An overview of the perspectives used in health economic evaluations.

The term 'perspective' in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders' viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence.

An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

A positive consequence of the COVID-19 pandemic: how the counterfactual experience of school closures is accelerating a multisectoral response to the treatment of neglected tropical diseases.

Global access to deworming treatment is one of the public health success stories of low-income countries in the twenty-first century. Parasitic worm infections are among the most ubiquitous chronic infections of humans, and early success with mass treatment programmes for these infections was the key catalyst for the neglected tropical disease (NTD) agenda. Since the launch of the 'London Declaration' in 2012, school-based deworming programmes have become the world's largest public health interventions. WHO estimates that by 2020, some 3.3 billion school-based drug treatments had been delivered. The success of this approach was brought to a dramatic halt in April 2020 when schools were closed worldwide in response to the COVID-19 pandemic. These closures immediately excluded 1.5 billion children not only from access to education but also from all school-based health services, including deworming. WHO Pulse surveys in 2021 identified NTD treatment as among the most negatively affected health interventions worldwide, second only to mental health interventions. In reaction, governments created a global Coalition with the twin aims of reopening schools and of rebuilding more resilient school-based health systems. Today, some 86 countries, comprising more than half the world's population, are delivering on this response, and school-based coverage of some key school-based programmes exceeds those from January 2020. This paper explores how science, and a combination of new policy and epidemiological perspectives that began in the 1980s, led to the exceptional growth in school-based NTD programmes after 2012, and are again driving new momentum in response to the COVID-19 pandemic. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Analyses of the return on investment of public health interventions: a scoping review and recommendations for future studies.

Return on investment (ROI) analysis is increasingly being used for evaluating the value for money of public health interventions. Given its potential role for informing health policies, it is important that there is a more comprehensive understanding of ROI analysis within the global health field. To address this gap in the literature, we conducted a scoping review of recent research articles reporting an ROI metric for a health intervention within the public sector in any country setting. The database search was limited to literature published in English and studies published between 1 January 2018 and 14 June 2021. Uses and settings where the ROI metric is being applied, key methodological features of the calculations and the types of economic benefits included were extracted. 118 relevant studies were included within this scoping review. We found that ROI analyses of health interventions differed between those that only included fiscal savings (such as prevented medical expenses) and those which incorporated a wider range of benefits (such as monetised health benefits). This highlights the variation in the definition of ROI analyses and supports the finding that ROI analyses are used for a range of different research questions/purposes within the healthcare sector. We also found that the methodologies used in ROI calculations were inconsistent and often poorly reported. This review demonstrates that there is notable variation in the methodology surrounding recent ROI calculations of healthcare interventions, as well as the definition of ROI analysis. We recommend that ROI metrics should be carefully interpreted before they are used to inform policy decisions regarding the allocation of healthcare resources. To improve the consistency of future studies, we also set out recommended use cases for ROI analysis and a reporting checklist.

Overview of the main methods used for estimating catastrophic health expenditure.

Out-of-pocket payments are expenditures borne directly by an individual/household for health services that are not reimbursed by any third-party. Households can experience financial hardship when the burden of such out-of-pocket payments is significant. This financial hardship is commonly measured using the "catastrophic health expenditure" (CHE) metric. CHE has been applied as an indicator in several health sectors and health policies. However, despite its importance, the methods used to measure the incidence of CHE vary across different studies and the terminology used can be inconsistent. In this paper, we introduce and raise awareness of the main approaches used to calculate CHE and discuss critical areas of methodological variation in a global health context. We outline the key features, foundation and differences between the two main methods used for estimating CHE: the budget share and the capacity-to-pay approach. We discuss key sources of variation within CHE calculation and using data from Ethiopia as a case study, illustrate how different approaches can lead to notably different CHE estimates. This variation could lead to challenges when decisionmakers and policymakers need to compare different studies' CHE estimates. This overview is intended to better understand how to interpret and compare CHE estimates and the potential variation across different studies.

What are economic costs and when should they be used in health economic studies?

Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources' opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource's value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.

An economic evaluation of Wolbachia deployments for dengue control in Vietnam.

INTRODUCTION: Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the benefits of such an intervention at a large scale. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam-targeted at the highest burden urban areas. METHODS: Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). The effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases was assumed to be 75%. We assumed that the intervention would maintain this effectiveness for at least 20 years (but tested this assumption in the sensitivity analysis). A cost-utility analysis and cost-benefit analysis were conducted. RESULTS: From the health sector perspective, the Wolbachia intervention was projected to cost US$420 per disability-adjusted life year (DALY) averted. From the societal perspective, the overall cost-effectiveness ratio was negative, i.e. the economic benefits outweighed the costs. These results are contingent on the long-term effectiveness of Wolbachia releases being sustained for 20 years. However, the intervention was still classed as cost-effective across the majority of the settings when assuming only 10 years of benefits. CONCLUSION: Overall, we found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains.

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.

Background: World Health Organization has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct-acting antiviral (DAA) therapy for hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome. Methods: Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4- or 8-week treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on days 0 and 28. Results: Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall, 38/51 (75%) were cured with first-line treatment (mean duration 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RASs), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS, SOF or DCV levels. Conclusions: Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. Funding: Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/296/Z/17/Z).

Hepatitis C is a blood-borne virus that causes thousands of deaths from liver cirrhosis and liver cancer each year. Antiviral therapies can cure most cases of infection in 12 weeks. Unfortunately, treatment is expensive, and sticking with the regimen for 12 weeks can be difficult. It may be especially challenging for unhoused people or those who use injection drugs and who have high rates of hepatitis C infection. Shorter durations of therapy may make it more accessible, especially for high-risk populations. But studies of shorter antiviral treatment durations have yet to produce high enough cure rates. Finding ways to identify patients who would benefit from shorter therapy is a key goal of the World Health Organization. Potential characteristics that may predict a faster treatment response include low virus levels before initiating treatment, patient genetics, drug resistance mutations in the virus, and higher drug levels in the patient's blood during treatment. For example, previous research showed that a rapid decrease in virus levels in a patient's blood two days after starting antiviral therapy with three drugs predicted patient cures after three weeks of treatment. To test if high cure rates could be achieved in just four weeks of treatment, Flower et al. enrolled 52 patients with hepatitis C in a study to receive the most widely accessible dual antiviral treatment (sofosbuvir and daclatasvir). Participants received four or eight weeks of treatment, depending on the amount of viral RNA in their blood after two days of treatment. The results indicate that a rapid decrease in virus levels in the blood does not adequately predict cure rates with four weeks of two-drug combination therapy. However, eight weeks may be highly effective, regardless of viral levels early in treatment. Thirty-four individuals with low virus levels on the second day of treatment received four weeks of therapy, which cured 21 or 62% of them. All seventeen individuals with higher viral levels on day two were cured after eight weeks of treatment. Twelve weeks of retreatment was sufficient to cure the 13 individuals who did not achieve cure with four weeks of therapy. Even patients with drug resistance genes after the first round of therapy responded to a longer second round. Flower et al. show that patient genetics, virus subtype, drug levels in the patient's blood, and viral drug resistance genes before therapy, were not associated with patient cures after four weeks of treatment. Given that retreatment is safe and effective, larger studies are now needed to determine whether eight weeks of therapy with sofosbuvir and daclatasvir may be enough to cure patients with mild liver disease. More studies are also necessary to identify patients that may benefit from shorter therapy durations. Finding ways to shorten antiviral therapy for hepatitis C could help make treatment more accessible and reduce therapy costs for both individuals and governments.

Burden of Postinfectious Symptoms after Acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.

How can health technology assessment support our response to public health emergencies?

Public health emergencies (PHEs), such as the COVID-19 crisis, are threats to global health and public order. We recommend that countries bolster their PHE responses by investing in health technology assessment (HTA), defined as a systematic process of gathering pertinent information on and evaluating health technologies from a medical, economic, social and ethical standpoint. We present examples of how HTA organizations in low- and middle-income countries have adapted to supporting PHE-related decisions during COVID-19 and describe the ways HTA can help the response to a PHE. In turn, we advocate for HTA capacity to be further developed globally and for increased institutional acceptance of these methods as a building block for preparedness and response to future PHEs. Finally, the long-term potential of HTA in strengthening health systems and embedding confidence and transparency into scientific policy should be recognized.

Direct Medical Costs of Tetanus, Dengue, and Sepsis Patients in an Intensive Care Unit in Vietnam.

Background: Critically ill patients often require complex clinical care by highly trained staff within a specialized intensive care unit (ICU) with advanced equipment. There are currently limited data on the costs of critical care in low-and middle-income countries (LMICs). This study aims to investigate the direct-medical costs of key infectious disease (tetanus, sepsis, and dengue) patients admitted to ICU in a hospital in Ho Chi Minh City (HCMC), Vietnam, and explores how the costs and cost drivers can vary between the different diseases. Methods: We calculated the direct medical costs for patients requiring critical care for tetanus, dengue and sepsis. Costing data (stratified into different cost categories) were extracted from the bills of patients hospitalized to the adult ICU with a dengue, sepsis and tetanus diagnosis that were enrolled in three studies conducted at the Hospital for Tropical Diseases in HCMC from January 2017 to December 2019. The costs were considered from the health sector perspective. The total sample size in this study was 342 patients. Results: ICU care was associated with significant direct medical costs. For patients that did not require mechanical ventilation, the median total ICU cost per patient varied between US$64.40 and US$675 for the different diseases. The costs were higher for patients that required mechanical ventilation, with the median total ICU cost per patient for the different diseases varying between US$2,590 and US$4,250. The main cost drivers varied according to disease and associated severity. Conclusion: This study demonstrates the notable cost of ICU care in Vietnam and in similar LMIC settings. Future studies are needed to further evaluate the costs and economic burden incurred by ICU patients. The data also highlight the importance of evaluating novel critical care interventions that could reduce the costs of ICU care.

A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000-2020).

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD). In 2000 the World Health Organization (WHO) established the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A key component of this programme is mass drug administration (MDA). Between 2000 and 2020, the GPELF has delivered over 8.6 billion treatments to at-risk populations. The last impact assessment of the programme evaluated the treatments provided between 2000-2014. The goal of this analysis is to provide an updated health impact assessment of the programme, based on the numbers treated between 2000-2020. METHODS: We updated and refined a previously established model that estimates the number of clinical manifestations and disability-adjusted life years (DALYs) averted by the treatments provided by the GPELF. The model comprises three different population cohorts that can benefit from MDA provided (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The treatment numbers were updated for all participating countries using data from the WHO. In addition, data relating to the estimated number of individuals initially at risk of LF infection were updated where possible. Finally, the DALY calculations were refined to use updated disability weights. RESULTS: Using the updated model and corresponding treatment data, we projected that the total benefit cohort of the GPELF (2000-2020) would consist of approximately 58.5 million individuals and the programme would avert 44.3 million chronic LF cases. Over the lifetime of the benefit cohorts, this corresponded to 244 million DALYs being averted. CONCLUSION: This study indicates that substantial health benefits have resulted from the first 20 years of the GPELF. It is important to note that the GPELF would have both additional benefits not quantified by the DALY burden metric as well as benefits on other co-endemic diseases (such as soil-transmitted helminths, onchocerciasis and scabies)-making the total health benefit underestimated. As with the past impact assessments, these results further justify the value and importance of continued investment in the GPELF.

Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. METHODS: In a 2  × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. FINDINGS: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66-1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75-1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. INTERPRETATION: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration. FUNDING: The Wellcome Trust.

An Introduction to the Main Types of Economic Evaluations Used for Informing Priority Setting and Resource Allocation in Healthcare: Key Features, Uses, and Limitations.

Economic evidence is increasingly being used for informing health policies. However, the underlining principles of health economic analyses are not always fully understood by non-health economists, and inappropriate types of analyses, as well as inconsistent methodologies, may be being used for informing health policy decisions. In addition, there is a lack of open access information and methodological guidance targeted to public health professionals, particularly those based in low- and middle-income country (LMIC) settings. The objective of this review is to provide a comprehensive and accessible introduction to economic evaluations for public health professionals with a focus on LMIC settings. We cover the main principles underlining the most common types of full economic evaluations used in healthcare decision making in the context of priority setting (namely cost-effectiveness/cost-utility analyses, cost-benefit analyses), and outline their key features, strengths and weaknesses. It is envisioned that this will help those conducting such analyses, as well as stakeholders that need to interpret their output, gain a greater understanding of these methods and help them select/distinguish between the different approaches. In particular, we highlight the need for greater awareness of the methods used to place a monetary value on the health benefits of interventions, and the potential for such estimates to be misinterpreted. Specifically, the economic benefits reported are typically an approximation, summarising the health benefits experienced by a population monetarily in terms of individual preferences or potential productivity gains, rather than actual realisable or fiscal monetary benefits to payers or society.

High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study.

BACKGROUND: Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis. METHODS: In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR). RESULTS: Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline. CONCLUSIONS: Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.

Are current preventive chemotherapy strategies for controlling and eliminating neglected tropical diseases cost-effective?

Neglected tropical diseases (NTDs) remain a significant cause of morbidity and mortality in many low-income and middle-income countries. Several NTDs, namely lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH) and trachoma, are predominantly controlled by preventive chemotherapy (or mass drug administration), following recommendations set by the WHO. Over one billion people are now treated for NTDs with this strategy per year. However, further investment and increased domestic healthcare spending are urgently needed to continue these programmes. Consequently, it is vital that the cost-effectiveness of preventive chemotherapy is understood. We analyse the current estimates on the cost per disability-adjusted life year (DALY) of the preventive chemotherapy strategies predominantly used for these diseases and identify key evidence gaps that require further research. Overall, the reported estimates show that preventive chemotherapy is generally cost-effective, supporting WHO recommendations. More specifically, the cost per DALY averted estimates relating to community-wide preventive chemotherapy for lymphatic filariasis and onchocerciasis were particularly favourable when compared with other public health interventions. Cost per DALY averted estimates of school-based preventive chemotherapy for schistosomiasis and STH were also generally favourable but more variable. Notably, the broader socioeconomic benefits are likely not being fully captured by the DALYs averted metric. No estimates of cost per DALY averted relating to community-wide mass antibiotic treatment for trachoma were found, highlighting the need for further research. These findings are important for informing global health policy and support the need for continuing NTD control and elimination efforts.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam.

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Health economic analyses of the Global Programme to Eliminate Lymphatic Filariasis.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established by the WHO in 2000. It aims to eliminate lymphatic filariasis as a public health problem. This paper summarises the key estimates of the cost-effectiveness and economic benefits related to the mass drug administration (MDA) provided by the GPELF. Several studies have investigated the cost-effectiveness of this MDA, estimating the cost per disability-adjusted life year (DALY) averted. These cost-effectiveness estimates have consistently classed the intervention as cost-effective and as favourable compared with other public health interventions conducted in low- and middle-income countries. Studies have also found that the MDA used for lymphatic filariasis control generates significant economic benefits. Although these studies are positive, there are still important gaps that warrant further health economic research (particularly, the evaluation of alternative interventions, further evaluation of morbidity management strategies and evaluation of interventions for settings coendemic with Loa loa). To conclude, health economic studies for a programme as large as the GPELF are subject to uncertainty. That said, the GPELF has consistently been estimated to be cost-effective and to generate notable economic benefits by a number of independent studies.

Towards a fair and transparent research participant compensation and reimbursement framework in Vietnam.

BACKGROUND: Providing compensation for participants in clinical research is well established and while international guidelines exist, defining a context-specific and fair compensation for participants in low-resource settings is challenging due to ethical concerns and the lack of practical, national compensation and reimbursement frameworks. METHODS: We reviewed Oxford University Clinical Research Unit (OUCRU) internal reimbursement documentation over a 10-y period and conducted a scoping literature review to expand our knowledge of compensation and reimbursement practices including ethical concerns. We developed a preliminary reimbursement framework that was presented to community advisory boards (CAB) and clinical investigators to assess its applicability, fairness and transparency. RESULTS: The main topics discussed at the workshops centered on fairness and whether the reimbursements could be perceived as financial incentives. Other decisive factors in the decision-making process were altruism and the loss of caregivers' earnings. Investigators raised the issue of additional burdens, whereas the CAB members were focused on non-monetary elements such as the healthcare quality the patients would receive. All elements discussed were reviewed and, where possible, incorporated into the final framework. CONCLUSION: Our new reimbursement framework provides a consistent, fair and transparent decision-making process and will be implemented across all future OUCRU clinical research in Vietnam.