Investing in a global pooled-funding mechanism for late-stage clinical trials of poverty-related and neglected diseases: an economic evaluation.

INTRODUCTION: Poverty-related and neglected diseases (PRNDs) cause over three million deaths annually. Despite this burden, there is a large gap between actual funding for PRND research and development (R&D) and the funding needed to launch PRND products from the R&D pipeline. This study provides an economic evaluation of a theoretical global pooled-funding mechanism to finance late-stage clinical trials of PRND products. METHODS: We modelled three pooled-funding design options, each based on a different level of coverage of candidate products for WHO's list of PRNDs: (1) vaccines covering 4 PRNDs, (2) vaccines and therapeutics covering 9 PRNDs and (3) vaccines, therapeutics and diagnostics covering 30 PRNDs. For each option, we constructed a discrete event simulation of the 2019 PRND R&D pipeline to estimate required funding for phase III trials and expected product launches through 2035. For each launch, we estimated global PRND treatment costs averted, deaths averted and disability-adjusted life-years (DALYs) averted. For each design option, we calculated the cost per death averted, cost per DALY averted, the benefit-cost ratio (BCR) and the incremental cost-effectiveness ratio (ICER). RESULTS: Option 1 averts 18.4 million deaths and 516 million DALYs, has a cost per DALY averted of US$84 and yields a BCR of 5.53. Option 2 averts 22.9 million deaths and 674 million DALYs, has a cost per DALY averted of US$75, an ICER over option 1 of US$49 and yields a BCR of 3.88. Option 3 averts 26.9 million deaths and 1 billion DALYs, has a cost per DALY averted of US$114, an ICER over option 2 of US$186 and yields a BCR of 2.52. CONCLUSIONS: All 3 options for a pooled-funding mechanism-vaccines for 4 PRNDs, vaccines and therapeutics for 9 PRNDs, and vaccines, therapeutics and diagnostics for 30 PRNDs-would generate a large return on investment, avert a substantial proportion of the global burden of morbidity and mortality for diseases of poverty and be cost-effective.

Effects of public financing of essential maternal and child health interventions across wealth quintiles in Nigeria: an extended cost-effectiveness analysis.

BACKGROUND: Maternal and newborn mortality rates in Nigeria are among the highest globally, and large socioeconomic inequalities exist in access to maternal, newborn, and child health (MNCH) services in the country. Inequalities also exist in catastrophic health expenditure among households in Nigeria. We aimed to estimate the health and financial risk protection benefits across different wealth groups in Nigeria if a policy of public financing of MNCH interventions were to be introduced. METHODS: We did an extended cost-effectiveness analysis to estimate the health and financial risk protection benefits, across different household wealth quintiles, of a public-financing policy that assumes zero out-of-pocket costs to patients at the point of care for 18 essential MNCH services. We projected health outcomes (deaths in children aged <5 years [under-5 deaths] and maternal deaths) and private expenditure averted using the Lives Saved Tool with data extracted from national surveys. We modelled three scenarios: 1) coverage expansion at a rate equal to the trend observed between 2013 and 2018 (status quo); 2) annual coverage expansion by 5% compared with the status quo (uniform scale-up scenario); and 3) annual coverage expansion by 10%, 8%, 6%, 4%, and 2% compared with the status quo from the poorest to the wealthiest quintiles, respectively (pro-poor scale-up scenario). FINDINGS: Our analysis shows that, if an additional 5% increase in coverage was provided for all wealth quintiles between 2019 and 2030, this uniform scale-up policy would prevent more than 0·11 million maternal deaths and 1·05 million under-5 deaths, avert US$1·8 billion in private expenditure, and avert 3266 cases of catastrophic health expenditure. The incremental cost effectiveness ratio would be $44 per life-year gained, which is highly cost-effective when compared with the gross domestic product per capita of Nigeria for 2018 ($2028). The policy would prevent a higher number of under-5 deaths and catastrophic health expenditure cases in poorer quintiles, but would prevent more maternal deaths and private expenditure in wealthier quintiles. If poorer populations experienced a greater increase in service coverage (ie, the pro-poor scale-up scenario), more maternal and under-5 deaths would be prevented in the poorer quintiles and more private expenditure would be averted than would be under previous scenarios. INTERPRETATION: Public financing of essential MNCH interventions in Nigeria would provide substantial health and financial risk protection benefits to Nigerian households. These benefits would accrue preferentially to the poorest quintiles and would contribute towards reduction of health and socioeconomic inequalities in Nigeria. The distribution would be more pro-poor if public financing of MNCH interventions could target poor households. FUNDING: WHO Partnership for Maternal, Newborn, and Child Health.

Tracking financing for global common goods for health: A machine learning approach using natural language processing techniques.

Objective: Tracking global health funding is a crucial but time consuming and labor-intensive process. This study aimed to develop a framework to automate the tracking of global health spending using natural language processing (NLP) and machine learning (ML) algorithms. We used the global common goods for health (CGH) categories developed by Schäferhoff et al. to design and evaluate ML models. Methods: We used data curated by Schäferhoff et al., which tracked the official development assistance (ODA) disbursements to global CGH for 2013, 2015, and 2017, for training and validating the ML models. To process raw text, we implemented different NLP techniques, such as removing stop words, lemmatization, and creation of synthetic text, to balance the dataset. We used four supervised learning ML algorithms-random forest (RF), XGBOOST, support vector machine (SVM), and multinomial naïve Bayes (MNB) (see Glossary)-to train and test the pre-coded dataset, and applied the best model on dataset that hasn't been manually coded to predict the financing for CGH in 2019. Results: After we trained the machine on the training dataset (n = 10,534), the weighted average F1-scores (a measure of a ML model's performance) on the testing dataset (n = 2,634) ranked 0.79-0.83 among four models, and the RF model had the best performance (F1-score = 0.83). The predicted total donor support for CGH projects by the RF model was $2.24 billion across 3 years, which was very close to the finding of $2.25 billion derived from coding and classification by humans. By applying the trained RF model on the 2019 dataset, we predicted that the total funding for global CGH was about $2.7 billion for 730 CGH projects. Conclusion: We have demonstrated that NLP and ML can be a feasible and efficient way to classify health projects into different global CGH categories, and thus track health funding for CGH routinely using data from publicly available databases.

Investing in late-stage clinical trials and manufacturing of product candidates for five major infectious diseases: a modelling study of the benefits and costs of investment in three middle-income countries.

BACKGROUND: Investing in late-stage clinical trials, trial sites, and production capacity for new health products could improve access to vaccines, therapeutics, and infectious disease diagnostics in middle-income countries. This study assesses the case for such investment in three of these countries: India, Kenya, and South Africa. METHODS: We applied investment case modelling and assessed how many cases, deaths, and disability-adjusted life years (DALYs) could be averted from the development and manufacturing of new technologies (therapeutics and vaccines) in these countries from 2021 to 2036, for five diseases-HIV, tuberculosis, malaria, pneumonia, and diarrhoeal diseases. We also estimated the economic benefits that might accrue from making these investments and we developed benefit-cost ratios for each of the three middle-income countries. Our modelling applies two investment case perspectives: a societal perspective with all costs and benefits measured at the societal level, and a country perspective to estimate how much health and economic benefit accrues to each middle-income country for every dollar invested in clinical trials and manufacturing by the middle-income country government. For each perspective, we modelled two scenarios: one that considers only domestic health and economic benefits; and one that includes regional health and economic benefits. In the regional scenarios, we assumed that new products developed and manufactured in India would benefit eight countries in south Asia, whereas new products developed and manufactured in Kenya would benefit all 21 countries in the Common Market for Eastern and Southern Africa (COMESA). We also assumed that all 16 countries in the Southern African Development Community (SADC) would benefit from products developed and manufactured in South Africa. FINDINGS: From 2021 to 2036, product development and manufacturing in Kenya could avert 4·44 million deaths and 206·27 million DALYs in the COMESA region. In South Africa, it could prevent 5·19 million deaths and 253·83 million DALYs in the SADC region. In India, it could avert 9·76 million deaths and 374·42 million DALYs in south Asia. Economic returns would be especially high if new tools were produced for regional markets rather than for domestic markets only. Under a societal perspective, regional returns outweigh investments by a factor of 20·51 in Kenya, 33·27 in South Africa, and 66·56 in India. Under a country perspective, the regional benefit-cost ratios amount to 60·71 in India, 8·78 in Kenya, and 11·88 in South Africa. INTERPRETATION: Our study supports the creation of regional hubs for clinical trials and product manufacturing compared with narrow national efforts. FUNDING: Bill & Melinda Gates Foundation.

Estimates of aid for reproductive, maternal, newborn, and child health: findings from application of the Muskoka2 method, 2002-17.

BACKGROUND: Four methods have previously been used to track aid for reproductive, maternal, newborn, and child health (RMNCH). At a meeting of donors and stakeholders in May, 2018, a single, agreed method was requested to produce accurate, predictable, transparent, and up-to-date estimates that could be used for analyses from both donor and recipient perspectives. Muskoka2 was developed to meet these needs. We describe Muskoka2 and present estimates of levels and trends in aid for RMNCH in 2002-17, with a focus on the latest estimates for 2017. METHODS: Muskoka2 is an automated algorithm that generates disaggregated estimates of aid for reproductive health, maternal and newborn health, and child health at the global, donor, and recipient-country levels. We applied Muskoka2 to the Organisation for Economic Co-operation and Development's Creditor Reporting System (CRS) aid activities database to generate estimates of RMNCH disbursements in 2002-17. The percentage of disbursements that benefit RMNCH was determined using CRS purpose codes for all donors except Gavi, the Vaccine Alliance; the UN Population Fund; and UNICEF; for which fixed percentages of aid were considered to benefit RMNCH. We analysed funding by donor for the 20 largest donors, by recipient-country income group, and by recipient for the 16 countries with the greatest RMNCH need, defined as the countries with the worst levels in 2015 on each of seven health indicators. FINDINGS: After 3 years of stagnation, reported aid for RMNCH reached $15·9 billion in 2017, the highest amount ever reported. Among donors reporting in both 2016 and 2017, aid increased by 10% ($1·4 billion) to $15·4 billion between 2016 and 2017. Child health received almost half of RMNCH disbursements in 2017 (46%, $7·4 billion), followed by reproductive health (34%, $5·4 billion), and maternal and newborn health (19%, $3·1 billion). The USA ($5·8 billion) and the UK ($1·6 billion) were the largest bilateral donors, disbursing 46% of all RMNCH funding in 2017 (including shares of their core contributions to multilaterals). The Global Fund and Gavi were the largest multilateral donors, disbursing $1·7 billion and $1·5 billion, respectively, for RMNCH from their core budgets. The proportion of aid for RMNCH received by low-income countries increased from 31% in 2002 to 52% in 2017. Nigeria received 7% ($1·1 billion) of all aid for RMNCH in 2017, followed by Ethiopia (6%, $876 million), Kenya (5%, $754 million), and Tanzania (5%, $751 million). INTERPRETATION: Muskoka2 retains the speed, transparency, and donor buy-in of the G8's previous Muskoka approach and incorporates eight innovations to improve precision. Although aid for RMNCH increased in 2017, low-income and middle-income countries still experience substantial funding gaps and threats to future funding. Maternal and newborn health receives considerably less funding than reproductive health or child health, which is a persistent issue requiring urgent attention. FUNDING: Bill & Melinda Gates Foundation; Partnership for Maternal, Newborn & Child Health.

Measuring development assistance for health systems strengthening and health security: an analysis using the Creditor Reporting System database.

Background: Health systems strengthening (HSS) and health security are two pillars of universal health coverage (UHC). Investments in these areas are essential for meeting the Sustainable Development Goals and are of heightened relevance given the emergence of the 2019 novel coronavirus disease (COVID-19). This study aims to generate information on development assistance for health (DAH) for these areas, including how to track it and how funding levels align with country needs. Methods: We developed a framework to analyze the amount of DAH disbursed in 2015 for the six building blocks of the health system ('system-wide HSS') plus health security (emergency preparedness, risk management, and response) at both the global (transnational) and country level. We reviewed 2,427 of 32,801 DAH activities in the Creditor Reporting System (CRS) database (80% of the total value of disbursements in 2015) and additional public information sources. Additional aid activities were identified through a keyword search. Results: In 2015, we estimated that US$3.1 billion (13.4%) of the US$22.9 billion of DAH captured in the CRS database was for system-wide HSS and health security: US$2.5 billion (10.9%) for system-wide HSS, mostly for infrastructure, and US$0.6 billion (2.5%) for system-wide health security. US$567.1 million (2.4%) was invested in supporting these activities at the global level. If responses to individual health emergencies are included, 7.5% of total DAH (US$1.7B) was for health security. We found a correlation between DAH for HSS and maternal mortality rates, and we interpret this as evidence that HSS aid generally flowed to countries with greater need. Conclusions : Achieving UHC by 2030 will require greater investments in system-wide HSS and proactive health emergency preparedness. It may be appropriate for donors to more prominently consider country needs and global functions when investing in health security and HSS.

International Funding for Global Common Goods for Health: An Analysis Using the Creditor Reporting System and G-FINDER Databases.

West Africa's Ebola epidemic of 2014-2016 exposed, among other problems, the under-funding of transnational global health activities known as global common goods for health (CGH), global functions such as pandemic preparedness and research and development (R&D) for neglected diseases. To mobilize sustainable funding for global CGH, it is critical first to understand existing financing flowing to different types of global CGH. In this study, we estimate trends in international spending for global CGH in 2013, 2015, and 2017, encompassing the era before and after the Ebola epidemic. We use a measure of international funding that combines official development assistance (ODA) for health with additional international spending on R&D for diseases of poverty, a measure called ODA+. We classify ODA+ into funding for three global functions-provision of global public goods, management of cross-border externalities, and fostering of global health leadership and stewardship-and country-specific aid. International funding for global functions increased between 2013 and 2015 by $1.4 billion to a total of $7.3 billion in 2015. It then declined to $7.0 billion in 2017, accounting for 24% of all ODA+ in 2017. These findings provide empirical evidence of the reactive nature of international funders for global CGH. While international funders increased funding for global functions in response to the Ebola outbreak, they failed to sustain that funding. To meet future global health challenges proactively, international funders should allocate more funding for global functions.

Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model.

Background: Funding for neglected disease product development fell from 2009-2015, other than a brief injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority "missing" products. Results: We found 685 neglected disease product candidates as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range $13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches.  Based on the current pipeline, there would be few launches of complex new chemical entities; launches of highly efficacious HIV, tuberculosis, or malaria vaccines would be unlikely. Estimated additional costs to launch one of each of 18 key missing products are $13.6B assuming lowest product complexity or $21.8B assuming highest complexity ($8.1B-36.6B). Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5B (low complexity missing products) or $5.8B/year (high complexity missing products). Conclusions: Since current annual global spending on product development is about $3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B.

How much donor financing for health is channelled to global versus country-specific aid functions?

The slow global response to the Ebola crisis in west Africa suggests that important gaps exist in donor financing for key global functions, such as support for health research and development for diseases of poverty and strengthening of outbreak preparedness. In this Health Policy, we use the International Development Statistics databases to quantify donor support for such functions. We classify donor funding for health into aid for global functions (provision of global public goods, management of cross-border externalities, and fostering of leadership and stewardship) versus country-specific aid. We use a new measure of donor funding that combines official development assistance (ODA) for health with additional donor spending on research and development (R&D) for diseases of poverty. Much R&D spending falls outside ODA--ie, the assistance that is conventionally reported through ODA databases of the Organisation for Economic Co-operation and Development. This expanded definition, which we term health ODA plus, provides a more comprehensive picture of donor support for health that could reshape how policy makers will approach their support for global health.

Piloting the Affordable Medicines Facility-malaria: what will success look like?

The Affordable Medicines Facility-malaria is an innovative financing mechanism, managed by the Global Fund to Fight AIDS, Tuberculosis and Malaria. This initiative aims to increase the use of artemisinin-based combination therapies for treating malaria. A pilot is underway in eight countries to determine whether the mechanism reduces the consumer price of these drugs and increases their availability in public and private outlets, their market share and their use. To evaluate the pilot, an analysis was done to estimate predetermined "benchmarks" of success at 1 and 2 years. The analysis used a mixed-methods approach, triangulating data from a literature review with information from 33 interviews with experts. A sensitivity analysis and other methods were used to verify the results. Benchmarks used to determine success include an increase in availability of artemisinin-based combination therapies of 40 percentage points from baseline, and an increase in their use of 10-15 percentage points from baseline at year 2. These benchmarks were based on evidence that national public health programmes aimed at increasing the use of a specific health commodity in developing countries have generally achieved only modest changes in use within a 2-year time frame. Evaluation should also take individual country contexts into account.