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

Minutes of the 93^rd Meeting
September 6, 2017
8:30 a.m. to 3:00 p.m.

September 6, 2017 Council Webcast

1. CALL TO ORDER

   The 93rd meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on September 6, 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. 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; Treasurer of the Scleroderma Foundation, Tri-State Inc Chapter
   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. Gwendolyn L. Powell Todd, Patient, Health Advocate, and Educator
   Dr. Christy I. Sandborg, Professor of Pediatrics, Stanford University
   Mr. Richard F. Seiden, Foley & Lardner LLP (via teleconference)
   Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center

   Staff and Guests

   The following NIAMS staff and guests attended:

   Staff

   Ms. Gema Souto Adeva Dr. D. Lee Alekel Ms. Pamela Beheler Dr. Amanda Boyce Mr. Gahan Breithaupt Dr. Nakia Brown Ms. April Brundidge Ms. Justine Buschman Dr. Robert Carter Ms. Cindy Caughman Dr. Faye Chen Dr. Thomas Cheever Ms. Jennifer Chi Dr. Ricardo Cibotti Ms. Teresa Do Dr. Jonelle Drugan Ms. Barbara Footer Dr. Nancy Garrick Ms. Aleisha James Ms. Katie Joffee Mr. Andrew Jones Dr. Stephen I. Katz Ms. Shahnaz Khan Mr. Mark Langer Dr. Helen Lin Ms. Anita Linde

   Dr. Yin Liu Dr. Kan Ma Dr. Kathryn Marron Dr. Joan McGowan Ms. Leslie McIntire Ms. Melinda Nelson Dr. Kristy Nicks Dr. Carol Parsons Mr. Rick Phillips Ms. Andree Reuss Dr. Kathy Salaita Dr. Vittorio Sartorelli Dr. Susana Serrate-Sztein Ms. Sheila Simmons Ms. Robyn Strachan Ms. Yen Thach Ms. Jamie Thompson Ms. Susan Toy Dr. Carol Torgan Dr. Bernadette Tyree Dr. Fei Wang Dr. Xibin Wang Dr. Chuck Washabaugh Ms. Esther Weiss Dr. Xincheng Zheng

   Guests

   Dr. Alexey Belkin, Center for Scientific Review, NIH
   Dr. Lauren Brodd, American Association of Immunologists
   Dr. Betty Diamond, Feinstein Institute for Medical Research (via teleconference)
   Dr. Guy Eakin, Arthritis Foundation
   Mr. Daniel Eckstein, NOVA Research Company
   Dr. Matthew Gillman, Environmental Influences on Child Health Outcomes (ECHO) Program Director, NIH
   Ms. Krystal Johnson, Office of Human Resources, NIH
   Dr. Walter Koroshetz, Director, National Institute of Neurological Disorders and Stroke, NIH
   Dr. Rajiv Kumar, Center for Scientific Review, NIH
   Ms. Haley Payne, Health and Medicine Council of Washington
   Ms. Kirstie Saltsman, IQ Solutions

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to approve the minutes of the 92nd NAMSAC meeting, held on June 21, 2017.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:

   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 with two announcements:

   • Drs. Douglas Lowy, Acting Chief of the National Cancer Institute (NCI) and John Schiller of NCI’s Laboratory of Cellular Oncology, have been named as recipients of the Lasker-DeBakey Clinical Medical Research Award for their work on the development of human papillomavirus vaccines.
   • The gene therapy for epidermolysis bullosa, particularly the dystrophic form, has been granted fast-track approval from the U.S. Food and Drug Administration. The therapy involves inserting a missing gene into normal patient cells for autologous transplant. Much of this work is based on the efforts of Stanford University’s Dermatology Department.

   Dr. Katz reminded Council members that the open session of this NAMSAC meeting was being videocast and will be archived on the NIH website. He invited members to encourage their colleagues to view the proceedings of this meeting online at Videocast.

   Drs. Econs, Holers, and Yaszemski were unable to attend this Council meeting; Mr. Seiden participated via teleconference.

   Four-year terms for the following Council members expire this month: Drs. Koretzky, Pavlath, Powell Todd, and Sandborg, and Mr. Silver. Due to uncertainties in appointing new members at this time (and whose terms would begin on October 1, 2017), Dr. Katz has asked these Council members to stay on through a 180-day “Administrative Extension.” All five have agreed to extend their terms through March 2018; Dr. Katz thanked them for their continued contributions.

   Dr. Katz thanked Dr. Bechtold for leading the Council Agenda Working Group, noting that two of this meeting’s agenda items are in direct response to the Working Group’s interest in learning more about how trans-NIH initiatives and activities intersect with the NIAMS portfolio. The first relates to pain—many diseases and conditions that fall under NIAMS mission areas are associated with chronic and debilitating pain. Following Dr. Katz’s Director’s Report, Dr. Walter Koroshetz, National Institute of Neurological Disorders and Stroke (NINDS) Director and Interagency Pain Research Coordinating Committee (IPRCC) Chair described major NIH efforts in this area. The second trans-NIH activity on the meeting’s agenda related to a talk by Dr. Matthew Gillman, Director of the Environmental Influences on Child Health Outcomes (ECHO) program. ECHO has been discussed at previous Council meetings within the context of the Validation of Pediatric Patient Reported Outcomes in Chronic Diseases Consortium (PEPR), which NIAMS oversees on behalf of the NIH.

   In the spirit of highlighting additional ways in which NIAMS programs intersect with other NIH efforts, Dr. Katz’s upcoming September Director’s Letter will focus on some of the trans-NIH and interagency activities in which the NIAMS participates and leads.

   Staff and Organizational Changes

   Dr. Josephine Briggs is retiring as Director of the National Center for Complementary and Integrative Health (NCCIH), formerly known as the National Center for Complementary and Alternative Medicine, or NCCAM, next month to become the Editor-in-Chief of the Journal of the American Society of Nephrology. NCCIH Deputy Director Dr. David Shurtleff will serve as the Center’s Acting Director while the NIH conducts a national search.

   At the NIAMS, Dr. Carl Baker retired at the end of August. Dr. Baker had more than 35 years of federal service and made significant contributions as a leader within the Institute and as Program Director for the Institute’s Keratinocyte Biology and Diseases Program.

   As announced during the January NAMSAC meeting, the NIAMS and NCI have a final agreement in place to transfer the Dermatology Branch from the NCI to the NIAMS Intramural Research Program (IRP). Dr. Katz commented that this move provides a great opportunity for synergy across the scientific programs within the NIAMS, as well as between the Institute’s laboratories and many others across the NIH. Additional information will be presented at the February Council meeting, when Drs. John O’Shea (NIAMS Scientific Director) and Richard Siegel (NIAMS Clinical Director) provide an update on the NIAMS IRP.

   Budget and Congress

   NIH’s Fiscal Year (FY) 2018 begins on October 1, 2017; it is likely that FY 2018 will begin under a Continuing Resolution. Although Congress will clarify the details as part of the legislative process, continuing resolutions typically mean that NIH can continue to operate at, or slightly below, its current budget.

   Since the last NAMSAC meeting, Dr. Katz participated in a series of Congressional courtesy visits organized by the American Academy of Dermatology Association (AADA). AADA President Dr. Henry Lim and Dr. Katz spent a full day on Capitol Hill, meeting with Senator John Kennedy (R-LA), Congresswoman Jaime Herrera Beutler (R-WA), Congresswoman Katherine Clark (D-MA), Congressman Mark Pocan (D-WI), and staff from the offices of Senators Patrick Leahy (D-VT) and Brian Schatz (D-HI). Members and their staff were particularly interested in how NIH-funded research has been translated into therapies that have dramatically improved patient outcomes in the last decade—especially in diseases such as metastatic melanoma, rheumatoid arthritis (RA), and psoriasis. Dr. Katz noted that NIAMS’ work provides the foundation for many of these advances.

   Highlights of Selected Recent Scientific Advances

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

   • Work by Dr. Richard Gallo’s group at the University of California-San Diego suggests that human skin hosts specific bacterial strains that protect against colonization by harmful Staphylococcus aureus by producing previously unknown antimicrobial peptides. The investigators incorporated these peptide-producing bacteria into a skin cream; five people with atopic dermatitis were treated with the cream on one of their arms while an unmodified skin cream was applied as a control on their other arm. The results were promising—a single application of the cream with the helpful bacteria decreased the amount of S. aureus on the skin. This suggests that a healthy microbiome provides a first line of defense against disease-causing bacteria. As such, the healthy skin microbiome has potential as a bacteriotherapy against atopic dermatitis (Sci Transl Med. 2017 Feb 22;9(378). pii: eaah4680. doi: 10.1126/scitranslmed.aah4680. PMID: 28228596).
   • Dr. Heidi Kong in the NIAMS IRP is leading work to provide additional evidence about the role of S. aureus in atopic dermatitis. When her team analyzed skin samples from pediatric patients and healthy controls to better understand the relationship between Staphylococcus colonization and this common skin condition, they found that bacterial diversity decreased during disease flares, with Staphylococcal species becoming more of a dominant presence. Staphylococcus epidermidis was the most abundant species in patients who had less severe disease, while S. aureus levels were greater in patients with more severe reactions (Sci Transl Med. 2017 Jul 5;9(397). pii: eaal4651. doi: 10.1126/scitranslmed.aal4651. PMID: 28679656).
   • Drs. Sun Jung Kim and Betty Diamond at the Feinstein Institute for Medical Research have discovered how a protein called Blimp-1 causes the immune system to mistakenly attack a body’s own tissues. Mouse studies revealed that female—but not male—mice with impaired Blimp-1 production contain a high level of the enzyme cathepsin S, which cleaves proteins into fragments that trigger an immune response. Like other animal models displaying high cathepsin S levels, these mice also exhibited signs of lupus. Moreover, inhibition of the enzyme eliminated the animals’ lupus-like characteristics and changed their immune system to more closely resemble that of normal animals (Nat Immunol. 2017 Jul 10. doi: 10.1038/ni.3793. [Epub ahead of print] PMID: 28692065).
   • Dr. Vasileios Kyttaris at Harvard is the first to demonstrate that IL-23 and its receptor are upregulated in systemic lupus erythematosus (SLE). Since discovery of the IL-23/Th17 immune pathway over a decade ago, scientists have been attempting to bring strategies that target components of this pathway to the clinic. Encouraging results have already been found for Crohn’s disease, RA, psoriatic arthritis (PsA), and ankylosing spondylitis. The finding that IL-23 accounts for the key aspects of lupus in people and mice—including the expansion of double-negative T cells, decreased IL-2, and increased IL-17 production—suggests that IL-23 blockage may also have therapeutic value in SLE patients (J Immunol. 2017 Aug 1;199(3):903-910. doi: 10.4049/jimmunol.1700418. Epub 2017 Jun 23. PMID: 28646040).
   • The recommendation for all asymptomatic HIV-infected individuals to begin antiretroviral treatment at the time of diagnosis instead of waiting for their disease to progress before getting treatment is based on a major international clinical trial, the Strategic Timing of AntiRetroviral Treatment (START) study, a major international clinical trial funded by the National Institute of Allergy and Infectious Diseases along with the NIAMS, other NIH Institutes, and international funding agencies. A sub-study of approximately 400 START participants showed that those who began antiretroviral treatment upon receiving their HIV diagnosis lost bone in the spine and hip more quickly than those who waited to begin antiretroviral treatment until after their immune system deteriorated. The decline was the greatest in the first year after people began antiretroviral treatment. Assuming the decreased bone mineral density in this population is associated with increased fragility, the need for strategies to preserve the bones of people infected with HIV is expected to gain attention as more people live longer due to the benefits of early antiretroviral treatment (J Bone Miner Res. 2017 Jun 26. doi: 10.1002/jbmr.3183. [Epub ahead of print] PMID: 28650589).
   • An estimated 1% of the entire U.S. population takes glucocorticosteroids as chronic therapy for a range of conditions. Although these drugs are beneficial for people who need them, long-term use leads to many side-effects. A research team led by Dr. Elizabeth McNally at Northwestern University in collaboration with the University of Florida Wellstone Muscular Dystrophy Center looked at the mechanisms by which glucocorticoids preserve muscle function in boys who have Duchenne muscular dystrophy. Their findings that weekly dosing upregulates two genes involved in muscle cell membrane repair—while daily dosing activates cell pathways that cause muscle to shrink and weaken—explain the seemingly contradictory results of other studies into the drugs’ effects (J Clin Invest. 2017 Jun 1;127(6):2418-2432. doi: 10.1172/JCI91445. Epub 2017 May 8. PMID: 28481224).
   • Most anterior cruciate ligament (ACL) tears require surgery—the NIAMS-funded Multicenter Orthopaedics Outcome Network (MOON) longitudinal cohort led by Dr. Kurt Spindler at the Cleveland Clinic is providing insights into the short- and long-term outcomes of the various reconstructive procedures that surgeons use. A recent paper by NIAMS K23 awardee Dr. Morgan Jones and Dr. Spindler describes baseline factors—independent of surgical approach—that strongly predict the development of symptomatic and radiographic osteoarthritis after reconstruction. In addition to linking articular cartilage damage and lateral meniscal tears to the development of post-traumatic osteoarthritis, the paper is particularly noteworthy when placed in the context of a 2016 publication by MOON investigators. That 2016 paper showed that patients who underwent a progressive strengthening and neuromuscular training regimen before surgery were more likely to be physically active than comparable patients who did not receive the preoperative training (J Orthop Res. 2017 Jul;35(7):1366-1374. doi: 10.1002/jor.23557. Epub 2017 Apr 28. Review. PMID: 28383764).

   NIH and NIAMS Activities

   Clinical trials such as the MOON study noted above have great potential to improve the quality of medical care that patients receive. On several occasions, the NAMSAC has discussed NIAMS efforts to strengthen the Institute’s clinical trials portfolio. Similar to the policies that NIAMS implemented several years ago, the NIH is making adjustments that are intended to improve its ability to: (1) identify proposed clinical trials, (2) ensure that key pieces of trial-specific information are submitted with each application, and (3) uniformly apply trial-specific review criteria. In 2014, the NIH announced its expanded definition of a clinical trial: “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

   This change prompted a discussion about the importance of what is sometimes referred to as “hybrid” R01 and R21 grants—these awards predominantly support basic or translational research, but contain a clinical aim that has a mechanistic, rather than clinical, outcome. At that time, Council members noted that investigators lacked a way to submit these applications and have them reviewed by an appropriate panel because the studies were now defined as clinical trials, and because the NIAMS required all clinical trial applications to come in through targeted funding opportunity announcements (FOAs) and be reviewed by a NIAMS standing study section (the AMSC)—which is rich in clinical trial expertise but was never intended to review basic and preclinical proposals. In response to Council’s input, the Institute decided that it would accept these types of applications under the NIH parent R01 and R21 announcements and that they would be reviewed through the Center for Scientific Review (CSR).

   As of January 25, 2018, the NIH will no longer accept clinical trial applications through parent FOAs or through other FOAs that are not specifically designed to accept clinical trials. The NIAMS has been doing this for most types of clinical trials through its AMSC study section for several years now, and the Institute will continue this practice. The NIAMS is exploring various options with other NIH Institutes and Centers (ICs) regarding applications focused on mechanistic questions that include a clinical study as a way to address the issue. Dr. Katz assured Council members that the NIAMS is committed to ensuring that all applications are submitted under the correct FOA and reviewed by the most appropriate panel of reviewers.

   Dr. Katz described another NIH policy change, one that affects clinical trial applications submitted for due dates on or after January 25, 2018, and one that supersedes a similar policy change that he mentioned during the June NAMSAC meeting. After January 25, 2018, appendix materials will be restricted to: blank data collection, survey, and questionnaire forms; simple lists of interview questions; blank informed consent/assent forms; and other items only if the FOA specifically permits them. The optional protocol submission is being removed from the Appendix Policy, as all applications will need to describe key elements from the protocol as part of the Public Health Service (PHS) Human Subjects and Clinical Trials Information Form. Failure to adapt to the last policy change regarding appendix materials led CSR to return 10 NIAMS clinical trial applications to investigators before review.

   Considerable progress is being made on the Pathways to Prevention Workshop on the Appropriate Use of Drugs for Osteoporosis Fracture Prevention that the NIAMS, National Institute on Aging, and the NIH Office of Disease Prevention are leading on behalf of many NIH ICs. The goal of these workshops is to provide an unbiased, evidence-based assessment of the state of the science and the research that is needed to move the field forward. Dr. Katz thanked Dr. Khosla as well as Dr. Joan McGowan (Director of the NIAMS Division of Musculoskeletal Diseases), Dr. Faye Chen (Program Director within the Division of Musculoskeletal Diseases), and other members of the Division of Musculoskeletal Diseases for their guidance and leadership with this effort.

   On an annual basis, the NIAMS brings together groups of investigators for roundtable discussions. Although these meetings are small, the Institute encourages participants to involve their colleagues by gathering input on key questions that serve as the basis for subsequent discussion. Later in this Council meeting, NAMSAC members were briefed on two of these roundtable discussions: Gaps and Emerging Opportunities in Psoriatic Arthritis, and Innovative Treatments for Enthesis Repair. Later in this meeting, the Council discussed initiatives that the Institute is considering for FY 2019 to promote research in arthritis and musculoskeletal and skin diseases. Dr. Katz asked Council members to keep in mind that the vast majority of the NIAMS budget supports investigator-initiated research projects. He thanked Ms. Justine Buschman of the NIAMS Division of Skin and Rheumatic Diseases for coordinating the operational aspects of the Institute’s initiative development process.

   Along with support of high-quality investigator-initiated research projects, activities to help investigators establish independent, sustainable research careers are among NIAMS’ highest priorities. Later in this Council meeting, Dr. Katz provided an update on where the NIAMS stands with regard to NIH’s Next Generation Researchers Initiative (NGRI). This new policy will require some changes to the way the Institute reports on the grants it funds—for example, the number of applications it receives and funds relative to its paylines for new and established investigators. Dr. Katz presented this data for FY 2016 and noted that the Institute will likely break out this information to specifically reflect early-stage investigators rather than the broader category of new investigators that it has been reporting on for the past 7 years.

   The NGRI also has implications for the NIAMS Supplements to Advance Research from Projects to Programs (STAR) initiative. The Institute has been making an average of four of these awards per year since it began in 2015. As a follow-up to the June NAMSAC discussion on this topic, the NIAMS has modeled possible changes it could make to the STAR eligibility criteria and has reached out to some Council members regarding possible changes. A more detailed update on the Institute’s plans for STAR was presented later in this Council meeting.

   On October 17, 2017, the NIAMS will host its 6th Outreach and Education Day for members of the NIAMS Coalition, an independent consortium of national professional and voluntary organizations that are committed to raising awareness about NIAMS-funded research. Dr. Katz thanked NIAMS Coalition Co-Chairs Mr. Robert Riggs (CEO of the Scleroderma Foundation), and Ms. Stephanie Hazlett (of the American Academy of Orthopaedic Surgeons), who are working with the NIAMS Office of Science Policy, Planning and Communications to plan the meeting’s agenda.

   Discussion

   Dr. Katz began the discussion session by addressing a number of questions posed by Dr. Khosla regarding the review of applications proposing various types of clinical trials (Dr. Khosla submitted these questions in advance of this Council meeting). For example, Dr. Khosla asked about applicants proposing true therapeutic clinical trials and whether these applications would come through a NIAMS-specific clinical trial FOA. Dr. Katz indicated that this is the case, and added that it would be reviewed in-house by the AMSC. However, a mechanistic study (with or without additional aims that are more basic involving mouse or in vitro studies) would not go through the same NIAMS-specific clinical trials FOA. Applicants proposing mechanistic studies will be required to submit the same information that is required for all clinical trials, such as the PHS Human Subjects and Clinical Trials Information Form and details about study timeline and milestones. Once the new parent FOA is released, NIAMS investigators will continue to be able to submit mechanistic clinical study applications for review by the CSR, while trials with clinical outcomes will continue to be submitted to the NIAMS clinical trial FOA. Because the new parent R01 FOA for mechanistic clinical studies is still being developed, Dr. Katz was unable to provide definitive answers to some of Dr. Khosla’s other questions related to pre-approval, planning grants, and application cycles.

   NIAMS Deputy Director Dr. Robert Carter added that the definition of “mechanistic studies” developed by the NIAMS is the definition being adopted across the NIH. Some NIH ICs will sign on to an NIH-wide parent study that allows mechanistic work (regular R01s); however, a separate group of ICs has a separate FOA for mechanistic studies only.

   Dr. Koretzky commented that with regard to the next generation of scientists—particularly physician—scientists—there are a number of new initiatives emerging to support individuals during residency who want to then devote themselves to scientific careers. He asked about any plans the NIAMS has in this area, both within its own portfolio and in terms of collaborating with other ICs. Dr. Katz voiced support for these types of initiatives. He explained that the Institute has career development awards for individuals in this situation (e.g., K awards), and that some of the professional and voluntary organizations have provided funding for those during a residency to participate in a formal training program.

5. NIH EFFORTS IN PAIN RESEARCH

   Dr. Koroshetz described the NIH Pain Consortium and its leadership, noting the large number of NIH ICs (including the NIAMS) who are members. The Consortium’s mission is to enhance pain research and promote collaboration among researchers across the NIH ICs that have programs and activities addressing pain. The NIH funds pain research at an estimated $425 million per year—the NIAMS contributes roughly 10% of this funding; only the NINDS (13%) and National Institute on Drug Abuse (11%) contribute more to NIH’s pain research portfolio.

   The NIH Pain Consortium issues RFAs and Program Announcements for research in certain areas. Dr. Koroshetz briefly described two of these funding opportunities:

   • Research on Chronic Overlapping Pain Conditions. The goal of this funding opportunity is to encourage epidemiological, clinical, and translational research to understand the natural history, prevalence, biological mechanisms, psychological variables, and clinical risk factors for the presence of multiple chronic pain conditions in people with pain.
   • Mechanisms, Models, Measurement, and Management in Pain Research. This opportunity is intended to inform the community of the pain research interests of the ICs at the NIH and to foster mission-relevant basic, clinical, and translational studies on pain.

   The Pain Consortium has awarded contracts to 11 NIH-funded Centers of Excellence in Pain Education, with the intent of creating, developing, evaluating, and distributing pain management curriculum resources (case-based studies and scenarios) for medical, nursing, dental, and pharmacy schools to enhance and improve how health care professionals are taught about pain and treatment of pain. The first set of cases is live, with more to follow soon. It is hoped to merge this set of cases with others from government and professional organizations in a central, accessible portal. The developed tools must be implemented at the award site and are or will be made publicly available (additional information can be found here). Dr. Koroshetz presented a short video highlighting the work of these Centers.

   The IPRCC is a Federal Advisory Committee charged with enhancing pain research efforts and promoting collaboration across the government, with the ultimate goals of advancing fundamental understanding of pain and improving pain-related treatment strategies. The IPRCC developed the National Pain Strategy (NPS) in response to recommendations from the Institute of Medicine in its report, “Relieving Pain in America.” The NPS was approved and released in 2016 and represents the government’s first broad-ranging effort to improve how pain is perceived, assessed, and treated. In support of the NPS, the IPRCC funded the validation of a set of questions for the National Health Interview Survey and found that:

   • 25.5 million U.S. adults have pain every day.
   • 23.4 million report a lot of pain.
   • 10.5 million adults report a lot of pain every day.
   • 8 million have pain that interferes with lifestyle.
   • Adults in severe groups have increased anxiety, depression, fatigue and cognitive impairment.
   • Adults in severe pain groups have worse health status, use more health care, and suffer from more disability than those with less severe pain.

   These findings suggest that pain should not be thought of as an isolated condition; rather, it is interwoven into the other medical problems people have. The NIH is also funding a project to examine how insurance companies address different models of pain care. Transdisciplinary pain management programs that focus less on opioids are generally not covered.

   While the NPS focuses primarily on the management of pain, the Federal Pain Research Strategy was developed with a focus on developing high-priority pain-related research by identifying critical gaps in basic and clinical research on the symptoms and causes of pain. This effort to develop a long-term research agenda is coordinated by the IPRCC and the NIH and will complete the core pain research recommendations put forth by the IOM. The Strategy is guiding the development of a coordinated roadmap for improving U.S. pain care in the prevention of acute and chronic pain, acute pain and pain management, the transition from acute to chronic pain, chronic pain and chronic pain management, and disparities. Research priorities associated with the NPS include (additional information is available on the IPRCC’s website):

   • Develop treatments for opioid use disorder and overdose prevention
   • Accelerate the development of effective and non-addictive treatments for pain
   • Understand the neurobiology of pain to facilitate the development of mechanistically based treatments

   The NIH Common Fund supports an initiative called the Health Care Systems Research Collaboratory; as part of this effort, pragmatic clinical trials for pain are being carried out in collaboration with large health care systems. The NIAMS administers one such study, “A Pragmatic Trial of Lumbar Image Reporting with Epidemiology (LIRE)” (additional information on this study is available here). Dr. Koroshetz also described recent pain-related science advances, including a NIAMS-funded study on the chemogenetic inhibition of pain neurons in a mouse model of osteoarthritis.

   Despite a recent decrease in opioid prescriptions in the United States, overdose deaths are increasing and are at a crisis level. To help address this crisis at the NIH level, Dr. Collins convened a series of meetings with industry representatives to establish a public-private partnership whereby NIH and industry funding, resources, and knowledge can be dedicated to addressing this problem. These meetings were held in June-July 2017 and focused on: (1) the development of treatments for opioid use disorders, overdose prevention, and reversal; (2) the development of safe, effective, non-addictive pain treatments; and (3) understanding the neurobiological mechanisms of pain. Dr. Koroshetz described the priorities that were identified during these meetings and highlighted the following next steps. Next steps in terms of the development of medications for opioid use disorders (OUD) and overdose prevention reversal include:

   • Convene workgroups to explore collaborative efforts to: (1) optimize formulations of existing medications for OUD and opioid overdose; (2) develop device-based approaches to treat OUD and prevent and treat overdose; (3) develop a clinical network of healthcare providers to accelerate research.
   • Engage the Centers for Medicare and Medicaid Services to improve reimbursement for medications and mobile health technologies.
   • Develop and validate quality of care metrics for treatment programs.
   • Explore opportunities to expedite NIH review and funding of quality grant proposals.

   Next steps related to pain research and analgesic development focus on building partnerships to accelerate the development of novel, safe pain therapies through:

   • Advancing pain therapeutics in the current pipeline.
   • Developing objective measures for pain and treatment response.
   • Building research infrastructure to bring new therapies to patients.

   Discussion

   Dr. Koretzky asked if pain issues are being incorporated into NIH’s All of Us Research Program. Dr. Koroshetz indicated that there are plans to incorporate a pain module that is based on validated questions.

   Dr. James noted that the Centers for Disease Control and Prevention (CDC) and other public health organizations/agencies are also working to address the opioid epidemic and asked about how NIH’s activities align with the work being conducted by these other groups. Dr. Koroshetz noted that a number of these groups were represented at the meetings convened by Dr. Collins and that there is an interagency task force being developed so that these groups can coordinate efforts.

   Ms. Castro-Lewis asked about the focus on disparities that is part of the NPS. Dr. Koroshetz explained that there is some evidence that different racial and ethnic groups respond differently to different pain stimuli and have higher or lower chances of developing chronic pain. There is also a treatment issue, in terms of how different racial/ethnic groups are being treated for pain. For example, African Americans are the group that is treated least with opioids.

   Dr. Lerner asked about whether other countries are experiencing a similar problem to opioid epidemic that is occurring in the United States. Dr. Koroshetz commented that it seems to be more of an American problem at this time. However, he has spoken with colleagues in Canada who are seeing similar problems. In Europe, it appears to be less of an emergent problem. Dr. Lerner suggested that prevention efforts might be more effective than work related to finding cures for opioid addiction. Dr. Koroshetz noted that different approaches are needed for acute pain versus chronic pain and agreed that prevention is a critical focus. He added that there are roughly 2 million Americans addicted to opioids and 100 opioid-related deaths per day.

   Dr. James suggested that finding ways to prevent chronic arthritis, particularly because of the aging population, may be an effective approach to addressing part of the opioid addiction problem facing this country. Dr. Katz closed the discussion session by noting that Dr. Koroshetz may be asked to return to a future Council meeting to provide additional updates in this area.

6. ECHO: ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES

   Dr. Gillman opened his presentation by thanking NIAMS staff—Drs. Susana Serrate-Sztein (Director of the Division of Skin and Rheumatic Diseases) and James Witter (Program Director of the Rheumatic Diseases Clinical Program) in particular—for their support throughout the development and implementation of the ECHO program. ECHO’s mission is to enhance the health of children for generations to come and its overall scientific goal is to answer crucial questions about the effects of a broad range of early environmental exposures on child health and development. One of the core values underlying ECHO’s work is that “a good start to life can last a lifetime.” To ensure this good start, there is a need to understand the potential risks and resiliencies and when and to whom they apply.

   The broad range of early environmental exposures being studied by ECHO include factors that span from society to biology (e.g., physical and chemical, societal, medical, psychosocial, behavioral, biological). ECHO defines its exposure period of interest from conception to 5 years of age. In terms of health outcomes, the program focuses on high-impact conditions throughout childhood and adolescence, centered on five conditions: (1) pre-, peri-, and postnatal outcomes; (2) upper and lower airway; (3) obesity and its metabolic consequences; (4) neurodevelopment; and (5) positive child health.

   ECHO is a nationwide and NIH-wide program, with 62 awards made to 110 principal investigators (PIs) and almost 1,300 key personnel in 44 states. Almost 20 NIH ICs helped develop the program. After describing ECHO’s organizational structure, Dr. Gillman explained that ECHO intends to meet scientific needs and inform programs, practice, and policies through addressing solution-oriented questions, observational studies, and clinical trials. One ECHO component, the Institutional Development Award (IDeA) States Pediatric Clinical Trials Network, provides access to state-of-the-art clinical trials for medically underserved and rural populations. At 17 clinical sites, the Network is building the national pediatric research capacity to conduct clinical trials. Additionally, 35 ECHO cohort awards have been made to 74 PIs covering 84 cohorts. These awardees are working towards the creation of the ECHO-wide Cohort, which will result in a single data platform to conduct etiologic and prediction research. The ECHO-wide Cohort aims to enroll more than 50,000 children by 2022 and will eventually serve as a national research resource. Dr. Gillman described the ECHO-wide Cohort data collection protocol, noting that the NIH has released an RFI with comments due by September 13, 2017.

   ECHO’s Person-Reported Outcomes (PRO) Core will: (1) maintain/provide parent and child assessments, (2) assist ECHO cohorts to include appropriate PROs and other observational measures, (3) develop and validate new measures, (4) modify existing measures as needed, and (5) advise on data analyses that include PRO tools. The PRO Core has been extremely successful in allowing for the development of a rubric for parent and child measures that are self or proxy reported.

   Dr. Gillman presented a schematic illustrating the ECHO model of positive health, explaining that health is the result of continuous and transactional person-environment interactions over the life course. He described ECHO’s positive health measurement strategies, noting that a pilot is underway to test ECHO’s Positive Health Instrument in five ECHO cohort awardees (global health, sleep disturbance, life satisfaction, meaning and purpose, and stress). Questions being pursued as part of this effort include:
   • How does positive health develop during childhood?
   • Are there sensitive periods when effects of specific exposures or biopsychosocial transitions on positive health are stronger?
   • How do children’s interactions with their social environments influence positive health?
   • Are there differences in exposure effects and/or positive health outcomes by sociodemographic subgroups?

   ECHO is focused on fostering a culture of collaboration, which involves engagement and trust building. As much as possible, ECHO is trying to allow investigators to drive the science. ECHO is taking a team science approach—Dr. Gillman explained that with the right people and tools, and a transdisciplinary approach, team science produces insights that result in the “whole being more than the sum of its parts.”

   Dr. Katz invited former Council member Dr. Betty Diamond to share her perspective. Dr. Diamond, who leads the Center for Autoimmune, Musculoskeletal, and Hematopoietic Diseases at the Feinstein Institute for Medical Research, has an ECHO grant to look at the relationship between maternal autoimmunity and the development of autism spectrum disorders. She described how her group’s research led to engaging with ECHO on the development of a project to determine whether brain reactive antibodies, evidence of autoreactivity, or increased maternal inflammation was associated with particular neurodevelopmental outcomes. To date, they have recruited a diverse population of approximately 300 mothers, about 10% of whom have an autoimmune disease (they are actively trying to increase enrollment of mothers with autoimmune disease). The team has shown that they can detect brain reactive antibodies in cord blood, and this correlates with what is present in maternal serum. This work has led to collaborations with a number of other research teams to look at brain reactive antibodies and inflammatory cytokines in cord blood, neurodevelopmental outcomes, and toxin exposure. With large enough cohorts, it is hoped that each of these variables can be examined both independently as well as synergistically.

   Discussion

   Dr. Powell Todd asked about the anticipated diversity within the ECHO-wide Cohort and whether ECHO will be studying differences in underserved populations. Dr. Gillman explained that ECHO will be examining issues related to diversity and underserved populations. It is likely that the ECHO-wide Cohort will include an overrepresentation of non-Caucasian enrollees—for example, it is estimated that the Cohort will include 17% African Americans, 26% Hispanics, and 3% Native Americans.

   Dr. James asked about how ECHO efforts might align with environmental monitoring work (e.g., personal monitors, geographic monitors, collecting environmental specimens). Dr. Gillman noted that ECHO has significant expertise in this space, particularly with regard to air pollution and the work being done by ECHO’s Geospatial Working Group. Most of this work relates to modeling outdoor air pollution from central site monitors, individual monitors, and satellite monitors.

   In response to a question about ECHO activities being incorporated into All of Us efforts, Dr. Gillman explained that ECHO and All of Us leadership groups have been engaged in ongoing discussions. All of Us recently established a Child Health Working Group; ECHO is represented in this group’s membership.

   Dr. Sandborg commended the NIH for developing and implementing the ECHO program and noted that the evidence of early prenatal, perinatal, and early childhood exposures on determinants of disease is significant. She asked about whether the ECHO-wide Cohort will be large enough to study the psychosocial determinants of changing one’s epigenome and whether the program will be able to dissect the effects of psychosocial deprivation from an urban environment with pollution. Dr. Gillman explained that ECHO is focusing on high-burden, common disorders. The development of health conditions from the prenatal period through childhood is a complex interaction of actions, actors, and the rules that govern the responses between them. The sciences of epidemiology and systems science are beginning to converge to the point where researchers are going to be able to unravel this complexity and identify leverage points, which will be especially critical in terms of translating into interventions. ECHO can introduce methodologic interventions, looking at multi-level longitudinal data in a way that makes sense and points to these leverage points. Dr. Diamond added that ECHO not only will be answering significant research questions, but will also generate many hypotheses for future work.

7. OVERVIEW OF NIAMS ROUNDTABLE DISCUSSION: PSORIATIC ARTHRITIS

   Dr. Ricardo Cibotti, Program Director of the Immunobiology and Immune Diseases of Skin Program, explained that to advance basic, translational and clinical psoriatic arthritis (PsA) research, the NIAMS held a roundtable in February 2017 on research gaps and emerging opportunities. The 6-hour meeting brought together representatives from academic institutions and funding agencies to exchange information, ideas, and perspectives about the current status of PsA. There was a particular focus on promoting collaborations between rheumatologists and dermatologists, as well as on how best to engage patients in research. A summary of the meeting is available on the NIAMS web site (Council members received a copy in their meeting binders).

   Dr. Cibotti reviewed the roundtable’s key discussion topics:

   Pathogenesis

   • Epigenetics of PsA/the role of genetic variants in non-coding regions
   • The microbiome in PsA
   • Similarities and differences between PsA and related conditions (e.g., psoriasis, RA)/learning from disease-specific and shared pathways

   Translational/Therapeutic Research

   • Gene editing technologies to generate new animal models
   • Cutting edge approaches (e.g., single cell RNA-seq) to investigate disease pathways in human tissue
   • PsA as a model for understanding preclinical autoimmunity

   Clinical Research, Outcomes and Trials

   • Big data approaches to investigate risk factors and disease pathways
   • Soluble and radiographic biomarkers of early disease, disease progression, and/or response to therapy
   • Cardiovascular/metabolic/adipose tissue abnormalities in PsA
   • Incorporating patient preferences into clinical research (e.g., innovative clinical trial designs to avoid “washout” periods)

   Partnerships to Enhance Psoriatic Arthritis and Psoriasis Research

   • Use of social media to engage patients
   • Mentoring and resources for early-stage investigators
   • Team science as an opportunity to engage new investigators and scientists from other fields in PsA research
   • Fostering interactions and collaborations with other medical specialties and research fields relevant to PsA

   Mr. Seiden provided his perspective as a lay representative at the meeting. Biologic drugs, particularly TNF inhibitors, have been quite successful in mitigating the symptoms of psoriatic disease, including partial or full remission in some patients. Mr. Seiden indicated that he was impressed with the high level of cooperation and coordination between researchers at different academic institutions and the NIAMS, and was excited to learn about the extent of shared knowledge regarding the research on psoriatic disease. Mr. Seiden added the following points to Dr. Cibotti’s summary:

   • There is a need to identify the genetic triggers, then the mechanisms, and then the means to interfere with the signaling and reception of triggers to control the disease.
   • Funding should be expanded to allow for genetic studies in children. There is also a need for longitudinal cohorts starting in childhood for people with psoriasis who then go on to become so-called “converters” or “non-converters” to PsA.
   • Research on the gut microbiome should be encouraged, particularly in light of recent discoveries.
   • There was an emphasis on the importance of identifying PsA at an early stage and intervening with appropriate treatment. The research community should be encouraged to understand this timing issue in a deeper way (i.e., what are the critical times for diagnosis, what are the reasons for progression, and what interventions are most sensitive?).
   • Only a few mouse models of PsA have been created. This is disappointing from the patient’s perspective, but there is an opportunity for work in this area. Research using patient samples represents an important opportunity for advancing translational research.
   • The Accelerating Medicines Partnership (AMP) could serve as a model for PsA research.
   • Better training of dermatologists is needed to help them identify the early signs of arthritis in their psoriasis patients.
   • A better understanding of which joints may be impacted by PsA is needed.
   • With regard to engaging patients in clinical research, several researchers pointed to the Psoriasis Foundation’s Citizen Scientist Program, an online psoriatic research network that allows participants to take surveys and use data to generate hypotheses.
   • It would be beneficial to have clinical facilities at which combinations of rheumatologists and dermatologists could assess and treat psoriasis and PsA patients—these cross-disciplinary teams are critical in research and clinical settings.

   Discussion

   Dr. Cibotti noted that the National Psoriasis Foundation has transitioned its focus and made PsA a high-priority topic. Dr. Paller applauded the attention paid to children during the roundtable, noting that this population has traditionally been understudied in terms of PsA. She added that simply educating dermatologists about how to examine joints is also a need. In the United States, roughly 10% of children with psoriasis report moderate to severe joint pain while in Europe, that percentage ranges from 1-4%. The reason(s) for this discrepancy is unclear.

   Dr. Cibotti commented that at present, there are very few clinics that integrate dermatology and rheumatology—as noted by Mr. Seiden, this integration should be encouraged.

8. CONCEPT CLEARANCE FOR FY2019 SCIENTIFIC INITIATIVES

   Dr. Serrate-Sztein explained that each year, the NIAMS undergoes a process to identify and develop a series of initiatives for consideration. In general, these concepts come from the community (e.g., investigators, progress reports from funded projects, scientific meetings, roundtable discussions, professional and patient advocacy organizations, etc.). The concepts for FY2019 consideration were presented (additional details on these concepts were provided in Council members’ meeting binders) and include:

   • Translational Research in Hidradenitis Suppurativa
   • New Insights into the Role of Adipose Tissue in Arthritis, Musculoskeletal, and Skin Diseases
   • Optimizing Clinical Use of Biologics in Orthopaedics
   • Skin Biology and Diseases Resource-based Centers
   • Musculoskeletal Diseases Resource-based Centers
   • Core Centers for Clinical Research (CCCR)
   • Mechanistic Ancillary Studies to Ongoing Clinical Projects
   • Research Innovation for Scientific Knowledge (RISK)
   • Supplements to Advance Research from Projects to Programs (STAR)
   • Clinical Observational Studies (COS) in Musculoskeletal, Rheumatic, and Skin Diseases
   • Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases Re-issue

   Discussion

   Dr. Koretzky asked about the RISK initiative; Dr. Katz indicated that the first round of RISK has finished and decisions have been made. The review for the second round will be held in October; after that point, there can be discussions about these decisions and what the Institute may change, possibly at the February Council meeting. Dr. Katz commented that the Institute is working with relevant professional organizations to disseminate information about the RISK initiative. Dr. Koretzky commented that partnering with these professional organizations could lead to additional funding as well as a higher level of engagement in terms of promoting the initiative.

9. ENTHESIS ROUNDTABLE

   Dr. Chuck Washabaugh, Program Director of the Orthopaedic Research Program, briefed Council members on the results of the Enthesis Roundtable discussions. The goals of this meeting, which included 13 extramural researchers, were to explore innovative strategies focusing on the repair of the bone-tendon enthesis and to identify unmet needs at the basic, translational, and clinical research levels. He reminded the group that the enthesis is a transitional tissue that exists between uninjured tendon and bone. It is not recreated during healing, so surgical reattachment of these two dissimilar biologic materials often fails (e.g., recurrent tears after rotator cuff repair range from 20% to 94%, depending on the patient population).

   Three overarching questions guided the roundtable’s discussions: (1) How are failures and limitations of the current treatment approaches to tendon injuries pointing to gaps in our understanding of the mechanism of action? (2) What are the most promising research areas for enthesis repair, what are the most immediate clinical needs, and how can the gaps be addressed? (3) What needs to happen to enable robust translational and clinical studies of these potential treatments/therapies? Key discussion topics were focused in the areas of basic science gaps, animal models for studying mechanisms and treatments, and clinical needs (with a focus on rotator cuff disease):

   Basic Science Gaps

   • Local and systemic cells involved in development, disease, repair, and regeneration of the enthesis.
   • Phenotype of enthesis cells, promotion of phenotype by local factors, and phenotypic alterations in context of pathology.
   • The role of inflammation in wound healing and strategies to modulate inflammation to promote healing over degeneration.
   • Signaling between muscle and tendon and the influence of muscle pathology on healing.
   • Signaling between bone and tendon and the influence of bone loss on healing.
   • Global tools (-omics) for local analysis are needed.
   • Zebrafish can be used as a model for studying tendon and enthesis development

   Animal Models for Studying Mechanisms and Treatments

   • Enthesis development and repair
     • Relevance of mouse models of tendon/enthesis development and growth to enthesis repair in adults
   • Overuse injuries
     • Mice, rats, and horses (a naturally occurring large animal model)
   • Rotator cuff disease
     • Mice and rats
     • Sheep and dogs
     • Lack similarity to human anatomy, pathogenesis, biomechanical loading, and re-tear rates
   • Safety and proof-of-concept studies
     • Mouse and rat models for cell, biologic, and scaffold therapies
     • Rabbit as a bridge between small (rodent) and large (sheep, dog) models
     • Standardized animal models (intra vs. extra articular)
     • Standardized outcome measures

   Clinical Needs (Rotator Cuff Disease)

   • Knowledge
     • Etiologies and pathologies
     • Role of genetics in healing
     • Sources of shoulder pain
   • Biochemical or imaging markers
     • Improve diagnosis and staging (tear size, tear location, tissue quality)
     • Predict and measure healing
   • Clinical care
     • Rehabilitation program
     • Large cohort studies
     • Existing resources (e.g., DOD serobank, VA Million Veteran Project, 3D human tissue models)
     • Functional shoulder test (e.g., PROMIS)?
   • Consensus—the group agreed on the following needs:
     • Imaging modality outcomes
     • Strength and range of motion outcomes
     • Measurement approaches (including rater variability and validation)

   Discussion

   Dr. Alison Cernich, who leads the National Center for Rehabilitation Research, was a key member of the roundtable. Along with Dr. Washabaugh, Dr. Cernich Co-Chairs the Trans-NIH Medical Rehabilitation Coordinating Committee. This group has been effectively increasing interest in rehabilitation research and surgical/rehabilitation collaborations.

   Dr. Bechtold commented that the work done at this roundtable will likely have broader implications than just the tendon area. Dr. Katz reminded the group that the NIAMS held a previous roundtable discussion on the intervertebral disc.

10. UPDATE ON NEXT GENERATION RESEARCHERS INITIATIVE

    Dr. Katz noted NIH’s concern regarding the long-term stability of the biomedical research enterprise—too many researchers vying for limited resources has led to a hypercompetitive environment in which many highly meritorious applications go unfunded. He presented a slide showing the proportion of investigators with NIH Research Project Grants and other select awards by age and explained that the current funding environment appears to be benefitting those who have more experience, with older PIs comprising an increasing percent of NIH grantees. In 2006, the success rate of new investigators submitting their first application to the NIH was 6%. NIH ICs began offering a differential payline for researchers who had never received a substantial NIH independent research award beginning roughly in FY 2008.

    The NIH is shifting toward a more focused approach to bolster support to early-stage and early-established investigators (ESIs and EEIs). Consistent with new NIH terminology, the NIAMS will use the term “early-established investigators” to describe researchers who are within 10 years of receiving their first R01 equivalent grant as an early-stage investigator. Dr. Katz clarified that ESI status ends upon receipt of first R01-equivalent award, 10 years post terminal degree, or 10 years after the end of clinical training. EEI status begins upon receipt of first R01-equivalent award as an ESI and continues for 10 years. Consistent with the provisions in the 21st Century Cures Act, this effort is called the Next Generation Researchers Initiative (NOT-OD-17-101, released August 31, 2017).

    The NGRI supersedes previous notices on new and early-stage investigators and requires NIH ICs to prioritize awards that will fund ESIs and EEIs. It prioritizes meritorious R01-equivalent applications from ESIs for funding. It also prioritizes meritorious applications from EEIs if: (1) the EEI lost or is at risk for losing all NIH research support if not funded by competing awards this year, or (2) the EEI is supported by only one active award. Dr. Katz noted that meritorious applications from new investigators who are not ESIs (i.e., those who have never before received R01-equivalent awards from NIH but completed their terminal degree or clinical training over 10 years ago) are of interest to all NIH ICs, but they will not be tracked through the NGRI. In FY 2017, the NIH has committed to fund roughly an additional 200 ESIs and EEIs than in FY 2016. Dr. Katz noted that as a result of this shift, it behooves all NIH ICs to look at ESIs and EEIs beyond their respective paylines with Council and programmatic staff input on the potential significance of what is being proposed.

    The NIH has established the NGRI Working Group of the NIH Advisory Committee to the Director to refine and implement this initiative. The Working Group includes investigators at all levels, from graduate students to full professors. The NIH will use public meetings, conferences, and the Office of Extramural Research’s public website to communicate progress to the community.

    Discussion

    Dr. Katz reminded Council members that the NGRI supersedes all previous notices, comments, etc., regarding ESIs and EEIs.

    Dr. Koretzky asked for clarification on how multi-PI grants will be considered, and whether submission of multi-PI grants preclude PIs from being considered as ESIs or EEIs. Dr. Katz explained that early-stage or early-established investigators who are part of multi-PI applications that include established investigators are not counted as ESIs or EEIs. In response to a question from Dr. James, Dr. Katz explained that the NIAMS has a select pay process and welcomes Council input on special considerations for applications. He estimated that 5-10% of applications that the Institute pays in a given year fall outside of its payline and reminded the group that the number of new ESI and EEI applications to be funded as part of this new NIH initiative will vary across ICs, and that it is the responsibility of each IC to allocate funding for these applications from within their existing budgets.

    Dr. Koretzky indicated that there is general agreement across the community with the goal of finding ways to protect ESIs and EEIs so that they can maintain their career paths. He acknowledged the significant challenges the NIH faced in developing its strategy to address these issues and commented that the NIAMS played a critical role in helping to overcome these challenges. He also noted that NIH Principal Deputy Director Dr. Lawrence Tabak greatly appreciated all of the feedback he received from NAMSAC members following his presentation that introduced the NGRI to the Council during its June 2017 meeting.

11. SUPPLEMENTS TO ADVANCE RESARCH (STAR) PROGRAM UPDATE

    Dr. Kathryn Marron, Health Science Analyst in the Division of Skin and Rheumatic Diseases, provided an update on the NIAMS STAR Program as a follow up to the presentation given during the June 2017 Council meeting. The NIAMS has undertaken a limited evaluation of the program to date based on the small amount of data available (the program is only a few years old) as well as a consideration of key components of the program in light of the downstream effects of the NGRI. A subgroup of Council members that included Drs. James, Koretzky, Lerner, and Tapscott provided valuable discussion and feedback on an initial proposal in August; NIAMS staff and leadership have refined the proposal based on their feedback and their own input.

    Two key questions to address in updating the STAR Program are: (1) How should the NIAMS alter the STAR Program with regard to other support? (2) Should the NIAMS alter the STAR Program in the context of the NGRI? The purpose of the STAR Program is to:

    • Facilitate the transition from a single research project to a research program for an EEI (per the 2015 Program Announcement; in this case, EEIs are defined as an investigator who has successfully renewed a NIAMS-supported New Investigator R01 received no earlier than 2009).
    • Explore new opportunities broadly within the scope of the research project.
    • Promote innovation and exploration of high-risk ideas.

    STAR awards are non-competing administrative supplements of up to $300,000 in direct costs over 2 years. The funds are not intended to provide additional support to the PI’s salary, but rather to provide flexibility to explore new opportunities within the broad context of their funded grant. Applications are generally submitted in the second or third year following renewal of the original R01.

    During the June 2017 Council meeting, it was noted that a number of STAR recipients at that time already had multiple R01-equivalent awards. For these individuals, who were already well funded and had likely succeeded in developing a research program, the STAR Program likely did not make much of an impact. To maximize the program’s impact, the NIAMS hopes to more effectively target these awards to those who are still developing their research programs. Dr. Marron noted that the STAR Program is distinct from but complementary to the NGRI, and that as the NGRI is implemented, it is expected that the number of STAR-eligible investigators will increase. For FY2019, the Institute is proposing the following changes to the STAR Program:

    • Limiting STAR awards to those who have no more than two active R01-equivalent NIH grants at the time of their STAR application (i.e., they can have the first R01 renewal and one other R01 equivalent). (Currently, there are no limits on other funding.)
    • Limiting STAR awards to investigators whose first R01 was from the NIAMS as an ESI and has been renewed. (Currently, investigators eligible for STAR awards are those whose first R01 was from the NIAMS as a new investigator or ESI and has been renewed.)

    Discussion

    Dr. Bechtold applauded the NIAMS for carefully reviewing the STAR Program and noted that the shift to limiting awardees to those who have no more than two active R01-equivalent NIH grants will effectively target those investigators who need the support. Dr. Koretzky voiced support for the STAR Program and NIAMS’ proposed changes. He suggested tracking important outcomes for the program, especially in terms of identifying retrospectively whether those who were most successful achieved the highest ranking at the time of study section evaluation.

12. BOARD OF SCIENTIFIC COUNSELORS REPORT

    This portion of the meeting occurred during closed session.

13. SPECIAL ACTIONS

    This portion of the meeting occurred during closed session.

14. CONSIDERATION OF APPLICATIONS

    In closed session, the Council reviewed 665 primary and 334 secondary applications. One application was deferred for re-review. 71 applications were taken to Early Concurrence. The total cost requested in year -01 for all applications was $418,897,660.

15. PORTFOLIO PRESENTATION

    This portion of the meeting occurred during closed session.

16. ADJOURNMENT

    The 93^rd 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.