Prevention Research at the National Institutes of Health

The National Institutes of Health (NIH) is the nation’s biomedical research agency, making discoveries that improve health and save lives. Disease prevention has been an important focus of the NIH mission from the beginning. The Marine Hospital Service (MHS) was established in 1798 to screen crew members and passengers arriving in the United States to prevent epidemics of infectious diseases, such as yellow fever and cholera. The Hygienic Laboratory was established as part of the MHS in 1887 to study the etiology of these diseases and to guide prevention and treatment efforts. The MHS became the Public Health Service in 1912 with responsibility for investigating all human diseases and their contributing factors. The National Hygienic Laboratory was renamed the National Institute of Health in 1930 and was charged with ascertaining the cause, prevention, and cure of human diseases. Today, research in health promotion and disease prevention is 1 of 3 key targets in the NIH-Wide Strategic Plan to advance opportunities in biomedical research (the other targets are research in fundamental science and treatments and cures).¹ Agencies from across the US Department of Health and Human Services (HHS), as well as academic and private-sector organizations, draw on the research supported by NIH to fulfill their missions.

Each NIH institute and center defines prevention to reflect its own mission. Even so, a general working definition for prevention research at NIH is this:

Prevention research encompasses both primary and secondary prevention. It includes research designed to promote health; to prevent onset of disease, disorders, conditions, or injuries; and to detect, and prevent the progression of, asymptomatic disease. Prevention research targets biology, individual behavior, factors in the social and physical environments, and health services, and informs and evaluates health-related policies and regulations. Prevention research includes studies for the identification and assessment of risk and protective factors; screening and identification of individuals and groups at risk; development and evaluation of interventions to reduce risk; translation, implementation, and dissemination of effective preventive interventions into practice; and development of methods to support prevention research.²

NIH provides leadership and financial support to prevention research across the United States and throughout the world. The NIH investment in prevention research for fiscal years 2010-2016, as shown in the Research Portfolio Online Reporting Tools,³ suggests an upward trend in the number of prevention awards and a slightly stronger upward trend in the total dollars spent on prevention research. In fiscal year 2016, new awards for prevention research represented 19.9% of all new awards at NIH and 23.7% of all dollars for new awards in the NIH research portfolio (Figure 1).

Figure 1.

Number and total costs of new National Institutes of Health prevention research awards, by fiscal year, 2010-2016. Data source: US Department of Health and Human Services, National Institutes of Health. Research Portfolio Online Reporting Tools (RePORT). https://report.nih.gov.³

The 2 institutes and centers with the largest investments in prevention research in 2016 were the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. The National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute also invested heavily in prevention research in 2016. These 6 institutes and centers are also in the top 10 in 2016 appropriations, so it is not surprising that they invest substantially in prevention research (Figure 2).

Figure 2.

Number of new prevention awards funded in fiscal year 2016 (n = 3512) by National Institutes of Health, by institutes and centers. Data source: US Department of Health and Human Services, National Institutes of Health. Research Portfolio Online Reporting Tools (RePORT). https://report.nih.gov.³ Abbreviations: FIC, Fogarty International Center; NCATS, National Center for Advancing Translational Sciences; NCCIH, National Center for Complementary and Integrative Health (formally NCCAM); NCI, National Cancer Institute; NEI, National Eye Institute; NHGRI, National Human Genome Research Institute; NHLBI, National Heart, Lung, and Blood Institute; NIA, National Institute on Aging; NIAAA, National Institute on Alcohol Abuse and Alcoholism; NIAID, National Institute of Allergy and Infectious Diseases; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; NIBIB, National Institute of Biomedical Imaging and Bioengineering; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIDA, National Institute on Drug Abuse; NIDCD, National Institute on Deafness and Other Communication Disorders; NIDCR, National Institute of Dental and Craniofacial Research; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIEHS, National Institute of Environmental Health Sciences; NIGMS, National Institute of General Medical Sciences; NIMH, National Institute of Mental Health; NIMHD, National Institute on Minority Health and Health Disparities; NINDS, National Institute on Neurological Disorders and Stroke; NINR, National Institute of Nursing Research; NLM, National Library of Medicine; OD, Office of the Director.

More than 90% of fiscal year 2016 prevention research was supported through extramural programs (ie, awards to scientists outside NIH, such as university researchers), with the balance supported through intramural programs (ie, research conducted by NIH staff scientists). Approximately 14% of prevention research was invested in clinical trials. In fiscal year 2016, substantial investment was made in prevention research related to the top 10 actual causes of death. For example, 18.8% of the total investment in prevention research was in diet/nutrition, 10.2% in substance abuse, 6.0% in physical activity, 4.5% in tobacco use, 4.2% in sexual behavior, and 3.5% in alcohol use.³ Funding decisions for prevention research generally reflect the scientific merit of the applications, as well as programmatic priorities of the institutes and centers.

An example of current prevention research is the development of vaccines for new and emerging infectious diseases, such as Ebola and Zika virus, as well as development of a universal influenza vaccine. Such vaccines would be used widely by state and local public health departments, as well as by other agencies, such as the Centers for Disease Control and Prevention and the World Health Organization.

Another example is the All of Us Research Program.⁴ This program to recruit at least 1 million participants and collect biological, self-report, and medical record information will provide a platform from which to launch future prevention studies. It will make it easier to identify potential participants who have the characteristics that make them ideal for recruitment to a particular trial, and it will provide rich data to identify new risk factors and new protective factors for various conditions. In addition, it will recruit participants to reflect the diversity of the US population, consistent with the NIH commitment to pursue research to reduce health disparities.

NIH often collaborates with other federal agencies to advance public health. A recent example was its leadership role in collaboration with 17 federal organizations to develop the National Nutrition Research Roadmap.⁵ The roadmap identifies research areas that could help to reduce nutrition-related diseases in the United States. Another example was NIH’s leadership role in collaboration with 14 federal organizations to conduct the first assessment of US microbiome research.⁶ The microbiome has become increasingly important during the last decade, as research has pointed to its critical role in normal biological activity and the role it could play in the prevention and treatment of disease.

To promote and coordinate prevention research across the agency, NIH established the Office of Disease Prevention (ODP) in 1986. The mission of the ODP is to improve the public health by increasing the scope, quality, dissemination, and impact of prevention research supported by NIH. The ODP works to fulfill this mission by providing leadership for the development, coordination, and implementation of prevention research in collaboration with NIH institutes and centers and other partners. The activities of the ODP are led by 7 teams; 6 are organized around the ODP’s 2014-2018 Strategic Plan⁷ and the seventh is organized around the Tobacco Regulatory Science Program (TRSP), which is located in the ODP.⁸

TRSP illustrates the ODP’s coordination role. It is a joint program between NIH and the US Food and Drug Administration (FDA). The FDA has expertise in tobacco regulatory science and the authority and resources to support research that can be used to inform its regulatory decisions. NIH has expertise in tobacco research and the infrastructure for receipt, review, and administration of research projects. Through TRSP, NIH supports the FDA’s mandate for research in regulatory science, and the FDA provides funding that complements existing NIH tobacco research. The FDA provided more than $100 million in support each year during fiscal years 2013-2016 through grants and cooperative agreements awarded by NIH.

Another example of the ODP’s coordination role is its work with the Agency for Healthcare Research and Quality (AHRQ) in support of the US Preventive Services Task Force (USPSTF). The USPSTF issues recommendations for primary care physicians on preventive practices for adults and children in the areas of screening, medication, and behavioral counseling, based on a review of the scientific evidence. Where the evidence is clear, the USPSTF can recommend for or against a practice; where the evidence is unclear, the USPSTF can ask for additional research. NIH is the source for much of the evidence that the USPSTF uses to develop its recommendations, and the USPSTF’s “insufficient evidence” statements are an important stimulus for new research at NIH.⁹ The ODP is the NIH liaison office for the USPSTF and coordinates communications related to the USPSTF between NIH and AHRQ.

The ODP is also developing better methods for analyzing NIH’s portfolio of prevention research studies. Existing methods do not provide sufficient information on the studies’ rationale, exposures, outcomes, settings, population(s) studied, study design, or type of prevention research. The ODP determined that a more detailed characterization of the NIH prevention research portfolio would enable better identification of levels and trends in funding in prevention research over time and facilitate the identification of research areas that might benefit from targeted efforts by NIH.

Pursuit of a robust prevention agenda at NIH faces numerous challenges. The first challenge is limited resources. Beginning in 2003, when NIH funded 1 in 3 applications, NIH purchasing power declined by almost 25% through 2015, so that fewer than 1 in 6 applications were funded.¹⁰ Although the situation improved in 2016, with the success rate approaching 1 in 5 applications, and should improve again in 2017, it remains below historic levels. One approach that could help address this challenge would be for the ODP to bring institutes and centers together to jointly fund projects that address common risk factors, use common intervention methods, and examine a common set of outcomes.

A second challenge for prevention research is documenting the long-term benefits of preventive interventions relative to their harms. The benefits of prevention programs, such as reduced morbidity and mortality, may not be realized for many years, but NIH typically funds projects for no more than 5 years, and it is difficult to obtain support for long-term follow-up for intervention studies.

A third challenge is the limited number of intervention studies. Because we already know a great deal about the risk factors and protective factors for the leading causes of death (ie, health conditions such as heart disease, cancer, and infectious disease) and actual causes of death (ie, health behaviors such as tobacco use, diet, physical activity, alcohol use, and drug use),¹¹ the country would be well served by applying that knowledge to the development and testing of more preventive interventions, with attention paid to their differential effects and the factors that predict those differential effects. It would also be helpful to focus the continuing etiologic research on identifying the interactions among genetic, environmental, lifestyle, and other factors that predict individual differences in risk for disease, so that the results could be used to guide the development of future interventions.

Even with these challenges, prevention research continues to make progress at NIH. A recent example is the treatment-as-prevention approach to human immunodeficiency virus (HIV)/AIDS, recognized as the 2011 breakthrough of the year by the journal Science.¹² That study, by Cohen et al,¹³ showed that transmission of HIV from an infected person to an uninfected partner was reduced by 96% by early administration of antiretroviral treatment to the infected partner. Greater focus on such intervention studies as those of Cohen et al, greater openness by the NIH to long-term follow-up of intervention studies, and cooperative funding of intervention studies when they share the same methods and study the same underlying risk factors will further improve the results from the investments that NIH makes in prevention research.