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

Minutes of the 76th Meeting
January 31, 2012
8:30 a.m. to 3:30 p.m.

1. CALL TO ORDER

   The 76th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on January 31, 2012, 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. Lynda F. Bonewald
   Dr. Leslie J. Crofford 
   Dr. Harry C. Dietz III
   Ms. Karen B. Evans
   Dr. David R. Eyre
   Dr. Gary S. Firestein
   Dr. Linda Griffith
   Ms. Michelle Hofhine
   Dr. Henry M. Kronenberg
   Dr. Ted Mala
   Dr. Katherine Mathews
   Dr. Regis J. O�Keefe
   Dr. Alice P. Pentland
   Ms. Jean Pickford
   Ms. Elizabeth Smith
   Mr. Bradley R. Stephenson
   Dr. Julio L. Vergara
   Dr. Xiao-Jing Wang

   Staff and Guests

   Staff

   Mr. Steven Austin Dr. Carl Baker Mr. Gahan Breithaupt Dr. Branden Brough Dr. Eric Brown Dr. Robert Carter Dr. Faye Chen Dr. Ricardo Cibotti Ms. Stephanie Craver Ms. Robin DiLiello Dr. Jonelle Drugan Mr. Erik Edgerton Ms. Elizabeth Elliott Ms. Sharon Fair Ms. Gerda Gallop-Goodman Dr. Nancy Garrick Ms. Kaitaia Huynh Mr. Andrew Jones Dr. Stephen Katz Ms. Mary Beth Kester Mr. Mark Langer Dr. Gayle Lester Ms. Anita Linde Ms. Leslie Littlejohn Dr. Marie Mancini Dr. Su-Yau Mao Dr. Kathryn Marron Dr. Joan McGowan

   Ms. Leslie McIntire Ms. Sherry Meltzer Dr. Laura K. Moen Ms. Regina Mong Ms. Melinda Nelson Dr. Glen Nuckolls Dr. James Panagis Ms. Vivian Pham Dr. Charles Rafferty Ms. Kelli Reid Ms. Natalie Reyes Ms. Trish Reynolds Dr. Louise Rosenbaum 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. Bernadette Tyree Dr. Fei Wang Dr. Chuck Washabaugh Ms. Sara Rosario Wilson Dr. James Witter

   Guests

   Dr. Andrea Baruchin, Foundation for the National Institutes of Health
   Mr. Michael Bykowski, Consolidated Solutions and Innovations
   Ms. Celeste Crouse, KAI Research, Inc.
   Ms. Tanya Dougans, National Heart, Lung, and Blood Institute, NIH
   Ms. Ann Elderkin, American Society for Bone and Mineral Research
   Dr. John Holden, Department of Veterans Affairs
   Dr. Robert Kaplan, Office of Behavioral and Social Sciences Research, NIH
   Ms. Annie Kennedy, Muscular Dystrophy Association
   Ms. Patricia Kobor, American Psychological Association
   Ms. Rebecca Kolberg, Office of the Director, NIH
   Dr. Raya Mandler, Center for Scientific Review, NIH
   Ms. Meg Pilarcik, Scleroderma Foundation
   Ms. Sheila Rittenberg, National Psoriasis Foundation
   Ms. Maria Spencer, Arthritis Foundation
   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 75th NIAMS Advisory Council meeting, held on September 27, 2011.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:

   June 5, 2012
   September 11, 2012
   February 5, 2013
   June 4, 2013
   September 10, 2013

4. DIRECTOR'S REPORT AND DISCUSSION

   Dr. Katz welcomed Council members, NIAMS staff, and guests. He invited attendees 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." Dr. Katz�s "Director�s Column" focuses on how the NIAMS can continue to encourage and support the best, most pressing, and meaningful science in light of the projected budget scenario (this has been a frequent topic of discussion during recent Council meetings). Dr. Katz noted that the NIAMS will continue to rely on the Council for its input on the budget as the Institute moves toward fiscal year (FY) 2013.

   Dr. Katz introduced four new Council members:

   • Ms. Michelle Hofhine, a Registered Nurse and Vice President of Marketing at Accredited Home Care Services in Southern California. Ms. Hofhine conducts community outreach research and comes to the Council with the perspectives of a health care provider and a parent of a child who has osteogenesis imperfecta.
   • Dr. Katherine Mathews, Director of the Division of Pediatric Neurology at the University of Iowa Children�s Hospital. Dr. Mathews has co-authored numerous basic, clinical, and epidemiologic publications. She serves as the Co-Principal Investigator (PI) on several large awards funded by the NIH and Centers for Disease Control and Prevention.
   • Ms. Elizabeth Smith, a patient advocate who has been involved with the Arthritis Foundation for more than 10 years. At the NIAMS 25th Anniversary Symposium, Ms. Smith�s daughter spoke about her experiences with juvenile arthritis and alopecia—two chronic diseases within the NIAMS mission.
   • Dr. Xiao-Jing Wang, Director of the Head, Neck, and Skin Cancer Research Program at the University of Colorado in Denver. Dr. Wang and her research team are interested in the molecular mechanisms of head and neck cancers and inflammatory skin diseases, and in identifying the factors that influence normal stem cell fate during embryonic skin development.

   Personnel Changes at the NIH/NIAMS

   At the NIH level, Dr. Toni Scarpa has retired from his role as Director of the Center for Scientific Review (CSR). Dr. Katz, who is a member of the search committee to replace Dr. Scarpa, noted that applications for this position will be accepted through February 17, 2012. Dr. Chris Kaiser has been selected as the new Director of the National Institute of General Medical Sciences (NIGMS). Dr. Kaiser comes to the NIH from the Massachusetts Institute of Technology, where he led the Department of Biology since 2004. The NIH expects Dr. Kaiser to start his new position in the spring of 2012.

   At the NIAMS level, the search for a new NIAMS Intramural Research Program (IRP) Clinical Director is ongoing. After 40 years of service, Ms. Robyn Strachan, who has led the NIAMS Financial Management Branch since 1994 and has been a key member of the NIAMS senior staff, has retired from the federal government. Ms. Strachan has agreed to work as a Senior Advisor to the NIAMS on a part-time basis. Ms. Robin DiLiello has been jointly serving as the Chief Budget Officer and will continue to lead the office. Dr. Janet Austin has retired as the Director of the Office of Communications and Public Liaison (OCPL) after 12 years of service in this role. Dr. Katz commented that during her tenure, Dr. Austin brought tremendous vision and energy to the position, greatly enhancing the productivity and visibility of the OCPL. Dr. Michael Bloom, who served as a Scientific Review Administrator for 6 years at the NIAMS has recently taken a new position at the CSR. The Institute is currently recruiting to fill this position.

   Update on Budget and Congressional Activities

   Dr. Katz reported that in FY 2011, the NIAMS funded 228 new and competing continuation applications for a success rate of 14.9 percent (a figure much lower than last year�s rate of 21.4 percent, and lower than the overall estimated NIH success rate of 17.7 percent). For the past 7-8 years, the NIAMS payline has ranged from 11.0 percent to 17.0 percent. The success rate during that time has remained at approximately 20 percent. The success rate is predicated on many factors, including how much money is available in the competing pool and the number of applications received. From 2006-2009, the NIAMS annually received between 1,200 and 1,300 research project grant applications. In 2010, the Institute received more than 1,400 applications and in 2011, more than 1,530 applications. This considerable increase in the number of applications has had a significant impact on the success rate.

   On December 23, 2011, President Obama signed the Consolidated Appropriations Act of 2012 into law. This includes nearly $30.7 billion for the NIH, which is $299 million over last year�s level. The NIAMS� portion is $536.8 million, representing a slight increase over the Institute�s FY 2011 budget. Dr. Katz reminded Council members that the Institute has posted a funding plan on its website. President Obama was expected to unveil his proposed FY 2013 budget during the week following this Council meeting; an update will be provided at the June Council meeting.

   With the passage of the FY 2012 Omnibus Appropriations Bill, the NIH established the National Center for Advancing Translational Sciences (NCATS) and dissolved its National Center for Research Resources (NCRR). As a result, many of NIH�s preclinical and clinical translational science programs are being reorganized into an integrated scientific enterprise with new leadership and a new agenda. The effort to recruit an NCATS Director is ongoing. Organizational changes and realignment of resources will move forward under the leadership of Acting Director Dr. Thomas R. Insel (Director of the National Institute of Mental Health, NIMH) and Acting Deputy Director Dr. Kathy Hudson (NIH�s Deputy Director for Science, Outreach, and Policy).

   As part of the National Defense Authorization Act for FY 2012, the House and Senate agreed to reauthorize the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. The bill extends the programs for another 6 years, and will gradually increase the amounts that the NIH and other agencies must invest annually. At present, the NIH must invest 2.8 percent of its extramural budget in the small business programs; that number will increase to 3.65 percent over the next 6 years. NIH Director Dr. Francis Collins recently charged the Scientific Management Review Board (SMRB) with recommending ways in which NIH�s SBIR and STTR programs could be more effective.

   The House and Senate continue to be interested in progress researchers are making in the area of stem cells. On the day before this Council meeting, senior staff from the Senate Committee on Health, Education, Labor, and Pensions met with NIH staff and representatives from the U.S. Food and Drug Administration (FDA) to discuss the state of the science and collaborative opportunities related to regenerative medicine.

   Highlights of Selected Recent Scientific Advances

   • A team of intramural scientists at the NIAMS led by Dr. Alasdair Steven (Senior Investigator in the Laboratory of Structural Biology Research), in collaboration with researchers at the University of Maryland Medical School, have found a way to better visualize the interaction between proteins inside viruses using a technique they termed "bubblegram imaging." The technique involves adjusting the levels of radiation during cryo-electron microscopy and superimposing the images using three-dimensional computer reconstruction. In the future, bubblegram imaging may yield further insights into the inner workings of viruses and suggest strategies for developing novel therapies (Science. 2012 Jan 13;335(6065):182. PMID: 22246767).
   • Scientists in the NIH�s Intramural Research Program, including NIAMS Acting Clinical Director Dr. Richard Siegel and Dr. Daniel Kastner (Scientific Director, National Human Genome Research Institute), conducted a long-term effectiveness study of etanercept for tumor necrosis factor-associated periodic syndrome (TRAPS) patients. After long-term follow-up, the research team found that attacks still occurred, but were shorter and less severe. Levels of inflammatory biomarkers were reduced, particularly during asymptomatic periods. The patients who remained on the drug continued to report benefits, suggesting that the drug can be an effective long-term treatment option for some patients. However, most patients discontinued the drug during the follow-up period due to a perceived lack of efficacy or painful injection site reactions. Dr. Katz noted that the study was unable to show whether etanercept could prevent the long-term consequences of TRAPS (Arthritis Rheum. 2011 Oct 17. doi: 10.1002/art.33416. [Epub ahead of print] PMID: 22006113).
   • Drs. Laura Schanberg of Duke University and Christy Sandborg of Stanford University and colleagues investigated the potential benefits of statin treatment to slow the progression of atherosclerosis in children with lupus. The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Study involved 20 sites across North America that participate in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and enrolled more than 200 pediatric lupus patients in a double-blind, prospective, placebo-controlled trial for a 36-month period that evaluated vascular outcome measures. The difference in the carotid intima-media thickness was not significant between the statin-treated and placebo-treated groups. Although the results do not demonstrate compelling evidence to support treatment with statins in children and adolescents with lupus for the prevention of atherosclerosis, there may be benefits to patient subgroups with severe disease, and such studies are ongoing (Arthritis Rheum. 2012 Jan;64(1):285-96. PMID:22031171).
   • Investigators led by Dr. William Robinson at Stanford University School of Medicine have shown that osteoarthritis (OA) development is driven, in part, by low-grade inflammation. The finding builds on observations that OA joints contain an abundance of migratory inflammatory cells and their products, and adds a new dimension to the paradigm that a lifetime of joint wear and tear leads to OA. The new results show that initial joint damage triggers a chain of molecular events that escalates into an attack on the joints by the "complement system" (a process by which the body fights infection). The complement system has been a pharmaceutical target due to its role in other diseases (Nat Med. 2011 Nov 6;17(12):1674-9. doi: 10.1038/nm.2543. PMID: 22057346).
   • Dr. David Fisher from Harvard Medical School and colleagues in the United States, Australia, and the United Kingdom characterized groups of inherited and spontaneous cases of malignant cutaneous melanoma and found a mutation that blocks microphthalmia transcription factor (MITF) sumoylation. Without sumoylation, a biochemical modification that occurs after MITF is made, MITF activity is abnormally enhanced, and the transcription of some MITF-regulated genes is concomitantly increased. This MITF mutation was found to double the risk for melanoma, which is similar to the risk arising from severe sunburn. Uncovering this potential mechanism for melanoma pathogenesis will guide further studies about the transformation of melanocytes into cancer cells and targeted treatment strategies (Nature. 2011 Nov 13;480(7375):99-103. PMID: 22080950).
   • Research into the genetics of facioscapulohumeral muscular dystrophy (FSHD) is uncovering hundreds of genes that are abnormally regulated by the transcription factor DUX4. An international team of researchers led by Dr. Stephen Tapscott at the Fred Hutchinson Cancer Research Center demonstrated that many of these genes, like DUX4 itself, may regulate stem cell development. The finding suggests that abnormal expression of these stem cell genes may cause the adult muscle cells to die, leading to the muscle degeneration that characterizes FSHD. If subsequent studies show that the abnormal expression of some of these genes lead to proteins that can be detected in patients� blood, this knowledge could be used for diagnosing or monitoring the disease in clinical trials or clinical practice (Dev Cell. 2011 Dec 28. [Epub ahead of print] PMID: 22209328).
   • Tissue culture experiments overseen by Drs. Eileen Shore and Frederick Kaplan at the University of Pennsylvania�s Perelman School of Medicine showed that RNA interference (RNAi) can prevent the molecular processes that lead to abnormal bone formation associated with fibrodysplasia ossificans progressiva (FOP). While the results must be confirmed in animal studies, and several safety and feasibility hurdles must be overcome before the RNAi approach can be tested in patients, this finding brings the team�s earlier discoveries about FOP one step closer to clinical practice (Gene Ther. 2011 Oct 20. doi: 10.1038/gt.2011.152. [Epub ahead of print] PMID: 22011642).
   • The U.S. Preventive Services Task Force recommends bone mineral density (BMD) testing for women aged 65 years and older. Although Medicare pays for the test every 2 years, the appropriate interval between tests is unclear. The longstanding NIH-supported Study of Osteoporotic Fractures has demonstrated that many women may not need to be tested as often, particularly if they have a healthy BMD when they are first tested, and if they do not have medical conditions that increase their risk of losing bone. The data suggest that some women could wait as long as 15 years before getting a second screening, while women at the highest risk of osteoporosis might benefit from annual testing. Dr. Katz thanked Dr. Joan McGowan, Director of the NIAMS Division of Musculoskeletal Diseases (DMD), for serving as the NIAMS spokesperson in a New York Times story prompted by this study (New Eng J Med. 2012 366:225-33. Epub Jan 19, 2012).
   • Dr. Josh Jacobs at Rush University Medical Center and colleagues have made a surprising discovery about the lubricating layer that forms in the joints of metal-on-metal hip implants. Although the all-metal joints are not designed with lubrication, a thin layer develops between the metal ball and socket once implanted in the body. Previously, researchers thought that the layer must be made of proteins, like the fluid in normal joints. This recent study demonstrated that this solid layer, made mostly of carbon, is more like an industrial lubricant than joint fluid. Knowledge that the film is graphitic carbon raises the possibility that researchers can create safer, longer-lasting hip implants which, in turn, could have a profound impact on the long-term success and societal costs of total hip and knee replacement (Science. 2011 Dec 23;334:1687-90).

   NIH/NIAMS Activities and Plans for the Future

   Dr. Katz provided an update on the Advisory Committee to the NIH Director�s Working Group on Diversity in the Biomedical Research Workforce. This Working Group is charged with providing concrete recommendations on ways to enhance the diversity of the scientific workforce throughout various career stages. Working Group members are particularly interested in the recruitment and retention of underrepresented minorities, persons with disabilities, and persons from disadvantaged backgrounds. Dr. Katz asked Council members to encourage their students, postdoctoral fellows, colleagues, scientific or patient-affiliated societies, and home institutions to respond to the Request for Information that was recently published in the NIH Guide to Grants and Contracts.

   The NIH is delaying the merger of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA) for one year to allow additional time for a detailed portfolio analysis among all the potentially relevant Institutes and Centers (ICs) and to obtain public input on the plan. Over the next year, the NIH will solicit comments regarding the gaps in knowledge and new opportunities that the new Institute might explore. As members of the NIH Scientific Management Review Board (SMRB), NIH Principal Deputy Director Dr. Larry Tabak and Dr. Katz have been working closely with the task force that is examining the portfolios.

   As Chair of the Clinical Center Governing Board, Dr. Katz has also been working on implementing another SMRB recommendation to enhance the utilization of the NIH Clinical Center and strengthen its funding base. As part of this effort, the NIH is proceeding with plans to broaden the Bench-to-Bedside Program at the Clinical Center to include extramural investigators, provided that outside teams include an intramural collaborator.

   With regard to NIAMS information dissemination and outreach activities, Dr. Katz noted that the Institute�s website has been refreshed with a new color scheme that provides better contrast and larger text. To aid public visitors who may be looking for resources on particular diseases or conditions, the Health Information Index has been positioned more prominently on the site. Materials from the Institute�s 25th anniversary celebration are posted on the website, including videos of presentations and panel discussions from the Scientific Symposium.

   The NIAMS recently celebrated the 10th anniversary of its Community Health Center (CHC), which has moved to a new location�the Spanish Catholic Center in Silver Spring, MD. Dr. Collins provided the keynote address at the anniversary celebration. The CHC was originally founded by the NIAMS in Washington, DC, in collaboration with area community stakeholders. Since its inception, the CHC has enrolled more than 2,000 patients and provided almost 10,000 patient visits in the Natural History of Rheumatic Disease in Minority Communities Study. Dr. Katz commented that the CHC is one of many examples of how the NIAMS partners with patients and the public to fulfill its mission. Another example is the NIAMS Coalition, which provides a forum through which professional and voluntary organizations can coordinate among themselves and with the Institute. In October, more than 50 representatives from 40 organizations gathered for a Coalition Outreach and Education Meeting, "Creating Connections for Science."

   As the lead Institute for the Trans-NIH American Indian and Alaska Native Health Communications and Information Work Group, the NIAMS partnered with NIDA, the National Institute of Dental and Craniofacial Research (NIDCR), the National Cancer Institute (NCI), and the National Library of Medicine (NLM) to host a meeting about reaching an under-recognized segment of the population: American Indians/Alaska Natives (AI/AN) who live in urban settings (more than 60 percent of AI/AN reside outside of reservations and have unique needs from those living on reservations). This workshop helped participants: (1) appreciate the histories and cultural identities of urban Indians across the country, (2) better understand the health care issues facing these diverse populations, and (3) identify partnership opportunities and best practices for health communications.

   The NIAMS is also participating in the National Institute on Aging�s (NIA) Go4Life Campaign, which is an exercise and physical activity initiative designed to help Americans aged 50 years and older to incorporate exercise and physical activity into their daily lives.

   Discussion

   Dr. Katz thanked Anita Linde, Director of the Office of Science Policy and Planning, and her staff for helping to prepare the information he discussed in his Director�s report. He noted that one of the challenges facing the Institute (and for which the NIAMS is seeking Council members� guidance) relates to the R01 payline, given current budgetary limitations.

5. OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH (OBSSR)

   Dr. Robert Kaplan, Director of the OBSSR, explained that the Office�s mission is driven by a focus on the next generation of measurement and data, delivering services in a changing health care system, and training future investigators. He said that many new and evolving electronic devices will affect how researchers carry out their work, and the way research is conducted will change because of the availability of information through electronic medical records (EMRs). The OBSSR is working to harmonize some of the information collected from EMRs and to develop methodologies to digest increasingly large amounts of information.

   In response to changes in health care systems, the OBSSR has been concentrating on new approaches to health care delivery that recognize the many complex determinants of disease, including social and environmental factors. Furthermore, the nature of education will change to accommodate social and environmental issues, as well as the large amounts of data that will be available. Dr. Kaplan noted that in 2015, the Medical College Admission Test will be revised so that approximately 20 percent of its content will relate to the behavioral and social sciences.

   Dr. Kaplan described two examples to highlight the next generation of data and measurement: (1) the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative, and (2) understanding gene-environment interactions. He noted that simple interventions, such as doing something nice for a patient just before asking a question affects the way the information is reported by the patient. For 30-40 years, experimental psychologists have been arguing for the need to shift to representative design and representative sampling. Instead of asking people to recall information/events or measuring something in laboratories, representative design and representative sampling involves real-time sampling of what happens to patients over a longer period of time, in the environments in which they live. To date, this has been a difficult endeavor.

   To address this challenge, the OBSSR has been exploring the concept of mHealth, which involves a diverse set of wireless applications that might be used to enhance health care research and the practice of medicine. mHealth uses three different types of devices: (1) sensors, (2) monitors, and (3) mobile phones. Mobile phones have many advantages because they are portable, scalable, provide rich data input, are personal, provide information in real time, and are becoming ubiquitous, including in the developing world.

   Dr. Kaplan reviewed an mHealth application to highlight measurement and assessment within the context of understanding gene-environment interactions. He described the term "exposomics," which involves measuring environmental exposures over time, assessing what diseases might occur, and what diseases might be prevented over the course of time. There is a tremendous imbalance between the current, robust approaches for evaluating genetic influences versus generally inadequate methods for measuring environmental exposures, which are necessary to understand gene-environment interactions. However, the proliferation of wireless devices and social networks, along with new opportunities for using sensors, are changing the landscape and are likely to have a significant impact on many areas of investigation.

   Dr. Kaplan discussed a number of examples, including an application that monitors heart rhythms in real time and alerts users if/when their cardiac activity deviates from the normative group and from their personal norms. He explained how such technology can allow people to live much more independently.

   Dr. Kaplan described the effects of these applications from a global health perspective. In 2002, there were only two countries that had the capability to carry out the types of wireless applications he discussed. In 2010, there were 97 such countries, and that number has likely increased since then.

   Dr. Kaplan commented that research is not keeping pace with technological advances and suggested that the NIH develop a research agenda to determine the extent to which these devices and technologies advance the agenda of helping people live longer and improving the quality of their lives. He noted that in 2014, the Affordable Care Act will allow reimbursement for remote monitoring. He also explained that many new research needs, particularly managing large and continuous flows of data, will surface as these technologies and applications are more widely adopted. Entirely new methodologies will likely be needed to advance this area.

   Discussion

   Dr. Kaplan was asked if the field is equipped to manage the large amount of data that will be generated through widespread use of these new technologies. He responded that there are problems associated with this flow of data at a number of levels. Storing the data is an issue, as is safeguarding data privacy and protection. In addition, creating the capability to analyze vast amounts of data represents a significant challenge. Across the NIH, ICs are realizing that more data than ever before are being generated in almost every area of study. The adoption of EMRs alone will make hundreds of millions of data points available.

   There were also questions about the gain researchers would see, compared with the tremendous investment required to adopt these types of technologies. For example, the recent development of electronic medical records (EMRs) required a $30 million investment at one clinic. A Council member commented that a recent study of OA patients he and his colleagues conducted found that sophisticated ultrasound techniques were not as effective in measuring the disease as simply asking patients how they felt over the last month. Dr. Kaplan noted that patients generally do perform well on self-report questionnaires, but there is room for improvement. More accurate and effective sampling techniques are not difficult to implement and can be cost effective. More research on these techniques is needed to fully gauge their effectiveness and their improvement over patient self-reports.

   It was also noted that the NLM has developed an add-on to their EMR product that brings up NIH citations; a Council member wondered if the NIH would be developing additional features that could be added to EMR products that would be useful without overwhelming patients and clinicians. Dr. Kaplan agreed that the NLM is a valuable resource and is engaged in numerous creative efforts. Dr. Katz added that almost everything the NIAMS does is in the public domain; however, disseminating the information to the appropriate audiences in a useful manner is challenging. Dr. Susana Serrate-Sztein, Director of the Division of Skin and Rheumatic Diseases (DSRD), explained that the PROMIS initiative is developing a series of tools and instruments to measure patient-reported outcomes. Many of the instruments developed through the PROMIS initiative are expected to facilitate clinical studies and clinical care.

   Council members asked about the exposome and whether there are methods for capturing prenatal environmental exposures. Dr. Kaplan explained that the National Children�s Study is attempting to gather data on prenatal exposures and acknowledged that this area represents a rich environment for future study. In response to a question regarding health care economics and compensating physicians for engaging their patients with new technologies, Dr. Kaplan explained that he feels that the health care system is likely moving towards a different reimbursement model that may focus more on a health care organization�s time rather than a specific physician�s time.

   Dr. Kaplan was asked about the gap between the activities engineers are engaged in compared with the state of the science and research, in general. He commented that the field of engineering is not sensitive to the impacts of new technologies on human health, the rapid pace of development can lead to unforeseen consequences (e.g., overtreatment), and more systematic trials on the implementation of new technologies are needed.

   It was suggested that one pitfall in advancing this field is moving from a single prototype device for use in a health care or research setting, to large-scale production of industrial-standard devices suitable for home use and clinical trials. This usually requires a significant financial investment and, without a market demand, finding the funds for this stage of development can be challenging. Another obstacle to development is that many personal use devices require active participation, which may decrease after an initial period of use. Dr. Kaplan noted that the OBSSR and other groups recognize these significant challenges. An additional problem is that it often requires 3-4 years to evaluate a device in a clinical trial, and it may be obsolete by the end of the study.

   In response to a question about private sector involvement, Dr. Kaplan explained that there is a tremendous amount of interest in these technologies and devices from industry, and more work on business modeling in this area is needed. Many device manufacturers and wireless technology companies recognize that a significant proportion of their income is and will be health-related. A Council member commented that the technologies and applications Dr. Kaplan discussed are being introduced into clinical medicine at a rapid pace. At the University of Rochester, biometric monitoring has been found to reduce costly 30-day cardiac readmission rates.

6. REPORT ON ROUNDTABLE DISCUSSIONS

   Dr. Serrate-Sztein noted that the Institute has been holding annual roundtable discussions for the last 20 years to obtain community input on issues of interest to the NIAMS. Prior to each roundtable, invited participants are asked to canvass their respective communities to bring a wide perspective to the discussion. This year, the NIAMS hosted five roundtables that focused on promising areas of science, pressing scientific needs, identifying the greatest challenges and potential options for overcoming them, and impediments to research translation. Dr. Serrate-Sztein emphasized the importance of the roundtable discussions, noting that they provide information to the NIAMS that help guide its scientific planning activities.

   The 2011 NIAMS roundtable topics were: (1) Arthritis Biology and Research, (2) Pediatric Dermatology, (3) Bone Biology and Bone Diseases Research, (4) Impact of Muscle Physiology Research on Common Diseases and Disorders, and (5) Musculoskeletal Biology and Diseases. Each roundtable was co-chaired by a member of the extramural scientific community, together with an NIAMS Program Officer. Dr. Serrate-Sztein summarized the Arthritis Biology and Research and Pediatric Dermatology roundtables, and Dr. McGowan then briefed the Council on discussions from the Bone Biology and Bone Diseases Research, Impact of Muscle Physiology Research on Common Diseases and Disorders, and Musculoskeletal Biology and Diseases roundtables. Council members were also told that summaries from the 2011 NIAMS roundtables would appear on the Institute�s website and were invited to provide feedback on the roundtables. The summaries are now available at http://www.niams.nih.gov/News_and_Events/Meetings_and_Events/Roundtables/2011/default.asp

   Dr. McGowan noted that each of the 2011 roundtable participants was also asked to provide input on how the NIAMS can manage science in the current fiscal environment, specifically with regard to sustaining research projects and the pipeline of researchers, protecting innovation, and maintaining critical resources. Council members were reminded that their input in these critical areas is also encouraged.

   Arthritis Biology and Research

   This roundtable focused primarily on rheumatoid arthritis (RA). The discussion followed current thinking about RA and was broken down into three phases: (1) preclinical (which precedes the onset of disease by several years), (2) onset of disease, during which joint manifestations of disease occur, and (3) progression to active disease. Major topics relating to the preclinical phase included the role of the microbiome and how it may predispose individuals to disease, and anti-citrullinated peptide antibodies as biomarkers for RA risk. In the area of disease initiation, the discussion focused on autoantibodies, structural elements of the joint, cellular mediators, and extra-articular disease. With regard to challenges in the area of arthritis biology and research, topics included biomarkers, data integration and biosignatures, access to tissue specimens, and leveraging existing resources.

   Pediatric Dermatology

   This roundtable featured a discussion on opportunities to advance research in pediatric dermatology, in areas such as linking genetics and phenotypes, biological mechanisms, and novel approaches to immortalizing keratinocytes. Research needs included epidermal permeability assays, more effective non-invasive imaging technologies, and optimization of cell-based therapies. Roundtable participants also discussed critical infrastructure needs, such as developing multidisciplinary collaborations/clinical research networks and partnerships with professional and patient organizations.

   Bone Biology and Bone Diseases Research

   This roundtable was broad in scope and included discussions on bone-related topics such as: (1) biomarkers for bone quality; (2) basic research that may lead to therapies for bone diseases; (3) opportunities and limitations associated with available mouse models and resources; (4) integration of research on bone with the study of other tissues and organ systems (e.g., muscle, pancreas); and (5) building on conceptual and technical advances to understand the genome, epigenome, transcriptome, and proteome influences on genetic bone diseases.

   Impact of Muscle Physiology Research on Common Diseases and Disorders

   This roundtable focused on mechanisms of muscle physiology that contribute to common conditions, such as muscle loss in cachexia, disuse atrophy, and sarcopenia,; the role of resting muscle in energy consumption and thermogenesis and relevance to obesity/metabolic syndromes; and the integration of skeletal muscle activity with other organ systems (e.g., skeletal, adipose, immune). Roundtable participants also discussed the role of muscle as an endocrine and paracrine organ, a store of essential amino acids, and a sensor and integral effector of the central nervous system.

   Musculoskeletal Biology and Diseases

   Roundtable participants focused on four specific areas within this broad topic. In terms of tissue engineering, they discussed cellular and bioengineering products for the repair of critical-sized defects in bone and cartilage, standardization and scalability of cell sources and tissues, and imaging tools to assess tissue biology and functional status. In the area of tissue interfaces, topics included reattachment of soft tissue to bone, and basic and translational research needs related to the intervertebral disc. Participants discussed the development of biologically active devices, such as those for securing soft tissues to bone or for fracture/implant fixation. Finally, this roundtable addressed issues related to clinical research and evidence-based clinical practice, including the development of criteria for the use of diagnostic procedures and treatments, evidence-based physical rehabilitation strategies following the repair of various joints or tissues, and epidemiologic evidence regarding the long-term impact of surgical and non-surgical treatments.

   Discussion

   Dr. Katz noted that these roundtable discussions enhance the NIAMS� communication with its various stakeholder communities. He commented that it was extremely valuable to obtain input from roundtable participants with regard to managing science in the current fiscal environment. They generally agreed that some negotiation for a lower award amount is possible to maximize usage of available funds; however, the funding level must be able to support the aims of the project.

   A Council member noted that last year, one of the top priorities identified by the American Society for Bone and Mineral Research (ASBMR) was the interaction between muscle and bone. The ASBMR is planning a muscle-bone interaction meeting in Kansas City July 17-18, 2012, to bring together investigators who do not normally interact and to identify where the field should move in the future. Representatives from NIH ICs have been invited to the meeting.

7. NIAMS INTRAMURAL RESEARCH PROGRAM (IRP)

   Dr. Siegel explained that the NIAMS IRP constitutes approximately 10 percent of the Institute�s budget and is virtually 100 percent federally funded. The IRP is subject to rigorous scientific review by the NIAMS Board of Scientific Counselors. The IRP�s funding model and approach to science provides: (1) sustained investigation of major research questions and high-risk/high-reward science, (2) rapid translation of discoveries into clinical trials, and (3) rapid implementation of new breakthroughs and technologies. Dr. Siegel gave an overview of the IRP, noting that the program has a staff of approximately 250, including 21 faculty members (14 laboratory-based PIs and 7 clinical PIs) as well as 150 trainees (e.g., medical, graduate, clinical, and postdoctoral trainees). The IRP�s Clinical Program sponsors a rheumatology fellowship training program that is more research-focused than most rheumatology fellowship training programs. The Clinical Program also sponsors clinical and translational research and community outreach at the NIH Clinical Center and the NIAMS CHC. The IRP has core facilities, as well as a Career Development and Outreach Branch to help oversee training and outreach programs (especially for trainees from minority and disadvantaged backgrounds) and an Administrative Branch.

   The IRP does not cover all of the entire scope of disease and research topics funded through the Institute�s Extramural Program (EP). Dr. Siegel described the areas of excellence within the IRP in the following categories: (1) immunology and rheumatology, with particular focus on cytokine biology and receptor signal transduction, by the Autoimmunity Branch, the Molecular Immunology and Inflammation Branch, the Laboratory of Molecular Immunogenetics, the Office of the Clinical Director, and the Pediatric Rheumatology Branch; (2) musculoskeletal and skin research, and structural biology by the Laboratory of Structural Biology, the Laboratory of Muscle Stem Cells and Transcriptional Regulation, the Orthopaedics Unit, the Laboratory of Skin Biology, the Laboratory of Oral Connective Tissue Biology, the Protein Expression Laboratory, and the laboratory of the Director of the National Institutes of Health Center for Regenerative Medicine (NIH-CRM); (3) core facilities and services, and technical expertise through the Office of Science and Technology, including the Biodata Mining and Discovery Section, the Flow Cytometry Group, the Laboratory Animal Care and Use Section, the Light Imaging Section, and the Translational Immunology Section.

   Dr. Siegel described the establishment of the NIH-CRM as an example of how the IRP can quickly implement new technologies. Shortly after the 2008 discovery of the "4 factor" method for inducing pluripotent stem cells (iPSCs) from mature tissue, the topic of iPSCs was discussed at the trans-NIH level and the NIAMS submitted a proposal to establish an intramural center to carry on this work. Shortly thereafter, the NIH-CRM was established to support translational uses of iPSC technology. The NIH-CRM demonstrates how a concept can rapidly progress to the point of having on-the-ground resources that will be useful both within and outside the NIH.

   Dr. Siegel explained that the NIAMS Clinical Program�s efforts are directed toward carrying out clinical trials; not only investigational drug trials, but also natural history protocols. The Program has long-standing partnerships with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NHGRI, and NIDCR.

   Following this overview, Dr. Siegel provided a number of examples to illustrate how research takes place within the Clinical Program. Natural history cohorts have catalyzed a number of discoveries from within the Clinical Program, including positional cloning of the Familial Mediterranean Fever gene and other work in the expanding spectrum of autoinflammatory diseases due to IL-1β activation disorders (e.g., neonatal onset multisystem inflammatory disease, deficiency of the IL-1 receptor antagonist). Dr. Siegel presented a slide illustrating how quickly IRP trials on these and other disorders began, following discovery of the causal genetic mutation.

   Dr. Siegel explained that the NIH Rheumatology Program gives advanced trainees protected time for clinical research courses and laboratory research, to develop skills, publication records, and the confidence to move forward in their careers.

   Some of the issues and challenges facing the IRP include a budget with largely fixed costs (allocated to personnel, the Clinical Center, facilities, and administrative costs), the development of working teams across the IRP and between NIH ICs (particularly for clinical research infrastructure needs and bioinformatics/statistical support), and collaboration with the extramural community and biotechnology industry. Dr. Siegel noted that, to help promote an open environment, new mechanisms for extramural investigators to propose collaborative projects with the NIH Clinical Center will soon be available.

   Discussion

   Dr. Katz noted that one of the challenges facing the IRP has been in the area of pediatric research. Dr. Siegel agreed, adding that the IRP does not have a categorical pediatric rheumatology training program, but has been fortunate to recruit some experts and trainees in this area.

   A Council member commented that the group of investigators within the IRP is impressive. He asked if the program�s focus on autoinflammatory and rheumatologic diseases was by design, and whether there are concerns that opportunities in other areas are not being addressed. Dr. Siegel explained that there are a number of examples of IRP projects available to the rheumatology fellows that are not rooted in rheumatology, and there is enthusiasm for expanding the IRP into other areas within the Institute�s mission. Dr. Katz added that other NIH ICs cover many of the topics of interest to the NIAMS that are not currently included in the IRP. He reminded Council members that a discussion of the NIAMS Board of Scientific Counselors� review of the IRP takes place annually during the closed session of Council meetings.

8. EVALUATION OF INITIATIVES

   Outcomes Instrument Development Funding Opportunity Announcements (FOAs)

   Dr. Gayle Lester, Program Officer within DMD, presented data gathered from the EP working group to evaluate the Clinical Trials Outcomes Instrument Requests for Applications (RFAs) that have been issued three times over the past six years. The purpose of this initiative is to: (1) develop, validate, and evaluate instruments or tools to objectively assess clinically relevant disease progression, measure the efficacy or effectiveness of therapies, and assess patient-important outcomes; and (2) facilitate the widespread acceptance and application of these products in clinical studies and trials of diseases, illnesses, and injuries within the NIAMS mission. Key components of the program include obtaining input on the merit and applicability of these measures from relevant communities and professional organizations, information dissemination plans (both in terms of publications by the PI and team, as well as working with relevant professional organizations), and relevant outcome measures, such as consensus development approaches and validation studies.

   Three identical RFAs were issued over a 6-year period. Dr. Lester noted that there was a wide diversity of applications to the three RFAs that have been issued. Initially, it was planned that these 3-year awards (at $150,000 per year) would be R01s; however, it was decided during the first year that the preferred mechanism would be a cooperative agreement (U01) to allow for more programmatic input.

   The focus of the evaluation for these three solicitations was based on whether the funded projects were meeting the program�s goals (in terms of the number of publications, number of citations, and the Program Officer�s professional judgment), whether funded investigators were able to achieve their proposed goals within the three-year period, and whether the submitted and awarded projects addressed a breadth of disease areas within the NIAMS mission.

   Dr. Lester emphasized that the funded projects have met the goals of the RFA. The funded projects cover a range of outcome measure topics, including consensus meeting, instrument testing/method development, mathematical/computer modeling, validation studies, and biomarker development. Investigators have been able to accomplish their aims, publications and presentations have resulted from these projects, new methods/instruments have been developed and are being used by others, and the projects cover many of the NIAMS mission areas.

   Discussion

   In response to a question about the low number of projects focused on skin, Dr. Lester explained that a total of four projects related to skin were submitted in response to the three RFAs, but they did not perform well in review. Similarly, a number of applications concerning orthopaedics and muscle research did not receive adequate scores for funding. When asked about the composition of the review panels that evaluated these applications, Dr. Lester explained that the Institute makes every effort to assign applications to reviewers who have the appropriate expertise. She added that the applications that were not funded either were not focused on the goals of the solicitation or did not adequately address potential weaknesses in their approach.

   Building Interdisciplinary Research Teams (BIRT) Awards Analysis

   Dr. Fei Wang, Program Officer within DMD, explained that the goal of the BIRT Program is to promote the development of new interdisciplinary, basic and translational research teams in NIAMS mission areas. The NIAMS� review of the BIRT Program focused on new collaborations and the potential impact of these projects, which are competitive awards to active NIAMS grants (predominantly R01s) funded with $100,000 in direct costs for 1 year.

   In 2008 and 2009, RFAs were issued for pilot programs in focused topics (e.g., autoimmunity, developmental biology, tissue engineering, regenerative medicine, soft tissue biology). The 2010 RFA solicited projects in all NIAMS mission-relevant areas. Each RFA asked that four subjects be addressed in the annual progress report: (1) applications for new collaborative projects, (2) new direction(s) for renewal of the parent grant, (3) new shared resources, and (4) new interdisciplinary scientific meetings. PIs were contacted to follow up on the four criteria. A fifth criterion, "other," was added to allow for additional reporting.

   Dr. Wang reported that most BIRT awards (33 awards, or 97%) met more than one criterion (4 awards met all 5 criteria). She noted that 23 new joint publications have resulted from the BIRT awards to date, as have 6 joint NIH grants. The BIRT Program evaluation was not able to capture publications that did not cite the grant number, include the BIRT collaborator or efforts that were supported by funding agencies outside of the NIH. The evaluation also did not capture new and/or renewal NIH grants based on BIRT results that did not include the BIRT collaborator, or potential collaborations among other laboratory personnel.

   Dr. Wang also shared two BIRT success stories. One BIRT award added magnetic resonance imaging expertise to a parent grant on enhanced clinical diagnosis of early OA. There has been a renewal of the parent grant, and continuation of the BIRT collaboration, with three joint publications. Another BIRT award added systems biology expertise to a parent grant on transcriptional co-regulators in the epidermis. The BIRT collaboration provided preliminary data for a new NIH grant and resulted in three joint publications.

   Discussion

   A Council member noted that a number of publications in the literature cite or give credit only to the NIH and not to a specific Institute or grant. He asked whether there should be some outreach to grantees, asking them to include specific NIH Institute information and/or specific grant numbers in their publication submissions. Dr. Katz agreed that identifying the funding source in publications is a significant issue for the NIH, particularly with respect to informing the public of NIH activities. Others added that publications often only identify the "Department of Health and Human Services" and do not even mention the NIH. It was also noted that some journals do not allow investigators to include specific funding information. Both Council members and Ms. Linde suggested that if the NIH wants to pursue this with journals, the NIH Council of Public Representatives, which advises the NIH Director, be involved.

   When asked if the NIAMS plans to renew the BIRT initiative, Dr. Katz explained that the discussions at this meeting are intended to gain input from Council members as the Institute considers whether or not to continue activities such as the BIRT initiative.

   Ancillary Studies to Large Ongoing Clinical Projects — Awards Analysis

   Dr. Ricardo Cibotti, Program Officer within DSRD, explained that the Ancillary Studies to Large Ongoing Clinical Projects initiative was inspired by and modeled after National Institute of Allergy and Infectious Diseases (NIAID) and National Heart, Lung and Blood Institute (NHLBI) ancillary studies programs. This topic was discussed at the 2008 NIAMS Scientific Retreat, where participants said that the initiation of clinical studies requires large financial and personnel commitment, clinical studies are typically designed to answer limited questions, and the NIAMS should consider new policies or mechanisms to enhance or facilitate the use of ancillary studies in its mission areas. Dr. Cibotti noted that a successful ancillary study supported through this program is expected to enhance the scientific content and value of the parent projects and improve understanding of a disease or organ system in the NIAMS portfolio, and thus identify targets for diagnosis, treatment, and prevention of disease. He listed several examples of research that can be carried out through ancillary studies, including mechanisms of disease, biomarker discovery/validation, and development of new clinical outcome measures and statistical methodologies.

   The goals of this program are to: (1) facilitate time-sensitive research opportunities, (2) enhance scientific content and value, and (3) maximize the return on investment through leveraging existing resources. The program features ongoing clinical trials, observational studies, and registries supported by any funding source(s), as well as an expedited review and award process that reduces the receipt-to-award time to roughly five-and-a-half-months. The first RFA was issued in 2009 and was reissued in 2010. Two awards were made in the area of bone, two in muscle, three in orthopaedics/osteoarthritis, two in skin, and one in rheumatic diseases. There were three awards addressing mechanisms of disease, three on biomarker discovery and validation, three on novel outcome measures, and one developing new methodologies to enhance parent study data analysis.

   Dr. Cibotti discussed progress to date, acknowledging that this is a relatively new initiative. Two publications have been produced from these projects; there is one dataset under analysis, and eight projects are in the sample and data collection phase. No major challenges have been identified. Dr. Cibotti offered the following preliminary observations: (1) community response to the program has been robust, (2) awarded projects have met the intended goals of the program, and (3) the expedited review process has enabled time-sensitive research.

   Discussion

   Dr. Katz explained that these three programs were presented to the Council as examples of initiatives resulting from NIAMS Scientific Retreat sessions and roundtable discussions. In addition, they comprise a modest portion of the NIAMS budget. In response to a question about the funding for these programs, Dr. Katz said that, for the BIRT initiative, the Institute sets aside $1 million for the first year, and $1.5 million for the second and third years. These funds come from the research project grant (RPG) pool, but in the form of supplements.

   Council members were asked if they felt the programs were serving a purpose beyond what would be seen through the regular application process, and the discussion continued with questions about how much of this progress was paradigm-shifting, new, or would only be derivative from these types of programs. Dr. Katz explained that the concept for the BIRT initiative arose from repeated comments from the community that there is not enough support for multidisciplinary research. He added that it will take some time to understand whether the outputs from these programs are paradigm shifting, but the fact that they are generating new applications, new publications, and new collaborations is positive.

   In their discussion, Council members also noted that BIRT is a mechanism for building collaborations, not a clinical program. While it is an inexpensive program and is engaged in measurable activities, its true value — whether these collaborations would have formed regardless of the BIRT initiative — is extremely difficult to gauge. Dr. Serrate-Sztein mentioned that a driver of BIRT was that it is very challenging to start new experiments with new collaborators. In response to a Council member�s comments, Dr. Wang noted that the NIAMS analyzed five unfunded BIRT applications and found that the investigators involved in these applications later became part of only one joint NIH grant. She also said that the response to the BIRT RFAs would likely have been much higher if the first two RFAs were not limited to specific areas and if the third RFA had not been released at the same time as an American Recovery and Reinvestment Act application deadline.

   Council members indicated that they would support renewal of the BIRT initiative, citing that a small NIAMS investment can create important multidisciplinary collaborations. Dr. Wang reminded the Council that R01s are multi-year commitments, while the BIRT awards are one-year commitments. Overall, the amount of money the NIAMS has put towards the BIRT initiative is roughly equivalent to three or four R01 awards.

9. COUNCIL OPERATING PROCEDURES

   Dr. Laura K. Moen, Director of the Division of Extramural Research Activities (DERA) and the Council�s Executive Secretary, explained that the NIAMS is required to present its current and new operating procedures annually for Council review and approval. She noted that the proposed procedures for 2012 have not changed since last year and provided an outline of the process on a slide as she briefly presented it to Council. Council members had no questions or comments.

   A motion was made and seconded to approve the 2012 Council operating procedures. The procedures were approved unanimously.

10. CONSIDERATION OF APPLICATIONS

    The Council reviewed a total of 761 applications in closed session requesting $919,512,998 and recommended 761 for $919,512,998.

11. OVERVIEW OF SBIR/STTR PORTFOLIO

    This portion of the meeting occurred during closed session.

12. ADJOURNMENT

    The 76th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:30 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.