Priority Setting
Setting priorities for R&D of interventions is both complex and critical in the context of severely constrained resources. A systematic approach that takes into account the disease burden as well as scientific opportunities has been proposed to guide decisions.
Approaches
The challenge is to ensure that available resources are targeted at major health problems.
Inherent Difficulties in Setting Priorities
The first part of this chapter underscored the immense scope of health problems and the potential of global health research to make a difference. Given the complexity of the task and the multiple participants involved in the process, defining priorities for the global health research agenda is daunting.
Scientists tend to argue that more research is urgently needed on the diseases they are studying. Their research may certainly include worthwhile issues, but they may not be priorities in the wider context of global health R&D.
Some hold the view that the choice of priorities should begin with a statement defining topics that should not be priorities—for example, the development of vaccines (such as a leprosy or hookworm vaccine) when cost-effective treatments are available. Others strongly disagree, given the interconnect-edness and unpredictability of science.
The failure of the U.S. "war on cancer" offers a useful caution on the limitations of rational planning of science. In the 1960s, a group of distinguished scientists developed a set of future research priorities for the National Cancer Program. Despite the importance of the problem, the requisite scientific knowledge was not then available to develop the modern tools that have recently been successful in treating and preventing cancer. Planning for where the new innovations and discoveries will come from is hard, and planners have to be open to changing their priorities and incorporating new approaches.
A key challenge is the problematic nature of anticipating scientific connections in advance. For example, the sequencing of a mouse leukemia virus genome as part of the National Cancer Program is what enabled scientists years later to classify HIV as a related member of the retrovirus family. Indeed, who would have predicted that research on the once arcane coronavirus would become essential to control the spread of SARS? Or that the esoteric question of whether tumor cells extinguished differentiated functions of normal body cells would lead to the discovery of monoclonal antibodies? Or that the study of sex in bacteria would give rise to the entire genetic revolution of the past half century? The need to recognize the unpredictability of science and the limitations of scientists at any time is best illustrated by Oppenheimer's statement at the beginning of this chapter.
Systematic and Evidence-based Approach to Priority Setting
The process of setting priorities for the global health research agenda is complex and includes accurate or perceived assessments of the burden of disease; developed countries' threat assessments, for example, in relation to bioterrorism and epidemic potential; scientific or technical opportunities; advocacy; political commitment; ethical considerations; and funding availability.
Using a systematic and evidence-based approach to priority setting, the WHO Ad Hoc Committee for Health Research Relating to Future Intervention Options (1996) undertook the first broadly based, systematic effort to formulate "best buys" for health R&D (table 4.3). The steps included assessments of the following:
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size of the disease burden
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reasons the disease burden persisted
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adequacy of the current scientific knowledge base
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cost-effectiveness of potential interventions and the probability of successful development of new tools
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adequacy of the current level of ongoing research and funding.
[Table .]
This five-step approach has been influential. The Global Forum for Health Research and the Special Programme for Research and Training in Tropical Diseases have endorsed it and further developed it. The Global Forum's combined approach matrix links the five steps with four actors or factors determining the health status (Global Forum for Health Research 2002):
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individual, family, and community
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health ministry, health research institutions, and health systems and services
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sectors other than health
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central government macroeconomic policies.
The five steps also provide the basis for the strategic emphases matrix for tropical diseases research (Remme and others 2002).
The individual disease chapters in this volume used a slightly modified version of the framework developed by the WHO Ad Hoc Committee to identify gaps and guide the formulation of research priorities on the basis of the following premise: even though the current mix of available cost-effective interventions averts a proportion of the burden of any particular disease and the remaining burden could be further reduced with improved application of existing technologies to affected populations, a fraction of disease remains that cannot be averted. Two reasons account for this fact. First, the cost for extending the existing technology to the remainder of the population would be prohibitive. Second, the existing interventions may simply not be sufficiently effective. These two categories define the magnitude of the need for new or better tools and, in essence, serve as a rationale and indicate priorities for research.
A clear example is the case of HIV/AIDS. Neither behavioral interventions, such as exhortations for abstinence and fidelity and the provision of condoms, nor antiretroviral therapy has stopped the global spread of HIV, which challenges the scientific community to undertake more research on preventive vaccines. The availability of highly active antiretroviral therapy challenges the research community to find ways of providing effective and life-saving treatment for HIV/AIDS patients in a manner that ensures proper use and compliance, averts the development of drug resistance, and thereby becomes a financially sustainable policy.
Participants and Decision Makers
Two main concerns lie at the core of most discussions of the priority-setting processes: the predominance of the industrial countries and the predominance of the scientific community in formulating research agendas. Two-thirds of respondents in a survey of researchers that was funded by the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health and was conducted in May 2004 were leading scientists from low-and middle-income developing countries and worked in the same region in which they held their citizenship. The survey highlighted their views about key factors influencing research priority setting as well as major barriers that hampered stronger participation by scientists from developing countries in global health research. According to the survey, the most important factors determining research priorities were the magnitude of disease burdens and the needs of the industrial countries. Major barriers to the success of research collaboration in global health were the lack of sustained funding; the difficulty of linking research, programs, and policy; the weak research leadership; and the absence of a science culture (Harley, Simonsen, and Breman 2004).
A more balanced participation of scientists from industrial and developing countries, a better gender mix, and the inclusion of major stakeholders are essential to the successful development of a truly global health research agenda. The challenge is to develop creative mechanisms for addressing current shortcomings.
The process for selecting the best research projects and programs within each priority area is well established and is grounded in scientific merit, based primarily on trust in peer review and expert judgment. Keeping this process independent from political pressures is extremely important. However, the peer review process has limitations, including a natural conservatism and risk aversion by scientists, given the responsibility for the allocation of public funding, their often narrow base of expertise in one discipline, and their specific cultural perspective. Alternative models of project selection from industry and other scientific, mission-oriented entities might offer interesting alternatives—for example, managerial systems or strategic planning processes, particularly for translating knowledge into successful interventions, an area that research is currently emphasizing.
Ethical considerations and pressures exerted by advocacy groups—such as public-private partnerships for targeted drug or vaccine development, fresh looks at "orphan drug" legislation, patent rules ensuring financial returns to industry as well as the affordability of new products in developing countries, and commitment before their development by the public and private sectors to subsidize their development or ensure markets for the products—are likely to counterbalance to some extent the lack of incentives for the pharmaceutical industry to develop drugs, diagnostics, and vaccines for which markets do not exist or are not profitable. In addition, one might hope that the growing pharmaceutical and vaccine industry in developing countries might place a higher priority on addressing nationally and regionally important health problems than do multinational companies.
The share of total R&D funds allocated to major causes of the disease burden in developing countries remains insufficient. As a result, the availability of funding to support global health R&D is ultimately the defining factor regarding the implementation of selected R&D priorities. Thus, the Bill & Melinda Gates Foundation has become a major driving force in defining priorities for global health R&D through its support of promising public-private partnerships. The new US$200 million it provided to finance the Grand Challenges in Global Health represents the newest large influx of funds in support of global health research (see Foundation of National Institutes of Health at http://www.grandchallengesgh.org).
Findings
Research agendas proposed in the various chapters fall into three broad categories:
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priorities that are already on the global health agenda
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important topics that are not yet on the global agenda, but should be pursued
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promising research topics that are not yet priorities, but should be pursued.
Michaud and others (2005) provide a more exhaustive account of the research priorities summarized here and recommended in the volume.
Priorities Already Part of the Global Health Agenda
Priorities that are already the most prominent part of the global health agenda relate almost exclusively to the unfinished agenda of infectious diseases and to the continuous threats of emerging infectious diseases, including bioterrorism. The largest investments pertain to the development of new drugs and vaccines that are needed to reduce the burden of HIV/AIDS, malaria, and TB; to the early detection and control of new highly pathogenic viral agents (for example, SARS); and to the prevention and treatment of infectious diseases resulting from microbial terrorism (for instance, anthrax and smallpox).
In 2001, the National Institute of Allergy and Infectious Diseases developed a global research plan for HIV/AIDS, malaria, and TB. The plan outlines a comprehensive approach for fighting infectious diseases that involves building a sustainable research capability domestically and internationally and enhancing global partnerships. It comprises short-, medium-, and long-term goals for research that "will lead to prevention and treatment strategies that are effective, feasible, and realistic for individual countries struggling with the burden of numerous infectious diseases" (National Institute of Allergy and Infectious Diseases 2001).
Since the mid 1970s, the WHO Special Programme for Research and Training in Tropical Diseases and a few other institutions have been key players in strengthening research and research capacity for tropical diseases that are endemic in specific developing regions—African trypanosomiasis, Chagas disease, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, onchocerciasis, and schistosomiasis. As a result, effective control measures are now available for Chagas disease, leprosy, lymphatic filariasis, and onchocerciasis—but questions remain regarding effective implementation strategies. The other diseases still lack effective control measures and, thus, require further research to develop better tools and effective control strategies (http://www.who.int/tdr/grants/strategic-emphases/default.htm).
The process that led to the formulation of the Grand Challenges in Global Health represents two important departures from earlier approaches to priority setting. First, the announcement of the call for ideas in May 2003 had an unprecedented dissemination worldwide and resulted in over 1,000 submissions from scientists and institutions in 75 countries. Second, the formulation of a grand challenge, described as "a call for specific scientific or technological innovation that would remove a critical barrier to solving an important health problem in the developing world with a high likelihood of global impact and feasibility" (Varmus and others 2003) was broad and had a clear goal.
The research agendas proposed in chapters 16, 18, and 21 are extensive and encompass research on basic epidemiology and risk factors and the development of new or better drugs, vaccines, diagnostics, and intervention methods. The fact that these priorities do not represent a marked departure from previous research priorities for these conditions attests to the complexity of these diseases and their importance in the poorest countries. They will require a broadly based and sustained global research effort to overcome the rapid spread of antibiotic and insecticide resistance, limited human resources, and poorly developed health systems that severely constrain the health community's ability to reduce the burden of disease.
Important Topics That Are Not Yet on the Global Research Agenda but Should Be Pursued
Cardiovascular diseases, neuropsychiatric disorders, obesity, diabetes, and cancers are causing a rapidly increasing share of the disease burden in all developing regions, with the exception of Sub-Saharan Africa; however, they do not yet figure prominently on the global health research agenda. The research priorities recommended independently by the authors of various chapters pertaining to major causes of noncommunicable diseases converge. Indeed, diet, lifestyle, obesity, tobacco, and alcohol are common risk factors for cardiovascular diseases, certain cancers, and diabetes. These diseases and risk factors represent a cluster of conditions that pose similar research challenges.
The first important cross-cutting theme emerging from this cluster of chapters is the issue of portability, or how to bring knowledge and programs from one location and define how they can become best practices elsewhere. Cost-effective preventive strategies and therapeutic approaches to reduce the burden of cardiovascular diseases, cancer, diabetes, and mental disorders have been developed and tested in industrial countries. Much of the extensive knowledge base accumulated in industrial countries to prevent the development of cardiovascular diseases, diabetes, and cancers is likely to be relevant to developing countries, yet few epidemiological studies have quantified the impact of major risk factors for chronic diseases in developing regions, and few trials have been conducted to assess the effectiveness of different intervention strategies. Research to explore the transferability of cost-effective interventions from industrial to developing countries therefore figures prominently in several chapters.
The primary prevention for noncommunicable diseases in industrial countries rests on the reduction of major risk factors—namely, diet, lifestyles, and tobacco and alcohol consumption. Research priorities include the development of epidemiological databases and of intervention studies to identify cost-effective strategies to reduce the prevalence of major risk factors in different contexts in developing countries. The transfer of personal and population-based interventions to reduce the risk of cardiovascular disease, which are based on decades of research in the industrial countries, is particularly promising. Research priorities include evaluating a range of intervention strategies, from simple dietary interventions to reduce the risk of cardiovascular disease (for example, food supplementation with folic acid and linolenic acid and reduction in the salt, saturated fat, and trans fat content of processed foods), to the hypothetical "polypill," which would combine drugs to lower cholesterol, clotting, and blood pressure. Reducing the risk of cardiovascular disease is particularly important for diabetes, which is itself an important risk factor for cardiovascular disease.
The second theme pertains to lifelong medical management of chronic conditions that cannot be cured but could be improved through the development and testing of public health prevention and treatment algorithms. This issue has been little considered in past discussions of priorities for global health research but now appears to be reasonably cost-effective. Examples include unipolar depression, bipolar disorders, schizophrenia, epilepsy, diabetes, and secondary prevention of ischemic heart disease and stroke.
The third theme pertains to crucial implementation research that combines operations research and health services and systems research. Such research is becoming central to ensuring the success of the rapid scaling-up of cost-effective interventions that is required to meet the health targets of the Millennium Development Goals, particularly in resource-poor countries with weak health systems. In this context, further research is critical to elucidate neglected areas of health system reforms, including the following (Mills 2004):
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improving public service provision
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enhancing human resources
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ensuring accountability for health outcomes, funds, and medicines
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ensuring a functioning central government
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providing evidence for policy.
Promising Research Topics Not Yet Global Priorities
Other important research topics emerge from the various chapters that are not yet global priorities but that are nevertheless worthwhile pursuing. Major themes pertain to the following:
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epidemiology of injuries and cost-effective interventions to reduce the burden resulting from both intentional and unintentional injuries, particularly motor vehicle crashes and road and vehicle safety
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major risk factors for disease in different contexts (for example, tobacco, obesity, physical activity)
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medical and surgical errors
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occupational and environmental health
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risk analysis and risk communication
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delivery of care at different levels of the health system
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performance of health systems
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management of health research
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reproductive and sexual health
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health effects of global warming.
The importance of strengthening the research agenda in those and other areas and the resultant opportunities to make a real difference have not been sufficiently recognized in the past.
