An evaluation of the national testing response during the COVID-19 pandemic in England: a multistage mixed-methods study protocol.

INTRODUCTION: In 2020, the UK government established a large-scale testing programme to rapidly identify individuals in England who were infected with SARS-CoV-2 and had COVID-19. This comprised part of the UK government's COVID-19 response strategy, to protect those at risk of severe COVID-19 disease and death and to reduce the burden on the health system. To assess the success of this approach, the UK Health Security Agency (UKHSA) commissioned an independent evaluation of the activities delivered by the National Health System testing programme in England. The primary purpose of this evaluation will be to capture key learnings from the roll-out of testing to different target populations via various testing services between October 2020 and March 2022 and to use these insights to formulate recommendations for future pandemic preparedness strategy. In this protocol, we detail the rationale, approach and study design. METHODS AND ANALYSIS: The proposed study involves a stepwise mixed-methods approach, aligned with established methods for the evaluation of complex interventions in health, to retrospectively assess the combined impact of key asymptomatic and symptomatic testing services nationally. The research team will first develop a theory of change, formulated in collaboration with testing service stakeholders, to understand the causal pathways and intended and unintended outcomes of each testing service and explore contextual impacts on each testing service's intended outcomes. Insights gained will help identify indicators to evaluate how the combined aims of the testing programme were achieved, using a mixed-methods approach. ETHICS AND DISSEMINATION: The study protocol was granted ethics approval by the UKHSA Research Ethics and Governance Group (reference NR0347). All relevant ethics guidelines will be followed throughout. Findings arising from this evaluation will be used to inform lessons learnt and recommendations for UKHSA on appropriate pandemic preparedness testing programme designs; findings will also be disseminated in peer-reviewed journals, a publicly available report to be published online and at academic conferences. The final report of findings from the evaluation will be used as part of a portfolio of evidence produced for the independent COVID-19 government inquiry in the UK. TRANSPARENCY DECLARATION: The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, accurate and transparent account of the study being reported; no important aspects of the study have been omitted, and any discrepancies from the study as planned have been explained.

Potential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine.

The high efficacy, low cost, and long shelf-life of the ChAdOx1 nCoV-19 vaccine positions it well for use in in diverse socioeconomic settings. Using data from clinical trials, an individual-based model was constructed to predict its 6-month population-level impact. Probabilistic sensitivity analyses evaluated the importance of epidemiological, demographic and logistical factors on vaccine effectiveness. Rollout at various levels of availability and delivery speed, conditional on vaccine efficacy profiles (efficacy of each dose and interval between doses) were explored in representative countries. We highlight how expedient vaccine delivery to high-risk groups is critical in mitigating COVID-19 disease and mortality. In scenarios where the availability of vaccine is insufficient for high-risk groups to receive two doses, administration of a single dose of is optimal, even when vaccine efficacy after one dose is just 75% of the two doses. These findings can help inform allocation strategies particularly in areas constrained by availability.

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19.

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries.

Modelling the COVID-19 pandemic in context: an international participatory approach.

The SARS-CoV-2 pandemic has had an unprecedented impact on multiple levels of society. Not only has the pandemic completely overwhelmed some health systems but it has also changed how scientific evidence is shared and increased the pace at which such evidence is published and consumed, by scientists, policymakers and the wider public. More significantly, the pandemic has created tremendous challenges for decision-makers, who have had to implement highly disruptive containment measures with very little empirical scientific evidence to support their decision-making process. Given this lack of data, predictive mathematical models have played an increasingly prominent role. In high-income countries, there is a long-standing history of established research groups advising policymakers, whereas a general lack of translational capacity has meant that mathematical models frequently remain inaccessible to policymakers in low-income and middle-income countries. Here, we describe a participatory approach to modelling that aims to circumvent this gap. Our approach involved the creation of an international group of infectious disease modellers and other public health experts, which culminated in the establishment of the COVID-19 Modelling (CoMo) Consortium. Here, we describe how the consortium was formed, the way it functions, the mathematical model used and, crucially, the high degree of engagement fostered between CoMo Consortium members and their respective local policymakers and ministries of health.

Estimating the risk of declining funding for malaria in Ghana: the case for continued investment in the malaria response.

BACKGROUND: Ghana has made impressive progress against malaria, decreasing mortality and morbidity by over 50% between 2005 and 2015. These gains have been facilitated in part, due to increased financial commitment from government and donors. Total resources for malaria increased from less than USD 25 million in 2006 to over USD 100 million in 2011. However, the country still faces a high burden of disease and is at risk of declining external financing due to its strong economic growth and the consequential donor requirements for increased government contributions. The resulting financial gap will need to be met domestically. The purpose of this study was to provide economic evidence of the potential risks of withdrawing financing to shape an advocacy strategy for resource mobilization. METHODS: A compartmental transmission model was developed to estimate the impact of a range of malaria interventions on the transmission of Plasmodium falciparum malaria between 2018 and 2030. The model projected scenarios of common interventions that allowed the attainment of elimination and those that predicted transmission if interventions were withheld. The outputs of this model were used to generate costs and economic benefits of each option. RESULTS: Elimination was predicted using the package of interventions outlined in the national strategy, particularly increased net usage and improved case management. Malaria elimination in Ghana is predicted to cost USD 961 million between 2020 and 2029. Compared to the baseline, elimination is estimated to prevent 85.5 million cases, save 4468 lives, and avert USD 2.2 billion in health system expenditures. The economic gain was estimated at USD 32 billion in reduced health system expenditure, increased household prosperity and productivity gains. Through malaria elimination, Ghana can expect to see a 32-fold return on their investment. Reducing interventions, predicted an additional 38.2 clinical cases, 2500 deaths and additional economic losses of USD 14.1 billion. CONCLUSIONS: Malaria elimination provides robust epidemiological and economic benefits, however, sustained financing is need to accelerate the gains in Ghana. Although government financing has increased in the past decade, the amount is less than 25% of the total malaria financing. The evidence generated by this study can be used to develop a robust domestic strategy to overcome the financial barriers to achieving malaria elimination in Ghana.

Predicting the cost of malaria elimination in the Asia-Pacific.

Over the past decade, the countries of the Asia-Pacific region have made significant progress towards the goal of malaria elimination by the year 2030. It is widely accepted that for the region to meet this goal, an intensification of efforts supported by sustained funding is required. However, robust estimates are needed for the optimal coverage and components of malaria elimination packages and the resources required to implement them. In this collection, a multispecies mathematical and economic modelling approach supported by the estimated burden of disease is used to make preliminary estimates for the cost of elimination and develop an evidence-based investment case for the region.

Malaria elimination transmission and costing in the Asia-Pacific: Developing an investment case.

Background: The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts. Methods: A transmission model was developed to project rates of decline of Plasmodium falciparum and Plasmodium vivax malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, individual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed. Results: The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment. Conclusion: This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy.

An interactive application for malaria elimination transmission and costing in the Asia-Pacific.

Leaders in the Asia-Pacific have endorsed an ambitious target to eliminate malaria in the region by 2030. The emergence and spread of artemisinin drug resistance in the Greater Mekong Subregion makes elimination urgent and strategic for the global goal of malaria eradication. Mathematical modelling is a useful tool for assessing and comparing different elimination strategies and scenarios to inform policymakers. Mathematical models are especially relevant in this context because of the wide heterogeneity of regional, country and local settings, which means that different strategies are needed to eliminate malaria. However, models and their predictions can be seen as highly technical, limiting their use for decision making. Simplified applications of models are needed to allow policy makers to benefit from these valuable tools. This paper describes a method for communicating complex model results with a user-friendly and intuitive framework. Using open-source technologies, we designed and developed an interactive application to disseminate the modelling results for malaria elimination. The design was iteratively improved while the application was being piloted and extensively tested by a diverse range of researchers and decision makers. This application allows several target audiences to explore, navigate and visualise complex datasets and models generated in the context of malaria elimination. It allows widespread access, use of and interpretation of models, generated at great effort and expense as well as enabling them to remain relevant for a longer period of time. It has long been acknowledged that scientific results need to be repackaged for larger audiences. We demonstrate that modellers can include applications as part of the dissemination strategy of their findings. We highlight that there is a need for additional research in order to provide guidelines and direction for designing and developing effective applications for disseminating models.

Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia.

BACKGROUND: Reactive case detection (RACD) is an active case finding strategy where households and neighbours of a passively identified case (index case) are screened to identify and treat additional malaria infections with the goal of gathering surveillance information and potentially reducing further transmission. Although it is widely considered a key strategy in low burden settings, little is known about the costs and the cost-effectiveness of different diagnostic methods used for RACD. The aims of this study were to measure the cost of conducting RACD and compare the cost-effectiveness of microscopy to the more sensitive diagnostic method loop-mediated isothermal amplification (LAMP). METHODS: The study was conducted in RACD surveillance sites in five sub-districts in Aceh Besar, Indonesia. The cost inputs and yield of implementing RACD with microscopy and/or LAMP were collected prospectively over a 20 months study period between May 2014 and December 2015. Costs and cost-effectiveness (USD) of the different strategies were examined. The main cost measures were cost per RACD event, per person screened, per population at risk (PAR); defined as total population in each sub-district, and per infection found. The main cost-effectiveness measure was incremental cost-effectiveness ratio (ICER), expressed as cost per malaria infection detected by LAMP versus microscopy. The effects of varying test positivity rate or diagnostic yield on cost per infection identified and ICER were also assessed. RESULTS: Among 1495 household members and neighbours screened in 36 RACD events, two infections were detected by microscopy and confirmed by LAMP, and four infections were missed by microscopy but detected by LAMP. The average total cost of conducting RACD using microscopy and LAMP was $1178 per event with LAMP-specific consumables and personnel being the main cost drivers. The average cost of screening one individual during RACD was $11, with an additional cost of diagnostics at $0.62 and $16 per person for microscopy and LAMP, respectively. As a public health intervention, RACD using both diagnostics cost an average of $0.42 per PAR per year. Comparing RACD using microscopy only versus RACD using LAMP only, the cost per infection found was $8930 and $6915, respectively. To add LAMP as an additional intervention accompanying RACD would cost $9 per individual screened annually in this setting. The ICER was estimated to be $5907 per additional malaria infection detected by LAMP versus microscopy. Cost per infection identified and ICER declined with increasing test positivity rate and increasing diagnostic yield. CONCLUSIONS: This study provides the first estimates on the cost and cost-effectiveness of RACD from a low transmission setting. Costs per individual screened were high, though costs per PAR were low. Compared to microscopy, the use of LAMP in RACD was more costly but more cost-effective for the detection of infections, with diminishing returns observed when findings were extrapolated to scenarios with higher prevalence of infection using more sensitive diagnostics. As malaria programmes consider active case detection and the integration of more sensitive diagnostics, these findings may inform strategic and budgetary planning.

Regional initiatives for malaria elimination: Building and maintaining partnerships.

Andrew Lover and colleagues discuss regional malaria initiatives, the strengths and challenges.

Tracking development assistance and government health expenditures for 35 malaria-eliminating countries: 1990-2017.

BACKGROUND: Donor financing for malaria has declined since 2010 and this trend is projected to continue for the foreseeable future. These reductions have a significant impact on lower burden countries actively pursuing elimination, which are usually a lesser priority for donors. While domestic spending on malaria has been growing, it varies substantially in speed and magnitude across countries. A clear understanding of spending patterns and trends in donor and domestic financing is needed to uncover critical investment gaps and opportunities. METHODS: Building on the Institute for Health Metrics and Evaluation's annual Financing Global Health research, data were collected from organizations that channel development assistance for health to the 35 countries actively pursuing malaria elimination. Where possible, development assistance for health (DAH) was categorized by spend on malaria intervention. A diverse set of data points were used to estimate government health budgets expenditure on malaria, including World Malaria Reports and government reports when available. Projections were done using regression analyses taking recipient country averages and earmarked funding into account. RESULTS: Since 2010, DAH for malaria has been declining for the 35 countries actively pursuing malaria elimination (from $176 million in 2010 to $62 million in 2013). The Global Fund is the largest external financier for malaria, providing 96% of the total external funding for malaria in 2013, with vector control interventions being the highest cost driver in all regions. Government expenditure on malaria, while increasing, has not kept pace with diminishing DAH or rising national GDP rates, leading to a potential gap in service delivery needed to attain elimination. CONCLUSION: Despite past gains, total financing available for malaria in elimination settings is declining. Health financing trends suggest that substantive policy interventions will be needed to ensure that malaria elimination is adequately financed and that available financing is effectively targeted to interventions that provide the best value for money.

An Investment Case to Prevent the Reintroduction of Malaria in Sri Lanka.

Sri Lanka has made remarkable gains in reducing the burden of malaria, recording no locally transmitted malaria cases since November 2012 and zero deaths since 2007. The country was recently certified as malaria free by World Health Organization in September 2016. Sri Lanka, however, continues to face a risk of resurgence due to persistent receptivity and vulnerability to malaria transmission. Maintaining the gains will require continued financing to the malaria program to maintain the activities aimed at preventing reintroduction. This article presents an investment case for malaria in Sri Lanka by estimating the costs and benefits of sustaining investments to prevent the reintroduction of the disease. An ingredient-based approach was used to estimate the cost of the existing program. The cost of potential resurgence was estimated using a hypothetical scenario in which resurgence assumed to occur, if all prevention of reintroduction activities were halted. These estimates were used to compute a benefit-cost ratio and a return on investment. The total economic cost of the malaria program in 2014 was estimated at U.S. dollars (USD) 0.57 per capita per year with a financial cost of USD0.37 per capita. The cost of potential malaria resurgence was, however, much higher estimated at 13 times the cost of maintaining existing activities or 21 times based on financial costs alone. This evidence suggests a substantial return on investment providing a compelling argument for advocacy for continued prioritization of funding for the prevention of reintroduction of malaria in Sri Lanka.

The economics of malaria control and elimination: a systematic review.

BACKGROUND: Declining donor funding and competing health priorities threaten the sustainability of malaria programmes. Elucidating the cost and benefits of continued investments in malaria could encourage sustained political and financial commitments. The evidence, although available, remains disparate. This paper reviews the existing literature on the economic and financial cost and return of malaria control, elimination and eradication. METHODS: A review of articles that were published on or before September 2014 on the cost and benefits of malaria control and elimination was performed. Studies were classified based on their scope and were analysed according to two major categories: cost of malaria control and elimination to a health system, and cost-benefit studies. Only studies involving more than two control or elimination interventions were included. Outcomes of interest were total programmatic cost, cost per capita, and benefit-cost ratios (BCRs). All costs were converted to 2013 US$ for standardization. RESULTS: Of the 6425 articles identified, 54 studies were included in this review. Twenty-two were focused on elimination or eradication while 32 focused on intensive control. Forty-eight per cent of studies included in this review were published on or after 2000. Overall, the annual per capita cost of malaria control to a health system ranged from $0.11 to $39.06 (median: $2.21) while that for malaria elimination ranged from $0.18 to $27 (median: $3.00). BCRs of investing in malaria control and elimination ranged from 2.4 to over 145. CONCLUSION: Overall, investments needed for malaria control and elimination varied greatly amongst the various countries and contexts. In most cases, the cost of elimination was greater than the cost of control. At the same time, the benefits of investing in malaria greatly outweighed the costs. While the cost of elimination in most cases was greater than the cost of control, the benefits greatly outweighed the cost. Information from this review provides guidance to national malaria programmes on the cost and benefits of malaria elimination in the absence of data. Importantly, the review highlights the need for more robust economic analyses using standard inputs and methods to strengthen the evidence needed for sustained financing for malaria elimination.

The path to eradication: a progress report on the malaria-eliminating countries.

In the past several years, as worldwide morbidity and mortality due to malaria have continued to decrease, the global malaria community has grown increasingly supportive of the idea of malaria eradication. In 2015, three noteworthy global documents were released-the WHO's Global Technical Strategy for Malaria 2016-2030, the Roll Back Malaria Partnership's Action and Investment to defeat Malaria 2016-2030, and From Aspiration to Action: What Will It Take to End Malaria?-that collectively advocate for malaria elimination and eradication and outline key operational, technical, and financial strategies to achieve progress toward malaria eradication. In light of this remarkable change in global attitudes toward malaria elimination and eradication, and as the malaria community debates how and when to embark on this ambitious goal, it is important to assess current progress along the path to eradication. Although low-income, high-burden countries are often the focus when discussing the substantial challenges of eradication, the progress toward elimination in middle-income, low-burden countries is a major driver of global progress and deserves better recognition. Additionally, although global support and guidance is essential for success, malaria elimination and eradication efforts will ultimately be driven at the country level and achieved in a collaborative manner, region by region. In this Review, we examine the present status of the 35 malaria-eliminating countries, summarise existing national and regional elimination goals and the regional frameworks that support them, and identify the most crucial enabling factors and potential barriers to achieving eradication by a theoretical end date of 2040.

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.

Global fund financing to the 34 malaria-eliminating countries under the new funding model 2014-2017: an analysis of national allocations and regional grants.

BACKGROUND: The Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM) has been the largest financial supporter of malaria since 2002. In 2011, the GFATM transitioned to a new funding model (NFM), which prioritizes grants to high burden, lower income countries. This shift raises concerns that some low endemic countries, dependent on GFATM financing to achieve their malaria elimination goals, would receive less funding under the NFM. This study aims to understand the projected increase or decrease in national and regional funding from the GFATM's NFM to the 34 malaria-eliminating countries. METHODS: Average annual disbursements under the old funding model were compared to average annual national allocations for all eligible 34 malaria-eliminating countries for the period of 2014-2017. Regional grant funding to countries that are due to receive additional support was then included in the comparison and analysed. Estimated funding ranges for the countries under the NFM were calculated using the proposed national allocation plus the possible adjustments and additional funding. Finally, the minimum and maximum funding estimates were compared to average annual disbursements under the old funding model. RESULTS: A cumulative 31 % decrease in national financing from the GFATM is expected for the countries included in this analysis. Regional grants augment funding for almost half of the eliminating countries, and increase the cumulative percent change in GTFAM funding to 32 %, though proposed activities may not be funded directly through national malaria programmes. However, if countries receive the maximum possible funding, 46 % of the countries included in this analysis would receive less than they received under the previous funding model. CONCLUSIONS: Many malaria-eliminating countries have projected national declines in funding from the GFATM under the NFM. While regional grants enhance funding for eliminating countries, they may not be able to fill country-level funding gaps for local commodities and implementation. If the GFATM is able to nuance its allocation methodology to mitigate drastic funding declines for malaria investments in low transmission countries, the GFATM can ensure previous investments are not lost. By aligning with WHO's Global Technical Strategy for Malaria and investing in both high- and low-endemic countries, the Global Fund can tip the scale on a global health threat and contribute toward the goal of eventual malaria eradication.

Costing the supply chain for delivery of ACT and RDTs in the public sector in Benin and Kenya.

BACKGROUND: Studies have shown that supply chain costs are a significant proportion of total programme costs. Nevertheless, the costs of delivering specific products are poorly understood and ballpark estimates are often used to inadequately plan for the budgetary implications of supply chain expenses. The purpose of this research was to estimate the country level costs of the public sector supply chain for artemisinin-based combination therapy (ACT) and rapid diagnostic tests (RDTs) from the central to the peripheral levels in Benin and Kenya. METHODS: A micro-costing approach was used and primary data on the various cost components of the supply chain was collected at the central, intermediate, and facility levels between September and November 2013. Information sources included central warehouse databases, health facility records, transport schedules, and expenditure reports. Data from document reviews and semi-structured interviews were used to identify cost inputs and estimate actual costs. Sampling was purposive to isolate key variables of interest. Survey guides were developed and administered electronically. Data were extracted into Microsoft Excel, and the supply chain cost per unit of ACT and RDT distributed by function and level of system was calculated. RESULTS: In Benin, supply chain costs added USD 0.2011 to the initial acquisition cost of ACT and USD 0.3375 to RDTs (normalized to USD 1). In Kenya, they added USD 0.2443 to the acquisition cost of ACT and USD 0.1895 to RDTs (normalized to USD 1). Total supply chain costs accounted for more than 30% of the initial acquisition cost of the products in some cases and these costs were highly sensitive to product volumes. The major cost drivers were found to be labour, transport, and utilities with health facilities carrying the majority of the cost per unit of product. CONCLUSIONS: Accurate cost estimates are needed to ensure adequate resources are available for supply chain activities. Product volumes should be considered when costing supply chain functions rather than dollar value. Further work is needed to develop extrapolative costing models that can be applied at country level without extensive micro-costing exercises. This will allow other countries to generate more accurate estimates in the future.