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

Minutes of the 79th Meeting
8:30 a.m. to 2:15 p.m.

1. CALL TO ORDER

   The 79th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on February 5, 2013, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 6. 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. Lynda F. Bonewald
   Dr. David R. Eyre
   Dr. Gary Firestein
   Dr. Sherine Gabriel
   Ms. Michelle Hofhine (via teleconference)
   Dr. Ted Mala
   Dr. Katherine Mathews
   Dr. Martha Murray
   Dr. Regis J. O’Keefe
   Ms. Jean Pickford
   Dr. Edward Anthony Rankin
   Dr. Elizabeth Shane
   Ms. Elizabeth Smith
   Mr. Bradley R. Stephenson
   Dr. Julio Vergara
   Dr. Xiao-Jing Wang

   Staff and Guests

   Staff

   Mr. Steven Austin Dr. Carl Baker Ms. Pam Beheler Ms. Susan Bettendorf Ms. Elizabeth Bouras Mr. Gahan Breithaupt Dr. Branden Brough Dr. Eric Brown Ms. Justine Buschman Dr. Robert Carter Dr. Faye Chen Dr. Ricardo Cibotti Mr. Richard Clark Ms. Stephanie Craver Ms. Robin DiLiello Ms. Theresa Do Dr. Jonelle Drugan Mr. Erik Edgerton Ms. Elizabeth Elliott Ms. Barbara Footer Ms. Gerda Gallop-Goodman Dr. Nancy Garrick Ms. Valerie Green Ms. Gail Hamilton Ms. Katie Joffee 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. Joan McGowan Ms. Leslie McIntire Dr. Laura K. Moen Ms. Regina Mong Ms. Clairisse Mullsteff Ms. Melinda Nelson Ms. Anna Nicholson Dr. Glen Nuckolls Dr. James Panagis Ms. Vivian Pham Dr. Charles Rafferty Ms. Kelli Reid Ms. Trish Reynolds Dr. Vittorio Sartorelli Dr. Susana Serrate-Sztein Dr. William Sharrock Dr. Richard Siegel Ms. Sheila Simmons Ms. Theresa Smith Ms. Allisen Stewart Ms. Robyn Strachan Ms. Yen Thach Ms. Jamie Thompson Dr. Phil Tonkins Dr. Hung Tseng Dr. Antonella Tullio Dr. Bernadette Tyree Dr. Robert Walker Dr. Fei Wang Dr. Xibin Wang Dr. Yan Wang Dr. Chuck Washabaugh Dr. James Witter Dr. Xincheng Zheng Dr. David Zielinski

   Guests

   Dr. Andrea Baruchin, Foundation for the National Institutes of Health
   Mr. Michael Bykowski, Consolidated Solutions and Innovations
   Mr. Dane Christiansen, Health and Medicine Council of Washington
   Ms. Celeste Crouse, KAI Research, Inc.
   Ms. Patti Brandt Hansberger, Office of Legislative Policy and Analysis, NIH
   Ms. Niva Haynes, National Psoriasis Foundation
   Ms. Leah Howard, National Psoriasis Foundation
   Dr. John Holden, Department of Veterans Affairs
   Ms. Kim Holmes, IQ Solutions
   Ms. Annie Joseph, National Heart, Lung, and Blood Institute, NIH
   Ms. Annie Kennedy, Muscular Dystrophy Association
   Dr. Rajiv Kumar, Center for Scientific Review, NIH
   Dr. Jan Li, Center for Scientific Review, NIH
   Dr. Wenchi Liang, Center for Scientific Review, NIH
   Dr. Yuan Luo, Center for Scientific Review, NIH
   Dr. Daniel McDonald, Center for Scientific Review, NIH
   Ms. Kimberly McGraw, IQ Solutions
   Ms. Karen Mowrer, Association of Independent Research Institutes
   Dr. Sally Rockey, Office of the Director, NIH
   Dr. Joseph Rudolph, Center for Scientific Review, NIH
   Mr. Richie Taffet, Ehlers-Danlos National Foundation
   Mr. Pat White, Office of Legislative Policy and Analysis, NIH
   Ms. Randi Williams, KAI Research, Inc.

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to accept with no changes the minutes of the 78th NAMSAC meeting, held on September 11, 2012.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:

   June 4, 2013
   September 10, 2013
   February 11, 2014
   June 3, 2014
   September 8, 2014

4. DIRECTOR'S REPORT AND DISCUSSION

   Dr. Katz welcomed Council members, NIAMS staff, and guests, and opened his Director’s Report by introducing four ad hoc Council members:

   • Dr. Sherine Gabriel, Dean of the Mayo Medical School, William J. and Charles H. Mayo Professor, and Professor of Epidemiology and Medicine at the Mayo Clinic College of Medicine. Dr. Gabriel is an investigator in the epidemiology of rheumatic diseases and heads the Methodology Core of the Patient-Centered Outcomes Research Institute (PCORI).
   • Dr. Martha Murray, an Associate Professor in the Department of Orthopaedic Surgery at Harvard Medical School and an orthopaedic surgeon at the Children’s Hospital and the Beth Israel Deaconess Medical Center. Dr. Murray was recently honored with the 2013 Kappa Delta Ann Donor Vaughan Award at the Orthopaedic Research Society’s Annual Meeting.
   • Dr. Edward Anthony Rankin, Chief of Orthopaedic Services at Providence Hospital, Clinical Professor in the Department of Orthopaedic Surgery at Howard University College of Medicine, and Clinical Associate Professor at Georgetown University School of Medicine. Dr. Rankin also serves as a member of the Observational Study Monitoring Board of the Osteoarthritis Initiative and is a former President of the American Academy of Orthopaedic Surgeons.
   • Dr. Elizabeth Shane, Professor of Medicine at New York-Presbyterian Hospital, Vice Chair of Medicine for Clinical and Epidemiological Research at Columbia University College of Physicians and Surgeons, and an attending physician at Columbia University Medical Center. Her research interests include osteoporosis in premenopausal women and secondary forms of osteoporosis, including bone loss following organ transplantation. The Irving Institute recently selected Dr. Shane as the inaugural recipient of the Mentor of the Year Award.

   Dr. Katz reported that Council member Dr. Ted Mala, Director of the Traditional Healing Clinic at the South Central Foundation, was inducted into the Royal Order of Kamehameha the First as an Honorary Ali’i (i.e., honorary member of the royal family). The Order’s purpose includes goals such as: (1) preserving and perpetuating the ancient culture, customs, and traditions of Hawaii; and (2) infusing the spirit of patriotism, loyalty, helpfulness, and kindness among its members. Dr. Katz also acknowledged NIAMS grantee Dr. Peter Gregersen, who will be receiving the Swedish Academy of Science’s Crafoord Prize from the King of Sweden in May.

   Dr. Katz then invited Council members to review the NIAMS ShortTakes online, a resource that contains information about NIH initiatives, highlights of Capitol Hill/Department of Health and Human Services/NIH activities, news about personnel changes at the NIH and NIAMS, updates on NIAMS communications and outreach efforts, and Dr. Katz’s “Director’s Column.” In the current ShortTakes, Dr. Katz’s “Director’s Column” focuses on ways in which the Institute interacts with Congress, a topic that has become increasingly important as a way to educate members and their staff about the mission of NIH and NIAMS.

   In October 2012, the NIAMS Coalition hosted NIAMS Awareness Day, which was attended by eight Congressional staff from key appropriations and authorizing committees. Dr. Katz recognized Ms. Sarah D’Orsie of the American Academy of Physical Medicine and Rehabilitation, who is replacing Ms. Tiffany Schmidt of the Muscular Dystrophy Association as Co-Chair of the NIAMS Coalition. Ms. D’Orsie joins Ms. Kim Cantor, of the Lupus Foundation of America, in serving as Co-Chair of the Coalition. Dr. Katz thanked all three for taking on the responsibility of leading the 70 professional and voluntary organizations that comprise the NIAMS Coalition to come together and advance the mission of the Institute.

   Personnel Changes at the NIH and the NIAMS

   In December, NIH Director Dr. Francis Collins announced Dr. Richard Nakamura as the new Director of the Center for Scientific Review (CSR). Dr. Nakamura had been serving as Acting CSR Director for the past 1.5 years. Dr. Nakamura has had a distinguished 32-year career at the National Institute of Mental Health (NIMH), where he served as NIMH Scientific Director, Deputy Director, and Acting Institute Director. Dr. Collins also announced Dr. Christopher Austin as the new Director for the National Center for Advancing Translational Sciences (NCATS). Dr. Austin joined the NIH from Merck in 2002, when he became the Senior Advisor to the Director for Translational Research at the National Human Genome Research Institute (NHGRI).

   At the NIAMS level, the Office of Science Policy, Planning, and Communications (OSPPC) welcomed Dr. David Zielinski to lead its Science Policy and Planning Branch. In this role, Dr. Zielinski will manage NIAMS’ strategic planning, program evaluation, and legislative liaison activities, and will serve as a senior advisor for a range of cross-cutting projects and special initiatives. Ms. Colleen Labbe has also joined the OSPPC as a Senior Science Writer-Editor in the Office’s Communications and Public Liaison Branch. Ms. Labbe will be involved in the Institute’s public outreach and social media efforts. Within the NIAMS Division of Extramural Research Activities (DERA), Ms. Elizabeth Bouras has been named as the new Council Support Specialist, replacing Ms. Sharon Fair who retired from Federal service. Ms. Bouras will assist with many of the activities associated with Council operations.

   Update on Budget and Congressional Activities

   Dr. Katz reported that in fiscal year (FY) 2012, the NIAMS funded 234 new and competing continuation research projects for a success rate of 15.6 percent—a figure higher than the Institute’s FY 2011 rate of 14.9 percent. The overall NIH success rate is estimated at 17.6 percent. He reminded the Council that this historical information is available on the NIAMS website, as is the latest version of the Institute’s funding trends for R01 applications that the NIAMS received and funded in FY 2012. Dr. Katz presented a graph showing the number of R01 applications and awards, as well as the R37s (which are R01-equvalent merit awards for experienced, new, and early stage investigators in 2010), as a function of the scores the applications received during the peer-review process. Council members were asked to let their colleagues know that this information is available.

   For FY 2013, the Federal Government is operating under a Continuing Resolution through March 27, 2013. Congress passed the American Taxpayer Relief Act on January 1, 2013, averting the immediate threat of an 8.2 percent reduction in NIH spending for FY 2013. Dr. Katz explained that when the Institute funds an application, it typically makes a commitment for 4-5 years. In any given year, the Institute has a commitment base representing 70-75 percent of its total budget. A 5 percent decrease in the NIAMS budget would represent a 20 percent decrease in what the Institute can fund with regard to new and competing grants. As Congress and the White House continue to work towards a balanced approach to addressing long-term spending and the budget deficit, the NIH and NIAMS remain committed to ensuring that the available dollars support excellent science.

   President Obama is expected to release his FY 2014 budget early this spring; Dr. Katz indicated that he will provide more information on the President’s FY 2014 budget at the June Council meeting.

   Dr. Katz informed the group that later in the meeting, Mr. Pat White, Associate Director for Legislative Policy and Analysis, would discuss the outcomes of the recent elections, changes to NIH’s authorizing and appropriations committees, and what these changes may mean for the NIH. He also reported that the U.S. Supreme Court decided not to review the Sherley v. Sebelius U.S. Court of Appeals ruling. This decision allows the Appeals Court ruling to stand, and enables the NIH to continue conducting and funding embryonic stem cell research following the strict ethical guidelines established in 2009.

   Highlights of Selected Recent Scientific Advances

   • One of the more devastating sports/recreational injuries is a tear in the anterior cruciate ligament (ACL). More than 100,000 ACL reconstruction surgeries are performed each year in the United States. Researchers participating in the Multicenter Orthopaedic Outcomes Network (MOON) Study, led by Dr. Kurt Spindler at Vanderbilt University, reviewed outcomes data for male and female soccer players who underwent ACL reconstruction. Less than 18 months after surgery, 72 percent of MOON soccer players had returned to competition. Most were playing at an equal or higher level than their pre-injury activities. However, older players and women were more likely to give up the sport following an injury. The researchers also found that the likelihood of suffering a second ACL injury was greater if the athlete was female or had injured the non-kicking leg. This finding suggests that these particular cohorts of patients may benefit from injury prevention programs (Am J Sports Med. 2012 Nov;40(11):2517-22. Epub 2012 Sep 21. PMID: 23002201). Dr. Katz added that roughly 70 percent of people who suffer ACL injuries develop some form of osteoarthritis (OA) within 14 years of their injury. Dr. Murray commented on the importance of this study, noting that the research group includes 13 surgeons from multiple centers and is now following a cohort of more than 2,000 patients. The group is also exploring issues such as which meniscus tears should be fixed, how they should be fixed, and who is more likely to get arthritis. She characterized this as a landmark study (that has been largely funded by the NIAMS) in the field of sports medicine.
   • Epidemiologic studies have indicated that OA progresses more slowly in those who have higher blood levels of vitamin D. Investigators at Tufts Medical Center, led by Dr. Timothy McAlindon, conducted a 2-year randomized, placebo-controlled clinical trial to determine whether vitamin D supplementation improves OA symptoms and alters the progression of knee OA. A total of 146 patients with moderate to severe knee pain and structural damage were enrolled in the study. At the end of the study, both the vitamin D supplementation and placebo groups reported similar levels of pain and had similar structural changes, indicating that vitamin D does not appear to be a suitable treatment for reducing pain or improving structure or function in patients who have knee OA (JAMA. 2013 Jan 9;309(2):155-62. doi: 10.1001/jama.2012. 1644787. PMID: 23299607).
   • It has long been thought that rheumatoid arthritis (RA) pain originated in the affected joints as a result of inflammation. However, evidence that the pain stimulus may originate in the brain or another part of the central nervous system is emerging. Dr. Dan Solomon and colleagues at Brigham and Women’s Hospital conducted one of the first studies to examine how sleep and other factors may influence an RA patient’s pain experience. They found that RA patients had significantly higher blood levels of C-reactive protein, tumor necrosis factor alpha, and interleukin 6 (IL-6) than individuals without RA. These patients also were more likely to experience anxiety, depression, sleep disruption, and “catastrophizing” (i.e., thinking that a situation is worse than it really is). The investigators also found that RA patients are more sensitive to pain. This sensitivity was magnified when sleep problems occurred (Arthritis Rheum. 2012 Nov 1. doi: 10.1002/art.37733. [Epub ahead of print] PMID: 23124650). Dr. Katz commented that this study challenges the conventional thought process that RA pain originates solely in the inflamed joint and could influence how RA patients are treated in the future.
   • Evidence is emerging to suggest that osteocytes send signals to the bone marrow and also influence hematopoiesis. A research team led by Dr. Paola Divieti Pajevic at Massachusetts General Hospital conducted a series of experiments using mice in which osteocytes lacked the G-protein Gs-alpha. Not surprisingly, the mice had disorganized osteocyte networks, fewer osteoblasts, and markedly reduced bone mass. However, the mice also had increased numbers of cells originating in the myelopoietic pathway, which produces cells that organize defenses against invaders and regulate the clotting of blood. Through several additional experiments, the group discovered that osteocytes control myelopoiesis via signals mediated by the Gs-alpha protein. Although further work in this area is needed, it is likely that osteocytes secrete one or more factors that act on hematopoietic cells. This work further underscores the intricate relationship between bone, marrow, and blood (Blood. 2012 Nov 16. [Epub ahead of print] PMID: 23160461). Council member Dr. Lynda Bonewald, Lefkowitz Professor in the Department of Oral Biology in the University of Missouri-Kansas City’s School of Dentistry, explained that it had been thought that the osteocytes sitting in bone were passive cells acting as placeholders. This and other work are changing that understanding, and indicating that there is an endocrine function whereby osteocytes make factors that target other tissues. Dr. Joan McGowan, Director of the NIAMS Division of Musculoskeletal Diseases, added that Dr. Divieti has been funded by the NIAMS to send osteocytes to the International Space Station for study.
   • Appropriate satellite cell activity is necessary for repair and regeneration after muscle injury or in response to muscle atrophy due to illness or aging. Understanding the satellite cell regulation process may enable therapeutic manipulation of the stem cell pool in muscle diseases and disorders for which repair and regeneration of muscle are inadequate. An international team led by Dr. Andrew Brack at Harvard University recently demonstrated how the activation of one signaling pathway can disrupt the repair system and how blocking it can correct it. Using mice, they discovered that satellite cells from aged animals are in the quiescent state for less time than cells from younger animals. Once activated, they do not divide and mature as efficiently as cells from younger animals. The researchers hypothesized that fibroblast growth factor (FGF) was an important part of this phenomenon and tested the effects of stimulating and repressing FGF activity. When they inhibited FGF signaling, aged animals retained more satellite cells. In younger adult mice, stimulation of FGF activity caused the satellite cells to leave their quiescent state (as if the animals were older). These findings show that the aberrant expression of FGF in the aged satellite cell niche leads to dysfunctional satellite cells, which ultimately leads to poor muscle healing (Nature. 2012 Oct 18;490(7420): 355-60. doi: 10.1038/nature11438. Epub 2012 Sep 26. PMID: 23023126).
   • Most facioscapulohumeral muscular dystrophy (FSHD) patients have a reduced number of repeated segments of DNA near one end of the fourth chromosome, and a specific sequence (called the permissive haplotype) in the DNA adjacent to this region. In this type of disease, known as FSHD1, the number of repeats is reduced from more than 100 to 10 or fewer. The repeated DNA units encode the DUX4 protein. In FSHD1, the reduced number of repeated segments, combined with the permissive haplotype sequence, changes the structure of the chromosome to allow the muscle cells to produce DUX4. The DUX4 protein appears to be toxic to mature muscle cells, thus leading to progressive weakness and wasting. Other FSHD patients have normal numbers of these DNA repeats on the fourth chromosome and are designated as having FSHD2. An international team including NIAMS-funded investigator Dr. Stephen Tapscott at the University of Washington, has significantly advanced the field’s understanding of FSHD mechanisms and further established DUX4 as a logical therapeutic target for both FSHD1 and FSHD2. They found that the gene SMCHD1, located on chromosome 18, is required for maintaining the structure of chromosome 4 and preventing DUX4 expression. This work demonstrates that FSHD can be caused by changes in the DNA on different chromosomes, but the common mechanism is increased DUX4 production in the muscle (Nat Genet. 2012 Nov 11;44(12):1370-4. doi: 10.1038/ng.2454. Epub 2012 Nov 11. PMID: 23143600).
   • A series of two papers by Drs. Paul Khavari and Howard Chang from Stanford University and colleagues focused on a class of long non-coding regulatory RNAs (lncRNAs) and identified an lncRNA called terminal differentiation-induced non-coding RNA (TINCR) as a master regulator of keratinocyte differentiation. When TINCR function is lost in the epidermis, genes related to differentiation are not expressed and there is a defect in the barrier layer of the skin. Dr. Katz commented that better understanding of the molecular processes that control keratinocyte proliferation and differentiation could lead to the development of improved drugs to treat a number of skin diseases (Nature. 2012 Dec 2. [Epub ahead of print] PMID: 23157412) (BMC Genomics. 2012 Nov 16;13(1):633. [Epub ahead of print] PMID: 23157412).
   • An international group of investigators led by Dr. Luis Diaz at the University of North Carolina at Chapel Hill identified a key environmental factor that may contribute to the development of endemic pemphigus foliaceus, also known as fogo selvagen (FS) in Brazil. The researchers found that autoantibodies specific for desmoglein 1 in FS patients also recognize the protein LJM11 expressed in the salivary gland of the sand fly (previous work has shown exposure to insect bites—including those from the sand fly—are linked to the development of FS). Dr. Diaz and colleagues also found that mice injected with the LJM11 protein produce antibodies that recognize human desmoglein 1. Based on these findings, they proposed a potential mechanism that may contribute to the onset and/or exacerbation of FS: an insect bite introduces LJM11 into individuals already susceptible to FS, which then initiates an antibody response to LJM11 (J Immunol. 2012 Aug 15;189(4):1535-9. Epub 2012 Jul 13. PMID: 22798673).

   Overview of NIH and NIAMS Activities and Plans

   Dr. Katz announced that NIAMS Scientific Director Dr. John O’Shea was named a 2012 Fellow of the American Association for the Advancement of Science for his distinguished contributions to the field of immunology, particularly for the discovery of the Janus kinase 3(JAK3) and its importance in human disease. The results of Dr. O’Shea’s work recently resulted in U.S. Food and Drug Administration (FDA) approval of the first JAK inhibitor for rheumatoid arthritis. He noted that later in the meeting, NIAMS Clinical Director Dr. Richard Siegel would provide Council members with an overview of progress made by investigators in the NIAMS’ Intramural Research Program (IRP), including a discussion of another NIAMS research activity that led to FDA approval of a drug (anakinra for use in children who have neonatal-onset multisystem inflammatory disease [NOMID]).

   Dr. Katz then discussed workforce issues and training, reminding the Council that training is a key component of the NIAMS mission. Last summer, two working groups of the Advisory Committee to the NIH Director issued recommendations on workforce competitiveness and sustainability as well as workforce diversity. In response to these recommendations, the NIH is proposing several initiatives: (1) two of the proposed programs to increase diversity focus on enhancing mentoring; (2) the NIH is planning to hire its first Chief Officer for Scientific Workforce Diversity, who will develop a comprehensive vision and strategy to strengthen the biomedical research enterprise; and (3) additional activities that will assess and enhance the training of graduate students and postdoctoral researchers who are supported by research grants. The NIH is also moving toward developing a more data-driven basis for assessing the workforce’s evolving needs and for planning its future training activities.

   NIH is changing the way it addresses non-compliance with its public access policy. The policy ensures that the results of NIH-funded research are accessible to everyone in an effort to collectively advance science and improve human health. As announced in a recent Notice in the NIH Guide for Grants and Contracts, beginning this spring, the NIH will delay processing of non-competing continuation grant awards if publications arising from these awards are not in compliance with the public access policy.

   Dr. Katz noted that in addition to research and training, the Institute is responsible for information dissemination. At the last Council meeting, samples of a series of health planners, entitled A Year of Health, were circulated. These planners were developed by the NIAMS National Multicultural Outreach Initiative to provide information and resources about staying healthy and managing conditions of the bones, joints, muscles, and skin. The planners are now available and the response to them has been tremendously positive. Thus far, more than 21,000 planners have been distributed to individuals and organizations across the country. Dr. Katz acknowledged the input received by Council member Dr. Ted Mala, Ms. Jean Pickford (Executive Director of the Foundation for Ichthyosis and Related Skin Types), and Mr. Brad Stephenson (an Attorney-at-Law and Member of the Muscular Dystrophy Association’s National Task Force on Public Awareness). He also thanked Dr. Robert Carter, Ms. Anita Linde (OSPPC Director), and Ms. Mimi Lising (Writer/Editor in the OSPPC’s Communications and Public Liaison Branch) for their leadership in this effort. Dr. Katz encouraged Council members to distribute flyers to groups in their local areas to make them aware of these health resources.

   Dr. Katz announced that the NIAMS has developed a mobile version of its website. At m.niams.nih.gov, users of mobile devices can view NIAMS health information in a layout suited to smaller screen sizes. The Institute’s health information pages now provide for better viewing and easier navigation across a wide range of devices, minimizing the need to resize and scroll. As with other NIH Institutes and Centers (ICs), NIAMS’ website traffic from mobile devices has been steadily increasing. In June 2011, mobile devices accounted for 10 percent of traffic to the NIAMS website. By September 2012, traffic from mobile devices had increased to 24 percent. Dr. Katz thanked the NIAMS Web Team, particularly Ms. Susan Bettendorf, Mr. Danny Heise, and Ms. Allisen Stewart, for their work. He also acknowledged the Institute’s Social Media Team for their continued efforts to advance NIAMS’ communications efforts via Twitter and Facebook. Together, the Institute’s Twitter and Facebook presence brought more than 38,000 visitors to the NIAMS website in 2012. Dr. Katz noted that attendees at conferences and scientific meetings often remark that they saw invitations to visit the NIAMS exhibit booth on Facebook or Twitter. Dr. Katz reported that the NIAMS logo has changed, as will the logos of all NIH ICs. NIH has adopted a single logo for all of the ICs. The new NIAMS logo already appears on the Institute’s website.

   He concluded his Director’s Report by reminding the Council that as a steward of taxpayer dollars, the NIH has a responsibility not just to conduct high-quality research with the goal of making meaningful improvements in people’s lives, but also to communicate back to the American people what they are getting from their investment. On September 8, 2012, the NIH hosted a day of compelling presentations and live remotes as part of a 3-day “Celebration of Science” in collaboration with FasterCures, the Milken Institute’s Center for Accelerating Medical Solutions. The day featured scientists, patients, and caregivers speaking on a variety of topics. There also were discussions with policymakers and industry leaders on the health and economic benefits of biomedical research. Dr. Katz presented a 5-minute video clip with highlights from the event.

5. NIH UPDATE

   Update on NIH Resubmission Policy

   Dr. Rockey informed the Council that in October 2008, following a protracted review of the NIH peer review policy, a Notice was posted in the NIH Guide indicating that: (1) the NIH will accept only a single amendment to an original new or competing renewal application, (2) failure to receive funding after two submissions (i.e., the original and the single amendment) will mean that the applicant should substantially redesign the project rather than simply change the application in response to previous reviews, and (3) it is expected that this policy will lead to funding high-quality applications earlier, with fewer resubmissions. Dr. Rockey explained that in the late 1990s and early 2000s, roughly 60 percent of all applications were funded as A0s (i.e., they were new). From the early 2000s through 2008, the number of A0s funded declined and the number of A2s funded increased, leading to a queue of A2s waiting to be funded.

   Dr. Rockey summarized the effects of this change in policy, explaining that the percentage of all awards made to original (A0) and A1 applications has increased and that A0 awards were funded more frequently in FY 2011 than were A1 awards. The average number of applications required to receive funding has fallen, despite lower overall success rates. Additionally, the time to award from original submission has fallen from 93 weeks in FY 2006 to 56 weeks in FY 2011.

   She then described a proposal for allowing unfunded A1s with percentile scores greater than 25 percent to submit an A2 application. For FY 2011 unsolicited applications, this would amount to 764 applications (546 T1s [new applications] and 218 T2s [renewals]). Dr. Rockey compared these 764 potential A2 applications to the numbers of A2 submissions prior to 2011, explaining that the 764 applications represent approximately 25 percent of the annual, historic A2 submissions between FY 2007 and FY 2010 (about 3,200 per year). Assuming that all of the 764 potential A2 applications are funded, roughly 20 percent fewer A0 and A1 applications would be funded. These displaced A0 and A1 applications are highly likely to come back as A1s and A2s (most displaced A1s would be eligible under the modified policy) and the average time to award would increase.

   NIH leadership has had numerous discussions on this issue, and the decision was made to keep the current policy in place for now (i.e., only one single resubmission of an idea), but its impacts will be closely monitored over the next few years. Dr. Rockey noted that the single resubmission policy is not disproportionately affecting any particular group (e.g., new investigators, women, racial/ethnic minorities, etc.).

   Discussion

   Council members had comments and questions:

   • It was asked whether any analysis has been performed to examine how much science that is judged to be outstanding during the peer review process is lost (i.e., not funded) because of the single resubmission policy. Dr. Rockey explained that there are no specific data on this issue, but most applicants in the “discussed” category tend to come back into the system with some form of another application. It is a difficult issue to analyze, because the NIH has stopped accepting A2 submissions, and it is funding more A0s.
   • Are any particular types of research preferentially favored or disproportionately impacted as a result of the peer review policy? Dr. Rockey indicated that this does not appear to be the case.
   • What about proposals that fall out of the system after the A1 application? Perhaps the NIH should revisit the possibility of changing the policy to allow unfunded A1s with percentile scores above a certain threshold to submit an A2 application, so that the unfunded A1 applications with scores that are not statistically significantly different than funded A1 applications are not lost. Dr. Rockey noted that NIH leadership discussed the possibility of instituting a system in which no amendments are allowed (i.e., every application is a new application). This system is used by some other granting agencies.
   • Some grantees with A1 applications that score, for example, in the 14th percentile are being advised by their institutions to wait for 3 years from submission of their A0 application and then resubmit. Dr. Rockey indicated that the NIH has no policy in this regard.
   • Eliminating A2 submissions and favoring A0 submissions is not a good combination given the current funding environment. In the past, investigators who submitted unfunded A2s had to develop new ideas because it typically would have been 2 years since submission of the original idea, and the science of that original application would be outdated. Now researchers are informed of unfunded A1s about 1 year from the original submission. Asking these individuals to develop brand new ideas when the science is still relatively current may not be the most effective approach. Dr. Katz indicated that the investigators do not necessarily need to develop “brand new” ideas. Dr. Rockey added that researchers do not need to start over and remove themselves from their areas of expertise.
   • The process in place works. The delay in grant funding with multiple submissions progressing to the A2 level slowed research significantly. Study sections have good continuity from first to second submission. However, mixed messages and confusion can result because that continuity is not necessarily in place when applications move from first, to second, to third submissions. The current process is excellent, and getting grants funded sooner and providing investigators with advice earlier is important.

   Biomedical Research Workforce Working Group

   Dr. Rockey then discussed deliberations by the Biomedical Research Workforce Working Group, which reports to the Advisory Committee to the NIH Director. The Working Group was charged with developing a model for sustaining the biomedical work force.

   Dr. Rockey presented a chart to provide a snapshot of the current postdoctoral training workforce. Of the roughly 128,000 biomedical U.S. Ph.D.s trained in 2008, 43 percent are in academic research or teaching, 18 percent are in science-related non-research fields, 18 percent are in industrial research, 13 percent are in non-science related fields, 6 percent are in government research, and 2 percent are unemployed.

   After analyzing a large amount of data, the Working Group made the following conclusions:

   • The large surge in U.S.-trained Ph.D.s, increased influx of foreign-trained Ph.D.s, and aging of the academic biomedical research workforce make launching a traditional, independent, academic research career increasingly difficult.
   • The long training time and relatively low early career salaries when compared to other scientific disciplines and professional careers may make a biomedical research career less attractive to the best and brightest young people. Dr. Rockey noted that the career earnings of biomedical scientists are approximately one-third less than those for individuals who have business degrees, largely due to the lengthy training period associated with advanced biomedical degrees.
   • The current training programs do little to prepare people for anything besides an academic research career, despite clear evidence that a declining percentage of graduates find such positions in the future.

   Dr. Rockey explained that to address these issues, the NIH has proposed:

   • Implementing a grant program to encourage innovative and diversified training approaches to better prepare people for careers in academic research or training, government research, industrial research, and science-related non-research careers.
   • Improving graduate student and postdoctoral training by putting individual development plans in place for all trainees.
   • Reducing the length of graduate training and providing F30s (Ph.D. fellowships) and F31s (multi-degree granting fellowships) from all ICs.
   • Increasing the postdoctoral stipend to $42,000 per year by 2015.
   • Increasing support for K99/R00 and Early Independence Awards.
   • Developing a simple and comprehensive tracking system for trainees.
   • Revising the training grant review processes so that study sections consider a range of career outcomes and all graduate students in relevant programs.
   • Encouraging fair consideration of Staff Scientists on grant proposals.
   • Initiating a discussion with the community to assess NIH support of faculty salary.
   • Creating a functional unit at the NIH to assess the biomedical research workforce.
   • Conducting an Advisory Committee to the NIH Director Working Group study on the optimal research training of individuals in clinical disciplines.

   Dr. Rockey suggested that Council members seeking additional information on these initiatives visit www.grants.nih.gov/grants/oer.htm. She concluded her remarks by inviting Council members to review her blog, called “Rock Talk,” which is available on the NIH Office of Extramural Research website.

   Discussion

   Council members raised the issue of compensation for postdoctoral trainees and noted that the levels of compensation have increased. However, at some institutions, it is less expensive to hire a project scientist or staff scientist who has completed postdoctoral training than it is to hire a postdoctoral trainee. In many cases, graduate students and postdoctoral trainees are unionized and staff scientists are not. Dr. Rockey reminded the group that the concept of having many postdoctoral trainees and graduate students conducting research is the construct that has been built up over the last 25-30 years and is productive. Changing this enterprise will be difficult. She added that there is an ongoing debate as to whether or not students and postdocs who are part of research grants should be considered trainees.

   Others commented that academic medical centers are also part of the equation. With funding levels from the NIH remaining steady for biomedical research, there will be a drop off in the ability for academic medical centers to support research activities and capabilities. In the next 5-7 years, a dramatic shortfall in funding is anticipated, and hospitals that have traditionally been able to make up some of the deficit for their partner academic medical centers are becoming increasingly unable to transfer funds for academic enterprises. The difficulties facing academic medical centers represent an additional challenge to the biomedical workforce of the future. Dr. Rockey noted that an additional recommendation made to the Advisory Committee to the NIH Director is to examine this very issue. Supporting the salaries of faculty members and others who are engaged in research that is totally dependent on NIH funding is a significant challenge, particularly if the NIH funding remains steady and the cost of conducting research continues to increase. A Request for Information will be released on this topic.

6. LEGISLATIVE UPDATE

   Mr. White explained that the new Congress that emerged from the November elections is less Republican—Democrats gained two seats in the Senate and eight seats in the House. Mr. White reviewed changes to the committees of jurisdiction for the NIH. The Senate Health, Education, Labor, and Pensions Committee, which authorizes the NIH, continues to be chaired by Senator Tom Harkin (D-Iowa). Senator Harkin has been a staunch advocate and defender of the NIH and of biomedical research in general. At the age of 73, he has decided not to run for re-election in 2014. The top Republican on the Senate Health, Education, Labor, and Pensions Committee is now Senator Lamar Alexander (R-Tennessee). Senator Alexander is a former President of the University of Tennessee and served as Secretary of Education during the George W. Bush Administration. Mr. White explained that Senator Alexander has a deep appreciation for biomedical research and research universities. Senator Alexander requested a recent National Research Council study on the future of research universities.

   The House Energy and Commerce Committee remains largely the same, and will be chaired by Representative Fred Upton (R-Michigan). Representative Henry Waxman (D-California) will be the ranking member.

   The Senate Labor, Health and Human Services, and Education Appropriations Subcommittee will continue to be chaired by Senator Harkin. It appears as though Senator Jerry Moran (R-Kansas) will become the ranking member. Mr. White noted that this is encouraging news—Senator Moran has worked closely with the University of Kansas and the Kauffman Foundation in support of biomedical research. As a member of this Subcommittee, Senator Moran has offered amendments in an attempt to increase NIH funding. During the last Congress, Senator Moran visited the NIH twice, and has expressed interest in visiting again in the near future.

   The House Labor, Health and Human Services, and Education Appropriations Subcommittee has a new Chair, Representative Jack Kingston (R-Georgia). The top Democrat in this Subcommittee will be Representative Rosa DeLauro (D-Connecticut), who has been a long-time supporter of the NIH.

   Mr. White then described some new roles and new faces in Congress. Senator Barbara Mikulski (D-Maryland), who has described herself as “the Senator from NIH,” is now the Chair of the Senate Appropriations Committee and the first woman to hold that position. She has expressed interest in visiting the NIH in the near future. Congressman Jack Kingston (R-Georgia) recently returned from a Congressional delegation that traveled to sites of NIH-supported activities in India and Bangladesh. Mr. White explained that Congressman Kingston is a strong advocate for the NIH and appreciates the value of biomedical research. Dr. Tim Murphy (R-Pennsylvania) is a psychologist and now chairs the House Energy and Commerce Committee’s Oversight Subcommittee. Dr. Murphy is an expert on children’s mental health and has taken a strong interest in issues of mental illness and violence, particularly in the wake of the Newtown, Connecticut, tragedy.

   He then turned to the topic of sequestration, which is supposed to be ordered by the President on March 1, 2013. Cuts are supposed to take effect on March 27, 2013. In September 2013, the Office of Management and Budget (OMB) released gross numbers associated with a then-expected 8.2 percent sequestration. Mr. White commented that the numbers are in flux and keep changing—currently it appears that, if sequestration occurs, the reduction will be less than 6.4 percent, and perhaps as low as 5.5 percent. However, the actual percentage reduction for the NIH is unclear at present.

   After reviewing the timeline for sequestration and the debt ceiling, Mr. White reminded the Council that the Government is operating under a Continuing Resolution through March 27, 2013. The American Taxpayer Relief Act was passed on January 1, 2013, and as a result, the immediate threat of an 8.2 percent cut in NIH spending for FY 2013 was averted.

   Discussion

   It was asked if sequestration is inevitable. Mr. White indicated that this appears to the case. The most significant development suggesting that sequestration is imminent is that there is a growing sentiment among House Republicans who are willing to accept cuts to the Department of Defense because of their strong commitment to deficit reduction. He added that although no one in Congress wants to see sequestration occur, it will make a significant down payment with regard to deficit reduction. In response to a question from Dr. Katz, Mr. White indicated that it is unlikely that there would be a Government shutdown.

7. NIAMS INTRAMURAL RESEARCH PROGRAM (IRP)

   Dr. Siegel opened his presentation by reminding the Council that the NIAMS IRP comprises roughly 10 percent of the Institute’s total budget and is almost completely funded by federal dollars. IRP projects are rigorously reviewed by the Institute’s Board of Scientific Counselors. The IRP enables the Institute to pursue sustained investigations of major questions over a long period of time, focusing on “high-risk, high-reward” science. As part of the NIH Campus that includes the Clinical Center, the IRP provides opportunities for the rapid translation of discoveries into clinical trials. The IRP is also flexible enough to allow for rapid implementation of new technologies and breakthroughs.

   The NIAMS IRP includes roughly 250 total staff in a small number of laboratories. Seven IRP Principal Investigators (PIs) are clinically trained. Dr. Siegel characterized the trainees as the “lifeblood” of the IRP. The NIAMS IRP includes summer students as young as 16 years old, postdoctoral students (graduate students, medical students, and M.D.-Ph.D. students), and clinical and postdoctoral trainees. The NIAMS IRP runs the Rheumatology Fellowship Training Program and houses the Office of Science and Technology. It also hosts Centers (e.g., the Center for Regenerative Medicine), and there are administrative support and career development components.

   Dr. Siegel discussed next-generation sequencing, an investment made by the NIAMS IRP a few years ago that has paid off tremendously. He explained that the way the human genome was originally sequenced was by taking individual pieces of DNA, cloning them, and sequencing them one by one. Next-generation sequencing has had an extremely significant impact (Dr. Siegel likened it to the impact that the iPhone and other smart phones have had on technology). The process starts with the same pieces of DNA, but is then carried out such that stored sequences of up to 50 base pairs are grown on various platforms that are read in parallel, resulting in the generation of millions of sequences at the same time. This approach has allowed for whole-genome approaches to almost every aspect of biology.

   Next-generation sequencing has evolved into a host of different techniques, such as direct sequencing of RNA (known as RNA-Seq), transcription factor binding or chromatin modification (known as Chip-Seq), whole-axome or whole-genome sequencing looking for disease-causing mutations, looking at modifications such as DNA methylation, examining chromatin-chromatin interactions and sequencing them, and sequencing translocations to make a genome-wide view.

   The results of next-generation sequencing yield tremendous amounts of data. The NIAMS IRP has become more efficient in synthesizing these data, which has driven down the cost of these types of experiments (to the point where a whole genome can be sequenced for as little as about $5,000). Dr. Siegel noted that there has been an impressively large amount of published work from NIAMS IRP investigators as a result of the investment in next-generation sequencing technology, which has been leveraged into major discoveries. Dr. Siegel briefly reviewed some of these discoveries (e.g., using Chip-Seq to make discoveries in the areas of transcription factor binding and programming of T cell differentiation and using translocation sequencing to produce translocation maps of the B cell genome).

   Dr. Siegel noted that the laboratory of Dr. Vittorio Sartorelli (newly appointed as NIAMS Deputy Scientific Director) recently made a discovery related to the EZH proteins, which regulate transcriptional activation and repression. He and his colleagues found that the transcriptional repressor EZH2 helps muscle stem cells remember what they are (i.e., EZH2 allows muscle stem cells to retain unique histone marks and transcriptional identity—that identity allows them to differentiate appropriately). Without EZH2, muscle cells essentially “forget what they are” and non-muscle transcripts start being made. Knockout mice lacking EZH2 do not appropriately regenerate their muscle and have lower muscle mass. Dr. Siegel explained that this work shows that EZH2 is a checkpoint where the partner transcription factor, EZH1, allows transcription to proceed unchecked. This fundamental observation was made through the help of next-generation sequencing, and was done in a cost-effective manner because the technology was available from within the NIAMS IRP.

   Dr. Siegel then discussed the NIAMS IRP Clinical Program, which has increased its focus on conducting investigational new drug trials and includes a fellowship program, consult services, clinics in subspecialty areas, and a community outreach center. He presented advances from the Clinical Program, one of which relates to the genetic causes of certain autoinflammatory diseases. Neonatal Onset Multisystem Inflammatory Disorder (NOMID) is a severe consequence of activating mutations in the CIAS1 gene. In 2003, soon after this mutation was discovered, NIAMS IRP investigators began treating a cohort of patients on a therapy based on the discovery that NOMID is an IL-1 related disease. This treatment, a drug called anakinra, was a tremendous success due to its ability to block the effects of IL-1beta. It normalized much of the skin, eye, brain, and ear inflammation in these patients. Anakinra had been FDA approved for use in adults with rheumatoid arthritis, but not for any indication in children. However, over the last 6 years, long-term outcome studies have shown that anakinra is effective and safe for use in children. A few weeks prior to this Council meeting, anakinra was approved by the FDA for use in children (the first pediatric approval for this IL-1 receptor antagonist).

   Dr. Siegel also discussed work on JAK3 inhibitors by scientists in the NIAMS IRP Clinical Program, noting that in 1994, it was discovered that the JAK3 protein controls cytokine signaling in immune cells. This discovery was made in the context of severe combined immunodeficiency in children who either lacked the gene or had mutations in the gene coding for JAK3. This finding led to the concept that JAK3 inhibitors could be immunosuppressive. In November 2012, tofacitinib was approved for moderate to severe RA. This is the first time in a decade that FDA has approved an oral disease modifying antirheumatic drug, or DMARD, for the treatment of RA. This broad class of drugs slows or halts the progression of damage from the disease, rather than merely providing relief from symptoms. Dr. Siegel reminded the group that FDA approval of a drug for use in one disease makes it significantly easier to pursue trials examining the safety and efficacy of the drug in treating similar diseases.

   Dr. Siegel described other ongoing studies within the NIAMS IRP Clinical Program, including the safety and tolerability of omalizumab in patients with lupus, and stopping the use of anti-TNF agents in patients with RA who are in clinical remission. He reminded Council members that information on the NIAMS IRP is available on the Institute’s website.

   Dr. Siegel concluded his remarks by discussing the NIH Rheumatology Fellowship Training Program, which is housed within the NIAMS IRP. Based on the realization that 2-3 years is not sufficient to create tenure-track faculty, the Institute developed the Scholars in Translational Research Program, which is a 4-year senior fellowship program for laboratory- or clinical-based researchers.

8. NIH COUNCIL OF COUNCILS UPDATE

   Dr. O’Keefe reminded the group that the NIH Council of Councils advises the NIH Director on matters related to the policies and activities of the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI). The Council of Councils has three face-to-face meetings and multiple conference calls per year. At the last meeting, NIH Principal Deputy Director Dr. Lawrence Tabak provided an overview of current major initiatives and described the budgetary issues facing the NIH. The Council of Councils was also updated on:

   • Ongoing efforts to integrate substance abuse programs housed at the National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA)
   • Workforce issues and the sustainability of the research enterprise
   • Communication issues (e.g., increasing the visibility of the excellent work done by the NIH, which is not as widely recognized as it could be)
   • Activities at the National Center for Advancing Translational Sciences (NCATS)

   Dr. Regis O’Keefe, Chair of the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center, noted that many DPCPSI activities relate to Common Fund programs that are cross-cutting throughout the NIH and focus on areas of emerging and important research (e.g., proteomics, workforce development, global health, etc.). A number of research grants are reviewed through DCPCSI programs. The NIH Council of Councils is responsible for grant concurrence, special reviews and appeals of these grants, and for providing input on concept clearance.

   The NIH Council of Councils has been addressing the use of chimpanzees in research for the last year. In December 2010, the NIH commissioned the Institute of Medicine (IOM) to assess the need for chimpanzees in behavioral and biomedical research. The IOM released a report roughly 1 year later, and made the following recommendations: (1) the knowledge gained must be necessary to advance the public’s health; (2) there must be no other research model by which the knowledge could be obtained, and the research cannot be ethically performed on human subjects; and (3) the animals used in the proposed research must be maintained either in ethologically appropriate physical and social environments (i.e., as would occur in their natural environment) or in natural habitats.

   Dr. Collins accepted the IOM’s recommendations and requested that the Council of Councils develop an implementation plan. The Council of Councils Working Group on the Use of Chimpanzees in NIH-Supported Research was formed to review in detail approximately 30 ongoing NIH grants that use chimpanzees for research purposes. Specifically, the Working Group was charged to:

   • Analyze currently active NIH-supported research using chimpanzees to advise on which studies currently meet the principles and criteria defined by the IOM report and advise on the process for closing studies if they do not comply with the IOM recommendations.
   • Advise on the size and placement of active and inactive populations of NIH-supported chimpanzees that may need to be considered as a result of implementing the IOM recommendations.
   • Develop a review process for considering whether potential future use of the chimpanzee in NIH-supported research is scientifically necessary and consistent with the IOM’s principles.

   The Working Group’s final report was delivered to the Council of Councils on January 22, 2013. Dr. O’Keefe commented that the use of chimpanzees in research is a controversial subject—their use has been part of the research enterprise for many years, and IOM’s recommendations represent a significant change. In its report, the Working Group indicated that chimpanzees offer tremendous value in the areas of behavioral research and genetic research. In infectious diseases, however, chimpanzee research has not been as valuable (with the exception of some hepatitis-related research). There appear to be other appropriate small animal models that could be used to replace the chimpanzee population with regard to the infectious disease research projects the Working Group reviewed. The Working Group recommended conditionally approving a number of applications and continuing some ongoing research projects while recommending that others end. Overall, the report had 28 recommendations, 10 related to ethologically appropriate environments, 9 related to colony size and placement, and 9 related to the review process. A committee has been formed to provide guidance on whether the IOM’s recommendations have been met for all future NIH-supported research grants that propose using chimpanzees.

9. OVERVIEW OF THE NIH POLICY ON INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH

   Ms. Shahnaz Khan, Clinical Coordinator in the NIAMS Division of Extramural Research Activities, reviewed the history of NIH’s policy on the inclusion of women and minorities in clinical research and provided an overview of the Council’s role in reviewing the biennial inclusion data. She noted that the NIAMS-specific data are included in the written Biennial Report that was distributed to each Council member.

   Ms. Khan explained that the idea of including women and minorities in biomedical and behavioral research began more than 25 years ago. In 1993, through a Congressional mandate (as part of the NIH Revitalization Act), the NIH was required to establish guidelines for the inclusion of women and minorities in clinical research. In 1994, the NIH revised its inclusion policy. This policy was amended in 2001 with four major updates: (1) an update on the definition of “clinical research” that had been used since 1997, (2) an update on racial and ethnic categories to more closely align with OMB standards, (3) clarification on the language for NIH-defined Phase III clinical trials, and (4) identification of the roles and responsibilities of NIH staff and the extramural community.

   There are several ways that the NIH and NIAMS ensure adherence to the inclusion policy. Ms Khan explained that during peer review, review committee members evaluate the inclusion plans and those applications that lack acceptable plans receive a bar to funding. In addition to including women and minorities, the acceptability of including children is also evaluated. Once studies are funded, Program Directors ensure that the investigators are complying with the proposed plans for including women and minorities by reviewing the inclusion enrollment tables submitted with annual progress reports. Every 2 years, the NIH Office of Research on Women’s Health, on behalf of the NIH Director, reports to Congress on the number of women and minorities that have been involved in all NIH-supported clinical research. This report includes a statement from each IC’s Advisory Council to confirm compliance with the NIH policy.

   The role of the NAMSAC is to ensure NIAMS’ compliance with the inclusion policy. The written report distributed to Council members includes a description of the Institute’s efforts to ensure compliance with the law and the numbers of women and minorities enrolled in Institute-supported research over the last 2 years. These data indicate that in 2011 and 2012, the total number of enrolled participants has decreased. However, fluctuations in the number of enrolled participants are expected, given that new studies are continuously starting enrollment while other studies end. Ms. Khan explained that the goal of the inclusion policy is to monitor trends in the recruitment of women and minorities. As in previous years, the NIAMS is funding clinical research that represents all of the minority groups and women in the United States.

   Dr. Katz commented that one of the goals of the inclusion policy is ensuring that investigators interpret and analyze data from NIH-funded studies so that the findings are as relevant for women, children, and minorities as they are for men.

   The Council unanimously voted to approve the Institute’s Biennial Inclusion Report.

10. UPDATE ON THE EVALUATION OF NIAMS CENTERS PROGRAMS

    Dr. Carter explained that the NIAMS is evaluating the Centers it funds as well as the structure of the Centers programs. The forward vision for Centers is to focus on areas of research in which progress would benefit from integrated, synergistic groups of investigators. Such synergy can be built through multidisciplinary research, shared resources, and cooperative technological innovation. NIAMS’ goal with regard to the Centers programs is to design funding strategies to optimally support synergistic groups of investigators, based on needs and opportunities identified by the community. Dr. Carter emphasized that this review is not taking into consideration the relative budget of the total Centers program (versus Research Project Grants), program project (P01) type projects, the performance of any individual Center, or clinical trials Center networks.

    To date, a number of meetings and listening sessions have been held to seek input from relevant stakeholders. Dr. Carter reported that these discussions have been overwhelmingly positive and have fostered a shared understanding that the Institute is trying to most effectively support groups of investigators in the future. Through these meetings and listening sessions, a number of themes have emerged. These include the need to share technical and clinical resources more broadly, the need for greater flexibility to pull groups of researchers together, the need for multidisciplinary science, and the need for Centers to bring groups together in a way that would be difficult to accomplish through R01s and related mechanisms. The Centers Evaluation Working Group is taking the themes that arose during the listening sessions and meetings and creating goals to summarize what the NIAMS may want to consider as it restructures its Centers program. A March 11, 2013, meeting of the Working Group will focus on refining and categorizing these themes and then making recommendations as to how the NIAMS can achieve its Centers-related goals. Dr. Carter noted that the NIAMS issued a Request for Information on this topic to obtain formal feedback from professional organizations, individuals, and institutions.

    The Council will receive an update on this effort at its June meeting.

11. NIAMS FORUM FOR CLINICAL MENTORED K AWARDEES

    Dr. Marie Mancini, Health Scientist Administrator in the NIAMS Division of Skin and Rheumatic Diseases, reminded the group that the K08 Awards (Mentored Clinical Scientist Development Research Career Awards) and the K23 Awards (Mentored Patient-Oriented Research Career Awards) are intended to provide protected time for clinicians to train under a mentor with the goal of research independence. The K08s are for clinicians who are conducting non-patient oriented research (e.g., basic translational research). The K23s are for clinicians conducting patient-oriented research.

    The NIAMS Forum for Clinical Mentored K Awardees was held on December 13-14, 2012, to: (1) discuss challenges junior investigators face in pursuing research independence, (2) allow awardees an opportunity to network with each other and interact with NIAMS extramural staff/leadership, and (3) enhance the Institute’s support of early stage physician scientists. From the NIAMS perspective, there were two overarching questions guiding the discussions at the Forum:

    • What are the obstacles to becoming an independent clinical scientist?
    • What can the NIAMS and the broader scientific community do to support these clinical scientists?

    Forum participants included third-year K08 and K23 awardees, recent K awardees who have independent research careers, and established investigators/representatives from professional/voluntary organizations. Prior to the Forum, participants were asked to complete a survey describing obstacles they face, what the NIAMS and the medical community can do to help clinician-scientists, and what challenges they see with regard to accessing NIH or university research resources. The Forum began with an overview of each K awardees’ research, followed by breakout sessions with NIAMS staff (for K awardees) and a presentation on the role of the NIAMS Centers program in career development activities (for all other participants). The Forum also included a review of historical data about these awards and a group discussion on the K Career Development Award and transitioning to an R01 award.

    Dr. Mancini noted that as part of a 2007 NIAMS training grant and career development award program evaluation, the following recommendations were made: (1) change the K Award structure to allow for more flexibility on the percent effort requirement and for other sources of funding; (2) create a bridge-type award to support trainees while they are pursuing a K award; and (3) support interdisciplinary approaches, reinforce the value of mentorship, and work together with other NIH ICs and private foundations. Dr. Mancini noted that the NIH has lowered the percent effort requirement from 75 percent to 50 percent for the last 2 years of a K Award to allow concurrent support from an R01 or equivalent to allow K awardees to transition to independent support more quickly. At the NIAMS, the percent effort requirement was lowered to 50 percent for surgeons from the start of the award.

    A 2011 NIH-wide program evaluation of the K01, K08, and K23 awards was conducted to examine who was applying for and receiving these awards, and the impact of participation on research productivity and independent careers. The evaluation included a comparison group of unfunded applicants (matched by IC and year) to test the impact of the program on research careers. It was found that K awardees were more likely to have research publications, were more likely to apply for subsequent NIH research funding, and had a significantly higher R01 award success rate than the pool of individuals with no prior career development support. Dr. Mancini explained that the K awards appeared to have the greatest impact on the subsequent NIH research involvement of M.D. recipients, followed by M.D./Ph.D. recipients, and then Ph.D. recipients.

    Turning the discussion back to the December 2012 NIAMS Forum for Clinical Mentored K Awardees, Dr. Mancini explained that the NIAMS focused on both the present (how to make the most out of K career development) and the future (planning a successful transition to an R01). The following key messages arose during the Forum:

    • K awardees would benefit from informational session(s) early in their award to discuss policy, other award options, etc.
    • The importance and roles of mentors was highlighted, and there is great value associated with the mentoring team approach.
    • Organizations that are committed to supporting research career development should consider a type of K Award supplement and/or bridge funding.
    • Increased interactions among the NIAMS, K awardees, and mentors may provide needed encouragement and impetus.

    Discussion

    Dr. Bonewald, who attended the Forum, indicated that there was a very high energy level at the meeting, and she was struck by comments from participants who said that they were unaware of the degree to which the NIH cares about these young investigators and what they are doing. She added that getting together in a face-to-face setting provided these awardees with a great deal of important information. She suggested that if possible, it would be extremely beneficial to hold a meeting like this on a regular basis.

    Dr. Shane, who also attended the Forum, commented that it was inspiring to see the quality of the research being conducted by these awardees. In many cases, the quality of the K award research was on par with what would be expected in an investigator’s first R01 award. She also was impressed with the resourcefulness of the K awardees in how they had sought out additional funding to help them achieve their goals. She echoed Dr. Bonewald’s comments about the advantages of holding subsequent face-to-face meetings with K awardees. Dr. Katz indicated that the NIAMS hopes to hold another meeting in 2013 for K awardees during the third year of their funding.

    Dr. O’Keefe commented on the importance of the K awards and noted that the clinical time commitment for surgeons who are K awardees is extremely challenging, particularly early in their career when they are trying to develop appropriate surgical skills and take care of patients. The NIAMS has been forward thinking in this area by reducing the percent of effort required for surgeons.

12. COUNCIL OPERATING PROCECURES

    Council Executive Secretary Dr. Laura K. Moen, Director of the NIAMS Division of Extramural Research Activities, presented the Statement of Understanding between the Advisory Council and the Institute, which was provided to Council members in advance of this meeting. As outlined in the Statement of Understanding, NIH and/or NIAMS policy requires that the following applications be called to the attention of the Council:

    • Any application with a concern identified by an initial review group in any of the following areas: animal welfare, human subjects, ethical issues, recombinant DNA, potential biohazards, and inclusion of women and minorities in clinical research.
    • MERIT Awards and MERIT extensions.
    • Any application from a foreign institution for which an award is planned.
    • Any application identified by members of the Council to be of special concern or as posing special policy issues.
    • Any application previously deferred for additional information or for re-review by Council.
    • Any application identified by NIAMS staff as requiring special consideration or discussion by Council. These applications are generally identified by a staff action to Council summarizing the concerns of staff.
    • Applications from investigators currently receiving $1 million or more in annual direct costs for research support from NIH.

    A motion to approve the Council’s Operating Procedures was made and seconded. The Operating Procedures were unanimously approved.

13. CONSIDERATION OF APPLICATIONS

    The Council reviewed a total of 721 applications in closed session requesting $901,247,559 in total costs and recommended 721 for $901,247,559 in total costs.

14. PORTFOLIO ANALYSIS

    This portion of the meeting occurred during closed session.

15. ADJOURNMENT

    The 79th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 2:15 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.