Department of Health and Human Services
Public Health Service
National Arthritis and Musculoskeletal and Skin Diseases Advisory Council
Minutes of the 91st Meeting
January 25, 2017
8:30 a.m. to 2:40 p.m.
CALL TO ORDER
The 91st meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on January 25, 2017, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 10. The meeting was chaired by Dr. Stephen I. Katz, Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Council members present
Dr. Joan E. Bechtold, Professor, Orthopaedic Surgery, University of Minnesota
Ms. Magdalena Castro-Lewis, former Vice President for Programs, National Alliance for Hispanic Health
Dr. Michael Econs (ad hoc), Glenn W. Irwin, Jr., Professor of Endocrinology and Metabolism; Director, Division of Endocrinology and Metabolism; and Professor of Medicine and Medical and Molecular Genetics, Indiana University School of Medicine
Dr. V. Michael Holers, Professor, Department of Medicine, University of Colorado Denver School of Medicine
Dr. Judith A. James, Chair and Member, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation
Dr. Sundeep Khosla, Dr. Francis Chucker and Nathan Landow Research Professor; Director, Mayo Clinic CTSA/Center for Clinical and Translational Science; Dean for Clinical and Translational Science, Mayo Clinic College of Medicine
Dr. Gary A. Koretzky, Dean, Weill Cornell Graduate School; Senior Associate Dean for Research, Weill Cornell Medical College
Dr. Ethan Lerner, Associate Professor of Dermatology, Massachusetts General Hospital
Rosemary J. Markoff, Co-Chair, Scleroderma Foundation National Advocacy Committee
Dr. William Mulvihill, The Mulvihill Advisory Group
Dr. Amy Paller, Professor, Dermatology, Feinberg School of Medicine
Dr. Grace Pavlath, Senior Vice President — Scientific Program Director, Muscular Dystrophy Association; Professor, Department of Pharmacology, Emory University School of Medicine
Dr. Christy I. Sandborg, Professor of Pediatrics, Stanford University, Lucile Salter Packard Children’s Hospital (via teleconference)
Mr. Richard F. Seiden, Foley & Lardner LLP
Mr. Alexander Silver, Chairman, Jackson Gabriel Silver Foundation
Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center (via teleconference)
Dr. Gwendolyn L. Powell Todd, Patient, Health Advocate, and Educator
Dr. Michael J. Yaszemski (ad hoc), Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic
Staff and Guests
The following NIAMS staff and guests attended:
Dr. D. Lee Alekel
Dr. Carl Baker
Ms. Pamela Beheler
Ms. Elizabeth Bouras
Dr. Amanda Boyce
Mr. Gahan Breithaupt
Dr. Nakia Brown
Ms. La’Tanya Burton
Dr. Stephanie Burrows
Mr. George Carr
Dr. Robert Carter
Ms. Cindy Caughman
Dr. Faye Chen
Dr. Thomas Cheever
Ms. Robin DiLiello
Ms. Teresa Do
Dr. Jonelle Drugan
Ms. Elizabeth Elliott
Ms. Barbara Footer
Dr. Nancy Garrick
Ms. Aleisha James
Ms. Katie Joffee
Mr. Andrew Jones
Dr. Stephen I. Katz
Ms. Shahnaz Khan
Ms. Stephanie Kreider
Mr. Mark Langer
Mr. Greg Lavino
Dr. Gayle Lester
Dr. Helen Lin
Ms. Anita Linde
Ms. Leslie Littlejohn
Dr. Yin Liu
Dr. Kan Ma
Dr. Marie Mancini
Dr. Kathryn Marron
Dr. Joan McGowan
Ms. Leslie McIntire
Dr. Laura K. Moen
Ms. Melinda Nelson
Dr. Kristy Nicks
Dr. John O’Shea
Dr. Carol Parsons
Dr. Charlotte Peterson
Ms. Vivian Pham
Mr. Rick Phillips
Ms. Andree Reuss
Ms. Trish Reynolds
Dr. Kathy Salaita
Mr. Tahir Seeba
Ms. Sheila Simmons
Ms. Robyn Strachan
Ms. Yen Thach
Ms. Jamie Thompson
Dr. Hung Tseng
Dr. Bernadette Tyree
Dr. Fei Wang
Dr. Chuck Washabaugh
Dr. James Witter
Ms. Robin Wolz
Dr. Xincheng Zheng
Dr. Lauren Brodd, American Association of Immunologists
Mr. Mike Bykowski, Consolidated Solutions and Innovations
Dr. Guy Eakin, Arthritis Foundation
Ms. Patti Brandt Hansberger, Office of Legislative Policy and Analysis, NIH
Mr. Blake McDonald, American Academy of Dermatology Association
Dr. Eliseo Peréz-Stable, Director, National Institute on Minority Health and Health Disparities, NIH
Mr. Joseph Stewart, Scleroderma Foundation
Ms. Randi Williams, KAI Research, Inc.
CONSIDERATION OF MINUTES
A motion was made, seconded, and passed to approve the minutes of the 90th NAMSAC meeting, held on September 13, 2016.
FUTURE COUNCIL MEETING DATES
Future Council meetings are currently planned for the following dates:
June 21, 2017
September 6, 2017
February 7, 2018
June 12, 2018
September 5, 2018
DIRECTOR'S REPORT AND DISCUSSION
Dr. Katz began his Director’s Report by reminding Council members that the public portion of this NAMSAC meeting was being videocast and will be archived on the NIH website. He welcomed four new Council members (two of whom were attending as ad hoc members, pending approval by the Secretary’s office): Dr. Michael Econs (ad hoc), Dr. Judith James, Ms. Rosemary Markoff, and Dr. Michael Yaszemski (ad hoc).
Dr. Katz also announced that NAMSAC Executive Secretary and NIAMS Division of Extramural Research Activities Director Dr. Laura Moen has accepted a position as Director of the Division of Extramural Research Activities at the National Heart, Lung, and Blood Institute. Dr. Moen joined the NIAMS in 2009, and has overseen the Scientific Review Branch, Grants Management Branch, and clinical operations team—she also has represented the Institute on a number of important trans-NIH and inter-agency committees. Dr. Katz thanked Dr. Moen for her service to the NIAMS and NAMSAC, and noted that while a national search is ongoing to fill her position, Ms. Melinda Nelson (Chief Grants Management Officer) has agreed to serve as the Acting Director of the NIAMS Division of Extramural Research Activities, and Mr. Andrew Jones (Deputy Grants Management Officer) will serve as the Acting Chief Grants Management Officer.
Administration Transition, Budget Update, and Congressional Outreach Activities
President Trump has nominated Representative Thomas Price, M.D. (R-GA) as Secretary of the U.S. Department of Health and Human Services. The Senate Health, Education, Labor, and Pensions Committee held a confirmation hearing for Dr. Price last week, and his hearing before the Senate Finance Committee (the Committee that will vote on whether to recommend confirmation) was yesterday. Dr. Price is an orthopaedic surgeon and has served in the U.S. House of Representatives since 2005. Dr. Katz also noted that Dr. Francis Collins is being "held over" as the NIH Director.
Congress plans to revisit the fiscal year 2017 budget for much of the Federal government now that the new Administration is in place. Meanwhile the NIH is operating under a continuing resolution through April 28, 2017. The NIAMS has developed an interim funding plan, which projects a flat budget, and has posted it online (available here). As noted in the plan, the Institute is paying competing R01s to the 10th percentile and competing R01s from new and early stage investigators to the 18th percentile. To accommodate this, the NIAMS cut the budget for non-competing grants by 3 percent.
On December 13, 2016, President Barack Obama signed the 21st Century Cures Act into law. The Cures Act provides the NIH with tools and resources to advance biomedical research. The most publicized aspect of the law relates to the funding of three highly innovative scientific initiatives launched by the Obama Administration: (1) the Brain through Advancing Innovative Neurotechnologies (BRAIN) Initiative, (2) the Precision Medicine Initiative (PMI), and (3) the Beau Biden Cancer Moonshot. Importantly, Congress made clear that these focused investments will be in addition to the support that each NIH Institute and Center (IC) receives through the regular appropriations process.
On October 5, 2016, the NIAMS and NIAMS Coalition hosted a Congressional staff tour of some of the laboratories in the Institute’s Intramural Research Program (IRP). During the tour, Hill staffers learned about NIAMS intramural and extramural research, training for the next generation of scientists, and NIAMS outreach programs. Dr. Katz thanked the intramural scientists who participated in the tour, as well as the Office of Science Policy, Planning and Communications staff who worked closely with the NIAMS Coalition Steering Committee to arrange the event. He reminded the group that the NIAMS Coalition is an independent consortium of nearly 90 professional and voluntary organizations that raises awareness about NIAMS-funded research.
The Institute greatly appreciates the work of its Coalition members, particularly those who volunteer to serve on the Coalition Steering Committee. Dr. Katz noted that Ms. Stephanie Hazlett of the American Academy of Orthopaedic Surgeons began her term as Coalition Co-Chair on January 1, 2017, working with Mr. Robert Riggs of the Scleroderma Foundation. Ms. Mary Wheatley, the outgoing Co-Chair, will continue to be involved in the Steering Committee through 2017 as the Past Co-Chair.
NIH and NIAMS Updates
The PMI was announced 2 years ago during President Obama’s State of the Union address. The PMI’s million-person cohort component—the largest health and medical research program on precision medicine—is now called the All of Us Research Program. The consortium involves more than 35 institutions that are developing the infrastructure and processes needed to begin enrolling participants. The June 2017 NAMSAC meeting will feature a presentation by All of Us Research Program Director Mr. Eric Dishman. Council members were asked to consider how the NIAMS can best take advantage of this initiative. Additional information about the All of Us Research Program is can be found on the NIH website and in a letter Mr. Dishman wrote for the October NIAMS Update (his letter describes the program’s efforts to ensure that it promotes the benefits of precision health to all populations).
As part of NIAMS’ efforts to improve the health of all Americans, the Institute has launched a new Community Outreach section of its website to provide health professionals and community advocates with easy access to NIAMS’ large collection of information and resources on bones, joints, muscles, and skin. The site provides an extensive library of publications in English, Spanish, Chinese, Korean, and Vietnamese.
Last week, the U.S. Department of Health and Human Services updated regulations known as the "Common Rule" to safeguard individuals who participate in research. The revisions are an effort to modernize, simplify, and enhance the current system of oversight that has been in place since 1991. They are intended to better protect human subjects involved in research while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. Most provisions in the new rule will go into effect in 2018.
In addition to supporting Department-wide efforts to enhance the clinical research enterprise, the NIAMS continues to focus on developing and sustaining the clinical research workforce. A few years ago, the Institute began holding a forum for clinical and patient-oriented investigators in the third year of their K08 or K23 career development awards. The Institute focuses on third-year awardees because they are at the stage when they should begin applying for their first independent R01 grant (Dr. Katz noted that the K-to-R01 transition is a particularly vulnerable period in the career timeline of clinician-scientists). The Institute is hoping to leverage its investment in early stage clinician-scientists by encouraging and enabling K08 and K23 awardees to continue performing research in their chosen fields.
As a next step in efforts to enhance operations of the NIH Clinical Center, Dr. Collins has appointed Major General James K. Gilman, M.D., U.S. Army (Retired), as the inaugural Chief Executive Officer of the Center. Dr. Katz and National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci led the search committee that recruited Dr. Gilman (a cardiologist with extensive experience in leading the operations of numerous hospital systems).
Dr. Katz reported on the following personnel changes at the NIAMS level:
- Mr. Rick Phillips has joined the Institute as its Deputy Executive Officer.
- Ms. Cindy Caughman has joined the Institute as Chief of the Science Policy and Planning Branch within the NIAMS Office of Science Policy, Planning, and Communications.
- Dr. Nancy Garrick, who has been serving as the deputy director of the Communications and Public Liaison Branch in our Office of Science Policy, Planning and Communications since 2011, is now its Branch Chief.
- Dr. Nakia Brown has joined the NIAMS Scientific Review Branch as a Scientific Review Officer.
- Dr. Charlotte Peterson has joined the Institute on a part-time basis. While maintaining her active skeletal muscle research program at the University of Kentucky, she is also the Project Scientist for the Molecular Transducers of Physical Activity Consortium (MoTrPAC) clinical and coordinating centers.
Dr. Katz announced plans to transfer the Dermatology Branch from the National Cancer Institute (NCI) to the NIAMS IRP. The move provides an opportunity for synergy across NIAMS scientific programs, as well as between NIAMS laboratories and many others across the NIH. It is expected that this transfer will benefit the NIH, the affected investigators, and the dermatology community as a whole, while the Institute moves forward with a commitment to preserve and enhance the long history of leadership of the Dermatology Branch in the skin research field.
Highlights of Selected Recent Scientific Advances
Dr. Katz described several scientific advances of interest to the Council.
- From the NIAMS IRP, Dr. Mike Ombrello’s laboratory and others at the NIH contributed to a genome-wide association study that uncovered more than 20 genetic regions associated with increased risk of systemic juvenile idiopathic arthritis (sJIA) this work was conducted as part of the International Childhood Arthritis Genetics Consortium. Additional analysis confirmed that the regions identified are unique to the systemic form of the disease; they are not shared with other JIA groups, which have much more localized symptoms (Ann Rheum Dis. 2016 Dec 7. pii: annrheumdis-2016-210324. doi: 10.1136/annrheumdis-2016-210324 [Epub ahead of print] PMID: 27927641].
- Council member Dr. Michael Holers (University of Colorado) and Dr. William Robinson (Stanford University) led a team investigating the pathological immune responses that occur in the preclinical phase of rheumatoid arthritis, as the disease begins many years before the onset of clinical symptoms. The team compared the antibody repertoire of immature blood cells called plasmablasts from three groups of people and found that those who express a certain type of IgA antibody were more prone to develop rheumatoid arthritis (Arthritis Rheumatol. 2016 Oct;68(10):2372-83. doi: 10.1002/art.39771).
- Former Council member and long-time NIAMS investigator Dr. Henry Kronenberg and NIAMS K08 grantee Dr. Marc Wein at Massachusetts General Hospital led an international team of researchers who identified the enzyme SIK2 and its down-stream signaling molecules as potential drug targets for strategies to boost bone mass. Cell and mouse studies show that small molecule inhibitors of SIK2 hold promise as new drug candidates (Nat Commun. 2016 Oct 19;7:13176. doi: 10/1038/ncomms13176. PMID: 27759007).
- Drs. Peter Marinkovich, Paul Khavari, and Alfred Lane at Stanford University have reported the preliminary results of the first four patients in a phase 1 clinical trial of ex vivo gene therapy to treat recessive dystrophic epidermolysis bullosa. The investigators used a virus to introduce a normal version of the type VII collagen gene into epidermal cells derived from patient biopsies. The genetically corrected cells were grown into patient-specific card-sized epidermal sheets and grafted onto six wounds on each patient. Eighty-seven percent of grafts were intact at 3 months after grafting, and 50 percent were intact at 12 months (JAMA. 2016 Nov 1;316(17):1808-1817. doi: 10.1001/jama.2016.15588. PMID: 27802546).
Dr. Lerner asked about the plans to transfer the Dermatology Branch from the NCI to the NIAMS IRP. Dr. Katz explained that between 50 and 60 years ago, the Branch was started within the NCI based on work related to the study of skin rashes resulting from chemotherapeutic agents used at the time. When the NIAMS was established roughly 30 years ago, Dr. Katz was the Dermatology Branch Chief, and the decision was made to keep the Branch within the NCI at that time. However, the timing for this planned move is now appropriate, given that: (1) the current Dermatology Branch Chief is retiring; (2) when the Clinical Center was renovated 6-7 years ago, the Dermatology Branch and the NIAMS Rheumatic Diseases Branch were placed in close proximity; and (3) the NCI was not planning to maintain the Branch in its current state. There has been general agreement between the NIAMS, NCI, and the intramural investigators that this change should be made. Funds allocated to the Branch will be transferred to the NIAMS, and a future Council meeting will include an update on Dermatology Branch activities.
DISCUSSION OF DR. HOLER’S WORKING GROUP REPORT
Dr. Holers presented the report of a NAMSAC Working Group charged with identifying means by which to enhance interactions of Council with Institute leadership. Council members who participated on the Working Group took part in a series of conference calls in the fall of 2016, with a summary of their discussions presented to and reviewed with Dr. Katz in November (Council members were provided with a copy of this report in advance of this NAMSAC meeting). In addition to discussing a number of specific grant mechanisms and research areas, the Working Group identified four major topic/interest areas:
- Interaction of NIAMS with the PMI. Council members would like to proactively prepare for the PMI presentation and discussion to be held during the June 2017 NAMSAC meeting. The Working Group suggested that the Institute consider the formation of a Council subcommittee to address planning for this discussion. There was also substantial interest in understanding how the Institute’s portfolio areas can effectively interact with and be supported by PMI. Other topics of interest discussed by the Working Group included: (1) assuring effective interactions of public and private genomic databases, (2) decreasing research silos through PMI efforts, and (3) assuring diversity in PMI research efforts and populations.
- Enhancing NIAMS Council organizational effectiveness and impact. The Work Group suggested: (1) establishing standing subcommittees of the Council to identify and address specific topical areas of mutual interest with leadership, (2) enhancing opportunities for unstructured interactions around Council meetings, (3) working to break down research silos at all levels in research funding and operations, and (3) helping to identify scientists from underrepresented minorities who could serve on the Council.
- Aligning funding mechanisms to take advantage of changing research environments. The Work Group recommended that the Institute work to assure the recruitment and retention of an ethnically diverse academic research workforce (inclusive of clinical, basic, and translational scientists as well as educational research specialists). The group also suggested enhancing opportunities for multidisciplinary research efforts and promoting collaborative research funding efforts that cross areas within NIAMS and other ICs. Other topics of interest included: (1) engaging community physicians in research, and (2) adapting "levels of evidence" for pre-clinical studies.
- Leveraging partnerships to broaden the impact of NIAMS. The Work Group recommended: (1) establishing interactions between the Council and NIAMS Coalition members, (2) engaging with other organizations to increase support for research within NIAMS portfolio, and (3) promoting the integration of research efforts between the Institute and lay funding organizations that support the same disease areas.
Dr. Paller noted that the Work Group also felt that there have been some lost opportunities for collaborating on projects and used the fields of rheumatology and dermatology as examples of areas where these opportunities exist and collaboration should be encouraged. Dr. Katz noted that all of the Institute’s programs promote interaction and collaboration and that there may be an increased effort to discuss additional opportunities for collaboration on work across areas of interest to the Institute at future NAMSAC meetings.
Dr. Koretzky noted that the Council is looking for ways to be better informed by (and to better inform) activities in areas of interest to the NIAMS that also cut across other Institutes. Dr. Katz commented that IC Directors and other representatives from ICs working on areas of interest to the NIAMS will continue to present at future Council meetings, and a greater emphasis may be placed on these types of cross-Institute activities. The NIAMS will consider forming a work group charged with making suggestions for future Council agenda items, and that the Institute will provide Council members with notification regarding future Council meeting agenda items so that members have ample time to research topics of interest and prepare feedback. Along these lines, Council members will have the opportunity to provide information about what activities in their related areas of interest may align with the PMI in advance of the June presentation.
Dr. Khosla suggested that the Institute could look to the National Center for Advancing Translational Sciences (NCATS) for opportunities to leverage trans-NIH efforts in support of NIAMS mission areas (e.g., NCATS’ Trial Innovation Network can provide various levels of support for clinical trials). Dr. Katz agreed and reminded Council members that the NIAMS is one of many ICs that allocates funds to support NCATS efforts. Mr. Mulvihill suggested that the NAMSAC is in a position to provide leadership to volunteer lay and professional organizations to help align and leverage their work with NIAMS activities. A future Council meeting may include a presentation on NIAMS activities with these types of organizations to provide examples of what types of engagement/collaboration are possible.
Dr. James volunteered to lead a new subgroup to develop questions and discuss issues related to NIAMS areas of interest and how they are being addressed (or could be addressed) through the PMI. Dr. Katz agreed to the formation of this subgroup under Dr. James’ leadership. NIAMS programs can be strongly encouraged to follow the PMI Standard Operating Procedures for data and specimen collection to leverage the PMI cohort (and in turn, the PMI may be able to leverage aspects of NIAMS programs moving forward). It was noted that the Institute could identify opportunities to place a greater emphasis on engaging community physicians, and practice-based research networks, particularly in the area of rheumatology.
Dr. Katz concluded the discussion session by noting that future presenters at Council meetings from outside NIAMS may be asked to provide specific information about how programs address the inclusion of different cultures/ethnicities.
STATE OF THE NIAMS IRP 2016
NIAMS Scientific Director Dr. John O’Shea provided Council members with an overview of the NIAMS IRP, focusing on an overview of the program itself, a series of scientific highlights, and new staff that have joined the IRP. He reminded Council members that the IRP is evaluated on an annual basis by the Board of Scientific Counselors (BSC) and represents the Institute’s single largest investment (currently about 10.4 percent of the Institute’s total budget, and projected to grow with the addition of the Dermatology Branch). The IRP includes scientific and clinical faculty members, the Office of Science and Technology (Cores), training and outreach initiatives, and programs that span from very basic to clinical issues.
Dr. O’Shea described a number of scientific highlights from the NIAMS IRP, including:
- Understanding the pathophysiology of x-linked macular degeneration by examining the structure of the protein retinoschisin and the location of the mutations associated with the disease.
- Genomics and next-generation sequencing work showing that superenhancers associate with cognate promoters by means of "stripes" (long stretches of highly interactive chromatin).
- Research using the 10x Genomics platform that allows for single cell digital gene expression. Examples include examining the transcriptional profile of regenerating muscle stem cells and studying the similarities and differences between different types of innate and adaptive lymphocytes.
- Exploring an unexpected mechanism by which Fas protects from autoimmunity in autoimmune lymphoproliferative syndrome.
- The discovery that engagement of CD11b suppresses lupus through the modulation of interferons.
- A phase Ib study on the use of tofacitinib to inhibit damage to kidneys and a clinical trial examining the role of PPAR-gamma in systemic lupus erythematosus.
Dr. O’Shea then provided an update on the activities and research interests of tenure-track and assistant clinical investigators, including Drs. Markus Hafner [CNBP (CCHC-type zinc finger nucleic acid binding protein) and RNA translation], Andy Mammen (myositis), Keith Sikora (rapidly progressive juvenile arthritis), Peter Grayson (vasculitis), Michael Ombrello (genetics of sJIA), and Brian Glancy (muscle energetics). He also described the research interests of members of the Dermatology Branch and identified IRP staff who will be reviewed by the BSC this year.
Dr. Holers asked about the composition of the BSC and whether all relevant clinical disciplines are represented on the Board. Dr. O’Shea explained that the BSC includes both permanent members as well as ad hoc members—the Institute makes every effort to include expertise in all areas of interest on the Board. Dr. Katz added that BSC membership is driven by the science that is conducted by the IRP and that the BSC’s collective knowledge is enhanced by numerous ad hoc members. He also clarified that the BSC does not design the activities of the IRP. Dr. Koretzky, who previously served as a member of the BSC, characterized the Board as an independent partner of the NIAMS IRP that helps evaluate science and provides guidance related to the vision of the IRP. Dr. Katz noted that the Institute relies heavily on the independent input from the BSC.
NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES VISION AND AGENDA
National Institute on Minority Health and Health Disparities (NIMHD) Director Dr. Eliseo Pérez-Stable provided a brief history of the NIMHD, noting that it began as an NIH Office in 1990, transitioned to a Center in 2000, and became an Institute in 2010. NIMHD’s FY 2016 budget was roughly $280 million.
NIMHD’s mission is to lead scientific research that advances understanding of minority health and health disparities. The Institute supports: (1) research in minority health, as defined by racial/ethnic groups in the U.S. Census; (2) research to understand the causes of and reduce health disparities in specific populations; and (3) training and development of a diverse scientific workforce as part of broad NIH mandate. Dr. Pérez-Stable explained that health disparity populations include racial/ethnic minorities, those with less privileged socio-economic status, underserved rural residents, and/or sexual gender minorities. Populations have poorer health outcomes that often are attributed in part to social disadvantage, and to being underserved in the full spectrum of health care. He defined the term "health disparity" as a health difference that adversely affects disadvantaged populations, based on one or more health outcomes. Health disparities research is devoted to advancing scientific knowledge about defining mechanisms of how health determinants affect disparities, and how this knowledge is translated into interventions to reduce disparities. Dr. Pérez-Stable described health disparity outcomes (e.g., higher incidence and/or prevalence, burden of disease) and the mechanisms leading to health disparities (e.g., individual behaviors, lifestyle, beliefs and response to stress, biological processes, physical and cultural environment, clinical events, and health care).
The inclusion of diverse participants in research activities (both in terms of study recruitment as well as in the workforce) is a critical issue. Clinical topics of mutual interest to the NIAMS and NIMHD include systemic lupus erythematosus, scleroderma, osteoarthritis, rheumatoid arthritis, atopic dermatitis, and vitiligo. NIMHD priorities include: (1) defining the science of health disparities and minority health, (2) promoting innovation from extramural scientists in these sciences that lead to R01 applications, (3) establishing a Health Services and Research in Clinical Settings program, and (4) promoting diversity in the workforce. Dr. Pérez-Stable discussed NIMHD’s new research areas for 2017, reviewed a series of scientific workshops that have been held or are being planned, and provided a brief overview of NIMHD’s IRP. He noted that additional information is available on the Institute’s website (www.nimhd.nih.gov).
Dr. James noted that many of the programs in the NIMHD portfolio are focused on diabetes and cardiovascular disease. She suggested that rheumatic and skin diseases present numerous opportunities of interest to the NIMHD as well. Dr. Pérez-Stable noted that applications to the Research Centers in Minority Institutions Program are being accepted until March 7. It is expected that about 10 awards will be made this cycle. A new Funding Opportunity Announcement (FOA) is also expected to be issued for NIMHD’s Centers of Excellence Program. Dr. James also asked about interactions between the NIMHD and the Native American Research Centers for Health (NARCH) Program. Dr. Pérez-Stable explained that the NIMHD has signed up as one of a number of NIH ICs as a participant in the NARCH Program.
In response to a question from Dr. Katz about future R01s submitted to the NIMHD, Dr. Pérez-Stable commented that the applications that are typically successful and highly valued at the NIH tend to be focused on laboratory science; yet many of the applications that generally are not as successful include critically important public health topics such as hypertension, minority health, and community health. Dr. Katz noted that there is significant potential for collaboration between the NIAMS and NIMHD IRP, particularly given the common interest in lupus.
MOLECULAR TRANSDUCERS OF PHYSICAL ACTIVITY CONSORTIUM: AN NIH COMMON FUND PROGRAM
Dr. Joan McGowan, Director of the NIAMS Division of Musculoskeletal Diseases, provided an update on the Molecular Transducers of Physical Activity Consortium (MoTrPAC), an NIH Common Fund program that launched in 2015. In December 2016, 19 awards were made in response to 6 FOAs, and the MoTrPAC Steering Committee held its first meeting in January of this year. MoTrPAC’s goal is to discover the molecules and pathways responsible for physical activity’s benefits to human health. It is a 6-year, $170 million study with a group of about 3,000 sedentary people from a variety of age ranges. Participants will begin an exercise program and then provide blood, fat, and muscle samples before and after they exercise. These samples will be studied to learn more about how the body changes as a result of physical activity. A non-exercising control group will be tracked as well.
Dr. McGowan presented an overview of MoTrPAC (https://commonfund.nih.gov/MolecularTransducers), noting that it is a trans-NIH effort led by the NIAMS, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, and National Institute of Biomedical Imaging and Bioengineering. She also presented a video clip that features Dr. Collins highlighting the importance of MoTrPAC.
The 19 awarded MoTrPAC components include a Consortium Coordinating Center, Bioinformatics Center, 7 Clinical Centers, 7 Chemical Analysis Sites, and 3 Preclinical Animal Study Sites. Dr. McGowan acknowledged the NIAMS team supporting MoTrPAC and described MoTrPAC’s committee structure and leadership. It is hoped that MoTrPAC can:
- Enable and encourage research to define the mechanisms for the health benefits of physical activity
- Provide measurable outcomes that will enable the use of a physical activity intervention (or equivalent) in basic and clinical studies of health and disease
- Provide novel molecular definitions for fitness and exercise response
- Provide predictors for the health response to physical activity
- Generate novel, testable, mechanistic hypotheses regarding normal human physiology and disease
Dr. Katz commented that MoTrPAC is a major effort intended not only to address the important research topics described by Dr. McGowan, but also to be used as a research resource in the future. Mr. Silver asked about the data being collected on the 3,000 study participants, within the context of collecting data that may be helpful beyond the immediate research needs associated with MoTrPAC. Dr. McGowan noted that MoTrPAC planning committees have been discussing these issues but acknowledged that researchers can only access the study participants for a limited amount of time. In response to a question by Dr. Pavlath, Dr. McGowan explained that MoTrPAC enrollees will primarily be sedentary volunteers. One site will be recruiting children and teens (ages 10-18); this site will not be collecting muscle biopsies.
Dr. McGowan described efforts being made to disseminate MoTrPAC information to interested stakeholders, noting that MoTrPAC is being discussed at a variety of scientific meetings. In addition, the Communications Office within the Office of the Director has a number of planned outreach activities.
Dr. Khosla noted that there is increasing evidence to suggest that people respond differently to different exercise routines. He asked if MoTrPAC interventions are designed to provide information about which exercise regimens might be most effective for certain populations. Dr. McGowan indicated that MoTrPAC studies themselves are not going to be able to make a determination about whether one type of exercise is "better" than another. Work is still underway to identify which exercise protocol(s) will be used. The goal of the exercise protocol is the discovery of molecules. Resistance and aerobic exercise will be compared, but the ability to identify an exercise "prescription" depends on the discovery of molecular transducers. Examining the pattern of molecular transducers should then allow for studying the responsiveness of individuals to different types and amounts of exercise.
Ms. Castro Lewis noted that there are a number of differences between Hispanic subgroups and asked whether MoTrPAC will include subgroups outside of Mexican Americans. Dr. McGowan reminded Council members that MoTrPAC enrollment is limited and acknowledged that the inclusion of different Hispanic subgroups will be affected by the geographic locations of enrollment. The overall intent in MoTrPAC enrollment is to be as diverse as possible.
NIAMS CENTERS UPDATE
Dr. Carl Baker, Health Scientist Administrator within the NIAMS Division of Skin and Rheumatic Diseases, reviewed the 2013 Centers Evaluation Working Group (CEWG) recommendations, described some of the changes to the center funding mechanisms, and presented results of recent Center solicitations. In 2013, NIAMS Centers included P30 Research Core Centers (P30; core services), Centers of Research Translation (P50; disease-focused translational projects), and Multidisciplinary Clinical Research Centers (P60; methodology cores and clinical research projects). The CEWG recognized that there was a set of common goals across these Centers:
- Foster interdisciplinary science to promote innovation
- Facilitate sharing of research resources
- Accommodate research community’s need for shared clinical methodologies
- Increase community awareness and use of shared resources
- Foster mentorship and training within Centers
The CEWG evaluated the Centers together and made the following recommendations: (1) the NIAMS should allow flexibility and dynamism in the design, structure, and conduct of its Centers; and (2) NIAMS Centers should foster synergistic interactions and interdisciplinary collaborations to enable innovative approaches to understanding diseases in humans (the CEWG report is available here). In restructuring its Centers program, NIAMS focused on innovation, flexibility, resource sharing and outreach efforts in support of resource sharing, and redefining the "research base." Three sets of solicitations were issued, and the NIAMS Centers program now includes the following:
- Resource-based Centers (P30). These centers feature a Research Core, Administrative Core/Center Enrichment Program, and a maximum budget of $500,000 in direct costs per year. Their focus may be broad or may be on a narrow disease, allowing for basic, translational, and/or clinical research. Three FOAs were released in 2015 supporting rheumatic diseases (4 awards), skin biology and diseases (3 awards), and musculoskeletal biology and medicine (3 awards).
- Centers of Research Translation (P50). These Centers are required to have an administrative Core and three research components, at least one of which is a translational Research Project (the other two can be Research Cores or Research Projects). Their focus can be on an overarching translational theme or a single critical question or challenge. Flexibility has been added so that the Research Cores can adjust their technical focus. Main outcomes are expected to improve understanding of disease and identification of targets and/or tangible products or deliverables. Two FOAs were released in 2015 and 2016; 4 awards have been made to date, with 2016 applications to be reviewed in March 2017. These Centers have a maximum budget of $1 million in direct costs per year.
- Core Centers for Clinical Research (P30). The goal of these Centers is to advance prevention, diagnosis and treatment of musculoskeletal, rheumatologic, and skin diseases by developing and fostering the implementation of novel methods, metrics, and outcome measures that address critical existing and emerging clinical research needs. Success is measured by adoption of metrics and methodologies resulting from Center work/resources into new clinical research projects, proposed clinical trials, and ultimately, patient care. These Centers should include, at all levels of clinical research from conceptualization to implementation, efforts to address the preferences and needs of patients. The FOA for these Centers was issued in September of 2016; applications have been received and will be reviewed this spring. These Centers have a maximum budget of $500,000 in direct costs per year.
Dr. Yaszemski asked about the total number of Center awards the Institute hopes to make and whether there are plans for additional FOAs in 2017 and/or 2018. Dr. Katz explained that the Institute cannot provide this information at this point; NIAMS’ budget in future years will play a large part in helping to answer those questions.
Dr. Koretzky commented on the importance of establishing both short- and long-term evaluation metrics for these Centers, noting that the importance of some of the work conducted by the Centers may not be fully appreciated for a number of years.
COUNCIL OPERATING PROCEDURES
Dr. Moen reminded Council members that on an annual basis, the Institute brings forward the Statement of Understanding between NAMSAC and the NIAMS for Council review. This Statement of Understanding outlines the operating procedures for the next year. No changes were made to the Statement, and the NIAMS does not intend to make any modifications at this time. Council members had no suggestions for making any change to the Statement of Understanding, which was unanimously adopted.
ADVANCING PEDIATRIC PROs
This portion of the meeting occurred during closed session.
STAR AWARDS DISCUSSION
This portion of the meeting occurred during closed session.
This portion of the meeting occurred during closed session.
CONSIDERATION OF APPLICATIONS
In closed session, the Council reviewed a total of 654 applications in closed session requesting $1,214,583,489 in total costs and recommended 654 for $1,214,583,489 in total costs. For the record, it is noted that secondary applications were also considered en bloc.
The 91st National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 2:40 p.m. Proceedings of the public portion of this meeting are recorded in this summary.
I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.
Stephen I. Katz, M.D., Ph.D.