Cost-EffectivenessofHealthSystemsStrengtheningInterventionsinImprovingMaternalandChildHealthinLow-andMiddle-Income

Countries:ASystematicReview

Wu Zeng

Guohong Li

Haksoon Ahn

Ha Thi Hong Nguyen

Donald S. Shepard

Dinesh Nair

August 17,

2017

2

ABSTRACTMaternalandchildhealth(MCH)remainsamajorhealthconcerninlow-andmiddle-incomecountries(LMICs).Despiteimpressiveprogressmadeduringthemillenniumdevelopmentgoalsera,lowefficiencyofhealthsystemssignificantlydelaystheeffortsingettingeffectivehealthinterventionstopopulationsinneed.RecognizingthestrongneedtostrengthenhealthsystemsinaddressingMCH,healthsystemsstrengtheninginterventionshavebeenincreasinglyimplementedinLMICsinthelastdecade.Thisstudyreviewsgloballiteratureoncost-effectivenessofhealthsystemsstrengtheninginterventionsinimprovingMCH.

Asystematicreviewwascarriedout.KeywordsforsearchingarticlesweredevelopedbasedontheWHO’sframeworkonhealthsystemsandpriorstudies.Articlesweresearchedfromfourbibliographicdatabases(PubMed,Econlit,AcademicSearchPremier,andWebofScience),onedatabaseforgreyliterature(Popline),aswellasthewebthroughGoogleScholar.Additionaleffortsweretakentoreviewreferencestoidentifymorearticles.Articlesthatestimatecost-effectivenessofhealthsystemsinterventionsinLMICswereincludedintheanalysis.AllselectedstudieswereassessedintermsofqualityandbiasesusingtheCochrane’scriteria.ReviewManagerandanExceltemplatewereusedtoextractdataandsynthesizefindings.Studycharacteristicsandcost-effectivenessofinterventionswerereported.

24publicationswereidentifiedfrom15countries.MoststudieswereundertakeninAfrica.Healthsystemsstrengtheninginterventionswereprimarilyconcentratedonservicedelivery,healthfinancingandhumanresources,whichincludedcommunitymobilization,qualityimprovement,payforperformance,voucherschemes,andtrainingtohealthproviders.Amongthe24studies,15studieswereratedashighquality,5asmediumand4aslowquality.Amajorityofstudiesreportedcostperdisability-adjustedlifeyear(DALY)avertedorcostperquality-adjustedlifeyear(QALY)gained;otherstudiesreportedcostperlifesavedorlifeyeargained.However,studiesusedmixedperspectivesofanalyses.Comparedtogrossdomesticproductpercapita,interventionsinstudiesreportingcostperDALYavertedorQALYgainedwereallcost-effective,includingperformancebasedfinancing,healthinsurance,andqualityimprovement.

ThisreviewshowsthediversityofhealthsystemsstrengtheninginterventionsinimprovingMCH,andtheirpotentialcost-effectiveness.However,thedifferentperspectivesemployedinthestudies,costingcomponentsincludedintheanalyses,andheterogeneousmeasuresofeffectivenessandoutputs,madeitchallengingtocomparecost-effectivenessacrossallstudies.Forpolicymaking,itiscriticaltoexaminelong-termcost-effectivenessofprogramsandcost-effectivenessofsynergisticdemandandsupplysideinterventions.

3

INTRODUCTIONMaternalandchildhealth(MCH)remainsamajorhealthconcerninlow-andmiddle-incomecountries

(LMIC).DuringtheMillenniumDevelopmentGoals(MDGs)era,stronginternationalcommitmentwasdirectedtoMCH:MCHservicesexpandedsubstantiallytopoorandvenerablepopulationsandequityofreproductiveandmaternalhealthservicescontinuouslyimproved1.Globally,theunder5mortalityrate

(U5MR)wasreducedfrom90.6in1990to42.5per1,000livebirthsin2000(53%reduction)2,andthematernalmortalityrate(MMR)from282in1990to196per100,000livebirthsin2015(30%reduction)3.Thesedeclinesareimpressive.However,onlyafewcountriesachievedallofMDGshealth-relatedgoals.

Forexample,onlytencountriesachievedMDG5onreductionofmaternalmortalityrate3.Tomaintainthemomentumofreducingmaternalandchildmortalityrates,internationalcommunitiesdevelopedtheSustainableDevelopmentGoals(SDGs)aimedtosustainhealthgainsincombatingMCH-related

illnesses.

ThereductionofMMRandU5MRsignificantlybenefitedfromincreasedfinancialcommitmentsfrom

donorsthoughofficialdevelopmentaid(ODA).Since2002,ODAhastripledfrom$54.8billionin2001to$167billionin20134.ODAfundingforhealthduringthesameperiodincreasedmorethanfive-times,risingfrom$4.4billionto$22.8billion4.Asubstantialamountofdonorsupportwasallocatedto

combatingHIV/AIDS,malaria,andtuberculosis,aswellasforprovidingMCHservices.Inspiteoftheincreaseinresources,thereisagreatneedtocontinueinvestinginhealthprogramstosustainhealthgains.Inthelastdecades,theinternationalcommunityhasincreasinglyrealizedthattreatment

expansioneffortshavebeenslowedbyinsufficienthealthinfrastructureandinefficienthealthsystems.Toacceleratethepaceofdeliveringeffectiveandavailablepreventionandtreatmenttopopulationsinneed,donorsarepayingincreasingattentiontohealthsystemsstrengthening(HSS),callingfor

interventionsforbuildingamoreefficientandeffectivehealthsystem5.TakingprojectsfundedbyUSAIDasanexample,therehavebeenmultipleglobalflagshipprojectsonHSSawardedtoimplementationpartners,includinga,$209millionhealthgovernanceandfinanceproject(2012-2017)6,

forstrengtheninghealthfinanceandgovernancesystems,ahealthpolicyplus(HP+)projectof$185millionforgeneratingevidenceforpolicymaking7,andDELIVERYProjectforenhancingsupplychains.Similarly,TheGlobalFundhasgraduallyswitcheditsfundingfromdisease-specificinterventionstoHSS.

Thirty-sevenpercent($362million)oftheGlobalFundRound8fundingwasallocatedforHSS8.HSSbecomesacriticalelementtocatalyzeeffortstoexpandservicecoverage.

AlongwithimprovingMCHservices,manyHSSprograms,withthesupportfromdonorsandgovernments,havebeendesigned.Forexample,performancebasedfinancing(PBF)programsprovidefinancialincentivestohealthfacilitiesfordeliveringMCHservices.WithsupportfromtheHealthResults

InnovationTrustFund(HRITF),35PBFprogramshavebeenimplementedin29countriessince2007,withatotalofcommitmentof$385.6millionasofSeptember20169.PBFaimstoimproveMCHthrough

improvingthemanagementandfinancialsituationofhealthfacilities.Voucherprogramsincentivizepregnantwomentoseekessentialmaternalcare,andhavebeenimplementedwidely10.InitialimpactevaluationshowspositiveimpactoftheseprogramsinimprovingtheuseofMCHservices10,11.However,

thereislittleevidenceconcerningcost-effectivenessoftheseprograms12,13.

4

Manyofsuchprogramshavebeensupportedbydonorsinitially,withtheexpectationthattheywillbetransferredtogovernmentsasprogramsmature.Thisraisesanimportantquestionastowhetherthe

governmentscanaffordtotakeonandsustaintheprograms.Eachgovernmenthastooperateprogramswithinitsbudget,andwhenmultipleprogramsareavailable,governmentsmustwiselychooseamongthem.Additionally,withsubstantialinvestmentinHSS,bothdonorsandgovernmentscallforvaluefor

moneytomaximizetheimpactofavailableresources14.AstudyintheUnitedStatesshowedthatusingcost-effectivenessinformationtoallocateresourceshadthepotentialtoimproveapopulation’shealthstatus15.Thus,itiscriticaltoincludecostsinassessingtherangeofavailableprogramsandinevaluating

programs’impact,tounderstandbettereconomy,efficiency,andeffectivenessofprograms14.

RecognizingthecriticalroleofhealthsystemsinimprovingMCH,thisstudyaimstoprovideasystematic

reviewofcost-effectivenessofHSSinterventionsinaddressingMCH.Thetermcost-effectivenessinthisreviewisusedinamoregenericway,anditincludesanystudieslinkingcoststotheimpactofprograms,encapsulatingcost-effectivenessanalysis(CEA),cost-utilityanalysis(CUA)andcost-benefitanalysis

(CBA).Throughthisreview,wehopetoprovideamorecompletepictureofHSSinterventionsinorderforcountriestomakeinformeddecisions,toidentifygapsinexistingeconomicevaluationsofHSSinterventions.

METHODSThisreviewconcentratedonthecost-effectivenessofHSSinterventions.WorldHealthOrganization

(WHO)developedaframeworkwithsixbuildingblocks(Figure1),providingacommonunderstandingofwhatahealthsystemisandwhatconstituteshealthsystemsstrengthening16.Buildingonthisframework,HSSinterventions,inthisreview,aredefinedasactivitiesaimingtoimprovethesixbuilding

blocksofahealthsystem(leadership/governance,healthfinancing,humanresources,medicalproductsandtechnologies,healthinformation,andservicedelivery).ThisdefinitionisconsistentwithwhatWarrenetal.usedtoanalyzeGlobalFundfundingforhealthsystemstrengthening8.

Figure1.Sixbuildingblocksofahealthsystem(Source:WHO,2007.)

5

Servicedelivery,amongthesixbuildingblocks,isslightlydifferentfromtheotherfiveblocks.Servicedeliveryisregardedasanimmediategoalofahealthsystem,whiletheremainingbuildingblocksserve

asinputsforeffective,safe,qualityserviceprovision.Giventhatservicedeliveryisoftenmeasuredbyaccess,coverage,andqualityofcareandthatoneofWHO’sprioritiesinrespondingtohealthsystemchallengesonservicedeliveryistodevelopeffectiveservicedeliverymodels16,HSSinterventionson

servicedeliveryarelimitedtoactivitiesforimprovingqualityofcare,enhancingengagementofthedemandside,anddevelopinginnovativeservicedeliverymodels(e.g.,communityengagement,public-privatepartnerships,andsocialmarketing).Activitiesdirectlytargetedtopatientsorpotentialpatients

forpreventiveandcurativepurposesareregardedasclinicalinterventions(e.g.,screening,testing,andtreatment),ratherthanHSSinterventions,andthusexcludedfromthereview.

DeskresearchstrategyToidentifyarticlesforreview,weusedthecombinationoftermsinthefollowingthreeareastoconductthedeskresearch:(1)cost-effectiveness;(2)maternalandchildhealth;and(3)thesixbuildingblocks.Forcost-effectiveness,weusedthetermsof“cost-effectiveness”,or“cost-benefit”,or“economic

evaluation”.Tocapturematernalandchildhealth,thesearchtermswere“reproductive",or"maternal",or"neonatal",or"child"or“motherhoodprogram”or“prenatalcare”.Astokeywordsforthesixbuildingblocks,giventhewidevariationofhealthsysteminterventionsforMCH,wefirstreviewedan

articlethatsynthesizedkeyinnovativeinterventionsaddressingMCH17,anddevelopedkeywordsforsearchingarticles.Table1showsthetermsthatweusedforeachofthesixbuildingblockstoconduct

thesearch.Ingeneral,thekeywordsstartedwithtermsorsynonymsofthebuildingblocks,andproceededwithmorespecificinterventionswithintheblock.

Table1.Keysearchtermsonthesixbuildingblocksofthehealthsystem

Servicedelivery Healthworkforce Information Medical

products Financing Leadership/governance

Searchwords

Qualityimprovement Humanresources Information Supplychain Financing GovernanceCommunity Humanworkforce Technology Cashtransfer LeadershipPublic-privatepartnership Training Incentives Healthpolicy Education Voucher Regulation Healthinsurance

Userfees

Performancebasedfinancing

Resultsbasedfinancing

Payforperformance

Weconductedsearchesinfourmajorelectronicbibliographicdatabasesonpublichealthand

economics:PubMed,EconLit,AcademicSearchPremier,andWebofScience,onJan12,2017andupdatedthesearchonFeb10,2017.WealsoconductedasearchforgreyliteraturethroughPoplinedatabase.AllsearcheswereconductedinEnglish.Withanadditionalthreearticlescollectedbyauthors,

theinitialsearchidentified4,197non-duplicatepublicationsthatwereeligiblefortitleandabstract

6

screening(Figure2).Toincludemoregreyliteratureforreview,wealsosearchedthroughGoogleScholarusingthesamekeywordsasthoseappliedtobibliographicdatabases.Theresearchteam

reviewedthefirst100recordsfromthesearchandcomparedthemwiththoseobtainedfromelectronicdatabases.WefurthercheckedtheireligibilityandfoundnoadditionalarticlesthatcouldbeincludedinthereviewfromGoogleScholar.

Figure2.Flowdiagramforstudyidentification

ExclusioncriteriaAllthesearchrecordswerefirstuploadedinEndnoteX8andindependentlyscreenedbytworeviewers(WZandHA).WeusedEndnotetoeliminateduplicatedrecords(1236records).Theremainingrecords

(4197records)werefirstreviewedthroughtitlesandabstractstoassesstheirrelevance:(1)studiesfocusedonmaternalandchildhealth;(2)interventionsconcernedwithHSS:(3)studiesthatreportedon

7

cost-effectivenessmeasures;and(4)studiesconductedinLMIC.Articlesthatmettheseinclusioncriteriaandthosethatpossiblymetthecriteriawereincludedinthefull-textreview.Asaresult,38articles

wereselectedforfull-textreview.Articleswereexcludediftheymetoneofthefollowingexclusioncriteria:

• Studiesnotrelatedtomaternalandchildhealth;

• Studiesnotconductedinlow-andmiddle-incomecountries;

• Studieswhereinterventionsdidnotfallinanyofthesixbuildingblocksofahealthsystem;

• Studieswhereinterventionsweredirectpreventiveandcurativeservices;

• Qualitativestudies;

• Studiessynthesizingpriorstudies;

• Studiesevaluatingprogramsthathadnotbeenimplemented;

• Studieswherethefinaleffectivenessintheeconomicevaluationwasnotmeasuredintermsof

healthoutcome(e.g.lifeyearssaved,disabilityadjustedlifeyears(DALYs)averted,qualityadjustedlifeyears(QALYs)gained,livessavedordeathsaverted);

• Studiesreportingaveragecost-effectivenessratiowithoutanycomparisongroup,ratherthanincrementalcost-effectivenessratio(ICER);and

• Studiespublishedpriorto1990.

ThefulltextreviewwasconductedindependentlybyWZandHAforall38articles,and18articleswereexcludedbasedonexclusioncriteria.Wefurtherreviewedreferencesfromtheremaining20articles,

andincluded4morearticles.Intheend,24articleswereselectedinthefinalreviewforsynthesizingfindings.Table2showsthereasonforexclusionforthe18articles.

Table2.Reasonsforexclusionof18outof38articles

Numberofarticles Reasonsforexclusion

10Cost-effectivenessmeasuresnotintermsofcostperoutcomemeasures

2Noempiricaldata,CEApurelybasedonassumptionsandsecondarydata

2 Reportingaveragecost-effectivenessratio

1 Duplication

1 NotrelatedtoMCH

1 NotconductedinLMIC

1 SynthesisofpriorstudiesCEAdenotescost-effectivenessanalysis;MCHdenotesmaternalandchildhealth;LMICdenoteslow-andmid-incomecountries.

StudyselectionanddataextractionAnExceltemplatewasdevelopedtoextractdatafromthe24articles.Thecollectedinformation

included:(1)characteristicsofstudies:publicationyear,interventionsunderexamination,researchdesignforimpactevaluation,outcomemeasuresofimpactevaluation,alongwithotherrelevantstudycharacteristics;and(2)componentsofeconomicevaluation:perspectiveofcostanalyses,cost

components,lengthofassessment,yearinwhichcostswereassessedandexpressed,cost-effectiveness

8

measures,valueofcost-effectiveness,whethersensitivityanalyseswereconducted,andthelike.Foreacharticle,correspondinginformationwasextracted.Dataextractionwasprimarilycarriedoutbyone

researcher,whileanotherresearcherreviewedandcheckedcollecteddata.Ifinformation(e.g.yearinwhichcostswereassessedandexpressed)wasnotavailableinthemaintext,tworesearchersdiscussedandmadebestguesses.

QualityassessmentorriskofbiasinindividualstudiesThefinal24studieswerethenimportedintoReviewManagersoftware5.3(RevMan)(Copenhagen:TheNordicCochraneCentre,TheCochraneCollaboration)andsubsequentlyevaluatedforqualityof

evidenceorriskofbiasusingtheCochraneEffectivePracticeandOrganisationofCare(EPOC)riskofbiascriteriaandstudyqualityguide18,19.

Thequalityofevidencewasassessedthroughexaminingtheriskofbiasofeachstudy.ThereweresevenmajorbiasesassessedusingthechecklistbasedontheCochranecriteria,andweassignedscorestoeachstudyonthefollowingsevencategories:(1)randomsequencegeneration(selectionbias);(2)allocationconcealment(selectionbias);(3)blindingofparticipantsandpersonnel(performancebias);(4)blinding

ofoutcomeassessment(detectionbias);(5)incompleteoutcomedata(attritionbias);(6)selectivereporting(reportingbias);and(7)otherrisksofbias,includingpublicationbias.

Foreachcategory,astudyreceivedaratingoflow,high,orunclearrisk.Numericalratingcodeswereassignedtoeachofthethreeratings:lowriskwasassignedanumericalcodeof1,highriskanumerical

codeof0,andunclearriskanumericalcodeof0.5.Acompositequalityscoreforeachstudywascalculatedbyaveragingthesevennumericalratingcodes.Wethenratedeachstudybasedontheoverallqualityscore:low(<60%),medium(anaverage60-80%),orhigh(>=80%).

DatasynthesisConsistentwiththeExceltemplate,thedataanalysesfocusontwodimensions.Thefirstdimensionconcernedcharacteristicsofoverallstudyandimpactevaluation,whichexaminedHSSstrategies,

buildingblockstowhichinterventions/strategiesbelong,studydesignofimpactevaluation,primarymeasuresforimpactevaluation,andimpactofinterventions/strategiesifthiswasreported.Itshouldbenotedthatsometimes,therewereoverlapswhencategorizingaparticularintervention/strategyinto

buildingblocks.Forexample,comprehensivequalityimprovementprograms(blockofservicedelivery)sometimesincorporatedtrainingofhealthproviders(blockofhumanworkforce).Whenencounteringsuchcircumstance,coreresearchmembers(WZandHA)furtherexaminedtheoverallinterventionand

categorizeditbasedonthekeycomponentsandpurposesoftheintervention.Forexample,ifatrainingprogramwasasingleinterventionforanexistingandconventionaldeliveryapproach,wecategorizeditintotheblockofhumanworkforce.Ifthetrainingwaspartofaqualityimprovementpackage,orthe

trainingofhumanresourceswasforimplementinganewservicedeliverymodel,thenitwascategorizedintotheblockofservicedelivery.

Theseconddimensionoftheanalysiswasforcharacteristicsofeconomicevaluation/cost-effectivenessforeacharticle.Themajorcharacteristicsincludedperspectivesofcost-effectiveness,costcomponents,measuresandvalueofcost-effectiveness,anduseofsensitivityanalysis,aswellaslengthofcost-

9

effectivenessassessment(long-term[>=4years]orshort-termassessment[<4years]).Thecost-effectivenesswasreportedasUSDollars(USD)pereffectivenessmeasureintheyearwhencostsof

programswereexpressedandevaluatedinthearticle.Tostandardizecost-effectivenessmeasures,wealsolistedgrossdomesticproduct(GDP)percapitainthesameyearforcomparison.Forcost-effectivenessofstrategiesthatreportedascostperDALYavertedorcostperQALYgained,theWHO’s

CommissiononMacroeconomicsandHealthconsidersinterventions/strategiestobehighlycosteffectiveiftheyarelessthanonetimesGDPpercapita,andbeingcost-effectiveiftheyarelessthanthreetimesGDPpercapita20,21.

RESULTSOverviewofstudiesOfthe24selectedarticles,21wereobtainedfrompeerreviewarticles,andthreefromgreyliterature;23werepublishedsincetheyear2000,andonepublishedafewyearsprior.The24studieswereconductedin15countries,withfourinZambia,threeeachinUgandaandIndia,twoeachinBangladesh

andMalawi,andoneineachofremainingcountries(Argentina,Gambia,Kenya,Myanmar,Nepal,Niger,Nigeria,PapuaandNewGuinea,Ukraine,andZimbabwe).Geographically,therewere14studiesconductedinAfrica,7inAsia,1inOceania,1inEasternEurope,and1inCentralAmerica.Table3

providesdetailedinformationoftheselectedstudies.

10

Table3.Interventions,studydesignandimpactevaluationofincludedstudies

Lastnameofthefirstauthor

Publi-cationyear

BuildingBlock Country Region Interventions

Studydesignforimpactevaluation

Keymeasuresoftheimpactevaluation

Impactofintervention

Shepard22 2017 Financing Zimbabwe AfricaProvidefinancialincentivestohealthprovidersformaternalandchildhealthservices

Pre-postcontrolleddesign

Qualityindictors;institutionaldelivery,post-partumcare

RBFincreasedtheshareofinstitutionaldeliveriesby13.4%,andpost-partumtetanusvaccinationsby20.0%.

Zeng23 2017 Financing Zambia AfricaProvidefinancialincentivestohealthprovidersformaternalandchildhealthservices

cRCT

Institutionaldelivery,familyplanning,andqualityofcare

ComparedtoINP,RBFimprovedutilizationofHibvaccination(15.0%)andfamilyplanning(21.8%),andresultedinqualityofcarechangesrangingfrom-0.8%to+4.9%.ComparedtoCON,RBFimprovedqualityofcare,rangingfrom2.3%to9.7%,andsignificantlyincreasedutilizationofpostnatalcare(7.8%),institutionaldelivery(12.2%),Hib(19.1%)andfamilyplanning(19.5%)

Wang24 2016 Financing Zambia AfricaProvide'Mamakit'incentivestomothersconditionalondeliveringbabyinfacilities

cRCTUseofinstitutionaldelivery

Theoddsofdeliveringatafacilitywereincreasedby63%(29%-106%),oranincreaseof9.9percentagepoints.

Bishai25 2015Servicedelivery

Myanmar Asia

AddoralrehydrationsaltsandZinc(ORS-Z)asanadditionalproductlineinanexistingsocialfranchiseprogram.

Pre-postcontrolleddesign

UseofORS7.6%increaseinzincandORSuse,whichwouldtranslateto2.85(SD=0.29)incrementaldeathsavertedinatotalcommunitypopulationof1million.

Colbourn26 2015Servicedelivery

Malawi Africa

1.Mobilizecommunityaroundmaternalandneonatehealththroughwomen'sgroup(CI).2.Improvequalityofhealthfacilitiesthroughtrainingstaff,implementingchangepackagesfocusedonobstetricandnewborncare,conductingdeathreviews,leadershiptrainingandprotocol-basedclinicaltrainings(FI)

cRCT

Neonatalmortalityrate;maternalmortalityrate

Theneonatalmortalityratewas22%lowerinFI+CIthancontrolclusters(OR=0.78,95%CI0.60–1.01),andtheperinatalmortalityratewas16%lowerinCIclusters(OR=0.84,95%CI0.72–0.97).Nointerventioneffectsonmaternalmortality.

11

Gomez27 2015 Financing Nigeria AfricaImplementahealthinsuranceprogram,whichprovidedaccesstocomprehensivehealthcare.

Cohortstudy

Useofantenatalcareandinstitutionaldelivery

Accesstoantenatalcareincreasedfromo.65to0.85;institutionaldeliveryfrom0.50to0.675,withanestimated47deathsavertedper10,000deliveries.

Saya28 2015 Financing Uganda Africa

Implementcommunityhealthinsuranceschemescoveringimmunizationsandcurativeservices,aswellastransportforpregnantwomentoandfromcontractedfacilities.

Healthinsurance:Assumptionbasedonpriorstudy

Useoffacilitydelivery

1%insuranceincreaseinthehealthinsuranceenrollmentrateoftheentirepopulationwouldraisetheproportionoffacilitydeliveriesby0.9%fromitsinitialvalue

Gerler29 2014 Financing ArgentinaCentralAmer-ica

Providefinancialincentivestohealthprovidersformaternalandchildhealthservices

Pre-postcontrolleddesign

Neonatalmortalityrate

Beneficiaries’probabilityoflowbirth-weightisestimatedtobereducedby19percent.Beneficiarieshavea74percentlowerchanceofin-hospitalneonatalmortalityinlargerfacilities.

Alfonso30 2013 Financing Uganda Africa

ProvideeligiblepregnantwomenwithahealthvouchersforasubsidizedpriceofUS$1.40coveringfourANCvisits,deliverycare,referralandtreatmentofeventualcomplications,andapostnatalcarevisit.

Pre-postcontrolleddesign

Useofinstitutionaldelivery

ThedemandforbirthsatHFsenrolledinthevoucherschemeincreasedby52.3percentagepoints.Outofthisvalue,conservativeestimatesindicatethatatleast9.4percentagepointsarenewHFusers.This9.4%bumpinIDCimplies20deathsaverted

Broughton31 2013Servicedelivery

Niger Africa

Implementqualityimprovementprogramthroughclinicalandimprovementcapacity-buildingsessionsforparticipants;coachingvisitstoparticipatingsites;learningsessions;officepersonnelandadministrativesupport;andotherresourcesusedtocoordinatetheseactivities

Pre-postdesign

Postpartumhemorrhage;adherencetonewborncarestandards;maternalmortalityratio

Probabilityofpostpartumhemorrhagedecreasedfrom0.0202to0.00216;probabilityofadherencetonewborncarestandardsincreasedfrom0.185to0.975;maternalmortalityratiodecreasedfrom7.11to0.98per10,000births.

Fottrell32 2013Servicedelivery

Bangla-desh

Asia

Convenewomen’sgroupsforparticipatorylearningandactioncycleinwhichtheyprioritizeissuesthataffectedmaternalandneonatalhealth,anddesignandimplementstrategiestoaddresstheseissues.

cRCTNeonatalmortalityrate

Theneonatalmortalityratewassignificantlylowerintheinterventionarm(21.3neonataldeathsper1,000livebirthsvs30.1per1,000incontrolareas),areductioninneonatalmortalityof38%(riskratio,0.62[95%CI,0.43-0.89])whenadjustedforsocioeconomicfactors.

LeFevre33 2013Servicedelivery

Bangla-desh

Asia

1.Recruitandtrainingcommunityhealthworkers(CHWs)toconducthomevisitsduringpregnancyandpost-natalperiod.

cRCTNeonatalmortalityrate

Neonatalmortalitywasreducedinthehome-carearmby34%(adjustedrelativerisk0.66;95%CI0.47–0.93)duringthelast6monthsversusthatinthecomparison

12

2.Conductotherhealthsystemstrengtheningactivities:trainfacility-levelprovidersinMNHcare,distributedrugs&supplies,andestablishsystemfortrackingneonatalcare.

arm.Nomortalityreductionwasnotedinthecommunity-carearm(0.95;95%CI0.69–1.31).

Lewycka34 2013Servicedelivery

Malawi Africa

1.Recruitedandtrainedfacilitatorstoconvenewomen'sgroups.Women’sgroupsencouragedtoidentifyandadoptlocalstrategiestoimprovematernalandchildhealth.2.Volunteerpeercounsellorsmadehomevisitsduringpregnancyandpost-birthtosupportbreastfeedingandinfantcare.

Factorialclusterrandomizedtrial

Neonatalmortalityrate

Afteradjustmentforparity,socioeconomicquintile,andbaselinemeasures,effectswerelargerforNMR(0.85,95%CI0.59–1.22)andMMR(0.48,95%CI0.26–0.91).Becauseoftheinteractionbetweenthetwointerventions,astratifiedanalysiswasdone.Forwomen’sgroups,inadjustedanalyses,MMRfellby74%(0.26,95%CI0.10–0.70),andNMRby41%(0.59,95%CI0.40–0.86)inareaswithnopeercounsellors,buttherewasnoeffectinareaswithcounsellors(1.09,95%CI0.40–2.98,and1.38,95%CI0.75–2.54).Factorialanalysisforthepeercounsellinginterventionforyears1–3showedafallinIMRof18%(0.82,0.67–1.00)andanimprovementinEBFrates(2.42,1.48–3.96)

Barasa35 2012Servicedelivery

Kenya Africa

Implementqualityimprovementthroughemployingguidelines,training,supervision,feedback,andfacilitation,calledtheEmergencyTriageandTreatmentPlus(ETAT+)strategy.

cRCT

14processmeasures(e.g.child'sweightdocumented)

Theimpactwasassumedthattheinterventionproduceda1%-10%relativereductionofmortalityrateof7%.

Sabin36 2012HealthWork-force

Zambia Africa

Conduct4-daysessionsoftrainingtotraditionalbirthattendants(TBAs)toperforminterventionstargetingbirthasphyxia,hypothermia,andneonatalsepsis,followedby1–2dayrefreshertrainingsapproximatelyevery3–4monthsforthedurationofthetrial.

cRCTNeonatalmortalityrate

Neonatalmortalitywas45%loweramongliveborninfantsdeliveredbyinterventionbirthattendantsthancontrolbirthattendants(rateratio0.55,95%CI0.33to0.90).Deathsduetobirthasphyxiawerereducedby63%amonginfantsdeliveredbyinterventionbirthattendants(0.37,0.17to0.81)andby81%withinthefirsttwodaysafterbirth(0.19,0.07to0.52).

Manasyan37 2011HealthWork-force

Zambia Africa

Offertheessentialnewborncarecourse,whichincludeduniversalprecautionsandcleanliness;routineneonatalcare;initiationofbreathingandresuscitation;preventionofhypothermia;earlyandexclusivebreastfeeding;kangaroo(skin-to-skin)care;small

Pre-postdesignNeonatalmortalityrate

All-cause7-day(early)neonatalmortalitydecreasedfrom11.5per1,000to6.8per1,000livebirthsafterENCtrainingoftheclinicmidwives(relativerisk:0.59;95%confidenceinterval:0.48–0.77;40615births).

13

infantcare;counselingoninfantcare;anddangersigns,recognition,andinitialmanagementofillnesses.

Somigliana38 2011Servicedelivery

Uganda AfricaUseanambulancewithinahospital-⁄community-basedreproductivehealthservice.

Cohortstudy ReferralsNinety-twoobstetricalreferralswererecorded.Eleven(12%)wereconsideredeffective,correspondingto611.7yearssaved.

Nizalova39 2010Servicedelivery

UkraineEasternEurope

Implementacomprehensivemotherandinfanthealthproject(MIHP).TheMIHPpromotednewevidence-basedmedicine(EBM)standards:partnerdeliveries;avoidanceofunnecessaryC-sections,amniotomiesandepisiotomies;useoffreepositionduringdelivery;immediateskin-to-skincontact;earlybreastfeeding;andtherooming-inofmothersandnewborns.

Pre-postcontrolleddesign

Maternalandinfantdeaths

ThenumberofC-sectionsintheMIHPparticipatingRayonsdecreasesby4.71%orby132.17deliveriesonaverageperyear.TheestimatessuggestthattheMIHPparticipationonaveragetranslatesinto1.69fewermaternaldeathspermaternityperyearand5.63fewerinfantdeathsresultedfromdeviationsinperinatalperiod

Tripathy40 2010Servicedelivery

India Asia

1.Recruitandtrainfacilitatorstoconvenemonthlywomen’sgroupmeetings,andencouragewomen’sgroupstoadoptstrategiestoimprovematernalandneonatalhealth.2.Implementotherhealthsystemstrengtheningactivities(includingtraininginnewborncare,equipment&supplies)

cRCTNeonatalmortalityrate

NMRwas32%lowerininterventionclustersadjustedforclustering,stratification,andbaselinedifferences(oddsratio0.68,95%CI0.59-0.78)duringthe3years,and45%lowerinyears2and3(0.55,0.46-0.66).Althoughwedidnotnoteasignificanteffectonmaternaldepressionoverall,reductioninmoderatedepressionwas57%inyear3(0.43,0.23-0.80).

Bang41 2005Servicedelivery

India Asia

1.Trainfemalevillagehealthworkers(VHWs)todiagnoseandmanagebirthasphyxia(whensupportedbyTBAsatdelivery)incomparisonwithcurrentpracticewithTBAstrainedtomanagebirthasphyxia.

Pre-postdesign

Incidenceofmildbirthasphyxia;casefatalityofneonateswithsevereasphyxia

Theincidenceofmildbirthasphyxiadecreasedby60%,from14%intheobservationyear(1995to1996)to6%intheinterventionyears.Theincidenceofsevereasphyxiadidnotchangesignificantly,buttheCFinneonateswithsevereasphyxiadecreasedby47.5%,from39to20%andASMRby65%,from11to4%.Mouth-to-mouthresuscitationreducedtheASMRby12%,tube–maskfurtherreducedtheCFby27%andtheASMRby67%.

14

Bang42 2005Servicedelivery

India AsiaTrainvillagehealthworkerstoprovideneonatalcare

Pre-postcontrolleddesign

Neonatalmortalityrate

TheNMRintheinterventionareadecreasedfrom62to25.Thereductionincomparisontothecontrolareawas70%.ThereductionintheNMRwascreatedbythereductioninboththeearlyNMR(24points)andthelateNMR(20points).TheSBRdecreasedby49%;thePMRdecreasedby56%.

Borghi43 2005Servicedelivery

Nepal Asia

Trainingcommunityfacilitatorstoworkwithwomen’sgroupstodevelopstrategiesforimprovementofmaternalandneonatalhealth

cRCT

Neonatalmortalityrateandmaternalmortality

Interventiongroupachieveda29%reductioninneonatalmortalityandasubstantialreductioninmaternalmortalityduring33months

Duke44 2000Servicedelivery

PapuaandNewGuinea

OceaniaIntroduceminimalstandardsofneonatalcarein10areas

Pre-postdesignNeonatalmortalityrate

Thein-hospitalneonatalmortalityinthe30-monthperiodaftertheinterventionsbeganwas44%lower(relativerisk(RR)0.56).Afteradjustmentforahighernumberofneonates<1.5kginthepre-interventionperiod,therelativeriskwas0.59.Themortalityintheinterventionphaseforverylowbirthweightbabieswas56%lower(RR0.44)andformoderatelowbirthweight(1.5-2kg)50%lower(RR0.50)

Fox-Rushby45

1996Servicedelivery

Gambia Africa

Conductmobileoutreachservices,withtwomidwivesprovidingantenatalandfamilyplanningcarefor22villages,andvisitingvillagesregularly.

Pre-postcontrolleddesign

Neonatalmortalityrateandmaternalmortalityrate

Neonatalmortalityratewasreducedfrom32.2to16per1000livebirths,andmaternalmortalityratefrom7to3.1per1000livebirths.

Notes:cRCTdenotesclusterrandomizedcontroltrial,RBFdenotesresults-basedfinancing,INPdenotesinputfinancing,Hibdenoteshaemophilusinfluenzatypebvaccine,SDdenotesstandarddeviation,CIconfidenceinterval,ANCdenotesantenatalcare,CHWdenotescommunityhealthworker,NMRdenotesneonatalmortalityrate,MMRdenotesmaternalmortalityrate,IMRdenotesinfantmortalityrate,SBRdenotesstillbirthrate,PMRdenotesperinatalmortalityrate,EBFdenotesexclusivebreastfeeding,TBAdenotestraditionalbirthattendant,ASMRdenotesasphyxia-specificmortalityrate,CFdenotescasefatality.

15

StrategyofhealthsystemstrengtheningUsingthesixbuildingblockstocategorizethestudies,15wereonenhancingservicedelivery25,26,31-35,38-45,7onfinancing22-24,27-30,and2studiesonworkforce36,37.However,wefoundnostudiesoncost-effectivenessofthebuildingblocksofleadership/governance,information,andmedicalsupplies.

Forservicedelivery,strategiesweretakenatbothcommunity-andhealth-facilitylevels.Atthecommunitylevel,fivestudiesexaminedcommunitymobilizationthroughparticipatorywomen’sgroupsorpeercounselorstodevelopstrategiestoimprovematernalandneonatalmortalityrate26,32,34,40,43;threestudiesinvestigatedtrainingtocommunityhealthworkersforprovidingMCHservices(e.g.conductinghomevisits)33,41,42;andonestudyusedasocialmarketingapproachtodistributeoralrehydrationsaltsandzinc(ORS-Z)25.

Atthehealth-facilitylevel,strategiesundertakenincludedqualityimprovement26,31,35,39,44throughtraininghealthproviders,coachingvisits,supportingadministrativemanagement,andstrengtheningadherencetotreatmentguidelinesandstandards.Inonestudy,conductedinTheGambia,healthproviderswerealsoencouragedtoconductmoreoutreachactivitiestoexpandservicestopregnantwomenandinfantswhowouldotherwisebeneglected45Strategiestoprovidetransportationwereundertaken38toremoveabarrierforpregnantwomentoaccessMCHservices.

Similarly,variousapproachesonfinancingstrategieswerealsoimplemented.Fromthesupplyside,therewerethreearticlesonPBF22,23,29conductedinZambia,ZimbabweandArgentinarespectively,wherehealthproviderswereofferedfinancialincentivesforprovidingMCHservices.Fromthedemandside,twoarticlesconcernedhealthinsurance27,28;oneexaminedvoucherschemesthatofferredfinancialincentivestopregnantwomenforseekingMCHservices30;andonefromZambiareportedoffering“Mamakit”,anon-financialincentiveconditionalongivingbirthinhealthfacilities.

Onstrategiesconcerningworkforce,themajorinterventionwasprovidingtrainingtohealthpersonnel.Asmentionedearlier,thereexistedoverlapoftraininghealthprovidersbetweentheblockofhumanresourcesandservicedelivery.Thetwostudiescategorizedintheblockofworkforcewereforcapacitybuildingonlyanddidnothaveothercomplementaryactivities.Sabinetal.examinedthecost-effectivenessoftrainingtraditionalbirthattendantsinZambia36,whileManasyanfocusedontrainingrelatedtohealthprovidersonessentialnewborncare37.

StudydesignandassessmentofstudyqualityOfthe24articles,10appliedclusterrandomizedcontroltrial(cRCT)design;7,pre-postcontrolleddesign;and4,pre-postdesignwithoutacontrolgroup.Thereweretwostudiesusingcohortstudydesign,followingupresearchsubjectsoveracertainperiodandobservinghealthoutputsoroutcomes.Thelaststudyusedparametersfromanothercountrytoestimateeffectiveness28.

Basedonthegradingprocessdescribedinthemethodssection,theaveragequalityscoreforthe24articleswas82%,with15articleswereratedashighquality,5asmediumquality,and4aslowquality.Theprimaryreasonsforlowqualitygradeweredefectedstudydesigninassessingtheprogram’simpact,inappropriateapproachestoconverthealthoutputstooutcomes,ormissingsomecostcomponents.

16

Dependingonperspectivesofthestudies,costcomponentsofthe24articlesvariedsubstantially.Fourstudiesexaminedcostsfromtheproject/program’sperspective37,39,40,43,whichdidnotaccountforcostsoccurredinhealthfacilities,eitherinpublicorprivatesettings.Nordiditaccountforcostsbornebyhouseholds.AsmostinterventionsintendedtoimproveutilizationofMCHservices,withoutconsideringpotentialincreasedcostsduetoimproveduseofservices,cost-effectivenessofinterventionsmaybeoverestimated.Onestudyonlycostedequipmentandsuppliers44,whichmightsubstantiallyinflatethecost-effectivenessoftheintervention.

MeasuresofcostandeffectivenessTable4providesdetailedinformationoncost-effectivenessfromthe24articles.Intotal,38cost-effectivenessvalueswereobtained.Onlyfivevaluesprovidethelongtermcost-effectivenessoftheprogram(Lengthofassessment>=4years).Astostudyperspectives,22values(57.89%)werefromthehealthprovider’sperspective,eight(21.05%)fromtheprogram/project’sperspective,andeight(21.05%)fromthesocietalperspective.

17

Table4.Characteristicsofcost-effectivenessanalysisofincludedstudies

Lastnameofthefirstauthor

Perspective

Yearofdollarexpressed

Lengthenof

assessment(months)

Intervention Comparator/scenarios CEvalue CEmeasure

Sensitivity

analysis

GDP/capita(USD)∆

TimesofGDP/capita

Colbourn26 Healthprovider 2013 27 Communitymobilization CIvsSQ 79 DALYaverted Yes 317 0.249

Colbourn26 Healthprovider 2013 27 Qualityimprovement FIvsSQ 281 DALYaverted Yes 317 0.886

Colbourn26 Healthprovider 2013 27 CI+FI CI+FIvsSQ 146 DALYaverted Yes 317 0.461

Gomez27 Healthprovider 2012 144 Healthinsurance IntvsSQ 46 DALYaverted Yes 2,798 0.017

Saya28 Healthprovider 2013* Notclear Healthinsurance IntvsSQ 298 DALYaverted No 681 0.438

Gerler29 Healthprovider 2005 60 PBF IntvsSQ 814 DALYaverted Yes 5,164 0.158

Bang42 Healthprovider 2003* 84 VHWstraining IntvsSQ 6.8 DALYaverted No 572 0.012

Broughton31 Healthprovider 2008 30 Qualityimprovement IntvsSQ 147 DALYaverted No 382 0.385

Barasa35 Healthprovider 2011 18 Qualityimprovement IntvsSQ(Bestcase) 40 DALYaverted Yes 1,062 0.037

Barasa35 Healthprovider 2011 18 Qualityimprovement IntvsSQ(Worstcase) 398 DALYaverted Yes 1,062 0.375

LeFevre33 Program 2010 30 CHWstraining IntvsSQ 103 DALYaverted Yes 808 0.128

Alfonso30 Program 2010 37 Voucherscheme IntvsSQ 338 DALYaverted Yes 594 0.569

Manasyan37 Program 2005 24 Midwifetraining IntvsSQ 5.2 DALYaverted No 692 0.008

Alfonso30 Societal 2010 37 Voucherscheme IntvsSQ 302 DALYaverted Yes 594 0.508

LeFevre33 Societal 2010 30 CHWstraining IntvsSQ 105 DALYaverted Yes 808 0.129

Bishai25 Societal 2010 10 Socialmarketing IntvsSQ 214 DALYaverted Yes 997 0.215

Sabin36 Societal 2011 120 TBAstraining IntvsSQ 74 DALYaverted Yes 1,636 0.045

Shepard22 Healthprovider 2013 27 PBF IntvsSQ 662 QALYgained Yes 1,005 0.659

Zeng23 Healthprovider 2013 27 PBF Intvsinputfinancing 1,350 QALYgained Yes 1,840 0.734

Zeng23 Healthprovider 2013 27 PBF Intvspurecontrol 809 QALYgained Yes 1,840 0.440

Lewycka34 Healthprovider 2010 72 Communitymobilization IntvsSQ 33-114 LYS No 443 0.075-0.257

Somigliana38 Healthprovider 2009 3 Ambulanceservice IntvsSQ 16 LYS Yes 565 0.028

Tripathy40 Program 2007 36 Communitymobilization Women'sgroupvsSQ 33 LYS Yes 1,081 0.031

Tripathy40 Program 2008 36 Communitymobilization women'sgroup+HSSvsSQ 48 LYS Yes 1,081 0.044

18

Borghi43 Program 2003 33 Communitymobilization IntvsSQ 211 LYS Yes 254 0.831

Fottrell32 Healthprovider 2011 24 Communitymobilization IntvsSQ 330 LYS No 857 0.385

Fox-Rushby45 Societal 1991 24 Mobileoutreach IntvsSQ(Best-Worstcase) 42.9-459.0 DiscountedLYS Yes 486 0.088-0.944

Nizalova39 Program 2005 72 Qualityimprovement IntvsSQ 0.01 Dollargained No 1,910 -

Wang24 Healthprovider 2013* 11 Mamakit IntvsSQ 5,183 Lifesaved No 1,840 2.817

Bang41 Healthprovider 2003* 84 VHWstraining IntvsSQ 13 Lifesaved No 572 0.023

Bang42 Healthprovider 2003* 84 VHWstraining IntvsSQ 150.5 Lifesaved No 572 0.263

Duke44 Healthprovider 1998* 30 Qualityimprovement IntvsSQ 445 Lifesaved No 1,158 0.384

Alfonso30 Healthprovider 2010 37 Voucherscheme IntvsSQ 22,933 Lifesaved Yes 594 38.608

Fottrell32 Healthprovider 2011 24 Communitymobilization IntvsSQ 10,053 lifesaved No 857 11.730

Manasyan37 Program 2005 24 Midwifetraining IntvsSQ 208 Lifesaved No 692 0.301

Alfonso30 Societal 2010 37 Voucherscheme IntvsSQ 20,575 Lifesaved Yes 594 34.638

Bishai25 Societal 2010 10 Socialmarketing IntvsSQ 5,955 Lifesaved Yes 997 5.973

Fox-Rushby45 Societal 1991 24 Mobileoutreach IntvsSQ(Best-Worstcase) 206.3-2,134.0 Lifesaved Yes 486 0.424-4.391

*Bestguess;∆source:internationalmonetaryfund,availableathttp://www.imf.org/external/pubs/ft/weo/2016/02/weodata/index.aspx.CEdenotescost-effectiveness,GDPdenotesgrossdomesticproduct,Intdenotesintervention,SQdenotesstatusquo,HSSdenoteshealthsystemstrengthening,CIdenotescommunityintervention,FIdenotesfacilityintervention,TBAsdenotestraditionalbirthattendants,VHWsdenotesvillagehealthworkers,PBFdenotesperformancebasedfinancing,LYSdenoteslifeyearsaved,DALYdenotesdisabilityadjustedlifeyear,QALYdenotesqualityadjustedlifeyear.

19

Ofthe38valuesofcost-effectiveness,17weremeasuredwithDALYsaverted,followedby10usinglivessaved,6usinglifeyearsaved,3usingQALYsgained,1usingdiscountedlifeyearsaved,and1usingdollarsgained.

Ifcost-effectivenesswereexaminedusingthesameperspective,forthestudiesreportingDALYorQALYs,thevaluescouldbecompared.ComparedtothebenchmarkofGDPpercapita,all13cost-effectivenessvaluesreportedascostperDALYavertedorQALYgainedfromthehealthprovider’sperspectivewerelessthanonetimesGDPpercapita(Table5),suggestingthatassociatedinterventionswerehighlycost-effective.Amongthem,thetrainingofvillagehealthworkersinIndiahadthelowestcost-effectivenessratioandthelowestrelativecost-effectivenesstoitsGDP/capita.ThethreePBFprogramshadcost-effectivenessratiosrangingfrom$662to$1350/DALYavertedorQALYgained.TheirrelativevaluestoGDPpercapitaspannedfrom0.158to0.734,indicatingthatPBFwasamongthehighlycost-effectiveinterventionsinaddressingMCH.

Table5.Cost-effectivenessreportedascost/DALYavertedorQALYgainedfromhealthprovider'sperspective

Lastnameofthefirstauthor Intervention Comparator/scenarios

Cost/DALYavertedorcost/QALYgained

TimesofGDP/capita

Bang42 VHWstraining IntvsSQ 6.8 0.012Gomez27 Healthinsurance IntvsSQ 46.4 0.017Barasa35 Qualityimprovement IntvsSQ(Bestcase) 39.8 0.037Gerler29 PBF IntvsSQ 814.0 0.158Colbourn26 Communitymobilization CIvsSQ 79.0 0.249Barasa35 Qualityimprovement IntvsSQ(Worstcase) 398.3 0.375Broughton31 Qualityimprovement IntvsSQ 147.0 0.385Saya28 Healthinsurance IntvsSQ 298.0 0.438Zeng23 PBF Intvspurecontrol 809.0 0.440Colbourn26 CI+FI CI+FIvsSQ 146.0 0.461Shepard22 PBF IntvsSQ 662.0 0.659Zeng23 PBF Intvsinputfinancing 1,350.0 0.734Colbourn26 Qualityimprovement FIvsSQ 281.0 0.886

Notes:DALYdenotesdisabilityadjustedlifeyear,QALYdenotesqualityadjustedlifeyear,GDPdenotesgrossdomesticproduct;VHWsdenotesvillagehealthworkers,Intdenotesintervention,SQdenotesstatusquo,CIdenotescommunityintervention,FIdenotesfacilityintervention,PBFdenotesperformancebasedfinancing.

DISCUSSIONThissystematicreviewidentified24articlesoncost-effectivenessofHSSinterventionsforimprovingMCH.ThemajorHSSinterventionsconcernservicedelivery,healthfinancing,andhumanworkforce.Noneofthearticlesreportedongovernance/leadership,supplychain,orinformationsystems.

20

Consistenttowhathadbeensynthesizedbeforeoncost-effectivenessofoverallstrategiesinimprovingMCH46,thisreviewofHSSstrategieshasalsofoundthatcountriestakediverseapproachestoaddresstheirhealthsystemgapsinrespondingtoMCHconcerns.Forexample,inBangladesh,whereawarenessofMCHservicesislowandthereexistsadynamicnon-governmentalorganizationsector47,communitymobilizationprogramsarepilotedandtested32,33.Incontrast,incountriessuchasKenyaandNigeria,wherequalityofhealthcareisamajorconcern,qualityimprovementprogramsthroughtrainingpersonnelandstrengtheningadherencetoprotocolareimplemented31,35.Toaddressfinancialbarriersforpregnantwomen,strategiessuchashealthinsuranceandvoucherschemes,aswellasprovidingambulanceservices,arecarriedouttoimproveMCHservicecoverageandoutcomes27,28,30,38.Eachcountryhasitsownhealthsystemconcerns.Todesigncost-effectivehealthsysteminterventions,itisimportanttoconducthealthsystemdiagnosistoidentifyhealthsystemmalfunctions48,inordertodesignmoretargetedandeffectiveinterventions.

WealsofoundthatthediversityofHSSstrategiesliesinboththesupply-anddemand-sideinterventions.Fromthesupplyside,HSSstrategiestargetinghealthservicesproviders(e.g.hospitals,healthclinics,andmedicalpersonnel)taketheformof,forexample,traininghealthpersonnel,directprovisionofequipment,andincentivizinghealthproviders,andtheyareinstrumentalinensuringqualityofcareandreachingouttotargetedpopulationstodeliverservices.Donorsplayanimportantroleinsupportingsupplyinterventions4.Ontheotherhand,demand-sidestrategiesaredirectlytargetedtousersofhealthcareservices,suchaspregnantwomenandchildren.Communityengagementandprovidingfinancialornon-financialincentivestoserviceusersarethemostcommondemandsideinterventions10.Asdemandforhealthservicesincreases,itisexpectedthattheuseofneededserviceswouldincrease.Areviewshowsthat,overall,demand-sideinterventionsincreasetheuseofhealthservices,butdonotnecessarilyimprovehealthoutcomes.10ToaddressMCHmoreeffectively,itiscriticaltoleveragestrengthsofbothsupply-anddemand-sidestrategies.InCambodia,itwasreportedthattheeffectsofPBFonMCHservicesquadrupledwhenitwasimplementedsimultaneouslywithavoucherscheme49.Similarly,Colbournetal.examinedcost-effectivenessofcombineddemandsideandsupplysideinterventionsandfoundalowercost-effectivenessratioforthecombinedapproachthansupplysideinterventionalone26,suggestingstrongsynergybetweendemandandsupplysideinterventions.Whendesigningcomprehensiveprograms,policymakersshouldtakeaholisticapproachthatconsiderssynergiesamongprogramsinordertoachievebetteroutcomeswithlowercosts.ThecomplementaritiesamongHSSinterventionsmayprecludealeaguetableapproachtoreporttheircost-effectiveness.

Weextractedcost-effectivenessvaluesfromthe24articles,inthehopeofmakingacomparisonamongthem.However,thestudiesuseddifferentcost-effectivenessmeasures,tookdifferentperspectivesofanalysis,andapplieddifferentassumptionsformodelling,whichsignificantlylimitedthecomparabilityamongstudies.Eventhoughsomestudiesunderthereviewusedthesamecost-effectivenessmeasuresandtookthesameperspective,someresultswerestillnotcomparable,dueto,forexample,costcomponentsincludedintheanalysis,asmentionedintheResultssection.Inaddition,costeffectivenesscomparisonsweredifficultbecauseoftheinconsistencyinapproachesusedinmeasuringeffectiveness.Somestudiesusedmeasuresofchangesofmortalityrate,fromwhichDALYsavertedorQALYsgainedcouldbederiveddirectly.Otherstudiescollectedchangesofutilizationofhealthservicesasimpact

21

measures.Thus,modellingwasneededtoconvertutilizationofservicestohealthoutcomesforcost-effectivenessanalyses.Oftenmodellingreliesoninternationalliterature,whichmaynotprovideaccurateparametersforthecountrywheretheprogramwasimplemented.Withonly24articlesfoundoneconomicevaluationofHSSinterventionsforMCH,itiscriticaltogeneratemorerelevantevidencethroughconductingcost-effectiveness/benefitstudies,inordertohelpdonorsandgovernmentsmakeHSSinvestments.

SpecificallyforPBF,oneofthemajorHSSinterventionsappliedinLMICs,impactevaluationofPBFprogramsgenerallydemonstratesapositiveimpactoffinancialincentivesonqualityandcoverageofMCHservices11,22,23,29,50,51,suchasprenatalcare,institutionaldeliveries,andpostnatalcare.Whencombiningwithassociatedcosts,althoughcostly,PBFprogramsprovetobehighlycost-effective,whethertheyaremodelledthroughhealthoutcomes22,23orthroughdirectexaminationofmaternalandneonatalmortalityrates29.AsthecoverageofservicesincreasesthroughPBF,PBFprogramsmayneedtoswitchtheirfocustotheimprovementofqualityofcareinthefuture.Giventhechallengeinmodellingthehealthimpactofqualityofcare,directexaminationofchangesofmortalityratesattributabletoPBFwouldbemoreappropriatewhenconductingcost-effectivenessanalysisortheimpactevaluationoffuturePBFprograms52.Table5showsthattherearethreeHSSinterventions,suchastrainingofvillagehealthworkers42,healthinsurance27,qualityimprovement35,havingalowerrelativecost-effectivenessratiothanthePBFprogramwiththelowestrelativecost-effectivenessratio29.Thosethreestudieswereconductedonarelativelysmallerscale(e.g.coveragepopulation)thanwastheRBFprogram.Itislikelythatasthoseprogramsscaleup,theircost-effectivenessratiomayincreasegivendiminishingreturnstoinvestment.

Itshouldalsobenotedthatamongthe24articles,onlyafewstudiesexaminedlong-termcost-effectivenessofinterventions.Perhaps,duetotimeandbudgetconstraints,mostcost-effectivenessstudiesincludedinthisreviewwereforshort-termassessmentwiththelengthofassessmentlessthanfouryears.Giventhatsomestart-upcostscouldbesharedforalongerperiodandthatprogrammanagementandimplementationskillsimproveovertime,cost-effectivenessofamatureprogramwithalongimplementationperiodtendstobelower.Bangetal.estimatedthatoverthesevenyearsoftheirstudy,thecost-effectivenessratiofortrainingvillagehealthworkersinIndiawasonly0.12timesofGDPpercapita41,oneofthelowestcost-effectivenessratiosamongalltheinterventions.Morestudiesshouldbeconductedtoexaminelong-termcost-effectivenessofaprogramforinformedpolicy-making.Atthesametime,policymakersshouldalsobeawareofthelengthofcost-effectivenessassessments,andgaugetheprogram’slong-termcost-effectivenesswhenmakingdecisions.

Severallimitationsofthisreviewshouldbeacknowledged.First,althoughweendeavoredtoobtainasmanystudiesaspossibleforscreening,wewerenotabletoreviewallrecordsfromthelargeamountofsearchresultsfromGoogleScholar.Missingsomerelevantstudiesispossible.Second,mostinterventionswerecost-effective,andsomestudieshadaverylowcost-effectivenessratio,whichmaysuggestunderreportingofnegativeresults.Third,giventhebroaddefinitionofhealthsystems,wehadtolimitthescopeofinterventionstosomedomainsofthehealthsystem,particularlyaroundservicedelivery,wherewelimitedthesearchtoqualityimprovementandinnovativedeliverymodels.Inspiteof

22

theselimitations,thisreviewassembledevidenceonHSSinterventions,contributingtoabetterunderstandingofHSSinaddressingMCHandevidence-baseddecisionmaking.

23

REFERENCES1. AlkenbrackS,ChaitkinM,ZengW,CoutureT,SharmaS.DidEquityofReproductiveandMaternalHealthServiceCoverageIncreaseduringtheMDGEra?AnAnalysisofTrendsandDeterminantsacross74Low-andMiddle-IncomeCountries.PloSone2015;10(9):e0134905.2. YouD,HugL,EjdemyrS,etal.Global,regional,andnationallevelsandtrendsinunder-5mortalitybetween1990and2015,withscenario-basedprojectionsto2030:asystematicanalysisbytheUNInter-agencyGroupforChildMortalityEstimation.Lancet2015;386(10010):2275-86.3. GBD2015MaternalMortalityCollaborators.Global,regional,andnationallevelsofmaternalmortality,1990-2015:asystematicanalysisfortheGlobalBurdenofDiseaseStudy2015.Lancet2016;388(10053):1775-812.4. ValentineA,WexlerA,OumS,KatesJ.Donorfundingsforhealthinlow-andmiddle-incomecountries,2002-2013.MenloPark,CA:KaiserFamilyFoundation,2015.5. AmericanPublicHealthAssociation.Strengtheninghealthsystemsindevelopingdountries.2008.http://www.apha.org/policies-and-advocacy/public-health-policy-statements/policy-database/2014/07/23/09/09/strengthening-health-systems-in-developing-countries(accessedFeb142017).6. HealthFinance&GovernanceProject.Projectinformation:Strongerhealthsystems:Expandingaccesstocare,improvinghealth.https://www.hfgproject.org/about-hfg/project-information/(accessedFeb142017).7. Palladium.USAIDawardshealthpolicyplus(HP+)toPalladium.2015.http://www.prnewswire.com/news-releases/usaid-awards-health-policy-plus-hp-to-palladium-300158862.html(accessedFeb142017).8. WarrenAE,WyssK,ShakarishviliG,AtunR,deSavignyD.Globalhealthinitiativeinvestmentsandhealthsystemsstrengthening:acontentanalysisofglobalfundinvestments.GlobalHealth2013;9(1):30.9. RBFHEALTH.Mission:Overview.2017.https://www.rbfhealth.org/mission(accessedMar182017).10. HurstTE,SemrauK,PatnaM,GawandeA,HirschhornLR.Demand-sideinterventionsformaternalcare:evidenceofmoreuse,notbetteroutcomes.BMCPregnancyChildbirth2015;15:297.11. BasingaP,GertlerPJ,BinagwahoA,SoucatAL,SturdyJ,VermeerschCM.EffectonmaternalandchildhealthservicesinRwandaofpaymenttoprimaryhealth-careprovidersforperformance:animpactevaluation.Lancet2011;377(9775):1421-8.12. WitterS,SomanathanA.Demand-sidefinancingforsexualandreproductivehealthservicesinlowandmiddle-incomecountries:areviewoftheevidence.TheWorldBank,PolicyResearchWorkingPaperSeries:6213;2012.13. Turcotte-TremblayAM,SpagnoloJ,DeAllegriM,RiddeV.Doesperformance-basedfinancingincreasevalueformoneyinlow-andmiddle-incomecountries?Asystematicreview.HealthEconomicsReview2016;6(1):30.14. DepartmentforInternationalDevelopment.DFID'sapproachtovalueformoney(VfM)London,UK:DepartmentforInternationalDevelopment,2011.15. ChambersJD,LordJ,CohenJT,NeumannPJ,BuxtonMJ.Illustratingpotentialefficiencygainsfromusingcost-effectivenessevidencetoreallocateMedicareexpenditures.ValueinHealth2013;16(4):629-38.16. WorldHealthOrganization.Everybodybusiness:strengtheninghealthsystemstoimprovehealthoutcomes:WHO’sframeworkforaction.Geneva,Switzerland:WorldHealthOrganization,2007.17. LunzeK,Higgins-SteeleA,Simen-KapeuA,VeselL,KimJ,DicksonK.Innovativeapproachesforimprovingmaternalandnewbornhealth--Alandscapeanalysis.BMCPregnancyChildbirth2015;15:337.

24

18. CochraneConsumer&CommunicationReviewGroup.Studyqualityguide:Guideforreviewauthorsonassessingstudyquality:TheCochrameCollaboration,2013.19. HigginsJPT,GreenS.Cochranehandbookforsystematicreviewsofinterventions:TheCochraneCollaboration;2011.20. HutubessyR,ChisholmD,EdejerTT.Generalizedcost-effectivenessanalysisfornational-levelpriority-settinginthehealthsector.CostEffectivenessandResourceAllocation2003;1(1):8.21. WorldHealthOrganization.Tables:Thresholdvaluesforinterventioncost-effectivenessbyregion.2017.http://www.who.int/choice/costs/CER_levels/en/.22. ShepardDS,ZengW,MutasaR,etal.Cost-effectivenessofresults-basedfinancinginZimbabwe:acontrolledpre-poststudy.Washington,DC:WorldBank,2017.23. ZengW,ShepardDS,NguyenHT,etal.Cost-effectivenessanalysisofresults-basedfinancinginZambia:Resultsfromaclusterrandomizedtrial.Washington,DC:WorldBank,2017.24. WangP,ConnorAL,GuoE,etal.Measuringtheimpactofnon-monetaryincentivesonfacilitydeliveryinruralZambia:aclusteredrandomisedcontrolledtrial.TropicalMedicineandInternationalHealth2016;21(4):515-24.25. BishaiD,SachathepK,LeFevreA,etal.Cost-effectivenessofusingasocialfranchisenetworktoincreaseuptakeoforalrehydrationsaltsandzincforchildhooddiarrheainruralMyanmar.CostEffectivenessandResourceAllocation2015;13:3.26. ColbournT,Pulkki-BrannstromAM,NambiarB,etal.Cost-effectivenessandaffordabilityofcommunitymobilisationthroughwomen'sgroupsandqualityimprovementinhealthfacilities(MaiKhandatrial)inMalawi.CostEffectivenessandResourceAllocation2015;13(1):1.27. GomezGB,FosterN,BralsD,etal.ImprovingMaternalCarethroughaState-WideHealthInsuranceProgram:ACostandCost-EffectivenessStudyinRuralNigeria.PloSone2015;10(9):e0139048.28. SayaU,ShepardDS,BasazaRK,etal.Cost-effectivenessofreproductivehealthvouchersandcommunity-basedhealthinsuranceinUganda:Arlington,Virginia,AfricanStrategiesforHealth,2015Jun.,2015.29. GertlerP,GiovagnoliP,MartinezS.Rewardingproviderperformancetoenableahealthystarttolife:EvidencefromArgentina'sPlanNacer.Washington,DC:WorldBank,2014.30. AlfonsoYN,BishaiD,BuaJ,MutebiA,MayoraC,Ekirapa-KirachoE.Cost-effectivenessanalysisofavoucherschemecombinedwithobstetricalqualityimprovements:quasiexperimentalresultsfromUganda.Healthpolicyandplanning2015;30(1):88-99.31. BroughtonE,SaleyZ,BoucarM,etal.Cost-effectivenessofaqualityimprovementcollaborativeforobstetricandnewborncareinNiger.Internationaljournalofhealthcarequalityassurance2013;26(3):250-61.32. FottrellE,AzadK,KuddusA,etal.Theeffectofincreasedcoverageofparticipatorywomen'sgroupsonneonatalmortalityinBangladesh:Aclusterrandomizedtrial.JAMApediatrics2013;167(9):816-25.33. LeFevreAE,ShillcuttSD,WatersHR,etal.Economicevaluationofneonatalcarepackagesinacluster-randomizedcontrolledtrialinSylhet,Bangladesh.BulletinoftheWorldHealthOrganization2013;91(10):736-45.34. LewyckaS,MwansamboC,RosatoM,etal.Effectofwomen'sgroupsandvolunteerpeercounsellingonratesofmortality,morbidity,andhealthbehavioursinmothersandchildreninruralMalawi(MaiMwana):afactorial,cluster-randomisedcontrolledtrial.Lancet2013;381(9879):1721-35.35. BarasaEW,AyiekoP,ClearyS,EnglishM.AmultifacetedinterventiontoimprovethequalityofcareofchildrenindistricthospitalsinKenya:acost-effectivenessanalysis.PLoSmedicine2012;9(6):e1001238.

25

36. SabinLL,KnappAB,MacLeodWB,etal.Costsandcost-effectivenessoftrainingtraditionalbirthattendantstoreduceneonatalmortalityintheLufwanyamaNeonatalSurvivalstudy(LUNESP).PloSone2012;7(4):e35560.37. ManasyanA,ChombaE,McClureEM,WrightLL,KrzywanskiS,CarloWA.Cost-effectivenessofessentialnewborncaretraininginurbanfirst-levelfacilities.Pediatrics2011;127(5):e1176-81.38. SomiglianaE,SabinoA,NkurunzizaR,etal.Ambulanceservicewithinacomprehensiveinterventionforreproductivehealthinremotesettings:acost-effectiveintervention.TropicalMedicineandInternationalHealth2011;16(9):1151-8.39. NizalovaOY,VyshnyaM.EvaluationoftheImpactoftheMotherandInfantHealthProjectinUkraine.HealthEconomics2010;19:107-25.40. TripathyP,NairN,BarnettS,etal.Effectofaparticipatoryinterventionwithwomen'sgroupsonbirthoutcomesandmaternaldepressioninJharkhandandOrissa,India:acluster-randomisedcontrolledtrial.Lancet2010;375(9721):1182-92.41. BangAT,BangRA,BaituleSB,ReddyHM,DeshmukhMD.ManagementofbirthasphyxiainhomedeliveriesinruralGadchiroli:theeffectoftwotypesofbirthattendantsandofresuscitatingwithmouth-to-mouth,tube-maskorbag-mask.JournalofPerinatology2005;25Suppl1:S82-91.42. BangAT,BangRA,ReddyHM.Home-basedneonatalcare:SummaryandapplicationsofthefieldtrialinruralGadchiroli,India(1993to2003).JournalofPerinatology2005;25Suppl1:S108-S22.43. BorghiJ,ThapaB,OsrinD,etal.Economicassessmentofawomen'sgroupinterventiontoimprovebirthoutcomesinruralNepal.Lancet2005;366(9500):1882-4.44. DukeT,WillieL,MgoneJM.Theeffectofintroductionofminimalstandardsofneonatalcareonin-hospitalmortality.PNGMedicalJoural2000;43(1-2):127-36.45. Fox-RushbyJA,FoordF.Costs,effectsandcost-effectivenessanalysisofamobilematernalhealthcareserviceinWestKiang,TheGambia.Healthpolicy(Amsterdam,Netherlands)1996;35(2):123-43.46. Mangham-JefferiesL,PittC,CousensS,MillsA,SchellenbergJ.Cost-effectivenessofstrategiestoimprovetheutilizationandprovisionofmaternalandnewbornhealthcareinlow-incomeandlower-middle-incomecountries:asystematicreview.BMCPregnancyChildbirth2014;14:243.47. AhmedSM,EvansTG,StandingH,MahmudS.HarnessingpluralismforbetterhealthinBangladesh.Lancet2013;382(9906):1746-55.48. BalabanovaD,McKeeM,MillsA,WaltG,HainesA.Whatcanglobalhealthinstitutionsdotohelpstrengthenhealthsystemsinlowincomecountries?HealthResearchPolicyandSystems2010;8:22.49. VandePoelE,FloresG,IrP,O'DonnellO.ImpactofPerformance-BasedFinancinginaLow-ResourceSetting:ADecadeofExperienceinCambodia.HealthEconomics2016;25(6):688-705.50. ZengW,CrosM,WrightKD,ShepardDS.Impactofperformance-basedfinancingonprimaryhealthcareservicesinHaiti.Healthpolicyandplanning2013;28(6):596-605.51. SoetersR,PeerenboomPB,MushagalusaP,KimanukaC.Performance-basedfinancingexperimentimprovedhealthcareintheDemocraticRepublicofCongo.HealthAffairs(Millwood)2011;30(8):1518-27.52. MakateM,MakateC.Theimpactofprenatalcarequalityonneonatal,infantandchildmortalityinZimbabwe:evidencefromthedemographicandhealthsurveys.Healthpolicyandplanning2016.