Statement for the Record
Posted on August 2, 2016
Prepared Statement of Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Chairman and Members of the Committee: I am pleased to present the President’s Fiscal Year (FY) 2017 budget request for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH).
As the primary Federal agency supporting medical research on diseases of the bones, joints, muscles, and skin, NIAMS touches the lives of nearly every American. Arthritis limits the activities of more than 22.7 million adults in the United States each year (National Health Interview Survey, 2010-2012); medical care and lost wages attributable to musculoskeletal conditions cost Americans $874 billion annually (Agency for Healthcare Research and Quality Medical Expenditures Panel Survey, 1996-2011); and skin conditions such as eczema and psoriasis affect more than 12 percent of people worldwide (Global Burden of Disease Study, 2010). NIAMS is working to enhance health, lengthen life, and reduce illness and disability by supporting basic, translational, and clinical research that will make a difference for patients; fostering innovation to meet current research needs and to support the next generation of biomedical researchers; and enhancing stewardship, while reducing administrative burdens on researchers.
BASIC RESEARCH LEADS TO NEW UNDERSTANDING OF DISEASE
NIAMS investments in basic research are uncovering the underlying mechanisms of biological systems and providing new understanding of the basis of disease. For example, NIAMS intramural researchers, as part of an international consortium, analyzed DNA from nearly 1,000 children with systemic juvenile idiopathic arthritis, a severe form of childhood arthritis. The researchers showed that changes in a section of the genome related to immune cell function are strongly associated with an increased risk of developing the condition; when combined with other knowledge about the gene region involved, the finding suggests that defects in both how the body immediately reacts to infection, and how it adapts over time, contribute to the disease.
Long-term investments in data resources to facilitate basic science discoveries continue to produce results. One such resource, the Osteoarthritis Initiative, was established a decade ago as a repository for medical images, clinical data, and biospecimens from people who were at high risk of developing knee osteoarthritis. Recently, researchers mining the publicly available database found joint changes that may predict who will go on to develop osteoarthritis. This discovery is calling into question long-held beliefs about how osteoarthritis arises and may open new avenues for halting joint disease at its earliest stages.
Basic research on fundamental biological processes in healthy tissues could inform future treatments. Only a limited number of tissues in adult humans are capable of regeneration, and currently, we know little about the signaling pathways that are involved. NIAMS-supported researchers are beginning to uncover the basic molecular events that underlie recovery of certain tissues, such as hair follicle regeneration after skin wounding. Recently, two key regulators of this process were identified in mouse models. Interestingly, both of the molecules are also involved in immune system functions, such as protection against viral infections. By understanding regeneration in this model, scientists may one day be able to develop methods to stimulate repair of other human tissues. In FY 2017, NIAMS plans to provide funding for small businesses to develop novel complex 3-dimensional (3-D) in vitro human musculoskeletal and skin tissue models. These models will facilitate the study of human tissue physiology and pathophysiology, and potentially lead to better interventions that prevent or cure diseases.
BIOMARKERS — A TOOL FOR DISCOVERY AND CLINICAL CARE
Biomarkers are measurable biological or chemical indicators of health or disease that are accurate and reproducible. NIAMS research to identify, validate, and utilize biomarkers across the spectrum from basic to clinical research is bearing fruit. In a recent study, NIAMS intramural researchers examined the blood of patients with ANCA-associated vasculitis (AAV), a systemic autoimmune disease that causes inflammation in the blood vessels. The researchers found that the amount of a distinct type of white blood cell in patients with vasculitis correlated with how they would respond to treatment. Once validated, this discovery could inform clinicians if a particular patient is likely to respond to an intervention, helping them to tailor treatment to the individual.
In addition, biomarkers are important tools in monitoring disease status. Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness, and biomarkers that distinguish among stages of the disease could enable researchers to rapidly assess how well a novel intervention is working. NIAMS-supported investigators have identified several different types of biomarkers for DMD using new techniques to monitor changes in muscle quality. Recently, other researchers found dozens of proteins in blood that were significantly different between DMD patients and individuals without the disease. Several of these proteins also changed during progression from early disease to its later stages. In the future, this information may help researchers develop new interventions, identify appropriate candidates for clinical trials, and more rapidly interpret trial results.
Other biomarkers are being evaluated as surrogate outcomes when examining new interventions for diseases. For example, NIAMS-supported researchers tested a new drug to prevent scarring in patients with systemic sclerosis, a severe form of the chronic connective tissue disease scleroderma. The researchers showed that the drug significantly reduced the amount of two proteins in the skin of patients, and these reductions correlated with improvement in skin condition assessed via traditional clinical measures. The study results demonstrate the value of a biomarker-based approach to measuring treatment response and confirming clinical data.
HELPING CLINICIANS BETTER CARE FOR PATIENTS
While basic research into the underlying mechanisms of disease will always be an important focus, NIAMS research also helps ensure that physicians have up-to-date information to facilitate treatment decisions based on the current state of the science. For example, children with an abnormal curvature of the spine, called adolescent idiopathic scoliosis (AIS), often are instructed to wear braces to prevent worsening of the curve, but the effectiveness of this treatment had not been rigorously tested. In 2007, NIAMS-supported investigators launched the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) to compare the risk of curve progression in tweens and teens with AIS who wore a brace versus those who did not. In January 2013, the trial was stopped early after finding that bracing significantly reduced the risk of curve progression and the need for surgery, and that more hours of brace wear were associated with higher success rates. These results were the primary reason several healthcare provider organizations recently updated their recommendations regarding scoliosis screening for adolescents. In addition, the United States Preventive Services Task Force is currently revisiting its screening recommendations for AIS.
NIAMS researchers are also leveraging existing data to aid physicians in everyday practice. Recently, NIAMS intramural scientists conducted a comprehensive review of clinical studies into the various treatments available for two major causes of back pain, ankylosing spondylitis and non-radiographic axial spondyloarthritis. Based on the systematic review, a series of treatment recommendations were developed, and they have been endorsed by the American College of Rheumatology. The recommendations provide clinicians with the current best-evidence for the treatment of these common conditions, and may facilitate the effective use of health care resources, reduce inappropriate care, and minimize variation in care.
Looking to the future, NIAMS will capitalize on prior investments and recent advances in the science of patient-reported outcomes (PROs) to improve the health and well-being of pediatric patients. The Patient Reported Outcomes Measurement Information System, or PROMIS®, was an NIH Common Fund project, co-led by NIAMS, to develop a system of highly reliable, precise measures of patient-reported health status for physical, mental, and social well-being. The PROMIS tools can give physicians a clearer understanding of how the patient is feeling and functioning, and can be used across a wide variety of chronic diseases and conditions in both research settings and in routine care. In FY 2015, NIH funded the Validation of Pediatric Patient-Reported Outcomes in Chronic Diseases (PEPR) Consortium that will expand existing and new PRO tools for pediatric patients, ultimately improving the treatment of chronic diseases in children. PEPR is part of a trans-NIH effort to lay the foundation for a new multi-year initiative called the Environmental Influences on Child Health Outcomes (ECHO) program set to begin in FY 2017.
FOSTERING INNOVATION AND ENHANCING STEWARDSHIP
NIAMS is actively working to enhance and strengthen our scientific stewardship and encourage innovation. As part of these efforts, NIAMS is supporting several programs targeting the next generation of researchers. In FY 2015, NIAMS launched a new program called the Supplements To Advance Research from Projects to Programs, or STAR, awards. STAR promotes innovation and exploration of high-risk ideas by providing flexible funding to early established investigators to expand upon their currently funded project and facilitate transition from a single project to a research program. NIAMS made three STAR awards in FY 2015, and anticipates another group of awards in FY 2016.
In addition to STAR, NIAMS has implemented several programs to support clinician researchers, a vital population that faces unique challenges in pursuing research careers. Since FY 2012, NIAMS has hosted an annual career development forum for extramural researchers who have received either a mentored clinical scientist development (K08) or patient-oriented research (K23) grant. The forum provides awardees with opportunities to network with each other, as well as NIAMS leadership and program, review, and grants management officials; and enhances the Institute’s support of early-stage physician-scientists by encouraging and enabling awardees to continue performing basic, translational, or patient-oriented research in their chosen fields. In addition to the forum in FY 2016, NIAMS will implement a new trans-NIH policy of increased salary support for these same K awardees, a year earlier than required by NIH. Finally, NIAMS is planning a new small grant program to assist early-stage clinician scientists as they pursue research independence through the so-called K-to-R transition, a particularly vulnerable period for investigators. Together, these and other training and fellowship programs will help ensure a robust pipeline of new investigators in the rheumatic, musculoskeletal, and skin disease mission areas.
NIAMS is also encouraging innovation and stewardship by collaborating with the research community and other stakeholders to elaborate on exciting new research opportunities. For example, NIAMS, on behalf of NIH, led the development of a new Action Plan for Lupus Research, and also participated in the development of the Action Plan for the Muscular Dystrophies. Both plans represent a synthesis of NIH internal input, as well as significant external input from the scientific, clinician, and patient advocacy communities. They will help to inform priority-setting processes among all interested organizations — Federal, private, and non-profit — and may inspire individual investigators as they develop innovative, independent research proposals. In addition, NIAMS is leading the Accelerating Medicines Partnership in Rheumatoid Arthritis and Lupus (AMP RA/Lupus). This unique public-private partnership with NIH, pharmaceutical companies, and non-profit organizations aims to transform the model for identifying and validating promising targets for the development of new drugs and diagnostics. The AMP RA/Lupus program was funded in late FY 2014, and researchers and other partners have developed a research plan with distinct milestones. Substantial progress has already been made incorporating cutting edge technologies and establishing standard operating procedures that the broader scientific community will be able to leverage in the future.