Department of Health and Human Services
Public Health Service
National Arthritis and Musculoskeletal and Skin Diseases Advisory Council

Minutes of the 92nd Meeting
June 21, 2017
8:30 a.m. to 3:00 p.m.

June 21, 2017 Council Webcast

1. CALL TO ORDER

   The 92nd meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 21, 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).

   Attendance

   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, 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. Michael V. 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
   Ms. Rosemary J. Markoff, Co-Chair, Scleroderma Foundation National Advocacy Committee
   Mr. 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 (via teleconference)
   Mr. Richard F. Seiden, Foley & Lardner LLP
   Mr. Alexander Silver, Chairman, Jackson Gabriel Silver Foundation (via teleconference)
   Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center
   Dr. Gwendolyn L. Powell Todd, Patient, Health Advocate, and Educator (via teleconference)
   Dr. Michael J. Yaszemski, Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic

   Staff and Guests

   The following NIAMS staff and guests attended:

   Staff

   Ms. Gema Souto Adeva Dr. D. Lee Alekel Mr. Steve Austin Ms. Pamela Beheler Ms. Elizabeth Bouras Dr. Amanda Boyce Dr. Nakia Brown Dr. Stephanie Burrows Ms. Justine Buschman Dr. Robert Carter Ms. Cindy Caughman Dr. Faye Chen Dr. Thomas Cheever Dr. Ricardo Cibotti Ms. Robin DiLiello Ms. Teresa Do Dr. Jonelle Drugan Ms. Elizabeth Elliott Ms. Barbara Footer Dr. Nancy Garrick Ms. Aleisha James Ms. Katie Joffee Dr. Stephen I. Katz Ms. Shahnaz Khan Ms. Stephanie Kreider Mr. Mark Langer Mr. Greg Lavine Dr. Gayle Lester

   Ms. Anita Linde Ms. Leslie Littlejohn Dr. Yin Liu Dr. Kan Ma Dr. Marie Mancini Dr. Kathryn Marron Dr. Joan McGowan Ms. Leslie McIntire Ms. Melinda Nelson Dr. Kristy Nicks Dr. Carol Parsons Ms. Amita Patel Mr. Rick Phillips Ms. Andree Reuss Dr. Kathy Salaita Dr. Susana Serrate-Sztein Ms. Sheila Simmons Ms. Yen Thach Ms. Jamie Thompson Dr. Carol Torgan Dr. Hung Tseng Dr. Bernadette Tyree Dr. Fei Wang Dr. Xibin Wang Dr. Chuck Washabaugh Dr. James Witter Ms. Robin Wolz Dr. Xincheng Zheng

   Guests

   Dr. Kayla Amodeo, American College of Rheumatology
   Ms. Megan Cohen, Scleroderma Foundation
   Mr. Eric Dishman, All of Us Research Program, NIH
   Ms. Patti Brandt Hansberger, Office of Legislative Policy and Analysis, NIH
   Ms. Daozhong Jin, All of Us Research Program, NIH
   Dr. Lynne Jones, Orthopaedic Research Society
   Mr. Zachary Kribs, American Society of Nephrology
   Dr. Rajiv Kumar, Center for Scientific Review, NIH
   Ms. Jessica Nagro, National Psoriasis Foundation
   Ms. Joy Nathan, BETAH Associates
   Mr. Blake McDonald, American Academy of Dermatology Association
   Mr. Ryan Murray, American Society of Nephrology
   Mr. Vincent Pacilio, Arthritis Foundation
   Ms. Deanna Portero, Fibrous Dysplasia Foundation
   Dr. Srikanth Ranganathan, Center for Scientific Review, NIH
   Mr. Robert Riggs, NIAMS Coalition Co-Chair/Scleroderma Foundation
   Ms. Kirstie Saltsman, IQ Solutions
   Dr. Tara Schwetz, Office of the Director, NIH
   Mr. Joseph Stewart, Scleroderma Foundation
   Dr. Lawrence Tabak, Principal Deputy Director, NIH
   Ms. Randi Williams, KAI Research, Inc.

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to approve the minutes of the 91st NAMSAC meeting, held on January 25, 2017.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:

   September 6, 2017
   February 7, 2018
   June 12, 2018
   September 5, 2018
   February 5, 2019
   June 12, 2019
   September 10, 2019

4. 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. In general, 75-100 individuals tend to watch the videocasts of NAMSAC open sessions in real time, while an additional 50-75 people watch the proceedings once the videocast is archived.

   Dr. Katz noted the Institute’s appreciation for Council members’ continued engagement and willingness to provide input. He thanked Dr. James, who chaired the Council subgroup responsible for developing and submitting questions in advance of the presentation on the All of Us Research Program (additional members of the subgroup included Dr. Econs, Dr. Paller, Dr. Todd, and Mr. Silver). He also acknowledged formation of the newly established Council Agenda Working Group, which is chaired by Dr. Bechtold and includes Ms. Castro-Lewis, Dr. Holers, Dr. James, Dr. Lerner, and Mr. Mulvihill.

   Budget and Congress

   Dr. Katz reported that the NIH is grateful for Congress’s bipartisan, bicameral support that resulted in a considerable budget increase for the NIH and NIAMS for the remainder of fiscal year (FY) 2017. The NIH received a $2 billion increase; much of this increase is dedicated to programs mentioned in the 21st Century Cures Act. NIAMS investigators stand to benefit from: (1) a targeted National Cancer Institute (NCI) led effort to support research into auto-inflammatory or autoimmune adverse events in the setting of cancer immunotherapy, and (2) a suite of funding opportunities to encourage clinical research studies aimed at furthering the field of regenerative medicine using adult stem cells. The increased funding also allowed the NIAMS to expand its R01 payline for established investigators to the 13th percentile and to pay competing R01 applications from new investigators through the 20th percentile. Dr. Katz reminded NAMSAC members that the Institute’s full funding plan is available online.

   Over the past few months, NIAMS has met with members of the new Administration, Congress and their staff to share ways that the research it supports is impacting people’s lives. Secretary of the Department of Health and Human Services, Dr. Thomas Price (an orthopaedic surgeon) met with NIH Director Dr. Francis Collins and several Institute and Center (IC) Directors. This meeting provided Dr. Katz with the opportunity to highlight the work of NIAMS investigators both in the intramural research program as well as at universities and medical centers across the United States.

   On June 12, Representatives Don Beyer (D-VA), Susan Davis (D-CA), Scott Peters (D-CA), and Kathleen Rice (D-NY) as well as several Congressional staffers visited the NIH Campus as part of the New Democrat Coalition. Dr. Katz thanked Drs. Mariana Kaplan (Chief of the Systemic Autoimmunity Branch) and John O’Shea (NIAMS Scientific Director) for hosting a tour of the Systemic Autoimmunity Branch’s laboratory and describing their research to better understand autoimmune diseases such as lupus and rheumatoid arthritis (RA). He also thanked staff of the NIAMS Office of Science Policy, Planning and Communications for arranging the visit and ensuring that NIAMS research was featured.

   On May 23, President Trump released his budget proposal for FY 2018. On the day following this NAMSAC meeting, the Senate’s Labor, Health and Human Services, and Education Appropriations Subcommittee will hold a hearing on the NIH Budget. Dr. Collins and several Institute Directors will participate. The comparable House hearing was held on May 17. The President’s proposed budget shows a 25% decrease in funding relative to FY 2016.

   NIH and NIAMS Policies and Plans

   Earlier this month, President Trump asked Dr. Norman Sharpless to direct the NCI. Dr. Sharpless comes to NIH from the University of North Carolina at Chapel Hill, where he directed the Lineberger Comprehensive Cancer Center and served as a Wellcome Distinguished Professor in Cancer Research. The NIAMS looks forward to working with Dr. Sharpless on activities related to the Beau Biden Cancer Moonshot and other areas of shared interest.

   The NIH unveiled the Next Generation Researchers Initiative (NGRI) earlier this month—this effort is expected to stabilize the biomedical research workforce by bolstering NIH funding for the next generation of researchers. Later in the meeting’s agenda, NIH Principal Deputy Director Dr. Larry Tabak provided an update on the NGRI.

   In August of last year, the NIH announced plans to eliminate most appendix materials for applications submitted for due dates on or after January 25, 2017. The NIH also published a second notice in the NIH Guide on January 13. However, quite a few of the clinical trial applications received by the NIAMS for this round were withdrawn as noncompliant because they contained unallowable appendices. Dr. Katz noted that the Institute will soon be reminding all of its grantees about this policy, and asked NAMSAC members to take this information back to their colleagues. Another NIH-wide policy that affects many NIAMS grantees is last year’s announcement that all sites participating in a multi-site clinical study are expected to rely on a single Institutional Review Board (IRB) to carry out the ethical review of the proposed research. Implementation of this policy has been pushed back to all competing grant applications with a receipt date on or after January 25, 2018.

   Dr. Katz noted that following his Director’s report, Dr. James Anderson, Director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) would be providing an update on the NIH Common Fund. The Common Fund was established 13 years ago (and was then called the NIH Roadmap for Medical Research), and the NIAMS has been involved with many of its trans-NIH initiatives from the earliest stages. The Patient-Reported Outcomes Measurement Information System (PROMIS), the Human Microbiome Project, and the Molecular Transducers of Physical Activity Consortium (MoTrPAC) are among the various Common Fund programs that are directly advancing NIAMS mission areas.

   This NAMSAC meeting also featured an update on the Rheumatoid Arthritis/Lupus Accelerating Medicines Partnership (AMP) program, which recently completed its phase 1 activities. AMP is a public-private partnership to develop new ways of identifying and validating promising biological targets for diagnostics and drug development and has three components: (1) Alzheimer’s disease, (2) type 2 diabetes, and (3) RA and systemic lupus erythematosus (SLE).

   Dr. Katz provided a brief update on the Pathways to Prevention Workshop that emerged in response to recommendations of current Council member Dr. Sundeep Khosla and former Council member Dr. Elizabeth Shane. A small group of NIH staff, led by Drs. Faye Chen (Program Director in NIAMS’ Division of Musculoskeletal Diseases) and Lyndon Joseph (of the National Institute on Aging), are working closely with the NIH Office of Disease Prevention on the Appropriate Use of Drugs for Osteoporosis Fracture Prevention. This effort includes partnering with the Agency for Healthcare Research and Quality to contract with an Evidence-based Practice Center that will conduct a systematic review of the literature. This evidence report will serve as a cornerstone of a subsequent workshop—likely to be held in October 2018—by objectively describing the state of the science, summarizing ongoing research, and evaluating research needs.

   NIAMS extramural program staff continuously scan the scientific landscape to identify unmet needs and opportunities that can be nurtured through the Institute’s basic, translational, and clinical research portfolios. On an annual basis, NIAMS brings together groups of investigators for roundtable discussions on some of these topics. After the meetings, summaries are posted on the NIAMS website. The NIAMS recently held two such roundtables: one on Gaps and Emerging Opportunities in Psoriatic Arthritis, and the other on Innovative Treatments for Enthesis Repair. Dr. Katz acknowledged and thanked NIAMS staff who coordinated these activities. (A presentation on the Gaps and Emerging Opportunities in Psoriatic Arthritis Roundtable was scheduled for this NAMSAC meeting but was deferred to the next Council meeting due to time constraints).

   Institute staff also engage in internal discussions on ways to improve administrative efficiencies and better leverage its resources. This year, Institute staff discussed: (1) examples of strategies that NIAMS has successfully used when partnering with professional and voluntary organizations, either individually or through the NIAMS Coalition (a group of more than 90 professional and voluntary organizations interested in NIAMS mission areas); (2) ways that NIAMS researchers can better leverage resources developed through large, trans-NIH initiatives; and (3) metrics to evaluate new and ongoing NIAMS initiatives. Updates on these topics, along with the outcomes of the Innovative Treatments for Enthesis Repair Roundtable, will be provided during the open session of a future Council meeting.

   Dr. Katz noted that this NAMSAC meeting would also include an update on the NIAMS Supplements to Advance Research from Projects to Programs (STAR), an initiative the NIAMS started in 2015 to enhance support for early established investigators.

   The NIAMS issues an electronic newsletter—the NIAMS Update—that includes information about scientific news and resources, along with Dr. Katz’s monthly Director’s Letter. His April column featured NIH resources to jumpstart and sustain research careers, while his May column emphasized the importance of communicating research progress, including NIH’s new guidance regarding the use of preprints and other interim research products to enhance the rigor and transparency of their work, speed information dissemination, and better communicate the impact of NIH-funded research. Dr. Katz’s June column featured a guest letter from Dr. Richard Nakamura, Director of the Center for Scientific Review, which encourages participation in peer review panels. Additionally, the Institute disseminates the NIAMS Community Outreach Bulletin, an online digest designed to inform community advocates and health professionals about resources for diverse audiences on conditions of the bones, joints, muscles and skin, and ways to stay healthy. The Digest’s Spring issue’s feature story describes a program that the NIAMS recently conducted with National Institute of Diabetes and Digestive and Kidney Diseases and Chi Eta Phi (a professional organization of African American nurses) to raise awareness about lupus.

   The Institute recently hosted a webinar for members of the NIAMS Coalition explaining how the NIAMS sets priorities and makes funding decisions. It will host its biennial Outreach and Education Meeting on October 17 on the NIH Campus—this will be the fifth such meeting, and NIAMS staff are working with Coalition colleagues to develop the agenda.

   Highlights of Selected Recent Scientific Advances

   Dr. Katz described several scientific advances of interest to the Council.

   • Dr. Zhou-Feng Chen at the Center for the Study of Itch at Washington University led a group of scientists who discovered a molecular explanation for the tendency of social animals to imitate certain behaviors, like yawning or scratching. They demonstrated that: (1) imitative scratching requires only sight by the imitator, and does not rely on other sensory functions such as smell or hearing; (2) a brain region located near the optical nerves that transmit visual information is responsible for the behavior; and (3) a molecule called gastrin-releasing peptide in that area of the brain is key for inducing imitative scratching. Their work provides a greater understanding of the biological circuits and pathways involved in itch and socially contagious behaviors, and opens the possibility of new interventions to treat chronic itch (Science. 2017 Mar 10;355(6329):1072-1076. PMID: 28280205).
   • At Columbia University, Dr. Stavroula Kousteni and colleagues discovered a new mechanism that regulates food intake and blood sugar. Their work revealed that bone-forming cells of mice produce a protein called lipocalin 2, which was thought to be primarily secreted by fat cells. Additional experiments demonstrated that osteoblast-derived lipocalin 2 enters the mouse brain, where it binds to and activates neurons that suppress appetite and regulate body weight and energy metabolism. Further evidence supporting the potential biological importance of lipocalin 2 comes from people with type 2 diabetes. Patients’ serum levels of lipocalin 2 inversely correlated with their body weight and hemoglobin A1c, which is a measure of long-term blood sugar levels (Nature. 2017 Mar 16; 543(7645):385-390. doi: 10.1038/nature21697. Epub 2017 Mar 8. PMID: 28273060).
   • Recent work from NIAMS K awardee Dr. Jason Knight and his group at the University of Michigan clarifies the role of immune cells called neutrophils in antiphospholipid syndrome (APS), an autoimmune disease that can cause dangerous blood clotting and pregnancy complications. They demonstrated that a specific type of antibody isolated from patients with APS causes neutrophils to release web-like fibers known as neutrophil extracellular traps (NETs). Under normal conditions, these NETs contribute to immunity by capturing and killing pathogens, but these structures have also been shown to drive blood clotting. Mice treated with antibodies from APS patients formed larger and more frequent blood clots than control mice, and neutrophils and NETs were required for this accelerated thrombosis (Arthritis Rheumatol. 2017 Mar;69(3):655-667. PMID: 27696751).
   • Researchers from Dr. Kaplan’s laboratory in the NIAMS intramural program also are studying the roles of NETs—particularly how they may contribute to the development and maintenance of autoimmune diseases such as rheumatoid arthritis. Her group determined that NETs can be taken up by fibroblast-like synoviocytes via a specific cell-surface receptor and companion protein. The NETs also cause increased expression of immune-stimulating proteins on the synoviocytes’ surfaces. These NET-activated cells activate the adaptive immune system and lead to generation of autoantibodies (Sci Immunol. 2017 Apr;2(10). pii: eaag3358. doi: 10.1126/sciimmunol.aag3358. Epub 2017 Apr 14. PMID: 28649674).
   • Dr. Michael Brenner at Brigham and Women’s Hospital and colleagues described a new population of T cells that display a unique capacity to infiltrate inflamed tissues and drive autoantibody production by B cells. The joints of patients with RA have many more of these cells, which the investigators termed “T peripheral helper” cells. Future studies may shed light on whether selective targeting of T peripheral helper cells can interrupt local production of autoantibodies and downstream inflammatory cascades, potentially providing a basis for new RA treatments (Nature. 2017 Feb 1;542(7639):110-114. PMID: 28150777).
   • A recent study by Dr. Jinoos Yazdany and his team at the University of California, San Francisco showed that a 10-item short form version of the PROMIS physical function bank, developed by the NIH-PROMIS initiative, is better able to measure the physical functioning of today’s RA patients than the widely used Health Assessment Questionnaire. They also found that the PROMIS short form is responsive to change with therapies, correlates with disease activity measures, and is feasible for use in routine practice in a racially and ethnically diverse RA population (Arthritis Care Res. 2017 March 69 (3): 338-346. doi: 10.1002/acr.22956. PMID: 27332620).
   • In osteoarthritis (OA), intra-articular steroid injections are a standard treatment for osteoarthritis pain. However, the clinical benefit of these injections is highly controversial, particularly over the long term. Investigators led by Dr. Tim McAlindon at Tufts University examined 140 symptomatic knee OA patients who received intra-articular injections of triamcinolone or saline once every 12 weeks for 2 years. Although their findings neither prove nor negate the effectiveness of intra-articular steroid injections for short term relief of pain, the investigators found no long-term effect on knee pain. In fact, the group that received the steroid showed signs of more extensive cartilage loss than the control group, suggesting that long term use may result in adverse effects on preservation of knee cartilage (JAMA. 2017 May 16;317(19):1967-1975. PMID: 28510679).
   • A research team led by Dr. Dwight Koeberl at Duke University developed a gene-transfer approach that, when tested in mice, shows promise for treating Pompe disease. The therapy uses a modified virus to deliver a gene to the liver where it produces acid alpha-glucosidase, an enzyme that is missing in people with Pompe disease. Although the study’s main goal was to see if the gene transfer strategy would induce immune tolerance to the lab-generated version of the enzyme that patients receive as treatment, it also demonstrated that this gene therapy could potentially replace the standard care. The results of this study directly contributed to an investigational new drug approval by the U.S. Food and Drug Administration to move this approach into clinical trials and ascertain whether this promising approach will be effective in humans (Mol Ther Methods Clin Dev. 2017 Jan 11;4:126-136. eCollection 2017 Mar 17. PMID: 28344998),

   Dr. Katz concluded his Director’s Report by inviting Council members to view the collection of scientific images displayed on the walls of the NIAMS offices on the fourth floor of Building 31. He explained that these visually intriguing and compelling pictures illustrate a specific cell or structure that has previously been difficult to visualize, or convey a complicated scientific concept in a clear and understandable way. Dr. Katz thanked the intramural and extramural researchers who shared these images and invited Council members to share additional scientific imagery with the NIAMS Office of Science Policy, Planning and Communications.

   Discussion

   Dr. Lerner commented on the itch study led by Dr. Chen at Washington University, noting that there are measures of itch using sound, rather than vision, to assess scratching behavior, and that it would be interesting to conduct the study by Dr. Chen and colleagues with vision removed from the equation.

   Dr. Khosla thanked NIAMS and NIH staff for considering stakeholder feedback and putting forward the Pathways to Prevention project. This effort addresses a critical need in terms of providing an objective external assessment and informing primary care physicians and patients. He also discussed NIH’s definition of a “clinical trial” and asked about the review of applications that are clinical studies embedded in an R01 that do not have a therapeutic intent, but rather attempt to define physiology and mechanisms. He noted that the NIAMS had issued an exception so that this type of application could be reviewed by an appropriate Center for Scientific Review study section rather than by the NIAMS Clinical Trials Study Section. However, a trans-NIH policy overruled this exception. Dr. Khosla noted that he has discussed this matter with NIH Deputy Director for Extramural Research Dr. Michael Lauer. Dr. Joan McGowan, Director of the Division of Musculoskeletal Diseases, noted that the NIAMS has engaged other ICs in discussing this concern, and it is hoped that they will collaborate to resolve this issue (possibly through a specific Funding Opportunity Announcement [FOA] designed to accommodate these mixed studies) so that the NIH as a whole can better accommodate all of the research applications it receives. She commented that the NIAMS still feels that some mixed studies that have basic translational and clinical components could be reviewed by appropriate study sections at the CSR. Dr. Khosla noted that in his communication with Dr. Lauer, he suggested that the NIH adopt the NIAMS approach that was superseded. Dr. Katz agreed to follow up with Dr. Lauer.

5. NIH COMMON FUND: OPPORTUNITIES, SUCCESSES, AND CHALLENGES

   Dr. Anderson explained that the NIH Common Fund supports a set of trans-NIH scientific programs and provides “venture capital” space for high-risk, innovative endeavors with the potential for extraordinary impact. The Common Fund supports short-term (5-10 year), goal-driven programs focused on developing specific deliverables (e.g., data, tools, technologies, etc.) to catalyze research. The Common Fund is managed by the Office of Strategic Coordination within the NIH Office of the Director, in partnership with the NIH ICs. Common Fund programs are intended to benefit the broad biomedical research community; the NIAMS has been active in numerous Common Fund programs (e.g., PROMIS).

   Criteria for Common Fund programs include being: (1) transformative; (2) catalytic, short term, and goal driven; (3) synergistic/enabling; (4) cross-cutting; and (5) novel. Dr. Anderson described ongoing Common Fund programs in the areas of new types of clinical partnerships, transformative workforce support, data/tools/methods, and new paradigms. The Common Fund has reached a steady state, such that each year it initiates 2-3 new projects while transitioning out of 2-3 projects. He noted that there is evidence demonstrating that Common Fund approaches (i.e., greater funding, longer periods of time, “de-risked” projects, etc.) can produce more innovative activities than standard R01s. The Common Fund has a budget of more than $565 million (not including the Precision Medicine Initiative Cohort Program).

   This year, the Common Fund is starting two programs:

   • The Molecular Transducers of Physical Activity in Humans, in which the NIAMS is heavily involved. The goals of this program are to: (1) assemble a comprehensive map of the molecular changes that occur in response to physical activity and when possible relate these changes to the benefits of physical activity, and (2) develop a user-friendly database that any researcher can access to develop hypotheses regarding the mechanisms whereby physical activity improves or preserves health (additional information can be found at www.commonfund.nih.gov/molecularTransducers).
   • The NIH Data Commons Pilot phase of the Big Data to Knowledge Program, which is an effort to sustain the large amounts of research data being generated and make them accessible and usable across data sets. This initiative will focus on making data findable, accessible, interoperable, and reusable through a pilot project (additional information is available at www.commonfund.nih.gov/bd2k).

   Next year, one of the NIH Common Fund programs to launch will be the Human Biomolecular Atlas Program, which will seek to catalyze the development of a comprehensive atlas of cellular organization in human tissues that will elucidate the principles of organization-function (see www.commonfund.nih.gov/HuBMAP/index for additional information).

   Dr. Anderson discussed how the success of NIH Common Fund programs is measured, using NIH’s investment in the Human Microbiome Project and other Common Fund initiatives as examples. He noted that funding for microbiome research outside of the Common Fund at the NIH has grown more than 40-fold in the 10 years since this program began. Dr. Katz noted that much of the newer research in RA and other autoimmune diseases has benefitted from the knowledge and technology created through the Human Microbiome Project. Dr. Anderson also commented that publications produced as a result of Common Fund programs tend to be influential (based on the relative citation ratio) and that Common Fund programs tend to lead to significantly more patents than other NIH grant programs.

   Dr. Anderson concluded his remarks by describing challenges and lessons learned from the Protein Capture Reagents Program, a pilot to test the feasibility of generating protein capture reagents that are reproducible, renewable, and cost effective on a large scale. As the program progressed, it was found that each reagent offered its own production and validation challenges. Furthermore, the effort did not scale well, the highest-priority reagents were not identified, and use has been low. This experience has highlighted the need to engage the user community early and to continuously to guide user-driven programs. Scientific and technical hurdles prevented the scale-up of this very high-risk endeavor; however, reagents of value have been produced—primarily monoclonal antibodies—and there is a need to ensure that the community utilizes these resources.

   Discussion

   Dr. Koretzky asked whether the evaluation metrics for Common Fund programs are identified prospectively or retrospectively. He also asked about sustainability plans for cross-cutting NIH programs that are not intended to answer a discrete scientific question or develop a specific tool (e.g., cataloging the human microbiome). Dr. Anderson explained that Congress recognizes that Common Fund initiatives should be sustained beyond 10 years. In terms of success metrics, Dr. Anderson explained that Common Fund programs are milestone driven and have specific goals that are mapped and measured throughout. Common Fund programs are extensively evaluated every year; Congress requires an NIH Common fund review publication every 2 years that is publicly available. Additionally, the Office of Portfolio Analysis within DPCPSI is working to develop new analytic approaches to measuring the success of Common Fund programs.

6. ACCELERATING PRECISION HEALTH FOR ALL OF US: THE ALL OF US RESEARCH PROGRAM

   Mr. Dishman explained that the mission of the All of Us Research Program (formerly known as the Precision Medicine Initiative, or PMI) is to accelerate health research and medical breakthroughs enabling individualized prevention, treatment, and care. The program has three primary objectives: (1) establish relationships with 1 million U.S. participant partners, from all walks of life, and maintain these relationships for decades; (2) deliver the largest, richest biomedical dataset ever that is easy and free to access while protecting participants’ privacy; and (3) catalyze a robust ecosystem of diverse researchers and funders who are eager to use and support this dataset.

   All of Us participation will be open to interested individuals, and the program will reflect the rich diversity of America. Participants will be partners in the program, and trust will be earned through robust engagement and full transparency. All of Us participants will have access to information and data about themselves; data from the program will be broadly accessible to empower research. Mr. Dishman explained that All of Us will adhere to the PMI privacy and trust principles and the PMI data security policy principles and framework. The program is intended to be a catalyst for innovative research programs and policies. The top priorities for All of Us are to:

   • Deliver a national resource of deep clinical, environmental, lifestyle, and genetic data from 1 million participants who are consented and engaged to provide data on an ongoing, longitudinal basis
   • Reflect the broad diversity of the United States—all ages, races/ethnicities, gender, socioeconomic status, geographies, and health status—by over-recruiting those groups that are underrepresented in biomedical research
   • Build the tools and capabilities that make it easy for researchers from citizen scientists to premier university laboratories to make discoveries using the data and biosamples and through ancillary studies with the cohort.

   There are currently two primary methodologies or paths associated with All of Us: direct volunteers and health care provider organizations. Mr. Dishman briefly described the roles of the six major program components: a Data and Research Center, Biobank, Participant Center, Participant Technology Systems Center, Health Care Provider Organizations, and Communications and Engagement. All of Us launched the first partners and sites with participants, protocol, and platforms in May; the beta phase at 137 locations will extend through the fall with the first 10-15,000 participants before the program launches nationally late this year. Mr. Dishman presented a list of current All of Us Consortium members broken out by direct volunteers, health care provider organizations, and overall program tracking and communication. He then described the IRB-approved version of the All of Us protocol, which will be published soon.

   The All of Us approach to diversity includes diversity in terms of people, health status, geography, and data types. Four primary strategies to ensure diversity are being employed:

   • Develop a national network of health care provider organizations with incentives and methods to reach most diverse people and places.
   • Create an innovative research network that places > 90% of Americans within 45 minutes of at least one direct volunteer partner.
   • Build a network of national and local community partners to help build lifelong, trusted relationships with key communities and areas in the country.
   • Drive programs that ease the way for diverse communities to participate.

   In describing the high-level All of Us approach to security and privacy, Mr. Dishman explained that researchers must agree to a code of conduct and that participants have control over their information. All of Us is developing a preference engine and tools for participants to share their data with family members, providers, other studies, etc. as they choose.

   All of Us is using secondary data analyses, pilots, and ancillary/substudies to build a resource for others to drive their science. Mr. Dishman presented a framework to illustrate the two paths envisioned for NIH IC engagement: (1) influencing the base platform and protocol (e.g., scientists helping to define requirements for the All of Us platform), and (2) investing in pilots and ancillary studies (e.g., ICs engaging their resources). He then presented the program’s current scientific framework across a number of high-level conditions/disease areas and cross-cutting areas of interest/themes.

   The All of Us Program is led in part by a Trans-NIH Liaison Coordinating Team (co-chaired by NIAMS Deputy Director Dr. Robert Carter) that will integrate the breadth and depth of NIH ICs into All of Us to help ensure the program capitalizes on its distinctive characteristics to achieve maximum value. The Team is charged with planning and convening a multi-day workshop (to be held in March 2018) involving relevant stakeholders to develop research priorities. Three subcommittees have been formed to help develop this workshop. In closing, Mr. Dishman invited Council members to learn more about the program at the All of Us website.

   Discussion

   Dr. James, who led the Council subgroup tasked with submitting questions to Mr. Dishman in advance of his presentation, noted that many of those questions, such as prioritization of ancillary studies and leveraging All of Us resources, might be more appropriate to revisit in roughly 1 year. There are many lessons learned from All of Us that are not just science based—for example, the need to consider curation costs. Mr. Dishman agreed, noting the need to informally publish and disseminate these lessons learned and to be very transparent about what is working and what is not.

   Dr. Holers noted that the Council has expressed an interest in the efficient use of available cohorts (both those funded by the NIH and those not funded by the NIH). Many existing cohorts are not disease centric, but could add considerable value to All of Us. Mr. Dishman explained that many of the current All of Us health care provider organizations have existing cohorts/biobanks and are recruiting from them. However, they must meet the diversity requirements. All of Us has been approached by a number of organizations who have their own funded cohorts and want to use the program’s protocol. Shared protocol elements are being explored with groups that have large available cohorts.

   Ms. Castro-Lewis asked about building relationships with the Hispanic community and other racial/ethnic groups as well as minority researchers. Mr. Dishman indicated that All of Us is in its infancy, and that it is too early to judge the success of these types of efforts. Each of the health provider organizations and direct volunteer sites are required to submit an Institutional Site-Specific Amendment to the IRB in which they describe their local engagement strategies.

   Dr. Carter noted that while the All of Us Program is reaching out to NIH ICs to raise awareness of its resources, it is critically important that the NIH ICs are informed by those who understand the All of Us protocol in detail and know how to take advantage of populations and study them using this protocol. He asked that All of Us leadership help the NIAMS reach out to the communities it serves to identify these individuals so that they can contribute to the workshop being planned. Mr. Dishman noted that the March 2018 workshop gives stakeholders another chance to provide significant input into the future direction of All of Us, and the program is still trying to build capacity so that it can provide this type of assistance.

   Mr. Silver asked about the role of private-public partnerships as part of All of Us and how they can be used to accelerate progress. Mr. Dishman commented that these partnerships are key to the program’s success, and some early partnerships may already be forming. For example, initial discussions have been held with a group of pharmaceutical companies that may be able to provide support for accelerating the advance from genotyping to whole-genome sequencing. New technology companies are also being engaged in pilot projects (e.g., for wearable technologies). The All of Us Program will be forming an Industry Advisory Group to help lead these types of efforts.

   Dr. Econs asked about what type of information participants will receive and how often they will be provided with updates. Mr. Dishman noted that All of Us has committed to providing participants with raw data when possible, and emphasized the need for providing this information in a responsible way. A significant challenge facing the program relates to genetics counseling issues and the capacity to provide this counseling within the appropriate clinical context.

7. ENHANCING STEWARDSHIP: THE NEXT GENERATION OF RESEARCHERS INITIATIVE

   Dr. Tabak explained that the Next Generation of Researchers Initiative is grounded in the NIH Strategic Plan and directly relates to the principle of enhancing the stewardship of the agency, particularly in terms of recruiting/retaining an outstanding research workforce and enhancing workforce diversity. It is well recognized that young people have other career options, and the current environment (i.e., an unsustainable, hypercompetitive system) is not conducive to drawing the best and brightest students into the research effort. While the number of NIH research project grant (RPG) applicants increased dramatically from 2003 to 2015, the number of awards has remained constant.

   Dr. Tabak presented a slide showing that from 1990-2015, the percentage of NIH funded late-stage investigators (those aged 60 years or older) increased significantly, from about 5% to more than 20%, while the percentage of funded of mid-stage investigators (aged 46-60 years) increased from about 36% in 1990 to roughly 53% in 2004 and then began declining. Alarmingly, the percentage of early stage investigators (those aged 45 years or younger) saw a sharp decrease from about 56% in 1990 to just over 30% in 2015. Dr. Tabak noted that a current trans-NIH policy provides a boost for first-time applicants, and that early stage investigators have success rates that are similar to that of more experienced investigators. Despite this, in FY 2016, there were 193 R01 applications from early stage investigators with either percentiles ≤ 25, or, for Requests for Applications (RFAs), priority scores of ≤ 35 that were not funded. Therefore, the payline for early stage investigators needs to be further extended.

   To stabilize the career trajectories of scientists, new support systems are needed to nurture investigators with 10 or fewer years as an NIH Principal Investigator (PI) who just missed funding for their first competitive renewal. In FY 2016, there were 263 R01 applications from investigators in this category with either percentiles ≤ 25, or, for RFAs, priority scores ≤ 35 that were not funded. Dr. Tabak explained that support must be prioritized for those investigators who are about to lose all NIH support and may be likely to leave the workforce. Furthermore, new support systems are needed to nurture investigators who have 10 or more years as an NIH PI and are seeking support for their second RPG. Program staff will be asked to identify these “rising stars” and prioritize support for these individuals.

   As part of a new proposed plan to ensure support for PIs at all career stages, all NIH ICs have committed to ensuring support for highly meritorious early stage and mid-career investigators. Starting immediately, the NIH Office of the Director will create an inventory of early stage investigators and mid-career investigators within the fundable range. The Office of the Director will track the IC funding decisions of early stage investigators and mid-career investigators with fundable scores and will evaluate to determine whether uniform decision making is taking place across the NIH. Based on 2016 numbers, it is estimated that roughly $210 million per year is needed to fund both those early stage investigators who have been a PI for 10 years or less and are about to lose all NIH funding as well as those PIs who are seeking a second award. Assuming these awards are each for 5 years, that would be a steady state cost of roughly $1.1 billion. Funding for this new plan will involve reprioritization of funds; some ICs may use ancillary means to help fund these investigators.

   Dr. Tabak discussed the development of productivity metrics to help develop a reliable approach to measure the interim influence of NIH funding. For such a short-term assessment, two types of metrics are needed: (1) validated metrics for output (i.e., productivity), and (2) metrics for grant support that are based on commitment, not dollars (e.g., clinical research is more costly than most basic research). Dr. Tabak described NIH tools for assessing the influence of publications, such as the relative citation ratio (a time-independent, field-normalized metric that measures the influence of publications in PubMed) and iCite (a publicly available dashboard of bibliometrics for publications selected by the user range of years, article type, etc.), noting that additional approaches also need to be considered.

   Beginning immediately, the NIH is committed to redistributing an estimated $210 million per year, reaching a steady state of approximately $1.1 billion over the next 5 years, to support additional meritorious early stage and mid-career investigators. The NIH will encourage independent analyses of metrics that can be used to assess the impact of the NIH portfolio. These analyses will be reviewed by a working group of the Advisory Committee to the NIH Director (ACD), and will be fully discussed at future ACD meetings. All actions will continue to be informed by stakeholder input.

   Discussion

   Dr. Koretzky commented that finding ways to support new investigators is a critical need and applauded the efforts of Dr. Tabak and his colleagues. He suggested that a panel of intramural and extramural scientists be formed to meet and discuss these issues within the context of the scientific workforce. A long-term solution requires understanding what the workforce should look like while allocating funds to that end, and having an open forum for community input might be a more effective approach than asking for feedback after a proposal is put forward. Dr. Tabak noted that these issues have been discussed in depth for multiple years, and the NIH issued a Request for Information in 2015. He also suggested that the working group of the ACD (which will include a few ACD members with a number of additional outside members) may be able to serve as a conduit to receive some of the feedback suggested by Dr. Koretzky.

   Dr. Khosla asked if different ICs, including NIAMS, have looked at the proposal described by Dr. Tabak to determine the impact on the payline for non-early stage investigators. Dr. Katz explained that it costs a certain amount of money to increase from the 12th to the 13th percentile—for the NIAMS, this repurposing would cost roughly $5 million. He also noted that the levelling off of new investigators was due to a 2006 decision to have a success rate for new investigators that was equal to established investigators submitting a new R01.

   Dr. Holers commented that many mid-stage investigators have been funded through grants that are held by senior investigators and expressed concern that investigators who are co-PIs or who have received NIH funding not as a PI represent a cohort that could get lost in these efforts. Dr. Tabak noted that the NIH is aware of this group, particularly investigators who are tied to a more senior investigator’s program. Dr. Holers added that the majority of these individuals are conducting clinical research.

   Ms. Castro-Lewis asked if Dr. Tabak’s group has broken down the career trajectories of scientists by race/ethnicity and how Hispanic and other ethnic groups perform compared to others. Dr. Tabak indicated that some of these analyses have been conducted and that currently, most of the senior investigators tend to be white males. It is hoped that as this redistribution of support is enacted, many of the early stage and mid-career investigators will be from more diverse backgrounds. Each IC is charged with reviewing applications on a case-by-case basis, and it is anticipated that this will open up additional opportunities for those who have been traditionally underrepresented in the scientific workforce.

   In response to a question from Dr. James, Dr. Tabak explained that the NIH is seeking to find the right balance between investigators who are new to NIH (but may have well established careers) and early stage investigators who have received NIH funding.

   Dr. Tapscott asked about the ideal number of new investigators per year required to sustain the scientific research enterprise. Dr. Tabak commented that the NIH has conducted some static modeling and hopes to formally engage workforce economists to help model what the optimum numbers of early stage, mid-career, and late-stage investigators. This work will be complicated by the heterogeneity of the workforce (e.g., clinician researchers are very different than Ph.D. researchers). For those Council members interested in learning more about modeling the scientific workforce, Dr. Tabak suggested reviewing a recent paper published in the Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci USA. 2017 Jun 20;114(25):6498-6503. doi: 10.1073/pnas.1609996114. Epub 2017 Jun 5. PMID: 28584129).

8. ACCELERATING MEDICINES PARTNERSHIP IN RHEUMATOID ARTHRITIS/LUPUS

   Dr. Carter began this session by noting that the RA and Lupus AMP is a partnership between the NIAMS, National Institute of Allergy and Infectious Diseases, and members of industry/advocacy organizations. The focus of this project is to examine the molecules in cells that are active in the target organ of the people with the disease (i.e., in the kidney for those with lupus and in the synovium in those with RA). He thanked Drs. Holers and James for their leadership on this important project and presented a brief video featuring NIH Director Dr. Francis Collins that introduces the RA/Lupus AMP.

   Dr. Holers presented a slide showing the organization and sites of the RA/LUPUS AMP, commenting that the unit is functioning effectively and generating data. The concept is a systemic disease deconstruction focused on human tissue and paired blood that employs single cell and cell subset approaches rather than whole tissue or blood. This AMP will utilize the most important informative cohorts and compare RA, SLE, and non-inflammatory controls to discover cell subsets and specific pathways in those cells that are shared across disease or distinct. The AMP will include molecular classification of RA synovium and lupus kidney that may stratify patients and identify biomarkers and new targets for drug development.

   Dr. Holers noted that for RA, the phase 1 samples have involved biopsies and arthroplasties, using OA as controls. The biopsies in particular are providing interesting insights into the disease. Dr. James noted that progress has also been made with regard to lupus—the phase 1 recruitment goals have been exceeded, with recruitment of 105 patients who had a kidney biopsy and met inclusion criteria. The patient group includes significant ethnic and racial diversity. She described the various studies being conducted in both the lupus and RA arms of this project and noted that significant time, effort, and energy has been dedicated to harmonizing protocols (tissue disaggregation methods in particular).

   Dr. James presented a list of completed activities associated with phase 1 of the RA/Lupus AMP, many of which related to “pipeline studies.” Highlights include establishing the first synovial biopsy program in the United States, conducting single cell RNA sequencing of tissue biopsies at scale, and conducting autoimmune disease tissue CyTOF analysis. Phase 2 sample collection is underway.

   After Drs. Holers and James reviewed examples of data from phase 1 of the RA/Lupus AMP, they summarized progress to date. The phase 1 data sets were larger than expected and brought with them the opportunity to move beyond feasibility into biological insights (e.g., identification of cell populations in tissue and blood that may not have been previously recognized, identification of aberrant cell subsets and pathways that may be pathologically relevant). Phase 1 data are currently being processed; the first public data release is anticipated for November 2017. The now successful network is primed to move forward with phase 2, containing sufficiently sized samples for extensive discovery/validation studies. She described a number of opportunities for NIAMS extramural scientists, including:

   • Streamlined data capture forms for lupus nephritis and RA
   • REDCap database code to capture SLE and RA information for sites with REDCap access
   • Rich clinical datasets from more than 100 lupus nephritis and 46 RA patients from phase 1 with plans for up to 200 SLE patients and 150 RA patients from phase 2
   • SLE kidney, skin, urine, and blood RNAseq and/or CyTOF from phase 1
   • RA synovial biopsy and blood RNAseq and/or CyTOF from phase 1
   • Serum, plasma, and peripheral blood mononuclear cells, from phase 1 SLE and RA patients, as well as urine/urine cells from SLE patients

   Dr. James closed the presentation by briefly describing RA/Lupus AMP interactions with other major programs, such as PRECISEADS (Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases), the All of Us Research Program, and Environmental Influences on Children Health Outcomes (ECHO).

   Discussion

   Dr. Paller asked if the AMP investigators have been examining disaggregation in skin and trying to correlate it with other organs. Dr. James explained that the skin component of this work is a nested study and not a focus of the AMP pipeline. However, the group doing this work is looking into the behavior of non-lesional skin compared to kidney.

   Dr. Koretzky noted that the AMP is currently in the hypothesis-generating stage, and suggested that the testing of these hypotheses should be conducted by the larger community. Given that this work is very technique-dependent, he asked if the AMP laboratories would be available to the larger community as part of the hypothesis-testing effort. Dr. Holers noted that one of the AMP’s major efforts has been to develop methodologies that are not laboratory specific in an attempt to broaden the ability of other laboratories/groups to use these methodologies. Moving forward, it is hoped that there are opportunities to extend these studies into unique/special populations.

   Mr. Mulvihill noted that AMP’s unique partnership of industry, government, and private non-profit will present significant learning opportunities and serves as a good example of leveraging assets from across these types of partners. Furthermore, the AMP may present an opportunity to learn from attempts to speed up the discovery process in certain disease areas. He expressed enthusiasm that the AMP and other NIAMS initiatives are moving towards more of a learning-centric culture with the sharing of data and ideas. He asked about what the Council can do to help sustain these approaches, particularly those related to accelerating discovery (and, ultimately, improving care). Dr. Serrate-Sztein noted that a significant concern when the RA/Lupus AMP was being developed was the willingness of patients and physicians to participate/donate biospecimens, and this challenge has been overcome. In particular, the culture of conducting RA and lupus research in this country has shifted because of the demonstrated advances in the ability to analyze tissue from patients.

9. NIAMS SUPPLEMENTS TO ADVANCE RESEARCH FROM PROJECTS TO PROGRAMS (STAR) EVALUATION

   Dr. Kathryn Marron, Research Program Analyst in the NIAMS Division of Skin and Rheumatic Diseases, explained that the STAR Program’s objectives are to: (1) facilitate the transition from a single research project to a research program for an early established investigator (i.e., one who has successfully renewed a NIAMS-supported new investigator R01 received no earlier than 2009), (2) explore new opportunities broadly within the scope of a research project, and (3) promote innovation and exploration of high-risk ideas. These non-competing administrative supplements of up to $300,000 in direct costs over 2 years and are not intended to provide additional support to the PIs salary. Applications are submitted in the second or third year of the R01 renewal.

   The application process involves NIAMS notifying eligible applicants, who are asked to submit a 4-page essay and institutional recommendation from the department Chair. Applications are vetted and reviewed by NIAMS staff and the NAMSAC. Applications are reviewed based on the following criteria:

   • The ability of the investigator to develop a research program based on his or her history of innovation and productivity as well as the commitment of the PI to the field of research based on his or her past research activity and their short-and long-term visions
   • Reasonableness of the budget and period of support for the proposed research
   • The significance and potential impact of the STAR supplement to enhance the parent award’s overall impact on the current research project and the field as a whole
   • Potential innovation, risks, and challenges of the proposed activities
   • Importance of the research area
   • Institutional commitment

   
   Dr. Marron then described proposed plans to evaluate the STAR program, noting that in the short term, the focus is on a process review to inform the Institute’s decisions regarding future STAR Funding Opportunity Announcements (FOAs), particularly in terms of identifying areas where the STAR application and review process could be improved. Feedback will be sought from STAR awardees, NIAMS extramural program staff, NIAMS leadership, and NAMSAC members. Examples of issues for which feedback is sought include clarity of the STAR FOA, whether there is enough information available to consider applications received, what information is needed—but not readily available—for monitoring STAR recipient progress, ideas for evaluating the STAR Program, and additional information that could be included in a future potential RFA. To help inform this process, Dr. Marron and colleagues showed the R01 funding history for the nine STAR recipients to date.

   Dr. Thomas Cheever discussed plans for the long-term evaluation of the STAR Program, which will focus on determining whether the Program is meeting the goals described earlier by Dr. Marron. The NIAMS plans to collect objective/quantitative data along with subjective/qualitative data from expert reviewers and compare both types of data with an appropriate control group. He emphasized that the Institute will be taking a holistic view of the Program and not relying on a single indicator to make its decisions. Quantitative data to be considered include additional NIH grants and non-NIH research support, measures of publications and citations, mentoring history, collaborations, and patents. Qualitative data may include assembling a package of information for an expert panel (that may include NIAMS program staff and leadership as well as Council members) to consider. This package would attempt to capture the entire history of a STAR award and may include new investigator type 1 R01s, type 2 R01s, and STAR applications; progress reports; publications; complete NIH application and funding history; and feedback from STAR awardees (e.g., what did the STAR support allow the investigator to do that could not have been done with only their R01 support).

   Dr. Cheever noted that the evaluation is essentially trying to assess whether STAR awardees continue to be outstanding investigators, whether the STAR support helped in that regard, and if so, how.

   Discussion

   Dr. Holers expressed his support for the STAR Program and noted a concern—funding for clinical researchers. He indicated that the STAR Program may not be adequately targeting clinical researchers and suggested that the NIAMS consider how best to support talented clinical investigators. Dr. Katz noted that one of the nine current STAR awardees is a clinical investigator.

   Dr. Khosla agreed that the STAR Program is a worthwhile initiative and asked about the degree of flexibility the NIAMS has to develop a portfolio of options (that could include the STAR Program) to address the issues mandate to enhance support for early stage investigators discussed by Dr. Tabak earlier in the meeting, rather than just meeting a threshold payline. Dr. Katz indicated that the Institute is working to identify all available options for operationally addressing these issues. Dr. Khosla noted that as opposed to supporting investigators who are at risk of transitioning out of the research enterprise, the STAR Program is focused on identifying investigators with great potential and providing them with additional resources—he commented that this is an important way to establish research programs for junior investigators. He proposed that moving forward, the applicants should be made aware that the Institute may be reviewing these supplements from that perspective. He also suggested that the Institute may need to limit the number of STAR supplements through more stringent criteria to accommodate the need to increase support for early stage investigators who are at risk of losing their NIH support.

   In response to Dr. Holer’s comments, Dr. Serrate-Sztein noted that the future success rate of receiving R01s from K23 awardees is much lower than that for K08 awardees, and therefore, the pool of clinical investigator applicants awarded a first R01 is smaller. There is a need to identify approaches for ensuring that there are an appropriate number of clinical researchers who receive STAR supplements.

   Dr. Tapscott asked about whether the STAR Program evaluation effort will be able to determine the degree to which STAR supplements have resulted in distinctly new programs for an investigator compared with simply expanding a current program. Dr. Katz clarified that the STAR supplement carries with it an expectation that the work will be conducted “within scope” while introducing innovation. Dr. Carter added that NIAMS program staff are equipped to review this expectation.

   Dr. Koretzky suggested that the previously proposed STAR Symposium be held to help highlight how the STAR Program helped awardees conduct new, innovative work. This input could help guide the evaluation effort.

   Dr. Lerner asked if the NIAMS was the only NIH IC that has the STAR Program. Dr. Katz indicated that this is the case. It is unclear whether it will expand to other ICs. He also summarized that the feeling of the Council appears to be that the STAR Program should be retained by the NIAMS. Additionally, Dr. Katz reminded Council members that this discussion should not impact any of the discussions that will take place in closed session.

10. INNOVATIVE APPROACHES TO ORTHOPEDIC THERAPIES

    Deferred to the next Council meeting due to time constraints.

11. STAR AWARDS DISCUSSION

    This portion of the meeting occurred during closed session.

12. SPECIAL ACTIONS

    This portion of the meeting occurred during closed session.

13. CONSIDERATION OF APPLICATIONS

    In closed session, the Council reviewed and recommended a total of 844 primary and 289 secondary applications requesting $313,934,963 in total first year costs. For the record, it is noted that secondary applications were also considered en bloc.

14. ADJOURNMENT

    The 92nd National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00 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.