Evaluating official development assistance-funded granting mechanisms for global health and development research that is initiated in high-income countries.

BACKGROUND: Several countries allocate official development assistance (ODA) for research on global health and development issues that is initiated in the donor country. The integration of such research within domestic research systems aligns with efforts to coordinate ODA investments with science, technology and innovation policies towards achieving the Sustainable Development Goals (SDGs). METHODS: Through a document synthesis and interviews with research funders in ODA donor and recipient countries, we evaluated the performance of this funding approach across seven donor-country programmes from five donor countries and examined the institutional design elements that increase its chances of advancing development goals and addressing global challenges. RESULTS: We found that carefully designed programmes provide a promising pathway to producing valuable and contextually relevant knowledge on global health and development issues. To achieve these outcomes and ensure they benefit ODA-receiving countries, programmes should focus on recipient-country priorities and absorptive capacity; translate research on global public goods into context-appropriate technologies; plan and monitor pathways to impact; structure equitable partnerships; strengthen individual and institutional capacity; and emphasize knowledge mobilization. CONCLUSIONS: Global health and development research programmes and partnerships have an important role to play in achieving the SDGs and addressing global challenges. Governments should consider the potential of ODA-funded research programmes to address gaps in their global health and development frameworks. In the absence of concrete evidence of development impact, donor countries should consider making increases in ODA allocations for research additional to more direct investments that have demonstrated effectiveness in ODA-receiving countries.

The effect of generic market entry on antibiotic prescriptions in the United States.

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)-aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin-and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.

Promoting Intersectoral Collaboration Through the Evaluations of Public Health Interventions: Insights From Key Informants in 6 European Countries.

BACKGROUND: Intersectoral collaboration is critical to the successful implementation of many public health interventions (PHIs). Little attention has been paid to whether and how processes at the stage of evaluation can promote intersectoral collaboration. The objective of this study was to examine European experiences and views on whether and how the evaluation of PHIs promote intersectoral collaboration. METHODS: A qualitative study design was used. We conducted semi-structured interviews with 15 individuals centrally involved in the evaluation of PHIs in 6 European countries (Austria, Denmark, England, Germany, Norway, and Switzerland). Questions pertained to current processes for evaluating PHIs in the country and current and potential strategies for promoting intersectoral collaboration. Transcripts were analyzed using thematic analysis to identify key themes responding to our primary objective. RESULTS: Experiences with promoting intersectoral collaboration through the evaluation of PHIs could be summarized in 4 themes: (1) Early involvement of non-health sectors in the evaluative process and inclusion of non-health benefits can promote intersectoral collaboration, but should be combined with greater influence of these sectors in shaping PHIs; (2) Harmonization of methodological approaches may enable comparison of results and facilitate intersectoral collaboration, but should not be an overriding goal; (3) Involvement in health impact assessments (HIAs) can promote intersectoral collaboration, but needs to be incentivized and be conducted without putting overwhelming demands on non-health sectors; (4) A designated body for evaluating PHIs may promote intersectoral collaboration, but its design needs to take account of realities of policy-making. CONCLUSION: The full potential for promoting intersectoral collaboration through the evaluation of PHIs appears currently unrealized in the settings we studied. To further promote intersectoral collaboration, evaluators and decision-makers may consider the full range of strategies characterized in this study. This may be most effective if the strategies are deployed so that they reinforce each other, value outcomes beyond health, and are tailored to maximize political priority for PHIs across sectors.

Global governance and the broader determinants of health: A comparative case study of UNDP's and WTO's engagement with global health.

This comparative case study investigated how two intergovernmental organisations without formal health mandates - the United Nations Development Programme (UNDP) and the World Trade Organization (WTO) - have engaged with global health issues. Triangulating insights from key institutional documents, ten semi-structured interviews with senior officials, and scholarly books tracing the history of both organisations, the study identified an evolving and broadened engagement with global health issues in UNDP and WTO. Within WTO, the dominant view was that enhancing international trade is instrumental to improving global health, although the need to resolve tensions between public health objectives and WTO agreements was recognised. For UNDP, interviewees reported that the agency gained prominence in global health for its response to HIV/AIDS in the 1990s and early 2000s. Learning from that experience, the agency has evolved and expanded its role in two respects: it has increasingly facilitated processes to provide global normative direction for global health issues such as HIV/AIDS and access to medicines, and it has expanded its focus beyond HIV/AIDS. Overall, the study findings suggest the need for seeking greater integration among international institutions, closing key global institutional gaps, and establishing a shared global institutional space for promoting action on the broader determinants of health.

Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study.

BACKGROUND: The Coalition for Epidemic Preparedness Innovations was established in 2016, to develop vaccines that can contribute to preparedness for outbreaks of epidemic infectious diseases. Evidence on vaccine development costs for such diseases is scarce. Our goal was to estimate the minimum cost for achieving vaccine research and development preparedness targets in a portfolio of 11 epidemic infectious diseases, accounting for vaccine pipeline constraints and uncertainty in research and development preparedness outcomes. METHODS: We assembled a pipeline of 224 vaccine candidates from preclinical through to phase 2 for 11 priority epidemic infectious diseases. We used a linear regression model to identify drivers of development costs from preclinical through to end of phase 2a. Drawing from published estimates of vaccine research and development probabilities of success, we simulated costs for advancing these 224 vaccine candidates through to the end of phase 2a. We combined these findings to determine minimum costs for progressing at least one vaccine through to the end of phase 2a per epidemic infectious disease by means of a stochastic optimisation model. FINDINGS: The cost of developing a single epidemic infectious disease vaccine from preclinical trials through to end of phase 2a is US$31-68 million (US$14-159 million range), assuming no risk of failure. We found that previous licensure experience and indirect costs are upward drivers of research and development costs. Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84-112 million ($23 million-$295 million range) starting from phase 2 to $319-469 million ($137 million-$1·1 billion range) starting from preclinical. This cost includes the cumulative cost of failed vaccine candidates through the research and development process. Assuming these candidates and funding were made available, progressing at least one vaccine through to the end of phase 2a for each of the 11 epidemic infectious diseases would cost a minimum of $2·8-3·7 billion ($1·2 billion-$8·4 billion range). INTERPRETATION: Our analysis provides new evidence on vaccine research and development pipelines and associated costs for 11 epidemic infectious diseases, highlighting both funding needs and research and development gaps for achieving vaccine research and development preparedness targets. FUNDING: This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme GLOBVAC.

Introduction and geographic availability of new antibiotics approved between 1999 and 2014.

BACKGROUND: Despite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014. MATERIAL AND METHOD: We identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies' lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin. RESULTS: Of the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes. CONCLUSION: Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.

Should Antibiotics Be Controlled Medicines? Lessons from the Controlled Drug Regimen.

This study aimed to identify the antibiotic-relevant lessons from the controlled drug regimen for narcotics. Whereas several elements of the United Nations Single Convention on Narcotic Drugs (1961) could be advantageous for antibiotics, we doubt that an international legally binding agreement for controlling antibiotic consumption would be any more effective than implementing stewardship measures through national AMR plans.

Insights into early stage of antibiotic development in small- and medium-sized enterprises: a survey of targets, costs, and durations.

BACKGROUND: Antibiotic innovation has dwindled to dangerously low levels in the past 30 years. Since resistance continues to evolve, this innovation deficit can have perilous consequences on patients. A number of new incentives have been suggested to stimulate greater antibacterial drug innovation. To design effective solutions, a greater understanding is needed of actual antibiotic discovery and development costs and timelines. Small and medium-sized enterprises (SMEs) undertake most discovery and early phase development for antibiotics and other drugs. This paper attempts to gather a better understanding of SMEs' targets, costs, and durations related to discovery and early phase development of antibacterial therapies. METHODS: DRIVE-AB, a project focused on developing new economic incentives to stimulate antibacterial innovation, held a European stakeholder meeting in February 2015. All SMEs invited to this meeting (n = 44) were subsequently sent a survey to gather more data regarding their areas of activity, completed and expected development costs and timelines, and business models. RESULTS: Twenty-five companies responded to the survey. Respondents were primarily small companies each focusing on developing 1 to 3 new antibiotics, focused on pathogens of public health importance. Most have not yet completed any clinical trials. They have reported ranges of discovery and development out-of-pocket costs that appear to be less expensive than other studies of general pharmaceutical research and development (R&D) costs. The duration ranges reported for completing each phase of R&D are highly variable when compared to previously published general pharmaceutical innovation average durations. However, our sample population is small and may not be fully representative of all relevant antibiotic SMEs. CONCLUSIONS: The data collected by this study provide important insights and estimates about R&D in European SMEs focusing on antibiotics, which can be combined with other data to design incentives to stimulate antibacterial innovation. The variation implies that costs and durations are difficult to generalize due to the unique characteristics of each antibiotic project and depend on individual business strategies and circumstances.

Allocating external financing for health: a discrete choice experiment of stakeholder preferences.

Most donors of external financing for health use allocation policies to determine which countries are eligible to receive financial support and how much support each should receive. Currently, most of these policies place a great deal of weight on income per capita as a determinant of aid allocation but there is increasing interest in putting more weight on other country characteristics in the design of such policies. It is unclear, however, how much weight should be placed on other country characteristics. Using an online discrete choice experiment designed to elicit preferences over country characteristics to guide decisions about the allocation of external financing for health, we find that stakeholders assign a great deal of importance to health inequalities and the burden of disease but put very little weight on income per capita. We also find considerable variation in preferences across stakeholders, with people from low- and middle-income countries putting more weight on the burden of disease and people from high-income countries putting more weight on health inequalities. These findings suggest that stakeholders put more weight on burden of disease and health inequalities than on income per capita in evaluating which countries should received external financing for health and that that people living in aid recipient may have different preferences than people living in donor countries. Donors may wish to take these differences in preferences in mind if they are reconsidering their aid allocation policies.

New approaches to ranking countries for the allocation of development assistance for health: choices, indicators and implications.

The distributions of income and health within and across countries are changing. This challenges the way donors allocate development assistance for health (DAH) and particularly the role of gross national income per capita (GNIpc) in classifying countries to determine whether countries are eligible to receive assistance and how much they receive. Informed by a literature review and stakeholder consultations and interviews, we developed a stepwise approach to the design and assessment of country classification frameworks for the allocation of DAH, with emphasis on critical value choices. We devised 25 frameworks, all which combined GNIpc and at least one other indicator into an index. Indicators were selected and assessed based on relevance, salience, validity, consistency, and availability and timeliness, where relevance concerned the extent to which the indicator represented country's health needs, domestic capacity, the expected impact of DAH, or equity. We assessed how the use of the different frameworks changed the rankings of low- and middle-income countries relative to a country's ranking based on GNIpc alone. We found that stakeholders generally considered needs to be the most important concern to be captured by classification frameworks, followed by inequality, expected impact and domestic capacity. We further found that integrating a health-needs indicator with GNIpc makes a significant difference for many countries and country categories-and especially middle-income countries with high burden of unmet health needs-while the choice of specific indicator makes less difference. This together with assessments of relevance, salience, validity, consistency, and availability and timeliness suggest that donors have reasons to include a health-needs indicator in the initial classification of countries. It specifically suggests that life expectancy and disability-adjusted life year rate are indicators worth considering. Indicators related to other concerns may be mainly relevant at different stages of the decision-making process, require better data, or both.

Pull Incentives for Antibacterial Drug Development: An Analysis by the Transatlantic Task Force on Antimicrobial Resistance.

New alternative market models are needed to incentivize companies to invest in developing new antibacterial drugs. In a previous publication, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) summarized the key areas of consensus for economic incentives for antibacterial drug development. That work determined that there was substantial agreement on the need for a mixture of push and pull incentives and particularly those that served to delink the revenues from the volumes sold. Pull incentives reward successful development by increasing or ensuring future revenue. Several pull incentives have been proposed that could substantially reward the development of new antibacterial drugs. In this second article authored by representatives of TATFAR, we examine the advantages and disadvantages of different pull incentives for antibacterial drug development. It is TATFAR's hope that this analysis, combined with other related analyses, will provide actionable information that will shape policy makers' thinking on this important issue.

Global public goods for health: weaknesses and opportunities in the global health system.

Since at least the 1990s, there has been growing recognition that societies need global public goods (GPGs) in order to protect and promote public health. While the term GPG is sometimes used loosely to denote that which is 'good' for the global public, we restrict our use of the term to its technical definition (goods that are non-excludable and non-rival in consumption) for its useful analytical clarity. Examples of important GPGs for health include standards and guidelines, research on the causes and treatment of disease, and comparative evidence and analysis. While institutions for providing public goods are relatively well developed at the national level - being clearly recognized as a responsibility of sovereign states - institutional arrangements to do so remain fragmented and thin at the global level. For example, the World Health Organization, mandated to provide many GPGs, is not appropriately financed to do so. Three steps are needed to better govern the financing and provision of GPGs for health: first, improved data to develop a clearer picture of how much money is currently going to providing which types of GPGs; second, a legitimate global political process to decide upon priority missing GPGs, followed by estimates of total amounts needed; and third, financing streams for GPGs from governments and private sources, to be channeled through new or existing institutions. Financing should go toward fully financing some GPGs, complementing or supplementing existing national or international financing for others, or deploying funds to make potential GPGs less 'excludable' by putting them into the public domain. As globalization deepens the degree of interdependence between countries and as formerly low-income economies advance, there may be less relative need for development assistance to meet basic health care needs, and greater relative need to finance GPGs. Strengthening global arrangements for GPGs today is a worthy investment for improved global health in the years to come.

What level of domestic government health expenditure should we aspire to for universal health coverage?

Global discussions on universal health coverage (UHC) have focussed attention on the need for increased government funding for health care in many low- and middle-income countries. The objective of this paper is to explore potential targets for government spending on health to progress towards UHC. An explicit target for government expenditure on health care relative to gross domestic product (GDP) is a potentially powerful tool for holding governments to account in progressing to UHC, particularly in the context of UHC's inclusion in the Sustainable Development Goals. It is likely to be more influential than the Abuja target, which requires decreases in budget allocations to other sectors and is opposed by finance ministries for undermining their autonomy in making sectoral budget allocation decisions. International Monetary Fund and World Health Organisation data sets were used to analyse the relationship between government health expenditure and proxy indicators for the UHC goals of financial protection and access to quality health care, and triangulated with available country case studies estimating the resource requirements for a universal health system. Our analyses point towards a target of government spending on health of at least 5% of GDP for progressing towards UHC. This can be supplemented by a per capita target of $86 to promote universal access to primary care services in low-income countries.

Distributing development assistance for health: simulating the implications of 11 criteria.

After years of unprecedented growth in development assistance for health (DAH), the DAH system is challenged on several fronts: by the economic downturn and stagnation of DAH, by the epidemiological transition and increase in non-communicable diseases and by the economic transition and rise of the middle-income countries. Central to any potent response is a fair and effective allocation of DAH across countries. A myriad of criteria has been proposed or is currently used, but there have been no comprehensive assessment of their distributional implications. We simulated the implications of 11 quantitative allocation criteria across countries and country categories. We found that the distributions varied profoundly. The group of low-income countries received most DAH from needs-based criteria linked to domestic capacity, while the group of upper-middle-income countries was most favoured by an income-inequality criterion. Compared to a baseline distribution guided by gross national income per capita, low-income countries received less DAH by almost all criteria. The findings can inform funders when examining and revising the criteria they use, and provide input to the broader debate about what criteria should be used.

Development assistance for health: what criteria do multi- and bilateral funders use?

After years of unprecedented growth in development assistance for health (DAH), the system is challenged on several fronts: by the economic downturn and stagnation of DAH, by the epidemiological transition and increase in non-communicable diseases, and by the economic transition and rise of the middle-income countries. This raises questions about which countries should receive DAH and how much, and, fundamentally, what criteria that promote fair and effective allocation. Yet, no broad comparative assessment exists of the criteria used today. We reviewed the allocation criteria stated by five multilateral and nine bilateral funders of DAH. We found that several funders had only limited information about concrete criteria publicly available. Moreover, many funders not devoted to health lacked specific criteria for DAH or criteria directly related to health, and no funder had criteria directly related to inequality. National income per capita was emphasised by many funders, but the associated eligibility thresholds varied considerably. These findings and the broad overview of criteria can assist funders in critically examining and revising the criteria they use, and inform the wider debate about what the optimal criteria are.

Towards a coherent global framework for health financing: recommendations and recent developments.

The articles in this special issue have demonstrated how unprecedented transitions have come with both challenges and opportunities for health financing. Against the background of these challenges and opportunities, the Working Group on Health Financing at the Chatham House Centre on Global Health Security laid out, in 2014, a set of policy responses encapsulated in 20 recommendations for how to make progress towards a coherent global framework for health financing. These recommendations pertain to domestic financing of national health systems, global public goods for health, external financing for national health systems and the cross-cutting issues of accountability and agreement on a new global framework. Since the Working Group concluded its work, multiple events have reinforced the group's recommendations. Among these are the agreement on the Addis Ababa Action Agenda, the adoption of the Sustainable Development Goals, the outbreak of Ebola in West Africa and the release of the Panama Papers. These events also represent new stepping stones towards a new global framework.