MDR-TB ELIMINATION: WHAT WILL IT COST? Emily A. Kendall, MD Assistant Professor, Infectious Diseases, Johns Hopkins University School of Medicine 48 th Union World Conference on Lung Health, Guadalajara, Mexico, 14 October, 2017
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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