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

Minutes of the 72nd Meeting
8:30 a.m. to 3:00 p.m.

1. CALL TO ORDER

   The 72nd meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council was held on September 28, 2010, 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

   Mr. George A. Beach
   Dr. S. Wright Caughman (via teleconference)
   Dr. Leslie J. Crofford
   Dr. Betty A. Diamond
   Dr. Harry C. Dietz III
   Dr. Kathleen J. Green
   Dr. Linda Griffith
   Dr. Henry M. Kronenberg
   Ms. Ann Kunkel
   Dr. Regis O’Keefe
   Ms. Jean R. Pickford
   Dr. Clifford J. Rosen
   Mr. Bradley R. Stephenson, J.D.
   Dr. H. Lee Sweeney
   Dr. Julio L. Vergara

   Staff and Guests

   The following NIAMS staff and guests attended:

   Staff

   Mr. Steve Austin Dr. Michael Bloom Dr. Amanda Boyce 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. Barbara Cohn Ms. Stephanie Craver Ms. Wilma Peterman Cross Ms. Robin DiLiello Ms. Theresa Do Dr. Jonelle Drugan Mr. Erik Edgerton Ms. Elizabeth Elliott Ms. Sharon Fair Ms. Valerie Green Ms. Gail Hamilton Ms. Kaitaia Huynh Ms. Katie Joffee Mr. Andrew Jones Dr. Daniel Kastner Dr. Stephen Katz Ms. Shahnaz Khan Mr. Mark Langer Dr. Gayle Lester Dr. Helen Lin Ms. Anita Linde Ms. Mimi Lising Ms. Leslie Littlejohn Dr. Kan Ma

   Dr. Marie Mancini Dr. Su-Yau Mao Dr. Kathryn Marron Ms. Melanie Martinez Dr. Joan McGowan Ms. Leslie McIntire Ms. Sherry Meltzer Dr. Laura K. Moen Ms. Regina Mong Ms. Melinda Nelson Ms. Anna Nicholson Dr. Glen Nuckolls Dr. John O’Shea Dr. James Panagis Dr. Charles Rafferty Ms. Kelli Reid Ms. Natalie Reyes Ms. Trish Reynolds Dr. Louise Rosenbaum Ms. Karin Rudolph Dr. Susana Serrate-Sztein Dr. William Sharrock Ms. Sheila Simmons Ms. Theresa Smith Ms. Allisen Stewart Ms. Robyn Strachan Ms. Yen Thach Ms. Jamie Thompson Dr. Hung Tseng Dr. Bernadette Tyree Dr. Xibin Wang Dr. Yan Wang Dr. Chuck Washabaugh Ms. Sara Rosario Wilson Ms. Catherine Yi

   Guests

   Dr. James Anderson, Division of Program Coordination, Planning, and Strategic Initiatives, NIH
   Ms. Roberta Biegel, National Osteoporosis Foundation
   Ms. Jennifer Blacker, IQ Solutions, Inc.
   Mr. Michael Bykowski, Consolidated Solutions and Innovations
   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
   Ms. Robin Kawazoe, Division of Program Coordination, Planning, and Strategic Initiatives, NIH
   Ms. Lora Kutkat, Division of Program Coordination, Planning, and Strategic Initiatives, NIH
   Ms. Tamara E. Lewis-Johnson, National Institute of Allergy and Infectious Diseases, NIH
   Ms. Kimberly McGraw, IQ Solutions, Inc.
   Dr. Madeleine Wallace, Division of Program Coordination, Planning, and Strategic Initiatives, NIH
   Mr. Pat White, Office of Legislative Policy and Analysis, NIH

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to accept with no changes the minutes of the 71st Council meeting, held on June 15, 2010.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:
   February 1, 2011
   June 14, 2011
   September 27, 2011
   January 31, 2012
   June 5, 2012
   September 11, 2012

4. DIRECTOR’S REPORT AND DISCUSSION

   Dr. Katz welcomed Council members, NIAMS staff, and guests. He invited attendees to review the NIAMS ShortTakes online, which include more details on many of the topics covered in his Director’s Report. He noted that his "Director’s Column" focuses on the new Web site for the NIH Osteoporosis and Related Bone Diseases ˜ National Resource Center. The site features quick and easy navigation tools to help identify and locate topics of interest. The National Resource Center is supported by the NIAMS with contributions from a number of NIH Institutes and Centers (ICs). Dr. Katz thanked staff from the NIAMS Office of Communications and Public Liaison for their work on this effort.

   Dr. Katz acknowledged and thanked the following departing Council members for their service and contributions:

   • Mr. George Beach, Chairman and CEO of Beach Communications
   • Dr. Betty Diamond, Chief of the Laboratory of Autoimmune Diseases at The Feinstein Institute of Medical Research, North Shore Health System, and Professor at Albert Einstein College of Medicine
   • Dr. Kathleen Green, Joseph L. Mayberry Professor in the Department of Pathology/Cancer Center at Northwestern University Medical School
   • Dr. Clifford Rosen, Director of Translational Research at the Maine Medical Center
   • Dr. James Weinstein, Professor and Chair, Department of Orthopaedics, Dartmouth-Hitchcock Medical Center.

   Dr. Katz noted with sadness the passing of Dr. Larry Raisz, a renowned clinician-scientist who served on the Council from 2005 to 2008. A long-time NIH grantee, Dr. Raisz’s work provided numerous insights into the mechanisms of bone resorption and formation, and how the interplay between the two processes can lead to osteoporosis. He served as the second President of the American Society for Bone and Mineral Research (of which he was a founding member), and an active member of the National Osteoporosis Foundation’s Scientific Advisory Board. Dr. Raisz also served as a mentor to many basic scientists, clinical researchers, and practicing physicians, and as a member and chair of several NIH study sections.

   At the NIH level, Dr. Larry Tabak has been named Principal Deputy Director of the NIH. Dr. Tabak most recently served as Director of the National Institute of Dental and Craniofacial Research, a position he held since September 2000. Dr. James Anderson joined the NIH as the Director of the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI). Dr. Anderson came to the NIH from the University of North Carolina at Chapel Hill, where he was Professor and Chair of the Department of Cell and Molecular Physiology. Dr. Sally Rockey, who has been serving as the Acting NIH Deputy Director for Extramural Research since 2008, has agreed to lead the Office of Extramural Research in a permanent capacity. Mr. Neil Shapiro has been selected to lead the NIH Office of Budget.

   At the Institute level, Dr. Katz announced that NIAMS Clinical Director Dr. Daniel Kastner has accepted the position of Scientific Director within the National Human Genome Research Institute. Dr. Richard Siegel, Acting Chief of the NIAMS Intramural Research Program’s Autoimmunity Branch, has agreed to serve as Acting Clinical Director while Institute leadership conducts a search for a permanent Clinical Director. Other NIAMS appointments include Ms. Liz Elliott as an Ethics Coordinator and Ms. Barbara Footer as a Health Science Specialist within the NIAMS Division of Extramural Research Activities.

   Dr. Katz also reported that five NIAMS staff members were recognized with NIH Director’s Awards for their outstanding achievements: Mr. Melvin Broadus (Deputy Associate Director for Management and Operations within the NIAMS Office of the Director), Ms. Sharon Glass (Chief of the NIAMS Management Policies, Programs, and Initiatives Branch), Ms. Anita Linde (Director of the NIAMS Office of Science Policy and Planning), Dr. Rafael Casellas (a Principal Investigator within the Institute’s Laboratory of Molecular Immunogenetics), and Dr. John O’Shea (Scientific Director of the NIAMS Molecular Immunology and Inflammation Branch).

   Update on Budget and Congressional Activities

   Dr. Katz reported that the House and Senate continue to work on the Labor, Health and Human Services Education, and Related Agencies fiscal year (FY) 2011 appropriations bills. Both measures include funding for the NIH at the level of FY 2011 President’s budget request of $32 billion (representing a $1 billion increase over the FY 2010 amount). Each of these appropriations bills also includes $50 million to create a new Cures Acceleration Network (CAN), which was called for in the Patient Protection and Affordable Care Act. The President’s budget includes $555.7 million for the NIAMS, which is a $16.6 million (or 3.1%) increase over what the Institute received in FY 2010. After the House and Senate pass their respective appropriations bills, a Conference Committee made up of members of both houses of Congress will reconcile the differences between the two bills. If a final bill is not passed by October 1, it is likely that a continuing resolution will be enacted.

   Dr. Katz reminded Council members that on August 23, 2010, a U.S. District Court issued a preliminary injunction to stop federal funding of human embryonic stem cell (hESC) research. On September 9, 2010, the U.S. Circuit Court of Appeals for the District of Columbia granted a request from the U.S. Department of Justice (DOJ) for a temporary stay to block the injunction. This allowed intramural researchers to resume hESC studies and ICs to make extramural awards and consider applications. NIH Director Dr. Francis Collins testified before the Senate Appropriations Committee on September 16, 2010, to explain the importance of this type of research. Oral arguments pertaining to the temporary stay are scheduled to begin the week of this Council meeting. Updated information will be available on the NIH Web site.

   On September 15, 2010, Dr. Tabak testified in front of the House Energy and Commerce Subcommittee on Health at a legislative hearing. The discussion focused on 22 bills, including the Arthritis Prevention, Control and Cure Act of 2009 (H.R. 1210) and the Scleroderma Research Awareness Act (H.R. 2408). On July 21, 2010, Eunice Kennedy Shriver National Institute of Child Health and Human Development Director Dr. Alan Guttmacher testified in front of the Senate Committee on Health, Education, Labor, and Pensions at a hearing that focused on the need to create incentives to promote research and therapeutic development, using epidermolysis bullosa as one example.

   During the week preceding this Council meeting, Dr. Collins announced the release of the Biennial Report of the Director, NIH, for FY 2008 and FY 2009. Dr. Katz noted that NIAMS activities are well represented throughout the report, particularly in the chapters on autoimmune diseases, chronic diseases and organ systems, and the Congressionally mandated Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers.

   As part of ongoing efforts to reach out to the communities it serves, the Institute has partnered with the NIAMS Coalition (a group of more than 70 professional and voluntary organizations concerned with the programs of the Institute) to host a NIAMS Awareness Day on October 27, 2010. Congressional health staffers will be invited to the NIH Campus to see how the Nation’s investment in biomedical research through the NIAMS is being used. These staffers will meet with senior Institute leadership and visit some of NIAMS’ intramural laboratories. Dr. Katz noted the Institute’s gratitude for the NIAMS Coalition members who have led this effort as well as the NIAMS staff who are organizing the event.

   Highlights of Selected Recent Scientific Advances

   • Scientists in the NIAMS Intramural Research Program led by Dr. Kastner have found susceptibility to Behcet’s disease, a painful, inflammatory condition, to be associated with genes involved in the body’s immune response. Investigation of the interleukin 10 (IL-10) gene associated with immune response showed that people with two copies of the Behcet’s disease IL-10 gene produced significantly lower levels of IL-10 protein than those with only one or no IL-10 disease gene. This finding indicates that IL-10 might be a risk factor for Behcet’s disease and suggests possible therapeutic targets for future studies (Nat. Genet. 2010 Aug 42. [Epub ahead of print.] PMID: 20622878).
   • Dr. Maureen Mayes led an international study on systemic sclerosis, identifying genetic risk factors in the immune system’s major histocompatibility complex as well as gene regions coding for other immune-related molecules (e.g., STAT4 and interferon regulatory factor 5). A significant, new systemic sclerosis-associated genetic difference also was identified in the CD247 gene region, which encodes a molecule involved in regulating the immune response (Nat. Genet. 2010 May;42(5):426-9. Epub 2010 Apr 11. PMID: 20383147).
   • Dr. Angela Christiano and colleagues investigated the genomes of alopecia areata patients, who display significant differences from healthy controls near genes that increase T and natural killer cell population growth, and near genes that regulate T and natural killer cell activation. Most of these differences occur in gene regions identified in genome-wide association studies (GWAS) for other autoimmune diseases and may influence the development of autoimmunity. Further investigation of alopecia areata patient hair follicles by Dr. Christiano’s team found increased expression of one of the genes identified in the genome scan. Higher levels of this gene product may enhance stimulation of neighboring natural killer cells, leading to autoimmune attack on the hair follicles and subsequent hair loss (Nature. 2010 Jul 1;466(7302):113-7. PMID: 20596022).
   • Dr. Bruce Morgan and colleagues have been investigating the interactions of different cell types that play critical roles in tissue engineering and regenerative medicine in skin, as well as other organs. New genetic tools to study the dermal papilla revealed that the size of the dermal papilla, which correlates with the size of the hair shaft, is maintained between hair cycles by the recruitment of new cells (J. Invest. Dermatol. 2010 Jun 24. [Epub ahead of print.] PMID: 20574444). The researchers used this experimental system to decipher the communications between mesenchymal cells and keratinocytes, showing that the Wnt/β-catenin signaling—which plays an important role in development in many tissues—is required to maintain proliferation of hair follicle keratinocytes and to regenerate hair follicles from stem cells (Dev. Cell. 2010 Apr 20;18(4):633-42. PMID: 20412777).
   • Another group of researchers studying hair follicles and led by Dr. Gian Paolo Dotto disrupted the Notch signaling pathway—a mechanism that controls keratinocyte differentiation—in the dermal papilla. As a result, the keratinocytes gave rise to a curled-up hair follicle, in contrast to the normal, elongated hair follicle (Genes Dev. 2010 Jul 15;24(14):1519-32. PMID: 20634318). Dr. Katz commented that these recent studies on the regulation of hair follicle regeneration through cellular communications have provided important information about the impact of the mesenchymal cells of the dermal papilla on hair follicle development. In addition to applications to regenerative medicine, these findings may provide insights into the pathogenesis of various forms of alopecia and identify future therapeutic targets.
   • Although a shortening of a D4Z4 repeat sequence at the end of chromosome 4 is associated with facioscapulohumeral muscular dystrophy (FSHD), the disease does not occur without a specific sequence variation, or haplotype, in a piece of adjacent DNA. Dr. Steve Tapscott and colleagues have found that the D4Z4 sequences contain an inactive gene, called DUX4. When the number of D4Z4 repeats diminishes to 10 or fewer, this region of chromatin becomes hypomethylated and relaxed, allowing for transcription of the DUX4 gene. However, the DUX4 transcripts are unstable. They do not accumulate unless the shortened repeats are accompanied by a permissive haplotype such as the common A161 sequence. All of the permissive haplotype sequences contain a functional polyadenylation signal that modifies the product of the DUX4 gene of the most distal repeat so that it is stable and accumulates in muscle. The current hypothesis is that the DUX4 protein causes muscle degeneration, but the mechanisms have not yet been uncovered. This study provides evidence that DUX4 is likely a key part of the disease process in FSHD, and suggests that it is a potential therapeutic target (Science. 2010 Aug 19. [Epub ahead of print.] PMID: 20724583).
   • Former NIAMS Council member Dr. Steven Teitelbaum and colleagues used a variety of in vitro and in vivo methods to show that an intracellular protein, Cdc42, is involved in multiple steps that control the number and activity of osteoclasts. Functional osteoclasts polarize and form a structure called the actin ring that helps create an environment that is conducive for bone resorption. The work by Dr. Teitelbaum and colleagues shows that Cdc42 is involved in multiple signaling pathways that influence how two proteins (RANKL and M-CSF) activate osteoclasts and how Cdc42 participates in the osteoclast polarization and actin ring formation processes that are essential for bone resorption (J. Clin. Invest. 2010 Jun 1;120(6):1981-93. Doi: 10.1172/JCI39650. Epub 2010 May 24. PMID: 20501942).
   • A team of investigators led by Drs. M. Neale Weitzmann and Igho Ofotokun used an animal model to show that HIV infection can cause B cells to produce RANKL and osteoprotegerin (a RANKL-binding protein) in an unbalanced ratio, which could lead to bone loss. Because HIV infection and AIDS in humans result in abnormalities in B cells and other cells of the immune system, it appears likely that alterations in B cell production of RANKL and osteoprotegerin are at least part of the explanation for bone loss in people with HIV infections and AIDS (Proc. Natl. Acad. Sci. USA. 2010 Aug 3;107(31):13848-53. PMID: 20643942).
   • Drs. Diane Mathis and Christophe Benoist tested the effects of the gut microbiome in a mouse model of rheumatoid arthritis. The joint inflammation in the mice is directly associated with high levels of autoantibodies against the self-protein glucose-6-phosphate isomerase (GPI). Some mice were kept in conditions that would allow them to develop a gut microbiome. Others lived in germ-free conditions. The mice with a gut microbiome had higher levels of anti-GPI autoantibodies, Th17 cells in their intestines, and they developed severe arthritis at a young age. In contrast, the germ-free mice had lower levels of autoantibody-producing immune cells, almost no Th17 cells in their guts, and milder, late-onset arthritis. These findings provide a model in which gut microbes are capable of inducing Th17 cells, leading to production of autoantibodies that drive arthritis development. It is possible that the gut microbiome can promote normal immune function by regulating the balance of T cell subsets, but an imbalance in these pathways may result in inflammatory and autoimmune diseases. In particular, one of these T cell subsets, Th17 cells, are induced in mice by commensal gut bacteria (Immunity. 2010 Jun 25;32(6):815-27).

   NIH/NIAMS Activities and Plans for the Future

   Congress established the NIH Director’s Scientific Management Review Board (SMRB) when it passed the NIH Reform Act of 2006. Dr. Katz serves on the SMRB, which is charged with: (1) establishing or abolishing Institutes; (2) reorganizing Offices within the Office of the Director; and (3) reorganizing Divisions, Centers, or other administrative units within an IC. In addition to the SMRB’s three initial working groups (Deliberating Organizational Change and Effectiveness; NIH Intramural Research Program; and Substance Use, Abuse, and Addiction) the Board recently added a Translational Medicine and Therapeutics Working Group. Dr. Katz is a member of the Translational Medicine and Therapeutics Working Group, which will consider how the NIH can leverage and organize the wide range of its resources in the context of the Cures Acceleration Network (CAN) that was called for in the Patient Protection and Affordable Care Act. This working group will report to the SMRB before the end of the calendar year.

   The SMRB is also engaged in trying to ensure that the NIH Clinical Center has a steady stream of funds instead of relying solely on support from individual ICs. In addition, the Board recently discussed the Substance Use, Abuse, and Addiction Working Group’s findings regarding whether reorganization within NIH could better advance research into substance use, abuse, and addiction, and could further improve human health and patient well-being. Dr. Katz reported that Board members voted strongly in favor of merging the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse. He reminded Council members that the NIH Director has discretion to accept or reject the Board’s recommendations in full or in part.

   Earlier this month, the NIAMS, National Cancer Institute, National Institute of Allergy and Infectious Diseases, and the NIH Office of Research on Women’s Health (ORWH) held a two-day conference titled "Systemic Lupus Erythematosus: From Mouse Models to Human Disease and Treatment." The meeting brought together basic research scientists working on models of autoimmune disease relevant to systemic lupus erythematosus (SLE), with clinicians treating lupus patients. Dr. Juan Rivera, Deputy Scientific Director of the NIAMS Intramural Research Program, was a key organizer of the meeting and chaired a session on autoantibodies and lymphocyte activation. He presented some of his work on basophils and the Th2 environment in the development of lupus nephritis. NIAMS Deputy Director Dr. Robert Carter moderated the event. Dr. Diamond gave the opening lecture and chaired a scientific session on new advances and clinical challenges in the treatment of SLE.

   On the day before this Council meeting, Dr. Katz and Council member Dr. Linda Griffith of the Department of Biological and Mechanical Engineering at Massachusetts Institute of Technology’s Biological Process Engineering Center participated in ORWH’s 20th Anniversary Scientific Symposium. Dr. Griffith spoke about the integration of tissue engineering and systems biology in women’s health. National Institute of Diabetes and Digestive and Kidney Diseases Director Dr. Griffin Rodgers, National Heart, Lung, and Blood Institute Acting Director Dr. Susan Shurin, and Dr. Katz provided the perspectives of NIH leaders who collaborate closely with the Office to advance women’s health research.

   Dr. Katz noted that the NIAMS will celebrate its 25th anniversary next year with several activities across the NIH Campus, including a scientific symposium on June 13, 2011. The theme of the anniversary event is "Improving Lives Through Discovery." He invited Council members to attend the anniversary activities, reminding them that the events take place on the day before the June 2011 Council meeting.

   Each September, the Institute provides Council members with an overview of the initiatives it is considering putting forth to promote research in arthritis and musculoskeletal and skin diseases. One of these initiatives is a reissuance of the Building Interdisciplinary Research Teams (BIRT) program. NIAMS launched this initiative in 2007 to promote collaborations among groups of investigators in disciplines that have not traditionally interacted. After making three rounds of awards, NIAMS staff are examining whether BIRT is meeting its intended purpose. Dr. Carl Baker, Director of the Keratinocyte Biology and Diseases Program in the NIAMS Division of Skin and Rheumatic Diseases, provided an update on this initiative later in the meeting.

   Dr. Katz provided an update on the recent Small Business Innovation Research (SBIR) initiative that NIAMS staff developed after conversations with the orthopaedics and wound healing communities and with input from the Council’s SBIR Working Group. The initiative, Translation and/or Commercialization of Musculoskeletal and Skin Tissue Engineering and Regenerative Medicine Research, encourages: (1) preclinical studies that have potential to immediately lead to Phase I human clinical trials, or (2) the development of preclinical animal models to assess safety and efficacy of potential commercial products in musculoskeletal and skin tissue engineering and regenerative medicine. After its June 2010 Council meeting, the NIAMS funded four scientifically meritorious applications, one of which is a Phase II competing renewal application. The Institute plans to continue its strategy of encouraging small businesses to explore targeted areas of arthritis, musculoskeletal, and skin research as part of a balanced SBIR portfolio.

   The NIAMS has established a working group of this Council to advise the Institute on the potential for proposed clinical trials to improve patient outcomes. Members of the Clinical Trials Working Group met for the first time on the evening before this Council meeting to discuss the group’s role in enhancing the Institute’s decision-making process and facilitating the selection of high-quality clinical trials. Formal updates on the group’s activities will be provided at future Council meetings.

   With regard to the Institute’s many information dissemination efforts, Dr. Katz explained that in June, the advisory councils of various Institutes (including the NIAMS) approved funding for the first round of grants from a trans-NIH effort to encourage biomedical research on the International Space Station. Following Dr. Katz’s Director’s Report, Dr. Joan McGowan, Director of the Institute’s Division of Musculoskeletal Diseases, provided Council members with an update about the partnership and its resulting projects. As part of an NIH vodcast series, a 4.5-minute video was prepared to provide information on the Funding Opportunity Announcement (FOA) and how research in space might improve health on Earth. Dr. Katz presented a shortened version of the clip and noted that the full video can be viewed online on the NIH YouTube channel.

   Dr. Katz concluded his Director’s Report with an update on NIAMS-related American Recovery and Reinvestment Act (ARRA) activities. Several NIAMS grantees have contacted the Institute to provide information on how ARRA has benefitted their research. Other grantees are beginning to publish papers citing their ARRA awards. The Institute features several of these reports on its Web site, including a recent report on an award received by Dr. Green. Dr. Katz emphasized that the NIAMS remains extremely interested in learning about stories related to its ARRA awards from Council members and their colleagues.

   Discussion

   Dr. Diamond noted that the SLE meeting Dr. Katz described during his Director’s Report was a timely event. There are dozens of models of lupus in laboratory animals. Being able to determine which to pursue, how to pursue them, what aspects of disease to pursue, how these models relate to human disease, and which models will move the field forward are critically important issues in lupus and other diseases.

   Dr. Griffith asked about how to improve doctor-patient conversations with a focus on extracting important information from patients so that physicians do not overlook the symptoms of lupus, which is notoriously difficult to diagnose and especially so for general practitioners. Dr. Diamond explained that there are abnormalities that precede the clinical manifestations of lupus, but often there are delays in physicians determining whether or not these symptoms in fact represent a diagnosis of lupus. Further complicating matters is the fact that there is now a diagnosis called "incomplete lupus," for which patients have three criteria instead of the four needed for a diagnosis of lupus. Efforts are being made to help physicians diagnose lupus and other diseases earlier, particularly because in theory earlier interventions can be less toxic and can prevent tissue damage. Dr. Diamond commented that she did not believe that there was a significant problem in awareness and using diagnostic tests for the most part. Rather, the issues are more related to the timing of physicians informing patients of a diagnosis of lupus. Dr. Katz commented that most people do not have access to rheumatologists and that most patients see physicians or health care providers who have never seen a patient with lupus. Increasing awareness is important, especially among more susceptible populations.

   Dr. Green asked about the ongoing stem cell discussions Dr. Katz referred to in his Director’s Report. Dr. Katz explained that legislators were engaged in discussions during the day preceding this Council meeting. Dr. O’Shea noted that the court has not been particularly positive towards the government’s arguments and has been equally critical of the plaintiff’s as well. Information on the decision regarding this matter was not available at the time of this Council meeting.

5. BIOMEDICAL RESEARCH ON THE INTERNATIONAL SPACE STATION

   On September 12, 2007, former NIH Director Dr. Elias Zerhouni and former National Aeronautics and Space Administration (NASA) Administrator Dr. Michael Griffin signed a Memorandum of Understanding (MOU) between the NIH and NASA. The MOU indicated that the NIH would use reasonable efforts to: (1) publicize to the intramural and extramural communities the availability of the International Space Station (ISS) as a research environment, and (2) give careful consideration through the standard review process to well-developed investigator-initiated extramural applications and potential intramural activities.

   The Biomedical Research on the International Space Station (BioMed-ISS) Program was developed to facilitate NIH mission-relevant research on the ISS. An NIH FOA was released on March 17, 2009 (with participation from NIAMS and eight other NIH ICs) with an emphasis on molecular- or cell-based studies. Dr. McGowan explained that the BioMed-ISS Program is complementary to NASA’s Human Research Program and is intended to promote investigator-initiated biomedical research that uses the unique microgravity and radiation environment as well as the resources of the ISS to test innovative hypotheses that will benefit human health on earth.

   The BioMed-ISS FOA is active for 3 years. The mechanism is a UH2/UH3 Cooperative Agreement with support for up to 5 years. A pre-application meeting was organized by NIH and NASA in June 2009. The first applications were received last September. A second pre-application meeting was held this August, and a second set of applications will be received in the days following this Council meeting. For applications to this FOA, the NIH peer review process only reviews scientific merit, not ISS feasibility. Scientifically meritorious applications are subject to administrative review for ISS feasibility in consultation with NASA. NIH ICs proceed to fund those scientifically meritorious applications that are deemed feasible for the ISS. Applicants whose work is found to not be feasible for the ISS may be given the opportunity to revise their applications in collaboration with an implementation partner.

   Dr. McGowan explained that the ground feasibility phase (UH2) allows investigators to focus on ground-based preparatory work to meet scientific milestones and technical requirements leading to the ISS experimental phase (UH3). The UH3 phase includes preparing the experiments for launch, conducting them on the ISS, and subsequent data analysis on Earth. The UH3s are awarded after administrative review of the eligible UH2s that have met the scientific milestones and feasibility requirements necessary to conduct research on the ISS. An NIH BioMed-ISS Management Committee makes the transition recommendations to NIH funding ICs. The Committee includes representatives from NIH participating ICs and an advisor from NASA.

   In September 2009, a total of 22 applications were received and assigned to 8 of the 9 participating NIH ICs. The National Institute of Biomedical Imaging and Bioengineering conducted the scientific review of these applications in January 2010. NASA then conducted the ISS feasibility review for the top scored applications to provide advice to the ICs on whether each application was feasible, not feasible but modifiable, or not feasible and not modifiable. Dr. McGowan noted that all of the top-ranked scientifically meritorious applications received in 2009 were found to be feasible for the ISS. Funding decisions were made by the ICs during their May 2010 advisory council meetings.

   Dr. McGowan provided details of the three applications that were accepted and are moving forward:

   • Osteocytes and Mechano-Transduction (Dr. Paola Diveti, Massachusetts General Hospital/Harvard Medical School, supported by the NIAMS).
   • Suppression of the Immune Response in Spaceflight and Aging (Dr. Millie Hughes-Fulford, Northern California Institute for Research and Education, supported by the National Institute on Aging).
   • Novel Effects of Gravity on Intestinal Epithelial Barrier Responses to Alcohol (Dr. Declan McCole, University of California, San Diego, supported by the NIAAA).

   Dr. McGowan noted that these awards were made in recent weeks, and more information will be made available as the work progresses.

   Discussion

   In discussion, Dr. Katz emphasized that the BioMed-ISS Program is not intended for studies of astronaut health. Furthermore, these studies are not meant to replace the deficit that resulted when NASA significantly decreased its investment in Earth science research. These studies are meant to facilitate science that NIH ICs support to advance the knowledge of the biology of various organ systems of interest to participating ICs.

   Council member Dr. Harry Dietz, the Victor A. McKusick Professor of Medicine and Genetics at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, congratulated NIAMS on its role in this impressive initiative. He asked about the restriction on animal studies, and whether this restriction was permanent or time limited. Dr. McGowan explained that the restriction was time limited. The intent was to begin with cell and molecular biology work. Because of upload and payload restrictions, animal experiments are very limited on the ISS (only approximately 12 mice could be flown for an experiment). One significant advantage of the BioMed-ISS Program is that NASA covers the cost to transport these experiments. Dr. Katz also noted that the expense associated with animal studies on the ISS was also a consideration.

   Council member Mr. Bradley Stephenson, Attorney at Law, PLLC, asked if this program represents the first NIH-funded research in space. Dr. McGowan explained that the BioMed-ISS Program is a continuation of previous NIH research in space, most of which has been through intramural programs. She also noted that NASA is hoping to engage additional agencies (and commercial entities) with these types of collaborations for research on the ISS. Mr. Stephenson asked if the NIH was anticipating an increase in applications to the FOA this year over the 22 received in 2009. Dr. McGowan indicated that a count of the letters of intent for these applications was not available.

   Council member Dr. Henry Kronenberg, Chief of the Endocrine Unit at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, commented that the difficulty and style of this research necessitates the establishment of interdisciplinary groups. This program is an example of the broad interdisciplinary research that the NIH is trying to encourage.

6. BUILDING INTERDISCIPLINARY RESEARCH TEAMS (BIRT)

   Dr. Baker provided the Council with an update on the NIAMS BIRT award program. He acknowledged Drs. Fei Wang and Xibin Wang (both Health Scientist Administrators within the NIAMS Division of Musculoskeletal Diseases) for their support in building and maintaining the program. He explained that the goal of the NIAMS BIRT awards are to build new interdisciplinary teams that add new dimensions to existing NIAMS grants and yield insights that could not have been achieved by an isolated laboratory or individual. These awards are competitive revision awards (predominantly R01s) and are peer reviewed. The review for these awards is focused more on the significance of the problem, the degree of innovation, and the potential impact of the collaboration both on the research project and on the field, and less on the exact approach. A considerable degree of risk is acceptable for these grants, provided that the risk is commensurate with the potential impact of the project.

   BIRT awards include $100,000 in direct costs for up to 1 year. The Institute does not expect that the Principal Investigators (PIs) will be able to complete their projects within this 1-year time period or within the $100,000 budget cap. The award is intended to jump-start the collaboration, with the expectation that the PIs will build these collaborations into competitive renewal of the parent grant.

   The BIRT Program has been ongoing for three years. The Request for Applications (RFA) was first released in 2007, with subsequent releases in 2008 and 2009. Awards were made in the following fiscal years for each. BIRT I and BIRT II were pilot programs that were limited to specific scientific areas or pairings. This restriction was imposed to limit the number of applications coming in for review and to provide a focus on scientific areas in which adding an interdisciplinary component was thought to make a significant contribution. BIRT III was open to all NIAMS scientific areas of interest.

   Dr. Baker reported that for BIRT I, 11 of the applications were funded. For BIRT II, 10 were funded. For BIRT III, 12 were funded this summer; a list was provided of these 12 BIRT III awards. For BIRT III, a significant increase in applications was expected, in large part because it was open to all areas of scientific interest to the Institute. However, there was a decrease in the number of applications compared to BIRT I and BIRT II, possibly due to the availability of ARRA funding.

   In addition to the standard reporting requirements for scientific progress, additional reportable outcomes were included in the BIRT RFAs to provide early indicators of success. These additional reportable outcomes include the development of new competitive research collaborative projects (such as new, multi-PI R01s), the development of new direction(s) for the competitive renewal of the parent grant, the creation of resources and facilities shared with the communities, and the establishment of interdisciplinary scientific meetings/workshops.

   Dr. Baker discussed the results of a preliminary evaluation of BIRT I and BIRT II. In terms of outcomes, there were 17 new applications involving the interdisciplinary research team, 17 instances of new directions for the parent grant, 11 cases of new shared resources or facilities, and 9 cases of BIRT awardees convening interdisciplinary meetings/workshops. Dr. Baker noted that the Institute received reported outcomes from all 21 funded BIRT I and BIRT II awards. Examples of the shared resources developed and made available to the community through BIRT I and BIRT II include software and Web tools primarily for bioinformatics and systems biology applications, animal models, and reagents such as monoclonal antibodies.

   Dr. Baker concluded his remarks by noting that this early evaluation of the BIRT Program suggests that it is going to be successful in establishing long-lasting interdisciplinary collaborations. However, the long-term success of these collaborations will depend on whether the PIs can obtain additional funding. There is initial evidence that the BIRT awards are enhancing existing research projects and creating new research directions. It appears that the BIRT Program is producing the intended results. Based on this and the fact that interdisciplinary collaborations are becoming increasingly important for biomedical research, the NIAMS is considering re-issuing the BIRT RFA for FY 2011.

   Discussion

   Dr. Green asked for a breakdown of the type of interdisciplinary groups that have been formed through BIRT. Dr. Baker indicated that these groups vary to a large extent. Dr. Katz noted that in general, these groups include engineering and biology, in addition to a variety of other disciplines. Dr. Baker noted that imaging modalities were a popular addition to research grants in this program, as was mathematical modeling, bioinformatics, and genetics.

   Council member Dr. Regis O’Keefe, Chair of the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center, asked about how this program reaches out to attract new investigators, women, and underrepresented minorities. Dr. Baker noted that by the time PIs have an R01, they are no longer considered to be new investigators. The BIRT Program is not intended to attract new investigators, although some of the parent grants were awarded as new investigator awards only 1 or 2 years prior to receiving the BIRT award. Dr. Baker noted that women are very well represented among BIRT PIs, although the demographic data for BIRT award recipients were not available. Dr. Diamond expressed some concern that many of these types of initiatives provide awards to established investigators and decrease the number of new investigators.

7. 2012 INITIATIVES

   Dr. Katz reminded Council members that every year at the September Council meeting, NIAMS leadership informs Council members in general terms of the Institute’s future plans. The NIAMS remains committed to investigator-initiated research. In recent years, between 65.5 and 67% of the NIAMS budget has been allocated to research project grants (most of it in the form of unsolicited applications). Investigator-initiated research is a core value for the NIAMS and for many of the other NIH Institutes.

   For the last five years, the NIAMS has maintained its success rate at 19-21 percent. For FY 2010, the success rate will be at least 20 percent. The Institute’s payline has been at 14.5-15 percent over the last 5 years as well. Dr. Katz reminded Council members to consider these numbers in the environment of a flat budget. The NIAMS remains committed to making plans and being positioned to generate new initiatives for its communities to respond to. Council members were provided with a list of initiatives that was generated through the results of roundtable discussions, scientific planning retreats, and the interactions of NIAMS Program Directors and Division Directors with various communities. These initiatives include:

   • Bridging the GaP Between Genotype and Phenotype With iPSC-Derived Disease Models
   • Functional Studies of Disease Risk Variants in Polygenic Skin and Rheumatic Diseases
   • Itch Research and Treatment
   • Natural History Studies To Enable Clinical Trials in Rare Rheumatic, Musculoskeletal and Skin Diseases
   • Advancing Ultrasonography for Musculoskeletal Soft Tissue and Skin
   • Integrated Analyses of Existing Multidimensional Datasets of Relevance to NIAMS Diseases
   • NIAMS SBIR To Promote Commercialization of NIAMS Mission Relevant Research Areas
   • NIAMS Building Interdisciplinary Research Team (BIRT) Awards.

   Discussion

   Dr. Green agreed with Dr. Diamond’s previous comment regarding her concern that the BIRT awards and similar initiatives tend to build up established investigators and decrease the number of new investigators. However, these types of programs can be seen as bringing young people into the system more so than other mechanisms. Through the BIRT awards, postdoctoral fellows and students from different types of disciplines are interacting with each other in ways that she has not seen before. She indicated that initiatives such as BIRT can be viewed as supporting these types of interactions that will help build the research infrastructure in the future.

   Dr. Kronenberg noted that the BIRT awards are small grants (one year, $100,000) and that almost by necessity, they must go to researchers who have established enterprises. He characterized the BIRT program as an experiment in how to best encourage interdisciplinary research, and noted that it is just one of what must be a variety of approaches to encouraging interdisciplinary research.

   Dr. Diamond clarified that she supports the BIRT awards and emphasized the importance of tracking and evaluating the success of these types of interdisciplinary grants in study sections. It is particularly challenging for study sections to include all of the necessary expertise required to review many of these interdisciplinary grant applications, and it is important to promote activities that enhance the comfort level of study section members with these types of applications.

   Dr. Katz commented that the BIRT Program requires a great deal of Institute staff time because each of these applications is scrutinized to ensure that it includes a new interdisciplinary interaction (e.g., if researchers have previously co-authored papers together, they are not eligible). A future Council meeting will include a discussion of the number of new investigator and early stage investigator awards made by the Institute. Dr. Katz explained that in the past, the NIAMS has used a differential payline of 3 to 5 percent for new investigators. Next year, it is likely that the Institute will initially not have a differential payline for new investigators, primarily because the Institute funded approximately 50 new investigators this year (a significant increase over what has been funded in previous years).

   Dr. Susana Serrate-Sztein, Director of the NIAMS Division of Skin and Rheumatic Diseases, added that the percentage of R01s awarded to new investigators is impressive and that this fact should be publicized to the community. Dr. Katz agreed, noting 1 out of every 3 or 3.5 R01s is awarded to new investigators. One of the biggest challenges is encouraging investigators to enter into and stay in research.

   Dr. Dietz reminded his fellow Council members that new investigators are not necessarily early investigators. Dr. Katz agreed, noting that data from NIAMS on new and early stage investigators will be shared at a future Council meeting, as will the success rate of an early stage investigator on a new submission compared to the success rate of an established investigator with a new submission.

8. NIH IMPLEMENTATION OF THE AFFORDABLE CARE ACT PROVISIONS, PATIENT-CENTERED OUTCOMES RESEARCH INSTITUTE (PCORI) AND THE CURES ACCELERATION NETWORK (CAN)

   Mr. Pat White, NIH Associate Director for Legislative Policy and Analysis, reminded Council members that the Affordable Care Act is a very complex document, and that implementing the law will be a very complex undertaking. There are numerous provisions in the law that are relevant to the NIH. Research provisions include pain research, congenital heart disease research, postpartum depression research, breast cancer screening research in young women, emergency medicine, and access to clinical trials. Organizational provisions include designating the National Center for Minority Health and Health Disparities as an official NIH Institute and codifying the reporting relationship between the ORWH Director and the NIH Director. In addition, financial conflicts of interest were featured in the bill. A so-called "physician sunshine" database that the Department of Health and Human Services (DHHS) must maintain was mandated.

   Mr. White then focused his presentation on the Patient-Centered Outcomes Research Institute (PCORI) and the Cures Acceleration Network (CAN). He explained that PCORI’s charge is to assist patients, clinicians, purchasers, and policymakers in making informed health decisions by advancing the quality and relevance of evidence on how health conditions can be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis that considers variations in patient subpopulations. The Affordable Care Act enables the establishment of a non-profit, tax-exempt institute (PCORI) to pay for comparative effectiveness research (CER) out of a new trust fund. Funding includes $10 million for FY 2010, $50 million for FY 2011, $150 million for FY 2012, and $150 million for 2013-2019 with a per capita charge per health insurance enrollee (per year). It is expected that these per capita charges will generate approximately $600 million per year to fund the operations, studies, and other activities of PCORI.

   PCORI will identify national research priorities and establish a research project agenda. The Institute will be overseen by a 19-member Board of Governors that will include Directors or designees of the NIH and Agency for Healthcare Research and Quality (AHRQ). Board of Governors members have been appointed by the General Accounting Office’s Comptroller General (NIH Director Dr. Collins is a member of the Board). The Board will be chaired by Dr. Eugene Washington, Vice Chancellor of the University of California, Los Angeles Health Sciences and Dean of the David Geffen School of Medicine. The Board will create and engage with a standing 15-member Methodology Committee to develop and improve the science and methods of comparative clinical effectiveness research.

   Mr. White explained that PCORI is authorized to award contracts or enter into agreements to carry out CER studies. PCORI is required to ensure that there is a peer review process in place and is authorized to use an existing peer review process. AHRQ, in consultation with the NIH, has been charged with disseminating PCORI research findings. PCORI is prohibited from mandating coverage, reimbursement, or other policies for any public or private payer. Similarly, the DHHS Secretary is prohibited from using PCORI research or recommendations as a basis for denying coverage. In concluding his remarks regarding PCORI, Mr. White noted that the NIH has a distinguished history of supporting landmark CER studies.

   Mr. White then discussed the CAN, explaining that the idea that NIH-funded research or the NIH itself should be more involved in translational or clinical research has been proposed for some time. In 2004, then presidential candidate Senator Joseph Lieberman made the creation of a “National Institute of Cures” one of the pillars of his presidential platform, in essence creating an independent Institute funded at $15 billion per year to pursue clinical and translational research. In early 2009, Senator Arlen Specter began promoting a similar concept that included having different stakeholders involved in the review process, broadening the eligible pool of grantees, providing an "X prize" follow-on to ARRA, and allowing the NIH "DARPA-like authorities." This vision of CAN was a centerpiece of Senator Specter’s campaign.

   As passed in the Affordable Care Act, the CAN was established within the NIH Office of the Director with an FY 2010 budget of $500 million. The following new awards have been created:

   • Cures Acceleration Partnership Awards, which include up to $15 million and require matching funds ($1 for every $3 awarded by the NIH).
   • Cures Acceleration Grants, which include $15 million per award.
   • Cures Acceleration Flexible Research Awards, which include a DARPA-like research authority and may represent up to 20 percent of the CAN budget.

   The CAN includes a 24-member Review Board that advises the NIH Director on barriers to successful translation of basic science into clinical applications. The Board includes representatives of the venture capital community, individual basic science disciplines, patient advocates, etc. One feature of the CAN is to facilitate U.S. Food and Drug Administration review for the high-need cures funded by CAN.

   Mr. White noted that if the current appropriations impasse can be resolved, the NIH will be in a position to establish the CAN. The Senate bill includes language appropriating $50 million to create the CAN. The House bill has not passed the full Committee but includes an appropriation of up to $50 million. He noted that the CAN has created a great deal of interest and enthusiasm among a variety of stakeholders, including venture philanthropy organizations, the biotechnology industry, patient advocates, and others.

   Discussion

   Dr. Griffith noted that CER studies have been conducted by insurance companies. Dr. Katz added that a recent classic example is a study on lipid-lowering agents sponsored by Bristol Myers Squibb that was published in The New England Journal of Medicine. Dr. Griffith commented that some insurance plans have started to examine outcomes as metrics and asked about how much innovation from the private sector has been included in PCORI activities. Mr. White explained that while PCORI was progressing through the legislative process, the vision of Senate Finance Committee staff was that stakeholders from the community, such as private sector health insurers, hospitals, etc., would be part of an advisory board to introduce new views and be in a position to negotiate and mediate for their respective communities. How successful this vision will be remains to be seen.

   Dr. Katz asked Mr. White to comment on the stay on hESC research referenced in his Director’s Report. Mr. White reminded Council members that on August 23, 2010, a preliminary injunction was issued to prohibit the NIH from funding hESC. The oral arguments before the U.S. Court of Appeals that took place on the day before this Council meeting related to whether or not the NIH would be granted an emergency stay of this preliminary injunction so that it could continue to pursue funding and the other activities associated with hESC research. The NIH currently is operating under an administrative stay, which is a temporary measure issued by the U.S. Court of Appeals on September 9, 2010. The arguments before the Court on the day prior to this meeting related to granting an emergency stay pending the outcome of the legal process. The judge will be considering arguments for a summary judgment, essentially a decision by the judge about whether the NIH and the hESC research it is pursuing and funding violates either the Dickey-Wicker Amendment (which prohibits the use of federal funds in the creation or destruction of embryos for research) or puts other stem cell researchers (e.g., adult stem cell researchers) at a competitive disadvantage. Mr. White acknowledged that both arguments are problematic and noted that the administration and DOJ are addressing them. There is no indication of when the decisions from yesterday’s deliberations will be made available.

   Dr. Katz asked Mr. White to discuss the expectations and reality of the CAN initiative. Mr. White noted that the CAN operates in an area in which 9 times out of 10, a project fails. In its initial stages, it is not reasonable to expect that the CAN will be more successful than this. The hope is to select some promising projects while at the same time beginning to re-engineer the drug development pipeline and process. He emphasized that these activities will take time and will require realism and restraint in terms of what can be expected from this new initiative in the next few years.

   Dr. Dietz asked about the PCORI initiative and expressed concern that if one incentive for PCORI is to limit the increasing cost of health care, evidence-based medicine will be prioritized for populations rather than for individuals. He asked if there are adequate safeguards in place for the principle of personalized or individualized medicine and the interests of persons with rare disorders who may be uniquely responsive to a treatment. Mr. White acknowledged that this is a concern, and one that Dr. Collins is aware of. He indicated that he did not know of any attempt to address this question relative to how PCORI will operate. Mr. White noted that to the extent that academic medicine is part of the discussion, it is hoped that the case for individualized therapies can be made. The tension between personalized therapies and population-based approaches will have to be monitored closely.

9. DIVISION OF PROGRAM COORDINATION, PLANNING, AND STRATEGIC INITIATIVES (DPCPSI)

   Dr. James Anderson, DPCPSI Director, explained that the Division was created by the NIH Reform Act of 2006. DPCPSI’s mission is to:

   • Identify emerging scientific opportunities, rising public health challenges that have not been met, and scientific knowledge gaps that merit further research
   • Develop and apply resources (databases, analytic tools, and methodologies) in support of portfolio analyses and priority setting
   • Plan and implement trans-NIH initiatives supported by the Common Fund
   • Plan, support, and provide technical assistance in the development of program evaluations
   • Coordinate research related to AIDS, behavioral and social sciences, women’s health, and disease prevention.

   Dr. Anderson presented a slide showing the organizational components of the DPCPSI and discussed each in detail. Within the immediate DPCPSI office are two main groups:

   • Evaluation and Performance Assessment. Staff in this group manage the evaluation set-aside program for the NIH, including the review and funding of evaluation proposals. They provide hands-on technical support and guidance on design and methodological issues in evaluation planning and implementation. Staff also are responsible for carrying out special projects to evaluate program performance, assess trans-NIH initiatives, and conduct needs assessments. They organize workshops to strengthen NIH’s capacity to evaluate programs and bring together the NIH evaluation community to share evaluation findings, lessons learned, and best practices. In addition, these staff members coordinate and prepare annual plans and reports required by the Government Performance Results Act.
   • Portfolio Analysis. This group’s mission is to develop and disseminate the capabilities to extract novel concepts and knowledge from the scientific achievements represented in the research portfolio and identify emerging areas of research and scientific opportunities. These activities involve the electronic integration and analysis of data from NIH research portfolios and other sources to identify emerging scientific concepts/areas, opportunities, and gaps in research, and to assist in understanding/planning areas of NIH support. This group aims to move away from manual analysis towards using information technology to generate a preliminary analysis of NIH’s scientific portfolio and provide an instantaneous indication of where science has been, is now, and might be headed. At NIAMS request, this group recently looked at NIAMS’ activities with a particular emphasis on wound healing and rheumatic diseases. This report will be presented at a future Council meeting.

   Dr. Anderson reminded Council members that the NIH Council of Councils was established by the NIH Reform Act of 2006, and that the Council of Councils advises the NIH Director on DPCPSI policies and activities. Specific Council of Councils tasks include: (1) advising on research responsive to emerging scientific opportunities, public health challenges, and knowledge gaps; (2) conducting concept reviews for proposed initiatives to be supported through the Common Fund; and (3) carrying out second-level reviews of the Transformative R01 Grant Program that is supported by the Common Fund. The next meeting of the Council of Councils is scheduled for November 8, 2010. At that meeting, the Institute will be represented by NIAMS Advisory Council member Dr. O’Keefe. Dr. Katz commented that in his view, the way in which this Council of Councils and the NIH ICs can best interact is if the representative from the IC is a current member of the respective ICs’ Advisory Councils.

   Dr. Anderson then described the Offices within the DPCPSI.

   • Office of AIDS Research (OAR). The OAR provides a coordinated, unified NIH research front against the AIDS pandemic. The Office functions as an "institute without walls," with the authority to plan, coordinate, and evaluate AIDS research; set scientific priorities; and determine budgets for all NIH IC AIDS research. OAR coordinates the annual Trans-NIH Strategic Plan with an annual trans-NIH budget linked to the Strategic Plan, and the annual Presidential By-Pass Budget, based solely on scientific opportunities. OAR ensures that the FY 2011 strategic plan aligns with the President’s National AIDS Strategy Goals. OAR’s planning process includes meeting with trans-NIH coordinating committees and NIH ICs; other government agencies with AIDS-related research responsibilities; and non-government experts from academia, foundations, and industry and community representatives.
   • Office of Behavioral and Social Sciences (OBSSR). OBSSR’s mission is to stimulate behavioral and social sciences research throughout the NIH, thereby improving understanding, treatment, and prevention of disease with a behavioral and social contribution. OBSSR’s role is to: (1) coordinate, plan, lead, and support trans-NIH initiatives; (2) provide training, education, and information about the behavioral and social sciences; and (3) inform NIH leadership, the behavioral and social sciences research community, Congress, and the public. Strategic priorities for the Office include "next generation" basic science, interdisciplinary research, systems-thinking approaches to health, and population impact.
   • Office of Disease Prevention (ODP). The ODP: (1) fosters and coordinates trans-NIH activities on prevention in collaboration with other agencies, academia, and non-government organizations with a focus on research, training, and information dissemination; (2) monitors and reports on prevention research advances and areas of research opportunities; and (3) provided input on DHHS prevention initiatives. The following three Offices are located within the ODP:
     • Office of Medical Applications of Research (OMAR). OMAR assesses, translates, and disseminates research findings to the biomedical community and the public. OMAR’s major activities include the NIH Consensus Development Program (which houses NIH Consensus Development and State-of-the-Science Conferences) and the Medicine in the Media course, which offers annual free training to journalists with the goal of improving medical reporting to the public.
     • Office of Rare Diseases Research (ORDR). The ORDR stimulates, coordinates, and supports research in response to the needs of patients who suffer from the almost 7,000 known rare diseases.
     • Office of Dietary Supplements (ODS). ODS’ mission is to strengthen the knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public.
   • Office of Research on Women’s Health (ORWH). The ORWH advises the NIH Director and staff on matters relating to women’s health. The Office: (1) focuses on research related to diseases, disorders, and conditions that affect women; (2) ensures that research adequately addresses issues regarding women’s health and that women are appropriately represented in studies; and (3) focuses on the recruitment, retention, re-entry, and advancement of women in biomedical careers. Dr. Anderson provided examples of interdisciplinary research and career development programs supported by NIAMS and the ORWH. In addition, NIAMS research supported by the Office includes osteoporosis research, SLE research, and the Osteoarthritis Initiative.
   • Office of Strategic Coordination (OSC). The OSC works with staff and leadership across the NIH to identify and promote NIH-wide scientific opportunities supported by the NIH Common Fund, including the NIH Roadmap. The Office also coordinates a strategic planning process that engages the broad community of stakeholders to identify emerging opportunities and priorities. It also manages the Common Fund, making funds available to the ICs that implement the programs.

   Dr. Anderson summarized that the DPCPSI has a number of Offices that have longstanding, ongoing efforts focused on fostering trans-NIH research in the areas of AIDS, women’s health, dietary supplements, and behavioral and social sciences. He noted that in the coming year, it is expected that the Common Fund will solicit research in the areas of health economics, ways to foster health maintenance organizations to use their data for research and share their data for research, and Early Independence Awards. Dr. Anderson commented that the NIAMS has participated in a number of Common Fund activities (e.g., a high-risk, high-reward project led by Dr. Griffith).

   Dr. Anderson concluded his remarks by listing his specific 6-month goals for DPCPSI. These include soliciting input from each IC, reviewing and refining the process for identifying Common Fund projects, working with DPCPSI Offices to ensure and enhance trans-NIH engagement and impact, and considering expectations related to portfolio analysis and how ICs use this information. He invited Council members to visit the DPCPSI Web site for additional information.

   Discussion

   Dr. Diamond asked about how, as resources become more limited and opportunities increase, the DPCPSI is considering what the entire portfolio of the NIH should be in terms of training, support at each level, the expectation of how many first-time R01s should be funded on competitive renewal, and how many independent laboratories looking at a question are needed. She expressed concern that there is a great deal of time spent on content areas but less time considering what the basic science should be at a national level. Dr. Anderson noted that he shares these concerns and has identified workforce training as an area of focus for the DPCPSI.

   Dr. Griffith asked about how DPCPSI staff determine in a portfolio analysis which projects are actually focused on a specific disease as opposed to those projects that are more basic science related but mention that specific disease. Lora Kutkat, Senior Advisor in the Office of the DPCPSI Director, explained that there are a few approaches to this issue. One example is to use a text-mining software that generates its own categorization of what is considered major research (e.g., by analyzing how frequently a term is used).

   Dr. Rosen asked about where the ODS was located prior to the creation of the DPCPSI, how the Division’s activities enhance those of the ODS, and whether the establishment of the DPCPSI will change how ODS functions. Dr. Anderson commented that ODS and all of the Offices that fall under the DPCPSI address trans-NIH efforts and have similar mechanisms for meeting with representatives from ICs and working with ICs as well as outside agencies to help prioritize activities. Dr. Katz clarified that most DPCPSI Offices report directly to Dr. Anderson, who reports to Dr. Collins. Overall coordination will flow through the DPCPSI.

10. BOARD OF SCIENTIFIC COUNSELORS REPORT

    This portion of the meeting occurred during closed session.

11. CONSIDERATION OF APPLICATIONS

    The Council reviewed a total of 1636 applications in closed session requesting $2,031,010,762 and recommended 1636 for $2,031,010,762. Approximately 180 of these applications were approved by early concurrence prior to this meeting.

12. PORTFOLIO ANALYSIS

    This portion of the meeting occurred during closed session.

13. ADJOURNMENT

    The 72nd National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00 p.m. Proceedings of the public portion of this meeting are recorded in this summary.

    I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.