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

Minutes of the 86th Meeting
8:30 a.m. to 3:07 p.m.

1. CALL TO ORDER

   The 86th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 16, 2015, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 6. The meeting was chaired by Dr. Stephen Katz, Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

   Attendance

   Council members present

   Dr. Joan E. Bechtold
   Dr. Sherine E. Gabriel (by teleconference)
   Ms. Michelle Hofhine
   Dr. Sundeep Khosla
   Dr. Gary Koretzky
   Dr. Amy Paller (by teleconference)
   Dr. Grace Pavlath
   Dr. Anthony Rankin (by teleconference)
   Dr. Christy I. Sandborg
   Mr. Richard F. Seiden
   Dr. Elizabeth Shane
   Mr. Alexander Silver
   Ms. Elizabeth Smith

   Staff and Guests

   The following NIAMS staff and guests attended:

   Staff

   Dr. Lee Alekel Mr. Steven Austin Dr. Carl Baker Ms. Susan Bettendorf Dr. Amanda Boyce Dr. Stephanie Burrows Ms. La’Tanya Burton Dr. Robert Carter Dr. Faye Chen Ms. Jennifer Chi Dr. Ricardo Cibotti Mr. Richard Clark Ms. Robin DiLiello Ms. Theresa Do Dr. Jonelle Drugan Ms. Elizabeth Elliott Ms. Barbara Footer Dr. Nancy Garrick Mr. Danny Heise Ms. Sara Hwang Ms. Aleisha James Ms. Katie Joffee Ms. Gail Hamilton Dr. Chao Jiang Mr. Andrew Jones Dr. Stephen Katz Ms. Mary Beth Kester Ms. Shahnaz Khan Ms. Stephanie Kreider Mr. Mark Langer Dr. Gayle Lester Dr. Helen Lin Ms. Anita Linde Ms. Leslie Littlejohn Dr. Kan Ma

   Dr. Su-Yau Mao Dr. Marie Mancini Dr. Kathryn Marron Mr. Deepak Mathur Dr. Joan McGowan Ms. Leslie McIntire Ms. Sherry Meltzer Dr. Laura K. Moen Ms. Regina Mong Ms. Melinda Nelson Ms. Anna Nicholson Dr. John O’Shea Dr. James Panagis Ms. Reaya Reuss Ms. Trish Reynolds Dr. Kathy Salaita Dr. Susana Serrate-Sztein Ms. Sheila Simmons Ms. Yen Thach Dr. Phil Tonkins Ms. Julie Townshend Dr. Bernadette Tyree Mr. Philip Waltz Dr. Fei Wang Dr. Yan Wang Dr. Chuck Washabaugh Ms. Sara Rosario Wilson Dr. James Witter Dr. Xincheng Zheng

   Guests

   Dr. Chris Austin, National Center for Advancing Translational Sciences, NIH
   Dr. Thomas Cheever, National Institute of Neurological Disorders and Stroke, NIH
   Mr. Dane Christiansen, Health and Medical Council of Washington
   Mr. Dale Dirks, Health and Medical Council of Washington
   Mr. Douglas Fesler, American Society for Bone and Mineral Research
   Dr. John Gallin, Clinical Center, NIH
   Dr. John Holden, Department of Veterans Affairs
   Ms. Leah Howard, National Psoriasis Foundation
   Dr. Joseph Laakso, Endocrine Society
   Dr. Sherry Mills, Office of Extramural Research, NIH
   Ms. Patricia Egwuatu, American Association of Colleges of Osteopathic Medicine
   Mr. Nate Robinson, IQ Solutions
   Ms. Kirstie Saltsman, IQ Solutions
   Dr. Monika Schneider, American Association of Immunologists
   Mr. Kyle Shah, American Academy of Orthopaedic Surgeons
   Ms. Kristin Stephenson, Muscular Dystrophy Association
   Mr. Joseph Stewart, Health and Medical Council of Washington
   Ms. Darlene Summers, Consolidated Solutions and Innovations
   Mr. Obi Casel, no affiliation

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to accept with no changes the minutes of the 85th NAMSAC meeting, held on February 4, 2015.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:

   September 8, 2015
   February 2, 2016
   June 7, 2016
   September 13, 2016
   January 25, 2017
   May 24, 2017
   September 6, 2017

4. DIRECTOR'S REPORT AND DISCUSSION

   Update on Budget and Congressional Outreach Activities

   The Institute’s fiscal year (FY) 2015 funding plan is now available on the NIAMS website. This information is posted online as part of the NIAMS’ commitment to transparency (i.e., to ensure that everyone who is interested in NIAMS activities has access to the same information).

   The House and Senate Subcommittees on Labor, Health and Human Services, Education, and Related Agencies have been holding hearings preliminary to the FY 2016 budget deliberations. Members of both chambers are immensely supportive of the NIH and are interested in how it encourages new investigators, sets priorities, and provides stewardship of taxpayer funds.

   For the past year, the House Energy and Commerce Committee has been developing legislation called the 21st Century Cures Initiative. This bipartisan effort, led by Representative Fred Upton (R-MI) and Diana DeGette (D-CO), is intended to accelerate the discovery, development, and delivery of treatments and cures for disease. It was unanimously reported out of both the House Energy and Commerce Health Subcommittee and full Committee last month. The Senate Health, Education, Labor and Pensions Committee is undertaking a related effort to examine: (1) the time and cost currently involved with the drug and medical device discovery and development process, and (2) how to better align public policies to support medical innovation. Both Committees have held hearings with NIH and FDA leadership to inform their deliberations. The most recent version of the Bill will reauthorize the NIH and establish an Innovation Fund. The NIH particularly welcomes the Innovation Fund—the additional money that it provides to encourage the exploration of new ideas is crucial to getting biomedical research support back on track. Dr. Katz noted that the bill will require matching funds for some innovation activities and that the NIAMS has been planning to initiate a new effort in this area.

   As discussed in depth at NIH Director Dr. Francis Collins’s Advisory Committee to the Director meeting last week, the Act will also call for the NIH to develop an overall Strategic Plan. Members of Congress first asked for an NIH Strategic Plan as part of the FY 2015 appropriations process. Building on this, Dr. Katz has been working with a small group of NIH Institute and Center (IC) Directors, led by NIH Principal Deputy Director Dr. Larry Tabak, to develop an approach that will fulfill the law’s requirements and intention while maintaining the research community’s flexibility to respond to emerging scientific opportunities in innovative ways.

   Consistent with congressional interest in improving efficiencies at the NIH, the Scientific Management Review Board (SMRB) has established a working group on the NIH’s Grant Review, Award, and Management Process. Dr. Katz is participating in this group, which is discussing strategies to improve the process of reviewing, awarding, and managing grants. Specifically, it is considering: (1) ways the NIH could streamline the grant-making process and shorten the time from application to allocation of funds; and (2) strategies for reducing administrative requirements on applicants and their institutions, scientific reviewers, Council members, and NIH staff while maintaining a high-quality review and management process. These suggestions and recommendations will be reported out in the near future.

   Personnel Changes at the NIH and NIAMS

   At the NIH level, Dr. Walter Koroshetz is now the permanent Director of the National Institute of Neurological Disorders and Stroke (NINDS); he had been serving in an acting capacity since October 2014. Dr. Koroshetz joined the NIH as Deputy Director of NINDS in 2007. The NIAMS works closely with the NINDS on many areas of shared interest and many trans-NIH programs, including the Muscular Dystrophy Coordinating Committee and the NIH Pain Consortium, and looks forward to continuing those interactions.

   The NIH has recruited Dr. Eliseo Pérez-Stable as the next Director of the National Institute on Minority Health and Health Disparities (NIMHD). Dr. Pérez-Stable, comes from the University of California, San Francisco and will be invited to speak at a future NAMSAC meeting.

   Dr. Harold Varmus, who has led the National Cancer Institute (NCI) for nearly 5 years, stepped down from his post at the end of March. NCI Deputy Director and long-time NCI intramural researcher Dr. Douglas Lowy will lead the NCI until a new Director is appointed. Dr. Lowy received the National Medal of Technology and Innovation from President Obama in 2014 for his research that led to the development of the human papillomavirus (HPV) vaccine.

   Within the NIH Office of the Director:

   • Dr. Sally Rockey recently announced that she will be leaving her post as Deputy Director for Extramural Research to lead the Foundation for Food and Agriculture Research. Drs. Katz and Lowy will be chairing the search committee for Dr. Rockey’s replacement.
   • Ms. Adrienne Hallett joins the NIH as Associate Director for Legislative Policy and Analysis after 14 years of experience on the staff of the Senate Committee on Appropriations.
   • Former Deputy Vice President for Federal Relations with the Association of American Universities Dr. Carrie Wolinetz is the new NIH Associate Director for Science Policy.
   • Dr. Jack Whitescarver will be stepping down as the Director of the Office of AIDS Research and the NIH Associate Director for AIDS Research. Dr. Robert Eisinger, Senior Health Science Policy Advisor in the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), will fill Dr. Whitescarver’s roles in an acting capacity while NIH conducts a national search.

    

   NIH-Wide and NIAMS Scientific Activities

   The funding opportunity announcement for the Lasker Clinical Research Scholars program—a joint partnership that involves the NIH intramural and extramural communities, as well as the Lasker Foundation— has been reissued. Dr. Katz reminded Council members that this program supports a small number of exceptional clinical researchers who are in the early stages of their careers.

   Dr. Katz reported that the Clinical Center has suspended operations of its Pharmaceutical Development Section due to serious manufacturing problems and lack of compliance with standard operating procedures. Dr. Collins is personally ensuring that NIH quickly remedies the situation. No products requiring sterile manufacturing methods will be made or distributed until all problems are fully understood and corrected. The NIH has notified the individual Principal Investigators (PIs) responsible for the affected protocols, and is in the process of notifying the participants in these protocols. The vast majority of these patients are not immediately due for treatment and NIH is working to secure alternative sources for the products. An external group of experts in microbiology and sterile manufacturing practices will be appointed to conduct a thorough review—including an assessment of all standard operating procedures, policies, staffing, and training—and make recommendations to the NIH Director on the corrective actions required. The NIH will provide an interim corrective action plan to the U.S. Food and Drug Administration (FDA).

   Another NIH-related issue that has been receiving much more favorable attention is the President’s Precision Medicine Initiative. The NIH is leading two components of the Initiative: (1) a near-term goal that will focus on cancer, and (2) a longer-term aim to generate knowledge that applies to a wide range of diseases. As part of the longer-term, broader goal, the NIH will launch a national research cohort of at least 1 million volunteers. The NIH is holding a series of public workshops to gather input from participant, scientific, and other stakeholder groups to develop recommendations for implementing the Initiative. The NIH is also is seeking feedback regarding strategies to engage communities that are medically underserved or historically underrepresented in biomedical research through a Request for Information. The Initiative will be rolled out at the September Advisory Committee to the Director meeting.

   For the past decade, the NIH has been working with the National Aeronautics and Space Administration (NASA) on a collaborative program to allow extramural researchers to access National Laboratory resources on the International Space Station (ISS). After many discussions, the NIH and NASA signed a formal Memorandum of Understanding to (MOU) publicize the biomedical research facilities on the ISS. One of the projects supported as part of this effort is in Dr. Faye Chen’s (Program Officer in the Division of Musculoskeletal Diseases) research portfolio: Dr. Paola Divieti Pajevic is studying osteocytes in microgravity. The project launched in April and the frozen cells were flown back to earth on May 21 via the SpaceX Dragon Capsule for analysis.

   The NIAMS is leading a collaborative program leveraging funds that became available with the closure of the National Children’s Study. The initiative, called the Validation of Pediatric Patient Reported Outcomes in Chronic Diseases (PEPR), will fund a consortium that will capitalize on recent advances in the science of patient-reported outcomes to assess the health of children with a variety of chronic diseases and conditions in clinical research and care settings. PEPR will use pediatric self-report and parent proxy instruments developed through the NIH Common Fund’s Patient Reported Outcomes Measurement Information System (PROMIS) initiative. The NIH expects to make awards after the September 2015 NAMSAC meeting.

   For the past 2 years, NIAMS staff including Drs. Joan McGowan (Director of the Division of Musculoskeletal Diseases), Amanda Boyce (Program Officer in the Division of Musculoskeletal Diseases), and Jonelle Drugan [Science Policy Analyst in the Office of Science Policy, Planning and Communication (OSPPC)] have been working on an NIH Common Fund Proposal to extensively catalogue the biological molecules that are affected by physical activity in people. The Molecular Transducers of Physical Activity in Humans Consortium, like most Common Fund efforts, is a multi-Institute endeavor. The NIAMS has been leading this effort along with Dr. Griffin Rodgers, Director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Dr. Richard Hodes, Director of the National Institute on Aging (NIA). Last week, the NIH announced that it is committing approximately $170 million to the program over the course of FY 2016-2020, pending the availability of funds. Dr. McGowan will provide an update during the September 2015 NAMSAC meeting.

   Dr. Katz reported that for now, the NIAMS will not be renewing its Small Grant Program for New Investigators (commonly known as the R03); this topic was discussed during the February NAMSAC meeting. Dr. Katz expressed appreciation for Council members’ input regarding the benefits and challenges associated with the R03 program, and indicated that in this time of constrained funding, the Institute has decided that the R03 funds could be better invested elsewhere.

   This year’s annual Extramural Scientific Planning Retreat focused on NIAMS’ scientific management issues and research opportunities in its mission areas. The agenda covered needs and opportunities that emerged from fall 2014 roundtable discussions. The Retreat also focused on: (1) potential intersections between NIAMS-supported cohorts and NIH-led components of the President’s Precision Medicine Initiative; (2) strategies for further supporting arthritis, musculoskeletal, and skin researchers through the Mentored Clinical Scientist Development Investigator Award (K08) and Mentored Patient-Oriented Research Career Development Award (K23) programs; and (3) approaches for encouraging investigators to propose innovative, transformative research in NIAMS-mission areas.

   Highlights of Selected Recent Scientific Advances

   • Several studies that build upon or complement the NIAMS-funded Spine Patient Outcomes Research Trial (SPORT) have been published recently. SPORT compared the outcomes of surgical and non-surgical treatments for the three most common reasons for surgery for low back pain (lumbar disc herniation, spinal stenosis, and degenerative spondylolistheses).

     • Several studies that build upon or complement the NIAMS-funded Spine Patient Outcomes Research Trial (SPORT) have been published recently. SPORT compared the outcomes of surgical and non-surgical treatments for the three mostAlthough SPORT’s primary analyses are looking at all non-surgical interventions as a single group, a study by Dr. Harley Goldberg at the Kaiser Permanente Northern California Spine Care Program looked at the risks and benefits of a single type of treatment—oral steroids. The investigators reported the surprising findings that a short course of oral steroids (5 days of 60 mg, 5 days of 40 mg, 5 days of 20 mg) resulted in only a modest improvement in function in these patients and no reduction of pain, compared with a placebo (JAMA. 2015 May 19; 313(19):1915-23. doi: 10.1001/jama.2015.4468. PMID: 25988461).

     • Dr. Anthony Delitto at the University of Pittsburgh compared surgery to a standardized physical therapy protocol for patients with lumbar spinal stenosis (a narrowing of the spinal cord, primarily in older individuals). On average, the 169 patients in this study had a successful long-term outcome and improvement in functional status, regardless of whether they received a standardized operative procedure or a standardized physical therapy intervention. The results of this study complement those of SPORT, which showed that patients who were comfortable with non-operative treatments and who did not have worsening symptoms, do well over time. Its positive findings go one step further by strongly suggesting a treatment strategy for lumbar spinal stenosis that starts with a standardized physical therapy regimen (Ann Intern Med. 2015 Apr 7; 162(7):465-73. doi: 10.7326/M14-1420. PMID: 25844995). As summarized in an accompanying editorial by Dr. Jeffrey Katz, Director of the Orthopedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, patients with lumbar spinal stenosis who are considering surgery should first be offered physical therapy. As Dr. Katz notes in his editorial, it is important for patients whose spinal stenosis symptoms do not improve with physical therapy to understand that the benefits of surgery are likely to diminish over time. And, because the two treatments have similar long-term outcomes but considerably different short-term risks, patient preferences are an essential consideration.

   • WNT and sclerostin are being studied in the context of osteogenesis imperfecta (OI), also known as brittle bone disease. Recent work from Dr. Kenneth Kozloff at the University of Michigan revealed that treatment with a sclerostin antibody improves the strength of leg bones when given to a mouse model of human pediatric OI type IV while the mice are still growing. Although it is worth noting that the sclerostin antibody used in this study currently is being tested in osteoporosis patients, further work is needed to test whether it might cause unwanted skeletal overgrowth if given to pediatric patients (Bone. 2015 Feb; 71:115-23. doi: 10.1016/j.bone. 2014.10.012. Epub 2014 Oct 23. PMID: 25445450).

   • Current therapies for lupus are based mainly on the use of non-specific immunosuppressive drugs that cause serious side effects. A research team involving NIAMS grantees Drs. Zaida Ramirez-Ortiz and Terry Means at Harvard describe how screening more than 8,000 genes enabled them to identify an inflammatory molecule, TREML4, which may play an essential role in the development of lupus via the toll-like receptor 7 pathway. Studies in TREML4-deficient mice suggest that TREML4 antagonists may dampen inflammation and suppress the lupus onset. The animals were more susceptible to infection, suggesting that chronic therapeutic inhibition of the TLR-7 or other pathways of the innate immune system could potentially lead to increased susceptibility to pathogens. However, increased susceptibility to viral infection has not been seen in lupus patients treated with hydroxychloriquine—which also inhibits TLR signaling—and the question of whether inhibition of TREML4 can provide long-term treatment of autoimmune disease without harmful complications remains to be answered (Nat Immunol. 2015 May; 16(5):495-504. doi: 10.1038/ni.3143. Epub 2015 Apr 6. PMID: 25848864).

   • Recent research has established that the specialized joint-lining cells, fibroblast-like synoviocytes, play an important role in rheumatoid arthritis (RA) by invading cartilage and promoting inflammation and bone destruction. However, these cells are currently untapped as a drug target. A study by Dr. Nunzio Bottini at the La Jolla Institute for Allergy and Immunology reported that a protein called RPTP-sigma, which is present at high levels in fibroblast-like synovial cells of RA patients, regulates synoviocyte invasiveness. Furthermore, disrupting such interactions by a decoy fragment decreased the synoviocyte invasiveness in human cells, and reduced the severity of disease in a mouse model of RA. Together, these findings suggest a new target for RA therapy (Sci Transl Med. 2015 May 20;7(288):288ra76. PMID: 25995222).

   • Building on knowledge that follicle injury can stimulate hair regeneration, Drs. Cheng-Ming Chuong and Chih-Chiang Chen at the University of Southern California reasoned that they might be able to leverage this phenomenon to activate more follicles. Plucking hairs in a low-density pattern failed to stimulate regeneration, but higher-density plucking of 200 hairs triggered the regeneration of 2-6 times as many hairs, including ones outside of the plucked region. Mathematical modeling and genetic techniques demonstrated that follicles located near each other make a coordinated decision whether to respond to injury by regenerating. The regulatory molecules and pathways identified in this study may provide targets for alopecia therapies. In addition, the principles identified in this study may also lead to future insights into the regeneration of other organs (Cell. 2015 Apr 9;161(2):277-90. doi: 10.1016/j.cell.2015.02.016. PMID: 25860610).

   • From within the NIAMS Intramural Research Program (IRP), a team led by Dr. John O’Shea (NIAMS IRP Scientific Director) built on earlier work that has shown that some variants in non-coding DNA elements called enhancers act as powerful switches, controlling genes important to the identity of each individual cell type. A large number of disease-associated genetic alterations fall within these super-enhancers, suggesting that disease occurs when these switches malfunction. Dr. O’Shea’s team began searching for super-enhancers in T cells, with the thought that these regions could steer them toward potential genetic risk factors for autoimmune diseases. They identified several hundred segments of the T-cell genome that resemble super-enhancers. In T cells, these regions mainly control the activities of genes for cytokine and cytokine receptors, which allow T cells to communicate and launch an immune response. Furthermore, a large fraction of previously identified genetic changes associated with rheumatoid arthritis and other autoimmune diseases localized to those super-enhancer regions (Nature. 2015 Apr 23;520:558-62. doi: 10.1038/nature14154. Epub 2015 Feb 16. PMID: 25686607).

   • Also from within the IRP, Dr. Michael Ward, Acting Chief of the Clinical Trials and Outcomes Branch, is researching whether specific questions about how a person’s health has changed are better than a single global question for estimating clinically important differences over the course of a study. Dr. Ward’s team examined almost 250 RA patients for changes in pain, physical function, joint swelling, stiffness, fatigue and depression over the course of treatment. The researchers correlated their clinical measures and patient responses to three different questionnaires. The results indicate that six specific questions about patient symptoms were more highly correlated with the clinical findings, and were at least as good in other statistical measures, than either a single global disease question or the health transition item from the SF-36. Based on these results, the investigators recommend using individual questions about changes in health status as anchors for clinical measures focused on a specific aspect of health, despite the potential additional time and resources that these types of surveys may require (J Clin Epidemiol. 2015 Jun; 68(6):655-61. doi: 10.1016/j.jclinepi. 2015.01.028. Epub 2015 Feb 11. PMID: 25769795).

    

   Communication and Outreach Activities

    

   Information about discoveries from NIAMS-funded investigators and NIAMS and NIH activities is available through monthly NIAMS Updates, NIAMS ShortTakes, and the Institute’s NIAMS Multicultural Outreach News. Dr. Katz’s June Director’s Letter features examples of how the NIAMS collaborates with other government agencies or non-governmental organizations to foster biomedical research.

   Council members are regularly updated on interactions with professional and patient advocacy communities through the NIAMS Coalition. Ms. Mary Wheatley, Executive Director of the Rheumatology Research Foundation, has agreed to fill the position of NIAMS Coalition Co-Chair that was vacated by Mr. Simit Pandya when he left the American Academy of Orthopaedic Surgeons. Ms. Wheatley joins Ms. Leah Howard from the National Psoriasis Foundation in co-chairing the NIAMS Coalition.

   The Institute has had several opportunities to participate in a number of outreach activities since the last NAMSAC meeting:

   • On June 15, Dr. Katz spoke to approximately 250 lupus patients and family members who were visiting Washington, DC, for the Lupus Foundation of America’s National Lupus Advocacy Summit.

   • The Institute hosted Representative Rodney Frelinghuysen (R-NJ), two of his constituents, and members of the Arthritis Foundation (AF) including Council Member Elizabeth Smith for a campus visit.

   • On May 19, Dr. Katz spoke at a Congressional briefing organized by the Sturge-Weber Foundation.

   • In March, Dr. McGowan represented the NIAMS at a Hill briefing sponsored by the Rare Bone Diseases Advocacy Alliance and moderated by Ms. Tracy Hart, former NIAMS Council Member and CEO of the Osteogenesis Imperfecta Foundation.

   Dr. Katz noted that NIAMS staff at all levels play crucial roles in explaining the Institute’s work to Congress, other researchers, and the American public. NIAMS intramural researcher Dr. Peter Grayson recently volunteered to be featured on LabTV, an online collection of videos of young and early stage investigators talking about their research, their career paths, and their aspirations (Dr. Katz presented a few excerpts from Dr. Grayson’s video). LabTV’s goal is to get these talented researchers to inspire others to pursue scientific careers. Several NIH intramural investigators have participated in the program thus far.

    

   Discussion

    

   Dr. Katz opened the discussion by asking Council members for their input on the advantages and disadvantages (other than the relatively minimal cost) associated with videocasting the public sessions of these NAMSAC meetings to reach a broader audience. Council member Dr. Sundeep Khosla, Professor of Medicine and Professor of Physiology at the Mayo Clinic, expressed support for videocasting the public sessions of NAMSAC meetings, noting that the topics discussed during these sessions are of interest to many of NIAMS’ stakeholders around the country.

   Council member Dr. Gary Koretzky, Dean of Weill Cornell Graduate School and Senior Associate Dean for Research at Weill Cornell Medical College, asked if the videocasting would be interactive (i.e., if viewers would have the opportunity to ask questions). Dr. Katz indicated that as currently envisioned, the videocasting would be passive.

   Alexander Silver, Chairman of the Jackson Gabriel Silver Foundation and a member of the Council, also expressed support for videocasting the open sessions of NAMSAC meetings, with some manner of moderated viewer participation. He also suggested archiving the videocasts to allow viewers to access the recordings after the meetings, and creating an instructional tool to assist viewers in accessing the videocasts. A number of additional Council members expressed similar support for the concept of videocasting the open sessions of these NAMSAC meetings.

5. THE NIH CLINICAL CENTER AS A NATIONAL RESOURCE

   Dr. Gallin noted that the Clinical Center is the largest building on NIH’s Campus, occupying roughly 4 million square feet. The hospital opened in 1953; since that time, more than 500,000 patients have been seen there. Today, the Clinical Center has 240 beds and a budget of $409 million (the Clinical Center is funded by each of the 18 ICs that make use of its services). Every Clinical Center patient is on a research protocol and their care is free. Roughly two-thirds of patients are referred to the Clinical Center by private physicians; most of the remaining patients self-refer. Patient travel/housing is provided as needed. The Clinical Center roughly 2,800 employees, plus another 4,000 employees from the ICs that use it. There are more than 1,600 active clinical protocols, most of which are either intervention/clinical trials or natural history studies.

   The NIH Clinical Center is the largest hospital in the world totally dedicated to clinical research. In 2011, the Center was awarded the prestigious Lasker Bloomberg Public Service Award, which is usually given to an individual. Dr. Gallin characterized the Center as representing a “window to the NIH” for Congressional leaders and administration. Honored visitors to the Clinical Center in the last year include the Dali Lama and President Obama.

   Dr. Gallin reviewed a number of selected Clinical Center inventions/discoveries/ accomplishments, including:

   • Chemotherapy for cancer

   • Use of blood lipid levels as biomarkers of cardiovascular disease

   • First three drugs for AIDS

   • Fluoride to prevent dental caries

   • Cell therapy for metastatic melanoma and other cancers

   • Discovery of autoinflammatory diseases (by former NIAMS Clinical Director Dr. Daniel Kastner)

   • New imaging approaches for diagnosis and management of prostate cancer

   • First in human candidate Ebola vaccines

   The major emphases of the Clinical Center are to study the pathophysiology of disease, conduct first in human studies with new therapeutics, and study patients with rare diseases (Dr. Gallin reminded the group that 18-25 million Americans have a rare disease).

   Specialized services and facilities offered at the Clinical Center include phenotyping (including a biomechanics laboratory and metabolic chambers), transfusion medicine/cell processing, imaging capabilities (including an MRI center and a PET program), and an isolation unit for the study of patients harboring potentially infectious pathogens and first in human vaccine studies. The Clinical Center also boasts a Biomedical Translational Research Information System to handle data management. The system allows for access to and merging data from multiple sources and the ability to download data for a variety of uses.

   Training is a key investment for the Clinical Center, which has trained many of the leaders of academic medicine throughout the United States and abroad. Since 1995, more than 35,000 students worldwide have participated in the NIH Curriculum in Clinical Research (many through distance learning approaches). In 1995, the Center launched the “Introduction to the Principles and Practice of Clinical Research” course; to date, 21,000 participants have taken the course. Roughly 11,000 participants have taken the “Principles of Clinical Pharmacology” course, which began in 1998. And, approximately 6,000 individuals have participated in the “Ethical and Regulatory Aspects of Human Subjects Research” course (which started in 1999). The Clinical Center also boasts other training programs, such as the Sabbatical in Clinical Research Management (which targets mid-career senior scientists and research administrators interested in running a clinical research facility) and the Clinical and Translational Research Course for Ph.D. Students.

   Dr. Gallin discussed opportunities for collaboration with the Clinical Center. When the NIH Scientific Management Review Board was created in 2010, one of its first actions was to review the Clinical Center and declare that “The role of the NIH Clinical Center should be to serve as a state-of-the-art national resource, with resources optimally managed to enable both internal and external investigator use.” In response to this charge, a new NIH funding opportunity was created, “Opportunities for Collaborative Research at the NIH Clinical Center (U01 grant). These renewable grants support collaborative research to enhance the translation of basic biological discoveries into clinical applications that improve health and have up to $500,000 per year in direct costs for 4 years. Successful applicant teams must have one outside and one intramural Co-PI (international partners are welcome and encouraged). Some work associated with the grant must be conducted at the Clinical Center. Dr. Katz added that the U01 was established in part to enhance patient utilization of the Clinical Center. A total of 18 NIH ICs (including NIAMS) have agreed to participate in this funding opportunity. Two cycles have now been completed, with 10 awards made the first year (2013) and 6 the second year (2014). The success rate has ranged between 18% and 20%.

   Another opportunity for collaboration lies in the Bench-to-Bedside Program. These seed awards provide $135,000 per year in direct costs for 2 years and involve partnerships between basic science and clinical investigators for projects at the Clinical Center. More than 90% of these awards are supplementing an extramural grant in partnership with an intramural investigator. NIAMS investigators have received a number of these awards since 1999. Additional opportunities for collaboration include the Cooperative Research and Development Agreements (CRADAs), participation in multi-site clinical trials, and informal partnerships. In an effort to facilitate, enhance, and streamline partnerships with the Clinical Center, Dr. Collins has asked Dr. Gallin to seek partnerships with institutions initially within a 150-mile radius of the Clinical Center and create a template MOU to make it easier to partner with the Clinical Center. Additional information on partnering with the Clinical Center is available at Translational Research Resources.

    

   Discussion

    

   Dr. Khosla noted that many institutions are moving towards formal databases that make it easier to identify potential collaborations that otherwise might not be considered. He asked if this is happening at the Clinical Center or at the NIH overall. Dr. Gallin agreed that these newer databases are making it easier to identify potential collaborations. There is an easily searchable annual report that NIH investigators produce each year—this report can be used to identify investigators and their research. The site clinicaltrials.gov is another tool that can be used to locate potential collaborators.

   Dr. Koretzky indicated that there is some sentiment that the Clinical Center has been, at times, underutilized, both internally within the NIH and from the extramural community. He commented that the efforts to engage the extramural community described by Dr. Gallin are critically important.

   Dr. Koretzky also asked if the NIH has considered a model or mechanism through which extramural investigators could use the Clinical Center without requiring collaboration with an intramural investigator. Such an approach might improve the utilization of the Clinical Center. Dr. Gallin replied that there has been significant thought given to this suggestion. The NIH does not want the Clinical Center to become a clinical research organization—a patient brought into the Clinical Center must be cared for with compassion, and investigators within the Clinical Center feel strongly that having meaningful intellectual partnerships are a necessary component of the Center’s operation.

   Council member Michelle Hofhine, Vice President of Marketing at Accredited Home Care Services, explained that her daughter suffers from osteogenesis imperfecta and is a patient at the Clinical Center. Her first visit to the Center was when she was 9 months old; she is now 21 years old. She thanked Dr. Gallin and his staff for the high-level of care her daughter has received. Dr. Gallin noted that one of the luxuries afforded those who work at the Clinical Center is time—the physicians, nurses, and others at the Clinical Center can spend as much time as needed with patients to help understand the diseases processes better. This in turn creates close relationships between patients and their families and the health care team.

6. ASSESSING PROGRESS IN “THE FUTURE DIRECTIONS OF LUPUS RESEARCH”

   Ms. Anita Linde (Director, OSPPC) provided Council members with an update on progress on the lupus research plan. As with the prior plan, the hallmark of this plan is a tremendous amount of input from the scientific community, patient-oriented groups, external experts, etc. She explained that the impetus for the plan was a request from the Congressional Lupus Caucus, a bipartisan Capitol Hill group that visited the NIH last summer and asked for an update on the prior lupus research plan (which was released in 2007) as well as the development of a new, coordinated action plan for lupus research. The request came to the NIAMS as the convener of the Lupus Federal Working Group, which is co-chaired by Drs. Katz and Susana Serrate-Stein (Director of the NIAMS Division of Skin and Rheumatic Diseases). The NIAMS is developing the plan on behalf of the entire NIH.

   Ms. Linde reviewed the plan’s development process, noting that on a parallel track, the NIAMS is developing two documents for public release later this year: (1) a progress report on the 2007 plan, and (2) the new coordinated plan that will guide research efforts in lupus going forward. A Request for Information (RFI) was issued at the end of 2014 to solicit input from the broader community and canvass across the NIH ICs that have an interest and investment in autoimmunity research (and lupus research in particular). A webinar was held in May to obtain input from the scientific community on the draft Action Plan. Later this summer, as the input from the RFI and webinar are incorporated, a subsequent draft of the Action Plan will be posted on the NIAMS web site for public comment. Later this year, it is hoped that a near-final version of the document will be presented to the Council before it is delivered to Capitol Hill.

   After identifying the many ICs that provided input, Ms. Linde described the areas for specific input that were highlighted in the RFI (e.g., most significant advances/publications since 2007, most important scientific opportunities in lupus research, etc.). Significant feedback was received from the RFI, with 36 total submissions from across the country. The areas these comments focused on mapped back to the 2007 research plan and served as the foundation for how the Institute structured the new document. The proposed Action Plan framework, was developed by integrating input from across the NIH and the RFI responses.

   The May webinar included approximately 60 participants, including national lupus experts, scientific and lay representatives from lupus-related professional and patient groups, and NIH IC representatives. The purpose of the webinar was to solicit additional input on the needs and opportunities in lupus research within the proposed Action Plan framework. Key topics discussed during the webinar included etiology and prevention, new treatments and interventions, biopsychosocial and health services research, mechanisms of disease, diagnosis and clinical care, special populations, and training and collaborations.

   In terms of process, next steps include: (1) posting a draft of the Action Plan on the NIAMS web site later this summer for comment, (2) revising the draft plan based on input, (3) providing an update on the Plan to the Council and the Lupus Federal Working Group in the fall, and (4) sending the final Plan to Congress in fall 2015 or winter 2016.

   Dr. Serrate-Sztein’s Division has been heavily involved in the development of the Plan. She commented that the Institute was extremely encouraged by the level of engagement on the part of the community. This is the first time that the NIAMS utilized an RFI and webinar as part of the means to build a plan such as this. To date, very insightful comments have been received, with many specific comments related to the future pathways of discovery in the area of lupus research. Ms. Linde added that, similar to the Institute’s Long-Range Plan (which has been discussed during previous NAMSAC meetings), the Lupus Action Plan is not intended to be comprehensive or prescriptive; rather, it will articulate research needs and opportunities at a broad level. The Plan will not identify specific milestones or objectives that could constrain future interest and future opportunities for the research community.

    

   Discussion

    

   Dr. Khosla asked if the goal of the Plan is to encourage targeted funding for lupus research and what the expected outcome will be. Dr. Katz indicated that the expectations for the Plan depend on the various communities. The research community may expect Funding Opportunity Announcements (FOAs) to arise as a result of the Plan. The Congress may have the same expectation or may call on the NIH for a different action. In recent years, the NIAMS has not issued many targeted FOAs because of its belief that the community should be the driver of good science. Dr. Katz emphasized that the Institute places high priority on meritorious research and on bringing early stage investigators into the Institute’s areas of interest.

7. THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES: CATALYZING TRANSLATIONAL INNOVATION

   National Center for Advancing Translational Sciences (NCATS) Director Dr. Chris Austin briefed NAMSAC members on NCATS activities. He explained that translation is the process of turning observations made in the laboratory, clinic, and community into interventions that improve the health of individuals and the public—from diagnostics and therapeutics to medical procedures and behavioral changes. He also defined translational science as the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. The NCATS studies translation as a scientific and organizational problem. Its mission is “To catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.”

   Dr. Austin explained that every activity of the NCATS is a collaboration, whether it is with another IC, a non-profit organization, a company, etc. The NCATS selects activities as demonstration projects of novel technologies or paradigms that move individual translational projects forward. He listed a number of the scientific translational challenges facing NCATS, including predictive toxicology, predictive efficacy, data interoperability, clinical trial networks, patient recruitment, harmonized Institutional Review Boards (IRBs), adaptive clinical trial designs, etc. The NCATS also faces a number of organizational translational challenges, including data transparency/release, intellectual property (IP) management, collaboration structures, integration of project management, incentives/credit for team science, etc.

   NCATS scientific initiatives are divided into three areas: (1) clinical translational science, (2) preclinical translational science, and (3) re-engineering translational sciences. The largest program within NCATS is the Clinical and Translational Science Award (CTSA) Program. The CTSA program supports a national consortium of medical research institutions; through this program, the CTSAs work together to improve the way clinical and translational research is conducted nationwide, accelerate the research translation process, and provide innovative training for clinical and translation researchers. The 62 current CTSA sites are located across the country. Individually, these centers represent virtually every area of biology in medicine. Collectively, they represent an enormous, rich resource for translational medicine. The NCATS has spent significant time and effort maintaining the local strengths of these CTSAs (which are essential for moving the program forward) while tying them together into a true national network for translational medicine.

   Dr. Austin continued his presentation with descriptions of NCATS’ efforts to:

   • streamline multi-site clinical studies, noting that the current atomized system is inefficient, costly, and often ineffective. Solutions that the NCATS is working on through its CTSAs include centralized IRB review, streamlined contracting through pre-negotiated master agreements, and good clinical practice (GCP) training across CTSA sites.

   • improve participant recruitment issues (e.g., slow or failed recruitment leading to delays, increased costs, and lost efficiency). The NCATS is building a national recruitment capacity across the CTSA network using data from electronic health records to identify potential trial participants who meet entry criteria.

   • train the translational research workforce and provide innovative, tailored curricula, including: (1) non-traditional areas such as regulatory science or entrepreneurship; (2) externships in industry, foundations, FDA, etc., to enrich the training experience; and (3) shared online courses/resources across the CTSA network.

   Dr. Austin also described other activities in which the NCATS is involved. These included:

   • the Office of Rare Diseases Research (ORDR). The ORDR includes the Rare Diseases Clinical Research Network (RDCRN; two groups within the RDCRN are co-funded and advised by the NIAMS—the Brittle Bone Disorders Consortium and the Vasculitis Clinical Research Consortium), the Genetic and Rare Disease Information Center, the Scientific Conferences Program, and the Global Rare Disease Registry.

   • the New Therapeutic Uses Program within the NCATS focuses on the translational problem that roughly 80% of drugs that get into clinical trials in humans are never approved (e.g., for toxicity-related issues, lack of efficacy, or changing business priorities). The concept of this program is match pharmaceutical companies that have clinically active compounds shown to be safe in humans but with no efficacy and therefore are not approved with academic investigators who have new indications for these drugs.

   • the NCATS-Organovo Skin Tissue Printing Project, which includes significant involvement from Dr. Maria Morasso, Chief of the NIAMS Laboratory of Skin Biology. The project is focused on a hydrogel cell paste-based method that can be added to syringes for tissue printing. Multiple cell types are added using the “raft” technique to develop artificial skin (not for use in people, but as a testing system for novel drugs).

   • the NCATS Chemical Genomics Center, which includes roughly 200 collaborations with worldwide experts in every area of biology/disease. He noted that one of the Center’s projects is focused on increasing alpha7 integrin levels for muscular dystrophy.

   • the NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) Program, a collaboration between NCATS laboratories with preclinical drug development expertise and extramural laboratories with disease-area/target expertise.

   • the tissue chip program, the goal of which is to develop an in vitro platform that uses human tissues to evaluate the efficacy, safety, and toxicity of promising therapies. The program began 3 years ago as a partnership with FDA and the Defense Advanced Research Projects Agency. All 10 physiological systems will be functionally represented by human tissue constructs in a modular, reconfigurable platform.

   In closing, Dr. Austin emphasized that NCATS activities are based on collaboration and encouraged Council members to visit www.ncats.nih.gov for additional information on the Center.

    

   Discussion

    

   Dr. Khosla described his institution’s experiences in the CTSA Program, characterizing them as “disruptive innovation” because in its previous iterations, the CTSA Program served a subset of the academic community. With all of the changes brought on by the NCATS, the CTSA Program has now engaged the entire institution, from basic scientists to clinical trialists to late-stage translation experts. From his perspective, the changes brought about by NCATS under Dr. Austin’s leadership have been highly effective.

   Council member Dr. Sherine Gabriel, Dean of the Mayo Medical School, William J. and Charles H. May Professor, and Professor of Medicine and Epidemiology at the Mayo Clinic, echoed Dr. Khosla’s comments and congratulated Dr. Austin for NCATS’ successes. Dr. Gabriel was Co-PI of Mayo’s CTSA in its early years and indicated that one of the differentiating characteristics of the CTSAs have been their efforts at community engagement. She asked Dr. Austin about partnership efforts along these lines with the Patient-Centered Outcomes Research Institute (PCORI) or other groups. She also asked him how the NCATS can help institutions address some of the many organizational challenges associated with translational research. Dr. Austin explained that there are a number of approaches to addressing the organizational challenges associated with translational research. For example, the NCATS is trying to change the system by demonstrating efficiency and cost savings, and by showing that participating organizations then become magnets for opportunities that currently are not available to them. With regard to community engagement activities, Dr. Austin reminded the group that the goal of NCATS is to improve health, and this is best done at the community level. Developing new technologies and interventions must extend to the community level, and there is significant work needed in the areas of engaging patients and communities. The NCATS is trying to inculcate a culture of experimentation, research, and rigor in the context of community engagement. He also noted that the NCATS works closely with PCORI and is engaged in a CTSA-PCORI working group.

   Mr. Silver commented that the RDCRN is very successful and highlights the fact that from the non-profit perspective, the focus is on therapies that can be commercialized, scalable, and turn into sustainable therapies to help patients in the near term. To get a drug through approval for a rare disease, it is becoming increasingly apparent that a network such as this is necessary because they bring with them patient registries and drive collaborations. He asked about institutionalizing the knowledge from the RDCRN such that those who can find funding from other sources can build their own networks (e.g., with industry, individual donors, etc.). Dr. Austin noted that one of NCATS’ operating principles is “develop, demonstrate, and disseminate.” The Center is fully aware that it cannot possibly work on every one of the 7,000+ diseases that affect humans, and so it must develop new approaches, disseminate knowledge, and teach others. This is a core function of the CTSA Program and is an effort that is just starting within the RDCRN. Organizations within the RDCRN are now being incentivized to share information.

8. NIAMS MANAGEMENT OF CLINICAL MENTORED K AWARDS (K08 AND K23)

   Dr. Marie Mancini, Program Officer in the NIAMS Division of Skin and Rheumatic Diseases, reminded Council members that the K08 and K23 awards are meant to enable those with clinical doctoral degrees to develop a research career. K23s are intended for those who plan to perform patient-oriented research. She asked Council members to consider whether the NIAMS can and should make changes to the K08/K23 program that will attract more/better qualified candidates to the program and facilitate more successful outcomes for its K08/K23 awardees (Dr. Mancini noted that there are many ways to define a successful outcome).

   Dr. Mancini presented extensive data and analysis for the numbers, categories and outcomes of K08 and K23 applicants and awardees to Council members. She was then joined by Dr. Boyce, and together they articulated the challenges facing K08/K23 awardees. These include salary limitations, paying for educational debt, protected time/clinical demands, mentoring support, time in training, and transition to independence. Council members were reminded that for the past 3 years, the NIAMS has held a K08/K23 Forum, during which participants are asked to provide information on the challenges they face. Mentors and new R01 recipients who previously had K awards are also asked about their current challenges.

   In considering what the NIAMS can do to address the challenges associated with training physician-scientists, Dr. Boyce asked Council members to consider the following three options:

   • Option 1: Increase the salary cap and/or research support for funded K awardees. The current salary cap for NIAMS K08/K23 awardees is $75,000. Some ICs provide higher levels of salary support. Dr. Katz noted that the NIAMS has maintained the same $75,000 salary cap since the Institute started awarding K08 and K23 awards (approximately 14 years ago). Among the advantages associated with increasing the salary and/or research support for NIAMS K08 and K23 awardees are the facts that there will be less pressure on awardees to write more grants, and there will be less pressure on institutions for salary supplementation. However, the Institute would be providing these additional funds, which would have to come from its budget.

   • Option 2: Enable K08/K23 awardees to collect a supplemental federal salary by reducing K years upon receipt of a research project grant. Dr. Boyce explained that K awardees cannot draw salary from any federal source while they have their award, with one exception: in the final 2 years of the K award, if the awardee successfully competes as a PI on another federal R01-like award, they can drop their effort to 50% and then draw salary up to the NIH salary cap. The NIAMS may be able to take advantage of this policy by: (1) educating Program Officers and K awardees about the option to decrease the length of the K award to accommodate the “50% effort in the last 2 years” rule, or (2) requiring K awardees to decrease the length of their K award to accommodate the “50% effort in the last 2 years” rule. With either option, K awardees would be able to increase their salaries by leveraging other funding sources. And if the length of K awards is decreased, the NIAMS may be able to fund more K awards. However, these options may lead to K awardees spending more time out of the laboratory and in the office writing grants or otherwise chasing down supplemental funds to reach their salaries. These options also will lead to shorter periods of protected time.

   • Option 3: Develop a limited competition FOA for K08/K23 awardees. Dr. Mancini noted that the NIDDK has been taking this approach over the last 10 years. The NIDDK has a small grant program for its K01/K08/K23 recipients to enhance the capability of its K award recipients to conduct research as they complete their transition to fully independent investigator status. Recipients of NIDDK-supported career development awards are encouraged to apply for grant support during the final 2 years of their awards; the grants provide $50,000 in direct costs per year for each of the 2 years. At the NIDDK, roughly 50% of those applying for these grants received them. Dr. Mancini noted that this type of approach provides funding to conduct research to generate data for an R01 submission, which may facilitate the transition to independence. Council members were reminded of data showing that K awardees with supplemental awards (during their K award) have improved outcomes. In addition to increased cost borne by the Institute and as is the case with Option 2 above, a drawback to this approach is that K awardees may end up spending more time out of the laboratory and in the office writing grants or otherwise trying to find supplemental funds to reach their salaries.

   Dr. Katz noted that an additional option is to increase the minimum salary for K awardees as well as the laboratory support for these individuals. Dr. Boyce commented that there are two policy issues that apply to K awardees. Currently, additional salary support from non-federal sources is not allowed; NIH staff are working on getting this changed. The NIH is also looking into possibilities related to the remaining 25% of time for K awardees.

    

   Discussion

    

   Dr. Koretzky noted that a number of K awardees move into industry and would be candidates to apply for an R01; if this was taken into account, the R01 success rates for K awardees would appear even more robust. He also voiced support for increasing laboratory support in the later years of the awards. If it is possible to increase the salary support for K awardees, he suggested that most, if not all, of this additional support be in the form of laboratory support.

   In response to a question from Council member Dr. Christy Sandborg, Professor of Pediatrics at Stanford University, Dr. Mancini explained that K08 and K23 awardees are generally more successful at obtaining an R01 than those without a K award. Dr. Sherry Mills (Director of the Office of Extramural Programs, Office of Extramural Research, NIH) commented that the data presented by Drs. Mancini and Boyce generally reflect trends that are seen across the NIH. She noted that there are important differences between the K08 and K23 applicant pools. While there are more M.D./Ph.D.s in the K08 applicant pool, the K23 applicant pool comprises mostly M.D.s who may have additional training, largely at the Masters’ level. Therefore, it is reasonable to expect that the K08 awardees are likely to see greater success in obtaining an R01 because they have been conducting research for a longer period of time than those in the K23 population. Dr. Mills also noted that because the NIH has seen a downward trend in the number of K award applicants, an RFI was issued to examine this issue.

   Dr. Mills noted that one of the recommendations from the Physician-Scientist Workforce’s Implementation Group was to increase research costs beginning in year 3 of the K award; this recommendation has been met with support from IC Directors as well as members of the Advisory Committee to the Director.

   Council member Dr. Elizabeth Shane, Professor of Medicine and Vice-Chair for Clinical and Epidemiological Research at Columbia University College of Physicians and Surgeons, commented that if the average time to get an R01 is 5+ years, cutting the length of the K award could result in a longer period of time between completing the K award and receiving an R01 award. Dr. Katz noted that during the K08/K23 Forum, awardees are encouraged to apply for R01s earlier in their K award.

   Dr. Koretzky commented that in his view, the most valuable component of the K08/K23 awards is the legislated protected time for the investigators and argued against any action that would decrease this protected time. Improving the salary situation would, in his opinion, be a much more preferred approach for K awardees. Dr. Katz agreed.

   Dr. Mills noted that the NIH as a whole is cognizant of and sensitive to the issues facing K08 and K23 awardees. The NIH is examining these issues and may have some recommendations, guidance, or even a solution for maximizing protected time and salary potential by the time of the next NAMSAC meeting.

   Council member Dr. Amy Paller, Professor of Dermatology in the Feinberg School of Medicine at Northwestern University, noted that grant writing is extremely important, particularly during the training period. She asked if there has been any consideration given to implementing a sliding salary scale similar to that used for R01s. She noted that dermatologists who receive a K award require higher salaries than many other K awardees in other disciplines because they need to be on par with dermatologists in the clinic in terms of base salary. Dr. Katz noted that the NIAMS has one sliding scale arrangement – because the NIAMS had no applicants in the area of orthopedics, the Institute decreased the requirement to 50% time based on an earlier NAMSAC recommendation. Since the implementation of this arrangement, the number of orthopedic applicants has increased. Dr. Katz agreed with earlier comments emphasizing the critical importance of the protected time associated with K08 and K23 awards. Dr. Mills added that reducing the protected time would disproportionately affect those doing clinical research, given that patient recruitment can be a slow process.

   Dr. Katz reminded Council members that the K awards are mentored awards, and that K awardees extend the laboratories’ efforts. Dr. Mills added that when individuals are at the end of their K awards and trying to move towards independence, they need to be less dependent on their mentored support and instead focus on generating their own independent data. This is another argument for providing additional support in the latter part of K awards.

   In response to a question from Council member Dr. Joan Bechtold (Professor of Orthopaedic Surgery at the University of Minnesota), Dr. Mancini explained that in a cohort of K awardees from FY 2001-2008, 12.5% of orthopedic surgeons (one of eight) received an R01 award. It was noted that at present, there are six orthopedic surgeon NIAMS K awardees. Dr. McGowan noted that there is a temporal factor to consider in that orthopedic surgeons with K awards may be participating in many research projects at their institutions before beginning their own R01 projects. It is possible that the number of orthopedic surgeons receiving NIAMS K awards and obtaining a subsequent R01 from this cohort will increase over time.

9. CONCEPT CLEARANCE: CLINICAL STUDIES MANAGEMENT AND SUPPORT

   Dr. Joan McGowan, Director of the Division of Musculoskeletal Diseases, updated Council members on two recent NIAMS roundtable discussions, one on developing 3-dimensional human tissue models to study musculoskeletal and skin physiology and pathophysiology, and one on the role of disc degeneration in neck and back pain. She reminded the group that the roundtable meetings are an integral part of the NIAMS planning process; a roundtable discussion on scleroderma is planned for the end of this month.

   Developing 3-Dimensional Human Tissue Models to Study Musculoskeletal and Skin Physiology and Pathophysiology

   Dr. Laura K. Moen (Director, NIAMS Division of Extramural Research Activities) explained that the Division is responsible for providing clinical trials oversight to the clinical trials that are supported by the Institute in the extramural community. One of the ways the Division accomplishes this charge involves a contractor. Shahnaz Khan, Clinical Coordinator in the NIAMS Extramural Program asked Council members for concept clearance to renew the contract for this work before the contract expires next year.

   Ms. Khan noted that the NIAMS has had a mechanism to assist with providing oversight of its clinical research studies for roughly 20 years. The current contractor provides oversight of approximately 70 active clinical research studies. In the last several years, the NIH has paid increasing attention to clinical trial policies, how studies are managed, better monitoring of study performance, etc. This has led to NIH-wide efforts to re-evaluate existing policies and processes. Due to an increasing demand for more rigorous oversight, there has been more time and effort spent by Institute program staff to manage the clinical study portfolios and by investigators trying to comply with NIAMS’ requirements.

   The specialized services contract that has been in place for the last 20 years has enabled the Institute to carry out functions necessary for adequately managing its clinical studies portfolio. The contract also helps the NIAMS keep pace with the constant changes taking place related to research policies for the use of human subjects. Ms. Khan explained that with the current contract expiring next year, the NIAMS felt that it was an opportune time to re-examine the scope of the activities that have been supported under this contract as well as to consult with its communities to seek out new and innovative ways to design the next phase of the project. The Institute recently issued an RFI and asked the community for input on three points: (1) perceived unmet needs in clinical research and support operations and how addressing these needs could improve an organization’s ability to effectively manage its clinical studies, (2) technological innovations and capabilities required for sharing clinical trial data (as well as the costs and limitations for providing such systems), and (3) critical areas needed to design a clinical support contract. The NIAMS received several responses to the RFI and is in the process of reviewing and evaluating them.

   The Institute’s need for this contract is driven by the following objectives:

   • Support operations and management activities for clinical research studies funded by the NIAMS

   • Provide technical and regulatory expertise that is not available in-house

   • Assist the NIAMS through a centralized and standardized approach to clinical study management and oversight

   Before concluding her remarks, Ms. Khan provided some examples of tasks that the contractor would help support. These include data and safety monitoring committee management and support, clinical study document development and review, biostatistical review and consultation, clinical site monitoring and study assessments, good clinical practice (GCP) training and other training related to the conduct of clinical research, and clinical trial data tracking using electronic systems.

    

   Discussion

    

   Dr. Bechtold asked if the contract requirements could be covered by the activities of NCATS in the future. Dr. Katz explained that the NIAMS will likely need contracted support for these types of activities. Dr. Khosla suggested that the GCP training initiative that the NCATS provides could be useful to the Institute. He also noted that most institutions are now developing electronic systems for monitoring studies to track items such as recruitment in real time. The contracted support is particularly needed for study-specific issues.

   NIAMS Deputy Director Dr. Robert Carter asked Council members at academic medical centers if their home institutions are moving towards allowing for more in-depth data tracking, such as participant-level data that can be accessed by others. Dr. Shane indicated that she is unaware of any institution currently providing participant-level data, but indicated that ultimately, academic institutions will need to move in this direction. Dr. Khosla however commented that his group has been asked to work in this direction; one of the critical aspects of these types of efforts is anonymization of the data to the greatest extent feasible. Dr. Sandborg noted that because of IRB, privacy, and other considerations, there is great reluctance to share these data on the part of academic institutions. Dr. Carter reminded the group that industry, however, is required to share this type of data.

   A motion was made, seconded and unanimously passed to approve the concept.

10. CONSIDERATION OF APPLICATIONS

    In closed session, the Council reviewed a total of 875 applications in closed session requesting $993,755,938 in total costs and recommended 875 for $993,755,938 in total costs. 30 of these applications were considered and approved via early concurrence voting.

11. NIAMS SPECIAL ACTIONS

    This portion of the meeting occurred during closed session.

12. BONE QUALITY

    This portion of the meeting occurred during closed session.

13. ADJOURNMENT

    The 86th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:07p.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.