Overview of NIH Research Portfolio
Identifying Public Health Needs—Epidemiology
The mission of NIH, along with the rest of the Public Health Service (PHS), is to address ongoing and newly emerging public health needs. In-depth understanding and monitoring of public health is therefore a vital function of the PHS. NIH works in concert with other PHS agencies (e.g., Centers for Disease Control and Prevention [CDC] to identify and monitor public health needs through its support of epidemiological studies). Epidemiological studies examine factors that contribute to health and disease in human populations using a broad range of approaches. Persons or groups can be followed over time in longitudinal studies, or a snapshot of information can be collected at a single point in time. Studies can be done retrospectively, examining outcomes that have already occurred and factors that may have contributed to health or disease, or they can be done prospectively, by beginning to monitor a population of interest before a particular disease-related outcome occurs. Many epidemiological studies are observational in nature, collecting information about and comparing groups—called cohorts—made up of individuals who share a characteristic of interest (e.g., tobacco use, age, educational status). Population studies are another type of epidemiological research, aimed at providing a better understanding of populations—how they change in size, composition, and distribution; the complex social, economic, and cultural factors that cause such changes; and the consequences of population change for health and well-being at the individual and societal levels.
Epidemiological research is a critical part of the activities undertaken to fulfill the NIH mission of pursuing fundamental knowledge of living systems and applying that knowledge to extend healthy life and reduce the burdens of illness and disability. Epidemiological research is important for investigating all types of disease, and draws on expertise from a wide range of disciplines; thus, it is not surprising that virtually all NIH ICs are involved with epidemiological research in some capacity. For example, NLM supports research to develop advanced, informatics-based, surveillance systems that monitor population health from a variety of sources ranging from formal clinical data to informal rumor-based surveillance as an innovative means for conducting public health surveillance.
As part of the continuum from basic to applied research, epidemiological studies often test the findings of laboratory or clinical research at the population level. For example, animal studies demonstrating the reproductive and neurological effects of bisphenol A (BPA)—a common component of plastics—have prompted large-scale epidemiological studies to ascertain the exposure and health effects of this chemical in humans. Additionally, observations made through epidemiological studies often result in the formulation of new or modified hypotheses that spur new basic, translational, and clinical studies. For example, epidemiological studies in the 1950s showing that tobacco smoking increases risk of lung cancer led to extensive research to identify the carcinogens and mechanisms involved in tobacco-related carcinogenesis. Thus, epidemiological studies are essential for linking results from the bench to the patient bedside to the general population.
The population-based perspective provided by epidemiological studies often helps to form a foundation for the practical application of scientific knowledge, including changes in clinical practice and the development of public policy. For example, the Framingham Heart Study, which was initiated in 1948, linked risk of cardiovascular disease to factors such as high serum cholesterol levels, hypertension, and cigarette smoking. Based on these results, clinicians were able not only to identify patients at high risk for cardiovascular disease but, even more important, to develop interventions that reduce risk. More recently, a series of NIH studies revealed an increased risk of cancer following exposure to benzene at low levels and documented blood toxicity following exposure levels of under one part per million.1,2 These data were used by the U.S. Environmental Protection Agency (EPA) as it developed a new rule in 2007 limiting the benzene content in gasoline and adopting new standards for passenger vehicles and portable fuel containers to limit emissions of benzene and other hazardous air pollutants.3
1 Hayes RB, et al. J Natl Cancer Inst. 1997;89(14):1065–71. PMID: 9230889.
2 Lan Q, t al. Science. 2004;306(5702):1774-6. PMID: 15576619.
3 U.S. Environmental Protection Agency. Control of hazardous air pollutants from mobile sources: final rule to reduce mobile source air toxics. EP A420-F-07-01. February 2007. Available at https://www.epa.gov/oms/regs/toxics/420f07017.htm#program.
In the area of epidemiological research, NIH often leverages its investment by working with other agencies. For example, numerous NIH Institutes collaborate with CDC to collect population-based information through CDC’s many surveys. For example, NIDCD collaborated with CDC to incorporate several measures into CDC surveys to boost knowledge on the prevalence of hearing, taste, and smell disorders. In the National Health and Nutrition Examination Survey (NHANES), NIDCD supports a hearing component (audiometry testing and related questions on hearing loss and noise exposure in adults ages 20 to 69) and a chemosenses component that consists of household interview questions with taste and smell testing.
A collaboration between the Department of Defense and NIMH, the Army Study to Assess Risk and Resilience in Service Members (Army STARRS) is the largest study of suicide and mental health among military personnel that has ever been undertaken. 4 The goal of the five-year project is to identify, as rapidly as possible, the risk and protective factors that will help the Army develop effective strategies to reduce rising suicide rates and to address associated mental health problems among soldiers. Army STARRS’ five components include historical data collected by the Army as well as current data being collected from soldiers in all phases of Army service. This research will help inform our understanding of suicide in the overall population, leading to more effective prevention and treatment for service members and civilians alike. Related to this research, NIMH and the U.S. Marine Corps signed a memorandum of agreement in August 2011 to begin collaboration with researchers from the Marine Resilience Study.
Another example of an intergovernmental collaboration is the Agricultural Health Study, cosponsored by two NIH Institutes (NCI and NIEHS) and EPA.5 With a cohort of more than 89,000 private and commercial pesticide applicators and their spouses, the study is exploring occupational, lifestyle, and genetic factors that may affect the disease rates in farming populations. Although current research suggests that agricultural workers are healthier overall than the general U.S. population, they may have higher rates of some types of cancer and other conditions including diabetes, asthma, neurologic disease, and reproductive problems. A recent Agricultural Health Study study showed that private and commercial pesticide applicators who used the common agricultural herbicide atrazine were at increased risk of thyroid cancer. 6 Another study evaluated the interaction between gene variants which have been shown in previous studies to increase prostate cancer risk and pesticide use. Interactions with these variants were observed with the organophosphates insecticides fonofos, terbufos, coumaphos, and phorate and the pyrethroid, permethrin.7
Given its stable budget and long existence, NIH has been able to invest in a number of important longitudinal studies. For example, NIA supports a robust portfolio of longitudinal demographic and economic research, including studies to estimate the health and economic consequences of aging. The Health and Retirement Study (HRS) is a premier source of data on the health and socioeconomic circumstances of older Americans, including information about retirement, income, pensions and health.8 It provides uniquely rich, nationally representative longitudinal data for the community of scientific and policy researchers who study the health, economics, demography, sociology, and psychology of aging, creating opportunities for new types of interdisciplinary research. Funds from the American Recovery and Reinvestment Act (ARRA) facilitated expansion of the study, including genotyping DNA samples from participants and doubling the minority sample to facilitate research on vulnerable populations. HRS has also become a model for an international collection of aging studies that support cross-national comparative research.
Cancer is the second most common cause of death in the U.S., exceeded only by heart disease. In the U.S., cancer accounts for nearly 1 of every 4 deaths. Childhood cancers are rare, representing less than 1 percent of all new cancer diagnoses. The Annual Report to the Nation on the Status of Cancer, 9 released by NCI, CDC, American Cancer Society, and the North American Association of Central Cancer Registries in March 2011, and reporting on a data period of 2003–2007, found for the first time that lung cancer death rates decreased in women, more than a decade after rates began dropping in men. The report was informed by the NCI SEER (Surveillance Epidemiology and End Results) Cancer Statistics review. The review was last updated in November 2011 and covers 1975–2008.
NIDDK’s The Environmental Determinants of Diabetes in the Young (TEDDY) study was established to identify potential environmental factors, including the infectious agents, dietary factors, or other environmental conditions that trigger type 1 diabetes in genetically susceptible individuals. The TEDDY study has completed enrollment of over 8,000 high-risk newborns and is collecting biosamples for analysis to identify potential triggers of type 1 diabetes. Children enrolled in the study are developing autoimmunity and type 1 diabetes at predicted rates, indicating that those at risk can be accurately identified, and that the study is on track to make a major contribution. Identification of an infectious agent that triggers autoimmunity could lead to a vaccine to protect against type 1 diabetes. Or, if dietary factors are identified that protect from or contribute to the development of the disease, changes in infant feeding practices could be recommended. NIAID, NICHD, and NIEHS also participate in this study.
The National Children’s Study (NCS) was mandated by Congress in the Children’s Health Act of 2000. Beginning in FY 2001, NICHD, designated as the lead agency, began planning for the study in collaboration with other federal partners. In FY 2007, Congress added new funding for the study through the Office of the Director, NIH, and has appropriated funds every year since then. The NCS is a longitudinal birth cohort observational study 10 with the goal of improving the health and well-being of children and to identify antecedents of healthy adulthood by examining the effects of a broad range of environmental influences and biological factors. The NCS will produce an unprecedented amount of information about children’s health and will provide a foundation for analyzing factors that contribute to growth, development, health, and disease to guide future science and policy.
The NCS Vanguard Study, a pilot study to test design and procedures aspects of the Main study, was launched in January 2009 and has already provided a rich source of data to guide the Main NCS Study. NIH announced funding opportunities in FY 2012 for continuation of the Vanguard Study and will begin recruiting the targeted 100,000 newborns who will be the subjects of the Main Study.
Initiated in 2011, the Population Assessment of Tobacco and Health (PATH) Study is the first large-scale NIH-FDA collaboration on tobacco regulatory research since Congress granted FDA the authority to regulate tobacco products under the Family Smoking Protection and Tobacco Control Act (FSPTCA in 2009). It is a national, longitudinal cohort study that will follow an estimated 59,000 adults and youth (12 to 18 years old) to assess susceptibility to tobacco use, patterns of use, risk perceptions, and resultant health impacts. The sample will include both males and females and persons of diverse racial, ethnic, and cultural backgrounds. Data collection is currently slated to begin in fall 2013, with plans for four or more annual data collection waves. Outcomes will inform current and future regulatory options for the FDA to protect public health, including setting tobacco product standards and communicating the risks of tobacco use to the general public.
Investments in the past continue to pay off. NIH has been investing in epidemiological research for most of its history, and some of this research involves longitudinal studies that have been ongoing for decades. Data collected from these studies continue to advance our understanding of disease and health in new and exciting ways and form the foundation for extraordinary opportunities in biomedical research today.
The Framingham Heart Study provides an example of research that leverages past and current investments in population-based studies to study the basis of disease. The original cohort of Framingham residents was first established in 1948 and has since been complemented by cohorts of their children and grandchildren. The DNA of more than 9,000 Framingham participants from all three generations has been analyzed as part of an initiative called the SNP Health Association Resource (SHARe). The genetic data, along with information about major disease risk factors (e.g., systolic blood pressure, cholesterol levels, cigarette use), have been added to the National Center for Biotechnology Information’s (NCBI) database of Genotypes and Phenotypes (dbGaP) and are available for use by researchers interested in investigating genetic contributors to disease.
NIH-supported studies also have been used to inform the decisions of policymakers and assess the short- and long-term effects of policies on health or health-related behaviors. For example, in 1975, NIDA launched the Monitoring the Future (MTF) project, a study that tracks drug use and related attitudes and behaviors of adolescents and young adults. MTF annually surveys approximately 50,000 students in grades 8, 10, and 12, and follow-up is conducted every two years with a subset of individuals from each graduating class until they reach age 30. MTF data have informed policy discussions on substance abuse and have been used by the White House Office of National Drug Control Policy to monitor progress toward national health goals.11 For example, when MTF began measuring nonmedical use of Vicodin among teens in 2002, it revealed an alarming rate of 1 in 10 high school seniors abusing this prescription pain reliever. This, along with other epidemiological research, has led to several NIDA and federal partner initiatives to address this problem.
A comprehensive understanding of health and disease requires consideration of factors from the molecular to the community level. Conducting studies in diverse contexts helps to elucidate how these contributors converge to influence health and also ensures that insights gained will benefit various populations. NIH supports a number of studies in the U.S. and worldwide aimed at building a comprehensive understanding of health and disease, with the goal of identifying new and more effective approaches for prevention and treatment. Three examples—the Environmental Polymorphism Registry (EPR), the Childhood Autism Risks from Genetics and Environment (CHARGE) study, and the Multi-Ethnic Study of Atherosclerosis (MESA)—illustrate NIH’s pursuit to build a comprehensive understanding of health and disease.
To facilitate research on the interactions of genes and the environment, NIEHS launched EPR, in collaboration with the University of North Carolina General Clinical Research Center, to collect DNA samples from more than 16,000 individuals in the greater Research Triangle Park, North Carolina region through local health care systems, health fairs, study drives, and other means. This region has a diverse population varying in age, ethnicity, economic and educational background, and health status. A unique feature of the EPR is that participants were recruited from two distinct groups—apparently healthy individuals from the general population and patients from area clinics and hospitals. Individuals in the clinic/hospital group had an array of medical conditions, and their inclusion in the EPR increases the likelihood of identifying subjects with both the genetic and clinical characteristics of interest. Unlike anonymous DNA registries, researchers using EPR are able to identify and contact registry participants—with their consent—for further study, if they are found to have potentially significant genetic variants. These aspects of the EPR give scientists the flexibility to design follow-up studies, while reducing biases that can occur in genetic epidemiology studies when subjects are recruited based primarily on their observable clinical or physical traits.
CDC estimates that about 1 in 88 children has been identified with an autism spectrum disorder. 12 CDC’s data indicate that ASD prevalence has increased 78 percent since 2002. Whether the cause is attributable to a change in diagnosis criteria or to genetic or environmental factors is unclear. Multiple factors are likely to be responsible for the increase in prevalence over time. Since 2006, NIEHS has supported the Childhood Autism Risks from Genetics and Environment (CHARGE) study, an epidemiologic investigation of a wide spectrum of chemical and biologic exposures, susceptibility factors, and genetic interactions that may contribute to autism. The study is examining and comparing three populations of children: those with autism, those without autism but with developmental delay or mental retardation, and typically developing children. In one recent study, scientists demonstrated an association between a mother’s living near freeways and major roadways during pregnancy and near time of delivery (a surrogate for air pollution) and the risk of having a child with autism.13
Research has shown that factors such as genetic background, geographic location, socioeconomic status, and cultural traits may contribute to variations in disease risk among different populations. This observation has important implications for biomedical research, as results in one population may not necessarily apply to another. Thus, it is important to include study participants with diverse backgrounds and characteristics to increase the likelihood that insights gained through study findings will benefit all groups of people. In this regard, NIH is supporting the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter epidemiological study of cardiovascular disease in 6,900 men and women from four ethnic groups—white, African American, Hispanic, and Americans of Chinese ancestry. This study, which began in 1999 and is funded through 2015, has measured and compared the value of chest computed tomography (CT), cardiac magnetic resonance imaging, carotid ultrasound, arterial compliance, endothelial function, biochemical markers, and genetic and environmental factors for predicting the development of cardiovascular disease. In one recent finding, researchers used MESA data to confirm that CT measurements of coronary calcium, previously shown to predict coronary heart disease among white populations, are effective predictors in African Americans, Hispanics, and Americans of Chinese ancestry as well. 14
Bridging the gap between research and application requires the contributions of numerous scientists with diverse expertise. Therefore, NIH fosters a culture of collaboration by encouraging researchers to build teams to conduct complex studies and analyses as well as promoting collaborations within NIH and between NIH and other federal agencies.
The Cohort Consortium is an example of an NIH initiative that encourages a team approach to understand the role of gene-gene and gene-environment interactions in the etiology of cancer. The collaboration allows Consortium partners to share data from 43 cohorts composed of more than 4 million people from diverse populations. Each cohort contains extensive information on known or suspected risk factors and biospecimens collected pre- and post-diagnosis. The pre-diagnostic specimens provide a valuable resource for studies of cancer etiology and early detection. Researchers can correlate changes in molecular profiles associated with the onset of different types of disease, thereby providing valuable insights into the actual mechanisms of human carcinogenesis.
The 27 NIH ICs collectively house expertise on a broad spectrum of diseases, populations, and research support methods. Large-scale epidemiological studies provide an ideal opportunity for researchers from the various NIH components to work together on innovative studies that examine diverse factors contributing to public health and disease. For example, the Hispanic Community Health Study, which is sponsored by six NIH Institutes (NHLBI, NIMHD, NIDCD, NIDCR, NINDS, and NIDDK) and the NIH Office of Dietary Supplements, includes 16,000 persons of Hispanic/Latino descent to identify factors that influence a wide variety of diseases and conditions such as heart disease, asthma, sleep disorders, diabetes, hearing loss (including noise-induced hearing loss), tinnitus, and cognitive impairment. 15 It is the largest long-term epidemiological study of health and disease ever conducted in people of Hispanic/Latino heritage living in the U.S. Particular attention will be given to the role of cultural adaptation and disparities in the prevalence and development of disease. The insights gained from this study will be invaluable because the U.S. Hispanic population, already the largest minority population in the country, is expected to triple by 2050.
4 For more information, see http://www.armystarrs.org .
5 For more information, see https://aghealth.nci.nih.gov/.
6Freeman LE, et al. Environ Health Perspect. 2011;119(9):1253–9. PMID: 21622085.
7 Koutros S, et al., Cancer Res. 2010;70(22):9224–33. PMID: 20978189.
8 For more information, see https://hrsonline.isr.umich.edu/ .
9 For more information, see https://www.cancer.gov/newscenter/pressreleases/2011/ReportNation2011Release and http://www.oxfordjournals.org/our_journals/jnci/press_releases/kohlerdjr077.pdf .
10In July 2012, the NCS Proposed Sampling Strategy: Main Study document was released to structure discussions about the future of the NCS’s sampling design for the National Children’s Study Advisory Committee: https://www.nationalchildrensstudy.gov/about/organization/advisorycommittee/Pages/Proposed%20Sampling%20Strategy%20Main%20Study%20%28July%202012%29.pdf. The NCS is proposing a multi-layered cohort approach that involves birth, prenatal, and preconception cohorts.
11 National Institute on Drug Abuse. Monitoring the Future National Results on Adolescent Drug use: Overview of Key Findings 2008. Available at: http://www.monitoringthefuture.org/index.html.
12 Autism and Developmental Disabilities Monitoring Network (CDC). Prevalence of Autism Spectrum Disorders — Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States 2008. MMWR. 2012/61(SS03);1–19. PMID: 22456193.
13 Volk H, et al. Environ Health Perspect. 2011; 119(6):873–877. doi:10.1289/ehp.1002835
14 Detrano R, et al. N Engl J Med. 2008; 358(13):1336–45. PMID: 18367736.
15 For more information, see https://www.cscc.unc.edu/hchs/ .
Epidemiological studies are fundamental to NIH’s mission, in that they play a key role in identifying public health needs, and they are essential to efforts to bridge the results of basic, translational, and clinical studies to practical applications such as clinical practice and public policy. Many NIH epidemiological studies have had substantial influence on public health, with current investments likely to follow suit. This success is due to a number of factors, including investment in long-term studies, pursuit of a comprehensive view of disease, and promotion of a culture of cooperation.