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Economic evaluation of Community Level Interventions for Pre-eclampsia (CLIP) in South Asian and African… Khowaja, Asif R; Mitton, Craig; Bryan, Stirling; Magee, Laura A; Bhutta, Zulfiqar A; von Dadelszen, Peter May 26, 2015

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STUDY PROTOCOL Open AccessEconomic evaluation of Community LevelInterventions for Pre-eclampsia (CLIP) in SouthTrial registration: ClinicalTrials.gov: NCT01911494ImplementationScienceKhowaja et al. Implementation Science  (2015) 10:76 DOI 10.1186/s13012-015-0266-5Research Institute, Vancouver, CanadaFull list of author information is available at the end of the articleKeywords: Economic evaluation, Cost-effectiveness, Community-based interventions, Pre-eclampsia,Low-middle-income countries* Correspondence: craig.mitton@ubc.ca2School of Population and Public Health, University of British Columbia,Vancouver, Canada3Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal HealthAsian and African countries: a study protocolAsif R. Khowaja1,3,4, Craig Mitton2,3*, Stirling Bryan2,3, Laura A. Magee1, Zulfiqar A. Bhutta4,5 and Peter von Dadelszen1AbstractBackground: Globally, hypertensive disorders of pregnancy, particularly pre-eclampsia and eclampsia, are the leadingcause of maternal and neonatal mortality, and impose substantial burdens on the families of pregnant women, theircommunities, and healthcare systems. The Community Level Interventions for Pre-eclampsia (CLIP) Trial evaluates apackage of care applied at both community and primary health centres to reduce maternal and perinatal disabilitiesand deaths resulting from the failure to identify and manage pre-eclampsia at the community level. Economicevaluation of health interventions can play a pivotal role in priority setting and inform policy decisions forscale-up. At present, there is a paucity of published literature on the methodology of economic evaluation oflarge, multi-country, community-based interventions in the area of maternal and perinatal health. This studyprotocol describes the application of methodology for economic evaluation of the CLIP in South Asia and Africa.Methods: A mixed-design approach i.e. cost-effectiveness analysis (CEA) and qualitative thematic analysis will be usedalongside the trial to prospectively evaluate the economic impact of CLIP from a societal perspective. Data on healthresource utilization, costs, and pregnancy outcomes will be collected through structured questionnaires embeddedinto the pregnancy surveillance, cross-sectional survey and budgetary reviews. Qualitative data will be collectedthrough focus groups (FGs) with pregnant women, household male-decision makers, care providers, and district levelhealth decision makers. The incremental cost-effectiveness ratio will be calculated for healthcare system and societalperspectives, taking into account the country-specific model inputs (costs and outcome) from the CLIP Trial. Emergingthemes from FGs will inform the design of the model, and help to interpret findings of the CEA.Discussion: The World Health Organization (WHO) strongly recommends cost-effective interventions as a key aspect ofachieving Millennium Development Goal (MDG)-5 (i.e. 75 % reduction in maternal mortality from 1990 levels by 2015).To date, most cost-effectiveness studies in this field have focused specifically on the diagnostic and clinicalmanagement of pre-eclampsia, yet rarely on community-based interventions in low-and-middle-income countries(LMICs). This study protocol will be of interest to public health scientists and health economists undertakingcommunity-based trials in the area of maternal and perinatal health, particularly in LMICs.© 2015 Khowaja et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.Khowaja et al. Implementation Science  (2015) 10:76 Page 2 of 14BackgroundGlobally, hypertensive disorders of pregnancy (HDP),particularly pre-eclampsia and eclampsia, are the leadingcause of maternal and neonatal mortality and impose sub-stantial burdens on the families of pregnant women, theircommunities, and healthcare systems [1, 2]. Pre-eclampsiaoccurs when the pregnant woman has concurrent hyper-tension and significant proteinuria [3]. In the absence ofearly identification and timely case management of pre-eclampsia, the trajectory can put women at high risk oflife-threatening complications [4]. Each year, it is esti-mated that HDP complicates 10 million pregnancies,resulting in 76,000 maternal and 500,000 foetal/newborndeaths [5]. Nearly all of these deaths (>99 %) occur in low-and-middle-income countries (LMICs), particularly inSouth Asia and Sub-Saharan Africa [6].Previously, the definitive management of HDP has fo-cused on health facility level interventions with antihy-pertensive [7] and anticonvulsant [8] therapies and timeddelivery to reduce risks. However, thousands of womenin hard-to-reach areas in resource-constrained LMICscontinue to suffer severe disability or lose their lives be-cause of delays in early identification, triage, transport andtreatment—clinical processes that could feasibly be man-aged within a woman’s own community at the level of aprimary health centre (PHC) or nearby via admission to amore central referral hospital [9].The CLIP TrialThe Community Level Interventions for Pre-eclampsia(CLIP) is an ongoing cluster randomized trial [Clinical-Trials.gov number ID NCT01911494] [10] that introducesevidence-based interventions applied at both communityand PHC levels to reduce maternal and perinatal disabil-ities and deaths resulting from the failure to identify andmanage pre-eclampsia at the community level. Specific-ally, the CLIP intervention consists of:I. Community engagement including women from thecommunities, dyadic household decision-makers(husbands, fathers-in-law) and community leadersabout: pre-eclampsia, its origins, symptoms, signsand potential consequences, pre-permissions formaternal transport and fundraising activities fortransport and treatment costs;II. Provision of HDP-oriented antenatal care throughhousehold visits by community healthcare providers(cHCPs) who carry a mobile health applicationfor identifying women at risk of pre-eclampsia[Pre-eclampsia Integrated Estimate of Risk(PIERS) [11] on the Move (POM) [12] app];III. Use of the CLIP package for women with a CLIP‘trigger’ (i.e. oral antihypertensive therapy orintramuscular (i.m.) magnesium sulphate (MgSO4)when indicated, and appropriate referral to acomprehensive emergency obstetric care (CEMOC)facility as needed).The cHCPs assess pregnant women with a target fre-quency of every 4 weeks at a minimum. These visits canoccur in the home or PHC, which are both consideredpart of the community for the purpose of the CLIP Trial.The cHCPs are trained to enquire about the woman’ssymptoms (using country-specific pictograms), take bloodpressure and check urine for protein using a dipstick onthe first visit or on any subsequent visits if the systolicblood pressure is ≥140 mmHg. This helps to inform diag-nosis of and risk assessment for pre-eclampsia. The con-trol group (without intervention) continues with routinepregnancy care related to antenatal visits, referral to ahealth facility and initiation of therapy.Cost and cost-effectiveness of interventions forpre-eclampsia/eclampsiaPre-eclampsia imposes very high financial burdens on thefamilies of the affected women and on the healthcare sys-tem in LMICs [2, 13]. Economic studies conducted in theUnited Kingdom (UK) report that pre-eclampsia/eclampsiais one of the most common reasons for antenatal admis-sion to hospital (20 %) and of obstetric admissions tointensive care units (25 %) [14]. Other studies from the USreport that hospitalization costs for the management of pre-eclampsia and associated complications were US$11,208per woman on average [15, 16]. Studies from LMICs re-port death or surviving serious illness of a mother to resultin lower household income [17] and to raise the risk ofdeath for children aged <10 years [18].There are few cost-effectiveness studies related to pre-eclampsia/eclampsia. Existing studies have focused ondiagnostic and clinical interventions in well-resourcedsettings and not on other issues at community or popula-tion levels. For example, a recent study from Israel evalu-ated the economic benefit of first-trimester screening ofmultiple markers compared with no screening. This studyfound a cost per quality-adjusted life year (QALY) lessthan US$10,000 for screening, given the prevalence of pre-eclampsia at 3 % [19].Another economic study in the context of the UK’sNational Health Service reported that the protein-creatinineratio (Pr:Cr) alone, when compared with automated reagent-strip reading device followed by Pr:Cr and/or 24-h measure-ment of proteinuria, was found less costly and gained themost QALYs [20].A large multi-country trial on prophylactic use of MgSO4in women with pre-eclampsia reported the incrementalcost of preventing one case of eclampsia as US$21,202in high-income, US$2473 in middle-income and US$456in low-income countries [21]. Another study from theKhowaja et al. Implementation Science  (2015) 10:76 Page 3 of 14UK found that the prophylactic administration of MgSO4to all women with pre-eclampsia had an incremen-tal cost of US$9994 for each additional seizure pre-vented [22].Other interventions in the context of the UK, such astreatment with aspirin compared with no aspirin, werefound to be cost saving (i.e. £7852) and resulted in 0.52additional QALYs per pregnancy in women at risk of pre-eclampsia [23]. The labour induction for immediate birthversus clinical management strategy was found to have anincremental cost-effective ratio (ICER) of £2900 per QALYgained in women diagnosed with mild or moderate pre-eclampsia [24].Cost-effectiveness studies have also evaluated other in-terventions that can be used to improve maternal [25] andneonatal health [26] in LMICs. However, their relevanceto pre-eclampsia/eclampsia interventions is limited giventhe restricted analysis of individual interventions on surro-gate health outcomes and the variability of settings.In relation to the proposed work, our literature reviewfound very limited information for cost-effective inter-ventions for pre-eclampsia/eclampsia in the context ofLMICs, which is where most of the disease burden andassociated mortality occur. Thus, it is critical to conductan economic evaluation alongside of the CLIP Trial, toinform decision makers not only of clinical outcomesbut the cost required to obtain those outcomes.Rationale for conducting economic evaluation of CLIPAdam et al. [27] conducted a cost-effectiveness analysisof WHO-recommended strategies for maternal and neo-natal health and demonstrated the benefits of comprehen-sive community-based antenatal, intrapartum and postnatalinterventions for reducing maternal and neonatal mor-tality in sub-Saharan Africa and Southeast Asia. Theyhighlighted that packages of maternal and newborn in-terventions can be more cost-effective than singularinterventions.In our context, the CLIP Trial combines a package ofotherwise singular evidence-based interventions (bloodpressure monitoring [15], urine dipstick testing [28], MgSO4[21], methyldopa [29], mobile health (mHealth) technol-ogy [12, 30], antenatal visits by cHCPs [18], communityengagement [31], timely referral and triage at a healthfacility [6]). This combined package of care must be evalu-ated to determine if it is a cost-effective intervention in re-ducing maternal and perinatal mortality.It is well recognized that economic studies embeddedwithin clinical trials have high internal validity and time-liness [32]. In this context, the International Society forPharmacoeconomics and Outcome Research (ISPOR) rec-ommended collecting trial outcome data, health resourcesused and health state utilities directly from the study par-ticipants recruited in the trial [33].The CLIP Trial is being conducted across four countries,and so assessment of the economic impact (costs andbenefits) alongside the trial (i.e. concurrent with it) willbe integral to building a robust cost-effectiveness modelto supplement the trial outcomes. This is critical be-cause the CLIP Trial introduces new costs in healthservice delivery (e.g. mHealth and task shifting tocHCPs), which will have budgetary implications forhealth systems in the selected CLIP countries. Post-trial program scale-up of CLIP interventions must beinformed through both the impact of the package ofintervention and the cost of achieving any incremen-tal benefits in the context of selected South Asian andAfrican countries.The CLIP Trial’s collaborating partners and Ministriesof Health (MoH) in the respective countries have a cleardesire to ascertain the long-term implications of theCLIP package of care. These stakeholders unanimouslyendorsed conducting an economic appraisal of CLIP tofurther inform policy decisions around resource alloca-tion and program scale-up, thereby serving as modelsfor other LMICs.Study hypothesisThe CLIP package combined with routine pregnancycare, compared to routine pregnancy care alone, will re-sult in a favourable (i.e. low) ICER in reducing maternaland perinatal mortality and major morbidities.Study objectivesThe primary objectives are to:1a) Determine the costs and benefits of the CLIP packageof care in order to design the cost-effectivenessmodel;1b) Estimate the ICER of the CLIP plus routinepregnancy care, compared with routine pregnancycare alone, in reducing maternal and perinatalmortality and major morbidities;1c) Assess health system budget impact, whenswitching from routine pregnancy care to CLIPplus routine pregnancy care.The secondary objectives are to:2a) Qualitatively identify the cost drivers (resourcesneeded) during trial implementation to informdesign of the model;2b) Explore implementation challenges and perceivedcost-benefits of CLIP plus routine pregnancy;2c) Inform health decision/policy makers about thefindings of cost-effectiveness of the CLIP package ofcare and budgetary implications in the selectedcountries.Study methodsResearch designWe propose to use CEA in conjunction with qualitativeanalysis alongside the trial to prospectively evaluate theeconomic impact of CLIP. Qualitative research has beenused effectively in other cluster RCTs to assess the im-plementation variations and local context of the inter-vention [34]. We will use a mixed-method approachbecause the CLIP Trial is being conducted in four countriesthat have different health delivery systems, health financing,resource allocation interests, diversity of community beliefsabout pre-eclampsia/eclampsia, care-seeking behavioursand treatment preferences. The mixed-method approach(CEA and qualitative) will inform the design of modellingand support interpretation of economic analysis for deci-sion makers who are considering evidence of economicvalue along with the effectiveness of CLIP.the cost-effectiveness model in the other three sites(i.e. India, Nigeria and Mozambique).Phase 3 will address Objectives 1b and 1c, once the finaltrial outcomes are analysed and available to run the cost-effectiveness analysis for all sites. In addition, it will addressObjective 2c to inform health decision/policy makers aboutcost-effectiveness and budgetary implications.Target populationBecause pre-eclampsia is a pregnancy-related illness, thisstudy will target pregnant women aged 15–49 years (ex-cept Mozambique where the eligibility age is 12–49 years),those recruited in the primary CLIP Trial in both inter-vention and control clusters.Settings and durationThe sites for the CLIP Trial include local governmentareas of Ogun State, Nigeria; the Provinces of Gaza andKhowaja et al. Implementation Science  (2015) 10:76 Page 4 of 14Research planThe research will be conducted in three inter-linkedphases over a 2-year period. (Please refer to Fig. 1).Phase 1 will contribute to objective 1a using cost esti-mation and outcome monitoring methods to design acost-effectiveness model for CLIP. Qualitative assessmentswill address objectives 2a and 2b to understand contextualaspects of the costs, challenges during trial implementa-tion and benefits from community perspectives to supportinterpretation of the economic analysis. Phase 1 activitieswill be undertaken in Pakistan, one of the four countriesengaged in the CLIP Trial.In Phase 2, based on the learning in Phase 1, we willuse similar, but contextually modified, methods guidedby within-country data collection to validate/extrapolateFig. 1 Research plan for economic evaluation of the CLIPMaputo in Mozambique; the districts of Matiari andHyderabad in the Province of Sindh, Pakistan; and theBelgaum and Bagalkot districts in the State of Karnataka,India. The economic evaluation of CLIP will be a criticalstep to guide policy decisions for post-trial programscale-up in all of these selected countries.The total duration of the proposed country-specificcost-effectiveness analysis will be 2 years (Sept 2015–Aug2017) (please refer to Table 1). Phase 1 will commence inSeptember 2015 and will include activities for cost calcula-tion and qualitative assessments at one site. The data fromphase 1 will be analysed by April 2016. Phase 2 will com-mence in May 2016 at the remaining three CLIP sitesand shall be completed by December 2016. Finally, thecountry-specific CEA will be completed by June 2017,n onan-Calculating incrementalKhowaja et al. Implementation Science  (2015) 10:76 Page 5 of 14Table 1 Project milestones (GANTT chart) for economic evaluatio2015 20161–4 (Sep–Dec) 5–8 (Jan–Apr) 9–16 (May–Dec)Phase I Phase IIDesigning/Testing thecosting model (Pakistan only)Validation/Extrapolatiomodel (India, Nigeria,Field level planning; andconducting qualitativefocus groups (FGs) anddata analysisCollecting costingdata and data analysisConducting FGs; andcollecting cost data-Baseline survey forcost estimation-FGs with community-FGs with healthproviders -FGD withPolicy makers communityand health workers-Collecting price listfor health services-Review of districtlevel cHCP budget-FGs with community-Baseline survey forcost estimation-Collecting price listfor health services-Review of districtlevel cHCP budget-Designing/Testingthe model-FGs with healthproviders-FGD withPolicy makersfollowed by report writing and result dissemination inAugust 2017.Study perspectiveThe CEA will be based on a societal perspective, account-ing for both costs to healthcare system and cost to familiesof the pregnant women.Designing the model: description of cost variablesThe standardized ingredient approach [35], which involvesgathering sufficient information about the quantities andunit cost of physical inputs needed in the interventionand control groups, will be used to calculate costs. Thiswill include cost to the healthcare system and cost tothe family.Cost to the healthcare systemThe cost to the health system will comprise the cost of theCLIP Trial interventions, including mHealth technologyand infrastructure, blood pressure devices, urine dipsticks,community engagement sessions, training and time ofhealthcare providers at the community and health facilitylevels. Additional costs will include:– Cost of follow-up household visits and time spenton blood pressure monitoring/urine dipstick bycHCPs in each of the selected sites, such asCommunity Health Extension Workers (CHEW) inCoAlaincaAtrofofofCoThlacost per DALY gained.Country-specific budgetaryanalysis17–22 (Jan–June) 23–24 (Jul–Aug)Phase IIIof the costingd Mozambique)Determining an evidence for economic impactof the CLIP (All four sites)Data analysisand extrapolationof modelGenerating country-specificcost-effectiveness modelsWriting report; andconducting final resultdissemination seminar-Calculating incremental costper combined maternal/perinatal outcomes averted-Model validationf the CLIP2017Nigeria, Agente Polivalente Elementar (communityhealth agents) in Mozambique, Lady Health Workers(LHW) in Pakistan and Accredited Social HealthActivists (ASHA) in India;– Cost of cHCPs’ additional time and transport costswhen accompanying any identified HDP woman to areferral health facility;– Health system costs such as managing triage forobstetric emergencies, in-patient/outpatient servicesfor obstetric emergencies, as well as diagnostic testsand drugs.st to the familyll relevant out-of-pocket (OOP) expenses for ambu-nce, hospitalization (physician fees, bed charges, nurs-g services), drugs and diagnostic workup related tore from the referral health facility would be included.lso, OOP cost for informal care (i.e. care sought fromaditional healers) will be captured, as well as the costlost productivity resulting from morbidity or mortalitypatients with or without paid jobs, and any lost wagestheir caregivers.st to societyhe total societal costs (i.e. combining of costs to theealthcare system and cost to the family) will be calcu-ted by summing across all cost categories.ComparatorsThis study will compare the costs and pregnancy out-comes ascertained from the intervention i.e. CLIP plusroutine pregnancy care; compared with control groupi.e. routine pregnancy care alone. In a primary CLIPcluster-randomized trial, the interventions are beingevaluated at the population level. Therefore, people inthe comparator group will continue to receive routinepregnancy care related to antenatal visits, referral to ahealth facility and initiation of therapy.Health resource utilization and costs: data collectionmethodsThe information about resources utilized and unit costs willbe collected from primary and secondary data sources inthe intervention and control groups. A consistent ap-proach will be followed to collect these data in the inter-vention and control clusters, except for POM utilization,Khowaja et al. Implementation Science  (2015) 10:76 Page 6 of 14which only occurs in the intervention clusters (seeTable 2).Health resource utilization dataStructured health resource utilization questionnaires areembedded into CLIP Trial surveillance forms and will beadministered to all pregnant women recruited in interven-tion and control clusters. These questionnaires have beentranslated into study site languages (Yoruba in Nigeria,Portuguese in Mozambique, Sindhi/Urdu in Pakistan andKannada in India) and are as follows:Form 1: Pregnancy registration: Project research staffwill complete this form only once for every pregnancyidentified during the trial period in the interventionTable 2 Methods for collecting resource utilization and costinformationType of data Intervention group ControlgroupHealth resourceutilizationHealth resource utilization questionnaire integratedwith CLIP Trial quarterly surveillance tools forintervention and control groups:Form 1: Pregnancy RegistrationForm 2: Regular community surveillanceForm 3: Health facility utilizationPIERS on the move (POM) data N/AUnit costs Cross-sectional household survey for family’sout-of-pocket expensesReview of price listing for diagnostic andclinical services offered at health facilitiesReview of district level program budget(costing for cHCP salaries)Review of site-specific CLIP Trial budget(costing for intervention package)N/Aand control groups. The key variables include healthresource utilization, such as frequency of hospital visits,type of health facility (public or private), level of healthfacility (primary, secondary, or tertiary), level of care(in-patient or out-patient), length of stay, diagnostictests and clinical interventions since conception tothe time of pregnancy registration. Also, informationwill be collected on mode of transport, number ofaccompanying family members and days of missedwages.Form 2: Regular community surveillance: Project staffwill complete this form once every 3 months untildelivery and once post-delivery capturing data for the42 days after childbirth, for each pregnant woman re-cruited in the intervention and control groups. The keyvariables include health resource utilization, such asfrequency of hospital visits, type of health facility (pub-lic or private), level of health facility (primary, second-ary, or tertiary), level of care (in-patient or out-patient),length of stay, diagnostic tests and clinical interventionsfor pregnant women and newborn. Also, informationwill be collected on mode of transport used, number ofaccompanying family members and days of missedwages.Form 3: Health facility utilization: This is based onpatient hospital admission chart review for womenrecruited in the CLIP Trial and will be completed byproject research staff during their monthly visits at allreferral health facilities in the catchments ofintervention and control groups. The key variablesinclude diagnostic and clinical services utilized bypregnant women and/or newborns at health facilities.The POM dataThe information about resource utilization as a result ofCLIP interventions will be captured from the POM dataset. Based on clinical triggers, CLIP interventions are clas-sified into five main categories: 1) treat with MgSO4 andtransport to hospital; 2) urgent transport (within 4 h) tohospital only; 3) non-urgent transport (within 24 h) tohospital only; 4) treat with MgSO4 and methyldopa andtransport to hospital; and 5) continue with routine ante-natal care. POM data is maintained electronically for allthe women recruited in the intervention clusters.Cross-sectional household surveyThe survey will be conducted in a sample of women fromintervention and control clusters to determine unit costsfor out-of-pocket expenses to the family associated withobstetric emergencies including HDP. The value of thelost wages will be estimated by using a mean wage rate tomissed work time, obtained from country-specific stan-dards. Assuming an incidence rate of pre-eclampsia at 8 %,95 % confidence interval and design effect of 1.0 for asimple random sample, the required sample size for base-line survey at each site is presented in Table 3.Review of price listing for maternal and newborn healthservicesIn order to obtain the unit cost of hospitalizations (e.g.bed charges, nursing services), drugs and diagnostics,Besides healthcare providers and care receivers in acommunity, studies have reported that women in LMICsare situated in cultural contexts, where men in their livesare traditionally the decision makers surroundingwomen’s health issues [37]. As inclusively as possible,the community perspectives will be obtained fromgroups of:orPKhowaja et al. Implementation Science  (2015) 10:76 Page 7 of 14the price lists will be obtained from all public and pri-vate health facilities where women with HDP will be re-ferred in the catchments of intervention and controlclusters. The weighted average will be calculated for esti-mating unit costs for similar types of services availableat private and public health facilities, with respect to thenumber of women utilizing such services for pregnancycare, delivery and newborn care.Reviewing district level cHCP program budgetThe salaries of cHCPs who are currently involved in theCLIP Trial will be determined through review of the dis-trict level program budget. Where resources are sharedwith other preventive programs, we will use simultan-eous allocation methods for determining the unit cost ofapplicable services. In addition, the transport expenseswill be calculated for the extra visits of cHCPs in theintervention clusters to be able to determine the cost oftask shifting.Review of site-specific CLIP Trial budgetThe unit cost estimates for the CLIP Trial interventionpackage include the cost of a blood pressure device,urine dipstick, oxygen saturation prop, cost of commu-nity engagement sessions, and cost of training doctors,nurses, midwives and community health workers andwill be determined from the trial budget for each site inthe CLIP Trial. These cost estimates will be verifiedfrom the central trial office (PRE-EMPT, UBC).Designing the model: qualitative data collection methodsFocus groups (FGs) are a commonly used method ofdata collection in qualitative research to gather groupopinions [36]. Specifically, the FGs in this study areaimed to better understand the contextual variations ofintervention delivery, resources used for costing workand perceived benefits from a community perspective.Table 3 Site-specific population and desired number of women fVariablesTotal population per clusterNumber of intervention and control clustersAnnual birth rate (/1000/year)Total number births during trial periodEstimated number of women with pre-eclampsia during trial periodNumber of women required for survey– Pregnant women identified as at risk due to a HDP;– Male decision makers (husbands/fathers-in-law) ofpregnant women identified as at risk of a HDP;– Community healthcare providers;– Medical doctors at referral health facilities;– District-level health decision/policy makers.Guided by relevant literature [37, 38], and investiga-tors’ experiences of CLIP Trial feasibility work in theCLIP countries, semi-structured interview guides havebeen developed following a priori themes:Theme I: Cost drivers and health resource utilization asa result of the CLIP package.Theme II: Perceived benefits of the CLIP package ofcare and task shifting to cHCPs.Theme III: Implementation challenges for the CLIPpackage of care.Theme IV: Strategies for knowledge translation of CLIPto the wider community.Theme V: Strategies for health policy advocacy andprogram scale-up of CLIP.The FG guides will be translated into local languagesand pilot tested in randomly selected intervention clus-ters before data collection. Digital voice recorders andwritten notes will be used to record the participants’ re-sponses during all FGs. The FG data will be transcribedinto the local language, followed by translation into English.All the translations will be confirmed by researchers withback-translation of randomly selected data segments forquality control.Study eligibility (inclusion and exclusion criteria)Pregnant women aged 15–49 years (except Mozambiquewhere the eligibility age is 12–49 years) recruited in thesurveyakistan India Nigeria Mozambique Total32,000 27,000 70,000 25,000 154,00020 12 10 12 5414 22 16 40 9219,800 19,200 26,880 24,400 90,2801584 1536 2150 1952 7220113 113 136 126 488CLIP Trial in both intervention and control clusters willbe eligible to take part in the economic data collection(i.e. Form 1, Form 2 and Form 3) for health resourceutilization. For qualitative assessments, eligible participantsinclude only women in the CLIP intervention group whowere identified as at risk of a HDP. Likewise, male decisionmakers of pregnant women (identified as at risk of a HDP)and those willing to participate in the session will be eli-Data analysisBecause outcomes of pregnancy can be assessed over ashort span (i.e. 40–42 weeks of time horizon), the decisionanalytic tree model [39] can be used for comparative ana-lysis of costs and effectiveness between two alternatives.Previously conducted cost-effectiveness studies for pre-eclampsia [19, 22] have mainly used a decision analytic treemodel. Our primary analysis for this study will be modelnirsKhowaja et al. Implementation Science  (2015) 10:76 Page 8 of 14gible. The cHCP handling the CLIP Trial package of inter-vention, the medical doctors at the referral health facilitiesand district health decision makers in the catchments ofintervention and control groups and those willing to par-ticipate in 45- to 60-min session will be eligible to partici-pate. Participants who will be excluded are those whoare not recruited in the primary CLIP Trial and/or re-fused to take part in the economic data collection proce-dures. The eligible participants for qualitative assessmentswill be approached by project research staff during homeand health facility visits for CLIP Trial surveillance andwill be invited to participate in FGs.Sample sizeThe sample size required to demonstrate the effective-ness of the primary CLIP Trial will be sufficient as it ispowered to detect 30 % effect size. We estimate a totalof 90,000 pregnant women will be registered in the CLIPTrial across four sites; and those who consent to surveil-lance (Form 1, 2, and 3) will be included in our eco-nomic analysis.Each FG will include 6–9 participants. We anticipate atotal of 40 FGs inclusive of all groups; however, the finalnumber of FGs will be determined by data saturation(see Table 4).Outcome variables (effectiveness): methods of collectingoutcomesThe CLIP Trial primary outcome is the reduction in com-bined maternal and/or perinatal adverse outcomes be-tween the intervention and control groups (see Table 5).The project research staff will assess the trial outcomesevery 3 months during community surveillance visits atthe households for all women recruited in the interventionand controls groups.Table 4 Number and distribution of FGs across CLIP countriesCLIP country Number of focus groups (anticipated)Pregnant womenwith HDPMale decisionmakersCommuprovidePakistan 2 2India 2 2Nigeria 2 2Mozambique 2 2Total 8 8based, guided by previous work in high-income countriesas no LMIC modelling in pre-eclampsia has been done.We will use parameter estimates for costs and effectivenesscoming from the CLIP Trial (see Fig. 2).The unit costs will be multiplied by identified healthresource utilization to calculate the total cost per preg-nancy, including both pregnant woman and newborns.The total cost will be calculated as the sum of the healthresource utilization cost, cost of implementing the CLIPpackage of care, cost of routine pregnancy care and soci-etal costs. The annual equivalent costs in local cur-rency of selected CLIP countries (PKR—Pakistani Rupee;INR—Indian Rupee, NGN—Nigerian Naira and MZN—Mozambican Metical) will be converted in US dollarexchange rate as of 2015. The pregnancy outcomes(i.e. health of mother and baby) will be modelled as the ef-fectiveness of the CLIP interventions. This will includeno-adverse outcomes (healthy mum and newborn at thetime of delivery) and adverse outcomes (death and/or dis-ability of mother and baby) observed in the interventionand control groups.In addition, costs and pregnancy outcomes will be mod-elled over the lifetime horizon to estimate the long-termimpact of CLIP. We will calculate disability-adjusted lifeyears (DALYs) averted through subsequent modelling toyield estimates of the years of life lost due to disabil-ity [40] taking into account the epidemiological rates andhealth state valuations on burden of disease for Africanand South Asian regions [41, 42]. Both costs and out-comes will be discounted at 3 % per year, the widely citeddiscount estimate for economic studies in the context ofLMICs [26, 43].Using the data and parameter estimates specific to eachCLIP country, the ICERs will be calculated first from ahealthcare system perspective and then from a societalTotalty healthcare Doctors at healthfacilitiesDistrict healthdecision makers2 2 2 102 2 2 102 2 2 102 2 2 108 8 8 40Table 5 Definitions of CLIP Trial outcomesDefinitionsMaternal outcomesMortality Defined as the number of deaths during pregnancy or within 42 days of pregnancy (or last contact day if contact not maintainedto 42 days)/1000 identified pregnancies), termed maternal death rate.Morbidities Defined as the number of women with one or more life-threatening complications of pregnancy during pregnancy or within42 days of pregnancy/1000 identified pregnancies.Serious end-organ complications of pre-eclampsia:Eclampsia: occurrence of generalized convulsions during pregnancy, labour or within 42 days of delivery in the absenceof epilepsy or another condition predisposing to convulsionsStroke: hemiparesis and/or blindness developed during pregnancy or in the 42 days postpartum lasting greater than 48 hComa: prolonged unconsciousness ≥12 hAntepartum haemorrhage: vaginal bleeding ≥15 mL with or without pain before the onset of labourDisseminated intravascular coagulation (DIC): abnormal bleeding from mucosa (mouth and/or ears)Other major causes of maternal mortality:Obstetric sepsis: In the community, defined as fever and one of: abdominal/uterine tenderness, foul smelling vaginaldischarge/lochia, productive cough and shortness of breath, dysuria or flank pain, headache and neck stiffness. In the facility,defined as presence of fever (>38 °C), a confirmed or suspected infection (e.g. chorioamnionitis, septic abortion, endometritis,pneumonia) and at least one of the following: heart rate >90/min, respiratory rate >20/min, leukopoenia (total leukocytecount [TLC] <4 × 109/L) or leukocytosis (TLC >12 × 109/L)Vesicovaginal or rectovaginal fistula: continuous loss of urine and/or faeces after deliveryLife-saving interventions:Cardiopulmonary resuscitation: a set of emergency procedures including chest compressions and lung ventilation appliedin cardiac arrest victimsDialysis: haemodialysis and/or peritoneal dialysisMechanical ventilation (other than for Caesarean section): intubation and ventilation not related to anaesthesiaBlood transfusion: ≥1 unitInterventions for major postpartum haemorrhage: brace sutures, external and internal uterine compression, anti-shockgarment use, internal iliac artery ligation and/or hysterectomy with or without transfusionPerinatal outcomesMortality Defined as stillbirth [≥20+0 and/or ≥500 g], early neonatal mortality [days 0–7 of postnatal life] and late neonatal mortality[days 8–28 of postnatal life]/1000 identified pregnancies]Morbidity Defined as non-lethal events of seizure and coma during days 0–28 of postnatal life/1000 identified pregnancies). The followingare the primary neonatal morbidities:Feeding difficultyBreathing difficultySeizureLethargyComaFeverHypothermiaUmbilical cord infectionSkin infectionBleedingJaundiceVomiting/DiarrhoeaKhowaja et al. Implementation Science  (2015) 10:76 Page 9 of 14Fig. 2 Decision analytic tree model for economic evaluation of CLIP. HDP, hypertensive disorder of pregnancyKhowaja et al. Implementation Science  (2015) 10:76 Page 10 of 14perspective. The country-specific ICER will be calculatedas follows:(i) Incremental cost per adverse pregnancy outcome(ii) Incremental cost per DALY gainedICERs for the system perspective as the reference casewill be of interest to country-specific health policy makersfor resource allocation decisions, when switching from rou-tine pregnancy care to CLIP plus routine pregnancy care,should CLIP be found effective. Critically, however, theICER from a societal perspective will facilitate discourseon the full opportunity cost in the context of the selectedCLIP country. In accord with the recommendation of theCommission for Macroeconomics and Health [44], we willcompare the country-specific ICER with the per capitavalue for the gross national income of each of the four se-lected CLIP countries for the year 2015.Given the uncertainties involved in CEA, we will useprobabilistic sensitivity analysis to produce cost-effectivenessplots [45]. The confidence region surrounding the cost-effectiveness ratio will be estimated using appropriate stat-istical methods, including bootstrap and Monte Carlosimulations. Life tables based on data from the WorldHealth Organization’s Southeast Asia and African regions[46] or the West level-26 model [47] will also be used in asensitivity analysis. Children in LMICs bear a dispropor-tionately large share of the total disease burden, becauseof the cause structure of the disease burden by age couldinfluence overall distribution of DALYs [48]. As reportedon previous cost-effectiveness studies in LMIC, no-age-weighting in the reference case was used on sensitivityanalysis [43]. Country-specific health system budget im-pact analysis will be conducted to facilitate policy deci-sions for resource allocation, when switching from routinepregnancy care to CLIP plus routine care, should theintervention be found effective.Qualitative data will be analysed using QSR NVivo v10software, and responses will be coded to form similarcategories. These will be refined through thematic ana-lysis. Data will be interpreted through close communica-tion between local researchers and international team toensure accuracy.Ethical considerationsThis study will utilize the existing CLIP Trial infrastruc-ture in the four countries and follow the human ethicsprotocol for the randomized control trial. There is nophysical harm and risk to participants in this economicstudy. The Institutional Review Board (IRB) approval fromKhowaja et al. Implementation Science  (2015) 10:76 Page 11 of 14Fig. 3 Map of interventional studies on the topic of maternal health—those registered with ClinicalTrials.govKhowaja et al. Implementation Science  (2015) 10:76 Page 12 of 14UBC has been obtained [ETHICS # H12-00132] for theeconomic evaluation of the CLIP. In addition, the country-specific formal letters of support and permission for dataaccess have been received from government health author-ities in all four CLIP countries. Study questionnaire anddata forms will be kept in a secured place accessible onlyto study staff. No personal identifiers will be used in anyreports or publications. Study procedures and benefits willbe explained to the study participants, and written consentwill be obtained for the baseline cost estimation surveyand for qualitative FGs in this study.Trial statusThe CLIP Trial has been registered at ClinicalTrials.gov(NCT01911494). It is funded by the Bill & Melinda GatesFoundation. The definitive phase of the CLIP Trial is cur-rently recruiting at all four sites and shall continue untilDecember 2016. The recruitment began in India on 1November 2014, in Pakistan on 19 January 2015, inMozambique on 1 March 2015 and in Nigeria on 15March 2015.DiscussionEconomic evaluation of innovative health interventionscan play a pivotal role in priority setting and can informhealthcare decision makers with evidence relevant to re-source allocation [49]. The World Health Organization(WHO) strongly recommends cost-effective interventionsas a key aspect of achieving Millennium DevelopmentGoal (MDG)-5 (i.e. 75 % reduction in maternal mortalityfrom 1990 levels by 2015) [50]. Our search for interven-tion studies registered on ClinicalTrials.gov revealed 1588studies that mentioned “maternal health” on the submittedprotocols [51]. Of these, 36 % were reported from Africaand South Asia, which is where most of the maternalmortality burden occurs [1] (see Fig. 3). Only 28 outof 1588 (i.e. ~2 %) included “cost-effectiveness analysis”on the submitted protocols.Given this, it seems that few recent maternal healthintervention studies have looked at how cost-effectivenessthese interventions may be to scale up. This is contrary tothe recommendations of WHO for maternal health inter-ventions and indicates a large knowledge gap for policydecisions. Consequently, the CLIP Trial is one of thefirst large-scale research trials to address this importantquestion in the real-world context in LMICs, and thusprovides a unique and timely opportunity for economicevaluation of a well-designed community-based trial thatdirectly aligns with MDG-5.Possible study limitationsThere is a possibility of recall bias for the cost to familyobtained on the baseline survey; however, we will limitthe recall length to the most recent hospitalization. Inaddition, some non-financial factors, such as patient andprovider preferences and altruism, could possibly influ-ence families’ healthcare utilization. The methodologicalconsistency in collecting costs and outcomes in both inter-vention and control groups, supplemented by the qualita-tive data for designing the cost-effectiveness model foreach site, will increase the internal study validity.Knowledge translationResults of the economic impact analyses will be communi-cated to community stakeholders, providers and policymakers through dissemination workshops organized ineach country site after CEA results have been completed.Policy briefs [52] will also be drafted to highlight key find-ings, and they will be distributed among healthcare pro-viders and district health authorities in other provinces ineach country. The progress of the study, findings from in-terim analysis and final CEA results, will be presented atrelevant national/international conferences. Manuscriptswill be submitted for publication in peer-reviewed openaccess journals.Potential impactThis study will definitively determine the costs incurredby the CLIP package of care and the number of mater-nal/perinatal deaths and major morbidities averted perUS dollar. In the long run, this study will supplement thescientific evidence around the effectiveness of the inter-vention and so facilitate policies which best mobilize localtechnology and employ human resources for maximizinghealthy pregnancy outcomes in the selected LMIC coun-tries. The qualitative findings will help to interpret thecost benefit findings of the CLIP Trial, to identify chal-lenges during trial implementation and to strategizeknowledge translation for strengthening policy advocacyfor post-trial programmatic scale-up and sustained imple-mentation within existing maternal health policies in theselected CLIP countries. Furthermore, we will have robustdata to propagate similar models for other non-CLIPLMICs in the developing world.Endnotes1DALYs are defined as a measure of overall diseaseburden, expressed as the number of years lost due to illhealth, disability or early death.AbbreviationsASHA: accredited social health activists; ANM: auxiliary nurse midwives;APE: agente polivalente elementar; CLIP: community level interventions forpre-eclampsia; CRRH: Centre for Research in Reproductive Health; CISM: TheManhiça Health Research Centre; CHEW: community health extensionworkers; DALYs: disability-adjusted life years; FGD: focus group discussions;ICER: incremental cost-effective ratio; IRB: institutional review board;ISPOR: International Society for Pharmacoeconomics and Outcome Research;LMIC: low- and middle-income countries; PHC: primary health centre;CEMOC: comprehensive emergency obstetric care; LHW: lady health worker;MoH: Ministry of Health; NPT: normalization process theory; OOP: out-of-pocket;Khowaja et al. Implementation Science  (2015) 10:76 Page 13 of 14PIERS: pre-eclampsia integrated estimate of risk; QALYs: quality-adjusted lifeyears; RCT: randomized control trials; SPA: service provision assessment.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsARK conducted literature search to conceptualize/develop the studyprotocol for economic evaluation of CLIP. CM served as the PrincipalInvestigator of this study and was involved in the conception and design ofthe study and reviewed the manuscript. SB, PvD, LM and ZAB served asCo-investigators, provided intellectual contributions to the methodology/plan of data analysis and were involved in review of the manuscript.All authors read and approved the final manuscript.Authors’ informationARK is a Vanier scholar and currently a PhD student in Reproductive andDevelopmental Sciences at University of British Columbia.AcknowledgementsThis research will be a collaborative project of the University of BritishColumbia, Canada, and partners in CLIP Trial sites: namely Division ofWomen and Child Health, Aga Khan University, Karachi, Pakistan; Centre forResearch in Reproductive Health (CRRH), Olabisi Onabanjo UniversityTeaching Hospital, Sagamu, Ogun State, Nigeria; KLE University’s JN MedicalCollege, Belgaum & SN Medical College, Bagalkot, India; Manhiça HealthResearch Centre (CISM), Mozambique and Faculty of Medicine, UniversidadeEduardo Mondlane (UEM), Maputo, Mozambique. The authors acknowledgeNeale Smith for his editorial review of this manuscript. All authorsacknowledge the valuable collaborations of the Principle Investigators ofCLIP Trail at all four CLIP Sites. The authors also acknowledge the supportand data access permissions received from government authorities asfollows:—Honourable Commissioner of Health, Ogun State Nigeria;—National Directorate of Public Health, Mozambique;—Registrar, KLE University, Belgaum Karnataka, India;—Director General Health, Government of Sindh, Pakistan.Source of fundingBill & Melinda Gates Foundation, through the PRE-EMPT initiative at theUniversity of British Columbia.Author details1Department of Obstetrics and Gynaecology; and Child and Family ResearchInstitute, University of British Columbia, Vancouver, Canada. 2School ofPopulation and Public Health, University of British Columbia, Vancouver,Canada. 3Centre for Clinical Epidemiology and Evaluation, Vancouver CoastalHealth Research Institute, Vancouver, Canada. 4Division of Women and ChildHealth, Aga Khan University, Karachi, Pakistan. 5Centre for Global ChildHealth, Hospital for Sick Children, University of Toronto, Toronto, Canada.Received: 14 April 2015 Accepted: 15 May 2015References1. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C,Heuton KR, et al. Global, regional, and national levels and causes of maternalmortality during 1990–2013: a systematic analysis for the Global Burden ofDisease Study 2013. Lancet. 2014;384:980–1004.2. Osungbade KO, Ige OK. Public health perspectives of preeclampsia indeveloping countries: implication for health system strengthening. Journalof Pregnancy. 2011;(2011):1-6. Online: http://dx.doi.org/10.1155/2011/481095. Accessed 20 May 2015.3. The American College of Obstetrician and Gynaecologists. Hypertension inpregnancy. Online available: http://www.acog.org/~/media/Districts/District%20VIII/HypertensionPregnancy.pdf?dmc=1&ts=20140527T0350044350. Accessed 20 May 2015.4. Yücesoy G, Sebiha Ö, Harika B, Temel T, Caliskan E, Vural B, et al. Maternaland perinatal outcome in pregnancies complicated with hypertensivedisorder of pregnancy: a seven-year experience of a tertiary care center.Archives of gynaecology and obstetrics. 2005;273(1):43–9.5. Preeclampsia Foundation. Some heavy facts. Available online: https://www.preeclampsia.org/advocacy/archive/332-preeclampsia-and-maternal-mortality-a-global-burden Accessed 20 May 2015.6. von Dadelszen P, Magee LA. Pre-eclampsia: an update. Curr Hypertens Rep.2014;16(8):454–9.7. Payne B, Gordon R, Vidler M. Pharmacotherapy for preeclampsia in low andmiddle income countries: an analysis of essential medicines lists. J OGC.2013;35:215–23.8. Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesiumsulphate and other anticonvulsants for women with pre-eclampsia.Cochrane Database Systematic Rev. 2010;11.9. Firoz T, Sanghvi H, Merialdi M, von Dadelszen P. Pre-eclampsia in low andmiddle-income countries. Clinical Obstetrics and Gynaecology.2011;25(4):537–48.10. von Dadelszen P, Magee L, Payne B, Bhutta ZA. Community level interventionsfor pre-eclampsia. The Lancet. Available online http://www.thelancet.com/protocol-reviews/13PRT-9313. Accessed 12 Apr 2015.11. Hutcheon JA, Lee T, Magee LA. Using clinical symptoms to predict adversematernal and perinatal outcomes in women with preeclampsia: data fromthe PIERS (Pre-eclampsia Integrated Estimate of RiSk) study. Journal ofObstetrics Gynaecology Canada. 2011;33(8):803–9.12. Dunsmuir DT, Payne BA, Cloete G, Petersen CL, Gorges M, Lim J, et al.Development of mHealth applications for pre-eclampsia triage. Journal ofBiomedical and Health Informatics. 2014;18(6):1857–64.13. Riaz S, Habib S, Jabeen A. Frequency of maternal mortality and morbidity inpregnancy-induced hypertension. J Ayub Med Coll Abbottabad. 2011;23(4):61–3.14. Rosenberg K, Sara T. Screening and surveillance of pregnancy hypertension—aneconomic approach to the use of daycare. Baillieres Clin Obstet Gynaecol.1990;4(1):89–107.15. Saftlas AF, Olson DR, Franks AL, Atrash HK, Pokras R. Epidemiology ofpreeclampsia and eclampsia in the United States, 1979–1986. Am J ObstetGynecol. 1990;163(2):460–5.16. Agency for Healthcare Research and Quality. Health care utilization project datasource. 2005. Online available at http://hcup.ahrq.gov. Accessed 3 Mar 201517. Tinker A. Safe motherhood as a social and economic investment. Paperprepared for technical consultation on safe motherhood. Colombo, Srilanka. Washington, DC: World Bank; 1997.18. Jowett M. Safe motherhood interventions in low-income countries: aneconomic justification and evidence of cost effectiveness. Health Policy.2000;53(3):201–28.19. Shmueli A, Meiri H, Gonen R. Economic assessment of screening forpre‐eclampsia. Prenat Diagn. 2012;32(1):29–38.20. NICE. Cost effectiveness of quantifying proteinuria in women with gestationalhypertension. 2010. Online available at http://www.ncbi.nlm.nih.gov/books/NBK62638/. Accessed 3 Mar 201521. Simon J, Gray A, Duley L. Magpie Trial collaborative group. Cost-effectiveness ofprophylactic magnesium sulphate for 9996 women with pre-eclampsia from 33countries: economic evaluation of the magpie trial. BJOG. 2006;113(2):144–51.22. Blackwell SC, Tomlinson MW, Berman S, Redman ME, Hassan SS, Berry SM,et al. The use of magnesium sulfate to prevent seizures in the pre-eclampticgravida: a cost-effectiveness analysis. Prenat Neonatal Med. 2001;6:310–7.23. NICE. Cost effectiveness of aspirin compared with no aspirin in preventingpre-eclampsia in women at risk of developing pre-eclampsia. 2010. Onlineavailable at: https://www.ncbi.nlm.nih.gov/books/NBK62633/. Accessed 20May 201524. NICE. Economic analysis of immediate birth (induction of labour) versusexpectant management in women who have pre-eclampsia with mild ormoderate hypertension at 34–37 weeks of gestation. 2010. Online availableat http://www.ncbi.nlm.nih.gov/books/NBK62659/. Accessed 20 May 201525. Hu D et al. The costs, benefits, and cost-effectiveness of interventions toreduce maternal morbidity and mortality in Mexico. PLoS One. 2007;2(8):750.26. Darmstadt GL, Bhutta ZA, Cousens S, Adam T, Walker N, de Bernis L, et al.Evidence-based, cost-effective interventions: how many newborn babiescan we save? Lancet. 2005;365(9463):977–88.27. Adam T, Lim SS, Mehta S, Bhutta ZA, Fogstad H, Mathai M, et al. Costeffectiveness analysis of strategies for maternal and neonatal health indeveloping countries. BMJ. 2005;331(7525):1107.28. NICE. Cost effectiveness of automated urinalysis compared with visualurinalysis in screening for proteinuria in women with gestationalhypertension. (2010). Online available at: http://www.ncbi.nlm.nih.gov/books/NBK62660/. Accessed 20 May 2015.29. Günenç O, Cicek N, Gorkemli H, Celik C, Acar A, Akyurek C. The effect ofSubmit your next manuscript to BioMed Centraland take full advantage of: Khowaja et al. Implementation Science  (2015) 10:76 Page 14 of 14methyldopa treatment on uterine, umbilical and fetal middle cerebral arteryblood flows in preeclamptic patients. Archiv GynObst. 2002;266(3):141–4.30. von Dadelszen P, Ansermino JM, Dumont G, Hofmeyr GJ, Magee LA, Mathai M,et al. Improving maternal and perinatal outcomes in the hypertensivedisorders of pregnancy: a vision of a community-focused approach.International Journal of Gynecology & Obstetrics. 2012;119:S30–4.31. Bhutta ZA, Ali S, Cousens S, Ali TM, Haider BA, Rizvi A, et al. Interventions toaddress maternal, newborn, and child survival: what difference canintegrated primary health care strategies make? Lancet. 2008;372:972–89.32. Ramsey S, Willke R, Briggs A, Brown R, Buxton M, Chawla A, et al. Goodresearch practices for cost-effectiveness analysis alongside clinical trials: theISPOR RCT-CEA task force report. Value Health. 2005;8(5):521–33.33. International Society of Pharmacoeconomics and Outcome Research (ISPR).Online available at: http://www.ispor.org/. Accessed 20 May 201534. Hawe P, Shiell A, Riley T, Gold L. Methods for exploring implementationvariation and local context within a cluster randomized communityintervention trial. J Epidemiology Community Health. 2004;58:788–93.35. Evans DB et al. Achieving the millennium development goals for health:methods to assess the costs and health effects of interventions forimproving health in developing countries. BMJ Br Med J.2005;331(7525):1137.36. Freeman T. Best practice in focus group research: making sense of differentviews. J Adv Nurs. 2006;56(5):491–7.37. Osubor KM, Fatusi AO, Chiwuzie JC. Maternal health-seeking behavior andassociated factors in a rural Nigerian community. Matern Child Health J.2006;10(2):159–69.38. Borghi J, Sabina N, Blum LS, Hoque ME, Ronsmans C. Household costs ofhealthcare during pregnancy, delivery, and the postpartum period: a casestudy from Matlab. Bangladesh J Health Popul Nutr. 2006;24(4):446.39. Petrou S, Gray A. Economic evaluation using decision analytical modeling:design, conduct, analysis, and reporting. BMJ. 2011;342.40. Shillcutt S, LeFevre A, Lee A, Baqui A, Darmstadt G. RE. Modeling the yearslost to disability (YLD) component to DALYs for economic evaluation ofneonatal health interventions. Health Policy Plan. 201341. World Health Organization. The World Health Report 2004:Changing history,annex table 3: burden of disease in DALYs by cause, sex, and mortalitystratum in WHO regions, estimates for 2002. Geneva: World HealthOrganization; 2004.42. Mathers, Colin D., Doris Ma Fat, and J. T. Boerma. The global burden ofdisease: 2004 update. World Health Organization. 2008.43. LeFevre AE, Shillcutt SD, Waters HR, Haider S, El Arifeen S, Mannan I, et al.Economic evaluation of neonatal care packages in a cluster-randomizedcontrolled trial in Sylhet. Bangladesh Bulletin of the WHO. 2013;91(10):736–45.44. Sachs J. Macroeconomics and health: investing in health for economicdevelopment. Geneva: World Health Organization; 2002.45. Drummond M, Sculpher M. Methods for the economic evaluation of healthcare. Oxford: Oxford University Press; 2005.46. Lopez AD, Salomon JA, Ahmad O, Murray CJL, Mafat D. Life tables for191 countries: data, methods, and results. GPE Discussion Paper SeriesNo 9. Geneva: World Health Organization; 2001. Online available at:http://www.who.int/healthinfo/paper09.pdf Accessed 20 May 201547. Coale AJ, Demeny P. Regional model life tables and stable populations.New York: Academic; 1983.48. Lopez AD, Mathers CD, Ezzati M, and et al. Sensitivity and uncertaintyanalysis. In global burden of disease and risk factors estimates. World Bank.2006. Online available at: https://books.google.ca/books?id=F8Abr-ofOwIC&pg=PA402&lpg=PA402&dq=age-weighting+in+sensitivity+analysis&source=bl&ots=5qGJrfPo-A&sig=akGBZJDmWfM8YzWNiNsS2Rz4B2A&hl=en&sa=X&ei=NbIMVcjcN4nioAThoIFQ&ved=0CDMQ6AEwAw#v=onepage&q=age-weighting%20in%20sensitivity%20analysis&f=false. Accessed 20 May 2015.49. Mitton C, Donaldson C. Health care priority setting: principles, practice andchallenges. Cost effectiveness and resource allocation. 2004;2(1):3–7.50. Millennium development goal 5: Improve maternal health. WHO. 2014.Online available at: http://www.who.int/topics/millennium_development_goals/maternal_health/en. Accessed 20 May 2015• Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistribution51. ClinicalTrials. Online available at: https://clinicaltrials.gov/ct2/results?term=maternal+health+and+cost+effectiveness+analysis&pg=1. Accessed 20 May201552. Bathala S. Delivering solutions to improve maternal health and increase accessto family planning. 2013. Online available at: http://www.wilsoncenter.org/sites/default/files/Delivering-Solutions-to-Improve-Maternal-Health-and-Increase-Access-to-Family-A-Wilson-Center-Policy-Brief.pdf. Accessed 20 May2015.Submit your manuscript at www.biomedcentral.com/submit


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