Publications
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Turner H, Kura K, Roth B, et al., 2024, An updated economic assessment of moxidectin treatment strategies for onchocerciasis elimination, Clinical Infectious Diseases, ISSN: 1058-4838
Background:Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control/elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas, has 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) implemented with minimal or enhanced coverage (65% or 80% of the total population taking the drug, respectively) in intervention-naïve 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 programme delivery when EoT90 was not reached earlier. Delivery costs do not include the drug costs. Results:aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with one 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 towards EoT and reduce programmatic delivery costs compared to ivermectin-based strategies. The costs of moxidectin to national programmes are needed to quantify whether delivery cost reductions will translate into overall programme cost reduction.
Bundy DAP, Schultz L, Manos A, et al., 2023, 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, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 378, Pages: 1-13, ISSN: 0962-8436
Global access to deworming treatment is one of the public health success stories of low-income countries in the 21st 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 to minimize COVID-19 pandemic transmission. 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 75 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 2020 levels. This paper explores how science, and a combination of new policy and epidemiological perspectives, 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.
Nguyen HA, Ahmed S, Turner HC, 2023, Overview of the main methods used for estimating catastrophic health expenditure, Cost Effectiveness and Resource Allocation, Vol: 21, Pages: 1-10, ISSN: 1478-7547
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.
Turner H, Hori Y, Revill P, et al., 2023, Analyses of the return on investment of public health interventions: a scoping review and recommendations for future studies, BMJ Global Health, Vol: 8, Pages: 1-12, ISSN: 2059-7908
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.
Turner HC, Quyen DL, Dias R, et al., 2023, An economic evaluation of Wolbachia deployments for dengue control in Vietnam, PLoS Neglected Tropical Diseases, Vol: 17, Pages: 1-16, ISSN: 1935-2727
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.
Turner H, Sandmann FG, Downey LE, et al., 2023, What are economic costs and when should they be used in health economic studies?, Cost Effectiveness and Resource Allocation, Vol: 21, Pages: 1-11, ISSN: 1478-7547
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.
McBride A, Hao NV, Nhat PTH, et al., 2023, THE COST OF DENGUE SHOCK AND SEPTIC SHOCK IN VIETNAM, Publisher: ELSEVIER SCI LTD, Pages: S18-S18, ISSN: 1201-9712
Flower B, Hung LM, Mccabe L, et al., 2023, Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study., eLife, Vol: 12, Pages: 1-30, ISSN: 2050-084X
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 206/29
Tam DTH, Clapham H, Giger E, et al., 2023, Burden of postinfectious symptoms after acute Dengue, Vietnam., Emerging Infectious Diseases, Vol: 29, Pages: 160-163, ISSN: 1080-6040
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.
Ananthakrishnan A, Luz ACG, KC S, et al., 2022, How can Health Technology Assessment support our response to public health emergencies?, Health Research Policy and Systems, Vol: 20, Pages: 1-7, ISSN: 1478-4505
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.
Huong NHT, Toan ND, Quy DT, et al., 2022, Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam, Wellcome Open Research, Vol: 6, Pages: 133-133
<ns4:p>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.</ns4:p><ns4:p> 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
Hung TM, Van Hao N, Yen LM, et al., 2022, Direct medical costs of tetanus, dengue, and sepsis patients in an intensive care unit in vietnam, Frontiers in Public Health, Vol: 10, ISSN: 2296-2565
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.
Turner HC, Ottesen EA, Bradley MH, 2022, A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000-2020), Parasites and Vectors, Vol: 15, Pages: 1-9, ISSN: 1756-3305
BackgroundLymphatic 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 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.MethodsWe 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 including 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-transmi
Van Hao N, Loan HT, Yen LM, et al., 2022, Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2x2 factorial randomized control trial, The Lancet Global Health, Vol: 10, ISSN: 2214-109X
Background: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. As tetanus toxin acts within the central nervous system, where there is limited penetration of peripherally-administered antitoxin, intrathecal antitoxin administration may improve clinical outcomes compared to intramuscular injection.Methods: In a 2x2 factorial trial, adults with tetanus in a single-centre in Vietnam were randomized first to 3,000 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 blind to treatment allocations. The primary outcome was requirement for mechanical ventilation. Secondary outcomes included in-hospital mortality, death and disability at 240-days, duration of intensive care unit (ICU) stay, and adverse events. The study was registered at ClinicalTrials.gov, NCT 02999815 (status: recruitment completed).Findings: 272 adults were randomized. Mechanical ventilation was given to 56/130 (43%) of patients allocated to intrathecal antitoxin and 65/131 (50%) allocated to sham procedure (RR 0.87; 95% CI 0.66 to 1.13; p=0.29). For the intramuscular allocation 48/107 (45%), patients allocated to human antitoxin received mechanical ventilation compared to 48/108 (44%) patients allocated to equine antitoxin (relative risk (RR) 1.01, 95% confidence interval (CI) 0.75, 1.36, p=0.95). No clinically-relevant differences in secondary outcomes or adverse events were seen except for shorter length of ICU stay in those treated with intrathecal antitoxin compared to sham. 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 Trus
Duc MT, Thwaites CL, Van Nuil JI, et al., 2022, Digital Health Policy and Programs for Hospital Care in Vietnam: Scoping Review, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 24, ISSN: 1438-8871
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Bundy DAP, Campbell SJ, Chami GF, et al., 2022, Epidemiology and Economics of Deworming, Helminth Infections and their Impact on Global Public Health, Second Edition, Pages: 1-34, ISBN: 9783031003028
Global access to deworming is one of the public health success stories of the twenty-first century and was the key catalyst for creating the neglected tropical disease (NTD) agenda. Human worm infections appear to have been with us since the domestication of household animals, some 10,500 years ago, and putative treatments are known from the earliest pharmacopoeias, but it has only been in the last 100 years that we have sought a public health solution and only in the last 5 years that real success at scale has been achieved. This is a success that depends on donated drugs and targeted treatment campaigns outside of the traditional health system. In this chapter, we explore the scientific foundations for this success and explore what this implies for the future management of soil-transmitted helminths (STHs) by health systems. This chapter describes the evolution of public health approaches to reduce the prevalence and morbidity of STH and the evidence of impact of mass drug administration on their target populations, and provides context for the debate that has surrounded these results. This chapter also details the costs of delivering these interventions as well as how future delivery approaches can align with Universal Health Care objectives.
Turner H, Archer R, Downey L, et al., 2021, An introduction to the main types of economic evaluations used for informing priority setting and resource allocation in healthcare: key features, uses and limitations, Frontiers in Public Health, Vol: 9, Pages: 1-17, ISSN: 2296-2565
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, summarizing 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.
Turner H, Stolk WA, Solomon AW, et al., 2021, Are current preventive chemotherapy strategies for controlling and eliminating neglected tropical diseases cost-effective?, BMJ Global Health, Vol: 6, ISSN: 2059-7908
Neglected tropical diseases (NTDs) remain a significant cause of morbidity and mortality in many low- 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 World Health Organization (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 estimates relating to community-wide preventive chemotherapy for lymphatic filariasis and onchocerciasis were particularly favourable when compared to other public health interventions. Cost-effectiveness estimates of school-based preventive chemotherapy for schistosomiasis and STH were also generally favourable but more variable. 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.
Flower B, McCabe L, Le Ngoc C, et al., 2021, High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: the Vietnam SEARCH study, Open Forum Infectious Diseases, Vol: 8, ISSN: 2328-8957
BackgroundGenotype 6 is the most genetically diverse lineage of hepatitis C virus (HCV), and predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the lowest costing 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.MethodsIn 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.FindingsOf 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a, 34% 6e. The remainder had 6h, 6k, 6l or 6o. 100% had viral load <500 IU/ml by day 14, meaning all received 12 weeks of SOF/DCV. 100% achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions (RAS) at baseline.Interpretation12 weeks of SOF/DCV achieves excellent cure rates in this population. This data supports the removal of costly genotyping in countries where genotype 3 prevalence in <5%, in keeping with WHO guidelines. NS5A-resistance associated mutations in isolation, do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
Huong NHT, Toan ND, Quy DT, et al., 2021, Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam [version 2; peer review: 1 approved, 1 approved with reservations], Wellcome Open Research, Vol: 6, ISSN: 2398-502X
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.</ns3:p><ns3:p> 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
Turner H, 2021, Health Economic Analyses of the Global Programme to Eliminate Lymphatic Filariasis, International Health, Vol: 13, Pages: S71-S74, ISSN: 1876-3405
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.
Hung TM, Shepard DS, Bettis AA, et al., 2020, Productivity costs from a dengue episode in Asia: a systematic literature review, BMC Infectious Diseases, Vol: 20, Pages: 1-18, ISSN: 1471-2334
BackgroundDengue is a mosquito-borne viral infection which has been estimated to cause a global economic burden of US$8.9 billion per year. 40% of this estimate was due to what are known as productivity costs (the costs associated with productivity loss from both paid and unpaid work that results from illness, treatment or premature death). Although productivity costs account for a significant proportion of the estimated economic burden of dengue, the methods used to calculate them are often very variable within health economic studies. The aim of this review was to systematically examine the current estimates of the productivity costs associated with dengue episodes in Asia and to increase awareness surrounding how productivity costs are estimated.MethodWe searched PubMed and Web of Knowledge without date and language restrictions using terms related to dengue and cost and economics burden. The titles and abstracts of publications related to Asia were screened to identify relevant studies. The reported productivity losses and costs of non-fatal and fatal dengue episodes were then described and compared. Costs were adjusted for inflation to 2017 prices.ResultsWe reviewed 33 relevant articles, of which 20 studies reported the productivity losses, and 31 studies reported productivity costs. The productivity costs varied between US$6.7–1445.9 and US$3.8–1332 for hospitalized and outpatient non-fatal episodes, respectively. The productivity cost associated with fatal dengue episodes varied between US$12,035-1,453,237. A large degree of this variation was due to the range of different countries being investigated and their corresponding economic status. However, estimates for a given country still showed notable variation.ConclusionWe found that the estimated productivity costs associated with dengue episodes in Asia are notable. However, owing to the significant variation in methodology and approaches applied, the reported productivity costs of dengue episod
Sansom L, Minh TPN, Hill I, et al., 2020, Towards a fair and transparent research participant compensation and reimbursement framework in Viet Nam, International Health, Vol: 12, Pages: 533-540, ISSN: 1876-3405
Background:Providing compensation for participants in clinical research is well established and whilst 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, nationalcompensation and reimbursement frameworks.Methods:We reviewed OUCRU (Oxford University Clinical Research Unit) internal reimbursement documentation over a ten-year 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 issueof 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 Viet Nam.
Turner HC, French MD, Montresor A, et al., 2020, Economic evaluations of human schistosomiasis interventions: a systematic review and identification of associated research needs, Wellcome Open Research, Vol: 5, Pages: 1-28, ISSN: 2398-502X
Background: Schistosomiasis is one of the most prevalent neglected tropical diseases (NTDs) with an estimated 229 million people requiring preventive treatment worldwide. Recommendations for preventive chemotherapy strategies have been made by the World Health Organization (WHO) whereby the frequency of treatment is determined by the settings prevalence. Despite recent progress, many countries still need to scale up treatment and important questions remain regarding optimal control strategies. This paper presents a systematic review of the economic evaluations of human schistosomiasis interventions.Methods: A systematic review of the literature was conducted on 22nd August 2019 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. The focus was economic evaluations of schistosomiasis interventions, such as cost-effectiveness and cost-benefit analyses. No date or language stipulations were applied to the searches.Results: We identified 53 relevant health economic analyses of schistosomiasis interventions. Most studies related to Schistosoma japonicum followed by S. haematobium. Several studies also included other NTDs. In Africa, most studies evaluated preventive chemotherapy, whereas in China they mostly evaluated programmes using a combination of interventions (such as chemotherapy, snail control and health education). There was wide variation in the methodology and epidemiological settings investigated. A range of effectiveness metrics were used by the different studies.Conclusions: Due to the variation across the identified studies, it was not possible to make definitive policy recommendations. Although, in general, the current WHO recommended preventive chemotherapy approach to control schistosomiasis was found to be cost-effective. This finding has important implications for policymakers, advocacy groups and potential funders. However, there are several important inconsistencies and research gaps (such as how the health benefits of interventio
Toor J, Rollinson D, Turner HC, et al., 2020, Achieving elimination as a public health problem for schistosoma mansoni and S. haematobium: when is community-wide treatment required?, Journal of Infectious Diseases, Vol: 221, Pages: S525-S530, ISSN: 0022-1899
The World Health Organization (WHO) has set elimination as a public health problem (EPHP) as a goal for schistosomiasis. As the WHO treatment guidelines for schistosomiasis are currently under revision, we investigate whether school-based or community-wide treatment strategies are required for achieving the EPHP goal. In low- to moderate-transmission settings with good school enrolment, we find that school-based treatment is sufficient for achieving EPHP. However, community-wide treatment is projected to be necessary in certain high-transmission settings as well as settings with low school enrolment. Hence, the optimal treatment strategy depends on setting-specific factors such as the species present, prevalence prior to treatment, and the age profile of infection.
Mathew CG, Bettis AA, Chu BK, et al., 2020, The health and economic burdens of lymphatic filariasis prior to mass drug administration programs, Clinical Infectious Diseases, Vol: 70, Pages: 2561-2567, ISSN: 1058-4838
BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem by 2020. Despite considerable progress, the current prevalence is around 60% of the 2000 figure, with the deadline looming a year away. Consequently, there is a continued need for investment in both the mass drug administration (MDA) and morbidity management programs, and this paper aims to demonstrate that need by estimating the health and economic burdens of LF prior to MDA programs starting in GPELF areas. METHODS: A previously developed model was used to estimate the numbers of individuals infected and individuals with symptomatic disease, along with the attributable number of disability-adjusted life years (DALYs). The economic burden was calculated by quantifying the costs incurred by the health-care system in managing clinical cases, the patients' out-of-pocket costs, and their productivity costs. RESULTS: Prior to the MDA program, approximately 129 million people were infected with LF, of which 43 million had clinical disease, corresponding to a DALY burden of 5.25 million. The average annual economic burden per chronic case was US $115, the majority of which resulted from productivity costs. The total economic burden of LF was estimated at US $5.8 billion annually. CONCLUSIONS: These results demonstrate the magnitude of the LF burden and highlight the continued need to support the GPELF. Patients with clinical disease bore the majority of the economic burden, but will not benefit much from the current MDA program, which is aimed at reducing transmission. This assessment further highlights the need to scale up morbidity management programs.
McCabe L, White IR, Nguyen VVC, et al., 2020, The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam, Trials, Vol: 21, Pages: 1-12, ISSN: 1745-6215
BackgroundEliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly.MethodsThe VIETNARMS trial will factorially randomly assign patients to two drug regimens, three treatment-shortening strategies or control, and adjunctive ribavirin or no adjunctive ribavirin with shortening strategies (14 randomly assigned groups). We will use Bayesian monitoring at interim analyses to detect and stop recruitment into unsuccessful strategies, defined by more than 0.95 posterior probability that the true cure rate is less than 90% for the individual randomly assigned group (non-comparative). Final comparisons will be non-inferiority for regimens (margin 5%) and strategies (margin 10%) and superiority for adjunctive ribavirin. Here, we tested the operating characteristics of the stopping guideline for individual randomly assigned groups, planned interim analysis timings and explored power at the final analysis.ResultsA beta (4.5, 0.5) prior for the true cure rate produces less than 0.05 probability of incorrectly stopping an individual randomly assigned group with a true cure rate of more than 90%. Groups with very low cure rates (<60%) are very likely (>0.9 probability) to stop after about 25% of patients are recruited. Groups with moderately low cure rates (80%) are likely to stop (0.7 probability) before overall recruitment finishes. Interim analyses 7, 10, 13 and 18 months after recruitment commences provide good probabilities of stopping inferior individua
Turner HC, Bundy DAP, 2020, Programmatic implications of the TUMIKIA trial on community-wide treatment for soil-transmitted helminths: further health economic analyses needed before a change in policy, Parasites and Vectors, Vol: 13, ISSN: 1756-3305
School-based deworming programmes are currently the main approach used to control the soil-transmitted helminths (STHs). A key unanswered policy question is whether mass drug administration (MDA) should be targeted tothe whole community instead, and several trials in this area have been conducted or are currently on-going. A recentwell-conducted trial demonstrated that successful community-wide treatment is a feasible strategy for STH controland can be more efective than school-based treatment in reducing prevalence and intensity of hookworm infection. However, we would argue that it is vital that these fndings are not taken out of context or over generalised, asthe additional health benefts gained from switching to community-wide treatment will vary depending on the STHspecies and baseline endemicity. Moreover, community-wide treatment will typically be more expensive than schoolbased treatment. The epidemiological evidence for an additional beneft from a switch to community-wide treatmenthas yet to be proven to represent “good value for money” across diferent settings. Further work is needed beforechanges in policy are made regarding the use of community-wide treatment for STH control, including comprehensive assessments of its additional public health benefts and costs across a range of scenarios, accounting for thepresence of alternative treatment delivery platforms.
Deribe K, Negussu N, Newport MJ, et al., 2020, The health and economic burden of podoconiosis in Ethiopia, Transactions of The Royal Society of Tropical Medicine and Hygiene, Vol: 114, Pages: 284-292, ISSN: 0035-9203
BackgroundPodoconiosis is one of the leading causes of lymphoedema-related morbidity in low-income settings, but little is known about the scale of its health and economic impact. This information is required to inform control programme planning and policy. In this study, we estimated the health and economic burden of podoconiosis in Ethiopia.MethodsWe developed a model to estimate the health burden attributed to podoconiosis in terms of the number of disability-adjusted life years (DALYs) and the economic burden. We estimated the economic burden by quantifying the treatment and morbidity-management costs incurred by the healthcare system in managing clinical cases, patients' out-of-pocket costs and their productivity costs.ResultsIn 2017, there were 1.5 million cases of podoconiosis in Ethiopia, which corresponds to 172 073 DALYs or 182 per 100 000 people. The total economic burden of podoconiosis in Ethiopia is estimated to be US$213.2 million annually and 91.1% of this resulted from productivity costs. The average economic burden per podoconiosis case was US$136.9.ConclusionsThe national cost of podoconiosis is formidable. If control measures are scaled up and the morbidity burden reduced, this will lead to Ethiopia saving millions of dollars. Our estimates provide important benchmark economic costs to programme planners, policymakers and donors for resource allocation and priority setting.
Tran BX, Nguyen LH, Turner HC, et al., 2019, Economic evaluation studies in the field of HIV/AIDS: bibliometric analysis on research development and scopes (GAPRESEARCH), BMC Health Services Research, Vol: 19, ISSN: 1472-6963
BACKGROUND: The rapid decrease in international funding for HIV/AIDS has been challenging for many nations to effectively mobilize and allocate their limited resources for HIV/AIDS programs. Economic evaluations can help inform decisions and strategic planning. This study aims to examine the trends and patterns in economic evaluation studies in the field of HIV/AIDS and determine their research landscapes. METHODS: Using the Web of Science databases, we synthesized the number of papers and citations on HIV/AIDS and economic evaluation from 1990 to 2017. Collaborations between authors and countries, networks of keywords and research topics were visualized using frequency of co-occurrence and Jaccards' similarity index. A Latent Dirichlet Allocation (LDA) analysis to categorize papers into different topics/themes. RESULTS: A total of 372 economic evaluation papers were selected, including 351 cost-effectiveness analyses (CEA), 11 cost-utility analyses (CUA), 12 cost-benefit analyses (CBA). The growth of publications, their citations and usages have increased remarkably over the years. Major research topics in economic evaluation studies consisted of antiretroviral therapy (ART) initiation and treatment; drug use prevention interventions and prevention of mother-to-child transmission interventions. Moreover, lack of contextualized evidence was found in specific settings with high burden HIV epidemics, as well as emerging most-at-risk populations such as trans-genders or migrants. CONCLUSION: This study highlights the knowledge and geographical discrepancies in HIV/AIDS economic evaluation literature. Future research directions are also informed for advancing economic evaluation in HIV/AIDS research.
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