Strategischer Plan für die Geschäftsjahre 2020

NIAMS is updating its Strategic Plan for 2025-2029. Click here for more information about the planning process.

PDF Version – Strategic Plan Fiscal Years 2020–2024 (1171 KB)

The below resources are designed to be printed or viewed electronically. They provide a quick overview of the NIAMS Strategic Plan to familiarize stakeholders, patients, and other audiences about the research interests of NIAMS.

Strategic Plan Tri-fold Brochure PDF (620 KB) NOTE: For best result, print in landscape mode on legal size (8.5”x14”) paper, flip along short edge.

About Our Strategic Plan - All PDF (1626 KB)

The NIAMS mission is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of basic and clinical scientists to carry out this research; and dissemination of information on research progress in these diseases.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is pleased to present its Fiscal Years 2020-2024 Strategic Plan. The fields that NIAMS supports have seen major advances in recent years and are now poised for additional rapid progress. Therefore, the NIAMS Strategic Plan conveys both the tremendous potential of the current research trajectory and the Institute’s aspirational vision for how work over the next 5 years may lead to meaningful improvements in human health.

Importantly, this plan is not intended to be a rigid roadmap for investigators to follow. While we will continue to invest in various well-defined areas, we will also seek to foster a rich and adaptable research environment that enables scientists to capitalize on opportunities as they arise. By putting structures in place to identify, promote, and support advances that we cannot predict at the present, we hope to stimulate new areas that are unexpected and transformative. Thus, this Plan for the next 5 years should be viewed not as directions to a defined destination, but rather as a point of departure for exploration to spark unanticipated discoveries.

The goal of the plan is to advance and accelerate research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. The ultimate goal of these efforts is to develop patient-centered, personalized ways to improve outcomes and thereby “turn discovery into health.”

This strategy of promoting the unexpected has important implications for priority setting. First, NIAMS must look to the research community for new ideas, rather than prescribing what gets done. Second, it requires maintenance of a broad base of researchers. Third, funding must be based on new and promising ideas and not just on past performance. Therefore, we will continue to value and support the best ideas proposed in investigator-initiated research project grants. Simultaneously, NIAMS must be poised to embrace unexpected opportunities for collaborations with other NIH components, advocacy organizations, and industry to fund larger scale, team science approaches, such as the Osteoarthritis Initiative, the Accelerating Medicines Partnership, the Molecular Transducers of Physical Activity Consortium, and the NIH Back Pain Consortium Research Program.

To support this strategy, the Strategic Plan describes potential research areas of interest over the next 5 years. Although it is not possible to reference every disease or condition within our broad portfolio, it covers the following five research objectives related to the core tissue- and disease-specific areas within the NIAMS mission, namely, advancing and accelerating:

Each of the sections devoted to the five objectives features a major project or activity to highlight a significant NIAMS accomplishment in that area. A number of these highlighted projects also showcase the Institute’s leadership in collaborative activities to advance science. Leveraging partnerships has been a major strength of NIAMS, and we will continue to pursue this strategy to accomplish our research objectives.

Looking across the NIAMS portfolio, many reasons exist to be hopeful. Progress related to the cross-cutting themes is relevant to several diseases and conditions within the NIAMS mission.

The new plan differs from previous NIAMS planning documents in two ways. First, it features four broad cross-cutting scientific themes that are relevant to all, or most, of the disease- and tissue-specific topics within the NIAMS mission. We chose these themes because they were heard across the “listening sessions” we held with representatives from each of our research areas. As such, research topics included in this section also appear throughout the disease- and tissue-specific sections both to provide additional detail in each of the areas and to ensure that these key points reach all audiences. These themes, which provide potential opportunities to better organize and conduct science across our mission areas, are:

The themes focus on the increasing convergence of scientific knowledge and approaches across fields, which represents an unprecedented opportunity to invigorate the conduct of science. To illustrate the potential of these areas, we have included several aspirations that provide examples of a vision for where cross-cutting, convergent research may lead us in the coming years or decades. Although NIAMS primarily funds individual investigator-initiated research projects, we encourage investigators to consider convergence with other scientific areas as they plan their own research and, when possible, to collaborate across disciplines.

Second, the plan includes a new section that addresses National Institutes of Health (NIH) and NIAMS activities related to:

Including these topics in our Strategic Plan is a key step in sharing information with the research community and the public about our commitment to responsible management, stewardship, and accountability. Over the next 5 years we will continue to support and promote these initiatives while looking for additional opportunities to be even more transparent about the Institute’s efforts in these areas.

Importantly, the development of this plan benefitted from the collective wisdom of members of both the scientific and lay communities interested in and affected by diseases and conditions within the NIAMS mission, and we thank all those who contributed their expertise and insights. We hope that the Fiscal Years 2020-2024 Strategic Plan will inspire those involved or interested in NIAMS research as investigators, research participants, patients, or the general public, and that it serves as a resource for all who have an interest in our mission. We encourage you to share the plan broadly with your colleagues.

/Robert H. Carter, M.D./Robert H. Carter, M.D.Acting DirectorNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institutes of Health

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) advances health through biomedical and behavioral research, as well as through research training. The NIAMS mission is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of basic and clinical scientists to carry out this research; and dissemination of information on research progress in these diseases.

The Institute’s research portfolio includes five core mission areas: (1) Systemic Rheumatic and Autoimmune Diseases; (2) Skin Biology and Diseases; (3) Bone Biology and Diseases; (4) Muscle Biology and Diseases; and (5) Joint Biology, Diseases, and Orthopaedics. Within these mission areas, NIAMS supports research at multiple levels, ranging from basic studies to enable comprehensive understanding of the molecular mechanisms underlying disease processes to preclinical research in model systems to translational studies to clinical and epidemiological research. In addition to research projects, NIAMS supports research training and career development, scientific conferences, and research infrastructure such as core facilities that enhance and accelerate NIH-funded research or research that is sponsored by other public and private organizations. The ultimate goal of these efforts is to develop patient-centered, personalized ways to improve outcomes and thereby “turn discovery into health.”

The NIAMS Strategic Plan for Fiscal Years (FYs) 2020-2024 is a part of the Institute’s scientific planning process. The goal of the plan is to advance and accelerate research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. The plan also serves as a platform to facilitate communication between the Institute and its many constituents—scientific communities, health care providers, health advocacy organizations, patients, the general public, and policymakers—about needs and opportunities related to the NIAMS mission. The plan is not intended to prescribe what investigators should pursue in their exploration of scientific problems that bear on the health of bones, joints, muscles, and skin. Rather, it is intended as a guide that might lead to unanticipated new scientific directions. As always, the Institute will continue to value and rely on investigator-initiated science as a critical source of innovation.

Although the plan includes research objectives related to the Institute’s five disease- or tissue-specific areas noted above, modern biomedical and behavioral research increasingly crosses those traditional disease- and tissue-specific boundaries. Many scientific challenges and opportunities within the NIAMS mission are not unique to any one field, disease, or scientific or clinical discipline. Therefore, the FYs 2020-2024 plan includes a new section highlighting cross-cutting scientific themes relevant to many areas of the NIAMS mission. These themes, briefly outlined below, provide a framework for understanding the convergence of ideas, knowledge, and approaches across fields.

Emerging technologies, such as techniques to analyze single cells and innovative genomic approaches, have yielded a wealth of data that can be integrated with clinical information to build sophisticated new models of health and disease. In the coming years, these approaches, which give researchers powerful new tools to address longstanding research questions, are expected to advance knowledge in many NIAMS mission areas and yield more personalized treatments for patients.

Increasingly, researchers are discovering commonalities among seemingly disparate diseases and revealing how basic processes such as immunity, inflammation, regeneration, and metabolism play a role in maintaining health or, when perturbed, in the development of disease. The discovery of shared molecular, physiological, and behavioral components and mechanisms of action across different diseases is blurring the traditional boundaries of biomedical science and challenging investigators to employ new approaches to explore scientific questions.

Over the past 5 years, efforts to integrate the patient perspective into research have progressed. New tools are available to capture patient-reported data for use in clinical trials and care. This integration offers promise for more holistic therapies to improve health and enhance the patient experience.

Different demographic groups often have distinct health concerns and disparities exist among groups with regard to health outcomes for diseases within the NIAMS mission. To achieve the goal of improving human health, NIAMS-funded research must be applicable to health and disease in many populations.

In addition to the new focus on the cross-cutting scientific themes described above, the plan also includes a section dedicated to the Institute’s commitment to managing, accounting for, and providing stewardship of the public resources that support its mission. This component of the plan describes the ways in which NIAMS sets priorities and invests taxpayer funds strategically. Through various activities, NIAMS fosters the next generation of researchers in NIAMS mission areas, supports investigation of bold and innovative hypotheses, encourages the development and sharing of state-of-the-art resources, ensures the inclusion of diverse populations in biomedical research, and provides information to the public about NIAMS-funded scientific advances. Specific topics related to this commitment include the following.

NIAMS employs a standard process for making funding decisions, the cornerstone of which is peer review by the research community coupled with careful consideration by Institute leadership. This process helps to ensure that the Institute invests in highly meritorious research that addresses promising scientific opportunities and pressing public health needs.

Biomedical and behavioral research is a human endeavor and NIAMS is committed to keeping the talent pipeline robust and diverse. Fostering early-stage investigators and supporting a range of research training and career development programs for mid-career clinicians and scientists are key NIAMS goals.

New and highly innovative hypotheses and approaches play important roles in moving science forward. Although exploring such hypotheses may entail higher risk than pursuing research that builds incrementally, highly novel research has tremendous potential to advance scientific knowledge and expand technological capabilities. In addition to supporting trans-NIH efforts to foster innovation, NIAMS supports targeted initiatives to encourage paradigm-shifting research in its mission areas.

NIAMS works closely with other NIH components to advance research in areas of shared interest. Through participation in trans-NIH working groups the Institute ensures that diseases within its purview are included in trans-NIH initiatives and avoids duplication of effort with other NIH entities. Like all NIH Institutes, Centers, and Offices, in addition to managing its own budget allocation, NIAMS employs agency-wide approaches and resources, drawing from the NIH Common Fund and other resources available across NIH to support cross-cutting research and address infrastructure needs not unique to any given NIH component. NIAMS also continues to partner with a variety of public and private organizations to advance the transformation of discovery to health. Through these efforts, NIAMS leverages existing resources and explores numerous scientific areas in ways that it would be unable to tackle alone.

NIAMS supports research to improve understanding about the unique health needs of women, children, older adults, minorities, and other groups and to address health disparities. This research is supported by tangible polices to ensure that women, racial/ethnic groups, and other populations are included as participants in NIAMS-funded clinical research. In addition, the Institute supports NIH-wide efforts to incorporate sex as a biological variable in preclinical research.

NIAMS uses quantitative and qualitative approaches to inform the development, conduct, and improvement of Institute programs. Through these careful assessments, the Institute enhances its efforts to further the ultimate goal of turning discovery into health.

To maximize return on its investment in research, NIAMS encourages the dissemination of research findings to health care providers and the public. NIAMS will continue working closely with stakeholders to promote broad dissemination of scientific and health-related knowledge to the Institute’s varied communities.

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Importantly, the NIAMS Strategic Plan for FYs 2020-2024 is a starting point, not a destination. While the plan is intended to provide a broad view of potential opportunities and challenges, research is likely to advance and evolve in many unanticipated ways over the 5-year period. The Institute is committed to communicating transparently with its stakeholders about its future plans to maximize the careful stewardship of federal funds and to respond appropriately to emerging needs and opportunities in science and health.

NIAMS supports research into causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of basic and clinical scientists to carry out this research; and dissemination of information on research progress in these diseases. It is critical to revisit program areas periodically because research needs, opportunities, and challenges change over time. The NIAMS Strategic Plan for FYs 2020-2024 will facilitate communication between the Institute and its many constituents—scientific communities, health care providers, health advocacy organizations, the general public, and policymakers—about needs and opportunities related to the NIAMS mission.

Arthritis and musculoskeletal and skin conditions of all types affect people of all ages and of all racial and ethnic backgrounds. Combined, they afflict tens of millions of Americans, cause tremendous human suffering, and cost the U.S. economy billions of dollars in health care costs and lost productivity. Most of the diseases covered by the NIAMS mission areas are chronic and many cause lifelong pain, disability, or disfigurement. Diseases within the NIAMS mission also may lead to or be associated with the development of other serious medical conditions, referred to as comorbidities or co-occurring conditions. Some of these conditions are very common, while some are rare, affecting only a few thousand people worldwide. The 2017 Global Burden of Disease data have provided a wealth of information about the extent to which many of these conditions affect society. For example, in 2017, low back pain was the leading cause of disability in the United States, as measured in years lived with disability (YLDs).1 Other musculoskeletal diseases, a category that includes many systemic rheumatic, bone, muscle, and joint diseases, was among the top 10 causes of YLDs. The Centers for Disease Control and Prevention (CDC) estimate that 57.9 million adults in the United States have arthritis,2 and a recent study suggests that this may be an underestimate.3 As the U.S. population ages, the prevalence of arthritis and its associated costs is expected to grow.

Whether common or rare, many diseases and conditions within the NIAMS mission affect women and minorities disproportionately, both in increased numbers of those affected and increased disease severity. For example, findings from recent CDC-funded population-based systemic lupus erythematosus (SLE) registries in Alaska, California, Georgia, Michigan, and New York provide additional information about lupus health disparities. These and earlier studies show that women with SLE significantly outnumber men, and the disease is more common in African American, Hispanic, Asian, and American Indian women than in white women.4 Furthermore, the CDC-funded research documents an earlier onset of lupus and higher burden of disease in African Americans than in whites.5 6 Rheumatoid arthritis, osteoporosis, and osteoarthritis (in people over 45 years of age) are also more prevalent among women, whereas certain forms of ankylosing spondylitis (inflammation of the joints in the spine) occur more frequently in men.

Socioeconomic status, education level, cultural issues, and medical practice variation are all factors that may contribute to health disparities after disease onset, potentially affecting disease progression and treatment response. Understanding the role these factors play can inform the development of strategies to reduce outcome disparities, and that knowledge will enable early diagnosis and disease management tailored to an individual’s needs.

In accordance with the 21st Century Cures Act (Public Law 114-255), enacted in 2016, the NIAMS Director consults with the Director of the National Institute on Minority Health and Health Disparities (NIMHD) and the Director of the Office of Research on Women’s Health (ORWH) regarding NIAMS objectives to ensure its future activities take into account the health needs of women and minorities and are focused on reducing health disparities. NIAMS works closely with NIMHD and ORWH, and NIAMS staff are active participants in standing and ad hoc committees related to NIH priorities for women’s health, minority health, and health disparities. These relationships enable the Institute to align its work in these areas with broader NIH efforts and to leverage and synergize with related activities across NIH.

The goal of the NIAMS FYs 2020-2024 strategic plan is to advance and accelerate research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. Like the previous plans, it is expected to continue to promote exploration of ideas and encourage new research directions as needed. Although NIAMS expects to continue to devote the majority of its extramural budget to funding the most meritorious investigator-initiated research, the Institute recognizes the need for flexibility in serving the scientific community in the best possible ways. The plan brings attention to many areas that could be explored in coming years to stimulate research progress related to improved understanding, diagnosis, treatment, and ultimately prevention of diseases within the NIAMS mission.

The plan is not meant to be comprehensive; it does not mention every research area or disease of interest by name. As a broad scientific outline for NIAMS, however, it elaborates some of the Institute’s known areas of interest, while enabling the Institute to adapt to rapidly changing biomedical and behavioral science landscapes.

1 The Institute for Health Metrics and Evaluation (IHME). (2017). United States. Available at http://www.healthdata.org/united-states2 Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. (2017). Arthritis. Available at https://www.cdc.gov/nchs/fastats/arthritis.htm3 Jafarzadeh SR, et al. Arthritis Rheumatol. 2018. PMID: 29178176.4 CDC. (2018). Lupus. Available at https://www.cdc.gov/lupus/funded/lupus-studies.htm5 Somers EC, et al. Arthritis Rheumatol. 2014. PMID: 24504809.6 Lim SS, et al. Arthritis Rheumatol. 2014. PMID: 24504808.

The Health Research Extension Act of 1985 (Public Law 99-158) authorized the establishment of NIAMS, which was formally established in 1986. The mission of NIAMS is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of basic and clinical scientists to carry out this research; and dissemination of information on research progress in these diseases.

NIAMS is one of 27 Institutes and Centers of NIH, the Nation’s premier biomedical research agency. NIH is the steward of medical and behavioral research for the Nation. The agency is responsible to Congress and the U.S. taxpayers for carrying out its mission to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, in a manner that not only facilitates research but does so cost-effectively and in compliance with applicable rules and regulations.

The NIAMS organizational structure includes an Office of the Director, which provides overall leadership for and administration of the Institute’s components, including the Division of Extramural Research (DER) and the Intramural Research Program (IRP). The NIAMS DER supports scientific studies and research training and career development throughout the country through grants and contracts to research organizations. The NIAMS IRP, located on the NIH campus in Bethesda, Maryland, conducts high-risk, high-reward basic, translational, and clinical research in NIAMS mission areas.

The NIAMS Strategic Plan for FYs 2020-2024 focuses primarily on the Institute’s extramural program because the NIAMS intramural strategic planning process is linked to a larger NIH-wide planning process for intramural research. Furthermore, the NIAMS IRP has a number of capabilities and resources that are purposefully different from, and complementary to, those supported by the NIAMS DER. The science conducted by the IRP has a more restricted focus than that of extramural research in part because of budgetary limitations, but also to focus on the unique strengths of the IRP. For example, the IRP has a long tradition of excellence in long-term, high-risk research into the genetics and pathophysiology of human disease and the development of innovative therapies for a number of serious disorders for which satisfactory treatments previously did not exist. The IRP also has several distinctive characteristics, including: a unique funding model using a largely retrospective review of investigators to inform funding decisions; a concentration of interactive outstanding investigators in a collaborative environment with fluid boundaries between basic, translational, and clinical research; exceptional research resources, including the NIH Clinical Center; a longstanding culture of mentoring trainees at all levels; and a rich environment for training physician-scientists due to the presence of basic, translational, and clinical researchers.

Many scientific challenges and opportunities within the NIAMS mission are not unique to any one field, disease, or scientific or clinical discipline. Rather, they transcend disease- and tissue-specific boundaries, have broad impact across many diseases and conditions, and can therefore serve as a framework to organize science across the assorted fields within the Institute’s purview. A commonality that links these themes is the concept of convergence science, which refers to the coming together of different scientific and technological fields to catalyze scientific progress. This section of the Strategic Plan describes the following four cross-cutting scientific themes:

Because they are cross-cutting, these themes resonate and create synergies with the scientific goals described in the disease- and tissue-specific sections of the plan. Many of the research areas described under these themes are addressed with greater specificity within those sections, depending on the stage of development of the field. For example, microbiome studies focus on mechanisms and effects of multiple microorganisms that are shared across many areas of health and disease, but such studies are more advanced in skin research than in many other areas.

The cross-cutting scientific themes represent areas that might benefit from an overarching approach, for example, the development of multi- and interdisciplinary teams to advance research on tissue interactions. In some cases, they highlight a collective need across mission areas for shared complex technologies, for example, in vivo visualization of molecules or cells. They are often areas for which multiple diseases require the same methodological approach, such as extensive phenotyping to better characterize disease heterogeneity. They also reveal emerging scientific opportunities such as improved understanding of environmental triggers of disease initiation and progression.

Looking across the NIAMS portfolio, many reasons exist to be hopeful. The list below provides a few examples of advances that are possible during the next 5 years. These aspirations exemplify the broad concepts, for example, precision medicine, described under the cross-cutting themes. Importantly, this list is neither comprehensive nor exhaustive. Progress related to the cross-cutting themes is relevant to several diseases and conditions within the NIAMS mission. In addition, many unanticipated advances in a range of areas are likely to occur. Although unable to guarantee that all of these aspirations will be realized, these are areas in which the state of the science suggests a clear path forward. They are intended to convey the promise of the science and a vision for improving health and quality of life.

The emergence of powerful new technologies and computational tools to measure and analyze biological mechanisms has advanced our understanding of the molecular basis of health and disease. These tools also present unique opportunities to realize the promise of precision medicine, that is, treatment targeted to an individual’s unique biology. Integrating multifaceted disease mechanism data with accurate and detailed clinical and patient-reported information offers new possibilities for understanding variations in symptoms, co-occurring conditions, and response to therapy among patients with the same diagnosis, and for precise targeting of disease pathways active in different patients. This integrated information could be used to identify patient subsets, inform the development of new therapies, tailor the specific range of drugs now available to individual patients, and enhance risk-benefit assessments.

7 “Deep phenotyping can be defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described.” See Robinson PN. Hum Mutat. 2012. PMID: 22504886

Several basic biological processes critical to maintaining or restoring health are common across dissimilar tissues and organ systems. For example, inflammatory, reparative, regenerative, and metabolic processes may be similar across tissues and are closely linked through the processes of immune system activation and stem cell stimulation. Sharing knowledge from research on one tissue system could inform investigations of others and lead to better understanding of the role of basic biological processes in promoting health or causing disease across a number of tissues. Because perturbations of these basic processes can lead to disease, comparisons among diseases could provide researchers with new insights into potential mechanisms and therapeutic targets.

Clinical research plays a vital role in translating basic knowledge into interventions to improve health. Researchers are developing innovative approaches to clinical research that incorporate existing patient data systems and other emerging resources. At the same time, there is growing recognition and awareness of the role of biopsychosocial factors as important contributors to both disease manifestations and responses to interventions. Careful analysis of patient characteristics as well as particular patterns of disease in a specific person (endotype), including patient-reported symptoms and preferences, will contribute to development of therapies personalized for the individual patient. The PROMIS® (Patient-Reported Outcomes Measurement Information System), described below, is an example of one tool to capture a patient’s daily quality of life through self-reporting. Finally, including patients and their caregivers as partners in the design and implementation of research projects, including the development of research questions, directions, priorities, and outcome measures, will be critical to the success of efforts to improve the development and testing of new therapies.

There are many ways to clinically measure a patient’s health status, such as through blood tests and X-rays. However, these may not capture features that affect daily quality of life, such as pain and fatigue. To address the need to incorporate patient input into clinical research and care, NIH is advancing patient-reported outcome (PRO) measures. These efforts, including the Patient Reported Outcomes Measurement Information System (PROMIS®)1, grew out of an NIH Common Fund initiative2 administered by NIAMS. The initiative supported the development and validation of a wide range of psychometrically and clinically robust instruments to gather information on health-related concerns, such as pain, fatigue, and physical functioning, across a wide range of disorders in adults and children. PROMIS adult and pediatric measures are being adapted for use across numerous diseases, languages, literacy levels, and ethnic groups. Patients can report their information in a variety of settings, including by phone or online. Today, the tools are being used to assess symptoms and measure changes over time and in response to treatment in both clinical trials and patient care settings both nationally and internationally. The measures are helping to better tailor and monitor treatments and understand diseases and their impact on patients’ symptoms, functioning, and quality of life. NIAMS is encouraging the use of these tools to foster patient-centric care for diseases within its mission.

Although the original Common Fund initiative that spurred the development and validation of PROMIS and other PRO measures has ended, the program has successfully shifted to a sustained research effort supported by a trans-NIH cooperative agreement. Current work is advancing the science of PRO measures (PRO-omics) and facilitating their integration in complementary and meaningful ways with other ‘omics’ (e.g., transcriptomics) data that assess a person’s disease and health status. Some of the available measures are designed to assess a specific disease or condition, while others, such as PROMIS, are applicable to many different conditions and can therefore be used to facilitate within or across disease comparisons.

PRO measures increasingly are being adopted for use in pediatric populations. For example, NIAMS administers the Pediatric Patient Reported Outcomes in Chronic Diseases (PEPR) consortium3, an initiative that capitalizes on recent advances in PROMIS pediatric measures to assess the health of children with a variety of chronic diseases and conditions in clinical research and care settings. The PEPR tools are informing and supporting the NIH Environmental Influences on Child Health Outcomes Program4 to capture the perspectives and experiences of children and their families who are participating in this groundbreaking pediatric consortium.

For further information see:

1 The Patient Reported Outcomes Measurement Information System (PROMIS®) webpage.2 The Common Fund PROMIS® webpage.3 Information about the Pediatric Patient Reported Outcomes in Chronic Diseases (PEPR) consortium.4 The Environmental Influences on Child Health Outcomes Program website.

Research funded by the Institute is relevant to a number of populations, including groups historically underrepresented in biomedical research. NIAMS supports research to explore biological, mechanistic, environmental, biopsychosocial, cultural, and other factors that affect the health of specific populations and how these factors may differ among groups, the interactions among these factors, and their potential contribution to health outcomes. The next 5 years offer exciting opportunities to develop interventions that could improve health and reduce health disparities. For example, the interface between patients and the health care system is emerging as an important area of research, and more is being learned about how an individual’s background affects communication with health care providers, perception of the risks and benefits of treatments, and individual patient preferences. Ultimately, NIAMS-funded research seeks to provide evidence to achieve health equity for all populations.

The goal of the NIAMS FYs 2020-2024 strategic plan is to advance and accelerate research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. The plan includes five objectives to advance and accelerate:

The following sections describe NIAMS objectives in each of these five areas. These objectives focus on research to understand basic mechanisms of biological processes, investigations of the genetic and environmental causes of disease, preclinical research to translate new knowledge into potential therapies, and clinical research to assess the efficacy or new interventions. Research related to the objectives includes hypothesis-driven research as well as discovery research depending on the stage of the research field and ability of the scientific approach to shed light on a particular research question. Many topics described in the preceding section on cross-cutting scientific themes are addressed more comprehensively in these sections.

Although much of the arthritis and musculoskeletal and skin diseases research landscape falls within the NIAMS mission, some is included in the missions of other NIH components. In practice, the NIAMS collaborates closely with other NIH Institutes, Centers, and Offices in these areas of shared interest to achieve synergies and avoid duplication of effort. Research areas that clearly fall outside of the NIAMS mission (e.g., cancer) are generally not included in this strategic plan.

As part of NIH, NIAMS is focused on the discovery of new biological knowledge and its application to improve human health. NIAMS helps to generate the evidence needed to advance new and improve existing treatments. Because the agency’s mission does not cover the entire healthcare continuum, the Institute works with partners in other Federal agencies, professional and patient groups, and industry to speed the translation of NIAMS-funded research.

NIAMS Systemic Rheumatic and Autoimmune Diseases programs address basic, translational, and clinical research, including clinical trials and observational and mechanistic studies, focused on immune-mediated arthritis and autoimmune-related acute and chronic disorders in adults and children. As noted in the introduction to this plan, many of these diseases disproportionately affect women and groups historically underrepresented in biomedical research. While the underlying causes for these differences are largely unknown, progress is occurring in understanding them and translating that knowledge into effective treatments.

The results of NIAMS-funded research have paved the way for biologic therapies for systemic rheumatic and autoimmune diseases. These therapies have improved outcomes and quality of life for many patients, highlighting the importance of fundamental research in improving health. Going forward, NIAMS will continue to build on this progress to further understanding of systemic rheumatic and autoimmune diseases and to develop even more effective and personalized treatment approaches.

In adults, systemic rheumatic and autoimmune diseases and disorders include, but are not limited to:

Pediatric diseases include all forms of juvenile idiopathic arthritis (JIA), childhood-onset lupus, scleroderma-related diseases, pediatric fibromyalgia, and periodic fever syndromes and other autoinflammatory disorders. Several aspects of these diseases differ between adults and children (e.g., risk factors, pathogenesis, outcomes), and these factors require special attention when conducting research on pediatric conditions.

Rheumatologists have long recognized the higher incidence of many rheumatic diseases within families and certain ethnic populations, suggesting that genetics play a role in risk. Perseverance in gathering biospecimens and clinical histories from patients and their relatives—along with the explosion of knowledge and technological advances in genetics and genomics—have opened new research avenues.

Genome-wide association studies (GWAS) and other genomic approaches, such as whole genome or exome sequencing, have identified a series of genes and gene polymorphisms, also referred to as genetic variants, that relate to disease risk and severity in different populations. Some of these polymorphisms point to common gene regulatory elements that may be shared in many autoimmune diseases. The discovery of genetic variants, most of which reside within non-protein-coding regions of the genome, has advanced understanding of disease mechanisms, facilitated identification of potential pathways to target for therapy, and improved the assessment of disease risk. Despite progress in understanding some of the genetic variants involved in autoimmune and systemic rheumatic diseases, and in genomics approaches that have identified tens of thousands of genetic variants, the functional significance of most variants remains largely unknown. Follow-up studies are needed to understand how they may interact with each other, regulate expression and activity of target genes, and contribute to changes in cell functions and cell biology in ways that may affect disease risk and pathology in disease target tissues.

Environmental factors (e.g., gut microbes, dietary components, chemicals, ultraviolet light, infectious agents) may interact with the host by influencing gene activities or turning on or off genes to affect an individual’s risk for diseases such as lupus, rheumatoid arthritis, and scleroderma. Environmental factors influence disease risk by interacting with the genome to alter gene expression without changing the underlying DNA. Analyses of these epigenetic changes, as well as genetics and transcriptomic data, are expected to provide novel insights into the development, progression, and severity of rheumatic diseases.

Broad areas of potential research directions include:

The rapidly progressing fields of genetics and genomics offer powerful tools for drug discovery and for investigating the influence of genomic variations on drug responses, including drug efficacy and toxicity. The application of genomic approaches to well-characterized longitudinal clinical cohorts holds great promise for development of personalized medicine for systemic rheumatic and autoimmune diseases.

Broad areas of potential research directions include:

Increased knowledge of basic functioning of the immune system, and in particular, the fundamental biology of autoimmunity, has advanced our understanding of systemic rheumatic and autoimmune diseases. The two arms of the immune system—the innate and adaptive arms—coexist as protective and potentially injurious forces. Successful immune response depends on the body’s ability to produce diverse receptors on the surface of immune cells. The innate immune system is the body’s first line of defense and reacts quickly and broadly to environmental or pathogenic insults to the body. It consists of anatomical barriers, networks of soluble mediators, and effector cells. In contrast to the innate immune system, the adaptive immune system provides more specific, targeted, and sustained responses. Because of the enormous number of antigens that the body routinely encounters and their potential similarity to the body’s own components, the adaptive immune system is at risk of producing self-reactive (autoreactive) cells that can trigger autoimmunity. The process of immune tolerance addresses this problem by either removing autoreactive cells from the system or by diminishing their reactivity enough to prevent disease. When there is a breach or dysregulation in immune tolerance, autoimmune disease can occur. Improved understanding of the immune system, the complex interplay between innate and adaptive immunity, as well as interactions between the immune system and various tissues in normal and pathological conditions will enhance development of antigen-specific and/or autoreactive, personalized, cell-specific therapies that leave protective, global immune function intact.

Broad areas of potential research directions include:

Chronic inflammation is a characteristic of many autoimmune and autoinflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory myopathies, and lupus. Inflammation likely causes or exacerbates joint swelling, acute and chronic pain, fatigue, sleep disorders, depression, and organ damage. Research advances detailing molecular and cellular contributors to inflammation have provided critical insights into potential causes and the development of therapeutics in many rheumatic diseases.

Broad areas of potential research directions include:

Pain is one of the most important symptoms affecting quality of life for patients with rheumatic diseases and chronic pain syndromes. Research on the biological mechanisms of pain in rheumatic diseases may lead to new approaches to manage pain.

Broad areas of potential research directions include:

Manifestations of rheumatic diseases can be diverse and may affect many organs and organ systems, including skin, joints, and other internal organs such as the kidneys, heart, lungs, intestines, blood vessels, and brain. Although immune dysregulation plays a major role in these diseases, the structure and function of target organs such as the vasculature may contribute significantly to the development of tissue damage and fibrosis in clinical disease. A better understanding of mechanisms of tissue damage may suggest how to modify contributing factors and lead to approaches to minimize or prevent some of the most serious complications of autoimmune disease.

Broad areas of potential research directions include:

Unraveling the complexity of rheumatic diseases to advance the development of effective and targeted interventions requires an understanding of how disease initiation and progression are integrated. Much of this research is conducted in model systems that lead to further refinement of therapeutic approaches and design before human testing.

Recent progress in developing molecular and genetic tools for basic research (e.g., single-cell analysis, ‘omics technologies, genome editing, and sequencing techniques for identifying bacterial isolates) has facilitated disease-specific investigations. Preclinical and translational studies are expected to advance knowledge of underlying mechanisms and facilitate development of therapies for application in clinical practice.

Model systems aim to define disease mechanisms, as well as to design and test approaches to prevent disease onset and progression. Animal models offer some of the best systems available for detailed phenotyping of various diseases and conditions, enabling scientists to identify human disease-related genes and gain a better understanding of how these disease genes function. Current mouse models focus on immune-cell function and can recapitulate many aspects of human diseases (e.g., rheumatoid arthritis and lupus), which provides important information about pathogenic and therapeutic pathways and their interactions. Ex vivo or in vitro human cell-based systems may also serve as important experimental models for studying systemic rheumatic and autoimmune diseases.

Given the complexity of immune responses, etiologic and mechanistic questions about disease are difficult to answer. By integrating large amounts of research data into dynamic computer-based models, systems biology approaches can be used to better understand, over time, interrelationships and regulation of various immune system components.

Broad areas of potential research directions include:

Advances in immunology, molecular biology, and genetics are yielding an emerging set of therapies for systemic rheumatic and autoimmune diseases. The goal of NIAMS-supported research is multifold: ensure a continuous supply of new targets for intervention, understand mechanisms of action of new and existing drugs, and develop adequate clinical trial methodologies to test these interventions. The Accelerating Medicines Partnership, described in the box “Progress in Accelerating New Therapies for Rheumatoid Arthritis and Lupus,” is an example of a program NIAMS has used to ascertain and define shared and disease-specific biological pathways that researchers can study to identify relevant drug targets for treating autoimmune diseases.

To increase the number of new diagnostics and therapies and reduce the time and cost of developing them, NIAMS is participating in the Accelerating Medicines Partnership (AMP)1, a collaboration among NIH, the Foundation for the NIH (FNIH), the U.S. Food and Drug Administration (FDA), biopharmaceutical companies, and nonprofit organizations. NIAMS, in partnership with the National Institute of Allergy and Infectious Diseases, contributes to the AMP in two disease areas: rheumatoid arthritis and lupus. The AMP in rheumatoid arthritis and lupus2 research network focuses on immune and tissue resident cells from organs affected by the diseases, including cells from the joints of individuals with rheumatoid arthritis and from the kidneys and skin of people with lupus. The network is adapting cutting-edge technologies to allow those cells to be analyzed individually using high-throughput approaches. At the same time, the network has pioneered important innovations in the conduct of research, including new models for collaboration among dispersed research institutions, groundbreaking strategies to build capacity for the acquisition of synovial and kidney biopsies in the United States, and standardization of sample processing protocols across multiple research sites. In addition, the program is making its data available to the broader research community to foster additional research on autoimmune diseases and enhance the return on investment in the program.

During the first phase of the program, investigators compared cells taken from the tissues of rheumatoid arthritis or lupus patients to cells from unaffected individuals with the goal of identifying changes in cells and biological pathways that occur in disease, but not in health. Results from phase I studies of rheumatoid arthritis revealed that certain subpopulations of immune cells and fibroblasts are increased in individuals with rheumatoid arthritis compared to controls.3 Phase I studies of lupus uncovered subsets of white blood cells that are active in the disease and identified specific proteins that could be explored as therapeutic targets.4 Other lupus phase I studies revealed differences between keratinocytes and kidney tubular cells of individuals with lupus nephritis versus healthy controls in the expression of genes that respond to type I interferon proteins.5,6

In the second phase, the network is exploring differences at the molecular level among patients with the same disease to determine why disease course and response to therapy can vary so widely among patients with the same disease. Understanding this variation could pave the way for precision medicine—the ability to tailor treatments to individuals. Early indications from the lupus studies suggest that differences in so-called “interferon signatures” between individuals with lupus can help predict whether a particular patient is likely to respond to therapy.6 Additional phase II studies are expected to provide further insights into differences that could be used to personalize therapy for rheumatoid arthritis and lupus.

For further information see:

1 The Accelerating Medicines Partnership website.2 The NIAMS website for the AMP Rheumatoid Arthritis/ Systemic Lupus Erythematosus Program.3 Zhang F, et al. Nat Immunol. 2019. PMID 31061532.4 Arazi A, et al. Nat Immunol. 2019. PMID 31209404.5 Der E, et al. JCI Insight. 2017. PMID 28469080.6 Der E, et al. Nat Immunol. 2019. PMID 31110316.

Broad areas of potential research directions include:

The goal of biomarker research is to use modern approaches to discover, validate, and qualify biomarkers for use in disease diagnosis, prognosis, and evaluation of therapies. In general, molecular/cellular biomarkers are measured in blood, body fluids, or tissues. For many disorders, a panel of biomarkers rather than a single biomarker may provide the most clinically useful information.

Broad areas of potential research directions include:

Imaging early or late changes in disease in target organs is increasingly important for characterizing disease status and determining responses to therapies. Advanced imaging technologies are providing insights into anatomic changes in disease states. For example, magnetic resonance imaging (MRI) has been used to detect structural pathology in rheumatoid arthritis and ankylosing spondylitis.

Broad areas of potential research directions include:

The complexity of systemic rheumatic and autoimmune diseases, the diverse presentation and progression of many of these illnesses across patient populations, and the occurrence of multiple comorbid (co-occurring) rheumatic and other complex diseases in the same person, creates significant challenges in the diagnosis and management of these conditions. NIAMS supports clinical research to advance understanding of these diseases and to develop effective therapies to prevent or treat them.

Many rheumatic diseases do not respond adequately to treatment, particularly due to the diverse presentation and progression of these illnesses within a patient population, along with complex interactions of disease-relevant biological pathways. Therapies that appear to be promising through preclinical modeling and testing require clinical testing in defined patient populations, or cohorts, as well as creative approaches to assessment of health outcomes. In addition, widely available modern imaging technologies (such as ultrasound, optical tomography, and MRI) as well as sophisticated wearable devices require testing in clinical trials to evaluate their utility in patient care and management.

Broad areas of potential research directions include:

The incidence, morbidity, and mortality of rheumatic diseases are important foci for epidemiological research, particularly for studying complex, systemic autoimmune diseases and comorbidities. Health services delivery requirements for people with rheumatic diseases is an important example of how illnesses with low mortality can still exert significant physical and quality-of-life effects.

Broad areas of potential research directions include:

There is a need to better understand social determinants of health (defined as the conditions in which people are born, grow, work, live, and age), and the wider set of forces and systems shaping the conditions of daily life, especially for health disparities. Behavioral and social science research is contributing important epidemiologic information and approaches to managing mental health and distressing symptoms of these disorders. Interdisciplinary investigations that integrate behavioral, social, and biomedical sciences will likely enhance treatment and management of patients with rheumatic diseases, reduce disability, and may shed light on complex mechanisms involved in disease processes.

Broad areas of potential research directions include:

Broad areas of potential research directions include:

Broad areas of potential research directions include:

NIAMS Skin Biology and Diseases programs fund basic, translational, and clinical research in skin, including both common and rare skin diseases. These programs include investigations of the basic molecular, cellular, and developmental biology of skin, as well as studies of skin as an immune, sensory, endocrine, and metabolic organ. Research on wound healing, autoimmunity, inflammation, heritable diseases, and birth defects is also included, with a focus on translating fundamental research findings into novel diagnostic tools, effective therapeutics, and efficient, cost-saving disease management.

Understanding skin biology in the context of whole-body physiology is a new horizon. Skin is an integral part of the human body, and skin function and skin diseases are influenced by internal and external environments. Increasing evidence suggests that skin homeostasis is modulated by the immune, nervous, and endocrine systems, as well as by circadian rhythms and resident microbial flora. Studying interactions between skin and other organs is increasingly important for advancing knowledge of skin health and disease and thus calls for multidisciplinary collaborations to invigorate and enrich the skin research field.

Advances in basic research on skin biology have been the foundation for improving skin health over the past century. Basic research will continue to be the driving force for innovation in combating diseases affecting skin as a whole or in specific regions of the body, as well as skin appendages such as hair and nails.

Understanding skin biology at the cellular and molecular levels is the foundation for elucidating normal and disease processes at the tissue level. These types of studies are intimately connected to the state-of-the-art technology and methodology used to understand DNA structure, chromatin organization, gene regulation, inter- and intracellular communication, and cellular control mechanisms and behavior in living tissues.

Broad areas of potential research directions include:

Skin structure and function are developed and maintained by a variety of stem cells (e.g., keratinocyte stem cells, hair follicle stem cells, melanocyte stem cells, sebaceous gland stem cells, mesenchymal stem cells). Understanding skin stem cells is a key research area.

Broad areas of potential research directions include:

Skin is an organ containing multiple tissue types and appendages. How this complex structure arises from a simple epithelial layer during embryonic development has fascinated researchers for more than a century. Understanding skin developmental biology has contributed to recent advances in promoting skin regeneration and wound healing and in combating diseases.

Broad areas of potential research directions include:

The primary function of skin is to provide a physical barrier that is flexible, resilient to mechanical force, properly sealed, and capable of blocking ultraviolet radiation, with regional specializations to accommodate movement, pressure, and friction. The skin barrier is also biological, keeping microbial flora at appropriate levels and repelling their infiltration. Defects in skin barrier structure and function are a major cause of diseases.

Keratinocytes are the principal cells that form the body’s outer physical barrier. They also contribute to other functions of skin (e.g., immune and sensory).

Broad areas of potential research directions include:

Electromagnetic radiation, visible or invisible, has many effects on normal and pathological skin physiology. A primary shield of this radiation is created by melanocytes, cells that possess unique properties that protect vital stem cells and subcutaneous tissues through the production and transfer of melanin to keratinocytes. Pathological conditions affecting melanocytes can lead to hyper and hypopigmentation of skin that can significantly affect an individual’s quality of life.

Broad areas of potential research directions include:

Basement membrane and dermis provide much of the structural support and mechanical strength of the skin barrier. Scientists are just now appreciating the role of extracellular matrix (ECM) in regulating cytokine activity and cellular behavior. A major focus of research in this area is determining how fibrosis develops. Another important area is understanding inherited defects in ECM proteins, that is, heritable connective tissue disorders (see also Genetics, below, for more information).

Broad areas of potential research directions include:

The cutaneous vascular plexus of the dermis/hypodermis is a dynamic, environmentally responsive network of blood vessels that provides nutrients, acts as a conduit for the immune system, and is involved in thermoregulation and wound healing. The skin is also home to an elaborate network of lymphatic vessels that parallels the major blood vascular plexuses and enables clearance of fluids, macromolecules, cells, and foreign material from the dermis.

Subcutaneous adipose tissue has been understudied, and recent advances suggest that in addition to thermo-insulation, its functions also include regulation of wound healing, fibrosis, hair cycling, and the innate immune response to bacterial infection.

Broad areas of potential research directions include:

Barrier defects and wounds can lead to a variety of skin diseases. Barrier leakage can cause excessive loss of water and other small molecules or increased infiltration of environmental substances including microorganisms that lead to skin immune reactions. More severe disruption of the skin barrier triggers a wound-healing response, a complex process shaped during evolution to ensure rapid restoration of tissue integrity. A large repertoire of cell types performs multiple functions during this process: covering the wound bed, fighting microbial infection, and rebuilding tissue architecture, an inherently multifaceted process.

Broad areas of potential research directions include:

Skin is not only a major physical barrier but also a complex neuroimmune organ densely coated by microbial communities and populated by keratinocytes, neurons, hair follicles, and resident immunocytes. In combination, these cells provide a robust immunological barrier to potential insults. In response to invading pathogens, groups of cells—including microbial commensals, keratinocytes, and immunocytes—together neutralize invaders and subsequently restore skin homeostasis. Failure to restore skin homeostasis may lead to microbial dysbiosis and deregulated cutaneous innate and/or adaptive immunity, resulting in inflammatory and/or autoimmune skin diseases.

Keratinocytes screen their microenvironment continuously and respond rapidly to signals by expressing pro-inflammatory cytokines, chemokines, and antimicrobial peptides (AMPs). In addition, keratinocytes can initiate adaptive immunity by presenting foreign antigens to resident skin memory T cells and effector T cells. Multiple other types of immunocytes, such as Langerhans cells, dermal dendritic cells, macrophages, monocytes, innate lymphoid cells, and others also screen the external microenvironment, epidermis, and/or dermis. Importantly, microbial commensals help the skin-based immune system mature and release factors such as AMPs that antagonize pathogen invaders. Skin is also innervated, and the functions of immunocytes, keratinocytes, and neurons are linked. Findings focused on the regulatory role of microbial commensals, keratinocytes, and immunocytes—and their expressed factors, such as cytokines, chemokines, microbial and keratinocyte AMPs, and neuropeptides—have opened new avenues to understanding the immunobiology of healthy and diseased skin.

Broad areas of potential research directions include:

The easy accessibility of skin facilitates molecular and cellular analyses of lesions and enables a systems biology approach to studying inflammatory and autoimmune skin diseases. These types of studies identify functional signatures of these diseases, for example, differentially regulated genomics, epigenomics, transcriptomics, proteomics, and metabolomics, and changes in activated cellular subsets, antibody and receptor repertoires, signal transduction pathways, and the microbiome.

Additional research is needed to improve understanding of cellular and molecular mechanisms that contribute to complex skin disease pathogenesis. Artificial intelligence and computational models that integrate information obtained from high-throughput proteomics, transcriptomics, genome-wide association studies (GWAS), deep genome-wide sequencing studies, the Encyclopedia of DNA Elements (ENCODE) project, 3D chromatin structure and epigenetic markers data, and functional genomic studies will reveal novel mechanism by which genomic and proteomic alterations result in clinical manifestations of skin immune diseases.

Broad areas of potential research directions include:

More research is needed to discover innate and/or adaptive cellular and molecular mechanisms that trigger and control pediatric and adult inflammatory and autoimmune skin conditions such as hidradenitis suppurativa, Steven-Johnson-TEN, pemphigus, pemphigoid, psoriasis, atopic dermatitis, ichthyosis vulgaris, alopecia areata, cicatricial alopecia, vitiligo, acne, rosacea, immune-mediated itch, and others, and to understand comorbidities associated with them. Activities described in the box “Understanding Co-occurring Conditions in Psoriasis” are examples of research to address comorbid conditions associated with psoriasis.

Certain chronic diseases seem to occur together. For example, psoriasis is associated with an increased risk of developing conditions such as cardiovascular disease, diabetes, depression, and psoriatic arthritis. Managing the care of patients with multiple simultaneous health issues, often referred to as comorbidities, is challenging. In addition, patients with multiple chronic conditions may have worse health outcomes and quality of life than other patients. Recognizing the importance of addressing co-occurring conditions, NIAMS supports research to understand why such conditions develop, identify patients at highest risk for them, and determine how best to treat their conditions.

As part of its investment in psoriasis research, NIAMS supports a varied portfolio of efforts related to co-occurring conditions. A 2017 NIAMS roundtable brought together researchers in dermatology and rheumatology to discuss research needs in psoriatic arthritis, a form of joint inflammation that can occur in people with psoriasis.1 A NIAMS-funded translational research center is using cutting-edge technologies and clinical and laboratory data from patients to help predict which patients are most likely to develop comorbidities and to identify drugs that could be repurposed to treat them.2

Several NIAMS-funded studies have provided information that could improve treatment and management of psoriasis comorbidities. One such project, which examined the risk of type 2 diabetes in people with psoriasis, suggests a link between psoriasis severity and the development of diabetes.3 The results underscore the importance of diabetes prevention in psoriasis, especially for those with severe disease. Another study showed that individuals with psoriasis, particularly those prescribed a systemic therapy, that is, a drug that spreads throughout the body, are at increased risk for developing liver disease. This suggests that patients on systemic therapy should minimize exposures, for example, to certain medications, that may damage the liver.4 Other work supported by NIAMS tested whether the anti-inflammatory drug adalimumab mitigates the increased cardiovascular risk seen in patients with severe psoriasis.5 Although the drug was not effective at reducing cardiovascular risk factors, the results provide important new information for clinicians as they decide the best course of treatment for their patients.

For further information see:

1Summary of the 2017 Roundtable.2The Center of Research Translation Project Information.3 Wan MT, et al. J Am Dermatol. 2017. PMID: 29128465.4 Ogdie A, et al. J Invest Dermatol. 2018. PMID: 29104161.5 Metha NN, et al. Circ Cardiovasc Imaging. 2018. PMID: 29776990.

Broad areas of potential research directions include:

Skin is the body’s largest interface with its immediate external environment and it is exposed to numerous physical, chemical, and biological stimuli. Thus, over time, skin has evolved into a sensory organ and an extension of the body’s nervous and immune systems that interacts with the external environment. Skin is also an endocrine organ, known as a site of hormone synthesis, and capable of communicating with the rest of the body via multiple endocrine pathways.

Research needs and opportunities related to itch were discussed in greater detail at a 2010 NIAMS roundtable discussion and remain relevant to this Strategic Plan.

Broad areas of potential research directions include:

Skin appendages, for example, hair, nail, sebaceous glands, and sweat glands, provide many of the auxiliary functions of skin. Compared to the epidermis, these epithelia-derived mini-organs/tissues are understudied. One exception is hair/the hair follicle—a powerful model system for understanding tissue/organ development and regeneration.

Broad areas of potential research directions include:

Many, if not all, aspects of skin function are known to be affected by genetic mutations, producing a spectrum of clinical manifestations ranging from minor, cosmetic, and irritant (deteriorating quality of life) to fatal. Genetic factors that affect skin conditions can be monogenic, polygenic, or mosaic, including sequence variations in protein-coding DNA and in noncoding regulatory regions that operate through genetic and epigenetic mechanisms. A better understanding of these genetic and epigenetic factors, as well as how the variants and mutations contribute to disease phenotype, is essential to develop effective therapies. A large repertoire of therapeutic modalities is employed to combat heritable skin diseases.

Broad areas of potential research directions include:

Regeneration mimics the embryonic process that shapes original tissue; therefore, it heals injury without the scarring and functional deficits associated with repair, which relies on the use of substitute, or “makeshift,” material to close a wound rapidly. Because only limited tissue regeneration occurs in humans, treatment of large-area acute skin wounds, such as extensive burns and trauma, involves both regeneration and repair and a key challenge is how to restore tissue function after a wound is closed. Regenerative medicine in skin involves research on developmental processes, tissue neogenesis, stem cells, the skin microenvironment, and engineering approaches to create temporary tissue substitutes or modify wounds for improved healing and functional restoration.

The concept and practice of regenerative medicine are firmly rooted in developmental biology. Knowledge of developmental biology principles related to skin provides important insights into tissue regeneration. Studies of hair follicle neogenesis have revealed that adult skin may possess more regenerative capacity than previously thought (see also Developmental biology, above).

Broad areas of potential research directions include:

Tissue neogenesis is the process of regeneration of lost or damaged tissues or organs in response to injury and contrasts with wound healing, which involves closing the injury site and scar formation. While non-mammalian vertebrates and some mammals can repair skin without scars, human adult skin has very limited regenerative capacity for scar-free repair. The complete regeneration of injured or diseased human skin remains the ultimate goal and a major challenge of regenerative medicine.

Broad areas of potential research directions include:

3D skin cultures mimic in vivo human skin better than monolayer cultures and provide the opportunity for the creation of patient-specific models of disease. These models can be used to study disease pathogenesis and genetics, and to test new therapies. Engineered skin can also be used directly as a therapy.

Broad areas of potential research directions include:

In biomedical research and therapeutic development, hypotheses and drugs must be evaluated in model systems. These can be living organisms or in silico (computer or mathematical) models.

Genetically modified organisms and many naturally occurring genetic variants are powerful tools for skin research. Even so, finding suitable models to address specific questions in skin research remains challenging. One recurring issue is whether findings in mouse models can be directly translated into humans. Transplantation of human skin to a mouse, or reconstituting the human immune system in a mouse, may be useful for investigating some human skin diseases. Some complex diseases can be modeled with transgenic mammals, and some polygenic diseases (e.g., alopecia areata) have emerged spontaneously in mice and in other large animals.

Broad areas of potential research directions include:

Cultured skin substitutes and other in vitro models of skin are in current use for experimental studies and toxicology screening.

Broad areas of potential research directions include:

Systems biology is a research approach used to understand the network behavior of biological systems, to predict effects of perturbations on a system, or to develop novel ways to modulate a system’s behavior. In systems biology modeling, conceptual and mathematical models are developed and trained by test data and then used to predict the behavior of real biological systems. To facilitate development of a successful systems biology model it is critical to attain consensus on standards for collecting and reporting research results.

Broad areas of potential research directions include:

Knowledge of pathogenic pathways and basic skin biology facilitates development of small-molecule and biologic therapies (e.g., antibodies) that target specific components of these pathways. Such approaches enable effective and systemic treatment with minimal side effects, which is desirable for widespread skin lesions. Because of the accessibility of skin, treating diseases of skin, hair, and nails—including diseases of the scalp and of skin appendages—need not be limited to chemical interventions, since physical methods have also been explored.

Needs and opportunities related to therapies for pediatric dermatologic disease were discussed in 2011 at a NIAMS roundtable, and that discussion remains relevant to this Strategic Plan.

Broad areas of potential research directions include:

Correcting defective genes may be possible to treat monogenic skin diseases such as epidermolysis bullosa (EB) simplex. One possible approach would be to use CRISPR/Cas technology in combination with iPS cells, thus addressing the disorder’s root cause. Another approach being tested for people with EB is treatment with donor-derived bone marrow stem cells.

Broad areas of potential research directions include:

The skin barrier makes targeted delivery of small molecules and biological drugs to the epidermis and dermis challenging. Conversely, the permeability of this barrier also presents an opportunity to consider transdermal delivery strategies to treat systemic diseases. Broad areas of potential research directions include:

Several types of physical therapies are used in dermatology practice. Examples include phototherapy (e.g., ultraviolet light irradiation) and chemically modified water baths.

Broad areas of potential research directions include:

Skin diseases, which frequently compromise quality of life, are not always seen as important research targets relative to illnesses with greater mortality and morbidity. However, the impact of skin disease on people’s lives is significant. Furthermore, some skin diseases are accompanied by systemic effects and comorbidities.

Clinical trials based on solid preclinical studies are essential for improving the public health. Combination therapies, evidence-based comparisons of treatments, and cost-effectiveness are critical topics for future research.

Broad areas of potential research directions include:

The incidence and morbidity of skin diseases are important subjects for epidemiological research. Optimal distribution of health services for skin diseases highlights the relevance of treating illnesses with significant physical and quality-of-life effects.

Broad areas of potential research directions include:

Prevention studies are critical to promote health through the identification of risk factors for skin diseases, disorders, or injuries. They are also important for detecting and preventing progression of asymptomatic or early-stage skin conditions.

Broad areas of potential research directions include:

Changing lifestyle and habits can prevent many skin diseases, which provides opportunities for behavioral intervention. Furthermore, people with skin diseases are frequently affected by psychosocial problems due to social stigma. These factors highlight the role of behavioral and biopsychosocial research in combating skin diseases.

Broad areas of potential research directions include:

The NIAMS Bone Biology and Diseases programs fund a broad spectrum of basic, translational, and clinical research on buildup and breakdown of bone. Acquisition and preservation of adequate bone mass, as well as maintenance of architectural and material qualities that confer bone strength, are crucial for protection against fracture. Osteoporosis, or low bone mass, increases risk of fracture with associated morbidity and reduced quality of life. In the United States today, more than 53 million people either already have osteoporosis or are at high risk due to low bone mass. Because osteoporosis is common among older people—particularly in women after menopause—prevention, diagnosis, and treatment of osteoporosis will continue to have major public health implications as the U.S. population ages. Healthy People 2030, the Nation’s public health agenda, will seek to improve osteoporosis-related outcomes.

NIAMS supports studies on the control of bone remodeling (bone formation, bone resorption) and mineralization, as well as the effects of hormones, growth factors, and cytokines on bone cells. The Institute has overseen several large epidemiologic cohorts to characterize the natural history of osteoporosis and identify genetic and environmental risk factors that contribute to fracture. NIAMS also supports clinical trials to test the effectiveness of interventions to prevent fractures associated with osteoporosis and other metabolic bone diseases. In addition, the NIAMS Bone Biology and Diseases programs support research on the causes, pathophysiology, and treatment of less common bone diseases, such as osteogenesis imperfecta and Paget’s disease of bone, as well as a wide range of developmental disorders of the skeleton, many of which are genetic.

Bone cells perform key processes in bone remodeling: formation of new bone by osteoblasts and resorption or breakdown of old or damaged bone by osteoclasts. In a healthy adult skeleton, these processes are balanced through the overall process of bone remodeling.

Osteocytes, fully mature osteoblasts embedded in mineralized bone, have emerged as a crucial population of cells for controlling bone physiology. In addition, cells lining the bone surface play an important role in normal and pathologic remodeling. Disproportionate resorption compared to formation results in bone loss and can increase risk of fracture. Understanding mechanisms that regulate osteoblasts, osteoclasts, and osteocytes and influence bone resorption or bone formation may yield new therapeutic targets. Manipulating such processes could also be essential for tissue-engineering technologies using bone-forming cells.

Broad areas of potential research directions include:

Researchers have made considerable progress in understanding interactions between bone physiology and the broad network of biologic processes involving various organs and tissues. For example, muscle function and muscle mass influence fracture risk and energy metabolism affects muscle tissue and bone cells. Scientists are now poised to make further discoveries to help explain the connection between the skeleton and other mesenchymal tissues (e.g., fat, muscle, cartilage, tendon, ligament), physiologic systems (e.g., nervous, vascular, immune, digestive), tissue-specific microbiome, and energy metabolism. Bone likely functions as a target and/or regulator as it interacts with various systems during development, aging, and disease. Many drugs for conditions putatively unrelated to bone may have unanticipated skeletal effects, and bone-building drugs may have unanticipated effects on other tissues. Bone researchers in collaboration with interdisciplinary scientists who specialize in other organ systems and metabolic pathways could begin to fully define these interactions. These teams should consider not only bone but also other organs and systems that associate with bone as an integrative unit. They should also seek to understand how inputs from multiple systems received by the bone affect the body.

Broad areas of potential research directions include:

Bone shaping and growth during infancy and childhood are important for adult skeletal health. Research into processes by which bones originate in the embryo and grow during skeletal maturation promises to illuminate causes and potential treatments of developmental disorders in humans. This knowledge may lead to more effective methods for enhancing repair and regeneration of bone damaged by disease or trauma. Bone cells arise from specialized progenitor or stem cells that can differentiate to produce several types of cells in response to various biochemical signals. Understanding these cells and the signals that guide them could improve tissue engineering and regenerative medicine approaches. Stem cells are also important targets of gene-based therapy strategies for genetic diseases of bone.

Broad areas of potential research directions include:

Heredity influences many aspects of skeletal physiology, including age-associated changes. Although genetic influences on the skeleton are complex, reflecting the contributions of numerous genes and post-transcriptional epigenetic modifications, technological advances have opened the door to an unprecedented understanding of individual risk for disease as well as personalized approaches to treatment. In recent years, high-throughput genotyping and sequencing technologies have been employed to analyze many clinical cohorts, largely substantiating the potential of genomic science to illuminate questions in skeletal biology and health.

Nonetheless, much of the heritability of skeletal traits, such as bone mass and fracture risk, remains to be identified. In addition, causal variants underlying skeletal disease, as well as the biochemical processes influenced by those variants, are still largely unknown. Filling in these gaps will require an integrated analytical approach, incorporating multiple data types (e.g., single-cell analysis, epigenomics, proteomics, transcriptomics, machine learning, computational modeling) and large sample sizes to reveal functional aspects of the genome in humans and in animal models.

Broad areas of potential research directions include:

Discovering the underlying pathobiological and pathophysiological basis of bone diseases will advance the field of bone biology. Interactions between laboratory and clinical researchers are essential for translating basic discoveries into new drugs, treatments, and diagnostics. These relationships also foster clinical observations that can prompt basic and translational research.

Broad areas of potential research directions include:

Translational research characterizing the cellular and molecular mechanisms of disease may lead to new biological insights that advance the diagnosis or prevention of bone disease and inform the development of novel therapeutic agents.

Broad areas of potential research directions include:

Measuring bone mineral density (BMD) is widely considered a good screening tool for osteoporosis, but is an imperfect test for assessing the strength and fracture resistance of bone. BMD does not account for specific contributions of bone geometry, microarchitecture, and material properties that influence the ultimate mechanical performance of bone. Dual energy X-ray absorptiometry (DXA), the standard clinical measurement of BMD, is widely available and economical. However, more sensitive and sophisticated methodologies have been developed and provide a more detailed picture of bone quality and strength, such as quantitative computed tomography (QCT) with finite element analysis, high-resolution peripheral QCT, and high-field magnetic resonance imaging (MRI). The application of these newer technologies has improved our understanding of bone structure and function, but has not yet provided an alternative method for assessment of osteoporosis. Further studies may lead to improved prediction of fracture risk and monitoring of treatment response.

Broad areas of potential research directions include:

Understanding how architectural, material, and biochemical factors contribute to bone strength may identify new treatment targets or novel markers of bone health.

Broad areas of potential research directions include:

In addition to basic and translational pathophysiological research, the NIAMS Bone Biology and Bone Diseases program supports clinical research to advance the diagnosis, management, and treatment of rare bone diseases. Knowledge of disease development and progression, diagnostic tools, and therapeutic options vary across the rare bone diseases. Rare bone diseases often manifest in organ systems other than the bone and musculoskeletal systems. Thus, multidisciplinary research efforts that incorporate integrative physiology approaches to study comorbid conditions are encouraged. Further, because of the limited number of patients affected by these diseases, innovative clinical study designs are necessary. To accelerate research, patients and patient advocacy groups are important partners and should be engaged throughout the clinical research process.

Broad areas of potential research directions include:

There is great need for discovery of therapeutic interventions for rare bone diseases.

Broad areas of potential research directions include:

Characterizing osteoporosis development through clinical research is necessary to decrease prevalence, alleviate suffering, and lessen economic costs. Utilizing individual and population-based data to determine disease effects will enable better prevention approaches, produce safer therapies, improve quality of life, facilitate earlier identification of those at high risk, and reduce disparities associated with osteoporosis. Both large cohort and personalized medicine studies can yield useful information to improve bone health, prevent and treat osteoporosis, and enhance the quality of life of the millions of Americans who develop this disease.

Broad areas of potential research directions include:

Intervention studies to prevent and treat disease are essential to bring basic knowledge and translational research into clinical guidelines and practice. NIAMS recognizes the importance of maintaining wellness in healthy populations and enhancing the well-being of individuals with bone disorders or diseases. Because motivating behavior change at a population level is an issue facing many NIH components, it may be possible to integrate research on bone health messages with other health promotion programs, such as dietary and exercise interventions. Novel study designs are needed for both prevention and treatment of osteoporosis. In addition, engaging patients and participants is essential to developing effective osteoporosis prevention studies and health promotion programs.

To better characterize specific research needs related to osteoporosis interventions, NIAMS participated in an NIH Pathways to Prevention effort, described in the box below.

More than 10 million people in the United States have osteoporosis.1 Lifestyle changes, including exercise and a healthy diet, may help reduce a person’s risk of fracture. However, medications are often needed to prevent fractures if a person has osteoporosis and are essential if a person has experienced a previous fragility fracture. Effective FDA-approved medications can prevent debilitating and sometimes life-threatening fragility fractures. Reducing osteoporosis prevalence and hip fracture incidence are among the major objectives of Healthy People 2020 and 2030, the U.S. Department of Health and Human Services’ national health promotion and disease prevention initiatives.

Rigorous clinical studies have demonstrated that 3 to 5 years of osteoporosis medication therapy prevents fractures. Clinical guidelines recommend bisphosphonates as a first line of treatment for most people who have osteoporosis, but treatment rates are low and medication adherence is poor. Reports of rare but serious adverse events and greater public concern about them have coincided with a marked decrease in the use of osteoporosis drugs and a leveling off in what had been a promising decline in the incidence of osteoporotic fractures.2,3 Furthermore, as osteoporosis is considered a lifelong condition, the use of medications continues to be the cornerstone of therapy for osteoporosis. However, the benefits and risks of long-term osteoporosis drug therapies are not fully known.

In October 2018, NIAMS, the National Institute on Aging, and the NIH Office of Disease Prevention hosted a Pathways to Prevention Workshop on the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention to identify research gaps and suggest focus areas that could move the field forward. As part of the workshop process, based on an Agency for Healthcare Research and Quality (AHRQ) systematic review of the scientific evidence,4 speaker presentations, audience input, and public comments, an independent panel issued a report that lays the foundation for future research activities.5 Strategies for disseminating and implementing these findings will be developed by federal agencies to improve public health in FY 2020 and beyond.

1 Wright NC, et al. J Bone Miner Res. 2014. PMID: 24771492.2 Wysowski DK, et al. Bone. 2013. PMID: 24063946.3 Michael Lewiecki E, et al. Osteoporos Int. 2017. PMID: 29282482.4 Fink HA, et al. Ann Intern Med. 2019. PMID: 31009947.5 Siu A, et al. Ann Intern Med. 2019. PMID: 31009943.

Broad areas of potential research directions, many of which are consistent with the recommendations from the Pathways to Prevention workshop, include:

Characterizing disease mechanisms in clinical studies may enable researchers and health care providers to distinguish among disease subtypes that have similar endpoints (e.g., fracture). Further, improved understanding of individual genetic variation in osteoporosis is expected to lead to better prediction of drug response and account for heterogeneity in response to treatment. Existing databases can be retrospectively mined for information about variations in disease manifestation and treatment response.

Broad areas of potential research directions include:

NIAMS recognizes the importance of disseminating and implementing research findings; yet such findings may not be widely disseminated or implemented across clinical and community health care settings. Behavioral and social science approaches should be incorporated, where appropriate, to facilitate their adoption and implementation across diverse populations.

Broad areas of potential research directions include:

The emerging links between race, ethnicity, sex, age, disease status, and socioeconomic status and bone density, bone quality, and fracture risk suggest areas of genetic, biologic, and environmental diversity ripe for exploration. A person’s ethnicity and race, like his or her sex, influences the likelihood that he or she will develop osteoporosis and suffer fragility fractures of the hip, spine, or wrist. For example, African ancestry is generally seen as protective against fracture, relative to European and Asian ancestry. However, bone health disparities are complex across and within groups. The changing demographics of the United States afford numerous opportunities for researchers to explore biologic and nonbiologic causes of disparities related to fragility fractures and to test strategies to ensure that all Americans benefit equally from efforts to monitor and improve bone health.

Broad areas of potential research directions include:

The NIAMS Muscle Biology and Diseases programs encourage basic, translational, and clinical research on the biology and disorders of skeletal muscle. Studies address questions about: muscle developmental biology, growth, maintenance, and hypertrophy; physiology of muscle contraction; structural biology of the contractile apparatus; mechanisms of muscle diseases and disorders; biomarkers and outcome measures for clinical and preclinical studies; and natural histories of muscle conditions. These programs also support development and testing of therapies for muscle diseases and disorders, including cell and gene therapies, small molecule drugs and biological products, and exercise and other physical interventions to slow or prevent disease progression.

Muscular dystrophies are an area of emphasis within the NIAMS muscle research portfolio. NIAMS participates in the Muscular Dystrophy Coordinating Committee (MDCC), which includes stakeholders from federal and private organizations. Research objectives for muscular dystrophies are presented in this NIAMS Strategic Plan where they overlap with objectives for other muscle diseases. A more specific and detailed description of research objectives for muscular dystrophies is found in the MDCC’s Action Plan for the Muscular Dystrophies. That plan includes input from experts in the fields of muscular dystrophy pathophysiology, diagnosis, treatment, and patient and family care. NIAMS also partners with the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), with additional support from the National Heart, Lung, and Blood Institute (NHLBI) to fund the Paul D. Wellstone Muscular Dystrophy Research Centers program, an evaluation of which is described in the box below.

The muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive degeneration of skeletal muscles. Many dystrophies also affect other organ systems, such as the heart, brain, blood vessels, and gastrointestinal tract. Some forms occur in infancy or childhood, while others typically appear later. NIH funds a broad portfolio of research into understanding and treating various forms of muscular dystrophy. One component of this research portfolio is the Paul D. Wellstone Muscular Dystrophy Research Centers program.

NIH established a muscular dystrophy Centers of Excellence program in 2003 in response to the Muscular Dystrophy Community Assistance, Research, and Education Amendments (MD-CARE) Act of 2001, and the centers became the Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers in 2008. Although NIH has refined the program over the past 15 years, the neuromuscular disease research landscape has changed significantly since its inception. As the next award competition cycle approached, the principle of good stewardship suggested that a comprehensive review of the Wellstone Centers program was timely and important. Therefore, the four NIH Institutes that support the Centers (NIAMS, NINDS, NICHD, and NHLBI) formed a Working Group of the NIAMS Advisory Council in FY 2018 to identify best practices for achieving the Wellstone Centers’ goals of:

The Wellstone Centers Evaluation Working Group advised the NIAMS Council, and the report was shared with the NINDS, NICHD, and NHLBI Advisory Councils to inform their discussions about the Wellstone Centers program, especially the development of Wellstone Center Funding Opportunity Announcements. The report’s executive summary, including the working group recommendations, is available online.

Understanding the process by which functional muscle fibers develop from their early, immature state may provide insights into disease mechanisms, regeneration strategies, and therapeutic targets.

Broad areas of potential research directions include:

Studying the behavior of mature muscle under various environmental conditions (e.g., use and disuse, health and disease) is critical for developing strategies to repair or regenerate muscle.

Broad areas of potential research directions include:

Studies of normal muscle-cell physiology are likely to uncover new pathways and processes that researchers could use to develop treatments for muscle diseases.

Broad areas of potential research directions include:

The mechanisms by which muscle activity directly or indirectly contributes to the causes, prevention, and treatment of diseases and disorders affecting the musculoskeletal and other organ systems are a promising area of inquiry. For example, better understanding of the processes connecting muscle activity in the context of physical activity to disease prevention/amelioration may contribute to the use of exercise as a treatment for non-muscle related health conditions.

Broad areas of potential research directions include:

Just as research on normal muscle physiology is likely to uncover new treatment targets, a better understanding of how specific molecular defects produce the abnormal phenotypes of muscle diseases will provide insights into normal muscle function.

Broad areas of potential research directions include:

Researchers can use model systems to define muscle development, function, and repair in healthy and disease states as well as to test approaches for preventing disease onset and progression. These models can be in vivo (animal), in vitro (cell culture or isolated tissue), or in silico (computer-based).

Broad areas of potential research directions include:

Several candidate therapies for muscle diseases, especially muscular dystrophies, have emerged in recent years. These include small molecules that act on cell or molecular processes, biologics such as antibodies or enzymes, gene and cell approaches, nucleic acids (e.g., oligonucleotides), as well as nutritional, behavioral, and mechanical interventions. In addition to the development of interventions specific for muscle, drugs for other conditions are being tested for muscle applications (a process called drug repurposing). The FDA has approved two therapies for Duchenne muscular dystrophy in the last 5 years, and several additional candidate therapies for muscle diseases, such as gene therapy approaches for muscular dystrophies, are rapidly moving into human clinical trials.

Broad areas of potential research directions include:

Observational cohort studies comprised of patients who have muscle diseases can provide essential information about disease symptoms, stages, and timing of disease progression, comorbid conditions, and outcomes that are important to patients. The development of biomarkers, clinical tools, and outcome measures could also inform clinical trials that are more efficient.

Broad areas of potential research directions include:

Numerous treatments of muscle diseases have demonstrated efficacy in animal models. Efficient testing of these promising interventions in humans are necessary for the development of effective treatments for various muscle diseases.

Broad areas of potential research directions include:

NIAMS Joint Biology, Diseases, and Orthopaedics programs fund a broad spectrum of basic, translational, and clinical research centered on the interplay among the body’s muscles, bones, and connective tissues. These programs include research on the biology, structure, and function of joints and surrounding tissues and the application of this knowledge to a variety of diseases and conditions. Other programs fund tissue engineering and regenerative medicine to facilitate repair of damage caused by trauma to otherwise healthy tissue; molecular biology to understand the mechanisms of joint tissue formation and defects thereof; imaging to improve diagnosis and treatment of bone and joint disorders; and clinical research focused on treatment and prevention of acute and chronic bone and joint injuries and orthopaedic conditions, including musculoskeletal pain. Other sections of this plan address basic, translational, and clinical research interests related to bone, muscle, and rheumatic diseases.

Understanding the basic biology of joints and associated tissues is critical for the development of future basic and translational research studies. The complex interactions among the cells and tissues help define the physiological differences between healthy and diseased states.

A complex series of biochemical pathways and cellular interactions underlie the physiology of healthy, damaged, and diseased musculoskeletal tissues. Understanding the process by which a multicellular organism develops from its early, immature form into a fully mature form may deepen knowledge of disease mechanisms, regeneration strategies, therapeutic targets, and treatment design. Likewise, understanding the behavior of mature cells in their own environment is critical for developing cell-based strategies to repair or regenerate musculoskeletal tissues. Insights into how biological, chemical, and mechanical conditions affect cell behavior, as well as the microenvironment and the tissues from which those cells originate, will facilitate progress in this area. Since tissues do not exist in a vacuum, improved understanding of tissue crosstalk in development of and response to mechanical stress, as well as integrated physiology, provides a basis for translational and clinical studies.

Broad areas of potential research directions include:

Research needs and opportunities related to innovative treatments for enthesis repair were discussed in greater detail at a 2017 NIAMS roundtable discussion.

Osteoarthritis (OA), the most common degenerative joint disease, affects not only articular cartilage lining bone surfaces, but also components such as subchondral bone, menisci, ligaments, capsule, synovial membrane, and periarticular muscles. Excessive, debilitating deterioration of joint tissues is a hallmark of OA, regardless of whether it is caused by an inherited mutation, a developmental or posttraumatic joint instability, a failure of the neuromuscular system to protect against repetitive loading, or metabolic events that cause excessive joint remodeling. Studies of the cellular and biomechanical factors responsible for OA onset and progression or promotion of healing and repair will likely require multidisciplinary research teams.

Broad areas of potential research directions include:

Research needs and opportunities related to inflammation’s role in OA were discussed in greater detail at a prior NIAMS roundtable discussion.

Although small animals, such as mice, have their utilities in biomedical research, their biological relevance for understanding adult human health is sometimes less robust. More research is needed to understand the parallels between small and large animal models. Some large animals (e.g., equines, certain breeds of canines) are predisposed to develop musculoskeletal conditions. How do large animal models compare with small animal models that also model risk for musculoskeletal disorders (e.g., guinea pigs)? How do results vary between male and female animals and among animals at different life stages, and what do these differences teach us about human physiology and treatment responses? Is it possible to agree on a single large-animal model to parallel research that has been conducted in mice?

Broad areas of potential research directions include:

Regenerative medicine is an area of science that seeks to develop new approaches for treating and even curing a variety of musculoskeletal injuries and diseases. It includes using stem cells and other technologies—such as engineered biomaterials and gene editing—to repair or replace damaged or aged cells, tissues, or organs, and aims to restore tissue/organ structure and function by tissue engineering and gene, cell, and pharmacological treatments. Multi- or interdisciplinary and collaborative research efforts involving both the life and physical sciences play key roles in moving this field forward.

Some of broad directions in regenerative medicine include the following topics.

Successful tissue engineering strategies require biomaterials and scaffolds that support structural and functional development and maintenance of regenerated or repaired musculoskeletal tissues. Studying the biology of tissue development and organization often informs the design of optimal biomaterials and scaffolds. Such materials could be used when regenerating tissues in vitro for subsequent implantation in vivo, as well as in direct in vivo tissue regeneration and repair.

Research on the integration of regenerated or engineered tissues within a host organism must reflect the complex physiological interactions that occur across multiple tissue types. Such systemic interactions include biological signaling processes, vascularization, innervation, and influences from the innate and adaptive immune systems. Preservation of structural and mechanical function, host and graft survival, and safety are also important.

In addition to research topics identified under Enabling technologies, above, broad research directions include:

Implants such as those used in total hip and knee replacements have been shown to be effective tools to treat end-stage arthritis that has not responded to nonoperative treatment. These implants improve an individual’s functionality and quality of life. If a joint implant fails, however, an individual may require a second surgery that is not likely to be as successful as the initial procedure. The main cause of failure is osteolysis (disappearance of bone surrounding an implant caused by a reaction to microscopic particles from an implant). Numerous research opportunities exist to develop improved biomaterials, tools to better assess implant wear, and increased knowledge of osteolysis biology and pathophysiology. Investigators are encouraged to avail themselves of data from registries of implant failures/retrievals, when appropriate.

Broad areas of potential research directions include:

Many musculoskeletal diseases are chronic and have long variable clinical courses. These conditions often take decades to develop and can be difficult to characterize. Disease progression and treatment responses are often determined through measurement of biochemical factors in blood or body fluids or through analyses of genetic biomarkers from tissues or peripheral blood cells. Broad, innovative use of imaging techniques, in combination with measurements of biochemical markers, could also allow early identification of disease onset, predict disease progression, facilitate surgical decision making, and enable direct monitoring of responses to tissue repair and therapeutic interventions.

For many musculoskeletal conditions, responses to therapies are difficult to determine. Researchers are beginning to believe that, as with many disorders, a battery of several biomarkers may be more useful than a single marker for assessing these conditions. In addition, when many different variables are collected, deducing connections among variables may require the aid of machine learning algorithms. These algorithms may result in computational models that can be used to subphenotype patients to improve diagnosis and treatment of musculoskeletal diseases. Moreover, leveraging the power of machine learning and automation of morphological grading of the tissues in the joints would enable the analysis of large sample sizes and assist the radiologist/clinician in the grading of images in a relatively short amount of time at significantly reduced cost. The box below describes an NIH effort to create a public resource to validate imaging and biochemical biomarkers for OA.

OA is the most common type of arthritis. It occurs when the tissue that covers the ends of bones in a joint is damaged, which allows the bones to rub together leading to pain, swelling, and loss of motion. A limited number of therapies exist for OA treatment. One barrier to the development of drugs that interrupt the underlying disease processes leading to OA is a lack of objective and measurable standards for disease progression for these new drugs. To overcome this problem, NIAMS, along with the National Institute on Aging (NIA), led the development of the Osteoarthritis Initiative (OAI), a nationwide, multicenter observational study to follow people who either have or are at risk for developing knee OA. This public-private partnership began more than a decade ago to gather and catalog longitudinal findings from a cohort of nearly 5,000 people with OA and healthy individuals.

All participant visits (baseline through 8 years follow-up) have been completed, which makes the OAI one of the largest and perhaps most important datasets in the history of OA research. The dataset contains clinical, genomic, patient-reported, and functional data; biological specimens; and X-ray and MRI images. The data are available free of charge at https://oai.nih.gov. In addition, genomic data from the ancillary Genetic Components of Knee Osteoarthritis (GeCKO) study, a genome-wide association study on the entire OAI cohort is available at the NCBI dbGaP website. Investigators can use this unique repository to track the natural history of knee OA across the complete spectrum of disease.

As NIAMS looks to FYs 2020-2024, extramural researchers are encouraged to examine OAI data to develop hypotheses about possible OA biomarkers of disease onset and progression, test their theories, describe the natural history of OA, and investigate factors that influence disease development and severity. These comprehensive datasets can be used to identify potential disease biomarkers and develop tools for measuring clinically meaningful improvements. The initiative also provides excellent training and research opportunities for early-stage investigators with limited funding to leverage this existing dataset and develop and test research hypotheses. In addition, OAI data serve as a novel resource for investigators with computational and machine learning expertise in other fields to apply big data methodologies to biomedical research.

For further information: https://www.niams.nih.gov/grants-funding/funded-research/osteoarthritis-initiative.

In addition to opportunities regarding biomarkers and imaging methods described under Preclinical and translational research into joint replacements above, broad areas of potential research directions include:

Characterization of disease in the context of clinical studies may enable researchers and health care providers to distinguish between disease subtypes that produce similar endpoints (e.g., OA, connective tissue injuries). As investigators consider clinical studies of musculoskeletal and orthopaedic conditions and trials of potential diagnostic strategies and treatments related to the broad areas described below, they are encouraged to consider the following issues:

The cost of childhood musculoskeletal conditions is enormous. Although some conditions can be treated effectively, resulting in full restoration of an active life, others can result in early death or progressive problems into adulthood. Still others present lifelong challenges for the affected individual and his or her family.

Prevention of childhood injury is addressed under Fractures and other types of musculoskeletal trauma, below. Other broad areas of potential research directions include:

OA is by far the most common type of arthritis, which affects an estimated 27 million Americans age 25 years and older. Although this prevalence is high, it is expected to increase even further with the increasing prevalence of obesity and the aging population. OA can affect quality of life and the ability to work and perform basic activities of daily living. Healthy People 2020 includes several objectives related to improved overall health and functioning of people who have arthritis. Current therapeutic regimens for OA are only partially effective and often have associated toxicities, and there are no disease-modifying drugs approved by the regulatory agencies at present. Further research is needed to develop effective therapies. Also see Joint replacement and Behavioral and psychosocial research sections for more information.

Broad areas of potential research directions related to risk factors include:

As described in Preclinical and translational research into joint replacements, above, implants for total hip and knee replacements are effective treatments for people with end-stage arthritis and for other surgical needs. Although infection at the site of a total joint replacement is rare, it can be devastating and require lengthy hospitalization. Other complications include implant loosening or failure, both of which require additional surgeries that are less likely to be as successful as the initial joint replacement. In addition to preclinical research examples noted in Preclinical and translational research into joint replacements and Biochemical and imaging biomarkers and computational modeling above, broad areas of potential patient-oriented research directions include:

Outcomes:

Many spinal disorders are common, costly, and potentially disabling. Low back pain affects millions of people globally and exerts an enormous socioeconomic impact. A frequent cause of disability, low back pain causes employees to lose many days of work each year. Its costs to society, and opportunities to reduce those costs, earned its position as a Healthy People 2020 objective, “Reduce activity limitation due to chronic back conditions.” Although low back pain is an important public health issue, little is known about its causes. A considerable investment in a study of surgical and nonsurgical therapies for common causes of low back pain has yielded important results. However, much remains to be discovered about strategies to improve the lives of people affected by back pain or related conditions. To facilitate research on chronic low back pain, an NIH task force developed research standards that include defining chronic low back pain, assessing its impact on people’s lives, identifying the minimum dataset that should be collected in chronic low back pain research, and defining optimal outcomes to evaluate treatment effectiveness. Recently, NIAMS established the NIH Back Pain Consortium Research Program (see Musculoskeletal pain below), a patient-centric program to promote understanding of the causes of and treatments for chronic low back pain.

Broad areas of potential research directions include:

In addition to treatment-associated health care expenditures from fractures and other types of musculoskeletal trauma, these conditions cost billions of dollars in terms of lost employment. Traumatic musculoskeletal injuries can lead to lifelong disability. Trauma is one of the leading causes of death after the first year of life. Treatment of people with fractures in conjunction with trauma to other organ systems (e.g., traumatic brain injury) is a challenge in musculoskeletal care. After-injury prevention methods to reduce complications, disability, and mortality are paramount. Further refinement of operative and nonoperative techniques and rehabilitation after fractures or skeletal trauma will improve patient outcomes, enhance the lives of patients and their caregivers, and facilitate return to the workforce.

Broad areas of potential research directions include:

Prevention:

Fitness is associated with good health and a sense of well-being. Numerous studies have shown beneficial effects of exercise in disease prevention; yet one problematic feature of exercise is potential injury. Musculoskeletal soft tissues are vulnerable to injury and damage as the result of overuse and/or trauma. These injuries are often life-altering.

In addition to examples noted under Osteoarthritis and Fractures and other types of musculoskeletal trauma above, broad areas of potential research directions include:

Musculoskeletal pain takes many forms in children and adults. From acute and chronic back pain to tendonitis, myalgia, joint pain, stress fractures, and growing pains, there are many unmet needs. These include an improved understanding of the biological underpinnings of the origins of pain and discovery, development, and testing of new nonaddictive pain treatments. For example, more rigorous studies are needed to improve our understanding of the mechanisms of chronic low back pain, improve its diagnosis and treatment, and prevent its transition from acute to chronic status. To improve understanding of chronic low back pain, NIAMS developed the NIH Back Pain Consortium Research Program (BACPAC), part of the NIH HEAL initiative (Helping to End Addiction Long-termSM). This research program is a patient-centric translational research initiative that will address the need for effective and personalized therapies for chronic low back pain by probing the biomedical mechanisms in a biopsychosocial context using interdisciplinary methods and innovative technologies.

Broad areas of potential research directions include:

Behavioral and psychosocial factors are involved in the onset, course, and outcome of chronic diseases. These factors are central in the experience of symptoms (such as pain and fatigue), disease-related distress, and coping with chronic disease, disability, and to varying extents the effectiveness of prevention and treatment. Interdisciplinary research that integrates behavioral and biomedical sciences is likely to result in enhanced management of and reduced disability from chronic diseases and may shed light on complex mechanisms involved in pathogenesis.

Broad areas of potential research directions include:

Through responsible management and scientific stewardship NIAMS promotes exploration of a broad spectrum of highly meritorious research. Several of the Institute’s current activities related to management, stewardship, and accountability are described in the following sections. The Institute will continue to support and promote these activities over the next 5 years while looking for new opportunities to promote scientific stewardship and accountability.

An important component of management at NIAMS is a planning and priority-setting process that incorporates input from the research community. NIAMS also considers assorted relevant data when making decisions about scientific programs and conducts quantitative or qualitative assessments of programs and research topics, as needed, to guide future activities.

NIAMS also implements trans-NIH activities to enhance management, stewardship, and accountability. For example, these include efforts to reduce administrative burden on investigators, proactively manage risks that might impede the agency’s mission, and ensure that NIAMS-funded research is conducted with a high degree of scientific rigor and in accordance with ethical standards.

NIAMS seeks to ensure the continuity and progress of research in its mission areas through training and career development programs for outstanding early-stage investigators and through dedicated funding for studies with the potential to positively shift scientific paradigms. The Institute fosters a vibrant research environment through investments in key research resources and facilitates access to those resources and data through partnerships with a wide array of public and private organizations in mission-relevant areas.

Accountability for taxpayer funds is a key guiding principle of NIAMS activities. The Institute seeks to ensure integrity, accountability, and transparency in the grant award and administration processes. Program Officers and Grants Managers work closely together to accomplish this goal. One group is responsible for the fiscal and administrative management of a grant award and the other for the scientific and programmatic aspects. Staff work closely with awardees to ensure effective management and oversight, while also providing excellent customer service and guidance.

Pre-award processes assure that established administrative, ethical, and financial requirements are met, including protection of human and animal subjects, monitoring of conflicts of interest, promoting data sharing, and requiring the responsible and ethical conduct of research. Post-award monitoring assures that projects are managed appropriately and that funds are being spent in a prudent and effective way. Grant closeout procedures assure final progress and expenditures are reported and that results are available to the public.

Further, the Institute is committed to supporting research that reflects the diversity of the Nation so that the results of NIAMS-funded research benefit all members of society. NIAMS also prioritizes outreach to the public and broad dissemination of research findings to encourage their implementation to improve health.

Like the rest of NIH, the process of setting NIAMS’s research priorities balances opportunities presented by the best science, public health needs, and the unique ability of the Institute to address challenges in human health that would otherwise go unmet. NIAMS’s long-standing priority setting process is predicated on three activities:

Going forward, NIAMS will continue to rely on these priority-setting activities and will seek out opportunities to enhance them.

NIAMS believes that investigator-initiated research is a key part of efforts to improve the health of people who have rheumatic, musculoskeletal, and skin diseases. The term “investigator-initiated” means that a researcher bases his or her grant proposal on any area of science that NIAMS supports instead of waiting for the Institute to publish a special funding opportunity announcement seeking applications on a specific topic. This has the dual advantages of positioning the Institute to receive the best, most interesting and promising ideas from the research community and of allowing investigators the creativity and freedom to explore the topics that they are most interested in and best poised to address.

The NIAMS portfolio covers a broad and diverse spectrum of research and training responsibilities and NIAMS does not set aside particular pools of money for disease- and tissue-specific topics within its mission. This provides the Institute the flexibility to fund the most outstanding research grant applications regardless of scientific discipline and to fund as many as possible of the myriad needs and opportunities across the broad base of science within its mission.

The decision to fund an application is based on the assessment of scientific merit by a peer review group and on the relevance of the proposed work to the Institute’s scientific and health priorities. While the Institute Director ultimately is responsible for deciding which applications to fund, the assessments of expert scientists and lay representatives from around the country factor heavily into the decision-making process.

Peer reviewers’ judgments of scientific merit are expressed in “priority scores” and in percentile rankings derived from these priority scores. At any point in a given fiscal year, budgetary projections are based on awarding funds to applications with rankings better than a certain percentile, sometimes referred to as the “payline.” However, applications that address topics of particular relevance to the Institute’s scientific and health priorities may be considered for awards even if their assigned scores and percentile rankings would not qualify for funding under the current payline. Normally, a small portion of each year’s budget is reserved for such “discretionary” or “select pay” awards. Projects to be funded on this basis are recommended by Institute staff or Advisory Council members. Applicants may not apply for select pay consideration. Final decisions are made by the Director, NIAMS, following staff discussion.

Rarely, NIAMS receives an application that is within the Institute’s payline but is deemed to be of low program priority. In such instances, these cases are discussed in depth with members of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council before the Institute Director makes a final funding decision. An application can be considered low priority for many reasons, including (but not limited to) redundancy with other projects or concerns about the ultimate relevance of the proposed study’s results or about the scientific premise.

NIAMS publishes its funding plan for each fiscal year on an annual basis on the NIAMS website.

NIAMS routinely invites input from the extramural scientific community and members of the broader public by issuing Requests for Information or through listening sessions with researchers and NIAMS Coalition members. Such activities have shaped this Strategic Plan and other NIAMS initiatives and programs, both large and small.

NIAMS has a history of carefully considering input from the National Arthritis and Musculoskeletal and Skin Advisory Council before making significant changes to existing programs and often presents data-driven analyses to the Council when soliciting its input. Recent examples include the decision to change the eligibility criteria for the Supplements to Advance Research (STAR) program (discussed below) and the Small Grant Program (R03). Council input also has shaped Institute policies regarding the clinical trial applications that it considers and the structure of the NIAMS Centers programs.

Biomedical and behavioral research is a human endeavor and NIAMS is committed to keeping the scientific workforce pipeline strong and diverse. Through ongoing assessment of needs and opportunities, NIAMS has maintained a multidimensional approach to training and career development. Nurturing a healthy pipeline of biomedical researchers focused on the diseases and disorders that are included within the NIAMS mission is critical to advancing scientific progress.

Many research questions important to the NIAMS mission will require multi- and interdisciplinary contributions and a thorough understanding of how to work within teams and across traditional scientific silos. NIAMS encourages investigators to design training experiences that include team science and multidisciplinary or interdisciplinary projects, as appropriate. In addition, NIAMS recognizes a need to incorporate additional areas of expertise, such as data science, biomedical engineering, clinical trial design, and patient engagement, to ensure the effective translation of scientific discoveries into health benefits. To meet these needs, NIAMS encourages new approaches to ensure individuals with nontraditional areas of expertise are represented in research teams.

Going forward, NIAMS will continue to leverage existing and emerging programs and mechanisms to ensure there is a robust and diverse pipeline of researchers and clinician-scientists to carry the Institute’s mission forward. The Institute remains interested in developing partnerships with research and professional societies or patient organizations to encourage trainees and clinicians to enter the scientific research workforce or to maintain research efforts as investigators make critical career-stage transitions.

Attracting and maintaining a robust, diverse scientific workforce is critical to the NIAMS mission. The Institute participates in many trans-NIH programs to encourage and foster the development of early-stage investigators as they pursue research projects on arthritis, rheumatic diseases, musculoskeletal conditions, and skin diseases. Predoctoral fellows in Ph.D. or formal dual-degree programs, such as M.D./Ph.D. programs, and postdoctoral fellows may be eligible for individual Ruth L. Kirschstein National Research Service Awards (NRSAs). Universities and other eligible organizations can apply for institutional NRSAs that provide support for both predoctoral and postdoctoral trainees.

In addition to encouraging trainees to pursue research in NIAMS mission areas, the Institute employs several approaches to encourage clinicians to enter into or continue their research careers. A suite of mentored career development awards aid emerging clinician-scientists as they develop independent research careers by providing resources and protected time for research. For example, the NIH Mentored Clinical Scientist Research Development Award (K08) supports clinicians for an intensive experience in basic and translational research. In addition, the NIH Mentored Patient-Oriented Research Career Development Award (K23) is targeted to individuals with a clinical doctoral degree who intend to focus their research on human studies and work directly with people. NIAMS also supports clinical K08 and K23 physician-scientists by offering special webinars and meetings to allow them to engage with NIAMS leadership and extramural staff. The long-term goal of these meetings is to enhance, encourage, and enable “K-awardees” to navigate critical transitions and retain them in independent research careers.

Clinician-scientists are also encouraged to apply to the NIH Loan Repayment Program (LRP). The escalating costs of advanced education and training in medicine and clinical specialties have led some scientists to abandon research careers for potentially more lucrative industry or private practice careers. The LRP counteracts that financial pressure by repaying a portion of the researcher's qualified educational debt in return for a commitment to engage in specified NIH mission-relevant research.

Several NIH and NIAMS programs address the development and retention of mid-career scientists. For example, the NIH Mid-career Investigator Award in Patient-Oriented Research (K24) provides protected time for mid-career clinicians to conduct research while serving as mentors for junior clinical investigators, particularly K23 grantees. The K24 award is intended to stabilize the careers of these investigators as they continue their research, directly interacting with patients while simultaneously supporting the development of the next generation of clinical researchers.

NIAMS also offers the Supplements to Advance Research (STAR) program to provide additional support for investigators to pursue innovative and high-risk research within the broader scope of a current NIAMS-funded, peer-reviewed research project. STAR provides supplemental funding to investigators who have renewed their first NIAMS R01 grant and aids investigators as they work to expand a single, structured research project into a broader multi-faceted research program. The STAR program allows space for flexibility, innovation, and risk-taking related to the research area of the parent R01 and is optimized to support principal investigators as they develop challenging, creative, and innovative scientific endeavors that will sustain a career.

A growing body of evidence shows that workforce diversity is associated with creativity and innovation—characteristics that are essential for tackling complicated research questions. As the Advisory Committee to the NIH Director Working Group on Diversity in the Biomedical Research noted in its 2012 report, a workforce that better resembles the population that it serves can provide stronger ties with global research networks and improve engagement of underrepresented racial and ethnic minorities in community-based studies. Many rare diseases and conditions within the NIAMS mission cannot be investigated adequately without international research teams and patient cohorts, making this a high priority for the Institute. In addition, many forms of arthritis and musculoskeletal and skin diseases disproportionately affect Americans from minority racial or ethnic backgrounds. Fostering a research community that includes diverse leaders is expected to improve health equity across NIAMS disease areas.

More than half of the U.S. population under 18 years of age will soon be non-white and many of these young people will aspire to enter scientific or biomedical careers in the future. NIAMS is committed to making biomedical research careers more attractive to students from traditionally underrepresented backgrounds. In addition, NIAMS encourages the inclusion of scientists from underrepresented groups in leadership teams and advisory groups to leverage diverse perspectives and improve the likelihood of generalizability of research results.

NIAMS participates in NIH programs designed to attract and encourage individuals from underrepresented populations to pursue research careers by providing a continuum of research training opportunities, from high school to higher education faculty levels. NIAMS recognizes a unique and compelling need to promote diversity in the biomedical, behavioral, and clinical research workforce through the Diversity Supplement Program. The overall goal of the program is to improve the diversity of the research workforce by recruiting and supporting students, postdoctoral researchers, and eligible investigators from diverse backgrounds, including those from groups that have been shown to be underrepresented in health-related fields.

NIAMS has a long-standing history of participation in trans-NIH initiatives and policies designed to facilitate early-stage investigators (ESIs) as they transition to independent careers by obtaining their first major NIH award. In alignment with the NIH-wide Next Generation Researchers Initiative (NGRI), ESI status is considered during review and ESIs are given special funding consideration. In addition, the Institute has established processes to give individual attention to meritorious applications from investigators who lost, or are at risk of losing, all NIH research support, or investigators supported by only one active award. NIAMS will revisit these policies annually to ensure they are reaching programmatic goals and to maintain alignment with evolving trans-NIH NGRI policies.

NIAMS leadership understands that innovation is the basis of scientific progress. It is nearly impossible to predict from where the next research direction or great scientific breakthrough will emerge; hence the Institute’s strong commitment to investigator-initiated research and the process of peer review to identify meritorious proposals. Nevertheless, challenging the status quo is often inherently risky, and when resources are constrained review tends to be conservative, supporting safe bets rather than high risks. NIH data have shown that of the five standard peer review criterion scores, “innovation” is not a primary predictor of funding for R01 applications.

NIAMS and NIH have implemented programs to promote innovative research concepts and the pursuit of scientific hypotheses that could steer science in new directions. For example, the NIH Common Fund’s High-Risk, High-Reward Research program supports exceptionally creative investigators pursuing highly innovative research with the potential for broad impact in biomedical or behavioral science. The program’s four constituent NIH Director’s awards provide a diverse set of funding opportunities for outstanding investigators at all career stages. NIAMS encourages the pursuit of its mission areas though these opportunities.

Discoveries in biomedical and behavioral research are often not ready for immediate clinical application or commercial development. The NIH Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are one mechanism available to address this gap. The SBIR/STTR program is one of the largest sources of research funding for small businesses and startups and it supports and encourages the translation of research discoveries and novel technologies into innovative commercial products. Awards provide 6 months (SBIR) or 1 year (STTR) of support for proof-of-concept testing and 2 years for research and development. The program encourages small businesses to develop new technologies and products with potential for commercialization across health domains. The NIAMS SBIR/STTR program aims to facilitate the translation of basic discoveries into commercial applications within the Institute’s mission areas.

In addition, NIAMS has initiated the Research Innovations for Scientific Knowledge (RISK) program. This novel mechanism focuses on innovative research within the NIAMS mission by encouraging applicants to pursue unusual observations, test imaginative hypotheses, investigate creative concepts, and build groundbreaking paradigms that deviate significantly from current prevailing theories or practice. RISK is particularly designed to encourage the submission of projects that are considered too risky, premature, controversial, or unconventional for other NIH mechanisms. While the program’s focus is on scientific innovation, the review and funding of proposals is also innovative, including a novel “anonymous” pre-application review phase prior to submission of an application for funding consideration. In addition, funded awards provide support for up to 2 years to perform critical experiments that rigorously test the proposed concept. The outcomes of these experiments are a central factor in determining whether the project will continue on to the second phase with additional support to further validate and explore the innovative concept. Through the RISK initiative, NIAMS supports bold and eclectic ideas and specifically fosters innovative proposals in concert with other NIH research project mechanisms.

The 21st Century Cures Act provides NIH with critical tools and resources to advance biomedical research across the spectrum, from foundational basic research studies to advanced clinical trials of promising new therapies. As part of the law, multiyear funding for four highly innovative scientific initiatives was authorized, including the All of Us Research Program, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the Cancer Moonshot℠, and the Regenerative Medicine Innovation (RMI) Project. NIAMS participates in these funding opportunities where there is overlap with the NIAMS mission. For example, NIAMS partnered with the National Cancer Institute and the National Institute of Allergy and Infectious Diseases on Cancer Moonshot efforts to clarify the relationship between cancer, autoimmunity, and immunology, and provided supplements to existing grants for research collaborations on immune-related adverse events associated with cancer immunotherapy. NIAMS also actively participated in RMI program funding opportunities with the goal of accelerating regenerative medicine discoveries related to NIAMS mission and enhancing support for innovative clinical research using adult stem cells while promoting the highest standards for carrying out scientific research and protecting patient safety. NIAMS plans to continue participation in these unique programs.

NIAMS works closely with other NIH Institutes, Centers, and Offices to leverage their unique strengths and avoid duplication of efforts. The Institute continues to encourage investigators to leverage research resources generated through the NIH Common Fund or other trans-NIH programs. The Institute also works to ensure that NIAMS-supported researchers are represented in trans-NIH meetings that are important to our communities. In turn, NIAMS includes researchers supported by other NIH Institutes, Centers, and Offices in NIAMS-led meetings, as appropriate.

The breadth of the NIAMS mission and its importance to the Nation’s health is evidenced in the involvement of Institute staff in the development of trans-NIH and interagency priority-setting documents, such as the following:

Investigators are encouraged to explore these and other resources, as well as the NIH and NIAMS Strategic Plans as they look for exciting ideas and opportunities to pursue. The most up-to-date list of NIH-wide strategic plans can be found at https://report.nih.gov/strategicplans/index.aspx.

Recognizing the need for collaborations to advance behavioral and biopsychosocial research, NIAMS participates in several relevant trans-NIH efforts (e.g., the NIH Pain Consortium and the National Center on Sleep Disorders Research) and works closely with the NIH Office of Behavioral and Social Sciences Research. These interactions allow the Institute to share information about NIAMS-funded research efforts and advances and to form partnerships with other NIH components in areas of common interest.

Below are a few historical examples of partnerships that NIAMS has led or contributed to. The resulting data sources are available for arthritis and musculoskeletal and skin researchers to leverage as they develop scientific proposals over the next 5 years.

As stated previously, many diseases that fall within the NIAMS mission exhibit sex, racial, ethnic, and other disparities. Given what is known about the populations affected by these diseases, it is critical to ensure that the research the Institute supports appropriately includes a diverse group of participants. NIH and NIAMS are committed to the inclusion of women and minorities in all NIH-funded clinical research. This is demonstrated through implementation of the NIH Revitalization Act of 1993 (Public Law 103-43), which requires inclusion of women and members of minority groups and their subpopulations in NIH-funded clinical research, including clinical trials, unless there is appropriate justification for not including them. Researchers need to consider factors such as sex, race, ethnicity, and socioeconomic status in the design, data collection, and analysis of clinical research studies and clinical trials. These studies serve as resources for data that could be leveraged to answer important, fundamental questions in health disparities research.

The 21st Century Cures Act (Public Law 114 -255), enacted in 2016, introduced new requirements related to inclusion of participants in clinical research. As a result, NIH updated its policy on the Inclusion of Women and Minorities as Subjects in Clinical Research. Additionally, NIH revised its Inclusion of Children Policy, which is now called the NIH Policy and Guidelines on the Inclusion of Individuals Across the Lifespan, to ensure that clinical research includes individuals of all ages unless there is an appropriate justification to do otherwise.

In addition to the efforts described above that relate to clinical research, NIH also encourages enhanced attention to sex as a critical factor in basic and preclinical studies. In 2015, the agency announced a policy on Consideration of Sex as a Biological Variable to foster research that improves understanding of the biology underlying sex differences and provides knowledge to improve the health of women, men, girls, and boys. NIAMS supports NIH’s overarching efforts on studying sex and gender, which call on researchers to take sex into account as they develop their research questions, design experiments, analyze data, and report results.

NIAMS, like NIH as a whole, supports research with the ultimate goal of curing disease and improving overall health. However, significant time elapses between basic discovery and development of clinical applications. Scientific discovery often involves years to decades worth of incremental advances that are critical to achieving the ultimate goal of turning discovery into health. While a direct link can sometimes be drawn between specific funding and an improvement in health, most often the story is complex. Thus, determining the extent to which NIAMS has met the objective of improving health can be a challenge. Furthermore, over the course of a 5-year period the scientific field can advance and evolve in many unanticipated ways. As noted in the Director’s Message, these unexpected breakthroughs also serve as indicators of progress and are a successful outcome of support. With this in mind, NIAMS will adopt a mixed methods approach that balances quantitative and qualitative methods to examine outputs and outcomes from this Strategic Plan for FYs 2020-2024.

An important management component at NIAMS is a planning and priority-setting process that incorporates input from the scientific community. The Institute’s focus on investigator-initiated research applications and identification of the most promising research projects through peer review requires performance measures that reflect the full scope of the NIAMS mission and the work funded based on these processes. In addition to the investigator-initiated peer-review process, NIAMS uses evidence-based information when making decisions about scientific programs and conducts quantitative or qualitative assessments of programs and research topics to guide activities. With a growing evolution in the use of evidence to inform policy decisions, the performance measures and metrics NIAMS uses may be adjusted and should be evaluated regularly to ensure they are providing the information needed to guide priority setting efforts. This section reiterates some of the ways in which NIAMS currently uses data to inform decision making and discusses several potential measures that NIAMS may use in the future to assess its research portfolio and progress toward its scientific objectives of advancing and accelerating research within its mission.

Investigator-initiated research supported by NIAMS, through funding mechanisms such as R01 awards, is conducted across the Institute’s disease- and tissue-specific mission areas described in this plan. Working with partners across NIH, such as the Office of Portfolio Analysis, Office of Evaluation, Performance, and Reporting, and other NIH components, NIAMS will identify appropriate measures and tools for a particular portfolio analysis and evaluation. For investigator-initiated research, such assessments could be used to evaluate and monitor innovation that results from this funding pool or to help guide select pay decisions and gauge their effects.

NIAMS also supports targeted programs that focus on early-stage investigators, high-risk research with potential to drive innovation, or establishing research resources for use by the larger scientific community, such as the OAI and AMP. For targeted efforts, NIAMS uses evaluation tools and data-driven assessments to help inform the creation of new programs and to revise and re-issue funding opportunity announcements for existing programs. Several examples of assessments of targeted programs are highlighted throughout this Strategic Plan. The section on Priority Setting notes that program assessments have shaped changes to the NIAMS Supplements to Advance Research (STAR) program and the Small Grant Program (R03). The section on Advancing and Accelerating Muscle Biology and Disease Research describes an evaluation of the Wellstone Centers program and how that effort is being used to identify program changes that could enhance efforts to achieve the Centers’ goals. Assessment of targeted programs over the short- and long-term will rely on both quantitative and qualitative measures and may include analysis of career trajectories for trainees and early-stage investigators or significant advances spurred by targeted program efforts. Moving forward, NIAMS will continue to use approaches that may include, but are not limited to, an analysis of outputs (e.g., publications, development of new methods), outcomes (e.g., significant conceptual advances, stories of discovery, influential papers), and bench-to-bedside translation resulting from supported research.

Consistent with the Institute’s emphasis on collecting stakeholder input, NIAMS will continue to hold roundtable discussions to assess research gaps and opportunities in specific mission areas, cross-cutting scientific themes, and clinical research efforts. NIAMS may also engage the community through listening sessions with researchers and NIAMS Coalition members to identify emerging research directions that could benefit from Institute encouragement.

Finally, NIAMS will work to ensure that the performance measure development and implementation process is incorporated across the Institute. Defining success prior to the launch of a new concept will facilitate gathering data to measure progress and allow identification of adjustments to improve performance.

The driving force behind NIAMS-funded research is to improve the lives of those who are affected by diseases and conditions of bones, joints, muscles, and skin. Sharing information about research progress and conducting outreach to multiple audiences are essential components of the NIAMS mission. The Institute is committed to communicating research advances to all segments of the public.

The Institute is dedicated to working closely with grantees and their institutions to disseminate research findings to constituents via multiple venues. Key priorities include:

NIAMS will continue to support and operate the NIAMS Information Clearinghouse and the NIH Osteoporosis and Related Bone Diseases ~ National Resource Center (NRC). Both clearinghouses distribute health information materials to patients, allied health professionals, voluntary and professional organizations, underserved and at-risk populations, the media, and the general public. The NIAMS Information Clearinghouse provides materials on diseases and conditions of bones, joints, muscles, and skin in a variety of formats and languages.

The NRC provides an important link to resources and information on metabolic bone diseases including osteoporosis, Paget’s disease of bone, and osteogenesis imperfecta. It is supported by NIAMS, with contributions from the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, and the NIH Office of Research on Women’s Health.

Social media has increasingly become a primary avenue through which people receive news and information, as well as a main vehicle for communicating with individuals and organizations alike. NIAMS has fully integrated social media into its information dissemination program. The Institute posts regular updates to Twitter (@NIH_NIAMS) and Facebook (NIH.NIAMS), featuring NIAMS health information, recently published research articles, news and announcements, training and funding opportunities, and other information and resources. NIAMS hosts live social media events with other NIH Institutes, Centers, and Offices and professional and voluntary organizations to address timely health topics. NIAMS regularly posts videos on its YouTube channel and scientific images on its Flickr photo stream. NIAMS will continue to evaluate efforts to reach more constituents through social media channels and to explore integration of other social media tools to target and increase direct interaction with diverse audiences.

NIAMS develops health information materials for patients and their families, health care providers, and the general public. NIAMS offers many of its materials in easy-to-read English formats, as well as in several other languages including Spanish, Chinese, Korean, and Vietnamese. A separate Spanish web portal and Asian languages web section let visitors easily access information in different languages.

The Institute produces several e-newsletters that are available by easy online subscription. These include the NIAMS Update, an electronic digest for those interested in the latest NIAMS/NIH-supported scientific news and resources on diseases of bones, joints, muscles, and skin. The Institute also develops the NIAMS Community Outreach Bulletin, an online digest designed to inform community organizers and health professionals about resources for diverse audiences. In addition, NIAMS disseminates Honoring Health: Resources for American Indians and Alaska Natives. Institute updates are also available through several social media channels.

The NIAMS clearinghouses have bilingual Spanish/English information specialists who respond to public inquiries about topics under the NIAMS purview. Assistance is easily available via phone, email, or letter (see Contact Us).

Looking ahead, NIAMS will continue to respond to the increased demand for online health and research information. The NIAMS website has been redesigned to be easily viewed on a phone, tablet, or computer. This key outreach platform will be regularly updated and refined based on user metrics and content development, in alignment with the NIAMS mission.

The Institute is dedicated to engaging the public and encouraging broad participation and input in NIAMS and NIH activities. Upcoming plans in this area include:

The Institute works closely with the NIAMS Coalition to share research advances and related developments, as well as to foster dialogue on future paths and directions of NIAMS-funded research. The Coalition is an independent consortium of professional and voluntary organizations that works to raise awareness about NIAMS research into the basic understanding, causes, treatment, and prevention of diseases of bones, joints, muscles, and skin. The Coalition plays a vital role as a voice of the researchers and patients for whom NIAMS works. The Institute will continue to engage regularly with Coalition partners through teleconferences and webinars, in-person meetings, and presentations at professional and voluntary meetings.

NIAMS will continue its Community Outreach Initiative to ensure that resources reach diverse populations. Through development and distribution of an e-newsletter, a social media toolkit, and other materials, health care providers and community organizers in multicultural communities nationwide receive access to health information and resources about health conditions that affect bones, joints, muscles and skin. In addition, NIAMS has implemented a Language Access Plan as part of NIH-wide efforts to help ensure that people who have limited English proficiency have meaningful access to all NIAMS programs and activities.

To broaden outreach to underrepresented groups, NIAMS is taking an active role in leading the NIH American Indian/Alaska Native (AI/AN) Health Communications and Information Work Group, a collaboration that represents more than 20 NIH Institutes, Centers, and Offices. The working group partners with the Indian Health Service (IHS) and the Administration on Aging/Administration for Community Living to develop and disseminate health information to IHS community health representatives and Title VI grantees nationwide.

The NIAMS Strategic Plan for Fiscal Years (FYs) 2020-2024 continues to build on the foundation of the Institute’s previous long-range plans. It also includes new additions to feature four broad cross-cutting scientific themes, selected based on input from the community, that are relevant to all, or most, of the disease- and tissue-specific topics within the NIAMS mission and to address NIH and NIAMS initiatives related to management, scientific stewardship, and accountability.

NIAMS solicited comments on how the NIAMS Long-Range Plan for FYs 2015-2019 should be updated via a Request for Information (RFI) (Appendix 2) and gathered additional information through listening sessions with the NIAMS stakeholder communities.

The RFI was posted on the NIAMS website and in the NIH Guide for Grants and Contracts, and it encouraged feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific and professional organizations, Federal agencies, and other interested members of the public. Information about the RFI was shared in emails to grantees, NIAMS Coalition members, and NIH components to encourage broad response. The comment period spanned 6 weeks. Respondents were asked to provide input on research needs and opportunities that should be modified because of progress over the last 5 years, emerging research needs and opportunities that should be added, and cross-cutting scientific themes or research-related themes common to all, or most, of the disease- and tissue-specific topics within the NIAMS mission that should be included. General comments were also encouraged.

In November and December 2018, seven listening sessions were held with more than 100 individuals. The listening session participants consisted of researchers and patients representing systemic rheumatic and autoimmune diseases, skin biology and diseases, muscle biology and diseases, bone biology and diseases, joint biology, diseases, and orthopaedics, as well as members of the NIAMS Coalition, a group of more than 90 professional and voluntary organizations interested in the Institute’s mission areas. Six of the listening sessions were held via conference calls. The seventh session was an in-person meeting with established researchers and professional and voluntary organization representatives who attended the NIAMS K Forum for Clinical Mentored K Awardees. All listening session participants were encouraged to gather and share the views of the broader research community by consulting a diverse set of colleagues in advance of the listening sessions. In addition to providing input on their tissue- or disease-specific topic, participants were asked about needs and opportunities that could be included in the new section of the plan on cross-cutting scientific themes. Part of the discussion was also devoted to health disparities and training and career development. Further, participants in the listening session with the NIAMS Coalition provided input on how the new NIAMS Strategic Plan for FYs 2020-2024 could be structured to be most useful to NIAMS varied stakeholders. Updates on the development of the NIAMS Strategic Plan for FYs 2020-2024 were provided at the September 2018 and February 2019 Advisory Council meetings. In February 2019, the NIAMS Acting Director convened a Working Group of the Advisory Council to review the draft plan, which was presented to the Working Group and Advisory Council in May 2019. The NIAMS Advisory Council Working Group for the Strategic Plan discussed the draft plan via a conference call in May 2019 and reported their findings and recommendations at the June 2019 Advisory Council meeting. Feedback from the Working Group and Advisory Council was incorporated into the draft plan after the meeting.

The Institute then issued a second RFI to invite public comments on the revised draft plan. The RFI was published in the NIH Guide for Grants and Contracts and information posted on the NIAMS website (Appendix 2). The comment period spanned 3 weeks. In addition to the outreach efforts similar to those associated with the first RFI, the Institute also issued a Federal Register Notice to further publicize this RFI. All comments received were reviewed carefully by Institute staff and incorporated into the document, as appropriate.

The final version of the NIAMS Strategic Plan for FYs 2020-2024 was presented to the NIAMS Advisory Council at the Council’s September 2019 meeting. After clearance to ensure compliance with the requirements described in the 21st Century Cure Act, the NIAMS Strategic Plan for FYs 2020-2024 was posted on the Institute’s public website and widely disseminated to NIAMS communities.

During the development of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Strategic Plan for Fiscal Years (FYs) 2020-2024, the Institute issued two Requests for Information: the first to solicit initial comments on how the previous plan for FYs 2015-2019 should be modified to reflect progress over the past 5 years, and the second to invite public feedback on the draft NIAMS Strategic Plan for FYs 2020-2024.

NOT-AR-19-009

Release Date: September 14, 2018Response Date: October 26, 2018

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is updating its Long-Range Plan to help guide the research it supports over the next 5 years. Public input on the topics to be included in the plan and suggestions regarding how to enhance the NIAMS research portfolio are critical initial steps in this effort. NIAMS leadership and staff will review and consider the comments as the Institute updates its Long-Range Plan.

Through this RFI, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public. Organizations are strongly encouraged to submit a single response that reflects the views of their organization and membership as a whole.

Please provide your perspective on the following issues:

NIAMS also welcomes your general comments, including those regarding the extent to which the FYs 2015-2019 Plan has guided and encouraged the field.

When commenting on a research need or opportunity, your comments can contain but are not limited to information pertaining to the following:

Responses to this RFI must be submitted electronically at https://grants.nih.gov/grants/rfi/rfi.cfm?ID=81.

Responses must be received by October 26, 2018.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, and individual feedback will not be provided to any responder. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder’s submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

Please direct all inquiries to:

Cindy Caughman, M.P.H.Chief, Science Policy and Planning BranchNational Institute of Arthritis and Musculoskeletal and Skin DiseasesTelephone: 301-496-8190

NOT-AR-19-010

Release Date: June 21, 2019Response Date: July 12, 2019

NOT-AR-19-009

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is updating its Strategic Plan for Fiscal Years 2020-2024 to help guide the research it supports over the next 5 years. The Institute issued a previous Request for Information (NOT-AR-19-009) to solicit initial comments on how the previous plan for fiscal years 2015-2019 should be modified to reflect progress over the past 5 years. The Institute also gathered additional input through listening sessions with the community. Based on this feedback, along with input from the NIAMS Advisory Council and its Working Group for the Strategic Plan, the Institute has drafted the NIAMS Strategic Plan for FYs 2020–2024 (https://grants.nih.gov/grants/rfi/NIAMS-Strategic-Plan-2020-2024.pdf). We are now seeking input on this draft.

Through this RFI, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public on the draft NIAMS Strategic Plan for FYs 2020-2024 (https://grants.nih.gov/grants/rfi/NIAMS-Strategic-Plan-2020-2024.pdf).

Organizations are strongly encouraged to submit a single response that reflects the views of their organization and membership as a whole.

Please provide your comments and feedback. The final draft of the Strategic Plan will be presented at the September 2019 meeting of the NIAMS Advisory Council and posted on the NIAMS website when it is approved.

Responses to this RFI must be submitted electronically at http://grants.nih.gov/grants/rfi/rfi.cfm?ID=89.

Responses must be received by July 12, 2019.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, and individual feedback will not be provided to any responder. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder’s submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

Please direct all inquiries to:

Cindy Caughman, M.P.H.Chief, Scientific Planning, Policy, and Analysis BranchNational Institute of Arthritis and Musculoskeletal and Skin DiseasesTelephone: 301-496-8271Email: [email protected]

2018

September

Update to NIAMS Advisory Council on the development of the plan.

September/October

Request for Information posted in the NIH Guide for Grants and Contracts and on the NIAMS website for public input on research opportunities that should be modified because of progress over the past 5 years, emerging research needs and opportunities that should be added to the plan, and cross-cutting scientific themes or research-related themes common to all, or most, of the disease- and tissue-specific topics within the NIAMS mission that should be included in the plan.

November/December

Listening sessions held as teleconferences for:

Listening session for training and health disparities with participants who attended the NIAMS Forum for Clinical Mentored K Awardees

2019

February

May

Draft plan presented to the NIAMS Advisory Council and its Working Group for the Strategic Plan for review and input.

June/July

August

Review of public comments on draft plan and updates incorporated, as appropriate.

September

Final plan presented to NIAMS Advisory Council and posted on the Institute’s website.