DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
Fiscal Year 2011 Budget Request
Witness appearing before the Senate Subcommittee on Labor-HHS-Education Appropriations
Susan B. Shurin, M.D., Acting Director
National Heart, Lung, and Blood Institute
April 28, 2010
Mr. Chairman and Members of the Committee:
I am pleased to present the President’s budget request for the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). The Fiscal Year (FY) 2011 budget of $3,187,516,000 includes an increase of $91,704,000 over the FY 2010 appropriated level of $3,095,812,000.
The NHLBI provides global leadership for a research and education program to promote prevention and treatment of heart, lung, and blood diseases. The vision is to enhance the health of all individuals and thereby enable them to lead longer and more productive lives. Through the generous support provided by the American people, the Institute has made remarkable strides in advancing its mission.
The major focus of NHLBI is on diseases that cause substantial suffering and limitations for our citizens. Non-communicable chronic diseases, including cardiovascular disease (CVD) and chronic lung disease, now represent the leading causes of loss of quality and duration of life across the globe. As children are less likely to die of acute infectious diseases, prevention and management of chronic diseases become more important both to maintain quality of life and to reduce the economic impact of illness on society. People affected by many potentially lethal genetic diseases now can live well into middle age and beyond.
This testimony is structured around five themes articulated by the NIH Director. The areas of research managed by NHLBI represent a broad spectrum of the continuum of diseases with both genetic and environmental causes. A common theme across the Institute is unraveling the relative contributions made by inherited factors and a wide variety of exposures to the expression and variability of human diseases. Much NHLBI-supported research over the past 4 years has identified genetic loci of interest for complex diseases such as arteriosclerosis, hypertension, and chronic obstructive pulmonary disease and begun to explore the reasons why diseases caused by single-gene mutations such as hemoglobinopathies, hemophilia, and cystic fibrosis may follow widely differing clinical courses.
Extraordinarily productive genome-wide association studies (GWAS) are capitalizing on the NHLBI’s long-running investments in cohort studies in which the health conditions of thousands of participants have been well characterized. Cohorts that include individuals with CVD and lung diseases, as well as healthy persons, and longstanding cohorts of patients with sickle cell disease (SCD) offer major opportunities to realize the promise of rapidly emerging genomic technologies. The greatest benefits to date have been in understanding the complex genetic contributors to CVD. The identification of genetic loci associated with hypertension, heart failure, and some forms of atherosclerosis has provided significant insight into the chronic processes that lead to these disorders. GWAS of other disease conditions are only now becoming available. The next generation of large-scale NHLBI-initiated studies focus on sequencing genetic areas of interest and obtaining additional information on the proteins and other metabolic products that may cause or reflect diseased states. These studies are beginning to identify targets for treatment and biomarkers of pre-clinical conditions that herald increased risk—findings that may help personalize our therapeutic approach to the individual patient. They are also helping us to understand the importance of the relative contributions which a variety of genetic factors play in causation of diseases which may require multiple factors to develop. Ongoing work is pursuing the underlying biological causes of disease and modifying environmental factors.
Clinical variability is also seen in persons with single-gene disorders. Subsets of patients with hemoglobinopathies develop specific complications such as pulmonary hypertension, while the majority do not. The course of cystic fibrosis varies depending upon both specific underlying gene defects and exposures to bacteria. By understanding the factors underlying variable manifestations, we hope to be able to personalize therapies and to apply lessons to other genetic diseases that exhibit unexplained variability.
MapGEN is a broad consortium that seeks to identify and characterize common pathobiologic traits and/or mechanisms that cross organ systems and diseases with the ultimate goal of redefining heart, lung, and blood disorders based on newfound knowledge of the underlying molecular and/or cellular pathobiology. The results are expected to provide a basis for rational, mechanism-based development of new diagnostic, prognostic, and therapeutic strategies.
The NHLBI has begun several programs to support translational medicine. The Centers for Advanced Diagnostics and Experimental Therapeutics in Lung Diseases, or CADET, will accelerate the development of novel agents for the diagnosis and treatment of lung diseases and sleep-disordered breathing. Centralized support will be available for early-stage drug development, including preparation of small molecules under a program called SMARTT, or Science Moving TowArds Research Translation and Therapy. The NHLBI supports centers that provide production assistance for cellular therapies and vectors for gene therapies.
A new program to be funded in 2011 will provide planning grants for pivotal clinical trials, with a major focus on hemoglobinopathies. The grants will enable investigators to assemble all of the necessary components to execute a successful clinical trial and to consult experts in relevant areas such as statistics, pharmacology, and diagnostic imaging, and will enable the NHLBI to focus major commitments to translational research on programs that have demonstrated substantial feasibility.
The NIH has made major investments in comparative effectiveness research (CER) over the last several decades, and much of NIH-sponsored has been supported by the NHLBI. Studies of drug treatments for hypertension, for instance, have found that older drugs are actually more effective and safer than newer ones. Studies of asthma have found that judicious use of long-acting beta agonists in combination with corticosteroids can yield better control of wheezing with fewer side effects in children whose asthma is particularly refractory. Studies in children with SCD who are at risk of stroke have demonstrated that trans-cranial Doppler can be used to identify susceptible patients and early, chronic transfusion can prevent stroke. Trials are now looking at whether hydroxyurea therapy, known to be effective for other complications, can protect against stroke without the risks of chronic transfusion. If the results of these trials are favorable, many affected youngsters will no longer have to undergo monthly blood transfusions and the treatments necessary to remove excess iron.
The NHLBI has a longstanding commitment to ensuring that the research discoveries it supports are made available to the public. The Institute is in the process of updating guidelines for management of cholesterol and hypertension, and is creating the first integrated guidelines for persons who have multiple risk factors for heart diseases, including high cholesterol, high blood pressure, and obesity. The Institute is also developing evidence-based guidelines for the care of individuals with SCD that can be used by health-care practitioners throughout the world. An educational campaign will be undertaken in partnership with patient advocacy groups, professional organizations, and public health entities to raise awareness.
The NHLBI and the CDC have launched a new surveillance and research program for hemoglobinopathies. The Registry and Surveillance in Hemoglobinopathies (RuSH) project will initially collect data in six states—California, North Carolina, Georgia, Michigan, Pennsylvania, and Florida—to determine the numbers, demographic characteristics, and geographic distribution of affected patients and examine the health-care resources that are available to them. This effort will provide critical information about the current state of care for patients and offer directions for improved provision of services.
CVD and chronic lung diseases are major threats to the global population, and their increasing prevalence raises significant scientific questions that can best be addressed on a global basis. Why does the incidence of CVD increase when people immigrate to the United States? What accounts for the extraordinarily high CVD risk of some persons from the Indian subcontinent who experience fatal heart attacks in early adulthood despite having none of the risk factors described in the NHLBI Framingham Heart Study? The Institute has initiated global Centers of Excellence and is working with public funders of research from other countries to explore such questions.
Although hemoglobinopathies are rare diseases in the United States, nearly half a million affected infants are born annually worldwide. Collaborations with investigators in sub-Saharan Africa, the Americas, and Southeast Asia are being planned to address scientific questions that require large populations to gain meaningful insights and, potentially, improve therapy for all. .
The Institute has for many years provided a variety of resources and programs to support investigators at all stages of their careers, particularly early-stage investigators who need senior mentors. New initiatives are targeting some areas in which special support is needed to enhance development of young investigators and to attract established investigators now active in other areas of research.
We at the NHLBI are grateful to be entrusted with investment of public resources to improve the health of people in this country and throughout the world. We thank the Congress and the American people, and renew our commitment to advancement of knowledge and the common good.
I would be pleased to respond to any questions that the Committee may have.
Susan B. Shurin, M.D., is the Acting Director for the National Heart, Lung, and Blood Institute (NHLBI). Dr. Shurin joined the NHLBI as deputy director in February 2006, coming from Case Western Reserve University in Cleveland, Ohio. Dr. Shurin leads and supervises the intramural and extramural activities of the NHLBI, and is responsible for oversight of the Institute’s clinical research portfolio. Dr. Shurin represents the NHLBI in a wide variety of activities across the National Institutes of Health (NIH), and represents the NIH in interagency activities across the Department of Health and Human Services. She is leading the NHLBI’s Global Health Initiative. She has served as acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and of the NHLBI’s Division of Blood Diseases and Resources.
Before joining the NHLBI, Dr. Shurin was professor of Pediatrics and Oncology at Case Western Reserve University; director of Pediatric Hematology-Oncology at Rainbow Babies and Children’s Hospital; director of Pediatric Oncology at the Case Comprehensive Cancer Center; and vice president and secretary of the Corporation at Case Western Reserve University in Cleveland, Ohio. Dr. Shurin received her education and medical training at Harvard University and the Johns Hopkins University School of Medicine. Her laboratory research focused on the physiology of phagocyte function, recognition and killing of pathogens; mechanisms of hemolysis; and iron overload. She has been active in clinical research in many aspects of pediatric hematology-oncology, including participation in the Children’s Cancer Group, Children’s Oncology Group, multiple studies in sickle cell disease and hemostasis.
Before joining the NIH, Dr. Shurin served on multiple NIH advisory panels. She has been on the boards or in leadership positions of numerous local and national professional organizations, including the American Board of Pediatrics. She is a member of the American Academy of Pediatrics; the American Society of Hematology; the American Society of Pediatric Hematology-Oncology; and the American Pediatric Society, where she is currently a member of the APS Council.