Two-year-old Hannah's56 great-grandmother, who was born in 1900,
died of tuberculosis in her thirties. Polio crippled her grandfather, and other
family members died at young ages of influenza and typhoid fever. Dramatic
improvements in public health and medical practice have made it considerably less
likely that these and many other infectious diseases will pose the same threat to
Hannah that they did to her ancestors. However, she and her family will almost
certainly be affected by one or more chronic diseases and conditions—for example,
type 2 diabetes, and obesity—whose incidence has risen dramatically in the United
States as the burden of infectious disease has diminished. Even more worrisome is
that although we think of many chronic diseases as more often affecting adults,
such conditions are increasingly appearing in the young. For example, some 16
percent of American children between the ages of six and 19 are overweight 57—a
number unprecedented in history—placing them at greatly increased risk of type
2 diabetes, depression, and, as they grow to adulthood, heart disease and a host
of other life-threatening conditions. In fact, former Surgeon General Richard
Carmona has said that today's obese children could be the first generation of
Americans with a life expectancy less than that of their parents, to say nothing
of the effects of obesity-related conditions on their quality of life. As the
burden of chronic disease in children and adults continues to grow in the United States
and around the world, biomedical research to understand, predict, prevent, and treat
chronic disease is critical.
Introduction
A chronic disease is one that lasts 3 months or longer. In general, chronic diseases
cannot currently be prevented by vaccine or cured by medication, nor do they resolve
on their own. Not all chronic diseases are fatal, and not all fatal conditions are
chronic. Nonetheless, 7 of every 10 Americans who die each year—more than 1.7 million
people—succumb to a chronic disease. Health-damaging behaviors, such as tobacco use,
lack of physical activity, poor eating habits, and excessive alcohol use contribute
to many chronic diseases, whereas others may represent the long-term effect of early
exposure to toxins and/or other environmental factors, especially in individuals with
a higher genetic risk of disease. A shared aspect of many chronic diseases is chronic
pain and other disease-associated disability that interferes with quality of life.
Many of the most burdensome chronic diseases develop over time and become more prevalent
with age; less commonly, chronic disease may manifest from birth as a result of one or
more faulty genes. Chronic diseases can be common in the U.S. population (e.g., heart
disease, the leading cause of death), relatively rare (e.g., cystic fibrosis, which
affects approximately 30,000 Americans), or represent a growing medical problem
(e.g., type 2 diabetes and obesity).
Most chronic diseases and conditions affect one or more organs. Thus, research to combat
chronic illness involves significant trans-NIH collaboration in addition to the
mission-specific work of each IC. NIH supports basic research on both normal and disease
states of organ systems to understand the initiation and progression of chronic diseases,
as well as translational and clinical research on new biomedical and behavioral strategies
to prevent, preempt, diagnose, treat, and cure these diseases. The ultimate goal is to reduce
or eliminate morbidity and mortality while improving the quality of life for those living with
these often debilitating conditions.
This section focuses primarily on a number of major chronic diseases within NIH's purview.
Additional major chronic diseases are discussed in this chapter in the sections Cancer
(cancers of all organs and tissues, including blood), Neuroscience and Disorders of the
Nervous System (e.g., Parkinson's disease, Alzheimer's disease), Autoimmune Diseases
(e.g., lupus, multiple sclerosis), and Infectious Diseases and Biodefense (e.g., HIV/AIDS).
Because some people with certain chronic diseases require transplantation to replace a diseased
organ or tissue, organ transplantation research is highlighted in this section. Research on
complementary and alternative medicine (CAM) approaches to combating chronic disease also is
discussed. Finally, NIH supports research to reduce the pain associated with long-term diseases
and to find innovative and effective forms of palliative care to relieve disease symptoms. Some
of these efforts are highlighted in this section; more information on NIH pain research can also
be found at the
NIH Pain Consortium
Web site.
Burden of Illness and Related Health Statistics
The prevalence and burden of chronic diseases are substantial. In fact, the burden of
chronic diseases is rapidly increasing worldwide. In 2005, chronic diseases contributed
approximately 60 percent of the 58 million total reported deaths in the world and almost
three-quarters of the burden of disease (measured in disability-adjusted life-years)
in those age 30 or older. By 2015, deaths from chronic disease will be the most common
cause of death even in the poorest countries.58 Considering the totality of chronic
diseases in the United States, more than 7 percent of adults age 45 to 54 have three
or more chronic conditions and 36 percent of adults age 75 and older have three or
more chronic conditions. Chronic disease disables or limits activity for almost 12
percent of all adults and more than 34 percent of adults age 65 and older. Moreover,
annual mortality from chronic diseases in the United States is more than 1.7 million.
For details on the depth and breadth of this burden, see the table of data, presented
by disease and condition, at the end of this section.
ABOUT VARIOUS CHRONIC DISEASES AND CONDITIONS
Links to detailed information on many specific chronic health conditions
can be found at
http://health.nih.gov. Following are examples of chronic
diseases and conditions addressed by NIH-funded research, with links to
major associated research programs and NIH research fact sheets.
Cardiovascular Diseases: Heart disease is the leading cause of death in the United States.59
Coronary heart disease, the most common type of heart disease, occurs when the arteries that supply
blood to the heart muscle become hardened and narrow. Coronary heart disease can cause angina (chest pain)
or a heart attack and, over time, contribute to serious disability or death. Other chronic, serious
cardiovascular conditions include hypertension, heart failure, atrial fibrillation, and peripheral
arterial disease. Rare cardiovascular disorders include Marfan syndrome, a connective tissue disorder
that affects growth and development, including the heart and blood vessels; long QT syndrome, a
disorder of the heart's electrical activity that may cause a sudden, uncontrollable, and dangerous
heart rhythm; and congenital heart defects.
Lung Diseases:
Chronic obstructive pulmonary disease, the fourth leading cause of death in the United
States,60 causes airflow obstruction in the lungs that makes breathing difficult.Asthma,
the most common chronic disease of childhood, is characterized by inflamed or swollen
airways. Asthma can be controlled so that individuals have fewer and less frequent
symptoms or can be more active. Rare lung diseases include cystic fibrosis, an inherited
disease that affects multiple organs, and idiopathic pulmonary fibrosis, in which lung
tissue becomes thick and stiff, resulting in loss of function.61
Diabetes Mellitus: Diabetes is characterized by abnormally high levels of
glucose (sugar) in the blood. It can be caused by either autoimmune destruction of
cells in the pancreas (type 1)
or the inability of tissues such as the muscles and
liver to properly use insulin (type 2).
Diabetes can result in complications such
as heart disease, stroke, hypertension, and nerve damage. It is also the leading
cause of kidney failure and nontraumatic lower limb amputation in the United States
and of new cases of blindness among working-age Americans.
Obesity: Obesity, which has risen to epidemic levels in the United States,
is a chronic, relapsing health problem caused by an interaction of genes, environment,
and behavior. A common measure of overweight and obesity in adults is body mass index
(BMI) a calculation based on height and weight. For most people, BMI correlates with
their amount of body fat, and it is used as an indicator of weight-related health risks.
An adult with a BMI between 25 and 29.9 is considered overweight, whereas an adult with
a BMI of 30 or higher is considered obese. BMI numbers are interpreted differently for
children; however, as with adults, rates of overweight and obesity have risen
dramatically for children in recent years. Obesity increases the risk of other
chronic conditions, including type 2 diabetes, heart disease, certain cancers,
osteoarthritis, liver and gallbladder disease, urinary incontinence, sleep apnea,
and depression.
Kidney Diseases:
Chronic kidney disease is the progressive, permanent loss of kidney function that
can result from physical injury or from a disease that damages the kidney, such as
diabetes, high blood pressure, or polycystic kidney disease. Patients with advanced
chronic kidney disease may progress to irreversible kidney failure and require
immediate, life-saving dialysis or a kidney transplant. Chronic kidney disease
is a growing problem in the United States; between 1990 and 2000, the number of
people with kidney failure requiring dialysis or transplantation doubled.
Digestive and Urologic Diseases:
Diseases of the digestive system involve many organs (e.g., intestine, stomach, liver,
gallbladder, and pancreas) and include disorders such as irritable bowel syndrome,
ulcerative colitis, Crohn's disease, celiac disease, peptic ulcer disease, gallstones,
gastroesophageal reflux disease, and chronic pancreatitis.
Illnesses of the genitourinary tract are similarly diverse and include chronic
prostatitis, benign prostatic hyperplasia, interstitial cystitis and painful bladder
syndrome, urinary incontinence, and urinary tract infections.
Liver Diseases: Chronic forms of liver disease include chronic viral
hepatitis (B and C), alcoholic and nonalcoholic fatty liver disease, genetic
diseases such as hemochromatosis, and autoimmune diseases such as primary
sclerosing cholangitis. Significant liver injury can sometimes result from
adverse reactions to medical drugs and other compounds. Although many organ
systems may be damaged by chronic alcohol use, alcoholic liver disease is the
leading cause of death from excessive and long-term alcohol consumption.
Blood Diseases: Chronic anemias result from a deficiency of red blood cells
or an abnormality in hemoglobin production, as is the case with
sickle cell disease and Cooley's anemia. Patients can experience pain, fatigue, and other,
serious health problems. Chronic inherited bleeding disorders such as hemophilia and von
Willebrand disease leave patients at risk for uncontrollable bleeding. Conversely, clotting
disorders such as deep vein thrombosis can lead to the formation of life-threatening blood clots.
Musculoskeletal Disease:
Osteoarthritis,
the most common form of arthritis, is a degenerative disease caused by the breakdown of
cartilage, leading to pain, swelling, and stiffness in joints.
Osteoporosis, another
musculoskeletal disease that causes significant disability, occurs when bones become
thin, weak, and fragile. Other chronic bone diseases include osteogenesis imperfecta,
a genetic disease that causes bones to become brittle and break for no known reason,
and Paget's disease of bone, in which bones grow larger and weaker than normal.
Skin Disorders: Skin, the largest organ of the body, separates the internal
organs from the outside environment, protects against bacteria and viruses, regulates
body temperature, and provides sensory information about surroundings. The most common
type of eczema—inflammation of the skin—is atopic dermatitis, which is characterized
by dry, itchy skin. Chronic wounds on the skin or impaired
wound healing
are common in elderly, bed-ridden, and diabetic populations.
Eye Diseases and
Deafness: Diseases of the eyes and ears can lead to chronic impairment or
loss of vision and hearing. Middle ear infections (otitis media) can cause temporary
hearing loss in children that can become permanent.
Age-related macular degeneration (loss of cells in the retina)
or hearing loss can reduce independence and quality of life in the
elderly. Uveitis (inflammation of the eye) and glaucoma (damage to the optic nerve)
are significant causes of new blindness in adults.
Dental and Craniofacial Disorders:
Periodontal disease is a disorder of the gingiva and tissues around the teeth.
It varies in severity but can lead to bleeding, pain, infection, tooth mobility, and
tooth loss. Periodontal disease can affect other organs and has been linked to
cardiovascular disease, diabetes, and pulmonary disease. Temporomandibular joint
and muscle disorders, commonly called TMJD, are a group of conditions that cause
pain and dysfunction in the jaw joint and the muscles that control jaw movement.
The primary symptom of these disorders is pain, which can become permanent and
debilitating.
Mental Illness and Addiction:
Mental disorders are the leading cause of disability in the United States and
Canada. Mental illness can also coexist with a number of other chronic diseases.
For example, unipolar depressive disorder, a major contributor to disability
worldwide, can be triggered by chronic diseases such as cancer or stroke in
those who are prone to the disorder. Conversely, depression is associated
with an increased risk for other diseases, such as coronary heart disease.
Mental disorders often co-occur with alcohol dependence and other substance
abuse, making treatment of either disorder more difficult.
Addictions to alcohol and other drugs of abuse also are chronic
diseases that have both physiological and behavioral components.62
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NIH Funding for Chronic Diseases and Organ Systems Research
Currently, NIH does not collect the data necessary to provide an aggregate
figure for expenditures on chronic diseases and organ systems research.
The table at the end of this chapter provides funding estimates for many
of the areas of research associated with chronic diseases and organ
systems (see Estimates of Funding for Various Diseases, Conditions,
and Research Areas). Because of overlap among the areas of research
listed in the table, and because research on chronic disease and organ
systems may account for only a portion of the funding for a given area,
the figures in that table cannot be used to provide an aggregate number.
Summary of NIH Activities
To alleviate the public health burden of chronic diseases,
NIH supports research on the development and progression, detection
and diagnosis, prevention, and treatment and management of these
diseases. Because of the impact such diseases have on public health
and the national economy, NIH directs significant resources toward
the study of common chronic diseases, such as asthma, heart disease,
diabetes, and many others. However, NIH also support research on many
less common chronic conditions. This research has the potential to
improve the health and quality of life of thousands of Americans who
suffer with these rare diseases but also can yield fundamental
information on normal physiology as well as the pathophysiology of
other, more common diseases. For example, long QT syndrome, which
results from genetic mutations that lead to disruption of the normal
electrical rhythms of the heart, affects an estimated 1 in 5,000
individuals and results in 3,000 deaths per year in the United States.
However, studies of long QT syndrome also have shed light on the causes
and treatments of more common, nongenetic cardiac arrhythmias that
contribute to 300,000 sudden deaths each year.
This section highlights some key examples of challenges, progress,
and emerging opportunities in NIH-supported research on chronic
diseases and organ systems. Through its multifaceted research
efforts, NIH is providing a solid foundation for improved
patient health and well-being.
Understanding Fundamental Mechanisms of Organ Health and Disease
Basic research supported by NIH provides the foundation for understanding and
addressing chronic diseases. Understanding fundamental biological mechanisms
at the molecular, cellular, tissue, and organ levels provides the basis for
formulating new theories of disease causation, identification of novel treatment
targets, and development of innovative strategies for disease prevention,
diagnosis, or treatment. For example, NIH has made advances in understanding
the mechanisms of chronic periodontitis, a disease that leads to tooth loss
and affects 80 percent of the U.S. adult population. NIH-supported scientists
have discovered that patients with chronic periodontitis have elevated levels
of SHIP, a protein that impairs their ability to mount a robust immune attack
on bacteria associated with the disease. In another study, NIH-supported scientists
identified two pathways associated with chronic periodontitis in diabetic patients
who experience increased incidence and severity of this disease. Although studied
in different contexts, each of these advances paves the way for potential new
targets for preventing or treating this highly prevalent disease. In another
effort to increase understanding of the mechanisms of a chronic disease, NIH
has initiated a Specialized Center of Clinical Research focused on understanding
the key structural and regulatory processes mediating mucus clearance and their
dysfunction in cystic fibrosis and COPD. The concepts emerging from the center
are expected to stimulate development of new therapies to enable treatment early
in the course of disease.
Some diseases, such as drug and alcohol addiction, affect nearly every organ system.
NIH supports research to uncover fundamental mechanisms of alcohol-induced tissue
injury that are common to many organs and tissues throughout the body, including
the brain and liver. Program initiatives to elucidate the underlying mechanisms
of alcohol-induced tissue injury will lead to the identification of biomarkers
for early detection of disease and new strategies for treatment. Other diseases,
such as osteoporosis, have a more limited but still significant impact on the
body by affecting key tissues or organs. Because bone loss occurs without symptoms,
people may not know that they have osteoporosis until a sudden strain, bump, or fall
causes a disabling fracture. NIH supports a number of research projects aimed at
elucidating the underlying mechanisms of osteoporosis and other bone diseases.
Still other chronic diseases, such as diabetes, affect multiple organs and body
systems but might be effectively treated or even cured by replacing a single
type of tissue. For example, death of the insulin-producing beta cells of the
pancreas results in type 1 diabetes, whereas type 2 diabetes arises when beta
cells are present but not working properly. The NIH-supported
Beta Cell Biology Consortium is studying how beta cells are made during development, maintained in
sufficient numbers in healthy individuals, and function to release insulin in precise
response to the body's needs. This research will provide the foundation for strategies
to replace beta cells in patients with type 1 diabetes and to repair defective beta
cells in those with type 2 diabetes.
A related line of inquiry is the study of processes that may either contribute to or signify
the presence of chronic disease. For example, inflammation is a normal and necessary reaction of
the body to infections, chemical irritants, and other harmful substances or injury. However,
unresolved or chronic inflammation underlies or contributes to many chronic diseases. Researchers
are working to elucidate the role of inflammation in a number of chronic diseases; for example,
using a mouse model of glaucoma, researchers have discovered that a key inflammation marker, TNF-a,
might be the link between elevated eye pressure and damage to the optic nerve. Another team found
that resolvin E1, a form of omega-3 fatty acid, can alter the course of inflammation associated
with periodontitis. In addition, researchers are building on advances in the fundamental biology
of inflammation to investigate age-related inflammatory processes in the elderly, such as vascular
inflammation and neurotoxicity in the brain and inflammatory responses to sleep loss.
A critical dimension of basic research on chronic diseases and organ systems is the development
of innovative technologies, research tools, and materials that are revolutionizing our understanding
of the human body and laying the groundwork for cutting-edge therapies. Heart and vascular diseases
represent only one example of many chronic diseases that benefit from technology research.
Use of new, noninvasive imaging techniques in the
Jackson Heart Study,
a longitudinal study of heart and cardiovascular disease in African Americans in Mississippi,
is expected to provide important new insights into the origins of heart disease in
this population. Likewise, advances from disciplines such as materials science,
tissue engineering, bioengineering, and computational sciences are providing a
foundation for the development of replacements for damaged or diseased small
blood vessels, from which thousands of patients with vascular disease could
benefit each year.
Detecting and Diagnosing Chronic Disease
Early detection and diagnosis of a chronic disease or of damage to an organ
allows patients to seek appropriate care and, in some cases, improve their
outcomes or prevent progression of the disease. NIH fosters research on
disease detection and diagnosis through the identification of biomarkers
that predict disease or its progression, as well as the development of
technologies or resources to promote early detection. For example, the
NIH-supported Drug-Induced Liver Injury Network
(DILIN) performs research on liver toxicity caused by prescription drugs
or CAM. Among many research projects, DILIN researchers are developing
better diagnostic tools and studying the mechanisms of liver injury.
Related clinical research on acute liver failure from drug-induced
liver injury conducted by the Acute Liver Failure Study Group
has identified a potential biomarker for liver injury caused by excessive
amounts of the over-the-counter pain reliever acetaminophen, which could be
used clinically to aid diagnosis. In another example, the Alcohol Biosensors
Program is engineering devices for the continuous measurement of alcohol
concentrations that will provide new tools for clinical and basic research
on alcohol use disorders.
In addition to advanced technology, the dissemination of knowledge to health
care providers is one of the most important tools for disease detection and
diagnosis. NIH has updated the booklet Helping Patients Who Drink Too Much: A Clinician's Guide to educate primary care and mental health clinicians
on evidence-based methods to screen, diagnose, and manage patients who may have
alcohol use disorders. In addition to traditional printed handouts and fact
sheets, NIH also offers information for doctors and other health professionals
in electronic formats. Two CD-ROMs, Bone Health Information for You and Your
Patients and Lupus and Other Related Information for You and Your Patients,
provide print-friendly PDF files of health education brochures and professional
educational resources, as well as Web links to current clinical trials and other
resources from Federal agencies and nonprofit organizations. Additional efforts
to convey information about chronic disease detection and diagnosis to the
medical community are described in the section Health Communication and
Information Campaigns and Clearinghouses in Chapter 3.
Identifying Risk and Preventing Chronic Disease
Many chronic diseases have genetic or hereditary components that increase the risk
of disease in certain individuals or population groups. Chronic diseases also may
have known, modifiable risks factors such as diet, smoking, chronic stress, exposure
to environmental toxins, or a variety of other factors. Often, disease results from
complex and poorly understood interactions among multiple genetic, environmental,
and behavioral risk factors. NIH supports research to identify all types of risk
factors for chronic diseases and to develop new strategies to modify risk to
prevent disease.
The completion of the Human Genome Project has opened new avenues of research
into the genetic causes of chronic diseases. Diseases and conditions for which
NIH-supported investigators have recently identified susceptibility genes include:
The datasets collected through many NIH-supported genetics studies are available,
with appropriate mechanisms in place to safeguard subjects' privacy, to qualified
researchers worldwide.
Ongoing initiatives such as the
ENDGAME (Enhancing Development of Genome-Wide
Association Methods)
consortium are developing new approaches to understanding the role of genetic
variation in normal physiology and disease, whereas two major ongoing studies
(the Candidate Gene Association Resource
and the Framingham SHARe Program)
are focusing onthe genetics of cardiovascular disease. In addition, a public-private
partnership led by NIH—the
Genetic Association Information Network (GAIN)—is
exploiting the completion of a detailed map of human genetic variation to
search for genes involved with specific diseases and to develop tools to
understand how environmental factors interact with genetic susceptibilities.
(For more on GAIN, see the section Genomics in Chapter 3.)
Genetic susceptibility is rarely the only risk factor for developing a chronic disease.
NIH also supports research to identify other, nongenetic risk factors that, either
alone or in conjunction with genetic factors, influence the development or progression
of chronic diseases. Identifying risk factors for a specific disease from the myriad
behaviors and environments of individuals requires studying large numbers of people
for extended periods of time. Two research studies of osteoporosis and other
age-related chronic diseases—the Study of Osteoporotic Fractures and Mr.
OS—have uncovered specific risk factors, such as bone mineral density of the hip,
that predict the risk of fractures in the elderly.
The Osteoarthritis Initiative
is tracking 4,800 individuals who are at high risk for knee osteoarthritis to
identify biological markers that predict disease progression. NIH-supported
researchers also are investigating the complex biological and behavioral f
actors underlying childhood and maternal obesity and testing behavioral
interventions in schools, homes, and the community in an effort to stem the
rising obesity epidemic.
Many population groups, whether stratified by race, ethnicity, sex, age, or
other characteristics, seem to be particularly vulnerable to specific chronic
diseases. NIH research programs that are exploring genetic and nongenetic
disease risk factors in specific populations include:
Knowing the factors that increase or decrease the risk of disease can help
researchers design innovative strategies to prevent disease in susceptible
individuals. Interventions are being developed and tested to prevent
trauma-related mental health disorders, such as posttraumatic stress
disorder, in persons engaged in high-risk occupations such as the military or
emergency response. The
Diabetes Prevention Program Outcomes Study
currently is assessing long-term outcomes in its subjects; the study previously had
demonstrated that lifestyle change or treatment with the drug metformin significantly
delayed the onset of type 2 diabetes in at-risk individuals. Lifestyle changes
(modifications in diet and physical activity) were nearly twice as effective as
drug treatment in reducing the risk of developing type 2 diabetes in that study.
Furthermore, the physical activity increases in the lifestyle modification group
were sustained for 4 years, indicating that modest changes in behavior can be
accomplished and maintained for long periods. A related clinical trial,
Look AHEAD
(Action for Health in Diabetes), is testing whether an intensive lifestyle
intervention for weight loss can reduce the incidence of cardiovascular events
in 5,100 overweight or obese subjects with type 2 diabetes. Testing strategies
for prevention and early treatment of type 1 diabetes is the focus of the
TrialNet
clinical research network. The network recently began a new clinical study of oral
insulin to prevent or delay type 1 diabetes in at-risk individuals.
Prevention of chronic diseases in children is a particularly important focus of
NIH research. The onset of a chronic disease in childhood often is associated
with serious comorbidities (disorders or diseases in addition to the primary disease);
therefore, many of these diseases, if left unchecked, have negative implications for
the health of the future adult population. HEALTHY is a multicenter clinical trial
testing behavioral interventions aimed at decreasing the risk of obesity and type
2 diabetes in middle school children. Likewise, the goal of the national public
education outreach program
Ways to Enhance Children's Activity & Nutrition (We Can!) is to reduce childhood obesity by helping children age 8-13 achieve
and maintain a healthy weight. Asthma, another serious disease of childhood,
is strongly related to environmental exposures such as indoor allergens.
Researchers in North Carolina are conducting a dust mite reduction study
in the homes of study subjects between ages 5 and 15 to determine whether
this strategy can reduce or prevent asthma and other adverse outcomes related
to dust mite exposure. The
Underage Drinking Research Initiative
supports multiple efforts to understand and prevent alcohol use by children and
adolescents and its progression to abuse and dependence, and the Rapid Response
Program supports the implementation and evaluation of programs to reduce underage
alcohol use on college campuses.
NIH also sponsors awareness campaigns and other educational efforts to disseminate
the results of its prevention research to the general public (see the section Health
Communications and Information Campaigns and Clearinghouses in Chapter 3). One such
campaign,
The Heart Truth,
takes a multifaceted approach to educate women on the risk factors for heart disease,
the leading cause of death in American women.
Treating Chronic Disease and Comorbidities
Despite the remarkable advances of modern medicine, chronic diseases, by definition,
require long-term medical or behavioral intervention or a combination of multiple
treatment modalities. For some diseases, no effective therapies or cures are
currently available, and the diseases can only be managed to control symptoms.
Daily management of chronic diseases to prevent or slow the progression or
development of comorbidities often imposes a significant burden on patients
and their families. For example, type 1 and type 2 diabetes can be managed by
injections of insulin or by taking insulin-sensitizing drugs; however, optimal
control of diabetes to reduce the risk of complications also requires careful
and continuous monitoring of blood glucose levels, diet, and physical activity
throughout the day. A major focus of NIH research is the development and testing
of new therapies for chronic disease that will cure disease, ease the process
of disease management, treat patients who are not helped by current therapies,
or otherwise reduce the burden of chronic illness. (For a general discussion
of treatment and other clinical research, see the section Clinical and
Translational Research in Chapter 3.) To facilitate clinical trials for
many diseases, NIH supports multiple networks of investigators at medical
centers across the country who can conduct studies more efficiently by working
together. In addition, NIH is investing in the development of a Patient-Reported Outcomes Measurement Information System
that will devise standardized measurements
of symptoms that affect quality of life. Validated measures of patient-reported
symptoms such as pain, fatigue, emotional distress, and others will revolutionize
clinical research across a spectrum of chronic diseases and conditions.
The NIH clinical research portfolio comprises numerous trials to evaluate the safety
and efficacy of therapies for many chronic diseases. The examples described here
illustrate the diversity of diseases and potential therapies being studied with
NIH support. Information about these and other NIH-supported clinical trials is
available at
http://clinicaltrials.gov.
- Diabetes: The long-running Diabetes Control and Complications Trial and its follow up, the
Epidemiology of Diabetes Interventions and Complications
study, have demonstrated that intensive insulin therapy, although not a cure for
diabetes, can dramatically reduce the risk of diabetic complications of the eyes,
nerves, kidneys, and heart.
- Chronic Obstructive Pulmonary Disease (COPD): The
Long-Term Oxygen Treatment
Trial is assessing the role of home oxygen therapy for patients with COPD and
moderate hypoxemia (low blood oxygen level).
- Idiopathic Pulmonary Fibrosis: A clinical research network has been
established to treat patients with newly diagnosed idiopathic pulmonary fibrosis,
using combinations of drugs that might attack the fibrotic process at multiple
points and thereby stabilize or improve the disease.
- Nonalcoholic Steatohepatitis (NASH):
The NASH Clinical Research Network
is investigating whether vitamin E or the drug pioglitazone is an effective
treatment for nondiabetic adults with NASH, a liver disease associated with
obesity and diabetes.
- Hepatitis C: The Hepatitis C Antiviral Long-Term Treatment Against
Cirrhosis (HALT-C)
Trial is studying whether long-term antiviral therapy can prevent the progression
of liver disease in patients who have hepatitis C infection and who were not
helped by short-term therapy.
- Polycystic Kidney Disease (PKD):The
HALT-PKD
trial is evaluating the use of blood pressure management in combination with
medication as a means to slow progression of PKD in patients with either early
or advanced disease.
- Age-Related Macular Degeneration (AMD): An NIH-supported trial reported
in 2005 that certain vitamin and mineral supplements reduce progression of AMD,
a leading cause of blindness in the elderly; the
Age-Related Eye Disease Study,
Part 2, is extending that result by testing additional supplements that might also slow down AMD.
- Uveitis: Localized steroid treatment is being testing in the
Multicenter Uveitis Steroid Treatment
(MUST) trial as a therapy for this major cause of blindness. If successful,
this trial would improve on current treatments for uveitis that expose the
entire body to corticosteroids and immune suppression drugs.
- Ulcerative Colitis: Many patients with ulcerative colitis do not
respond to currently available treatments. A clinical trial is under way to
determine whether a drug used to treat type 2 diabetes (rosiglitazone) can also
control the symptoms of ulcerative colitis.
- Drug Abuse and Addiction: NIDA's National Drug Abuse Clinical Trials
Network is a multisite research project that tests the effectiveness of new and
improved behavioral, pharmacological, and integrated treatment interventions in
real-life community settings with diverse populations.
Children do not always respond to treatments in the same way as adults. For this reason,
NIH is committed to conducting clinical intervention trials to identify therapies that
are safe and effective for use in children with chronic diseases. For example, the
NASH Network (see above) is testing the use of the drug metformin or vitamin E as a
treatment for fatty liver disease in children. Type 2 diabetes—a disease that was
previously seen primarily in adults—is becoming more prevalent in children, and the
safety of long-term use of adult diabetes drugs in children is not known. The
Treatment Options for Type 2 Diabetes in Youth
(TODAY)
study is evaluating three
strategies for treating children and adolescents with type 2 diabetes. NIH supports
a multipronged approach to developing and testing therapies for asthma. The
Inner-City Asthma Consortium (ICAC) evaluates immune-based therapies for asthma
in inner-city children, who are disproportionately affected by the disease. At
the same time, the Asthma Exacerbations: Biology and Disease Progression program
is conducting basic and clinical research to facilitate development of new
treatments to control asthma symptoms in children and adults.
In addition to drug development and evaluation, NIH supports research on
nonmedicinal interventions for chronic diseases, including behavioral and
surgical approaches. For example, researchers have developed two effective
behavioral therapies—the Matrix Model and Motivational Incentives for Enhanced
Drug Abuse Recovery—that help people overcome methamphetamine addiction. A
clinical trial infrastructure also has been set up to facilitate testing of
innovative treatments for mental disorders such as schizophrenia, bipolar
disorder, and depression that include medical and/or behavioral therapies.
The Health Maintenance Consortium is fostering collaboration among
independent research projects aimed at promoting behavior change in areas
such as diet, exercise, HIV prevention, smoking cessation, and others.
Many diverse strategies are being tested for treatment of obesity,
including the use of bariatric surgery. The Longitudinal Assessment of
Bariatric Surgery (LABS) is evaluating the risks and benefits of bariatric
surgery in obese adults, and a related observational study, Teen-LABS, is
collecting data on the use of this procedure in obese adolescents.
Organ transplantation is a surgical option for some chronic diseases.
Transplantation can alleviate disease, prolong survival, and improve
quality of life, but the procedure carries its own risk of complications,
including those caused by drugs that prevent organ rejection. Researchers
are investigating the use of MRI to noninvasively monitor transplant rejection.
If successful, this technology could be used by physicians to modulate drug
regimens to precise levels that prevent rejection while allowing the patient's
body to maintain enough immune activity to ward off infections. NIH established
the Clinical Trials in Organ Transplantation program to further improve the
outcome of organ transplantation. Researchers also are studying transplantation
of specific organ tissues to treat disease, such as transplanting the insulin-producing
islet cells of the pancreas to treat type 1 diabetes. The international Clinical Islet
Transplantation Consortium is developing and conducting clinical studies that could
improve this treatment approach for people with type 1 diabetes.
An important aspect of the NIH mission is to communicate the results of its research so that
patients and the public can benefit from up-to-date information on treatment options
(see the section Health Communication and Information Campaigns and
Clearinghouses in Chapter 3). Sometimes this goal is accomplished through
public awareness campaigns, such as one for COPD called
COPD: Learn More, Breathe Better,
which distributes materials on COPD to patients, persons at risk, health care
professionals, and community-level organizations to raise awareness of COPD.
COPD is a disease that often goes undiagnosed, and therefore untreated, in an
estimated 12 million Americans. For other diseases, translational researchers
are exploring the best ways to transfer knowledge from controlled research settings
into standard medical practice and the community to achieve maximum benefits for
public health. Research is ongoing to find sustainable and cost-effective means to
translate the successes of clinical trials for the treatment of diabetes and obesity
into the real world. NIH-supported scientists also are identifying ways to promote
the use of evidence-based interventions for treatment of mental illnesses.
A 2002 survey conducted by NIH and CDC found that one-third of American adults use
some form of complementary and alternative medicine (CAM) to prevent or treat
disease, including diverse modalities such as acupuncture, meditation, megavitamin
therapy, herbs, special diets, chiropractic care, prayer, and other methods.
The goal of NIH research on CAM is to provide an evidence-based assessment of the
safety and effectiveness of CAM practices in order to guide and protect patients
and consumers who are making treatment choices. NIH has developed a 5-year strategic
plan to define priorities for CAM research, much of which pertains to a variety of
organ systems and chronic diseases.
NIH-supported studies of popular dietary supplements have reported mixed results.
One study showed that high doses of a form of vitamin E did not lower cholesterol
in the blood, whereas in another study, glucosamine and chondroitin sulfate
supplements did not relieve osteoarthritis pain in the general study population,
although patients with moderate-to-severe pain did benefit. In other ongoing
research, multidisciplinary teams are uncovering scientific explanations for some
of the effects of acupuncture in relieving pain and are evaluating the use of this
technique in patients with coronary artery disease, spinal cord injury,
post-thoracotomy pain syndrome, and a number of other chronic conditions.
Addressing Pain and Palliative Care in Chronic Diseases
Pain and palliation—care to alleviate the symptoms of disease and improve
quality of life—are issues associated with many chronic diseases, regardless
of the organ system affected. NIH supports research to understand the origins
of pain, develop therapies to manage pain effectively, and design palliative
therapies to reduce suffering and improve disease outcomes. NIH is pursuing
multidisciplinary approaches to the discovery of non-opioid pain medications
that can selectively and safely treat chronic pain without creating drug dependence.
For example, basic pharmacological research has uncovered previously unknown
receptor combinations in the body that represent new targets for pain control.
Nonpharmacological strategies for pain management also are being closely studied.
For example, researchers have confirmed that acupuncture is an effective add-on to
conventional treatment for osteoarthritis, a common cause of pain and reduced
quality of life in elderly patients. The Spine Patient Outcomes Research Trial
has determined which patients with back pain are most likely to benefit from
surgical intervention. The Orofacial Pain: Prospective Evaluation and Risk Assessment
study is seeking better ways to manage the chronic pain of temporomandibular muscle
and joint disorders.
Because of the broad diversity of chronic diseases associated with pain, NIH
established the NIH Pain Consortium
to enhance research and promote collaboration among the many ICs that have an interest
in pain and pain management research. Since its establishment, the consortium has
sponsored two symposia featuring new and exciting advances in pain research and pain
management. Consortium ICs also have issued an NIH-wide research initiative to encourage
pain research and delineate cross-cutting NIH interests in pain.
NIH research addresses the application of palliative care at all stages of a disease
process, including at the end of life, and encompasses the needs of patients and
their caregivers. Behavioral strategies have been shown to improve patient outcomes
for several chronic diseases, including diabetes, irritable bowel syndrome, and
asthma. Researchers also have developed a support intervention that significantly
improves the quality of life for caregivers of patients with Alzheimer's disease;
further research is needed to determine how best to implement this intervention
through community health service networks so that more caregivers can benefit.
In FY 2006, the proceedings of an NIH-sponsored State-of-the-Science Conference
on Improving End-of-Life Care were published as a supplement to the Journal of
Palliative Medicine. This special supplement reported on the state of the science
in end-of-life care and proposed new research directions to improve care for all
patients and their families in the final stages of disease.
Notable Examples of NIH Activity
Key for Bulleted Items:
|
E = Supported through Extramural research
I = Supported through Intramural research
O = Other (e.g., policy, planning, or communication)
COE = Supported through a congressionally mandated Center of Excellence program
GPRA Goal = Concerns progress tracked under the Government Performance and Results Act
|
|
Understanding Fundamental Mechanisms of Organ Health and Disease
Innovative Technologies for Engineering Small Blood Vessels: NIH has initiated
a program of basic research studies for the future development of replacements for
damaged or diseased small blood vessels. Thousands of patients each year could
benefit from small blood vessel substitutes (e.g., to bypass coronary artery or
peripheral vascular occlusions or to establish arteriovenous shunts for hemodialysis),
but currently available replacement grafts have a high failure rate. Recent advances
in materials science, bioengineering, and tissue engineering, as well as the
availability of better computational tools, are providing opportunities for the
development of replacement blood vessels with properties that closely match those
of natural blood vessels.
- This example also appears in Chapter 3:
Molecular Biology and Basic Sciences and Chapter 3: Technology Development.
- (E) (NHLBI)
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS):
In a joint effort, NHLBI, the Center for Medicare and Medicaid Services, and FDA
created INTERMACS, a national registry for patients who are receiving mechanical
circulatory support device therapy to treat advanced heart failure. Data from
INTERMACS are expected to improve patient evaluation and management; aid in the
development of safer, more effective devices; and enhance research.
- For more information, see
http://www.uab.edu/ctsresearch/mcsd
- This example also appears in Chapter 3:
Disease Registries, Databases, and Biomedical Information Systems
- (E) (NHLBI)
Women's Health Initiative: In January 2007, NIH awarded support for a dozen
2-year research projects to apply genomics, proteomics, and other innovative
technologies to improve understanding of several major diseases that commonly
affect postmenopausal women. The new endeavor builds on the long-running Women's
Health Initiative, which conducted several clinical trials and an observational
study to examine strategies for preventing heart disease, breast and colorectal
cancers, and osteoporosis in a cohort of more than 160,000 subjects. Investigators
will use stored blood, DNA, and other biological samples and associated clinical
data to analyze genetic factors and biological markers that may be useful in
predicting disease outcomes or the effects of therapeutic and preventive regimens
in postmenopausal women.
Inflammation in the Elderly: Inflammatory processes, particularly those
mediating chronic inflammation, have been implicated as predictors or initiators
of or contributors to a number of chronic diseases and conditions of aging. NIH
currently supports research to determine relationships of age-related changes in
inflammation and inflammatory mediators to physiologic and pathophysiologic aging
changes, risks and progression of age-related morbidity and disability, and changes
in tissue and organ function. Funded projects include studies of vascular
inflammation and neurotoxicity in the aging brain and inflammatory responses to
sleep loss.
Neurobiology of Appetite Control: NIH supports research to elucidate the
complex biologic pathways that converge in the brain to regulate appetite. Examples
include research on how serotonin reduces appetite; the actions of the protein mTOR
in sensing nutrients in the body so as to modulate food intake; and a strategy to
block ghrelin, a stomach-secreted hormone that signals the brain to increase food
intake. This research has implications for new therapies for obesity.
Lymphatic System in Health and Disease: NIH recently announced two funding
opportunities for research to increase understanding about the lymphatic system and
its function in health and disease. The lymphatic system plays a critical role in
the well-being of many other systems in the body. When it is not working properly,
a broad array of diseases and disorders can result, including lymphedema
(characterized by accumulation of lymph fluid that often results in swelling
of the arms or legs), inflammation and infections, cancer, and metabolic disorders.
In July 2007, NIH issued the Program Announcement Lymphatic Biology in Health and
Disease to encourage research on the biology of the lymphatic system and potential
new therapeutic approaches. In addition, in December 2006, NIH re-issued the Program
Announcement Pathogenesis and Treatment of Lymphedema and Lymphatic Diseases to
stimulate research on the lymphatic system and lymphatic dysfunction and related
diseases, as well as to develop new diagnostic methods and treatment interventions.
Understanding the Mechanisms of Alcohol-Induced Tissue Injury: Virtually every
organ system of the body is impacted by heavy alcohol use (the most vulnerable being
the brain and liver), and the resulting pathological conditions contribute to
increased mortality and morbidity among all age and racial/ethnic groups and genders.
NIH is especially interested in elucidating mechanisms of injury common to multiple
body and organ systems. A number of Program Announcements and RFAs have been issued
to support research to increase our understanding of the underlying cellular and
molecular mechanisms of tissue injury caused by alcohol consumption, including
alcohol's genetic, epigenetic, and metabolic effects. The long-term goals of these
initiatives are to identify biomarkers for alcohol exposure and for the early
detection of alcohol-induced tissue injury, and to develop new therapeutics that
control or modify outcomes of chronic alcohol use.
Jackson Heart Study Advanced Imaging Component: The Jackson Heart Study is a
longitudinal study of heart disease and cardiovascular disease in about 5,000
African Americans in the Jackson Mississippi area. Data collection for this study
began in 2000. New imaging techniques that include dynamic MR imaging of the heart
to assess cardiac function and CT imaging to assess visceral abdominal fat and
calcification of the aorta and coronary vessels can provide significant additional
understanding of heart disease in this minority population. NIH is in the process
of adding these valuable components to the study of heart disease. The CT studies
began in spring of 2007 and the MR studies are being set up now and will begin in
early 2008.
Systems Biology Approach to Salivary Gland Physiology: Previous research has
catalogued the genes and proteins expressed in the salivary glands. This initiative
puts those catalogues into context by defining when and where genes and proteins are
expressed and how they function as parts of a fully integrated biological system.
The initiative combines the power of mathematics, biology, genomics, computer
science, and other disciplines to translate this highly detailed information
into more precise and practical leads to treat Sjõgren's syndrome, a debilitating
autoimmune disorder that affects millions of Americans. The initiative also will
help in learning to use saliva as a diagnostic fluid for a variety of conditions,
from AIDS to cancer to diabetes.
Beta Cell Biology Consortium (BCBC): The BCBC is collaboratively pursuing key
challenges relevant to the development of therapies for type 1 and type 2 diabetes,
including studying pancreatic development to understand how insulin-producing beta
cells are made, exploring the potential of stem cells as a source for making islets,
and determining the mechanisms underlying beta cell regeneration. The BCBC has
generated key research resources, such as animal models, microarrays, and antibodies,
which are available to the scientific community.
- For more information, see http://www.betacell.org
- This example also appears in Chapter 2: Autoimmune Diseases and Chapter 3: Molecular Biology and Basic Sciences
- (E) (NIDDK)
Urinary Tract Infections: NIH supports a Specialized Center of Research on
Sex and Gender Factors Affecting Women's Health. This program advances new
understanding of host-pathogen interactions that occur throughout the infectious
cycle, including host defense response in the bladder and the virulence mechanisms
by which bacterial pathogens subvert the defenses.
Systems Science and Health: Solutions to complex problems like chronic disease
require approaches that can address a broad range of factors within a single
framework—from genetic to environmental, cellular to behavioral, and biological
to social. A 2007 Symposium Series on Systems Science and Health focuses on
approaches that consider how numerous factors interact nonlinearly over time
in multiple feedback loops to influence health. These approaches show promise
for unlocking the secrets of complex, multidimensional health problems and for
transforming this knowledge into effective interventions that can fundamentally
change population health.
Mechanisms of Action of CAM: Important and potentially promising findings from
recently reported research aimed at elucidating the fundamental mechanisms of various
CAM interventions include the following:
- Extracts of turmeric (a common component of Ayurvedic traditional Indian
medicines and ingredient in Indian cuisine) containing compounds known as
curcuminoids prevent experimental rheumatoid arthritis in an animal model.
- Green tea is widely promoted for a variety of health-related benefits.
It contains a group of chemicals called catechins, one of which is known as
epigallocatechin gallate (EGCG). Investigators recently reported that an
EGCG-enriched extract of green tea significantly improves glucose and
lipid metabolism in an animal model of obesity/insulin resistance/metabolic
syndrome.
Inflammatory Factor Mediates Nerve Degeneration in
Glaucoma Model: In glaucoma, elevated eye pressure
plays a role in damaging fibers in the optic nerve,
which relays visual signals to the brain. However,
the link between pressure and nerve damage is not
well understood. Recent research in mice suggests
a critical role for the protein TNF-a in developing
glaucoma. A molecular target in the glaucoma disease
pathway opens up doors for drug therapy.
Wound Healing and Skin Biology: Recent advances in
wound healing research have brought greater understanding
to skin biology, with implications for hair growth and skin
diseases, as well as treatment of chronic wounds. When skin
is wounded, a protein, S100A7, is released and attaches to
and reduces survival of potentially disease-causing bacteria
on the skin, preventing the development of wound-related
infections.
Leiomyomata Uteri (Uterine Fibroids): Some estimates
suggest that uterine fibroids could affect as many as 77
percent of women nationwide and that more than 25 percent
have active symptoms. NIH researchers recently found that,
unlike normal uterine tissue, abnormal fibroid tissue is
not affected by reproductive hormones. This suggests that
the conventional hormone therapies used to treat fibroid
tumors are unlikely to yield lasting improvements. Based
on the findings, NIH researchers are planning studies to
test two new drug treatments. One would block collagen from
forming to help keep existing fibroids from growing larger;
the second would help to break apart collagen fibrils in an
attempt to shrink existing tumors.
Anti-inflammation/Resolution Regulator May Be Involved in
a Wide Range of Human Diseases: Resolvin E1 (RvE1) is a
new family of bioactive products of omega-3 fatty acid.
Using periodontitis as a model disease, a team of NIH-funded
researchers recently reported that RvE1 can dramatically
alter the progression of microbe-initiated local inflammatory
disease. RvE1 therapy demonstrates greater efficacy without
the side effects of chronic antibiotic usage. The results of
their study provide new directions for treatment of localized
aggressive periodontitis and other inflammation-related bone
disorders. In many chronic disorders similar to periodontitis,
prolonged and unresolved inflammation contributes to
pathogenesis. It is now clear that several endogenous
biochemical pathways activated in the host during defense
reactions can counter-regulate inflammation. This study
provides evidence for the role of resolvin E1 as an
endogenous anti-inflammation/resolution regulator that
may be involved in the pathogenesis of a wide range of
human diseases.
New Molecular Targets to Halt Periodontal Bone Loss::
Approximately 80 percent of American adults have some form of
periodontal disease. Chronic periodontitis erodes supporting
structures of the tooth, leading to tooth loss. The risk of
periodontal diseases is higher in smokers and individuals
with diabetes; 18 million Americans suffer from diabetes and
related complications, including increased incidence and
severity of periodontitis. This higher incidence and
severity is associated with increased cell death in bone
and tissue-forming cells called osteoblasts and fibroblasts.
The loss of these cells results in decreased capacity to
repair tissue and bone. NIH-supported investigators published
two separate papers describing the mechanisms by which the
diabetic state enhances cell death. The papers suggest that
d iabetes-induced cell death and compromised tissue repair
are mediated by the TNF-a pro-apoptotic pathway, the major
effector being caspase-3. Inhibition of TNF-a or caspase-3
activity rescues cell death and restores repair capacity.
Discrimination between harmful microbes and commensal species
is a critical property of the mucosal immune system, which
is essential for maintaining health. Host immune cells have
surface receptors that recognize bacterial species such as
those known to be associated with periodontitis. Host immune
cells can selectively learn to respond strongly or to
tolerate endotoxin produced by recognized bacteria.
NIH-supported scientists found that patients with chronic
periodontitis overproduce a molecule known as SHIP, which
plays an important regulatory role in signaling immune cells
to tolerate endotoxin. Data from these studies suggest
possible targets for developing new ways to treat or prevent
chronic periodontitis.
Advances in Treatment Development for Mental Disorders:
NIH continues to fund research into the development of new,
targeted medications and treatments for mental disorders:
- Drug Development for Cognitive Impairments in
Schizophrenia:The Treatment Unit for Research on
Neurocognition in Schizophrenia program is a network
that is testing the safety and efficacy of new
therapeutic compounds for treating the cognitive
deficits of schizophrenia.
- Studies of Fragile X Syndrome:NIH has entered
into a public-private partnership to study and test
possible medications for treating fragile X syndrome,
the most common cause of inherited mental impairment.
Fragile X syndrome is caused by a single gene mutation
that ultimately results in exaggerated activity of a
brain protein called mGluR5. Researchers will study,
in animals, the safety of chemical compounds known to
block this mGluR5 activity. If this phase goes well,
researchers will move forward with clinical studies.
- Faster-Acting Depression Treatments:A recent
NIH-funded study found that people with
treatment-resistant depression experienced relief in
as little as 2 hours after a single intravenous dose
of ketamine, a medication usually used in higher doses
as an anesthetic. Used in very low doses, ketamine is
important for depression research but at higher doses
could have side effects that may limit its clinical use.
Nevertheless, this research could inform the development
of faster- and longer-acting medications for treating
depression.
- For more information, see
http://www.nimh.nih.gov/press/ketamine.cfm
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System and Chapter 3: Clinical and Translational Research.
- (I) (NIMH)
Detecting and Diagnosing Chronic Disease
Helping Patients Who Drink Too Much: A Clinician's Guide:
In January 2007, NIH issued an update to its 2005 edition of
this clinician's guide. Targeted to primary care and mental
health clinicians, the guide presents a user-friendly,
research-based approach to screening, diagnosing, and
managing patients with heavy drinking and alcohol use
disorders. The updated guide offers the following new
resources: CME/CE credits for physicians and nurses available
through Medscape; support for medication-based therapy in
non-specialty settings; a new handout with strategies to
help patients reduce or quit drinking; a new dedicated Web
page devoted to the guide and supporting resources for
clinicians and patients; and an updated PowerPoint
presentation for educators and instructors. NIH has
worked closely with several organizations to disseminate
the guide to their memberships.
Alcohol Biosensors Program: This Advanced Research
Program, modeled on DoD's DARPA (Defense Advanced Research
Projects Agency) program, was developed by NIH to generate
a technical solution to address the need for continuous
measurement of alcohol concentrations over time in clinical
and basic research on alcohol use disorders. NIH awarded five
research and development contracts for alcohol biosensor
development. Each research group employed a different
technological approach for alcohol measurement, and all
have made substantial progress in engineering commercially
viable alcohol biosensors, some of which are likely to make
their way to market in the next few years.
- This example also appears in Chapter 3: Technology Development.
- (E) (NIAAA)
Drug-Induced Liver Injury Network (DILIN):DILIN is
addressing the problem of drug-induced liver toxicity,
which is increasing in the United States and has serious
consequences for individuals and society. This Network
enables research on liver toxicity due to prescription
drugs or complementary and alternative medicines. Current
studies are developing better tools for diagnosing, and
ultimately preventing, drug-induced liver injury, as well
as enhancing knowledge of disease processes. The Network
has evolved into a resource on drug-induced liver toxicity
for the national clinical community and the public.
Identifying Risk and Preventing Chronic Disease
Genome-Wide Association (GWA) Studies and Database of Genotype and Phenotype (dbGaP):
In December 2006, NIH released the initial dbGaP dataset,
using GWA data from the Age-Related Eye Diseases Study
(AREDS), a landmark study of the clinical course of
age-related macular degeneration (AMD) and cataracts.
AREDS documents, protocols, and aggregated data are made
available with no restrictions. To protect patient
confidentiality, de-identified, individual-level patient
characteristics and family data are accessible only by
authorized investigators. Correlating phenotype and
genotype data provides information about the genetic
and environmental interactions involved in a disease
process or condition, which is critical for better
understanding complex diseases and developing new
diagnostic methods and treatments. Using these data,
recent studies have linked two genes with progression
to advanced AMD. After other factors were controlled for,
certain forms of the genes increased the risk of AMD
progression by 2.6- to 4.1-fold; smoking and body weight
further increased risk with these gene variants.
Diabetes Prevention Program Outcomes Study (DPPOS): The
landmark NIH Diabetes Prevention Program (DPP) clinical trial
showed that lifestyle change or treatment with the drug
metformin significantly delayed the development of type
2 diabetes in people at high risk. The DPPOS is a long-term
follow-up study of DPP subjects that is determining the
durability of the interventions in preventing disease.
DPP researchers recently confirmed that a variant in a
gene predisposes people to type 2 diabetes. DPP subjects
at highest genetic risk benefited from healthy lifestyle
changes as much or more than those who did not inherit the
variant. Participants over 60 years of age responded
especially well to the lifestyle intervention, showing a
71 percent risk reduction in the incidence of diabetes,
compared to groups treated with metformin or standard
medical advice. The lifestyle intervention had greater
impact with increasing age (from age 25 to over 60);
the metformin treatment had progressively less impact
with increasing age.
- Florez JC, et al. N Engl J Med 2006;355:241-50, PMID: 16855264
- For more information, see http://tinyurl.com/24okog
- For more information, see http://tinyurl.com/295h4l
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Epidemiological and Longitudinal Studies.
- (E) (NIDDK, CDC, IHS, NCMHD, NEI, NHLBI, NIA, NICHD, ORWH)
The Heart Truth: The Heart Truth, NIH's national
awareness campaign for women about heart disease,
continues to extend the reach of campaign messages
and promotion of the Red Dress as the national symbol for
women and heart disease. Hundreds of locally sponsored Heart
Truth events have taken place, and more than a billion media
impressions have been achieved. The Heart Truth Road Show
helps subjects learn about heart disease risk factors,
provides free health screenings, and disseminates educational
materials. In April 2006, the campaign launched the Heart
Truth Champions program to recruit health advocates and
educators in local communities to increase awareness about
women and heart disease. National Wear Red Day—the first
Friday in February—has become an annual event when Americans
wear red clothing and accessories in recognition of the
importance of heart disease in women.
Ways to Enhance Children's Activity & Nutrition (We Can!):
This national public education outreach program, focusing on
parents and families in home and community settings, is
designed to help children 8-13 years old achieve and maintain
a healthy weight. We Can! program materials offer tips and
activities to encourage healthy eating, increase physical
activity, and reduce sedentary or computer and television
screen time. Many national partners and supporting
organizations are promoting the We Can! messages and
materials, and the program is being implemented in a
variety of settings. In 2007, NIH began the We Can!
city program to assist towns and cities in mobilizing
their communities to prevent childhood obesity. The first
three cities that will participate in the new effort have
pledged to offer We Can! evidence-based obesity prevention
programs to parents and youth in collaboration with
community-based partners. In addition, each city will
distribute We Can! tips and information to city employees.
National Epidemiologic Survey on Alcohol and Related
Conditions (NESARC):This nationally representative
survey collected comprehensive, detailed data from
approximately 40,000 individuals on alcohol consumption,
use of 10 categories of drugs, and symptoms of alcohol and
specific drug use disorders, as well as mood, anxiety, and
personality disorders. In addition to diagnostic criteria,
NESARC assessed indicators of impairment and distress due
to each disorder, as well as disorder-specific treatment
and help seeking. Analysis of these data is ongoing and
continues to provide valuable information such as prevalence
and comorbidity of mental health and substance use disorders.
In addition, because NESARC data include a representative
sample of ethnic and racial minority populations in the
United States, a better assessment of the needs of specific
populations can be made. One recent study using these data
examined differences in the use of alcohol treatment services
across the three largest ethnic groups in America. It showed
that Hispanics and African Americans with higher levels of
problem severity were less likely to have used treatment
services than were Whites with problems of comparable
severity, providing useful information about disparities
in treatment utilization.
Osteoporosis: NIH supports several longstanding
prospective cohort studies, including the Study of
Osteoporotic Fractures (SOF) in women and Mr. OS, a
study of osteoporosis and other age-related diseases
in men. Major contributions from the SOF, which began in
1986, include findings that bone mineral density of the hip
is one of the best predictors of fracture for women. Recently,
Mr. OS researchers identified specific lifestyle, medical,
and demographic characteristics associated with low bone
mass and fracture risk in older men.
Childhood and Maternal Obesity: As the maternal and
childhood obesity epidemic grows, researchers are trying to
understand the interaction among the many complex biological
and behavioral factors that contribute to this rise, identify
the long-term impact on mother and child, and develop
effective interventions to reverse these trends. NIH obesity
research, which includes a range of racial and ethnic groups,
is examining topics such as:
- Basic research on the physiology, psychology, and genetics of obesity in children
- Developing working definitions of the metabolic syndrome in children and adolescents
- Linking maternal obesity, reproductive health, and pregnancy to adverse health outcomes
- Behavioral intervention trials in schools, the home, and the community
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation.
- (E/I) (NICHD, NCCAM, NCI, NCMHD, NHLBI, NIDCR, NIDDK, NINR, OBSSR, ODP/ORD)
Trial to Reduce the Incidence of Type 1 Diabetes for those Genetically at Risk (TRIGR):
Researchers are conducting a study to determine whether the
onset of type 1 diabetes can be delayed or prevented by
weaning genetically susceptible infants to Nutramigen®,
a hydrolysate of cow milk protein, instead of to a standard
cow milk-based infant formula. Earlier studies in animal
models have shown that hydrolyzed protein diets prevented
the onset of type 1 diabetes. TRIGR is the first large
effort designed to ascertain whether a simple nutritional
intervention during infancy can delay or prevent the onset
of type 1 diabetes in children who are at high genetic risk
for the disease. Enrollment for the study was recently
completed, totaling more than 2,000 children from 15
countries.
HEALTHY: The HEALTHY multicenter clinical trial aims
to prevent risk factors for type 2 diabetes in middle-school
children. A pilot study for HEALTHY found that an alarmingly
high 15 percent of students in middle schools enrolling
mainly minority youth had three major risk factors for
diabetes; about half of the children were overweight.
These data suggest that middle schools are appropriate
targets for efforts to decrease the risks for obesity and
diabetes. In the full-scale HEALTHY trial, 42 enrolled middle
schools receive the intervention, which includes changes to
school food service and physical education classes, behavior
change, and communications campaigns. Over 80 percent of the
enrolled students are from minority populations.
Inflammatory Bowel Disease Genetics Consortium: This
consortium of researchers in the United States and Canada
applies knowledge from the Human Genome Project to the
identification of genetic factors influencing the development
of inflammatory bowel diseases. A genome-wide screen of
samples collected recently identified three new inflammatory
bowel disease susceptibility genes. The identification of
such genetic factors can provide key insights into disease
development and targets for designing more effective
therapies for inflammatory bowel disease.
Irritable Bowel Syndrome: Center for Neurovisceral Sciences
and Women's Health: Irritable bowel syndrome is a common
disorder that occurs much more frequently in females than
in males. The Women's Health and Functional Visceral
Disorders Center at the University of California—Los
Angeles studies the role of sex-related factors in the
development of irritable bowel syndrome and its response
to treatment. Basic and clinical research involving patients,
animal models, and functional brain imaging techniques are
exploring sex differences in stress responses within the
central nervous system, colon, and hormonal and immune systems.
Researchers hope to identify factors that can form the basis
of more effective treatment options for irritable bowel
syndrome.
Environmental Intervention in the Prevention of Asthma:
Asthma is strongly related to environmental exposures.
Exposure to indoor cat, dog, house dust mite, cockroach,
and mold allergens is of particular concern because about
75-80 percent of children with asthma have significant
allergies, which can trigger asthma, and thus these allergens
have considerable medical and economic impact. Recent data
have documented the ubiquity and specific levels of critical
indoor allergens. In addition, a number of studies have shown
that sensitization to indoor allergens (including those that
derive from house dust mites, cats, dogs, rodents, cockroaches,
and fungi) is a risk factor for the subsequent development of
asthma. These studies include case-control studies, prospective
studies, and allergen avoidance trials. Because house dust mites
have been shown to be one of the strongest risk factors for
persistence of asthma, an environmental intervention dust
mite reduction study is under way in North Carolina. Volunteers
between the ages of 5 and 15 years who are allergic or sensitive
to dust mites are being recruited for the study. A study team
will visit the homes of subjects four times over a 12-month
period to measure indoor dust mite levels and collect
information about the home. The results of the study will
provide information that will help reduce or prevent adverse
health outcomes from exposure to house dust mites and other
allergens.
Head Off Environmental Asthma in Louisiana: Nearly 20
million people, 6.5 million of them children, suffer from
asthma in the United States, and minorities are
disproportionately represented. NIEHS, with the National
Center on Minority Health and Health Disparities (NCMHD)
and others, co-funds the Head Off Environmental Asthma in
Louisiana (HEAL) project to assess the impact on asthma of
environmental health conditions that were caused and
exacerbated by Hurricane Katrina in New Orleans children,
as well as implement an intervention program to address
these problems. The Project's three main goals are (1) to
conduct an extensive epidemiology study to assess the nature
of the environmental and psychological impacts on children
in New Orleans of Hurricane Katrina and subsequent flooding;
(2) to examine the genetic and environmental risk factors
for asthma, including genetic susceptibility to mold toxins,
and gene interactions; and (3) to design, implement, and
evaluate a case management program to meet the health care
needs of children with asthma in a disrupted and highly
challenging environment. The project has a clear plan for
informing the community of the goals, implementation, and
outcomes, as well as for receiving input from the community.
- For more information, see http://heal.niehs.nih.gov
- This example also appears in Chapter 2: Minority Health and Health Disparities and Chapter 3: Clinical and Translational Research.
- (I) (NIEHS, NCMHD)
The Collaborative Study on the Genetics of Alcoholism (COGA):
In its 18th year, COGA is a multisite, multidisciplinary family
study with the overall goal of identifying and characterizing
genes that contribute to the risk for alcohol dependence and
related phenotypes. COGA investigators have collected data
from more than 300 extended families (consisting of more than
3,000 individuals) who are densely affected by alcoholism.
Several genes have been identified, including GABRA2, ADH4,
ADH5, and CHRM2, that influence the risk for alcoholism and
related behaviors, such as anxiety, depression, and other
drug dependence. In addition to genetic data, extensive
clinical neuropsychological, electrophysiological, and
biochemical data have been collected, and a repository
of immortalized cell lines from these individuals has
been established to serve as a permanent source of DNA
for genetic studies. These data and biomaterials are
distributed to qualified investigators in the greater
scientific community to accelerate the identification of
genes that influence vulnerability to alcoholism. COGA will
continue to identify genes and variations within the genes
that are associated with an increased risk for alcohol dependence
and will perform functional studies of the identified genes to
examine the mechanisms by which the identified genetic variations
influence risk.
- For more information, see http://zork.wustl.edu/niaaa
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System, Chapter 3: Genomics, and Chapter 3: Molecular Biology and Basic Sciences
- (E) (NIAAA) (GPRA Goal)
Look AHEAD (Action for Health in Diabetes): This
multicenter NIH-led clinical trial is examining the health
effects of an intensive lifestyle intervention designed to
achieve and maintain weight loss over the long term through
decreased caloric intake and increased physical activity.
The impact of the intervention on the incidence of major
cardiovascular events will be evaluated in 5,100 overweight
or obese subjects with type 2 diabetes. Look AHEAD is one of
four trials that collectively address GPRA Goal SRO-6.2.
International Tobacco and Health Research and Capacity Building Program:
Without a significant shift in worldwide smoking patterns,
tobacco is projected to cause approximately 10 million
deaths each year by 2025; 70 percent of this increase will
occur in developing countries. To address this rising
epidemic, NIH reissued the International Tobacco and Health
Research and Capacity Building Program for funding in 2007.
Grantees are generating a solid evidence base that can
inform effective tobacco control strategies and policies.
The program focuses on five critical areas: (1)
epidemiology and surveillance, (2) susceptibility and risk
for smoking uptake, (3) behavioral and social sciences,
(4) effective interventions, and (5) policy-related research.
The program also emphasizes research on determinants of youth
smoking in diverse cultural and economic settings. A central
goal of this program is to strengthen capacity in tobacco
research in low- and middle-income nations, which advances
the science and permits greater international collaboration.
Jackson Heart Study: The Jackson Heart Study, a large
epidemiological study of cardiovascular disease among more
than 5,300 African American residents of Mississippi, has
been renewed through FY 2013. The project is exploring
genetic, biological, and environmental factors that influence
the development and course of cardiovascular disease in
African Americans. It is also seeking to expand minority
participation in public health and epidemiological research
by providing classes and hands-on training to interested
undergraduate students. Moreover, a community health
education component is using data derived from the study
cohort to develop and disseminate up-to-date information
on reduction of risk factors, practice of healthy lifestyles,
and adherence to proven risk-reducing therapies.
- For more information, see http://jhs.jsums.edu/jhsinfo
- This example also appears in Chapter 2: Minority Health and Health Disparities and Chapter 3: Epidemiological and Longitudinal Studies.
- (E) (NHLBI, NCMHD)
Osteoarthritis Initiative (OAI): The OAI is a long-term
effort, developed with support from private sector sponsors
and with the participation of the Food and Drug Administration,
to create a resource to identify and evaluate biomarkers of
osteoarthritis to be used in clinical research. The OAI,
which began in FY 2002, has recruited 4,800 subjects who
are at high risk for knee osteoarthritis.
Genetics of Kidneys in Diabetes (GoKinD): This program
facilitates investigator-driven research into the genetic
basis of diabetic kidney disease through a biospecimen
repository. Individuals with type 1 diabetes were screened
to identify two subsets, one with clear-cut kidney disease
and another with normal kidney function despite long-term
diabetes. Nearly 10,000 DNA, serum, plasma, and urine
samples—plus genetic and clinical data—from more than
1,700 adults with diabetes have been collected. The
entire GoKinD collection is being genotyped for
whole-genome association studies as part of the
previously described Genetic Association Information
Network (GAIN).
The Environmental Determinants of Diabetes in the Young:
Pinpointing the environmental factors, such as infectious
agents or diet, that can trigger type 1 diabetes in
genetically susceptible individuals is crucial to developing
prevention strategies. To address this knowledge gap, NIH
established The Environmental Determinants of Diabetes in
the Young (TEDDY) consortium. This international consortium
is enrolling newborns at high genetic risk and following them
until age 15 to identify environmental triggers for type 1
diabetes. The study is amassing the largest set of data and
samples in the world for newborns at risk for type 1 diabetes.
- For more information, see http://teddy.epi.usf.edu
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation and Chapter 3: Epidemiological and Longitudinal Studies.
- (E) (NIDDK, CDC, NIAID, NIEHS)
The Gila River Indian Community Longitudinal Study: :
NIH's Phoenix Epidemiology and Clinical Research Branch
studies type 2 diabetes as it occurs among Pima Indians
of Arizona, who have the highest prevalence of diabetes
in the world. Working closely with Pima volunteers, the
Branch has made substantial progress in identifying genetic,
physiologic, and behavioral factors that lead to obesity and
diabetes. The Branch also has facilitated improved treatment
and prevention services in this community, leading to
improved blood glucose control and blood pressure in Pima
with diabetes. One important result is that the rate of
kidney failure due to diabetes in Pima age 45 and older
has declined since 1990.
Type 1 Diabetes TrialNet: NIH is supporting this
international network of investigators, clinical centers,
and core support facilities that conducts research to advance
knowledge about type 1 diabetes and tests strategies for
its prevention and early treatment. TrialNet recently
launched a clinical trial to test whether oral insulin
could prevent or delay type 1 diabetes in people with a
certain disease marker. The network also completed enrollment
of two trials to determine whether medicines to slow the
immune response could prevent further insulin-producing
beta cell destruction in people newly diagnosed with type
1 diabetes. The TrialNet infrastructure is critically
important for testing emerging therapies for prevention and
early treatment.
Prevention of Trauma-Related Mental Disorders in High-Risk
Occupations: NIH is supporting a research initiative to
develop and test preemptive interventions to prevent
trauma-related disorders, such as posttraumatic stress
disorder, among occupational groups at high risk for
trauma exposure, such as the military, fire fighters,
police, and rescue workers.
The U.S. Surgeon General's Family History Initiative:
Many people see most diseases as the result of interactions
of multiple genes and environmental factors. Health care professionals
have known for a long time that common diseases, such as
heart disease, cancer, and diabetes, and rare diseases,
such as hemophilia, cystic fibrosis, and sickle cell anemia,
can run in families. The U.S Surgeon General's Family History
tool was created in a collaborative effort among the Office
of the Surgeon General, NIH, CDC, AHRQ, and the Health
Resources and Services Administration (HRSA). The U.S.
Surgeon General's Family History tool (available in both
English and Spanish) is free and has proven to be an
effective personalized tool for individualizing preventive
care and disease prevention—in other words, maintaining
good health. Recently updated, this tool allows an individual
to record health conditions that have affected his or her
relatives. It utilizes a three-generation pedigree to gather
information on health conditions in one's family to help
doctors take action to keep individuals and families healthy.
Transdisciplinary Tobacco Use Research Centers:Multiple
Institutes at NIH are co-funding seven collaborative,
transdisciplinary centers to identify familial, early
childhood, and lifetime psychosocial pathways related
to smoking initiation, use, cessation, and patterns of
dependence. Research on genetics of addiction, physiological
biomarkers, and the use of advanced imaging techniques can
lead to individualized and community approaches for tobacco
prevention and treatment. This model demonstrates the
feasibility and benefits of scientific collaboration across
disciplines and public-private partnerships.
- For more information, see http://dccps.nci.nih.gov/tcrb/tturc
- This example also appears in Chapter 2: Cancer and Chapter 2: Life Stages, Human Development, and Rehabilitation.
- (E) (NCI, NIAAA, NIDA)
Retinopathy Occurs in Middle-aged Adults Even Without
Diabetes: Signs of retinopathy are common in the eyes
of the elderly, particularly in those with diabetes. In
the Atherosclerosis Risk in Communities (ARIC) study,
African American subjects were significantly more likely
to have signs of retinopathy (13 percent) compared with
White subjects (5.5 percent). Among people with diabetes,
27 percent had signs of retinopathy. Unexpectedly,
retinopathy signs were also observed in 4.3 percent
of people who did not have frank diabetes but tended to
have elevated blood pressure. Future studies will examine
whether these signs of retinopathy result from high blood
pressure and whether they indicate an increased risk of
systemic cardiovascular disease or predict a subsequent
diagnosis of diabetes.
Environmental Triggers and Skin Diseases: CDC has
excluded patients with eczema (also known as atopic
dermatitis) from smallpox vaccination programs
(in response to bioterrorism threats). There is
concern of the risk of spreading vaccinia virus
from the vaccine to the skin, which can cause eczema
vaccinatum, an overwhelming and potentially lethal
systemic infection. Researchers have learned that
vaccinia virus grows much more in atopic dermatitis
skin samples than in normal skin. Also, atopic dermatitis
skin samples have lower levels of naturally occurring
antimicrobial peptides, which could contribute to atopic
dermatitis patients' susceptibility to eczema vaccinatum.
Osteoarthritis: African Americans have a higher risk
of bilateral radiographic (x ray-defined) osteoarthritis
of the knee and hip than Whites. Two NIH-funded studies
have revealed that mechanical stress can increase the
production and release of osteoarthritis-related biomarkers.
The research highlights the importance, when analyzing
biomarkers, of considering the type and degree of physical
activity in which patients with osteoarthritis participate.
Bone Health: NIH researchers have established reference
curves for bone mineral content and density in children.
The early findings are now available according to age, sex,
and race and can be used to help identify children with bone
deficits and to monitor changes in bone in response to
chronic diseases or therapies. Early study findings showed
that bone minerals continue to accrue beyond the teenage
years, so the study will continue as the adolescent subjects
approach young adulthood. In another study, NIH scientists
discovered two genes for osteogenesis imperfecta, or brittle
bone disease. The genes affect how collagen, an important
building block for bone, is formed. Although there is no
treatment for the disorder, the findings allow researchers
to test families who have lost a child to osteogenesis
imperfecta for the presence of the defective genes.
The Rapid Response Program: In April 2002, the Task
Force on College Drinking released its seminal report A Call
to Action: Changing the Culture of Drinking at U.S. Colleges.
As part of its college focus, NIH initiated support of
collaborations between university personnel who have
responsibility for alcohol programs on various campuses
and established researchers in college drinking to
implement and evaluate programs to reduce underage alcohol
use and its consequences. These programs include:
- RFA AA-03-008: Research Partnership Awards for Rapid
Response to College Drinking Problems. Five U01
(cooperative agreement) 5-year grants were awarded
in December 2002.
- PAR-03-133: Rapid Response to
College Drinking Problems. Fifteen 3-year grants were
awarded in June 2003.
This rapid funding mechanism (U18, cooperative agreement)
supports timely research on interventions to prevent or
reduce alcohol-related problems among college students.
It was intended to support studies of services or
interventions that could capitalize on natural
experiments (e.g., unanticipated adverse events,
policy changes, new media campaigns, campus-community
coalitions, etc.). Each U18 grantee was required to
partner with a U01 grantee. Together, these pairs,
working with NIH Scientific Staff Collaborators,
jointly design, develop, implement, and evaluate
college drinking projects on their campuses.
- This example also appears in
Chapter 2: Life Stages, Human Development, and
Rehabilitation, Chapter 3: Epidemiological and
Longitudinal Studies, and Chapter 3: Health
Communication and Information Campaigns and
Clearinghouses.
- (E) (NIAAA)
Underage Drinking Research Initiative: In 2004,
NIH launched this ongoing initiative with the goal of
obtaining a more complete and integrated scientific
understanding of the environmental, biobehavioral, and
genetic factors that promote initiation, maintenance,
and acceleration of alcohol use among youth, as well
as factors that influence the progression to harmful
use, abuse, and dependence, all framed within the
context of overall development. Activities and
accomplishments in 2007 include:
- Provided the scientific foundation for The Surgeon
General's Call to Action to Prevent and Reduce Underage
Drinking (released March 6, 2007) and for the ongoing
work of the Interagency Coordinating Committee on
Preventing Underage Drinking
- Convened scientific meetings of experts, including
the Underage Steering Committee, which met four times
over a 2-year period; a Meeting on Diagnosis of Alcohol
Use Disorders among Youth (April 2006); and a Meeting on
Screening for Child and Adolescent Drinking and Alcohol
Use Disorders Among Youth (June 2007)
- Issued three RFAs, including Underage Drinking:
Building Health Care System Responses (four projects
awarded in FY 2006), Impact of Adolescent Drinking on
the Developing Brain (five projects awarded in FY 2007),
and Alcohol, Puberty and Adolescent Brain Development
(three projects awarded in FY 2007)
- Published Alcohol Research & Health Volume 28,
Number 3, Alcohol and Development in Youth: A
Multidisciplinary Overview
- Published a supplement of seven developmentally
focused papers covering a broad range of underage
drinking topics (accepted for the journal Pediatrics).
Specialized Centers of Research on Sex and Gender Factors
Affecting Women's Health (SCORs): ORWH led the development
and implementation of a second round of SCORs with
co-funding from five NIH institutes and FDA. The
interdisciplinary nature of these research centers provides
innovative approaches to advancing research on the influence
of sex and gender as it relates to health and disease.
Primary research areas funded include chronic pain,
pregnancy, substance abuse, irritable bowel syndrome and
interstitial cystitis, mental health, polycystic ovarian
syndrome, and urologic health.
Gene Influences Antidepressant Response: Whether
depressed patients will respond to an antidepressant
depends in part on which version of a gene they inherit.
Having two copies of one version of a gene that codes for
a component of the brain's mood-regulating system increased
the odds of a favorable response to an antidepressant by up
to 18 percent, compared to having two copies of the other,
more common version.
Genetic Resources/Tools
Medical Sequencing: The completion of the human genome
sequence, as well as genomic sequences of numerous other
organisms, has already made a substantial impact on both
biological and medical research. Public access to the raw
data produced from these large-scale sequencing efforts has
empowered many additional studies about the genomic
contributions to disease. To expedite the transition from
research data to medical practice, NIH supports initiatives
that both drive technology that will make whole-genome
sequencing affordable and produce data useful to biomedical
research. Making affordable the sequencing of any
individual's complete genome will allow personalized
estimates of future disease risk and improve prevention,
diagnosis, and treatment of disease. NIH's medical
sequencing program is utilizing DNA sequencing to identify
the genes responsible for rare, single-gene diseases;
sequence all of the genes on the X chromosome to identify
the genes involved in sex-linked diseases; and survey the
range of variants in genes known to contribute to common
diseases.
Population Genomics, GAIN, and GEI: In February 2006,
HHS announced the creation of two related groundbreaking
initiatives in which NIH is playing a leading role. The
Genetic Association Information Network (GAIN) and the
Genes, Environment, and Health Initiative (GEI) will
accelerate research on the causes of common diseases.
GAIN is a public-private partnership among NIH, the
Foundation for NIH, Pfizer, Affymetrix, Perlegen, the
Broad Institute, and Abbott. GEI is a trans-NIH effort
combining comprehensive genetic analysis and environmental
technology development to understand the causes of common
diseases. Both GAIN and GEI are powered by completion of
the HapMap, a detailed map of the 0.1 percent variation
in the spelling of our DNA that is responsible for
individual predispositions for health and disease.
Data from GAIN will help to narrow the hunt for genes
involved in six common diseases. In June 2007, the first
GAIN dataset, on attention deficit hyperactivity disorder,
was released. GEI will provide data for approximately
another 15 disorders and will develop enhanced technologies
and tools to measure environmental toxins, dietary intake,
and physical activity, as well as an individual's biological
response to those influences.
Multiplex Initiative: With the completion of the
sequence of the human genome, genetic susceptibility tests
that give personalized information about risk for a variety
of common health conditions are now being developed and
marketed. This genetic information ultimately will improve
primary care by enabling more personalized treatment
decisions for common diseases like diabetes and heart
disease. This information also might motivate patients
to change unhealthy behaviors. NIH investigators have teamed
with the Group Health Cooperative in Seattle and the Henry
Ford Health System in Detroit to launch a study to
investigate the interest level of healthy young adults in
receiving genetic testing for eight common conditions.
Called the Multiplex Initiative, the study will also look
at how people who decide to have the tests interpret and
use the results in making health care decisions. One
thousand subjects who meet the study's eligibility
requirements will be offered free multiplex genetic
testing. The testing is designed to yield information
about 15 different genes that play roles in common
diseases such as type 2 diabetes and coronary heart
disease. Trained research educators will make follow-up
telephone calls to help subjects interpret and understand
test results, and subjects will receive newsletters to
update them on new developments about the tested genes.
This research should provide insights into how best to
utilize the powerful tools of genomic medicine to improve
health.
- For more information, see http://www.genome.gov/25521052
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Genomics.
- (E/I) (NHGRI)
Candidate Gene Association Resource: Over the years,
NHLBI has supported a number of major population studies
that have collected extensive data on cardiovascular disease
and its risk factors and manifestations. To increase the
utility of the data for conducting genetic association
studies, NIH initiated the Candidate Gene Association
Resource program in FY 2006. This new resource will have
the capacity to perform high-throughput genotyping for up
to 50,000 subjects in cohort studies that have stored
samples and data available on a wide array of
characteristics (phenotypes) associated with heart,
lung, blood, and sleep disorders. The linked
genotype-phenotype data will form an invaluable resource
for investigators seeking to identify genetic variants
related to those disorders.
Enhancing Development of Genome-wide Association Methods
(ENDGAME): The ENDGAME consortium, which comprises
11 interactive teams of investigators, has been initiated
to explore new approaches for designing and conducting
genome-wide association studies (GWAS) of complex diseases.
ENDGAME investigators are developing and testing innovative,
informative, and cost-effective study designs as well as
analytical strategies and tools for performing the studies.
All strategies and tools developed will be made available
to the scientific community. Results from ENDGAME are
expected to greatly enhance the utility of GWAS for
increasing understanding about genetic variations and
their role in health and disease.
- This example also appears in Chapter 3:Genomics
- (E) (NHLBI, NCI, NHGRI, NIEHS, NIGMS)
Framingham SNP-Health Association Resource (SHARe): The
Framingham SHARe is a comprehensive new effort by NIH and
the Boston University School of Medicine to pinpoint genes
underlying cardiovascular and other chronic diseases. The
program builds on the Framingham Heart Study, which was
begun in 1948 to identify factors that contribute to
cardiovascular disease, and on other NIH-funded research
demonstrating that common but minute variations in human
DNA, called single nucleotide polymorphisms (SNPs), can be
used to identify genetic contributors to common diseases.
The initiative will examine more than 500,000 genetic
variants in 9,000 study subjects across three generations.
NIH will develop a database to make the data available to
researchers around the world. The database will help
researchers integrate the wealth of information collected
over the years in the Framingham study with the new
genetic data, resulting in an increased understanding
of genetic influences on disease risk, manifestation,
and progression. Because of its uniqueness in including
three generations of subjects with comparable data
obtained from each generation at the same age, the
Framingham Heart Study is the first study to be
included in the SHARe initiative. NIH is currently
considering expansion of SHARe to include other large
longitudinal studies, such as the Jackson Heart Study
and the new Hispanic Community Health Study.
Hispanic Community Health Study: In October 2006, NIH
began the largest long-term epidemiological study of health
and disease ever conducted in people of Latin American
heritage living in the United States. The project, which
will include about 16,000 subjects, is designed to identify
factors that predispose individuals to develop heart disease,
stroke, asthma, COPD, sleep disorders, dental disease, hearing
loss, diabetes, kidney disease, liver disease, cognitive
impairment, and other chronic conditions. Characteristics
such as diet, physical activity, obesity, smoking, blood
pressure, blood lipids, acculturation, socioeconomic status,
psychosocial factors, occupation, health care access,
environment, and use of medications and dietary supplements
will be assessed.
- For more information, see http://www.nhlbi.nih.gov/new/press/06-10-12.htm
- This example also appears in Chapter 2: Minority Health and Health Disparities and Chapter 3: Epidemiological and Longitudinal Studies.
- (E) (NHLBI, NCMHD, NIDCD, NIDCR, NIDDK, NINDS, ODS)
Treating Chronic Disease and Comorbidities
HBO Addiction Documentary: NIH collaborated with
Home Box Office (HBO) to create a 90-minute documentary,
Addiction, which aired on March 15, 2007. An NIH expert
in the treatment of alcoholism was one of several principal
spokespersons for the documentary and was featured in a
supplementary broadcast on treatment advances. Several NIH
grantees appeared in the documentary. A general-audience
HBO book was produced to accompany the film.
- For more information, see http://www.hbo.com/addiction
- This example also appears in Chapter 3: Health Communication and Information Campaigns and Clearinghouses.
- (E) (NIAAA, NIDA)
Success in Treating Drug Addiction Internationally:
International efforts to disseminate effective drug abuse
treatments have seen success in countries with epidemic
opiate addiction and/or HIV problems. Because of NIH
research demonstrating that addiction is a chronic,
relapsing disease that can be effectively treated, a
culture change is starting to occur in these countries.
For example, despite experiencing severe drug problems,
Malaysia lagged behind in the treatment of drug addiction and
related disorders, even as it coped with having the
second-highest HIV prevalence rate among adult populations
and the highest proportion of HIV cases from injection drug
use. Historically, drug abusers were rehabilitated
involuntarily in correctional facilities, and although 60
percent of prisoners had drug-related offenses, no or
minimal treatment was available in prison and no medications
were permitted. This primarily criminal treatment approach
had limited effectiveness, which led to widespread public
dissatisfaction and the recent introduction of medications
for addiction. These include naltrexone (1999),
buprenorphine (2001), and methadone (2003). These drug
treatment programs, which were rapidly embraced by the
country's medical community, have resulted in tens of
thousands of opiate-dependent patients receiving medical
treatment. Now the Ministry of Health, rather than the
Ministry of Security, has authority for providing medical
treatment for heroin addiction. This shift signals a
remarkable change in Malaysian policies and approaches to
addiction and an important opportunity to develop,
implement, and disseminate effective treatments. A similar
success story is starting to unfold in China as well.
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC):
The DCCT demonstrated that intensive control of blood
glucose levels reduced complications of the eyes, nerves,
and kidneys in patients with type 1 diabetes. Long-term
findings from the follow-on EDIC study show that intensive
control lowers risk of heart disease. This research
revolutionized disease management, leading to the
recommendation that patients should begin intensive therapy
as early as possible. EDIC recently found that recurrent
hypoglycemia associated with intensive control does not
affect patients' long-term cognitive function. After more
than 20 years of studying this patient cohort, crucial
insights continue to emerge.
Practical Clinical Trials: NIH has completed primary
and secondary phases of several practical clinical trials
that have examined treatment effectiveness for mental
disorders such as schizophrenia, bipolar disorder, and
depression. The infrastructure developed for each of these
large multisite trials—involving more than 10,000 subjects
at more than 200 sites—has forged efficient, effective, and
collaborative relationships between scientists and
clinicians throughout the country. To capitalize on the
national networks established for the trials, NIH will
fund infrastructure-only support for the platform of
clinical sites and an administrative core. It is anticipated
that the platform will serve as a critical foundation for
supporting subject enrollment, facilitating communication
among trial sites, maintaining up-to-date training in
diagnosis and treatment, and providing needed administrative
organization.
Scientific Basis of the Placebo Effect: The placebo
effect can be defined as the measurable, observable, or felt
changes that occur during, but are not directly attributable
to, a specific health intervention. It is a ubiquitous and
frequently powerful phenomenon that operates in all forms of
medicine, so good clinical research is designed to account
for its effects as well as those of the intervention under
study. Because of the power of the placebo effect, it is
equally important to understand the mechanisms by which it
operates and to explore how its benefits might be maximized
to enhance the quality and effectiveness of all forms of
health care. An ongoing NIH initiative is examining multiple
aspects of the placebo effect through interdisciplinary
investigations employing molecular, physiological,
biochemical, immunological, genetic, behavioral, and social
science approaches. This work is beginning to shed light on
many facets of the placebo effect. For example, one recently
published study showed that placebo-associated pain relief
was correlated with activation of areas of the brain that
are associated with pain relief that occurs through both
innate mechanisms and with use of opioid narcotics. Other
ongoing studies are examining the role and importance of the
placebo effect in the relationship between patient and
health care provider.
The Scientific Basis of Acupuncture: Ongoing research
on acupuncture includes a substantial portfolio of basic and
translational studies employing state-of-the-art
neuroimaging technology. This work is beginning to provide
powerful scientific insight into the potential
neurobiological mechanisms of action by which acupuncture
might work. Clinical trials of acupuncture for a number of
medical conditions are also under way, including studies
examining (1) the potential role of traditional acupuncture
as an additive/alternative treatment for the prevention of
acute cardiac events in patients with coronary artery disease,
(2) whether manual or electro-acupuncture contributes to
neurological recovery after spinal cord injury, and 3)
the efficacy of acupuncture in relieving post-thoracotomy
pain syndrome (severe and persistent aching or burning pain
along surgical scars in the chest).
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System and Chapter 3: Clinical and Translational Research.
- (E) (NCCAM)
Gene Therapy for Leber's Congenital Amaurosis (LCA):
LCA is a rare, inherited retinal degenerative disease that
causes severe vision loss in infancy. Although the disease
is currently untreatable, NIH-funded investigators have
restored vision in dogs with LCA by using gene therapy to
replace defective copies of the retinal gene RPE65.
Furthermore, new evidence suggests retinal activity
also restores function to the brain's visual center.
Investigators have recently begun to translate this
promising therapy to patients with LCA.
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NEI)
Multicenter Uveitis Steroid Treatment (MUST) Trial:
Uveitis, a disease that causes inflammation in middle layers
of the eye, is a major cause of blindness in the United
States and often requires systemic, long-term treatment
with oral corticosteroids and immunosuppressants. Ideally,
a local therapy impacting only the eye is preferable to
systemic therapy. This comparative effectiveness trial
tests a new intraocular implant therapy in patients with
severe uveitis.
- For more information, see http://www.musttrial.org
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NEI)
COPD: Learn More, Breathe Better: Through its new
education campaign, COPD: Learn More, Breathe Better,
NIH is raising public and professional awareness about
chronic obstructive pulmonary disease (COPD). Launched in
January 2007, the campaign is a cooperative effort, engaging
the public, health care providers, health insurers, and
researchers in improving COPD diagnosis and treatment. The
campaign relies on print and radio public service
announcements and printed informational materials intended
for distribution to patients with COPD, persons at risk for
the disease, health care professionals, and community
organizations. Joining NIH in implementing this new campaign
by promoting it among their constituencies are more than 20
partners, including the American Academy of Family Physicians,
the American Lung Association, the American Thoracic Society,
the American College of Chest Physicians, and the U.S. COPD
Coalition.
Pediatric Circulatory Support: Options for the
circulatory support of pediatric patients younger than
age 5 are currently limited to short-term extracorporeal
devices, the use of which is often complicated by infection,
bleeding, and blood clots. Recognizing the need for
additional options, NIH established a program to facilitate
the development of new circulatory support systems for
infants and children with congenital or acquired
cardiovascular diseases. The program supports five
research groups developing a variety of devices for
different pediatric applications. The common objective
for the devices is to provide reliable circulatory support
for infants and children while minimizing adverse effects.
Sildenafil for Pulmonary Hypertension in Adult Patients
with Sickle Cell Disease: In 2006, NIH began a new
study to evaluate a course of treatment with sildenafil
in patients with sickle cell disease who have pulmonary
hypertension. A randomized, double-blind, placebo-controlled,
Phase II clinical trial is testing the drug's safety and
efficacy in improving exercise capacity, symptoms, and
measures of circulatory function. The trial involves
approximately 180 patients at extramural sites and at
the NIH Clinical Center. Because pulmonary hypertension
occurs frequently in persons with sickle cell disease and
confers a high risk of death, a positive outcome of this
trial would represent an important step toward improved
patient care.
Monitoring Organ Rejection Using MRI: Organ
transplants give patients a new lease on life. However,
preventing their immune systems from rejecting the
transplanted organ sometimes presents a challenge.
Physicians must strike a balance between suppressing the
immune system so that it does not reject the organ and
maintaining enough immune activity to ward off infections.
Tracking how the body accepts the new organ is critical to
this process. The current gold standard for monitoring
organ rejection is tissue biopsy, an invasive procedure in
which a physician removes a small sample of the transplanted
organ for testing. Biopsy has two drawbacks: patient
discomfort (the physician must perform the procedure
multiple times) and poor selectivity (biopsy removes tissue
from only a limited number of sites and can miss rejection
starting elsewhere in the organ). To overcome these
limitations, NIH-supported researchers are developing a
new method to monitor organ rejection with MRI. They label
macrophages (immune cells) with polymer-coated, micron-sized
iron oxide particles. These magnetic particles allow the
migration of the macrophages to rejection sites in the
transplanted organ to be clearly tracked by MRI. At present,
this work is being performed on rats, but the investigators
are extending it to large animals and humans. If successful,
the approach could be used to optimize the administration of
immunosuppressant drugs in clinical situations.
Asthma Exacerbations—Biology and Disease Progression:
In FY 2005, NIH began a basic and clinical research
initiative to improve understanding of the causes of
asthma exacerbations and to facilitate the development of
more effective treatments to control symptoms. Twelve
projects have been funded under this initiative. As part
of NIH GPRA reporting activity, NIH is assessing the
progress of the initiative through an ongoing GPRA goal,
to identify and characterize two molecular pathways of
potential clinical significance that may serve as the
basis for discovering new medications for preventing and
treating exacerbations, by 2014.
Long-Term Oxygen Treatment Trial (LOTT): Although
oxygen therapy is known to benefit patients with COPD who
experience severe hypoxemia (low blood oxygen level) when
resting, the value of this treatment in patients with less
serious disease is not known. In November 2006, NIH and the
Centers for Medicare and Medicaid Services launched the LOTT,
the largest-ever randomized clinical trial of the
effectiveness and safety of long-term, home oxygen therapy
for patients with COPD and moderately severe hypoxemia.
Results are expected to shed light on the role of oxygen
therapy in the management of these patients and to provide
a basis for Medicare coverage decisions. The LOTT trial is
the focus of a new NIH GPRA goal to be included in GPRA
reporting in 2007: by 2012, assess the efficacy of long-term
oxygen treatment in patients with COPD and moderate hypoxemia.
Programs to Accelerate Medication Development for Alcoholism Treatment:
Alcoholism is a complex heterogeneous disease caused by the
interaction between multiple genetic and environmental
factors that differ from one drinker to another. Therefore,
a diverse repertoire of medications is needed to provide
effective therapy to a broad spectrum of alcohol-dependent
individuals. Although promising compounds have been
identified, developing medications is a long and costly
process with a low probability of success for any single
agent. NIH has initiated collaborations with the
pharmaceutical industry to ensure their interest in
taking promising compounds through the final phase of
clinical trials and subsequent FDA consideration. As
part of this approach, two new programs have been initiated:
- Laboratories have been established to screen promising compounds with animal models, enabling faster determination of those that merit advancement to large, multisite studies. Animal studies have already produced several targets for human studies that are now under way, such as rimonabant, a cannabinoid CB1 receptor blocker, and antalarmin, a corticotropin-releasing factor receptor blocker.
- A network of sites is being developed to conduct early Phase II proof-of-concept human trials. NIH will encourage the pharmaceutical industry to screen proprietary compounds in the preclinical models and, when results are positive, test them in the early human trials network.
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System and Chapter 3: Clinical and Translational Research.
- (E/I) (NIAAA) (GPRA Goal)
Improving Transplantation Outcomes: Organ
transplantation prolongs survival and improves quality of
life for children and adults with a wide range of diseases.
Yet despite advances in organ transplantation, organ
recipients rarely achieve normal life expectancy and
health-related quality of life. To improve the outcome
of organ transplantation, NIH supports the Clinical Trials
in Organ Transplantation (CTOT) initiative, a cooperative,
multisite consortium that conducts interventional and
observational clinical studies, as well as studies of
the mechanisms of graft rejection. The consortium
includes 34 clinical sites and 30 immunology laboratories
at 13 universities. Five clinical trials are currently
enrolling individuals undergoing kidney, heart, liver, or
lung transplantation.
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NIAID, NHLBI, NIDDK) (GPRA Goal)
Blending Initiative: Bench to Bedside to Community:
Efforts to systematically move science-based interventions
and practices into community settings are exemplified in the
testing of drug abuse treatment approaches directly in the
community settings where they will be used by drug treatment
professionals who are trained to implement them. This work
is occurring through the National Drug Abuse Treatment
Clinical Trials Network at NIH, which involves practitioners
from community treatment programs not only in formulating
research protocols, but also in providing real-world feedback
on their success and feasibility. The adoption of the addiction
medication buprenorphine by a growing number of community
treatment programs treating patients with opioid addiction
is an example of real culture change issuing from NIH clinical
research. A similar approach is under way to enhance treatment
for drug-addicted individuals involved with the criminal
justice system through research supported under the Criminal
Justice-Drug Abuse Treatment Studies (CJ-DATS) initiative.
It seeks to achieve better integration of drug abuse treatment
for criminal offenders with other public health and public
safety forums and is a collaborative effort by NIH and multiple
Federal agencies and health and social service professionals.
These initiatives are helping to change the culture of how drug
abuse treatment is delivered in this country.
Treatments to Fight Methamphetamine Addiction: The
abuse of methamphetamine—a potent and highly addictive
psychostimulant—is a serious problem in the United States.
Methamphetamine abuse can have devastating medical,
psychological, and social consequences. Adverse health
effects include memory loss, aggression, psychotic behavior,
heart damage, and abnormal brain function. Methamphetamine
abuse also contributes to increased transmission of
hepatitis and HIV/AIDS and can spawn increased crime,
unemployment, and other social ills. The good news is
that methamphetamine abuse and addiction are treatable,
and people do recover. As methamphetamine abuse has
increased, so has NIH's support of research to combat
it, including research on genetics, brain development,
and translation of findings. This research has led to the
development of two effective behavioral therapies for
methamphetamine addiction: (1) the Matrix Model, consisting
of a 16-week program that includes group and individual
therapy and addresses relapse prevention, behavioral
changes, establishment of new drug-free environments, and
other issues; and (2) Motivational Incentives for Enhanced
Drug Abuse Recovery, a cost-effective incentive method for
cocaine and methamphetamine addiction that has been shown to
sustain abstinence in twice the number of subjects engaged
in treatment as usual. Increasingly, community treatment
providers nationwide are implementing motivational
incentives as part of drug addiction treatment.
Nonalcoholic Steatohepatitis (NASH) Clinical Research
Network: : NASH is strongly associated with obesity
and type 2 diabetes, conditions that have increased
dramatically in recent decades. Network research addresses
GPRA Goal SRO-4.3. The Network is conducting a randomized
clinical trial to evaluate the safety and efficacy of the
insulin-sensitizing drug pioglitazone or vitamin E compared
to placebo for the treatment of non-diabetic adults with NASH.
Also, in a separate trial in children, the Network is
comparing the insulin-sensitizing drug metformin, vitamin E,
and placebo in treating nonalcoholic fatty liver disease.
- For more information, see http://www.jhucct.com/nash
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation
- (E) (NIDDK, NCI, NICHD) (GPRA Goal)
Age-Related Eye Disease Study, Part 2 (AREDS2):
Age-related macular degeneration (AMD) is the leading cause
of blindness in the elderly in the United States and will be
an increasing burden in future years, based on demographics.
The original AREDS study, completed in 2005, demonstrated
that antioxidant vitamin and mineral supplements reduced
the progression to advanced AMD by 25 percent. Building on
these landmark findings, AREDS2 is assessing additional
supplements (lutein, zeaxanthin, and long-chain omega-3
fatty acids) as a treatment for AMD and cataracts. AREDS2
is also evaluating the effects of eliminating beta-carotene
and/or reducing zinc in the original AREDS formulation on
AMD progression. AREDS2 investigators will also explore
gene-environment interactions in the development of these
conditions, cognitive function, and cardiovascular health.
- For more information, see http://public.drcr.net
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NEI)
Diabetic Retinopathy Clinical Research Network (DRCR.net):
Diabetes, a leading cause of blindness in working-age adults, causes blood vessels in the retina to leak and can lead to retinal
detachment. Laser treatment is effective but is not optimal. DRCR.net is a collaborative, nationwide, public-private network of eye
doctors and investigators in 165 clinical sites conducting clinical research of diabetes-induced retinal disorders (diabetic
retinopathy and diabetic macular edema) with the aim of evaluating promising new therapies. DRCR.net serves as a model network to
provide the infrastructure to facilitate multiple concurrent and consecutive clinical trials of innovative therapies, to rapidly
develop and initiate new protocols, and to interact with industry partners while ensuring scientific rigor and high ethical standards.
- For more information, see http://public.drcr.net
- This example also appears in Chapter 3: : Clinical and Translational Research.
- (E) (NEI)
Comprehensive Sickle Cell Centers (CSCCs): The CSCCs
were established in 1972 in response to a Presidential
initiative and a Congressional mandate to support
multidisciplinary research to expedite the development
and application of new knowledge for improved diagnosis
and treatment of sickle cell disease. In addition to basic
research, training, and patient services activities, the
CSCCs currently support multicenter Phase II trials,
neurocognitive and neuroimaging studies, development of a
collaborative database, and a study on the epidemiology of
priapism (painful, prolonged erection) among patients with
sickle cell disease. Ten centers are funded through FY 2007,
and the program will be renewed in FY 2008.
Improving the Lives of Asthmatic Children in the Inner
City: The NIH Inner-City Asthma Consortium (ICAC)
evaluates the safety and efficacy of promising immune-based
therapies to reduce asthma severity and prevent disease
onset in inner-city children, who are disproportionately
affected by asthma. An ICAC longitudinal birth cohort study
involving 500 inner-city children is investigating the
immunologic causes of the development of recurrent wheezing,
a surrogate marker for asthma in children younger than age 3.
The ICAC is also conducting a multicenter trial to evaluate
the safety and efficacy of Xolair (omalizumab) in children
with moderate to severe allergic asthma whose symptoms are
inadequately controlled with inhaled steroids. Finally,
researchers are conducting a clinical trial to determine
the safety and dosing levels of a potential new allergy
immunotherapy for cockroach allergen, which previous ICAC
findings showed are a major determinant of asthma severity
among inner-city children.
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Epidemiological and Longitudinal Studies.
- (E) (NIAID)
Dialysis Access Consortium: Arteriovenous fistulas
and grafts are the two most common methods of gaining
repeated access to the circulation of patients on
hemodialysis. The Dialysis Access Consortium (DAC)
is conducting two trials to assess the impact of
anticlotting reagents in preventing early failure in
arteriovenous fistulas and grafts. The Arteriovenous
Fistula Trial is evaluating the ability of clopidogrel
to maintain access patency, while the Arteriovenous Graft
Trial is evaluating the ability of aspirin combined with
extended-release dipyridamole to maintain access patency.
Inflammatory Bowel Disease: Randomized Trial of
Rosiglitazone for Ulcerative Colitis: Current
treatments for ulcerative colitis, a form of inflammatory
bowel disease, are not effective for all patients.
NIH-supported scientists demonstrated that rosiglitazone,
a medication used to treat type 2 diabetes, reduced
inflammation in an animal model of ulcerative colitis.
Subsequently, a small clinical study showed that
rosiglitazone was effective in controlling ulcerative
colitis symptoms. NIH is now supporting a full-scale
clinical trial of this potential new therapy for
ulcerative colitis.
Longitudinal Assessment of Bariatric Surgery (LABS):
The multicenter, NIH-funded LABS consortium is analyzing the
risks and benefits of bariatric surgery as a treatment for
extreme obesity in adults. Because bariatric surgery is also
sometimes used in clinical practice as a treatment for
severely obese adolescents, NIH is also supporting an
observational study of teens already scheduled for surgery,
Teen-LABS, to collect data to help determine whether it is
an appropriate treatment option for extremely obese
adolescents.
- For more information, see http://tinyurl.com/399zmt
- For more information, see http://tinyurl.com/yoer3l
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation and Chapter 3: Clinical and Translational Research.
- (E) (NIDDK, ORWH)
Polycystic Kidney Disease (PKD): The Consortium for
Radiologic Imaging Studies of PKD (CRISP) showed that MRI
could accurately track structural changes in the kidneys of
people with the more common form of PKD. An extension, CRISP
II, will continue to monitor these patients to determine
whether these changes in kidney volume predict changes in
kidney function. NIH is also conducting two clinical trials
of people with the most common form of PKD; one is in
patients with early kidney disease and another is in
patients with more advanced disease. These two trials are
the largest multicenter studies of PKD conducted to date and
are collectively termed HALT-PKD. They are testing whether
optimum blood pressure management, in combination with
medication, will slow the progression of PKD.
Stress Incontinence Surgical Treatment Efficacy (SISTEr) Trial:
The first of several studies to be conducted by the
NIDDK-funded Urinary Incontinence Treatment Network,
the SISTEr trial recently showed that the sling surgical
procedure helps more women achieve dryness than the Burch
surgical technique. Two years after surgery, 66 percent of
women who had the sling procedure and 49 percent who had the
Burch were continent.
Studies of Diabetes in Youth: Previously known as a
disease of adults, type 2 diabetes is increasingly being
observed in youth. The Treatment Options for Type 2 Diabetes
in Youth study is comparing three different treatment
strategies for children with the disease. The SEARCH for
Diabetes in Youth Study is providing key data on childhood
diabetes incidence and prevalence. SEARCH estimated that 1
of every 523 youths had physician-diagnosed diabetes in 2001.
While type 2 diabetes is increasing in children over age 10,
particularly minorities, type 1 diabetes accounts for most
new cases, with an estimated 15,000 youths diagnosed annually.
The Clinical Islet Transplantation Consortium:
The purpose of this international consortium is to develop
and implement a program of single- and/or multicenter clinical
studies, accompanied by mechanistic studies, in islet transplantation
with or without accompanying kidney transplantation, for the
treatment of type 1 diabetes. Research pursued through this
consortium aims to make improvements in the field of islet
transplantation and to share the data and results with the broad
scientific community.
Translational Research for the Prevention and Control of Diabetes and Obesity:
NIH is supporting research projects to explore ways to bring
knowledge from successful clinical research into medical
practice and community settings. Studies are seeking to
develop effective, sustainable, and cost-effective methods
to prevent and treat type 1 and type 2 diabetes and obesity
in clinical health care practice and other real-world
settings. Many of these studies focus on minority
populations disproportionately burdened by type 2 diabetes
and obesity.
Maintenance of Long-Term Behavioral Change: Behavioral
factors contribute to the development and outcomes of many
chronic diseases. Successful prevention of and treatment
for chronic diseases depend, in part, upon the sustained
maintenance of behavior change over time. This initiative
supports research projects that examine biopsychosocial
processes and test interventions designed to achieve
long-term health behavior change. Funded projects focus
on diet, physical activity, HIV prevention, smoking
cessation, drug abstinence, suicide prevention and
mammography screening. In addition, A Health Maintenance
Consortium (HMC) comprising NIH program staff, research
investigators at the individual sites, and representatives
from cosponsoring private foundations has been established
to explore the opportunities for further collaboration
across the studies.
- For more information, see http://grants.nih.gov/grants/guide/rfa-files/RFA-OB-03-003.html
- For more information, see
http://obssr.od.nih.gov/Content/Research/Request_for_Applications_%28RFAs%29/Behavioral+Change+RFA+Outcome.htm
- For more information, see http://hmcrc.srph.tamhsc.edu/default.aspx
- (E) (OBSSR, NCI, NEI, NIA, NIAAA, NICHD, NIDA, NIDDK, NIMH, NINR, ODP/ORD)
Patient-Reported Outcomes Measurement Information System
(PROMIS): This NIH Roadmap initiative is developing ways
to measure symptoms—such as pain, fatigue, physical functioning,
social-role participation, and emotional distress—that influence
quality of life across numerous chronic diseases.
Comprehensive Review of Meditation Research: A
recent comprehensive literature review on meditation
research included more than 800 studies of a variety of
forms of meditation for a number of chronic conditions,
including hypertension, coronary artery disease, and
substance abuse. The review concludes that there are
promising indications that meditation may have beneficial
effects on a variety of outcomes, including blood pressure,
perceived stress, anxiety, and behavioral modification, but
additional and higher-quality research is needed.
Mind-Body Medicine: NIH supports a substantial
portfolio of multidisciplinary clinical, translational,
and basic research on mind-body interventions, such as
meditation and Tai Chi Chuan. This effort is based on
(1) promising findings from preliminary controlled clinical
investigations and (2) laboratory evidence suggesting that
these interventions often involve or invoke well-known
biological mechanisms that are known to play key roles in
the cause of and recovery from illness and in the
preservation of health and wellness. For example:
- Investigators recently demonstrated that patients who practiced Tai Chi Chuan, a form of moving
meditation based on traditional Chinese medicine, experienced significant augmentation in levels of
immunity to the virus that causes shingles after vaccination against the virus.
- Other investigators have demonstrated that patients with chronic heart failure show
improvements in quality of life, exercise ability, and biomarkers of cardiac health
when Tai Chi Chuan is added to conventional medical care.
Research on Popular Dietary Supplements: A significant
body of research on CAM practices focuses on documenting the
safety and efficacy of various widely used dietary supplements.
Important recently reported findings include the following:
-
The combination of glucosamine plus chondroitin sulfate
did not provide significant relief of pain from
osteoarthritis of the knee in the overall study
population, although a subset of the study subjects
with moderate-to-severe pain showed significant relief
with the combined supplements.
- The dietary supplement alpha-tocopherol (a form of
vitamin E), administered at a high dosage of 1,200
IU/day for 2 years, had no effect on serum
concentrations of total, low-density lipoprotein, or
high-density lipoprotein cholesterol.
Losartan Offers Promise for the Treatment of Marfan
Syndrome: New research offers hope that losartan, a
drug commonly prescribed to treat hypertension, might
also be used to treat Marfan syndrome, a genetic disorder
that often causes life-threatening aortic aneurysms. After
discovering that Marfan syndrome is associated with a
mutation in the gene encoding fibrillin-1, researchers
tried for many years, without success, to develop
treatment strategies that involved repair or replacement
of fibrillin-1. A major breakthrough occurred when
NIH-funded researchers discovered that one of the functions
of fibrillin-1 is to bind to another protein, TGF-beta,
and regulate its effects. After careful analyses revealed
aberrant TGF-beta activity in patients with Marfan
syndrome, researchers began to concentrate on treating
the disease by normalizing the activity of TGF-beta.
Losartan, which is known to affect TGF-beta activity,
was tested in a mouse model of Marfan syndrome. The
results showed that the drug blocked the development of
aortic aneurysms as well as lung defects associated with
the disease. Based on the promising results, the NHLBI
Pediatric Heart Network, in partnership with the National
Marfan Foundation, began a clinical trial in 2007 to assess
losartan therapy in patients with Marfan syndrome.
Acute Liver Failure Study Groups: The adult and
pediatric Acute Liver Failure Study Groups address the
problem of acute liver failure due to drugs or other
factors. The groups' research has provided knowledge
and tools for managing the clinical and public health
burden of acute liver failure. In 2002, the adult Study
Group highlighted a dramatic increase in liver injury
due to the over-the-counter pain reliever acetaminophen.
The groups then developed a serum-based assay to detect
acetaminophen-induced acute liver failure in adults and
children. Current studies are testing potential therapies
to improve survival in patients with acute liver failure.
Hepatitis C Antiviral Long-Term Treatment Against
Cirrhosis (HALT-C) Trial: The HALT-C trial studies
whether long-term antiviral therapy can prevent the
progression of liver disease in people with hepatitis
C who do not respond to standard, short-term therapy.
The trial has advanced understanding of the impact of
disease severity and antiviral drug dose on response to
long-term therapy and yielded a new tool to monitor
treatment response. These advances can help health care
providers to determine which patients are unlikely to
respond to long-term antiviral therapy, so that those
patients can be spared from ineffective treatment and
its side effects.
Multidisciplinary CAM Research: Investigators are
utilizing increasingly sophisticated, multidisciplinary,
bedside-to-bench and bench-to-bedside approaches to
elucidate the efficacy, safety, and mechanisms of action
of a wide variety of CAM practices. Ongoing research
encompasses virtually all organ systems and medical and
scientific disciplines, as well as numerous CAM modalities
and practices spanning the four major CAM domains
(biologically based practices, manipulative and body-based
practices, energy medicine, and mind-body medicine),
as well as the alternative whole medical systems of which
they are a part. Guided by its 5-Year Strategic Plan,
recommendations of the National Advisory Council for
Complementary and Alternative Medicine, the plans of
other ICs, and input from expert panels and various
stakeholders, NCCAM establishes priorities to fill gaps
in the CAM research portfolio, capitalize on emerging
opportunities, and leverage resources.
Advancing Novel Science in Women's Health Research
(ANSWHR): In FY 2007, NIH published two Program
Announcements for a new grants program called Advancing
Novel Science in Women's Health Research (ANSWHR). Both
announcements are intended to promote innovative,
interdisciplinary research that will advance new concepts
in women's health research and the study of sex and gender
differences.
- For more information, see http://grants.nih.gov/grants/guide/pa-files/PAS-07-381.html
- For more information, see http://grants.nih.gov/grants/guide/pa-files/PAS-07-382.html
- (E) (ORWH, NCI, NEI, NHLBI, NHGRI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NICHD, NIDCD, NIDCR, NIDA, NIEHS, NIGMS, NIMH, NINDS, NINR, NLM, FIC, NCCAM, OBSSR, and ODS)
Research Enhancement Awards Program (REAP): NIH
successfully implemented a trans-NIH Research Enhancement
Awards Program (REAP) in both FY 2006 and FY 2007 by
awarding a total of more than $6.8 million dollars.
Sixteen grants were awarded in each fiscal year. This
program is directed at meritorious grants that have just
missed the IC pay line that will advance research on
women's health and/or the study of sex and gender factors.
Scientific areas covered by these grants include diabetes,
fibromyalgia, genetic studies of ovarian failure, health
disparities, heart failure evaluation in postmenopausal
women, HIV/AIDS, interstitial cystitis, lupus,
neuroendocrine development, pain control, rheumatoid
arthritis, smoking in pregnancy, substance abuse, and
breast cancer and CAM.
Trans-NIH Chronic Fatigue Syndrome Research: NIH
coordinates chronic fatigue syndrome research through the
trans-NIH Working Group on Research on Chronic Fatigue.
This working group developed an action plan to enhance
the status of chronic fatigue syndrome research at NIH
and among the external and intramural scientific
communities. The working group held a workshop on
grantsmanship in FY 2007 to provide researchers with
an overview of funding opportunities, an understanding
of the NIH funding process, and an opportunity to meet
with program officials. In addition, the Office of
Research on Women's Health and a subset of the working
group ICs issued an RFA in FY 2006 to explicate how the
brain, as the mediator of the various body systems involved,
fits into the schema for understanding chronic fatigue syndrome.
This RFA solicited proposals from multidisciplinary teams of
scientists to develop an interdisciplinary approach to the
study of chronic fatigue syndrome in men and women across
the lifespan and resulted in seven new research projects on
chronic fatigue syndrome.
- For more information, see http://orwh.od.nih.gov/cfs.html
- For more information, see http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-06-002.html
- For more information, see http://orwh.od.nih.gov/cfs/2006NIHfundedCFSstudies.html
- For more information, see http://orwh.od.nih.gov/cfs/cfsFundingGMWs.html
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System.
- (E) (ORWH, NIAID, NIAMS, NIAAA, NIA, NICHD, NIDA, NIDDK, NINDS, NCRR, CSR, NIEHS, NIDCR, NINR, NHLBI, NIMH, NCCAM, FIC, ODS, OBSSR)
Research to Strengthen the Dissemination and
Implementation of Evidence-Based Mental Health
Interventions: NIH continues to support
research designed to strengthen the dissemination
and implementation of evidence-based mental health
practices. NIH released a Program Announcement to
encourage transdisciplinary teams of scientists and
practice stakeholders to work together to deveop
innovative approaches for identifying and overcoming
barriers to the adoption of evidence-based interventions.
This Program Announcement also serves as the basis for a
GPRA Goal. NIH also supports research designed to enhance
implementation by providing evidence of intervention
benefits not just to the individual, but to a broader
system as well. For example, a recent study reported
that providing a minimal level of enhanced care for
employees' depression would result in significant savings
to employers.
- Wang PS et al, Arch Gen Psychiatry 2006;63:1345-53, PMID: 17146009
- For more information, see http:grants.nih.gov/grants/guide/pa-files/PAR-07-086.html
- For more information, see http://www.nimh.nih.gov/press/cost-benefitsimulation.cfm
- This example also appears in Chapter 3: Clinical and Translational Research.
- (I/E) (NIMH, NCI, NIDA, NIDCD, NINR, NIAAA, NIDCR, NIDDK, NICHD) (GPRA)
Addressing Pain and Palliative Care in Chronic Diseases
Improving End-of-Life Care: Special Supplement to the
Journal of Palliative Medicine:: In FY 2005, NIH
sponsored the State-of-the-Science Conference on Improving
End-of-Life Care. This conference addressed the current
state of end-of-life care and proposed important new
directions for end-of-life research. Key conclusions to
emerge from the conference included: the rapid increase
in older adults facing the need for end-of-life care
requires the development of research infrastructure to
better examine end-of-life issues; enhanced communication
between patients, families, and providers is crucial to
end-of-life care; and improved outcome measures are needed
to better conduct end-of-life research. In FY 2006, a
special issue of the Journal of Palliative Medicine
presented a series of papers developed from this workshop
on a wide variety of topics. The supplement includes
articles on measuring end-of-life care outcomes; analyzing
racial, cultural, and ethnic factors that influence
end-of-life care; improving care for dying children and
their families; and examining factors in the health care
system that influence end-of-life care.
Promising Approaches to Treating Chronic Pain: Opioid
analgesics are the most powerful pain medications currently
available; unfortunately, they can produce drug dependence.
Thus, an area of enormous need is the development of potent
non-opioid analgesics, for which NIH has implemented an
aggressive and multidisciplinary research program. Many of
these initiatives are yielding tangible results that stand
to revolutionize the field of pain management. At the
molecular level, cannabinoid research has shown that it
is possible to selectively activate the cannabinoid system
to provide analgesia with minimal or no psychotropic side
effects or abuse liability. New findings in basic
pharmacology reveal previously unrecognized complexity
emerging from the natural mixing of different receptors,
the targeting of which could provide a vastly expanded range
of pharmacotherapeutic effects. This approach has already
ushered in the development of promising designer molecules
that can block pain more selectively and safely. At the
cellular level, active research on a non-neuronal brain cell
type, glia, has led to the realization that glia activation
can amplify pain. This discovery suggests that targeting glia
and their pro-inflammatory products may provide a novel and
effective therapy for controlling clinical pain syndromes and
increasing the utility of analgesic drugs. At the brain
circuit level, a new approach has been developed to harness
the brain's intrinsic capacity to train itself through a
strategy in which subjects learn how to regulate pain by
viewing and then controlling images of their own brains in
real time.
Resources for Enhancing Alzheimer's Caregiver Health II
(REACH II): Family members and friends who care for
people with dementia face a variety of challenges that
can seriously compromise their own well-being.
Investigators have found that a personalized
intervention consisting of home visits, structured
telephone support sessions, and telephone check-ins
can significantly improve the quality of life for
caregivers of Alzheimer's disease patients. The study
is the first randomized, controlled trial to look at
the effectiveness of an Alzheimer's disease caregiver
support intervention for ethnically diverse populations.
Follow-up studies are needed to examine how this
intervention might be used through existing community
health service networks.
NIH Pain Consortium: The aims of the NIH Pain Consortium
are to enhance pain research and promote collaboration among
researchers across the many NIH Institutes and Centers that
have programs and activities addressing pain. The consortium
held its second annual symposium, Advances in Pain Research,
on May 1, 2007, to feature new and exciting advances in pain
research and pain management. Topics included neuropathic pain,
visceral pain, inflammatory pain, and treatment-induced pain.
Topics included NIH and extramural scientific communities,
health care providers, and the public. Consortium ICs also
issued an NIH-wide Funding Opportunity Announcement,
Mechanisms, Models, Measurement, and Management in
Pain Research, to encourage pain research and delineate
cross-cutting NIH interests in pain.
- For more information, see http://videocast.nih.gov/PastEvents.asp
- For more information, see http://painconsortium.nih.gov/index.html
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System
- (E/I) (NIDCR, CC, FIC, NCCAM, NCI, NCRR, NIA, NIAAA, NIAMS, NIBIB, NICHD, NIDA, NIDCD, NIGMS, NIMH, NINDS, NINR, OBSSR, OD, ODP/ORD, ORWH, OTT)
Behavioral Strategies to Improve Quality of Life and
Chronic Disease Outcomes: As health care advances
continue to transform previously acute conditions into
chronic conditions and individual life expectancy is
increasing, issues of quality of life have become ever
more important. Studies focusing on the management of
disease- and treatment-related symptoms have demonstrated
the capacity for behavioral strategies to mitigate the
effects of symptoms and contribute to improving short-
and long-term patient outcomes. For example, behavioral
strategies have been shown to improve patient outcomes
across various diseases, including diabetes, irritable
bowel syndrome, and asthma. In recognition of the need
for new behavioral strategies to manage chronic illness,
NIH has established a goal to develop and test, by 2012,
at least two behavioral strategies for the management of
symptoms to reduce the effects of disease, disability, or
psychological distress on quality of life and outcomes.
Beginning in FY 2008, progress toward achieving this
goal will be updated annually in the NIH section of the
President's budget submission in a report on NIH GPRA
responsibilities.
Acupuncture for Osteoarthritis of the Knee: Clinical
trials supported by NIH and others suggest that acupuncture
may have a useful role in treating a variety of chronic
painful conditions, hypertension, and obesity. For example,
in 2006 NIH-funded investigators reported findings from the
longest, largest, randomized, controlled clinical trial of
acupuncture ever conducted. The results demonstrated that
acupuncture is an effective adjunct to conventional
treatment for osteoarthritis, the most common form of
arthritis and a major cause of pain, limitation of
activity, and health care utilization among the elderly.
Study subjects receiving acupuncture had significantly
reduced disability and improved quality of life. The
innovative trial design resulted from an interdisciplinary
collaboration of rheumatologists, licensed acupuncturists,
and biostatisticians, ensuring that the research
methodology was scientifically sound and accurately
reflected acupuncture as traditionally practiced.
Orofacial Pain: Prospective Evaluation and Risk
Assessment (OPPERA): This 5-year clinical study's
longitudinal design will greatly accelerate the
identification of better treatments to control the pain
of temporomandibular muscle and joint disorders. The
OPPERA study marks one of the first prospective clinical
studies of a chronic pain disorder. A prospective study
is the gold standard of medical research: it looks
forward in time, monitoring the health of those in the
study over several years to track the onset or progression
of a disease. With the study's 5-year vantage point,
investigators will begin identifying individual genetic,
physiologic, and psychological factors that cause or
contribute to temporomandibular muscle and joint
disorders and advance virtually all aspects of
understanding and caring for these disorders.
Spine Patient Outcomes Research Trial (SPORT):
Before SPORT, many patients with back pain were
conflicted about whether to undergo surgery. Now,
people who have back pain due to a herniated disc
can be assured that a surgical procedure called lumbar
diskectomy is generally effective in relieving pain from
herniated discs, but, if their pain is tolerable, their
symptoms will probably subside, even without surgery,
over time. On the other hand, if a patient has
spondylolisthesis with stenosis, they are likely
to benefit more from decompression and fusion surgery
than from nonoperative treatments.
- Weinstein JN, et al. JAMA 2006;296:2441-50, PMID: 17119140
- Weinstein JN, et al. JAMA 2006;296:2451-9, PMID: 17119141
- Weinstein JN, et al. N Engl J Med 2007;356:2257-70, PMID: 17538085
- For more information, see
http://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2006/backpain_surgery.asp
- For more information, see
http://www.niams.nih.gov/News_and_Events/Press_Releases/2007/06_28.asp
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NIAMS, NIOSH, ORWH)
NIH Strategic Plans Pertaining to Chronic Diseases and Organ Systems
National Heart Lung and Blood Institute (NHLBI)
National Cancer Institute (NCI)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Reports from Planning Activities:
National Institute of Allergy and Infectious Diseases (NIAID)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Mental Health (NIMH)
National Institute on Drug Abuse (NIDA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Recommendations of the NIAAA Extramural Advisory Board (EAB):
National Institute of Nursing Research (NINR)
National Center for Complementary and Alternative Medicine (NCCAM)
John E. Fogarty International Center (FIC)
Office of AIDS Research (OAR)
Office of Dietary Supplements (ODS)
Trans-NIH Strategic Plans
- Strategic Plan for NIH Obesity Research
(CSR, DNRC, FIC, NCCAM, NCI, NCMHD, NCRR, NHGRI, NHLBI, NIA, NIAAA, NIAMS, NIBIB, NICHD, NIDA, NIDCR, NIDDK, NIEHS, NIMH, NINDS, NINR, OBSSR, ODP, ODS, ORWH, OSP)
- Advances and Emerging Opportunities in Type 1 Diabetes Research: A Strategic Plan
(CC, CSR, NCCAM, NCMHD, NCRR, NEI , NHGRI, NHLBI, NIA, NIAAA, NIAID, NIBIB, NICHD, NIDA, NIDCD, NIDCR, NIDDK, NIEHS, NIGMS, NIMH, NINDS, NINR, NLM)
- Action Plan for Liver Disease Research
(CSR, FIC, NCCAM, NCI, NCRR, NHGRI, NHLBI, NIA, NIAAA, NIAID, NIBIB, NICHD, NIDA, NIDCR, NIDDK, NIEHS, NIGMS, NINDS, NINR, NLM)
- NIH Action Plan for Transplantation Research (2007)
(NCI, NHLBI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NIDA, NIDCR, NIDDK, NIMH, NINDS)
Detailed Burden of Illness and Related Health Statistics
The following summary illustrates the depth and breadth
of chronic disease burden (all statistics refer to the
U.S. population unless otherwise specified):
Cardiovascular Diseases 63 |
Coronary heart disease
Mortality: 452,000 (2004)
Prevalence: 15.8 million (2004)
Heart failure
Mortality: 58,000 (2004)
Prevalence: 5.2 million (2004)
Arrhythmias
Prevalence:> 2 million with atrial fibrillation
Congenital heart defects
Incidence: 8 of every 1,000 newborns (35,000 per year)
Prevalence: 1 million adults
Peripheral arterial disease
Prevalence: 8-12 million
|
Lung Diseases64 |
Chronic obstructive pulmonary disease
Mortality: 120,000 (2004)
Prevalence: 12 million people diagnosed; additional 12 million undiagnosed (2004)
Asthma
Mortality: 4,000 (2004)
Prevalence: 22 million (2004)
Total costs (direct and indirect): $12.7 billion (1998)
Cystic Fibrosis
Prevalence: 30,000
Incidence: 1 in every 3,000 newborns
|
Diabetes Mellitus 65 |
Mortality: 224,092 (2002); 6th leading cause of deathe
Prevalence: 20.8 million (diagnosed and undiagnosed); type 1 diabetes accounts for 5-10% of diagnosed cases (2005)
Total costs (direct and indirect): $132 billion (2002)
|
Obesity66 |
Prevalence: 34.1 percent of adults are
overweight; 32.2% adults are obese; 18.8%
children (aged 6-11) and 17.4% adolescents
(aged 12-19) are overweight (2004) Total
health care costs (direct and indirect):
$117 billion (2000)
|
Chronic Kidney Disease67 |
Prevalence: 3.83% adults (7.7 million people)
(1999-2000)
Costs: $32.5 billion for
treating end-stage renal disease
(ESRD) (2004)
|
Urologic Diseases68 |
Benign prostatic hyperplasia
Prevalence: 6.5 million Caucasian men aged 50-79 (2000)
Cost (direct): $1.1 billion (2000)
Painful bladder syndrome/interstitial cystitis
Prevalence: 0.8% of women (1.2 million) and 0.1% of men (0.08 million) (1988-1994)
Cost (direct): $65.9 million (2000)
Kidney stones
Prevalence: 5% of adults (1988-1994)
Cost: $2.07 billion (2000)
Urinary incontinence
Prevalence: 38% of women and 17% of men, aged 60 and older (1999-2000)
Cost (direct): $463.1 million
Urinary tract infection
Prevalence: 34% of adults (62.7 million) self-reported at least one occurrence (1988-1994)
Cost (direct): $3.5 billion (2000)
|
Digestive Diseases69 |
Mortality: 234,000 (2002)
Prevalence: 60-70 million people (1996)
Disability: 1.9 million people unable to perform daily activities (1990-1992)
Costs: $85.5 billion (direct); $20 billion (indirect) (1998)
|
Chronic Liver Disease 70 |
Chronic liver disease or cirrhosis
Mortality: 27,013; 12th leading cause of death (2004)
Prevalence: 5.5 million people (2-3% of adults) (1998)
Cost (direct and indirect): $1.6 billion (1998)
Gallbladder disease
Mortality: 3,086 (2004)
Prevalence: 12% of adults (20 million) (1998)
Cost: $6 billion (1998)
Viral hepatitis
Mortality: 5,000 (Hepatitis B); 8,000-10,000 (Hepatitis C)
Prevalence: 1.25 million (Hepatitis B); 3.2 million (Hepatitis C) with chronic infection (1999-2002)
Alcoholic liver diseases
Mortality: 12,201 (2001)
Years of potential life lost (YPLL): 316,321 (2001)
|
Blood Diseases71 |
Sickle cell disease
Prevalence: 70,000; 1 in 500 African American births; 1 in 1,000-1,400 Hispanic-American births
Thalassemia (includes Cooley's anemia)
Prevalence: 1,000
Hemophilia
Prevalence: 18,000
Incidence: 400 newborns each year
|
Musculoskeletal Diseases72 |
Osteoarthritis
Prevalence: 12.1% of adults (21 million)
Osteoporosis
Prevalence; 10 million adults, 80% of whom are women; 34 million have low bone mass
Disability: >1.5 million fractures
Costs (direct): $14 billion
Osteogenesis Imperfecta
Prevalence: 20,000-50,000
Paget's disease of bone
Prevalence: 1 million
|
Skin Diseases and Conditions73 |
Prevalence: At any given time, 1 in 3 people has a skin disease.
Total health care costs: >$34.3 billion (2003)
Atopic dermatitis
Prevalence: >15 million
Costs (to health insurance companies): >$1 billion
|
Eye Diseases74 |
Age-related macular degeneration
Prevalence: 1.75 million; leading cause of vision loss in persons age 65 or older (2004)
Uveitis
Prevalence: 115.3 cases per 100,000 persons (2004)
Disability: 30,000 new cases of blindness (1990)
Diabetic retinopathy
Prevalence: 4.1 million adults aged 40 or older (2004)
Glaucoma
Prevalence: 2.2 million
|
Deafness75 |
Hearing loss
Prevalence: 2-3 of 1,000 newborns; 15% (32.5 million) adults; 10% (22 million) adults aged 20-69 suffer hearing damage due to noise exposure
Otitis media (middle ear infection)
Cost: $5 billion
Balance and dizziness
Prevalence (balance): 4% (8 million)
Prevalence (dizziness): 1.1% (2.4 million)
Cost: $8 billion for falls by older adults
|
Dental and Craniofacial Disorders76 |
TMJ disorder
Prevalence: 5-12% of the population; twice as prevalent in women as men
Chronic periodontitis
Prevalence: 80% of adults with 1 in 5 having severe periodontitis
Mental disorders
Prevalence: 6% of adults (approximately 12.5 million) have a serious mental disorder
Disability: No. 1 leading cause; accounts for 29.6% of all disability adjusted life years (DALYs) (U.S. and Canada)
Cost: $63 billion lost to decreased productivity
Depression
Prevalence: 2% of adults (approximately 4.4 million) have a serious depressive disorder
Disability: leading cause among mental health disorders; accounts for 11.2% of all DALYs (U.S. and Canada)
Cost: $36.2 billion due to lost work; $51.5 billion including lost productivity while at work
|
Mental Illness77 |
Alcohol use disorders
Prevalence: 18 million (8.5% of the population aged 18 or older)
Alcohol-attributable chronic disease
Total costs: $122 billion (est.)
Disability: Alcohol use is the 7th leading cause of DALYs
|
Alcohol Use Disorders78 |
Total cost: >$500 billion (est.; includes health- and crime-related costs as well as losses in productivity)-approximately $181 billion for illicit drugs, $168 billion for tobacco, and $185 billion for alcohol.
Abuse or dependence on alcohol and illicit drugs
Prevalence: 22.2 million people or 9.1% of the population aged 12 or older (est.) (2005)
Cigarette smoking
Mortality: 440,000 (2002)
|
Addiction79 |
Total cost: >$500 billion (est.; includes health- and crime-related costs as well as losses in productivity)—approximately $181 billion for illicit drugs, $168 billion for tobacco, and $185 billion for alcohol.
Abuse or dependence on alcohol and illicit drugs
Prevalence: 22.2 million people or 9.1% of the population aged 12 or older (est.) (2005)
Cigarette smoking
Mortality: 440,000 (2002)
|
|
56 A composite.
57
Hedley AA, et al. JAMA 2004;291:2847-2850, PMID: 15199035
58Quam L, et al. Lancet 2006;368:1221-3, PMID: 17027712
59 For more information, see:
http://www.cdc.gov/nchs/products/pubs/pubd/hestats/leadingdeaths03/leadingdeaths03.htm
60 For more information, see:
http://www.cdc.gov/nchs/products/pubs/pubd/hestats/leadingdeaths03/leadingdeaths03.htm
61For more information, see:
http://heal.niehs.nih.gov/about.htm http://www3.niaid.nih.gov/research/topics/allergies/default.htm
62 For more information, see
http://www.nih.gov/about/researchresultsforthepublic/AlcoholDependenceAlcoholism.pdf;
http://www.nih.gov/about/researchresultsforthepublic/DrugAbuseandAddiction.pdf;
http://www.nih.gov/about/researchresultsforthepublic/Tobaccoaddiction.pdf;
63For more information, see http://www.nhlbi.nih.gov/about/factbook/toc.htm (chapter 4. Disease Statistics);
http://www.nhlbi.nih.gov/health/dci/index.html
64For more information, see http://www.nhlbi.nih.gov/about/factbook/toc.htm (chapter 4. Disease Statistics);
http://www.nhlbi.nih.gov/health/dci/index.html; Weiss KB. J Allergy Clin Immunol 2001;107:3-8, PMID: 11149982
65For more information, see http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2005.pdf
66For more information, see http://win.niddk.nih.gov/statistics/index.htm; Ogden CL et al. JAMA 2006;295:1549-55, PMID: 16595758
67For more information, see http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm
68For more information, see http://kidney.niddk.nih.gov/statistics/uda/index.htm;
http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm
69For more information, see http://digestive.niddk.nih.gov/statistics/statistics.htm
70http://www.cdc.gov/nchs/data/nvsr/nvsr55/nvsr55_19.pdf;
http://www.cdc.gov/ncidod/diseases/hepatitis/resource/dz_burden.htm;
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5337a2.htm; National Vital Statistics Report 2007;55:1-119, PMID: 17867520;
Sandler RS, et al. Gastroenterology 2002;122:1500-1511, PMID: 11984534
71http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5337a2.htm; http://www.cdc.gov/ncbddd/hbd/thalassemia.htm
72http://www.niams.nih.gov/Health_Info/Osteoarthritis/default.asp;
73For more information, see http://www.niams.nih.gov/Health_Info/Atopic_Dermatitis/default.asp
74For more information, see Friedman DS, et al. Arch Ophthalmol 2004;122:564-72, PMID: 15078675;
Gritz DC, Wong IG. Ophthalmol 2004;111:491-500, PMID: 15019324;
Nussenblatt RB. Int Ophthalmol 1990;14:303-8, PMID: 2249907;
Kempen JH et al. Ophthalmol 2004;122:552-63, PMID: 15078674;
Friedman DS, et al. Arch Ophthalmol 2004;122:532-8, PMID: 15078671
75For more information, see http://www.nidcd.nih.gov/health/hearing;
http://www.nidcd.nih.gov/health/balance;
76For more information on TMJ disorder, see see http://www.nidcr.nih.gov/DataStatistics/FindDataByTopic/FacialPain/; for more information on chronic periodontitis, see http://www.nidcr.nih.gov/DataStatistics/FindDataByTopic/GumDisease
77For more information, see http://www.who.int/whr/2004/annex/topic/en/annex_3_en.pdf;
http://www.mentalhealthcommission.gov/reports/FinalReport/toc.html;
Kessler RC, et al. Arch Gen Psych 2005;62:617-27PMID: 15939839;
Greenberg PE, et al. J Clin Psychiatry 2003;64:1465-75 PMID: 14728109
78For more information, see http://pubs.niaaa.nih.gov/publications/economic-2000/alcoholcost.PDF;
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5337a2.htm;
Grant BF, et al. Arch Gen Psychiatry 2004;61:807-16, PMID: 15289279;
Michaud et al. Population Health Metrics 2006;4:11, PMID: 17049081
79For more information, see http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5337a2.htm;
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5425a1.htm; Office of National Drug Policy. The Economic Costs of Drug Abuse in the United States: 1992-2002. Washington, DC: Executive Office of the President (Publication No. 207303);
http://www.oas.samhsa.gov/NSDUH/2k5NSDUH/2k5results.htm;
http://www.cdc.gov/MMWR/preview/mmwrhtml/mm5114a2.htm;
|