How to increase and maintain high immunization coverage: Vaccination Demand Resilience (VDR) framework.

BACKGROUND: Resilience in vaccination demand is ever more critical as the COVID-19 pandemic has increased our understanding of the importance of vaccines on health and well-being. Yet timid demand for COVID-19 vaccines where available and reduced uptake of routine immunizations globally further raise the urgent need to build vaccination resilience. We demonstrate the complexity of vaccination demand and resilience in a framework where relevant dimensions are intertwined, fluid, and contextual. METHODS: We developed the Vaccination Demand Resilience (VDR) framework based on a literature review on vaccination demand and expert consultation. The matrix framework builds on three main axes: 1) vaccination attitudes and beliefs; 2) vaccination seeking behavior; and 3) vaccination status. The matrix generated eight quadrants, which can help explain people's levels of vaccination demand and resilience. We selected four scenarios as examples to demonstrate different interventions that could move people across quadrants and build vaccination resilience. RESULTS: Incongruence between individuals' attitudes and beliefs, vaccination behavior, and vaccination status can arise. For example, an individual can be vaccinated due to mandates but reject vaccination benefits and otherwise avoid seeking vaccination. Such incongruence could be altered by interventions to build resilience in vaccination demand. These interventions include information, education and communication to change individuals' vaccination attitudes and beliefs, incentive programs and reminder-recalls to facilitate vaccination seeking, or by strengthening healthcare provider communications to reduce missed opportunities. CONCLUSIONS: Vaccination decision-making is complex. Individuals can be vaccinated without necessarily accepting the benefits of vaccination or seeking vaccination, threatening resilience in vaccination demand. The VDR framework can provide a useful lens for program managers and policy makers considering interventions and policies to improve vaccination resilience. This would help build and sustain confidence and demand for vaccinations, and help to continue to prevent disease, disability, and death from vaccine-preventable diseases.

Impact of the COVID-19 Pandemic on Medical Product Procurement, Prices, and Supply Chain in Zimbabwe: Lessons for Supply Chain Resiliency.

BACKGROUND: The COVID-19 pandemic has disrupted global health supply chains including manufacturing, storage, and delivery of essential medicines, testing kits, personal protective equipment, and laboratory reagents. We sought to document how pandemic impacted the procurement, prices, and supply chain of medical products in Zimbabwe. METHODS: We conducted semistructured in-depth key informant interviews with 36 health system stakeholders in Zimbabwe involved in medicine procurement. Respondents included pharmacists, regulatory officers, and procurement and supply chain management professionals from public and private sectors. RESULTS: Before the COVID-19 pandemic, respondents described experiencing long-standing resource constraints, medicine shortages, foreign currency shortages, and supply chain inefficiencies. The pandemic exacerbated this situation due to supply constraints, export restrictions, medicine shortages, and movement restrictions that disrupted logistical and stock management systems. Competitive bidding and tendering processes experienced reduced participation by international suppliers. Significant price increases were initially observed among internationally shipped medicines and for personal protective equipment to cover additional freight costs. COVID-19 pandemic impacts were moderated by reduced patient demand and lower health services utilization, resulting in fewer supply shocks and less price volatility. Further, health system adaptations such as switching treatment regimens, modifying dispensing schedules based on stock availability, redistributing stock of medicines among facilities, and new service delivery models such as integrated outreach services helped ensure continued patient access to medicines. CONCLUSIONS: Our findings highlight the need for policies that ensure continuity in access to health services and medical products, even during a pandemic, by avoiding blanket restrictions on medical product exports and imports. Pooled procurement, especially at regional and global levels, with long-term service agreements may help achieve greater resiliency to supply and price shocks from supply chain disruptions. Interventions across manufacturing, trade, and regulatory policy and service delivery models are also needed for supply chain resiliency.

Impact of the COVID-19 pandemic on the quality of medical products in Zimbabwe: a qualitative study based on key informant interviews with health system stakeholders.

OBJECTIVE: To explore the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the quality of medical products in Zimbabwe, including market risks for substandard and falsified products and impacts on quality assurance activities. DESIGN: Qualitative study based on in-depth key informant interviews. SETTING: Health system stakeholders across the medical product supply chain in Zimbabwe. PARTICIPANTS: 36 key informants were interviewed between April and June 2021. RESULTS: We found that the COVID-19 pandemic disrupted quality assurance and regulatory activities of medical products in Zimbabwe, resulted in observations of poor-quality personal protective equipment (PPE) and other COVID-19-related products and led to increased risks to quality. Risks to quality due to COVID-19-related disruptions included increased layers of agents in the supply chain and an influx of non-traditional suppliers. COVID-19-related movement restrictions reduced access to health facilities and thus may have increased the usage of the informal market where smuggled and unregistered medical products are sold with less oversight by the regulator. Most reports of poor-quality medical products were for PPE, such as masks and infrared thermometers, used for the COVID-19 response. Besides these reports, many participants stated that the quality of essential medicines in the formal sector, not related to COVID-19, had largely been maintained during the pandemic due to the regulator's stringent quality assurance process. Incentives for suppliers to maintain quality to retain large donor-funded contracts, and the need for local wholesalers and distributors to comply with quality-related aspects of distribution agreements with global manufacturers of brand-name medical products, mitigated threats to quality. CONCLUSIONS: The COVID-19 pandemic presented opportunities and market risks for circulation of substandard and falsified medical products in Zimbabwe. There is a need for policymakers to invest in measures to safeguard the quality of medical products during emergencies and to build resiliency against future supply chain shocks.

Variations in global prices of chemotherapy for childhood cancer: a descriptive analysis.

Background: The stark disparity in survival for children with cancer across the world has inspired a global call to expand chemotherapy access in low and middle income countries. Among the numerous barriers to success, a paucity of reliable information regarding chemotherapy pricing hinders the ability of governments and other key stakeholders to make informed budget decisions or negotiate lower medication prices. The aim of this study was to generate comparative price information on both individual chemotherapy agents and comprehensive treatment regimens for common childhood cancers using real-world data. Methods: Chemotherapy agents were selected based on their inclusion in the World Health Organization (WHO) Essential Medicines List for Children (EMLc) and their use in frontline regimens for the tracer cancer types prioritized by the WHO's Global Initiative for Childhood Cancer (GICC). Sources included IQVIA MIDAS data, obtained under license from IQVIA, and publicly available data from Management Sciences for Health (MSH). Data on chemotherapy prices and purchase volumes spanning 2012-2019 were aggregated according to WHO region and World Bank (WB) income classification. Cumulative chemotherapy prices for treatment regimens were compared across WB income classification. Findings: Data representing an estimated 1.1 billion doses of chemotherapy were obtained for 97 countries: 43 high income countries (HICs), 28 upper middle income countries (UMICs), and 26 low and lower middle income countries (LLMICs). Median drug prices in HICs were 0.9-20.4 times those of UMICs and 0.9-15.5 times those of LMICs. Regimen prices were generally higher for HICs, hematologic malignancies, non-adapted protocols, and higher risk stratification or stage, albeit with notable exceptions. Interpretation: This study represents the largest price analysis to date of chemotherapy agents used globally in childhood cancer therapy. The findings of this study form a basis for future cost-effectiveness analysis in pediatric cancer and should inform efforts of governments and stakeholders to negotiate drug prices and develop pooled purchasing strategies. Funding: NB received funding support from the American Lebanese Syrian Associated Charities and Cancer Center Support grant (CA21765) from the National Cancer Institute through the National Institutes of Health. TA received funding through the University of North Carolina Oncology K12 (K12CA120780) and the University Cancer Research Fund from the UNC Lineberger Comprehensive Cancer Center.

Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries.

Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2-14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8-2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3-32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0-18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7-17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

Educational and economic returns to cognitive ability in low- and middle-income countries: A systematic review.

There is growing interest to use early cognitive ability to predict schooling and employment outcomes in low- and middle-income countries (LMICs). Rather than using educational attainment and school enrollment as predictors of future economic growth or of improving an individual's earning potential, mounting evidence suggests that cognitive ability may be a better predictor. The relationship between cognitive ability, education, and employment are essential to predict future development in LMICs. We performed a systematic literature review and meta-analysis of the evidence regarding the relationship between cognitive ability and educational outcomes, and between cognitive ability and economic outcomes across LMICs. We searched peer-reviewed studies since 2000 that quantitatively measured these relationships. Based on an initial search of 3,766 records, we identified 14 studies, including 8 studies that examined the cognition-education link and 8 studies that assessed cognition-employment returns in LMICs. Identified studies showed that higher cognitive ability increased the probability of school enrollment, academic achievement, and educational attainment across LMICs. A meta-analysis of returns to wages from cognitive ability suggested that a standard deviation increase in cognitive test scores was associated with a 4.5% (95% CI 2.6%-9.6%) increase in wages. Investments into early cognitive development could play a critical role in improving educational and economic outcomes in LMICs. Further research should focus particularly in low-income countries with the least evidence, and examine the impact on education and economic outcomes by cognitive domains to provide more robust evidence for policy makers to take action.

Systematic review of the costs for vaccinators to reach vaccination sites: Incremental costs of reaching hard-to-reach populations.

INTRODUCTION: Economic evidence on how much it may cost for vaccinators to reach populations is important to plan vaccination programs. Moreover, knowing the incremental costs to reach populations that have traditionally been undervaccinated, especially those hard-to-reach who are facing supply-side barriers to vaccination, is essential to expanding immunization coverage to these populations. METHODS: We conducted a systematic review to identify estimates of costs associated with getting vaccinators to all vaccination sites. We searched PubMed and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the following costs to vaccinators: (1) training costs; (2) labor costs, per diems, and incentives; (3) identification of vaccine beneficiary location; and (4) travel costs. We assessed if any of these costs were specific to populations that are hard-to-reach for vaccination, based on a framework for examining supply-side barriers to vaccination. RESULTS: We found 19 studies describing average vaccinator training costs at $0.67/person vaccinated or targeted (SD $0.94) and $0.10/dose delivered (SD $0.07). The average cost for vaccinator labor and incentive costs across 29 studies was $2.15/dose (SD $2.08). We identified 13 studies describing intervention costs for a vaccinator to know the location of a beneficiary, with an average cost of $19.69/person (SD $26.65), and six studies describing vaccinator travel costs, with an average cost of $0.07/dose (SD $0.03). Only eight of these studies described hard-to-reach populations for vaccination; two studies examined incremental costs per dose to reach hard-to-reach populations, which were 1.3-2 times higher than the regular costs. The incremental cost to train vaccinators was $0.02/dose, and incremental labor costs for targeting hard-to-reach populations were $0.16-$1.17/dose. CONCLUSION: Additional comparative costing studies are needed to understand the potential differential costs for vaccinators reaching the vaccination sites that serve hard-to-reach populations. This will help immunization program planners and decision-makers better allocate resources to extend vaccination programs.

Promoting, seeking, and reaching vaccination services: A systematic review of costs to immunization programs, beneficiaries, and caregivers.

INTRODUCTION: Understanding the costs to increase vaccination demand among under-vaccinated populations, as well as costs incurred by beneficiaries and caregivers for reaching vaccination sites, is essential to improving vaccination coverage. However, there have not been systematic analyses documenting such costs for beneficiaries and caregivers seeking vaccination. METHODS: We searched PubMed, Scopus, and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the costs for beneficiaries and caregivers to 1) seek and know how to access vaccination (i.e., costs to immunization programs for social mobilization and interventions to increase vaccination demand), 2) take time off from work, chores, or school for vaccination (i.e., productivity costs), and 3) travel to vaccination sites. We assessed if these costs were specific to populations that faced other non-cost barriers, based on a framework for defining hard-to-reach and hard-to-vaccinate populations for vaccination. RESULTS: We found 57 studies describing information, education, and communication (IEC) costs, social mobilization costs, and the costs of interventions to increase vaccination demand, with mean costs per dose at $0.41 (standard deviation (SD) $0.83), $18.86 (SD $50.65) and $28.23 (SD $76.09) in low-, middle-, and high-income countries, respectively. Five studies described productivity losses incurred by beneficiaries and caregivers seeking vaccination ($38.33 per person; SD $14.72; n = 3). We identified six studies on travel costs incurred by beneficiaries and caregivers attending vaccination sites ($11.25 per person; SD $9.54; n = 4). Two studies reported social mobilization costs per dose specific to hard-to-reach populations, which were 2-3.5 times higher than costs for the general population. Eight studies described barriers to vaccination among hard-to-reach populations. CONCLUSION: Social mobilization/IEC costs are well-characterized, but evidence is limited on costs incurred by beneficiaries and caregivers getting to vaccination sites. Understanding the potential incremental costs for populations facing barriers to reach vaccination sites is essential to improving vaccine program financing and planning.

A systems map of the economic considerations for vaccination: Application to hard-to-reach populations.

BACKGROUND: Understanding the economics of vaccination is essential to developing immunization strategies that can be employed successfully with limited resources, especially when vaccinating populations that are hard-to-reach. METHODS: Based on the input from interviews with 24 global experts on immunization economics, we developed a systems map of the mechanisms (i.e., necessary steps or components) involved in vaccination, and associated costs and benefits, focused at the service delivery level. We used this to identify the mechanisms that may be different for hard-to-reach populations. RESULTS: The systems map shows different mechanisms that determine whether a person may or may not get vaccinated and the potential health and economic impacts of doing so. The map is divided into two parts: 1) the costs of vaccination, representing each of the mechanisms involved in getting vaccinated (n = 23 vaccination mechanisms), their associated direct vaccination costs (n = 18 vaccination costs), and opportunity costs (n = 5 opportunity costs), 2) the impact of vaccination, representing mechanisms after vaccine delivery (n = 13 impact mechanisms), their associated health effects (n = 10 health effects for beneficiary and others), and economic benefits (n = 13 immediate and secondary economic benefits and costs). Mechanisms that, when interrupted or delayed, can result in populations becoming hard-to-reach include getting vaccines and key stakeholders (e.g., beneficiaries/caregivers, vaccinators) to a vaccination site, as well as vaccine administration at the site. CONCLUSION: Decision-makers can use this systems map to understand where steps in the vaccination process may be interrupted or weak and identify where gaps exist in the understanding of the economics of vaccination. With improved understanding of system-wide effects, this map can help decision-makers inform targeted interventions and policies to increase vaccination coverage in hard-to-reach populations.

A systematic review of the role of pharmacists in vaccination services in low-and middle-income countries.

BACKGROUND: Pharmacists' role in vaccination has expanded in some countries with pharmacists having greater authority to perform various immunization activities, from vaccine storage, vaccine adverse event reporting, vaccination education and advocacy, to vaccine administration. However, pharmacists' present involvement in vaccination services is poorly understood across low- and middle-income countries (LMICs). OBJECTIVE: To identify and synthesize evidence on pharmacists' roles in offering vaccination services in LMICs. METHODS: We searched three databases (PubMed, Embase, Scopus) and the gray literature to identify articles which described pharmacist involvement in vaccination services in LMICs. We abstracted data on reported roles of pharmacists in vaccination, as well as relevant country, vaccines, and populations served. RESULTS: From the initial 612 records we identified, twenty-five (n = 25) studies representing 25 LMICs met our inclusion criteria. The most commonly reported role of pharmacists in vaccination across identified LMICs was vaccine advocacy and education (n = 15 countries). Pharmacist administered vaccination and storage of vaccines at pharmacies was reported in 8 countries. An additional 6 countries reported allowing vaccination at community pharmacies by other healthcare professionals. Immunization related training for pharmacists was reported or required in 8 countries. Fewer studies reported that pharmacists have access to patient immunization records in their respective LMICs (n = 6 countries) or had reported pharmacist involvement in vaccine adverse event reporting (n = 4 countries). CONCLUSIONS: Pharmacists have the potential to play an important role in increasing access to vaccines and improving coverage, yet evidence of their role in vaccinations remains limited across LMICs. Greater documentation of pharmacists' involvement in vaccination services in LMICs is needed to demonstrate the value of successful integration of pharmacists in immunization programs.

Health versus other sectors: Multisectoral resource allocation preferences in Mukono district, Uganda.

OBJECTIVES: To elicit citizen preferences for national budget resource allocation in Uganda, examine respondents' preferences for health vis-à-vis other sectors, and compare these preferences with actual government budget allocations. METHODS: We surveyed 432 households in urban and rural areas of Mukono district in central Uganda.We elicited citizens' preferences for resource allocation across all sectors using a best-worst scaling (BWS) survey. The BWS survey consisted of 16 sectors corresponding to the Uganda national budget line items. Respondents chose, from a subset of four sectors across 16 choice tasks, which sectors they thought were most and least important to allocate resources to. We utilized the relative best-minus-worst score method and a conditional logistic regression to obtain ranked preferences for resource allocation across sectors. We then compared the respondents' preferences with actual government budget allocations. RESULTS: The health sector was the top ranked sector where 82% of respondents selected health as the most important sector for the government to fund, but it was ranked sixth in national budget allocation, encompassing 6.4% of the total budget. Beyond health, water and environment, agriculture, and social development sectors were largely underfunded compared to respondents' preferences. Works and transport, education, security, and justice, law and order received a larger share of the national budget compared to respondents' preferences. CONCLUSIONS: Among respondents from Mukono district in Uganda, we found that citizens' preferences for resource allocation across sectors, including for the health sector, were fundamentally misaligned with current government budget allocations. Evidence of respondents' strong preferences for allocating resources to the health sector could help stakeholders make the case for increased health sector allocations. Greater investment in health is not only essential to satisfy citizens' needs and preferences, but also to meet the government's health goals to improve health, strengthen health systems, and achieve universal health coverage.

Importance of medicine quality in achieving universal health coverage.

OBJECTIVE: To assess the importance of ensuring medicine quality in order to achieve universal health coverage (UHC). METHODS: We developed a systems map connecting medicines quality assurance systems with UHC goals to illustrate the ensuing impact of quality-assured medicines in the implementation of UHC. The association between UHC and medicine quality was further examined in the context of essential medicines in low- and middle-income countries (LMICs) by analyzing data on reported prevalence of substandard and falsified essential medicines and established indicators for UHC. Finally, we examined the health and economic savings of improving antimalarial quality in four countries in sub-Saharan Africa: the Democratic Republic of the Congo (DRC), Nigeria, Uganda, and Zambia. FINDINGS: A systems perspective demonstrates how quality assurance of medicines supports dimensions of UHC. Across 63 LMICs, the reported prevalence of substandard and falsified essential medicines was found to be negatively associated with both an indicator for coverage of essential services (p = 0.05) and with an indicator for government effectiveness (p = 0.04). We estimated that investing in improving the quality of antimalarials by 10% would result in annual savings of $8.3 million in Zambia, $14 million in Uganda, $79 million in two DRC regions, and $598 million in Nigeria, and was more impactful compared to other potential investments we examined. Costs of substandard and falsified antimalarials per malaria case ranged from $7 to $86, while costs per death due to poor-quality antimalarials ranged from $14,000 to $72,000. CONCLUSION: Medicines quality assurance systems play a critical role in reaching UHC goals. By ensuring the quality of essential medicines, they help deliver effective treatments that lead to less illness and result in health care savings that can be reinvested towards UHC.

Screening for Traumatic Experiences and Mental Health Distress Among Women in HIV Care in Cape Town, South Africa.

Traumatic events can negatively affect clinical outcomes among HIV positive women, particularly when those events result in ongoing psychological distress. Consequently, there have been calls to integrate screening and treatment of traumatic experiences and associated mental health disorders into HIV care. In South Africa, screening for traumatic experiences and mental health is not a routine part of HIV care. The goal of this study was to examine the prevalence of traumatic experiences and mental health distress among women in an HIV clinic in Cape Town, South Africa, and to explore the acceptability of routine screening in this setting. Seventy HIV positive women were screened following referral from health care workers in the clinic. Among the participants, 51% reported a history of sexual abuse and 75% reported physical intimate partner violence (physical IPV). Among all participants, 36% met screening criteria for depression; among those with traumatic experiences (n = 57), 70% met screening criteria for posttraumatic stress disorder (PTSD). Compared with reporting no sexual abuse or physical IPV, having experienced both sexual abuse and physical IPV was significantly associated with higher odds of depression, while reporting either sexual abuse or physical IPV individually was not significantly associated with increased odds of depression. Among women reporting sexual abuse, 61% were disclosing their experience for the first time during the screening; 31% of women with physical IPV experience were disclosing for the first time. Overall, 98% of participants thought screening should be routine and extended to all women as part of clinic care. Screening women for sexual abuse and physical IPV may be an important component of ensuring HIV care engagement.

Trust in vaccines and medicines in Uganda.

Trust underlies numerous decisions in health care, affecting vaccine uptake as well as care seeking rates, treatment adherence, and health outcomes. Although trust in the doctor-patient relationship has garnered much attention, trust in health care commodities such as vaccines and medicines has rarely been examined. We report findings from a cross-sectional survey to assess trust in vaccines vis-à-vis their trust in conventional medicines and traditional medicines in Uganda. Trust in vaccines, conventional and traditional medicines were assessed by adapting the vaccine hesitancy scale developed by the SAGE Working Group on Vaccine Hesitancy. Reported trust in vaccines and conventional medicines was much higher than trust in traditional medicines. Significant associations were observed between trust in vaccines and trust in conventional medicines. Of the trust components explored, respondents were most concerned about access to and safety of vaccines and medicines. Further, respondents' previous health care experiences, primary source of health information, and trust in providers' skills were significantly associated with reported trust in vaccines and medicines. Although strong levels of trust in vaccines and conventional medicines were observed overall, the findings identify areas where policies and communication efforts can focus to strengthen trust.

Defining hard-to-reach populations for vaccination.

Extending the benefits of vaccination to everyone who is eligible requires an understanding of which populations current vaccination efforts have struggled to reach. A clear definition of "hard-to-reach" populations - also known as high-risk or marginalized populations, or reaching the last mile - is essential for estimating the size of target groups, sharing lessons learned based on consistent definitions, and allocating resources appropriately. A literature review was conducted to determine what formal definitions of hard-to-reach populations exist and how they are being used, and to propose definitions to consider for future use. Overall, we found that (1) there is a need to distinguish populations that are hard to reach versus hard to vaccinate, and (2) the existing literature poorly defined these populations and clear criteria or thresholds for classifying them were missing. Based on this review, we propose that hard-to-reach populations be defined as those facing supply-side barriers to vaccination due to geography by distance or terrain, transient or nomadic movement, healthcare provider discrimination, lack of healthcare provider recommendations, inadequate vaccination systems, war and conflict, home births or other home-bound mobility limitations, or legal restrictions. Although multiple mechanisms may apply to the same population, supply-side barriers should be distinguished from demand-side barriers. Hard-to-vaccinate populations are defined as those who are reachable but difficult to vaccinate due to distrust, religious beliefs, lack of awareness of vaccine benefits and recommendations, poverty or low socioeconomic status, lack of time to access available vaccination services, or gender-based discrimination. Further work is needed to better define hard-to-reach populations and delineate them from populations that may be hard to vaccinate due to complex refusal reasons, improve measurement of the size and importance of their impact, and examine interventions related to overcoming barriers for each mechanism. This will enable policy makers, governments, donors, and the vaccine community to better plan interventions and allocate necessary resources to remove existing barriers to vaccination.

Economic value of vaccinating geographically hard-to-reach populations with measles vaccine: A modeling application in Kenya.

BACKGROUND: Since special efforts are necessary to vaccinate people living far from fixed vaccination posts, decision makers are interested in knowing the economic value of such efforts. METHODS: Using our immunization geospatial information system platform and a measles compartment model, we quantified the health and economic value of a 2-dose measles immunization outreach strategy for children <24 months of age in Kenya who are geographically hard-to-reach (i.e., those living outside a specified catchment radius from fixed vaccination posts, which served as a proxy for access to services). FINDINGS: When geographically hard-to-reach children were not vaccinated, there were 1427 total measles cases from 2016 to 2020, resulting in $9.5 million ($3.1-$18.1 million) in direct medical costs and productivity losses and 7504 (3338-12,903) disability-adjusted life years (DALYs). The outreach strategy cost $76 ($23-$142)/DALY averted (compared to no outreach) when 25% of geographically hard-to-reach children received MCV1, $122 ($40-$226)/DALY averted when 50% received MCV1, and $274 ($123-$478)/DALY averted when 100% received MCV1. CONCLUSION: Outreach vaccination among geographically hard-to-reach populations was highly cost-effective in a wide variety of scenarios, offering support for investment in an effective outreach vaccination strategy.

Modeling the Economic Impact of Substandard and Falsified Antimalarials in the Democratic Republic of the Congo.

Substandard and falsified medicines pose significant risks to global health, including increased deaths, prolonged treatments, and growing drug resistance. Antimalarials are one of the most common medications to be of poor quality in low- and middle-income countries. We assessed the health and economic impact of substandard and falsified antimalarials for children less than 5 years of age in the Democratic Republic of the Congo, which has one of the world's highest malaria mortality rates. We developed an agent-based model to simulate patient care-seeking behavior and medicine supply chain processes to examine the impact of antimalarial quality in Kinshasa province and Katanga region. We simulated the impact of potential interventions to improve medicinal quality, reduce stockouts, or educate caregivers. We estimated that substandard and falsified antimalarials are responsible for $20.9 million (35% of $59.6 million; 95% CI: $20.7-$21.2 million) in malaria costs in Kinshasa province and $130 million (43% of $301 million; $129-$131 million) in malaria costs in the Katanga region annually. If drug resistance to artemisinin were to develop, total annual costs of malaria could increase by $17.9 million (30%; $17.7-$18.0 million) and $73 million (24%; $72.2-$72.8 million) in Kinshasa and Katanga, respectively. Replacing substandard and falsified antimalarials with good quality medicines had a larger impact than interventions that prevented stockouts or educated caregivers. The results highlight the importance of improving access to good quality antimalarials to reduce the burden of malaria and mitigate the development of antimalarial resistance.

Systematic review of the incremental costs of interventions that increase immunization coverage.

Achieving and maintaining high vaccination coverage requires investments, but the costs and effectiveness of interventions to increase coverage remain poorly characterized. We conducted a systematic review of the literature to identify peer-reviewed studies published in English that reported interventions aimed at increasing immunization coverage and the associated costs and effectiveness of the interventions. We found limited information in the literature, with many studies reporting effectiveness estimates, but not providing cost information. Using the available data, we developed a cost function to support future programmatic decisions about investments in interventions to increase immunization coverage for relatively low and high-income countries. The cost function estimates the non-vaccine cost per dose of interventions to increase absolute immunization coverage by one percent, through either campaigns or routine immunization. The cost per dose per percent increase in absolute coverage increased with higher baseline coverage, demonstrating increasing incremental costs required to reach higher coverage levels. Future studies should evaluate the performance of the cost function and add to the database of available evidence to better characterize heterogeneity in costs and generalizability of the cost function.

Out-of-Pocket Household Expenditures on Medical Injections in Cambodia.

BACKGROUND: Cambodia has one of the highest rates of overall medical injection usage worldwide. Therapeutic injections, which are often unnecessary, contribute to the spread of blood-borne diseases. OBJECTIVE: This study describes injection practices and associated household expenditures in rural northwest Cambodia. METHODS: We assessed care-seeking patterns of surveyed adult family members who sought healthcare in the previous 30 days, including location of care, medical injection use, and out-of-pocket household expenditures for treatment. A regression model was used to explore the impact of injection use on out-of-pocket household expenditures. RESULTS: Among 480 households sampled, 298 included members who had been sick within the previous 30 days; a total of 342 episodes of care had been sought. Private providers accounted for over 66% (n = 226) of all episodes of care, with public and informal providers accounting for 20% (n = 69) and 14% (n = 47), respectively. Injections were administered in over 120 (35%) episodes of care, with 81% of injections administered by private providers. Patients who received injections incurred total out-of-pocket household expenditures that were, on average, 126,590 Cambodian Riel (KHR) (US$31.65) higher than those who did not receive injections (p < 0.01), equivalent to nearly half of the country's total annual health expenditure per capita. Receiving injections and perceived severity of illness were significantly associated with higher out-of-pocket household expenditures. CONCLUSION: This study found high levels of medical injection use, particularly among private healthcare providers, which was significantly associated with high healthcare expenditures. Reducing the number of medical injections would not only reduce disease transmission risk but also contribute to reduced healthcare costs and greater financial protection.

Prevalence and Estimated Economic Burden of Substandard and Falsified Medicines in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

Importance: Substandard and falsified medicines burden health systems by diverting resources to ineffective or harmful therapies, causing medical complications and prolonging illnesses. However, the prevalence and economic impact of poor-quality medicines is unclear. Objective: To conduct a systematic review and meta-analysis to assess the prevalence and estimated economic burden of substandard and falsified essential medicines in low- and middle-income countries. Data Sources: Five databases (PubMed, EconLit, Global Health, Embase, and Scopus) were searched from inception until November 3, 2017. Study Selection: Publications were assessed to determine whether they examined medicine quality and the prevalence and/or economic burden of substandard and falsified medicines in low- and middle-income countries. Studies with a sample size of 50 or more were included in the meta-analysis. Data Extraction and Synthesis: The study is registered in PROSPERO and reported via the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Study quality was assessed using an adapted Medicine Quality Assessment Reporting Guidelines scoring metric. Multiple reviewers conducted the data extraction and quality assessment independently. Main Outcomes and Measures: Prevalence and/or estimated economic impact of substandard and falsified medicines. Results: Two hundred sixty-five studies that estimated the prevalence of poor-quality essential medicines in low- and middle-income countries were identified. Among 96 studies that tested 50 samples or more (67 839 total drug samples), overall prevalence of poor-quality medicines was 13.6% (95% CI, 11.0%-16.3%), with regional prevalence of 18.7% in Africa (95% CI, 12.9%-24.5%) and 13.7% in Asia (95% CI, 8.2%-19.1%). Of studies included in the meta-analysis, 19.1% (95% CI, 15.0%-23.3%) of antimalarials and 12.4% (95% CI, 7.1%-17.7%) of antibiotics were substandard or falsified. Eight approximations of the economic impact, focused primarily on market size, with poor or undisclosed methods in estimation were identified, ranging from $10 billion to $200 billion. Conclusions and Relevance: Poor-quality essential medicines are a substantial and understudied problem. Methodological standards for prevalence and rigorous economic studies estimating the burden beyond market size are needed to accurately assess the scope of the issue and inform efforts to address it. Global collaborative efforts are needed to improve supply-chain management, surveillance, and regulatory capacity in low- and middle-income countries to reduce the threat of poor-quality medicines. Trial Registration: PROSPERO Identifier: CRD42017080266.