A Funding Gap

Development agencies do spend on research (for example, the UK, Swedish, Swiss, Canadian, and Australian agencies spend between 2%–3% of their programmatic aid budgets in research and between 10%–40% of this on health research [10]), but their focus is often on operational and field research, not technology innovation or product development.

In 2013, only 11 of the world’s development agencies funded any global health R&D, with eight of these investing less than US$10 million per year. Three agencies—USAID, DFID, and the Directorate-General for International Cooperation (DGIS)—accounted for 86% (US$190 million) of the total (Table 1).

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Table 1. Development agency funding for global health R&D (2013).

https://doi.org/10.1371/journal.pbio.1002363.t001

In reality, the vast bulk of public funding for the new tools needed by public health programmes comes not from the public health field but from domestic science and research agencies (83% of public funding), with aid agencies providing only 10%. The remainder comes from multilaterals and other government funders. In 2013, 48 science and technology agencies provided US$1.7 billion for global health R&D (eight times more than development agencies), with 70% of this coming from the US National Institutes of Health (NIH) and 14 other science agencies providing US$10 million or more to global health research (Table 2) [9].

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Table 2. Top 15 science agencies funding global health R&D (2013).

https://doi.org/10.1371/journal.pbio.1002363.t002

Some might argue that this doesn’t matter—if science agencies provide the R&D funding, then well and good. However, science funding differs from development agency funding in ways that crucially matter for global health. Science funding is shaped by biomedical research paradigms rather than global health paradigms; it has a predominantly domestic rather than an international focus; and it is often investigator driven, rather than being linked to development priorities and strategies—for instance, while new tools for post-partum haemorrhage (PPH) are a development priority, they receive very little science funding (science agencies reported PPH grants of only US$81,476 in 2013) [6]. Science funding is also skewed towards basic research rather than product development. In 2013, aid agencies invested 88% of their funding into product development and less than 1% into basic research; by comparison, science agencies invested 35% into basic research—and close to 40% during the global financial crisis when spending at home was a priority.

A Strategy Gap

The innovation disconnect is not restricted to funding; it also appears at the most fundamental level of global health planning. The SDGs include 17 goals and 169 targets for development in the next 15 years: these include one health goal, which has nine health-related targets. Most of these nine health targets cannot be achieved with today’s tools, including for HIV, TB, and reproductive health as noted above, yet neither the health goal nor any of its nine targets mention R&D. Indeed, health R&D is mentioned only once in the SDG documents, in one of the four “means of implementation” targets appended to the health goal, and then it omits key areas of need (diagnostics, microbicides, reproductive health tools, vector control agents, and platform technologies are all missing) and is conflated with language on access to existing medicines. Global health agencies, including WHO, the United Nations Population Fund (UNFPA), the UN Children's Fund (UNICEF), the UN Office on Drugs and Crime (UNODC), the Joint UN Programme on HIV and AIDS (UNAIDS), UN Women, the UN Environment Programme (UNEP), and others, were asked to recommend health-specific indicators for the SDG process, but R&D was not included (or mentioned) in either their long list of 40 indicators or in their subsequent shortlists [11,12].

In November 2014, 19 global health agencies, led by the director-general of WHO, compiled a Global Reference List of 100 Core Health Indicators “that the global community prioritizes for the purposes of monitoring global progress, maintaining programme support, and advocating for resources and funding” (Fig 1) [13]. R&D was again absent, including from the inputs needed to achieve the desired health impacts; instead, these inputs focused on traditional public health issues such as workforce, infrastructure, health data, and financing for health services.

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Fig 1. Global Reference List of 100 Core Health Indicators (by results chain).

Source: Reprinted from Global Reference List of 100 Core Health Indicators 2015, World Health Organization, 100 Core Health Indicators 2015, p.20, Copyright 2015 [cited 2015 August 13]. Available from http://www.who.int/healthinfo/indicators/2015/en/.

https://doi.org/10.1371/journal.pbio.1002363.g001

Unless there is a dramatic change, and a far greater focus on new tools to manage common causes of mortality such as PPH (27% of maternal deaths) [14] and neonatal infections and asphyxia (59% of neonatal deaths) [15], the SDG maternal and child health goals are even less likely to be met than their MDG counterparts. This is of particular concern given that the maternal health goal (Goal 5) is still the furthest from being reached of any of the MDGs [16].

Innovation Starvation

For many decades, innovation was not a subject for public health. Aid dollars had to stretch across many more countries and to support many more people living on under US$1.25 a day (Fig 2) [17]. The imperative for public health programmes was to “make do with what we have,” deploying available low-cost tools for the greatest good: historically, around 95% of drugs on the WHO’s Essential Medicines List were older off-patent medicines [18]. New, more expensive innovations were seen as something for Western health systems, with long delays in their developing country introduction accepted as the norm. The first Hib vaccine was registered in 1985 but not recommended by WHO for developing country use until 2006, and WHO officials explicitly advocated “restraint in the adaptation of new technologies by nonindustrialised nations” [19].

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Fig 2. Decrease in aid dependency.

Source: Gates, B. Innovation with impact: financing 21st century development. Cannes, France; 2011 [cited 2015 August 13]. Available from http://www.gatesfoundation.org/What-We-Do/Global-Policy/G20-Report.

https://doi.org/10.1371/journal.pbio.1002363.g002

In many cases, there were no new technologies to hanker for: only 16 new chemical entities were marketed for tropical diseases and TB between 1975 and 1999 [20]. Even today, TB relies on first-line drugs developed between 1952 and 1963; and first-stage sleeping sickness is still treated with five weeks of suramin (1920) or daily injections of pentamidine (1940). As a result, the public health community became inured to insufficient resources and old tools, and—beyond the medical research fraternities—often had limited exposure to product innovation and innovators.

A False Dichotomy

These historical factors have sometimes led to an unproductive tension between global health and innovation, with an implicit (and even explicit) view that scarce health funds should be spent on programmes and service delivery, not on developing new tools. In 2014, advocates from the European Union (EU), the US, and Australia identified that domestic global health academics, concerned about competition for funding, were one of the key barriers to securing new resources for product development [21]—arguing, for instance, that the reduction in malaria deaths since 2000 supported the case for investment in programme delivery (rolling out bed nets), not for product development [22]. These statements repeat the WHO argument, from as far back as 1994, that “there is a danger that their (new technologies) introduction would divert attention and money away from the real issues” [23].

This “us or them” dichotomy is unhelpful and also unfounded: a health programme is only as good as the tools it uses, and the tools are only as useful as the programme that delivers them. Innovation doesn’t compete with programme funding; rather, it frees up funding by cutting disease burdens and programmatic costs. Vaccine vial monitoring devices are estimated to have saved immunisation programmes and procurement agencies more than US$140 million in wasted vaccines in the past decade [24]. Health systems have seen huge savings as measles, diphtheria, whooping cough—and more recently polio, Haemophilus flu, and meningitis A—have diminished. These are all now vaccine preventable, while better malaria tools in expanded malaria programmes have averted an estimated 274 million malaria cases between 2001 and 2010. The cost of R&D, which seems so high during the innovation process, becomes vanishingly small over decades of use and millions of patients and even more so when set against the saving of lives and health dollars that is the hallmark of good innovation.

Picking up the Baton

A final issue, and one that extends beyond the global health community to governments as a whole, is that we have entered a new world when it comes to R&D for neglected areas. Traditionally, when new medicines are needed, governments provide science funding for early academic research, and industry then commercialises these leads as new products for patients. However, there is no commercial industry for neglected diseases (hence their title), and there has not been since infections like malaria and TB receded from the West after WWII.

When it comes to the neglected and reproductive health needs of the developing world, governments, including both science and development agencies, must therefore drive the entire R&D process, from basic research through to and including final product development. Science agencies have more than kept up their end of the deal, providing over 80% of public funding for global health R&D and in particular for basic research, as noted earlier, but product development has been badly underfunded, with development agencies in particular failing to pick up the baton. Philanthropy has been generous in making up some of the shortfall, providing over half of all funding to the Product Development Partnerships [5] that have created over 70% of all new drugs and vaccines registered between 2000 and 2011 [25], but philanthropists cannot bear the entire funding burden, nor should their priorities be the dominant force in determining which global health products are developed.

A further area in which governments could make a difference is in improving and aligning regulatory requirements or reviews for new global health products to avoid expending valuable funds (and valuable patient time) on often repetitive, sequential approvals in each country.

In 2012, a WHO official, when asked why malaria R&D was not included in the draft Ministerial Communique of the Asia-Pacific Malaria Summit, responded “because companies look after that” [26]. Unless this belief changes at the most fundamental levels of the global health community, patients may wait even more decades for the better and more effective medicines they deserve.