Author + information
- Received September 13, 2017
- Revision received October 31, 2017
- Accepted November 2, 2017
- Published online December 18, 2017.
- Valentin Fuster, MD, PhDa,b,∗ (, )
- Jendayi Frazer, PhDc,
- Megan Snair, MPHd,
- Rajesh Vedanthan, MD, MPHa,
- Victor Dzau, MDe,
- on behalf of the Committee on Global Health and the Future of the United States: A Report of the National Academies of Sciences, Engineering and Medicine
- aIcahn School of Medicine at Mount Sinai, Zena and Michael A. Wiener Cardiovascular Institute, New York, New York
- bCentro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
- cCouncil on Foreign Relations, Studies Department, Washington, DC
- dNational Academies of Sciences, Engineering, and Medicine, Board on Global Health, Washington, DC
- eNational Academy of Medicine, Office of the President, Washington, DC
- ↵∗Address for correspondence:
Dr. Valentin Fuster, Icahn School of Medicine at Mount Sinai, Zena and Michael A. Wiener Cardiovascular Institute, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
U.S. global health investment has focused on detection, treatment, and eradication of infectious diseases such as tuberculosis, malaria, and human immunodeficiency virus/acquired immunodeficiency syndrome, with significant results. Although efforts should be maintained and expanded to provide ongoing therapy for chronic infectious disease, there is a pressing need to meet the challenge of noncommunicable diseases, which constitute the highest burden of diseases globally. A Committee of the National Academies of Sciences, Engineering, and Medicine has made 14 recommendations that require ongoing commitments to eradication of infectious disease and increase the emphasis on chronic diseases such as cardiovascular disease. These include improving early detection and treatment, mitigating disease risk factors, shifting global health infrastructure to include management of cardiovascular disease, developing global partners and private-public ventures to meet infrastructure and funding challenges, streamlining medical product development and supply, increasing research and development capacity, and addressing gaps in global political and institutional leadership to meet the shifting challenge.
Global heath is not only measured in the number of lives saved; it is linked to economic productivity and growth worldwide. Benefits from investment in global health can exceed costs by a factor between 9 and 20 for low- and middle-income countries (LMICs), respectively (1,2). Preventing, detecting, and responding to infectious disease (ID) outbreaks can save an estimated $15 billion annually (3).
The United States has long been a leader in global health, through programs such as the President’s Emergency Plan for AIDS Relief (PEPFAR); the President’s Malaria Initiative; the Global Fund to Fight AIDS, Tuberculosis and Malaria; Gavi, the Vaccine Alliance; and the more recent Global Health Security Agenda (GHSA). A commitment to global health is needed, and the new U.S. administration faces the challenge of ensuring that gains in global health are sustained and poised for further growth.
Foreign assistance is not “charity,” but is an investment in the health of the recipient country, the United States, and the world at large. Although the burden of ID, for example, falls predominantly in LMICs, these same diseases represent threats to all countries, including the United States. Growing international travel and trade, interconnectedness, and interdependency of countries heighten a variety of health threats, such as avian influenza, Ebola, and Zika. A moderate influenza pandemic would result in an estimated 2 million excess deaths. The 2003 SARS outbreak cost the world $40 to $54 billion. In 2014, the United States committed $5.4 billion in response to the Ebola outbreak.
As a result of improvements in sanitation and ID prevention, the burden of disease in LMICs is now shifting from IDs to noncommunicable diseases (NCDs). Cardiovascular disease (CVD) and other NCDs, such as cancer, threaten the gains in life expectancy, productivity, and quality of life that have been achieved in LMICs. Brazil, Russia, India, and China currently lose more than 20 million productive life-years annually to NCDs, and that number is projected to increase 65% by 2030. The costs of disability, unplanned work absences, and accidents can exceed those of treatment of the underlying condition or injury by 400% (4). Research also shows that investors are less likely to enter markets with heavy disease burden (5,6). Human capital clearly contributes to economic growth, and thus, having a healthy population is critical for economic prosperity, which can then help create more stable partners and increased security for the United States.
The Institute of Medicine (IOM) (now renamed the National Academy of Medicine) Board on International Health was commissioned 20 years ago to report on addressing U.S. commitment to global human health (7). Their report demonstrated appreciation for the growing global interconnections, and the interdependency of the United States with other countries in health matters. Twelve years later, an independent committee appointed by the IOM Board on Global Health prepared a new report for the incoming Obama administration. The U.S. Commitment to Global health: Recommendations for the New Administration (2009) called upon the U.S. research sector to collaborate globally, establish information-sharing networks, and support academia and health systems in LMICs (8). They recommended improving coordination across the U.S. government. U.S. coordination efforts, such as Feed the Future, PEPFAR, the President’s Malaria Initiative, and GHSA, have consequently been successful (3).
As a follow-up to the first 2 reports, the National Academies of Sciences, Engineering, and Medicine was charged with identifying current global health priorities and making recommendations to the U.S. government and other stakeholders to increase responsiveness, coordination, and efficiency in addressing global health (3). Based on a rigorous and evidence-based consensus process, the Committee settled on 14 recommendations that, if implemented, would deliver a strong global health strategy and maintain the role of the United States as a leader in global health. A detailed description of the Committee’s approach and meeting agendas, as well as full reference lists, can be found in the Committee’s full report (3).
1. Achieving global security;
2. Maintaining a sustained response to the continuous threats of communicable diseases;
3. Saving and improving the lives of women and children; and
4. Promoting cardiovascular health and preventing cancer.
They also identified 3 additional cross-cutting areas to maximize the returns on investment, achieve better health outcomes and use funding more effectively:
1. Catalyze innovation through accelerated development of medical products and integrated digital health infrastructure;
2. Employ more nimble and flexible financing mechanisms to leverage new partners and funders in global health; and
3. Maintain U.S. status and influence as a world leader in global health while adhering to evidence-based science and economics, measurement, and accountability.
This paper presents the Committee’s findings, recommendations, and rationale regarding a growing priority area in global health—detection and management of CVD—together with the various cross-cutting measures that can potentially maximize returns on investments in CVD management, achieve better outcomes, and use funding more effectively to achieve better cardiovascular global health:
1. Global cardiovascular health;
2. Screening for early detection and treatment of CVD;
3. Catalyzing innovation;
• Accelerating drug development;
• Research and development (R&D) capacity;
• Digital health;
4. Smart financing strategies; and
5. Global health leadership.
Global Cardiovascular Health
With increasing success in ID prevention and sanitation improvement, a greater proportion of children are surviving to adulthood. However, this increased longevity, along with changes in diet and lifestyle, has fostered a rise in the chronic illnesses of adulthood. The most common of these, CVD, chronic obstructive pulmonary disease, cancer, and diabetes, are all associated with increased prevalence of behavioral risk factors, such as tobacco use, sedentary lifestyle, and diets high in calories, sugar, and salt.
Chronic NCDs, including CVD, kill 40 million people annually, almost 75% of whom live in LMICs (10). NCD results in lower national productivity, higher health and welfare expenditures, unplanned work absences, and increased accident rates. Investors are also less likely to enter markets where the labor force carries a high disease burden. Although NCDs are often portrayed as being a western, high-income country challenge, NCDs actually disproportionately affect the poor in middle-income countries, and that trend will continue to grow with rising urbanization.
U.S. interests are affected by the human and economic effects of the rise in NCDs in LMICs; countries with a higher NCD burden tend to have lower national productivity and higher health and welfare expenditures. Costs resulting from productivity losses due to disability, unplanned work absences, and increased accidents are as much as 4× the cost of treatment (3). Furthermore, investors are less willing to enter markets where the labor force has a heavy disease burden.
Rising economic burden of NCDs
It is estimated that the increase in the global economic burden of CVD, chronic respiratory disease, cancer, diabetes, and mental health will result in cumulative output losses of $47 trillion by 2030, representing about 75% of the 2010 gross domestic product (GDP) (5). As of 2015, the estimated annual global cost of CVD is expected to increase by 16%, from $906 billion to more than $1 trillion by 2030 (3). CVD accounts for the highest health care expenditures in most countries, ranging from 12% to 16.5% of the overall health care budget (11). The mortality from CVD is growing, with an increase globally of 12.5% between 2000 and 2015, and CVD is now the leading cause of death globally (12)—in 2015, CVD was responsible for about 18 million deaths (3). See Figure 2 for a representation of economic costs and mortality.
Barriers to adequate care
A considerable barrier to adequate care for NCDs is that most LMICs lack adequate health care infrastructure. Other challenges are a lack of well-trained health care providers and a lack of regulations on harmful substances such as tobacco. Health systems in LMICs are typically designed to handle IDs, not NCDs, and are not geared to meet patients’ long-term health needs. Taken together, these weaknesses in system design and lack of training can lead to poor quality of care, which can further drive people from seeking health care (13). High out-of-pocket expenditures (up to 50% of total health care expenditures ) cause many patients to opt out of seeking or persisting in chronic medical treatments, or to steer toward the informal sector, where there may be less regulation around safest and best practices (15).
Policymakers often focus on the health care issue immediately confronting them, and find it difficult to prioritize health objectives that may seem distant or merely abstract. Countries often have difficulties in effecting national policy changes regarding NCDs, because they are not prioritized in political agendas in the same way IDs often are. The “slow epidemic” of NCDs simply does not create the type of panic or rapid response that IDs like Ebola, multidrug resistant tuberculosis (TB), or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) can generate.
Motivation for U.S. involvement
The growing global burden of CVD and other NCDs poses a significant strategic problem that the United States cannot afford to ignore. Currently, the majority of U.S. spending on global health is directed toward IDs, such as HIV/AIDS, TB, and malaria. There is currently no dedicated U.S. funding for NCDs, and there are no presidential initiatives to reduce their burden. Yet, the United States benefits in many different ways from investing in the fight against global CVD and other NCDs. Three key benefits stand to be realized by incorporating CVD and other NCD programs into existing U.S. global health programs: 1) the adoption of a universal purpose; 2) economic prosperity and trade benefits; and 3) the safeguarding of U.S. global health investments.
1 Universal purpose
Because NCDs are a leading cause of morbidity and mortality across high-, middle-, and low-income countries, there is opportunity for shared innovative approaches to develop solutions to common problems for everyone. U.S. investment in CVD and prevention abroad affords the U.S. more opportunities to identify cost-effective domestic strategies for these diseases. For example, a mobile health solution for NCD management in King County, Washington, is based on successful interventions developed in Bangladesh, China, and India (16). Research done in other countries, such as Cuba’s research on CIMAvax lung cancer vaccine (17), may accelerate the discovery of cures and more effective treatments within the United States. Prevention and management strategies for CVD can similarly benefit from universal efforts.
2 Economic prosperity and trade benefits
When other countries have a healthy population and workforce, the United States benefits from their more stable economies, which encourage business expansion and consumption of U.S. goods.
3 Raising the return on other U.S. global health investments
Patients who have already received U.S. global health aid for IDs, such as malaria, TB, and HIV/AIDS, and survived may later become the victims of NCDs. If they become unable to work or die prematurely because of CVD, that initial investment in their health, with resulting benefits in terms of healthier societies and stabilized economies, will be lost.
Cost-effective global interventions
A 2011 World Economic Forum report identified a set of highly cost-effective “best buy” interventions and risk factor reductions that can feasibly be implemented at the population and individual level in LMICs (18). The cost of implementing the full suite of recommendations across all LMICs between 2011 and 2025 would be $170 billion, or <5% of overall health spending in these countries (18). Implementing only “best buy” recommendations, at a cumulative cost of $120 billion, would drive a 10% decrease in CVD-attributable mortality and a $377 billion projected economic benefit (18).
Interventions that may affect CVD on that list of “best buys” are listed in Table 1 and include preventive and treatment measures such as regulations, policies, and patient care delivery. A 2015 working paper for the Disease Control Priorities project found that substantially increasing 4 prevention and treatment interventions over 15 years would reduce projected NCD mortality by 25% in LMICs (19). These interventions also align with the committee report recommendation, which called for targeting and managing risk factors for major NCDs, particularly through the adoption of fiscal policies and regulations that facilitate tobacco control and health diets, as well as detecting and treating hypertension early—integrated with services at the community level (3).
Risk factor interventions can be classified into 2 approaches: fiscal and regulatory policies, and those targeting service delivery. Examples of the former are tax increases on cigarettes and requiring smoke-free work environments. Examples of the latter include integrating additional services into health care visits, and conducting screening programs in high-traffic areas.
Fiscal and policy approaches (e.g., food labeling, taxation of sugar-sweetened beverages, worksite interventions, and mass media interventions to address obesity) have been found in Brazil, China, Mexico, Russia, and South Africa to be cost saving. They generated the largest or second largest 20- and 50-year projections compared with other interventions (20). A “sugar tax” in Mexico of 1 peso/l resulted in a 7.6% reduction in purchases, and the reduction was even greater in poorer households (21). The tax is expected to save Mexico $983 million by lowering the incidence of diabetes, stroke, and myocardial infarction, with subsequent reductions in mortality (22). Additional studies and simulations have also shown positive effects from taxing sugar-sweetened beverages in Australia, Brazil, France, Mexico, and the United States (23–26). Conversely, a recent meta-analysis demonstrated that a 10% reduction in the price of healthful foods and beverages increased consumption by 14% (27). Although the evidence is not fully conclusive with respect to the overall effect of beverage taxes on health behaviors and cardiovascular risk factors, this approach increasingly appears to be beneficial for cardiovascular health.
Similar approaches have also been shown to curb tobacco abuse in over 100 studies (28). The Lancet Commission on Investing in Health found that a 50% price increase in cigarettes taxes in China would avert 20 million deaths and generate $20 billion in revenue over 50 years (28).
Regulatory changes other than taxes can also influence behavior and environmental factors that contribute to CVD and cardiovascular-related mortality. Tobacco warning labels have been proven effective in raising awareness and reducing consumption (29). With tobacco-related illnesses projected to kill 8 million people annually by the year 2030 (30), a combination of taxation and regulatory measures can be expected to decrease tobacco-related CVD significantly.
Finally, air quality is a manageable environmental factor that contributes to CVD and pulmonary disease and mortality. Deaths from air pollution cost the global economy $225 billion in lost labor and $5 trillion in welfare losses in 2013 (31). Regulatory opportunities include limiting the open burning of waste, limits for emissions by major industrial polluters, and vehicle emission standards. Many countries have already paved the way for progress in this area and should be followed.
Screening for Early Detection and Treatment of CVD
Early detection and treatment of CVD
Early intervention in CVD once it is established can prolong life, improve quality of life, and improve socioeconomic health in LMICs. Blood pressure screening, for example, is relatively inexpensive and simple, and can easily be integrated into existing U.S. health programs by using the same facilities and staff already in place to manage IDs. Early detection can prompt behavioral changes, promote regular health visits, and improve medical management.
An early detection and screening strategy is only effective if medical management can be subsequently initiated, and this requires trained staff, an appropriate physical infrastructure, and an entire supply chain of treatment regimens. Thus, simply improving screening is not enough to realize long-term results. The Academic Model Providing Access to Healthcare (AMPATH) Chronic Disease Management Program, partially supported by AstraZeneca’s Healthy Heart Africa (HHA) initiative, provides integrated, quality CVD care in western Kenya. Challenges were ascertained to be identification of patients, poor laboratory and diagnostic equipment, and mistrust among the people of public-sector services. AMPATH’s answer to the challenges was to provide door-to-door, home-based screening services, supply rural health centers with diagnostic materials, and concentrate efforts to improve relationships within the community and with tribal elders (32).
Transforming health systems for NCDs
“Single-disease” programs are less efficient and likely less effective in tackling the burden of CVD than in managing outbreaks of ID. U.S. programs have opportunities to leverage existing stakeholders and programs to create a multilevel attack on CVD. One example is the Global Hearts initiative, a collaboration of the World Health Organization (WHO), the U.S. Center for Disease Control and Prevention, the World Heart Federation, the World Stroke Organization, the International Society of Hypertension, and the World Hypertension League (33). This collaboration provides governments with technical support to implement interventions to reduce blood pressure and prevent heart attacks and strokes. In addition to leveraging existing programs, redesigning health systems to be more holistic and integrated in nature and decentralizing services in communities can improve efficiency and sustainability.
The private sector has a clear interest in participating in these transformative efforts: a healthy and productive workforce improves profitability. Companies in the health care sector also benefit from growing markets in LMICs. Sustainable health care translates into a sustainable and growing economy, improved markets, and growth of company business.
Changing models of community service
Disease burdens in LMICs are exacerbated by interactions between NCDs and IDs. For example, TB infection is associated with an increased risk of stroke (34), and HIV/AIDS is associated with increased risk of CVD (35), due both to side effects of antiretroviral therapy and due to the increasing longevity of HIV/AIDS patients. Disease-specific care systems that were effective in management of ID outbreaks cannot adequately address IDs and NCDs if they remain siloed. In fact, effective management of both IDs and NCDs can be improved by integrating services—through sharing staff, locations, systems, tools, and strategies. Two examples of successful integration are the Practical Approach to Health Care Kit, developed by the University of Cape Town Lung Institute (3), and the HIV/AIDS-hypertension integrated care model in Cambodia (36). The Practical Approach to Health Care Kit empowers front-line nurses in communities with scarce resources. The program was originally designed to improve access to diagnoses and treatment of TB and HIV, but has been expanded to include chronic conditions, including CVD. In Cambodia, 12% to 15% of the population has hypertension (3). The Cambodian Ministry of Health and Médecins San Frontières established clinics to integrate chronic care for hypertension and diabetes with HIV/AIDS care. This effort resulted in an increased influx of patients and improved patient health by promoting achievement of health blood pressure targets.
Task shifting is the broadening health of care roles and use of the existing workforce for new objectives. Many health care workers who are without high-level training, such as community health workers, can be shifted into health care screening and patient identification roles, freeing up higher-level professionals to focus on tasks that require more expertise. A 2015 assessment of community health workers in Bangladesh, Guatemala, Mexico, and South Africa found that health workers without formal professional training can be adequately trained to effectively screen for and identify people with a high risk of CVD (37). Additionally, researchers in Argentina recently found improved hypertension control among low-income populations following community health worker–led multicomponent interventions (38). For example, an international public-private partnership is undertaking a cost-benefit analysis of a community-based hypertension program to enhance the capacity of the Ghana Health Service, as an estimated 27% of the population is hypertensive, but only 4% of patients achieve blood pressure control (39). This program includes task shifting, by pushing blood pressure screening and monitoring out of health facilities to community health officers and private drug outlets, shifting management of uncomplicated moderate hypertension from doctors to community-based nurses, and shifting the dispensing of blood pressure medications from pharmacists to private drug outlets (3,39,40).
Leveraging private sector involvement
The willingness of private and public sectors to invest together in health care programs depends on the presence of appropriate investment mechanisms, assurance that returns on investments will materialize, and business models that enable benefit sharing. A recent collaborative initiative among 20 companies was launched at the World Economic Forum Annual Meeting in 2017 (41), demonstrating interest and willingness of the private sector to participate in advancing knowledge and infrastructure to augment efforts to tackle NCDs globally.
Health companies are particularly vested in reaching populations in LMICs that experience NCDs, such as CVD. These populations can create market opportunities for large numbers of patients who currently do not have access to the right medications to purchase and rely on their medical products (medications, vaccines, and devices), and that will eventually translate into larger profits and sustainable business growth.
Examples of companies that already hold such investments include Novartis, Pfizer, and Medtronic (3). The Novartis Access Program offers 15 medications addressing CVD, type 2 diabetes, breast cancer, and respiratory illnesses as a basket to countries for $1/treatment/month, with a goal to provide access to 20 million patients annually by 2020 (3). Pfizer is also tackling NCDs, and joined with HelpAge International in 2012 to reduce NCD burdens in the elderly in Tanzania (3). Finally, the Medtronic Foundation is involved in a 5-year, $17 million global effort to expand access to CVD and diabetes care to underserved populations of Brazil, India, South Africa, and the United States (3). These are just a few examples of the many initiatives operated by private sector companies to address NCDs that have much more to offer than historical financial support. A more comprehensive listing of development programs involving the research-based pharmaceutical industry can be found in the Federation of Pharmaceutical Manufacturers and Associations Health Partnerships Directory (42).
Apart from direct health care screening and delivery, other challenges include promotion of drug and vaccine development for ID and NCDs. Advances in information technology can revolutionize global health and may provide the opportunity to bypass many costly brick-and-mortar health services, enabling better delivery of care for NCDs, including CVD.
Accelerating development of medical products
The development and deployment of new medical products is constrained by many problems: uncertain commercial potential and costly development and approval processes that decrease the likelihood that a commercial entity will take the risks necessary to develop truly innovative therapies, lack of manufacturing capacity, and poor laboratory and workforce capacities in LMICs that reduce global markets. Innovation in trial designs, the streamlining of regulatory barriers, improving manufacturing capacity and market incentives, and building R&D capacity in LMICs can accelerate the supply of medical products globally.
Traditional trials are limited by rigidity or poor adaptability to real-life circumstances. Randomized clinical trials often require large sample sizes and lengthy study durations. The cost of drug development has increased nearly 100-fold between 1950 and 2010 when adjusting for inflation, and fewer drugs are approved by the U.S. Food and Drug Administration (FDA) (43). Three approaches can improve the efficiency of clinical trials: adaptive clinical trials, pragmatic clinical trials, and surrogate endpoints or biomarkers.
Adaptive trial design
Adaptive trial design allows flexibility to modify study hypothesis and design based on analysis of interim data—possibly shortening trial and development time (44–46). The FDA issued guidance for adaptive clinical trials in 2010 (45), but has been slow to clarify how they would be evaluated. The recently passed 21st Century Cures Act of 2016 (47) pushes the FDA to host public discussion of adaptive and other novel trial designs, and to issue additional guidance regarding their use.
Randomized clinical trials use strict controls to produce results that are clinically credible, but are not always applicable in real-world circumstances. Real-world clinical evidence, such as electronic health records, medical claims data, disease registries, and data obtained through personal devices, can complement clinical trial data. Pragmatic trials relax controls in a trial, but still involve randomization and require large sample sizes. They also present new challenges, such as participant recruitment and consent, practice variations, and risk determinations.
Natural experiments also have utility in this regard, because they can sometimes be more feasible than a formal clinical trial. Although the evidence is quasi-experimental, there are methodological approaches that can be used to assess the effects of existing local and national-level health policies—demonstrating “real-world” impacts (48,49).
Biomarkers as surrogate endpoints
Clinical endpoints provide clear metrics for the success or failure of an investigational treatment, but can take years to develop after a trial’s end. Biomarkers can provide interim evidence about safety and effectiveness and can address this issue, speeding up drug development. Validation of a biomarker as a surrogate endpoint requires strong evidence (50), and thus, the FDA approves use of biomarkers as surrogate endpoints on a provisional basis, and requires phase IV studies to prove correlation (3). The 21st Century Cures Act charges the FDA with providing guidance on a review pathway and collaborating with scientific partners to develop qualification plans to ensure safety in more rapid product development processes (47).
U.S. drug approval takes 12 to 15 years, at an average cost of $2.5 billion (51,52). Only 9.6% of all new drugs make it all the way from Phase 1 trials to approval (53). Private companies rely on assessment of risks and potential financial returns when deciding which products to develop. Development is unlikely if risks and costs to the company are too high, and if the market for the drug is small or uncertain. To mitigate some of these costs, the Center for Drug Evaluation and Research at the FDA has 4 different mechanisms at their disposal to expedite review for new drug applications: fast-track, breakthrough therapy, accelerated approval, and priority review (52,54–57). Although these options are designed to help share the burden of costs and “push” a product through the development pipeline, they have not sufficiently incentivized private sector engagement and should be re-evaluated for expansion to further streamline the approval process for critical global health products.
In addition to accelerated review processes, legislation such as the Orphan Drug Act (ODA) (58), the Priority Review Voucher (PRV) (59), and the Generating Antibiotic Incentives Now Act (60) incentivizes industry to develop products for which a commercial market is uncertain or limited.
The ODA was intended to incentivize drug development for rare diseases by providing drug companies 7 years of market exclusivity, a tax credit covering 50% of clinical trial costs, R&D grants, and a waiver of some FDA fees. The act was developed to address diseases in domestic markets, and because neglected diseases typically affect the world’s poorest populations, most pharmaceutical companies do not pursue drug development through the ODA. Although the FDA had granted 2,923 diseases orphan status as of November 2013, it has only granted approval to 447 drugs (61). Leveraging this act may foster drug development for neglected CVDs globally.
The PRV program established in 2007 rewards innovators for developing novel treatments for diseases that would otherwise not attract commercial interest. In exchange, the FDA grants the manufacturer a voucher allowing them to designate another product in their pipeline for priority review—a market advantage potentially worth millions of dollars in profit (59). The program suffers from concerns over possible exploitation; the first PRVs granted were for products either already developed or in late-stage development, raising questions of whether the program was incentivizing development, or merely a giveaway to companies already doing that type of work. Furthermore, some have been sold to other companies for prices as high as $350 million (62). Current provisions in the program prevent innovations in treatments, such as follow-up formulations that could be applied in poor resource settings, from qualifying for PRVs. PRVs can nevertheless be another tool in the “incentive toolbox.”
Creating market incentives and ensuring supply
Having a sufficient supply of medical products to meet fluctuating global demand means ensuring both adequate manufacturing capacity and sufficient product stockpiles. Although this is especially true for products intended to treat ID outbreaks in which demand fluctuates dramatically, it is also true of products to treat NCDs, such as CVD. Continued work is needed to ensure access to medications through adequate distribution methods and supply chain networks. Stock-outs of even routine products is an ongoing challenge in many countries (63).
To incentivize pharmaceutical, vaccine, and device companies to invest in R&D of products in risky markets, in 1997 the IOM called for allowing multitiered pricing, safeguarding of intellectual property rights, and increased incentives for product development (8). So-called “pull” incentives for product development, such as reducing market uncertainty by guaranteeing volumes and prices, require sustained political commitment, which can be challenging when governmental leadership can change every few years.
Tiered pricing can expand access to affordable drugs and other health products, but is most effective when market risks are low. The success of tiered pricing also depends on a tacit agreement among high- and middle-income countries that the poorest countries will receive lower prices. It also requires that mechanisms be in place to prevent low tier–priced products from leaking back into higher-income markets.
Increasing R&D capacity
Building local capacity and developing local workforce to conduct clinical trials in LMICs is critical. Research capacity abroad allows for the development of treatments for diseases not only in LMICs, but also in the United States. Duke University’s Global Health Institute and the Lancet Commission both agree that developmental assistance for health should be directed to individual countries for the purpose of developing their own R&D capacity and thereby promoting the development of treatments for diseases that plague both LMICs and the United States (3,64). An example is a recent accord between the U.S. Department of Health and Human Services (DHHS) and Cuba’s Ministry of Public Health; Cuba has promising treatments that have been unavailable to U.S. patients since the 2006 trade embargo, such as treatments that can prevent amputations in diabetics, and CIMAvax (17). Similar cooperative pacts can be targeted for CVD.
Training local researchers promotes sustainable research programs and fosters independence in LMICs through academic partnerships. Such partnerships provide benefits for both the LMIC and the more developed institution. An academic partnership between AMPATH, an Indiana University-led initiative, and Moi University in Kenya provides 30% of medical students with financial aid to increase the number of Kenyan medical professionals. The partnership supports development of a sustainable workforce in Kenya, and creates mentorship opportunities for students and faculty with an interest in global health (3,65). Funding for such partnerships can be leveraged through the Fogarty International Center at the National Institute of Health (NIH) and the U.S. Agency for International Development (USAID). An NIH-sponsored grant between Vanderbilt University and Zambia, as well as another connecting Vanderbilt University and Tulane University with the Kenema Government Hospital in Sierra Leone, provides training to local researchers (3). Such programs also provide other benefits: local experts have more success than “outsiders” in influencing health policy in LMICs, and can also act as advisors to aid programs such as PEPFAR. USAID has programs to strengthen local research systems, such as the Partnerships for Enhanced Engagement in Research, which funds international scientists in partnership with U.S. funding (66), and the Higher Education Solutions Network, which works with 7 U.S. universities to spur local solutions in partnership with international academic institutions (67). A separate 2017 National Academies report advising USAID calls for continuing partnerships with programs such as both Partnership for Enhanced Engagement in Research and the Higher Education Solutions Network (3).
Laboratory research capacity is also needed for sustainable local research. Examples of the barriers presented by poor laboratory capacity can be found in ID outbreaks. Poor research capacity in West Africa in the 2003 Ebola outbreak hindered efforts to identify the source of the outbreak, which was erroneously first attributed to cholera (68). The U.S. Department of Defense’s Cooperative Biological Engagement Program deployed mobile laboratories in Sierra Leone and Guinea in 2014 and 2015, allowing quick detection of Ebola cases in both countries (69). Lessons from successes with ID can inform efforts for NCDs as disease burden shifts in LMICs.
Taken together, both workforce and laboratory capacity are essential to build a strong health system able to respond to infectious disease outbreaks before they lead to catastrophic consequences, and in a cost-effective manner. But, it should be done with the end users and local context in mind. According to Costello and Zumla (70), by helping to create an independent researching body in LMICs, researchers are trained in their home countries and are encouraged to stay there because of the existing infrastructure; in-country grants investigate the problems most of interest to the nation’s people; and results have a higher likelihood of leading to policy changes, as compared with research conducted by individuals from other, high-income countries (70). Similarly, local mental health research conducted in LMICs is found to be much more easily adaptable to solve local problems compared with research conducted by high-income countries that is based on evidence from high-income countries (71).
Promoting digital health
Telecommunication and wireless multimedia contribute significantly to advancement of global health, such as promotion of adherence to chronic disease management. However, many programs have suffered from a short-term approach and narrow program perspective, which facilitates faster and easier results, but is insufficient to prevent unnecessary duplication and inefficiencies and to address broad health system needs. The establishment of digital platforms and training of the workforce has upfront costs, but commitment to their long-term development can reduce future costs and improve program efficiencies. Strategic planning for digital global health innovations, with emphasis on long-term system gains, multidisciplinary approaches, and individual country ownership is needed. Digital tools can facilitate disease surveillance, patient tracking, inventory maintenance, and telemedicine. The Committee designates 3 broad application areas for digital systems: data system creation, health care service optimization, and research efficiency. Although all 3 have examples of successful software and applications to real-world needs, the current state of tools can be improved. Data systems often do not interact with each other and cannot aggregate information easily. A common digital health platform architecture can create interoperability across systems but could still allow for user flexibility. Although digital tools have provided solutions to health care services, a common platform could also maximize this capacity and expand the scope of a health workforce to match the demand for more integrated health services. Finally, in terms of research efficiency, a common platform can improve on efficiencies already gained through data-sharing among investigators, potentially allowing for novel research inquiry with low added costs. This could also enable more targeted studies and faster recruitment.
Digital health application investments
The enthusiasm surrounding digital applications in global health has not always lead to the best solutions. A multitude of applications and investors has caused a fragmented approach to digital health systems in many countries. Multiple donors and organizations may be funding and operating multiple digital surveillance systems for different diseases in the same country. Siloed digital applications frequently are not interoperable with one another, and may duplicate functions already present in other systems. There is a need to promote more efficient investment in digital health applications, reduction of redundancy, and interoperability of applications. Uganda issued a temporary moratorium on digital health pilots in 2012, for example, because its health system became overrun with fragmented applications (72). Investment in a common digital health platform with connected systems to ensure that data can be aggregated and shared, as well as digital tools for real-time collection of health data, are needed. Digital health applications must be adaptable to local needs. Such systems optimize health care service capacity and maximize research efficiency.
To improve standardization and coordination, and to facilitate implementation of digital health tools, the WHO, in cooperation with partner organizations, is developing a Global Digital Health Index to track, monitor, and evaluate any digital technology solution for a community or country’s health needs (73). The Index is intended to guide governments in monitoring effects of digital health investment, guide where investment is needed, establish best practices regarding digital health, identify and promote public and private sector engagement in digital health, and promote better creation and use of digital tools.
Many national governments have adopted national e-health strategies, including Ghana, Nigeria, and Tanzania (74–76), opening the door for better coordination of digital system driven by country-level priorities. In 2015, 25% of Africa and 58% of Asia had an internet connection (77). Beyond this percentage is the large number of people who have access to additional services that have been created without internet access, through cellular networks using mobile phones. With these advances in country ownership for e-health and growing connectivity rates, the United States has an opportunity to better integrate digital health efforts in countries to reduce fragmentation and improve coordination and efficiency (77,78).
Smart Financing Strategies
Without global collaboration and appropriately structured financing, global health progress will be difficult to realize. Future U.S. investments should focus on the greatest return, and on those that require strong leadership and commitment where the United States could play a role.
Returns for “global public goods”—those that require too many resources for 1 country to create alone, such as R&D advancements in medical products or digital health technologies—are positive and sustainable. For example, the rotavirus vaccine was developed jointly by the United States and India, and has significantly reduced the burden of rotavirus in India, with improved health and economic benefits (3). Yet, often times these global public goods can be hard to track and attribute. The Organization for Economic Cooperation and Development recently proposed a measure to better enable this process, called Total Official Support for Sustainable Development, to track donor investment on global public goods, facilitate learning exchange, track progress on global challenges, and inform policy discussions using empirical evidence (79).
A shift in emphasis to incorporate long-term investments, such as the building of a hospital in a remote district to prevent the need for travel for health care, is necessary to create lasting change. A historic example was the effort to eradicate smallpox—a costly endeavor that involved continued vaccination programs in countries where smallpox was not endemic to meet the objective. Returns on the investment in smallpox eradication continue to pay dividends to the United States and the world to this day. Returns on the investment in the Global Polio Eradication Initiative of 1988 have already reached $27 billion, and are projected to reach $40 to $50 billion by 2035 (80). Similar types of investments geared toward NCDs, such as CVD, may pay similar dividends.
Increased recruitment of donor country resources and transitioning to domestic financing will be possible as many low-income countries are propelled toward middle-income status. The United States can partner with ministries of finance in these countries to structure tax initiatives and other private or donor funds to best leverage the rising income levels. The United States has already mobilized funds by increasing private capital flow, incorporating more private sector and nongovernmental organization partners, and investing in more science, technology, and innovation. The USAID strengthened its Development Credit Authority to unlock larger sources of capital, and the Overseas Private Investment Corporation found that the United States mobilized $10 billion from the private sector through guarantees in 2012 to 2014 to facilitate participation in the development of LMICs (81). Continuing this trend of supported country ownership can lead to reduced spending for the United States on development assistance for health.
Domestic funding sources
To complement this increased mobilization of funds, domestic government health expenditure rose as a source of funding in LMICs by 8.5% annually from 2000 to 2013 (82), and middle-income country use of government health funds exceeded external developmental assistance for health nearly 80× in 2013 (82). Additionally, growth projections from the International Monetary Fund show emerging market and developing economies experiencing an increase in GDP of 4.6% for 2017 (83). This growth in GDP, coupled with sound fiscal policies, suggests the potential for targeted transition for those countries to domestic funding and graduation from development assistance for health. Models for transition for NCDs can be found in the transitioning of existing ID programs; Gavi, the Vaccine Alliance, has a long-term strategy of phasing partner countries out of support. From 2013 to 2014, Gavi countries increased their domestic spending on vaccines per child by 47% (84).
Tax revenues are often the main source of funds for local health systems in LMICs, but consumption taxes often provide the majority of revenue and are not a stable tax base. However, the value-added tax, a variant of the consumption tax, is an efficient and reliable means of stabilizing tax revenue. Unfortunately, due to large informal sectors in LMICs, the benefits of a value-added tax may not be readily realized (85). As a result, countries should consider a mix of tax revenues—including corporate and capital gains taxes. This more balanced approach to revenue mobilization must be weighed against the business-attracting power of lower corporate taxes for many countries (86).
The role of the private sector
The private sector will play a critical, expanding role to achieve many sustainable development goals. In recent years, private companies’ philanthropic activities that have previously been considered “corporate social responsibility” have shifted toward becoming global health investments, with expectations of shared value in the efforts and results. This linkage of economic and social impact moves companies toward greater innovation with an eye to greater value creation. Some companies have adopted a “triple bottom line” approach that requires consideration of social, financial, and environmental impacts when making such investments. An example of private investment in cardiovascular health is AstraZeneca’s HHA program, launched in Kenya in 2014 (87) with a goal of treating 10 million people with hypertension over 10 years. CVD is the third leading killer in the region and the fastest growing. Working with local partners, HHA provided training and established centers for screening and treating patients. By August 2016, the program had screened 2 million people (88). The program also strengthens supply chains and works at the community level with sustainability at the forefront of their program design. AstraZeneca worked with local partners and the Mission for Essential Drugs to ensure that medicines are always available to the patients of their implementing partners, and enabled a cost reduction of up to 90% (87). AstraZeneca expanded partnerships in 2016 with PEPFAR, jointly investing up to $10 million over 5 years to integrate hypertension services into existing HIV platforms. They will target services for men ages 25 to 50 years, who typically access HIV/AIDS testing less frequently than women (88). Other examples of private sector programs include the Sanofi partnership in the International Telecommunication Union’s “Be Healthy, Be Mobile” program, which uses short message service messaging to provide advice for patients with diabetes to improve communications with their providers across the care continuum (3). Finally, the Novartis initiative Arogya Parivar was launched in 2007 to improve access and affordability of health services to patients in rural India by increasing access to capital for patients. Arogya Parivar now reaches 72 million people, increased health seeking behavior, and has become a profitable endeavor for the company (89).
Public private partnership investment is an important way to expand R&D in LMICs. Countries can find it difficult to trust private corporations to make decisions to improve outcomes for people living in poverty. A notable example of private engagement is the use of public and philanthropic funds to incentivize R&D. A total of 82% of capital that reaches LMICs comes from the private sector, and it is imperative to ensure that it is used effectively. Linking social and business impact pushes companies toward greater innovation and value creation. Once generic alternatives were approved by the FDA in 2006, PEPFAR and WHO began increasing demand for inexpensive antiretroviral drugs, leading to a competitive market for generics (90). Similar approaches can positively affect costs of NCD management.
Front-loading investments and results-based financing (RBF) also bring more value to U.S. global health spending. Front-loading investments allows for more initial resource use, while maintaining investment over time. For example, in an advanced-purchase agreement for vaccines, a front-loaded payment increases the incentive for a manufacturer to bring products to market quickly. RBF transfers money or goods either to patients when they take health-related actions or to providers when they achieve performance targets. RBFs have demonstrable evidence-based transformational effects on maternal and child health, resulting in a decrease in mortality of 74% in Argentina for neonates whose mothers were enrolled in an RBF program (91). NCDs and CVD in particular may benefit from similar approaches.
Maintaining U.S. Global Health Leadership
International architecture for global health governance is complex and often driven by political motives. It includes institutions with an explicit health mandate, such as WHO; organizations that may have direct or indirect effects on health, such as the United Nations; and institutions and mechanisms to contribute to global health, including regional strategies for global health. The WHO has an important role to play to coordinate many new global health players and to set norms and standards in health care, but the 2014 Ebola outbreak exposed major vulnerabilities for WHO, in both emergency response capabilities and leadership structure. These included poor compliance with the International Health Regulations, lack of technical capacity, unstable financing, and lack of accountability (92).
Leadership vulnerabilities have ramifications for management of both ID and NCD global health issues. Reform is needed in WHO’s outbreak response and in global governance. With regard to governance issues, commissions convened after the Ebola outbreak recommended that the WHO lead assessments of countries’ implementation of core capacities outlined in the International Health Regulations, and made other recommendations to strengthen WHO internal structure through better management of human resources, increased transparency, and accountability (92).
The United States also has activities within the GHSA and WHO, the World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations. GHSA has shifted the U.S. government health security approach from a fragmented one to a more cohesive one. Many international agencies, organizations, and partnerships are now critical elements of the global health architecture.
Global health diplomacy
U.S. efforts in global health represent a form of diplomacy that reinforces American values, improves perceptions of the United States through promotion of peace and prosperity, and contributes to U.S. security by building stability abroad. How countries spend money overseas reflects their priorities, and many countries realize this. As examples, China has recently increased its health and development programs around the world (93), and Cuba has sent medical staff and medical diplomats to about 70 countries and provided free medical training in return for benefits, such as oil from Venezuela (94).
The United States has opportunities, as LMICs transition away from foreign aid, to help countries mobilize their own resources and develop health fiscal policies and surveillance systems. Many low-income countries will still be dependent on foreign donors for aid until their economies advance.
The U.S. State Department is the primary agency responsible for foreign affairs, and global health is interwoven into its structure and activities. Almost every U.S. embassy has foreign service officers assigned to work on global health, and some become Environment, Science, Technology, and Health (ESTH) officers. ESTH officers receive inadequate health training (95), and ESTH postings are outside the mainstream foreign service career track, making them unattractive to strong professionals looking to advance their careers. These deficiencies are most apparent during large-scale global health events—for example, during the 2014 Ebola outbreak, the State Department formed an Ebola coordination unit comprised almost entirely of foreign service officers, only 2 of which had a science background (92)—but can affect management of chronic diseases as well.
The DHHS, Center for Disease Control, FDA, and NIH play important roles in health diplomacy, providing health program implementation, technical advisory, and workforce training. DHHS has workers known as health attachés, who provide critical connections between public health and foreign affairs stakeholders, although funding limitations restricts placement of health attachés at U.S. missions and currently there are only 5 placements worldwide. In addition, DHHS uses term-limited appointments for workers abroad, making such positions less attractive to talented candidates. Employees often leave the government at the end of their term, taking valuable knowledge, experience, and skills with them. Establishing a global health career track within DHHS and within the State Department would reduce this problem and provide a greater pool of health expertise to be tapped during an international health emergency. To provide appropriately trained candidates, establishment of such a workforce would require academic institutions to supply interdisciplinary education for such careers (3).
Improved travel, trade, and interdependency among countries call for a common vision of health around the world. All countries are vulnerable to threats from ID and to the chronic negative economic and health effects of NCDs, such as CVD. There are opportunities for shared innovation and universal purpose as countries strive to develop best practices and strong health care systems.
The Committee’s report focuses on where the United States may have the most immediate and substantial effect despite limitations in resources. The Committee has highlighted priority areas that demand continued investment and underscored the imperative to change the way the United States approaches global health, to a more proactive and integrated strategy. One targeted area is CVD, as part of general expansion of the global health vision to encompass chronic NCDs. The outcome of investment in global health, now shifting to include NCDs, will be resilient countries with positive health outcomes, robust trade partners, safer travel destinations, and more active collaborators in preventing and controlling global health problems that affect citizens of every country, at every income level.
The members of the Committee on Global Health and the Future of the United States are: Jendayi Frazer (Co-Chair), Council on Foreign Relations; Valentin Fuster (Co-Chair), Mount Sinai Medical Center, New York; Gisela Abbam, General Electric Healthcare; Amie Batson, PATH; Frederick Burkle, Jr., Harvard University; Lynda Chin, University of Texas System; Lia Haskin Fernald, University of California, Berkeley; Stephanie Ferguson, Lynchburg College and Stanford University; Peter Lamptey, FHI 360; Ramanan Laxminarayan, Centers for Disease Dynamics, Economics, and Policy; Michael Merson, Duke University; Vasant Narasimhan, Novartis; Michael Osterholm, Center for Infectious Disease Research and Policy; and Juan Carlos Puyana, University of Pittsburgh. The authors thank Gail Van Norman, MD, for assistance with editing this manuscript.
Dr. Dzau has vested shares in Medtronic and Alnylam that are managed independently and blindly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Deepak L. Bhatt, MD. MPH, served as Guest Editor for this paper.
- Abbreviations and Acronyms
- Academic Model Providing Access to Healthcare
- cardiovascular disease
- gross domestic product
- infectious disease
- low- and middle-income countries
- noncommunicable disease
- Priority Review Voucher
- research and development
- results-based financing
- Received September 13, 2017.
- Revision received October 31, 2017.
- Accepted November 2, 2017.
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