugspending
Increaseinavailabledrugbudget
ShorterandbeAerregimenalsoreducesincidenceandimproveshealthoutcomes
2.Costeffec/venessperspec/ve:• Over(me,beAerregimensreducenumberofpa(entsrequiringtreatment.• Reduc(onsinmorbidityandmortalityalsohavevalue.
Addi(onalvalueofimprovedhealthoutcomes
Time
$300/DALYaverted(120,1040)
Economic benefits to acAng now Example:second-lineDST+regimenop(miza(on.
Supposeit:◦ reducesriskofMDRtreatmentfailurefrom30%to20%,and
◦ reducesacquiredpre-XDR/XDR(costlytore-treat)from10%to5%.
40RRTBcases
12RRTBnotcured
!DST+regimenadjustmentswouldbecost-neutralat>$400/pa@ent
–evenbeforeaccoun(ngforthepreventedMDRandXDRtransmissions.
*Assumingthatretreatmentcosts$3000forMDRalone,$6000forpre-XDR/XDR
…aswellasincreaseinvestmentsinMDR-TBnow.
ToeliminateMDRTB,wemustreducethecostofdiagnosisandeffec(vetreatment…
So what will MDR TB eliminaAon cost? Ican’tnameaprice.◦ HardtocostglobalTBelimina(oneveninabsenceofdrugresistance◦ Dependsinpartonfuturetechnologicaladvances
But…
So what will MDR TB eliminaAon cost? MDRelimina(onrequiresamul(-prongedstrategy.◦ Wemustworktomakethesemoreaffordable◦ Understandlocalepidemicstoiden(fymostefficientpackages
Sucheffortsmaybecost-effec(veorevencost-saving◦ givendownstreamcostsofnotdoingthem
…Butwillstraincurrentbudgetsandcapacity.
Globalcommitmentandinvestmentarerequired.
ü Case-findingü Contacttracingü Preven(onü Regimenselec(onü Treatmentmonitoringü Pa(entsupport
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