Health impact and cost-effectiveness of expanding routine immunization coverage in India through Intensified Mission Indradhanush.

Many children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. Evidence is even scarcer on the cost-effectiveness of strategies for reaching 'zero-dose children', who have not received any routine vaccines. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage. We focused on Intensified Mission Indradhanush (IMI), a large-scale PIRI intervention implemented in India in 2017-2018. In 40 sampled districts, we measured the incremental economic cost of IMI using primary data, and used controlled interrupted time-series regression to estimate the incremental vaccination doses delivered. We estimated deaths and disability-adjusted life years (DALYs) averted using the Lives Saved Tool and reported cost-effectiveness from immunization programme and societal perspectives. We found that, in sampled districts, IMI had an estimated incremental cost of 2021US$13.7 (95% uncertainty interval: 10.6 to 17.4) million from an immunization programme perspective and increased vaccine delivery by an estimated 2.2 (-0.5 to 4.8) million doses over a 12-month period, averting an estimated 1413 (-350 to 3129) deaths. The incremental cost from a programme perspective was $6.21 per dose ($2.80 to dominated), $82.99 per zero-dose child reached ($39.85 to dominated), $327.63 ($147.65 to dominated) per DALY averted, $360.72 ($162.56 to dominated) per life-year saved and $9701.35 ($4372.01 to dominated) per under-5 death averted. At a cost-effectiveness threshold of 1× per-capita GDP per DALY averted, IMI was estimated to be cost-effective with 90% probability. This evidence suggests IMI was both impactful and cost-effective for improving vaccination coverage, though there is a high degree of uncertainty in the results. As vaccination programmes expand coverage, unit costs may increase due to the higher costs of reaching currently unvaccinated children.

Framework for determining the optimal course of action when efficiency and affordability measures differ by perspective in cost-effectiveness analysis-with an illustrative case of HIV treatment in Mozambique.

BACKGROUND: Cost-effectiveness analysis (CEA) is a standard tool for evaluating health programs and informing decisions about resource allocation and prioritization. Most CEAs evaluating health interventions in low- and middle-income countries adopt a health sector perspective, accounting for resources funded by international donors and country governments, while often excluding out-of-pocket expenditures and time costs borne by program beneficiaries. Even when patients' costs are included, a companion analysis focused on the patient perspective is rarely performed. We view this as a missed opportunity. METHODS: We developed methods for assessing intervention affordability and evaluating whether optimal interventions from the health sector perspective also represent efficient and affordable options for patients. We mapped the five different patterns that a comparison of the perspective results can yield into a practical framework, and we provided guidance for researchers and decision-makers on how to use results from multiple perspectives. To illustrate the methodology, we conducted a CEA of six HIV treatment delivery models in Mozambique. We conducted a Monte Carlo microsimulation with probabilistic sensitivity analysis from both patient and health sector perspectives, generating incremental cost-effectiveness ratios for the treatment approaches. We also calculated annualized patient costs for the treatment approaches, comparing the costs with an affordability threshold. We then compared the cost-effectiveness and affordability results from the two perspectives using the framework we developed. RESULTS: In this case, the two perspectives did not produce a shared optimal approach for HIV treatment at the willingness-to-pay threshold of 0.3 × Mozambique's annual GDP per capita per DALY averted. However, the clinical 6-month antiretroviral drug distribution strategy, which is optimal from the health sector perspective, is efficient and affordable from the patient perspective. All treatment approaches, except clinical 1-month distributions of antiretroviral drugs which were standard before Covid-19, had an annual cost to patients less than the country's annual average for out-of-pocket health expenditures. CONCLUSION: Including a patient perspective in CEAs and explicitly considering affordability offers decision-makers additional insights either by confirming that the optimal strategy from the health sector perspective is also efficient and affordable from the patient perspective or by identifying incongruencies in value or affordability that could affect patient participation.

Unit cost repositories for health program planning and evaluation: a report on research in practice with lessons learned.

BACKGROUND: Most low- and middle-income countries have limited access to cost data that meets the needs of health policy-makers and researchers in health intervention areas including HIV, tuberculosis, and immunization. Unit cost repositories (UCRs)-searchable databases that systematically codify evidence from costing studies-have been developed to reduce the effort required to access and use existing costing information. These repositories serve as public resources and standard references, which can improve the consistency and quality of resource needs projections used for strategic planning and resource mobilization. UCRs also enable analysis of cost determinants and more informed imputation of missing cost data. This report examines our experiences developing and using seven UCRs (two global, five country-level) for cost projection and research purposes. DISCUSSION: We identify advances, challenges, enablers, and lessons learned that might inform future work related to UCRs. Our lessons learned include: (1) UCRs do not replace the need for costing expertise; (2) tradeoffs are required between the degree of data complexity and the useability of the UCR; (3) streamlining data extraction makes populating the UCR with new data easier; (4) immediate reporting and planning needs often drive stakeholder interest in cost data; (5) developing and maintaining UCRs requires dedicated staff time; (6) matching decision-maker needs with appropriate cost data can be challenging; (7) UCRs must have data quality control systems; (8) data in UCRs can become obsolete; and (9) there is often a time lag between the identification of a cost and its inclusion in UCRs. CONCLUSIONS: UCRs have the potential to be a valuable public good if kept up-to-date with active quality control and adequate support available to end-users. Global UCR collaboration networks and greater control by local stakeholders over global UCRs may increase active, sustained use of global repositories and yield higher quality results for strategic planning and resource mobilization.

Non-anaesthetist-administered ketamine for emergency caesarean section in Kenya: cost-effectiveness analysis.

OBJECTIVES: Lack of anaesthesia services is a frequent barrier to emergency surgeries such as caesarean delivery in Kenya. This study aimed to estimate the survival gains and cost-effectiveness of scaling up the Every Second Matters (ESM)-Ketamine programme that trains non-anaesthetist providers to administer and monitor ketamine during emergency caesarean deliveries. SETTING: Hospitals in Kenyan counties with low rates of caesarean delivery. PARTICIPANTS: Patients needing emergency caesarean delivery in settings without availability of standard anaesthesia service. INTERVENTIONS: Simulated scales up of the ESM-Ketamine programme over 5 years (2020-24) was compared with status quo. OUTCOME MEASURES: Cost of implementing the programme and corresponding additional emergency caesarean deliveries. Maternal and fetal/neonatal deaths prevented, and corresponding life-years gained due to increased provision of emergency caesarean procedures. Cost-effectiveness was assessed by comparing the cost per life-year gained of the ESM-Ketamine programme compared with status quo. RESULTS: Over 5 years, the expected gap in emergency caesarean deliveries was 157 000. A US$1.2 million ESM-Ketamine programme reduced this gap by 28 700, averting by 316 maternal and 4736 fetal deaths and generating 331 000 total life-years gained. Cost-effectiveness of scaling up the ESM-Ketamine programme was US$44 per life-year gained in the base case and US$251 in the most pessimistic scenario-a very good value for Kenya at less than 20% of per capita GDP per life-year gained. CONCLUSION: In areas of Kenya with significant underprovision of emergency caesarean delivery due to a lack of availability of traditional anaesthesia, an ESM-Ketamine programme is likely to enable a substantial number of life-saving surgeries at reasonable cost.

Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project.

BACKGROUND: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision referrals increased coverage and decreased incidence over ∼29 months of follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population. SETTING: Rural and periurban communities in Botswana. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications model to estimate lifetime health impact and cost of (1) earlier ART initiation and (2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio [US$/quality-adjusted life-years (QALY)] for CP vs. standard of care. RESULTS: In CP, 1418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an incremental cost-effectiveness ratio of $79 per QALY. CONCLUSIONS: Enhanced HIV testing, linkage, and early ART initiation improve life expectancy, reduce transmission, and can be cost-effective or cost-saving in settings like Botswana.

WHO-led consensus statement on vaccine delivery costing: process, methods, and findings.

BACKGROUND: Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization's (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement. METHODS: The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed. RESULTS: The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made. CONCLUSIONS: Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context.

Estimating the cost of COVID-19 vaccine deployment and introduction in Ghana using the CVIC tool.

BACKGROUND: This study estimated cost of COVID-19 vaccine introduction and deployment in Ghana. METHODS: Using the WHO-UNICEF COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool Ghana's Ministry of Health Technical Working Group for Health Technology Assessment (TWG-HTA) in collaboration with School of Public Health, University of Ghana, organized an initial two-day workshop that brought together partners to deliberate and agree on input parameters to populate the CVIC tool. A further 2-3 days validation with the Expanded Program of Immunization (EPI) and other partners to finalize the analysis was done. Three scenarios, with different combinations of vaccine products and delivery modalities, as well as time period were analyzed. The scenarios included AstraZeneca (40%), Johnson & Johnson (J&J) (30%), Moderna, Pfizer, and Sputnik V at 10% each; with primary schedule completed by second half of 2021 (Scenario 1); AstraZeneca (30%), J&J (40%), Moderna, Pfizer, and Sputnik V at 10% each with primary schedule completed by first half of 2022 (Scenario 2); and equal distribution (20%) among AstraZeneca, J&J, Moderna, Pfizer, and Sputnik V with primary schedule completed by second half of 2022 (Scenario 3). RESULTS: The estimated total cost of COVID-19 vaccination ranges between $348.7 and $436.1 million for the target population of 17.5 million. These translate into per person completed primary schedule cost of $20.9-$26.2 and per dose (including vaccine cost) of $10.5-$13.1. Again, per person completed primary schedule excluding vaccine cost was $4.5 and $4.6, thus per dose excluding vaccine also ranged from $2.2 - $2.3. The main cost driver was vaccine doses, including shipping, which accounts for between 78% and 83% of total cost. Further, an estimated 8,437-10,247 vaccinators (non-FTEs) would be required during 2021-2022 to vaccinate using a mix of delivery strategies, accounting for 8-10% of total cost. CONCLUSION: These findings provide the estimates to inform resource mobilization efforts by government and other partners.

Utilization patterns, outcomes and costs of a simplified acute malnutrition treatment programme in Burkina Faso.

Access to treatment for acute malnutrition remains a challenge, in part due to the fragmentation of treatment programmes based on case severity. This paper evaluates utilization patterns, outcomes and associated costs for treating acute malnutrition cases among a cohort of children in Burkina Faso. This study is a secondary analysis of a proof-of-concept trial, called Optimizing treatment for acute Malnutrition (OptiMA), conducted in Burkina Faso in 2016. A total of 4958 eligible children whose mid-upper arm circumference (MUAC) was less than 125 mm or with oedema were followed weekly and given ready-to-use therapeutic foods (RUTF). We evaluated the service utilization and outcomes among patients and estimated resource use and variable cost per patient, and examined factors driving variation in resource use. Children with lower initial MUAC level grew faster but required more time to recover than those with higher initial MUAC level. They also had higher rates of death, default and nonresponse. The simplified OptiMA approach for treating acute malnutrition achieved high rates of recovery overall (84%), especially among less severe cases, with modest quantities of RUTF. The average overall variable cost per child admitted was US$38.0 (SD: 20.5) half of which was accounted for by the cost of RUTF. Cost per recovered case was correlated with case severity, ranging from US$35.1 to US$132.8. If simplified integrated programmes using severity-based RUTF dosing can increase access to treatment at earlier, less severe stages of acute malnutrition, they can help avoid more serious and costlier cases.

Cost of vaccine delivery strategies in low- and middle-income countries during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has disrupted immunization services critical to the prevention of vaccine-preventable diseases in many low- and middle- income countries around the world. These services will need to be modified in order to minimize COVID-19 transmission and ensure the safety of health workers and the community. Additional budget will be required to implement these modifications that ensure safe delivery. METHODS: Using a simple modeling analysis, we estimated the additional resource requirements associated with modifications to supplementary immunization activities (campaigns) and routine immunization services via fixed sites and outreach in 2020 US dollars. We considered the following four categories of costs: (1) personal protective equipment (PPE) & infection prevention and control (IPC) measures for immunization sessions; (2) physical distancing and screening during immunization sessions; (3) delivery strategy changes, such as changes in session sizes and frequency; and (4) other operational cost increases, including additional social mobilization, training, and hazard pay to compensate health workers. RESULTS: We found that implementing a range of measures to protect health workers and communities from COVID-19 transmission could result in a per-facility start-up cost of $466-799 for routine fixed-site delivery and $12-220 for routine outreach delivery, and $12-108 per immunization campaign site. A recurrent monthly cost of $137-1,024 for fixed-site delivery and $152-848 for outreach delivery per facility could be incurred, and a $0.32-0.85 increase in the cost per dose during campaigns. CONCLUSIONS: By illustrating potential cost implications of providing immunization services through a range of strategies in a safe manner, these estimates can provide a benchmark for program managers and policy makers on the additional budget required. These findings can help country practitioners and global development partners planning the continuation of immunization services in the context of COVID-19.

Role of data from cost and other economic analyses in healthcare decision-making for HIV, TB and sexual/reproductive health programmes in South Africa.

An increasing focus on the use of the results of cost analyses and other economic evaluations in health programme decision-making by governments, donors and technical support partners working in low- and middle-income countries is accompanied by recognition that this use is impeded by several factors, including the lack of skills, data and coordination between spheres of the government. We describe our experience generating economic evaluation data for human immunodeficiency virus, tuberculosis and sexual/reproductive health programmes in South Africa alongside the results of a series of in-depth interviews (IDIs) among decision-makers within the South African government and implementing organizations (data users) and producers of economic evaluations (data producers). We summarize results across (1) the process of implementing a new intervention; (2) barriers to the use of cost data and suggested solutions and (3) the transferability of experiences to the planned South African implementation of universal health coverage (UHC). Based on our experience and the IDIs, we suggest concrete steps towards the improvement of economic data use in the planning and the establishment of structures mandated under the transition to UHC. Our key recommendations include the following: (1) compile a publicly available and regularly updated in-country cost repository; (2) increase the availability of programmatic outcomes data at the aggregate level; (3) agree upon and implement a set of primary decision criteria for the adoption and funding of interventions; (4) combine the efforts of health economics institutions into a stringent system for health technology assessments and (5) improve the link between national and provincial planning and budgeting.

The incremental cost of improving immunization coverage in India through the Intensified Mission Indradhanush programme.

Intensified Mission Indradhanush (IMI) was a strategic endeavour launched by the Government of India aiming to achieve 90% full immunization coverage in the country by 2018. The basic strategy of this special drive involved identifying missed children and vaccinating them in temporary outreach sites for 1 week over consecutive 4-month period starting from October 2017. This study estimated the incremental economic and financial cost of conducting IMI in India from a government provider perspective. Five states-Assam, Bihar, Maharashtra, Rajasthan and Uttar Pradesh were purposefully selected because of high concentration of IMI activities. The stratified random sample of 40 districts, 90 sub-districts and 289 sub-centres were included in this study. Cost data were retrospectively collected at all levels from administrative records, financial records and staff interviews involved in IMI. The weighted incremental economic cost per dose (including vaccine costs) was lowest in Uttar Pradesh (US$3.45) and highest in Maharashtra (U$12.23). Incremental economic cost per IMI dose was found to be higher than a recent routine immunization costing study by Chatterjee and colleagues in 2018, suggesting that it requires additional resources to immunize children through an intensified push in hard-to-reach areas. Incremental financial cost of the IMI programme estimated in this study will be helpful for the government for any future planning of such special initiative. The reasons for variation of unit costs of IMI across the study districts are not known, but lower baseline coverage, high population density, migration, geography and terrain and vaccinating small numbers of children per session could account for the range of findings. Further analysis is required to understand the determinants of cost variations of the IMI programme, which may aid in better planning and more efficient use of resources for future intensified efforts.

Impact of campaign-style delivery of routine vaccines: a quasi-experimental evaluation using routine health services data in India.

The world is not on track to achieve the goals for immunization coverage and equity described by the World Health Organization's Global Vaccine Action Plan. Many countries struggle to increase coverage of routine vaccination, and there is little evidence about how to do so effectively. In India in 2016, only 62% of children had received a full course of basic vaccines. In response, in 2017-18 the government implemented Intensified Mission Indradhanush (IMI), a nationwide effort to improve coverage and equity using a campaign-style strategy. Campaign-style approaches to routine vaccine delivery like IMI, sometimes called 'periodic intensification of routine immunization' (PIRI), are widely used, but there is little robust evidence on their effectiveness. We conducted a quasi-experimental evaluation of IMI using routine data on vaccine doses delivered, comparing districts participating and not participating in IMI. Our sample included all districts that could be merged with India's 2016 Demographic and Health Surveys data and had available data for the full study period. We used controlled interrupted time-series analysis to estimate the impact of IMI during the 4-month implementation period and in subsequent months. This method assumes that, if IMI had not occurred, vaccination trends would have changed in the same way in the participating and not participating districts. We found that, during implementation, IMI increased delivery of 13 infant vaccines, with a median effect of 10.6% (95% confidence interval 5.1% to 16.5%). We did not find evidence of a sustained effect during the 8 months after implementation ended. Over the 12 months from the beginning of implementation, we estimated reductions in the number of under-immunized children that were large but not statistically significant, ranging from 3.9% (-6.9% to 13.7%) to 35.7% (-7.5% to 77.4%) for different vaccines. The largest effects were for the first doses of vaccines against diphtheria-tetanus-pertussis and polio: IMI reached approximately one-third of children who would otherwise not have received these vaccines. This suggests that PIRI can be successful in increasing routine immunization coverage, particularly for early infant vaccines, but other approaches may be needed for sustained coverage improvements.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Cost-effectiveness of Frequent HIV Screening Among High-risk Young Men Who Have Sex With Men in the United States.

BACKGROUND: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. METHODS: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). RESULTS: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). CONCLUSIONS: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.

Producing Standardized Country-Level Immunization Delivery Unit Cost Estimates.

BACKGROUND: To plan for the financial sustainability of immunization programs and make informed decisions to improve immunization coverage and equity, decision-makers need to know how much these programs cost beyond the cost of the vaccine. Non-vaccine delivery cost estimates can significantly influence the cost-effectiveness estimates used to allocate resources at the country level. However, many low- and middle-income countries (LMICs) do not have immunization delivery unit cost estimates available, or have estimates that are uncertain, unreliable, or old. We undertook a Bayesian evidence synthesis to generate country-level estimates of immunization delivery unit costs for LMICs. METHODS: From a database of empirical immunization costing studies, we extracted estimates of the delivery cost per dose for routine childhood immunization services, excluding vaccine costs. A Bayesian meta-regression model was used to regress delivery cost per dose estimates, stratified by cost category, against a set of predictor variables including country-level [gross domestic product per capita, reported diphtheria-tetanus-pertussis third dose coverage (DTP3), population, and number of doses in the routine vaccination schedule] and study-level (study year, single antigen or programmatic cost per dose, and financial or economic cost) predictors. The fitted prediction model was used to generate standardized estimates of the routine immunization delivery cost per dose for each LMIC for 2009-2018. Alternative regression models were specified in sensitivity analyses. RESULTS: We estimated the prediction model using the results from 29 individual studies, covering 24 countries. The predicted economic cost per dose for routine delivery of childhood vaccines (2018 US dollars), not including the price of the vaccine, was $1.87 (95% uncertainty interval $0.64-4.38) across all LMICs. By individual cost category, the programmatic economic cost per dose for routine delivery of childhood vaccines was $0.74 ($0.26-1.70) for labor, $0.26 ($0.08-0.67) for supply chain, $0.22 ($0.06-0.57) for capital, and $0.65 ($0.20-1.66) for other service delivery costs. CONCLUSIONS: Accurate immunization delivery costs are necessary for assessing the cost-effectiveness and strategic planning needs of immunization programs. The cost estimates from this analysis provide a broad indication of immunization delivery costs that may be useful when accurate local data are unavailable.

A novel method to estimate the indirect community benefit of HIV interventions using a microsimulation model of HIV disease.

BACKGROUND: Microsimulation models of human immunodeficiency virus (HIV) disease that simulate individual patients one at a time and assess clinical and economic outcomes of HIV interventions often provide key details regarding direct individual clinical benefits ("individual benefit"), but they may lack detail on transmissions, and thus may underestimate an intervention's indirect benefits ("community benefit"). Dynamic transmission models can be used to simulate HIV transmissions, but they may do so at the expense of the clinical detail of microsimulations. We sought to develop, validate, and demonstrate a practical, novel method that can be integrated into existing HIV microsimulation models to capture this community benefit, integrating the effects of reduced transmission while keeping the clinical detail of microsimulations. METHODS: We developed a new method to capture the community benefit of HIV interventions by estimating HIV transmissions from the primary cohort of interest. The method captures the benefit of averting infections within the cohort of interest by estimating a corresponding gradual decline in incidence within the cohort. For infections averted outside the cohort of interest, our method estimates transmissions averted based on reductions in HIV viral load within the cohort, and the benefit (life-years gained and cost savings) of averting those infections based on the time they were averted. To assess the validity of our method, we paired it with the Cost-effectiveness of Preventing AIDS Complications (CEPAC) Model - a validated and widely-published microsimulation model of HIV disease. We then compared the consistency of model-estimated outcomes against outcomes of a widely-validated dynamic compartmental transmission model of HIV disease, the HIV Optimization and Prevention Economics (HOPE) model, using the intraclass correlation coefficient (ICC) with a two-way mixed effects model. Replicating an analysis done with HOPE, validation endpoints were number of HIV transmissions averted by offering pre-exposure prophylaxis (PrEP) to men who have sex with men (MSM) and people who inject drugs (PWID) in the US at various uptake and efficacy levels. Finally, we demonstrated an application of our method in a different setting by evaluating the clinical and economic outcomes of a PrEP program for MSM in India, a country currently considering PrEP rollout for this high-risk group. RESULTS: The new method paired with CEPAC demonstrated excellent consistency with the HOPE model (ICC = 0.98 for MSM and 0.99 for PWID). With only the individual benefit of the intervention incorporated, a PrEP program for MSM in India averted 43,000 transmissions over a 5-year period and resulted in a lifetime incremental cost-effectiveness ratio (ICER) of US$2,300/year-of-life saved (YLS) compared to the status quo. After applying both the direct (individual) and indirect (community) benefits, PrEP averted 86,000 transmissions over the same period and resulted in an ICER of US$600/YLS. CONCLUSIONS: Our method enables HIV microsimulation models that evaluate clinical and economic outcomes of HIV interventions to estimate the community benefit of these interventions (in terms of survival gains and cost savings) efficiently and without sacrificing clinical detail. This method addresses an important methodological gap in health economics microsimulation modeling and allows decision scientists to make more accurate policy recommendations.

Systematic review of the costs and effectiveness of interventions to increase infant vaccination coverage in low- and middle-income countries.

BACKGROUND: In recent years, several large studies have assessed the costs of national infant immunization programs, and the results of these studies are used to support planning and budgeting in low- and middle-income countries. However, few studies have addressed the costs and cost-effectiveness of interventions to improve immunization coverage, despite this being a major focus of policy attention. Without this information, countries and international stakeholders have little objective evidence on the efficiency of competing interventions for improving coverage. METHODS: We conducted a systematic literature review on the costs and cost-effectiveness of interventions to improve immunization coverage in low- and middle-income countries, including both published and unpublished reports. We evaluated the quality of included studies and extracted data on costs and incremental coverage. Where possible, we calculated incremental cost-effectiveness ratios (ICERs) to describe the efficiency of each intervention in increasing coverage. RESULTS: A total of 14 out of 41 full text articles reviewed met criteria for inclusion in the final review. Interventions for increasing immunization coverage included demand generation, modified delivery approaches, cash transfer programs, health systems strengthening, and novel technology usage. We observed substantial heterogeneity in costing methods and incompleteness of cost and coverage reporting. Most studies reported increases in coverage following the interventions, with coverage increasing by an average of 23 percentage points post-intervention across studies. ICERs ranged from $0.66 to $161.95 per child vaccinated in 2017 USD. We did not conduct a meta-analysis given the small number of estimates and variety of interventions included. CONCLUSIONS: There is little quantitative evidence on the costs and cost-effectiveness of interventions for improving immunization coverage, despite this being a major objective for national immunization programs. Efforts to improve the level of costing evidence-such as by integrating cost analysis within implementation studies and trials of immunization scale up-could allow programs to better allocate resources for coverage improvement. Greater adoption of standardized cost reporting methods would also enable the synthesis and use of cost data.

Rapid, point-of-care diagnosis of tuberculosis with novel Truenat assay: Cost-effectiveness analysis for India's public sector.

BACKGROUND: Truenat is a novel molecular assay that rapidly detects tuberculosis (TB) and rifampicin-resistance. Due to the portability of its battery-powered testing platform, it may be valuable in peripheral healthcare settings in India. METHODS: Using a microsimulation model, we compared four TB diagnostic strategies for HIV-negative adults with presumptive TB: (1) sputum smear microscopy in designated microscopy centers (DMCs) (SSM); (2) Xpert MTB/RIF in DMCs (Xpert); (3) Truenat in DMCs (Truenat DMC); and (4) Truenat for point-of-care testing in primary healthcare facilities (Truenat POC). We projected life expectancy, costs, incremental cost-effectiveness ratios (ICERs), and 5-year budget impact of deploying Truenat POC in India's public sector. We defined a strategy "cost-effective" if its ICER was

Incorporating costing study results into district and service planning to enhance immunization programme performance: a Zambian case study.

Donors, researchers and international agencies have made significant investments in collection of high-quality data on immunization costs, aiming to improve the efficiency and sustainability of services. However, improved quality and routine dissemination of costing information to local managers may not lead to enhanced programme performance. This study explored how district- and service-level managers can use costing information to enhance planning and management to increase immunization outputs and coverage. Data on the use of costing information in the planning and management of Zambia's immunization programme was obtained through individual and group semi-structured interviews with planners and managers at national, provincial and district levels. Document review revealed the organizational context within which managers operated. Qualitative results described managers' ability to use costing information to generate cost and efficiency indicators not provided by existing systems. These, in turn, would allow them to understand the relative cost of vaccines and other resources, increase awareness of resource use and management, benchmark against other facilities and districts, and modify strategies to improve performance. Managers indicated that costing information highlighted priorities for more efficient use of human resources, vaccines and outreach for immunization programming. Despite decentralization, there were limitations on managers' decision-making to improve programme efficiency in practice: major resource allocation decisions were made centrally and planning tools did not focus on vaccine costs. Unreliable budgets and disbursements also undermined managers' ability to use systems and information. Routine generation and use of immunization cost information may have limited impact on managing efficiency in many Zambian districts, but opportunities were evident for using existing capacity and systems to improve efficiency. Simpler approaches, such as improving reliability and use of routine immunization and staffing indicators, drawing on general insights from periodic costing studies, and focusing on maximizing coverage with available resources, may be more feasible in the short-term.