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

Minutes of the 71st Meeting
June 15, 2010
8:30 a.m. to 3:00 p.m.

Closed Session

1. CALL TO ORDER

   The 71st meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council was held on June 15, 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 Beach
   Dr. Leslie Crofford
   Dr. Betty Diamond
   Dr. Hal Dietz
   Ms. Karen Evans
   Dr. Kathleen Green
   Dr. Linda Griffith
   Dr. John H. Klippel
   Dr. Henry Kronenberg
   Ms. Ann Kunkel
   Dr. Regis O�Keefe
   Ms. Jean Pickford
   Dr. Clifford J. Rosen
   Mr. Bradley Stephenson
   Dr. H. Lee Sweeney (via teleconference)
   Dr. Julio Vergara
   Dr. James Weinstein

   Staff and Guests

   The following NIAMS staff and guests attended:

   Staff

   Dr. Janet Austin Mr. Steve Austin Dr. Carl Baker Dr. Teresa Bernaciak Ms. Susan Bettendorf Dr. Amanda Boyce Dr. Branden Brough Ms. Justine Buschman Dr. Robert Carter Dr. Faye Chen Mr. Robert Chen Dr. Ricardo Cibotti Ms. Barbara Cohn Ms. Stephanie Craver Ms. Wilma Peterman Cross Ms. Robin DiLiello Ms. Teresa Do Dr. Jonelle Drugan Mr. Erik Edgerton Ms. Sharon Fair Ms. Barbara Footer Ms. Gerta Gallop-Goodman Ms. Valerie Green Ms. Gail Hamilton Ms. Kaitaia Huynh Ms. Katie Joffee Dr. Stephen I. 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. Su-Yau Mao Dr. Marie Mancini Mr. Carl McCabe Ms. Lei McCabe Dr. Joan McGowan Ms. Leslie McIntire Dr. Laura K. Moen Ms. Regina Mong Ms. Melinda Nelson Dr. Leon Nesti Dr. John O'Shea Dr. James Panagis Dr. Charles Rafferty Ms. Kelli Reid Ms. Natalie Reyes Ms. Trish Reynolds Dr. Susana Serrate-Sztein Dr. William Sharrock Ms. Sheila Simmons Ms. Theresa Smith Ms. Allisen Stewart Ms. Jamie Thompson Dr. Phil Tonkins Dr. Hung Tseng Dr. Bernadette Tyree Dr. Fei Wang Dr. Xibin Wang Dr. Yan Wang Ms. Sara Wilson Dr. James Witter

   Guests

   Dr. Chris Austin, National Human Genome Research Institute, NIH
   Dr. Andrea Baruchin, Foundation for the NIH
   Mr. Mark Beckwith, Nevus Outreach, Inc.
   Ms. Kimberly Beer, Arthritis Foundation
   Mr. Michael Bykowski, Consolidated Solutions and Innovations
   Ms. Tanya Dougans, National Heart, Lung, and Blood Institute, NIH
   Mr. Jamie Gregorian, American Academy of Orthopaedic Surgeons
   Mr. Joe Heastie, JADA Creative Communications, Inc.
   Dr. John Holden, Department of Veterans Affairs
   Ms. Annie Kennedy, Muscular Dystrophy Association
   Ms. Jennifer McBride, Arthritis Foundation
   Ms. Kimberly McGraw, IQ Solutions
   Dr. Rebecca Minnillo, Society for Investigative Dermatology
   Ms. Maggie Owner, Lewis-Burke Associates, LLC
   Ms. Michelle Rodrigues, SRI
   Ms. Courtney Schoessow, Nevus Outreach, Inc.
   Ms. Lisa Swanberg, IQ Solutions
   Mr. Cecil Wallace, Arthritis Foundation

2. CONSIDERATION OF MINUTES

   A motion was made, seconded, and passed to accept with no changes the minutes of the 70th Council meeting, held on February 2, 2010.

3. FUTURE COUNCIL MEETING DATES

   Future Council meetings are currently planned for the following dates:
   September 28, 2010
   February 1, 2011
   June 14, 2011* 
   September 27, 2011
   January 31, 2012
   June 5, 2012
   September 11, 2012

   * Dr. Katz commented that on the day before the June 14, 2011, Council meeting, the NIAMS will be holding a scientific symposium to celebrate the 25th anniversary of the Institute�s founding. Some Council members may be asked to participate in the symposium.

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 report. He noted that his "Director�s Column" focuses on the NIH International Clinical Research Fellows Program, an initiative that supports mentored clinical research in a developing country setting for medical residents and fellows, as well as Ph.D. scientists in health-related fields.

   Dr. Katz noted that Dr. Regis O�Keefe (Chair of the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center), Ms. Jean Pickford (Executive Director of the Foundation for Icthyosis and Related Skin Types), Mr. Bradley Stephenson (Attorney at Law, PLLC), and Dr. Julio Vergara (Distinguished Professor in the Department of Physiology at the University of California, Los Angeles School of Medicine), who joined the Council as ad hoc members in February 2010, have been officially appointed as Council members. He also introduced Council member Dr. Hal Dietz (the Victor A. McKusick Professor of Medicine and Genetics at Johns Hopkins University School of Medicine), who was attending his first Council meeting.

   Dr. Katz reported that Council member Dr. S. Wright Caughman was recently named as Interim Executive Vice President for Health at Emory University. He also recognized Council member Dr. Linda Griffith, of the Department of Biological and Mechanical Engineering in the Biological Process Engineering Center at the Massachusetts Institute of Technology, for sharing her experiences as described in a recent New York Timesarticle.

   Personnel Changes at the NIH/NIAMS

   Dr. Katz noted with sadness the passing of Dr. Greg Mundy, a renowned bone biologist who served on the NIAMS Council from 1997 to 2001. At the time of his death, Dr. Mundy was the Director of the Vanderbilt Center in Bone Biology and the John A. Oates Chair in Translational Medicine and Professor of Medicine, Pharmacology, Orthopaedics, and Cancer Biology. The NIH honored the legacy of Dr. Ruth Kirschstein, who passed away last year at the age of 82, after spending more than 50 years as a civil servant in the Department of Health and Human Services (HHS). Dr. Kirschstein was the first woman to direct an NIH Institute (the National Institute of General Medical Sciences). She served as NIH Deputy Director and as Acting NIH Director, and she led the Office of Research on Women�s Health (ORWH) at its inception. A scientific symposium was held in her honor; Dr. Katz co-chaired a session during which former Ruth L. Kirschstein National Research Service Award recipients presented their work on cancer metastasis

   At the NIH level, NIH Deputy Director Dr. Raynard Kington will be leaving the NIH at the end of July to accept the position of President of Grinnell College; a search is underway to recruit a new principal NIH Deputy Director. Former NIH Director Dr. Harold Varmus will be returning to the NIH as Director of the National Cancer Institute (NCI) in July. Most recently, Dr. Varmus served as President of Memorial Sloan-Kettering Cancer Center. In March, Mr. Pat White joined the NIH as its Legislative Director. Before taking this position, Mr. White was the Vice President for Federal Relations at the Association of American Universities (AAU), where he developed and executed advocacy strategies for AAU�s president and the leadership of the 60 top research universities in the United States. Mr. White will be invited to speak at a future Council meeting.

   At the NIAMS level, Dr. Juan Rivera, Chief of the Laboratory of Molecular Immunogenetics, has been appointed as NIAMS Deputy Scientific Director. Dr. Rivera will be leading a strategic plan for the NIAMS Intramural Research Program, among his other duties.

   Highlights of Selected Recent Scientific Advances

   • A recent genome-wide association study (GWAS) made an unbiased comparison of the genetic make-up of vitiligo patients from across the United States and the United Kingdom with healthy controls. A team of researchers led by Dr. Richard Spritz found that the genomes of vitiligo patients displayed significant differences from healthy controls in genes coding for immune function, including some involved in the development of autoimmunity and other autoimmune diseases, and in the tyrosinase gene. Different and unrelated variations in the tyrosinase gene are associated with melanoma, suggesting that susceptibility to vitiligo and melanoma attributable to tyrosinase may work through different mechanisms (N Engl J Med. 2010 May 6;362(18):1686-97. Epub 2010 Apr 21).
   • Another GWAS study reported this year by an international consortium, including NIAMS-supported extramural and intramural researchers, focused on genetic risk factors associated with ankylosing spondylitis. Most individuals who have ankylosing spondylitis have a genetic marker�a specific human leukocyte antigen, HLA-B27, which is part of a family of genes known as the major histocompatibility complex (MHC) that plays a central role in the immune system. However, only 1-5 percent of individuals who have HLA-B27 develop ankylosing spondylitis, suggesting that there are other genes or factors contributing to the disease. Dr. Mike Ward and colleagues found strong association with the MHC, and confirmed previously reported associations at ERAP1 and IL23R, which contain genes associated with immune functions. The investigators also discovered two new genes: IL1R2, which encodes another protein involved with immune function, and ANTXR2, which codes for a protein associated with tissue development (Nat Genet. 2010 Feb;42(2):123-7. Epub 2010 Jan 10).
   • Corticosteroids are the most common treatment for infantile hemangiomas, but there is new understanding of the mechanism of action of corticosteroids in infantile hemangiomas. Recently, investigators reported that administration of the corticosteroid dexamethasone suppressed the formation of hemangiomas in a mouse model. Dexamethasone specifically inhibited the ability of hemangioma-derived stem cells to generate new blood vessels, in contrast to its effects on vascular progenitor cells from other sources. Further investigations with cultured hemangioma-derived stem cells showed that dexamethasone decreased the expression of vascular endothelial growth factor-A, a molecule that promotes the formation of new blood vessels. These findings provide important new information about potentially targeting hemangioma stem cells in future therapeutic development (N Engl J Med. 2010 Mar 18;362(11):1005-13).
   • Council member Dr. Hal Dietz and colleagues have been studying the role of fibrillin-1, an extracellular matrix protein, in the disease stiff skin syndrome. The researchers found excessive amounts of fibrillin-1 in the skin of stiff skin syndrome patients, and a cluster of mutations in these patients� fibrillin-1 genes. The identification of mutations in the fibrillin-1 gene and the observation of the consequences of these mutations in cellular behavior have generated important insights into the cause of stiff skin syndrome. These findings may contribute to the development of more effective therapies for the treatment of stiff skin syndrome, as well as other forms of scleroderma (Sci Transl Med. 2010 Mar 17; 2(23):23ra20).
   • Dr. Mariana Kaplan and colleagues found a unique neutrophil subset called low-density granulocytes that are found in much greater quantities in the blood of lupus patients than in healthy control subjects. Lupus patients with the largest amounts of low-density granulocytes had more severe clinical characteristics, including vascular involvement, than lupus patients with fewer of these granulocytes. Low-density granulocytes also had an enhanced capacity to kill endothelial cells that line blood vessels, which could be another factor in vascular damage and another potential contributor to cardiovascular disease in lupus (J Immunol. 2010 Mar 15;184(6):3284-97. Epub 2010 Feb 17).
   • Building upon many years of research, Drs. Daniel Kastner, NIAMS Clinical Director and NIH Deputy Director for Intramural Research, and Richard Siegel, Acting Chief of the NIAMS Autoimmunity Branch, studied a mouse model and found that having one mutant gene and one normal gene for TNFR1 caused greater disease inflammation than having two mutant TNFR1 genes. The researchers concluded that mutant TNFR1 and normal TNFR1 must both be present to cause an increased inflammatory response in TNFR-associated periodic syndrome (TRAPS). This finding not only suggests new strategies to combat inflammation in TRAPS, but also provides insight into the function of the TNF receptor inside the cell, which could inform the treatment of other inflammatory diseases (Proc Natl Acad Sci USA. 2010 May 10. [Epub ahead of print] PubMed PMID: 20457915).
   • K-24 (Midcareer Investigator Award in Patient-Oriented Research) recipient Dr. Charles Thornton and colleagues conducted two clinical trials to test whether the drug mexiletine could improve the muscle function of patients who have myotonic dystrophy. Results from the double-blinded, placebo-controlled studies of 30 patients showed that mexiletine was effective in treating the muscle relaxation symptoms of myotonic dystrophy with no detectable adverse effects on cardiac activity (Neurology74(18):1441-8. PMID: 20439846).
   • A team of researchers led by Dr. Rick Deyo published data showing a 15-fold increase in the rate of complex lower back surgeries performed on older Americans from 2002 to 2007. Compared with less invasive procedures, the complex fusion procedures for spinal stenosis and degenerative spondylolisthesis were more costly, produced more major complications, and resulted in more post-operative deaths than simple decompression procedures. Additional long-term study is needed to determine the comparative effectiveness and cost effectiveness of various fusion procedures to relieve pain and improve function in elderly patients who have degenerative spondylolisthesis (JAMA. 2010 Apr 7;303(13):1309-10. PMID: 20371793).
   • Dr. Connie Chu and colleagues have developed optical coherence tomography, a method to evaluate the health of the cartilage surface during arthroscopic surgery. In addition to being potentially useful for identifying patients who would be likely to benefit from treatment, methods such as optical coherence tomography provide opportunities for researchers to: (1) identify molecules that are responsible for early tissue damage, and (2) develop treatments to prevent or delay the cartilage degradation that is thought to be associated with knee osteoarthritis (J Orthop Res. 2010 Apr; 28(4):546-52. Published Online: 15 Oct 2009 PMID: 19834953).
   • A team of researchers led by Dr. Mary Bouxsein and colleagues published a paper showing the deleterious effects of caloric restriction on the overall bone health of juvenile mice. The study received funding from the American Recovery and Reinvestment Act (ARRA) for this and other research into the effects of caloric restriction on growing bone. Because postnatal diet is a modifiable factor for families who have sufficient resources, knowledge that it affects the skeleton during the period of peak bone acquisition may lead to public health awareness of the deleterious effects of anorexia on bone as well as ways to improve skeletal health through better nutrition for all Americans throughout life (J Bone Miner Res. 2010 Mar 12. [Epub ahead of print]. PMID: 20229598).
   • Dr. Katz called Council members� attention to a media release from the University of Florida College of Public Health and Health Professions, which was one of four institutions that received a five-year, $7.5 million grant to launch a natural history study of boys who have Duchenne muscular dystrophy. Dr. Katz presented a video clip that personalizes the disease by focusing on a local family affected by Duchenne, talks about the study�s promise and acknowledges NIH support (the awards were funded by NIAMS and the National Institute of Neurological Disorders and Stroke).

   Update on Budget and Congressional Activities

   At the last Council meeting, Dr. Katz reported on the President�s Budget request for FY 2011, which had just been released and provides $32 billion for NIH, an increase of approximately $1 billion, or 3.2 percent, over the FY 2010 level. The proposed funding level for the NIAMS under the request is $555.7 million, which is approximately $16.9 million, or 3.1 percent, over FY 2010. This spring, the House and Senate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies invited Dr. Collins� testimony on the President�s budget proposal.

   Last month, Drs. Katz, Carl Baker (Health Scientist Administrator within the NIAMS Division of Skin and Rheumatic Diseases), and Branden Brough (Program Analyst within the NIAMS Office of Science Policy and Planning) met with staff from the office of Senator Sherrod Brown and a constituent from the Dystrophic Epidermolysis Bullosa Research Association (DebRA). The meeting presented an opportunity to describe how volunteer organizations can leverage NIH resources to promote research in their areas of interest.

   The Patient Protection and Affordable Care Act was signed into law by President Obama on March 23, 2010. The Act elevated the National Center for Minority Health and Health Disparities to the Institute level. The legislation also called for a new, non-profit institute to support comparative effectiveness research, and established the Cures Acceleration Network (CAN) at NIH with expanded authorities to advance new therapies, technologies, and pharmaceuticals. The CAN aims to bridge the �valley of death� between research discoveries and the manufacture of new drugs, vaccines, and technologies. NIH leadership is discussing how best to implement this new mandate, as the NIH has not yet received any appropriations for it.

   NIH/NIAMS Activities and Plans for the Future

   Consistent with the goals of the CAN, the NIH and U.S. Food and Drug Administration (FDA) launched a new partnership to accelerate the process from scientific breakthroughs to available therapies.

   Dr. Katz summarized highlights from the NIH Common Fund, an appropriated line item in the NIH budget. Common Fund programs for FY 2010 include regulatory science (with FDA), a library of integrated network-based cellular signatures, protein capture reagents, a knockout mice phenotyping center, science of behavior change, global health, and translational applications of stem cells. As part of the Common Fund initiative related to translational applications of stem cells, Dr. John O�Shea, Scientific Director of the NIAMS and Chief of the Institute�s Molecular Immunology and Inflammation Branch, has been tapped to lead the new NIH Induced Pluripotent Stem Cell Center. NIH Director Dr. Collins recently hosted a Big Think symposium to identify Common Fund areas of emphasis for the future. Researchers and NIH leaders brainstormed about projects related to the: (1) application of high-throughput technologies to important research problems, (2) translation of basic research into beneficial diagnostics and therapeutics, and (3) utilization of science to benefit health care reform.

   Dr. Katz reminded Council members that ARRA�s considerable investment in NIH-funded biomedical research was due largely to the efforts of longtime appropriator Senator Arlen Specter, who was defeated in Pennsylvania�s Democratic primary election. His departure, coupled with the retirement of Congressman David Obey, (both strong supporters of the NIH) underscores the urgency of communicating the importance of biomedical research to the American tax payers who support NIH�s work. Dr. Katz provided some examples of how the NIAMS publicizes the use of federal funds. For example, several NIAMS grantees have contacted the Institute to inform NIAMS staff about how ARRA has benefited their research. Others are beginning to publish papers citing their ARRA awards. In addition, NIAMS staff met with several Challenge- and Grand Opportunity-awardees during the annual Orthopaedic Research Society Meeting. Similar activities are planned for other major upcoming scientific conferences.

   Dr. Katz reported that the HHS currently is soliciting comments on proposed changes to the financial conflict of interest regulations for recipients of grants or contracts from the NIH and other HHS agencies.

   As part of efforts to maintain a robust peer-review system, the NIH recently published an NIH Guide notice encouraging Principal Investigators (PIs) to volunteer to be permanent or ad hoc reviewers. To recognize outstanding review and advisory service by members of the scientific community, and to minimize disincentives to such service, the NIH provides an alternate plan for submission and review of research grant applications from appointed members of NIH review and advisory groups and temporary members of NIH review groups with high levels of service.

   As discussed at previous Council meetings, the Institute has identified several key steps necessary for selecting investigator-initiated trials that are as timely and informative as possible. The NIAMS is currently developing new funding opportunity announcements that will create a two-stage process for supporting investigator-initiated interventional trials. All investigators seeking support for a clinical trial must first submit a clinical trial planning grant (U34) application. After successful completion of the U34, investigators will be able to apply for a clinical trial implementation cooperative agreement (U01). Prior to the submission of either the U34 or the U01 application, investigators will be asked to submit a Letter of Request seeking approval from the NIAMS. The Advisory Council Working Group on Clinical Trials, led by Dr. Carter, has been created and charged with examining the incoming Letters of Request at a conceptual level. The Working Group will provide advice to the Institute as to the potential for the clinical trial to improve patient outcomes.

   Dr. Katz provided the Council with an update on NIAMS staff members who have been recognized for their accomplishments. Dr. Kastner was elected to the National Academy of Sciences. A paper published by Dr. Carter was selected by the Journal of Immunology as one of its Pillars of Immunology and therefore regarded as a classic in the field. In March, the Journal featured a paper that Dr. Carter and Dr. Douglas Fearon published in Science, which focused attention on CD19 as an important cell surface receptor that critically regulates antigen-specific B cell responses. Marcia Vital, Mimi Lising, Sara Rosario Wilson, and Richard Clark, of the NIAMS Office of Communications and Public Liaison, received a bronze NIH Plain Language award for the booklet Joint Replacement Surgery (Cirug�a de reemplazo articular).

   With regard to the Institute�s information dissemination efforts, Dr. Katz noted that later in the meeting, Dr. Carter, along with NIAMS Office of Communications and Public Liaison Director Dr. Janet Austin, would provide an update on the Institute�s Multicultural Outreach Initiative. Since the NIAMS� inception, the NIAMS Coalition has played a vital role as a liaison among the researchers that the NIAMS supports, the patients who benefit from our research investments, Congress, and the general public. Coalition Co-Chairs Sheila Rittenberg from the National Psoriasis Foundation and Annie Kennedy from the Muscular Dystrophy Association recently invited member organizations to join Drs. Katz and Carter for a conference call update of Institute programs.

   Dr. Katz concluded his report by showing a video clip provided by Council member Dr. John Klippel, President and CEO of the Arthritis Foundation. The video, prepared by the Arthritis Foundation, the Ad Council, and the American College of Rheumatology, highlighted the fact that people who have osteoarthritis are not endangering their health by engaging in exercise.

   Discussion

   Council member Dr. James Weinstein, Professor and Chair of the Department of Orthopaedics at Dartmouth-Hitchcock Medical Center, suggested that there is still an epidemic of spine surgery in the United States for unknown reasons. The work by Dr. Rick Deyo described by Dr. Katz in his Director�s Report highlights this problem. The notion of comparative effectiveness research and how that is going to be funded in the Patient Protection and Affordable Care Act (P.L. 111-148) will be interesting. Dr. Weinstein noted that he is troubled by this issue and others that relate to how medical resources are utilized in this country.

   Dr. Carter thanked Council members who agreed to serve on the Advisory Council Working Group on Clinical Trials and noted that the group�s first meeting is being planned. At that meeting, the Working Group will review the ground rules and mission; it is hoped that this initial meeting will be face to face, with subsequent meetings held via video conference, Web conference, or teleconference.

5. THERAPEUTICS FOR RARE AND NEGLECTED DISEASES PROGRAM

   Dr. Chris Austin, Senior Advisor for the Director of Translational Research at the National Human Genome Research Institute (NHGRI), discussed NIH�s Therapeutics for Rare and Neglected Diseases (TRND) Program. He explained that much of what the NIH does involves studying basic biology and basic mechanisms of disease. Often during this process, researchers identify a target for intervention that, they believe, has the potential to reverse the pathophysiology of disease. The molecular libraries program that is part of the NIH Roadmap starts with assay development for high throughput screening. Although high-throughput screening garners a significant amount of attention, it is only the beginning of the process. The more difficult work lies within the medicinal chemistry phase, in which between 3,000 and 4,000 compounds will be made to try to improve the properties that come out of a screen to give them the efficacy and lack of toxicity properties necessary for advancement into animal and human studies.

   Dr. Austin described the "valley of death" Dr. Katz alluded to during his Director�s Report. This is the point at which the costs of drug development for a given disease skyrocket while the likelihood of success decreases dramatically. Organizations both public and private try to avoid work in this area because it is very expensive and likely to fail. However, to move from basic understanding of a disease to the patient, this phase must be undertaken; the TRND Program focuses on crossing this gap.

   The NIH TRND Program is a Congressionally mandated effort to speed the development of new drugs for rare and neglected diseases. TRND is a trans-NIH initiative, with governance/ oversight through the NIH Office of Rare Disease Research, which is administered by the NHGRI. TRND is a collaboration between intramural scientists who have expertise that typically does not exist in academic settings with extramural laboratories that have appropriate expertise. Dr. Austin noted that NIAMS Advisory Council member Dr. Hal Dietz is working on a TRND incubator project focusing on Marfan syndrome. Projects will enter TRND at a variety of stages of development and be taken to the phase needed for external organizations to adopt for clinical development.

   Dr. Austin described the TRND Program timeline, with infrastructure development a focus during FY 2009. He also described some of the distinguishing features of the TRND model: TRND takes a "disease agnostic" approach, takes advantage of cross cutting mechanisms, and to some degree is a practical adaptation to the scope of the problem (a brute force approach to the 6,000 rare and neglected diseases will not be effective). TRND confronts the science of preclinical drug development, and unlike in the private sector, reasons for successes and failures will be investigated and published. Project-specific activities include medicinal chemistry efficacy, pharmacology, toxicology, compound scale-up, formulation, first-in-human clinical trials, etc.

   TRND will have two primary panels involved in guiding the program. An external panel of representatives from academia, industry, patient advocacy groups, and elsewhere will perform a technical evaluation of proposed TRND projects as well as periodic assessments of project progress. A trans-NIH advisory group also will be overseeing the program (Dr. Carter represents the NIAMS on the group) and integrating TRND with other drug development programs across the NIH.

   TRND is expected to release a Request for Applications (RFA) this summer. The FY 2011 President�s Budget proposes an increase in funding for TRND up to $50 million, although it is unclear whether this budget will pass. If a $50 million budget becomes a reality, it is expected that four or five new projects will be selected. Projects can be submitted from intramural researchers, extramural researchers, biotech companies, pharmaceutical companies, foundations, and others. First-level review will be carried out by a special emphasis panel; second-level review will be carried out by the NIH Advisory Committee to the Director.

   Project and program review will involve built-in milestones and timelines; TRND leadership will be rigorous about stopping projects that do not meet their deadlines. Monthly project meetings will be held to evaluate progress and, every three months, TRND leadership will brief the trans-NIH advisory group. In addition, two annual reviews will be conducted—one on individual projects and one on TRND operations. In FY 2012, TRND will be fully operational; the goal is to work on approximately five projects per year. The average TRND project is expected to require two years to complete.

   Discussion

   Dr. Katz opened the discussion session by asking about intellectual property (IP) issues. Dr. Austin explained that IP is going to be handled in the same way as it is in a biotechnology or pharmaceutical company. The goal is to outsource or license IP to for-profit companies; there has to be IP on the compounds made through TRND. The idea is that the IP will be held in common between the collaborator and the NIH.

   Dr. Weinstein asked about the political strategy involved in getting drugs for rare and neglected diseases through the process, noting past delays associated with the development of HIV and tuberculosis drugs. Dr. Austin noted that he has had many conversations with representatives from the World Health Organization and other groups that are focused on the delivery of current therapies or repurposing existing therapies. There is very little activity in the gap between basic research and clinical application because of all of the inherent challenges (i.e., work in this area is expensive and likely to fail).

   Dr. Dietz characterized TRND as a good approach to a large, difficult problem and pointed to the need for a corporate partner at the end of the process. He asked how this program can succeed in the absence of a business model. Dr. Austin agreed with the need for business partners and noted that this topic is part of an ongoing discussion within the TRND Program. For example, should one of the selection criteria for TRND be that there is either a partnership agreement or expressed opinion that there is a business model to be made? Even if the Phase III trial or definitive trial for a rare disease is carried out, the NIH does not want to be in the business of manufacturing and marketing drugs. The difficulty is that a priori evaluations of business or prospective evaluations of business models are sometimes incorrect.

   Mr. Stephenson asked how the TRND program is reaching out to non-government organizations, disease advocacy groups, and foundations. Dr. Austin explained that until now, these activities have taken place on an ad hoc basis. TRND has approximately 15 different collaborations with various disease advocacy groups, and releasing the RFA will be a more formal way to forge these relationships. Of particular interest to rare disease organizations is a large-scale repurposing program that TRND is developing to identify existing therapies that may be efficacious for rare or neglected diseases. Dr. Katz noted that NIH ICs also have responsibility for disseminating information about the TRND Program to their various stakeholders.

   Council member Dr. Hank Kronenberg, Chief of the Endocrine Unit at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, indicated that Dr. Austin�s presentation makes the case that this activity is something the NIH has an obligation to carry out. He commented that the TRND current budget of $24 million may not be enough to make a serious impact. He asked what would prevent this initiative from being a failure, with an incredibly worthy goal but a mismatch of funding, particularly when the pharmaceutical industry has tried and failed in many of these areas. Dr. Austin commented that Dr. Kronenberg�s question effectively describes one of the most significant challenges facing the TRND program. He noted that there are a number of programs for rare diseases that are in a holding pattern for nonscientific reasons that can be freed up with funding of less than $10 million per project, and the quality of the science is significantly improved compared with 1-2 decades ago. It also is hoped that the TRND budget will expand in future years.

6. NIAMS RETREAT

   Drs. Kronenberg and Kathleen Green (the Joseph L. Mayberry Professor in the Department of Pathology/Cancer Center at Northwestern University Medical School) attended this year�s NIAMS Scientific Retreat as representatives of the Council. Dr. Kronenberg reported that a number of topics were discussed during the retreat, and from the perspective of an "outsider looking in," he characterized it as an extremely interesting and worthwhile event. One primary goal of these retreats is for NIAMS staff to educate themselves and think more deeply on various topics within the Institute�s mission. The nature of the process is that experts on certain topic areas give talks and lead wide-ranging discussions. Dr. Kronenberg indicated that he was impressed by the quality of the discussions and by the commitment of NIAMS staff to make it a worthwhile activity.

   Following these opening comments, Dr. Kronenberg described several topic sessions covered at the retreat: chronic low back pain, comparative effectiveness research, and natural history studies. He noted that chronic low back pain issues include its burden and prevalence; epidemiology; causal factors; use of medication and MRI; and therapy (biological vs. non-biological, overtreatment vs. no treatment, rest vs. activity, optimal surgical treatment).

   In the area of comparative effectiveness research, discussion topics at the retreat included:

   • Diseases within the NIAMS mission that are ready for comparative effectiveness research. Considerations include multiple interventions, the fact that the medical community has not agreed on the preferred treatments, and the burden to society and individual patients.
   • Infrastructure needs. Needs include cohorts, electronic medical records that capture patient-relevant outcomes, standardized outcome measures, practitioners who will practice evidence-based medicine, and mechanisms to evaluate whether comparative effectiveness research guides patient care.
   • Appropriate study designs. These extend beyond randomized clinical trials and should include medical records and adaptive designs, as well as "shared decision making" in a real-world setting.
   • Approaches to identify high-priority research questions, including collaborations and partnerships with sibling agencies and constituents.
   • Strategies to engage constituents as the NIAMS further develops its comparative effectiveness research portfolio. Such strategies may involve: (1) publishing a Request for Information in the NIH Guide, (2) holding workshops or roundtables, (3) using social networking approaches, and (4) tapping members of the NIAMS Coalition.

   Retreat participants discussed the fact that natural history studies collect health status information on human subjects over a time course of the disease or disorder. It was noted at the retreat that the NIAMS Intramural Research Program provides the unique flexibility for projects to adapt and therefore is well situated for natural history studies. Needs and opportunities identified related to natural history studies fell into three main areas: (1) patient involvement (taking advantage of patient advocates and networks, utilizing new technologies and other convenience factors, and involving culturally sensitive recruitment/retention strategies); (2) measures of success (the effective use of data collected through natural history studies, new hypotheses of pathophysiology, and more effective design of clinical trials); and (3) identifying key design elements that promote success. Dr. Katz emphasized the need to identify less costly ways of conducting these types of studies.

   Dr. Green briefed the Council on discussions related to the human microbiome and oligonucleotide therapeutics that took place during the retreat. She reminded Council members that the human microbiome represents the community of microorganisms and their genomes that reside in and on the human body. The major discussion topics included: (1) the state of the science, (2) microbiome composition and variation (and whether there is a core microbiome), (3) the role of the microbiome in skin and rheumatic diseases, (4) animal models, (5) diagnostic and therapeutic implications (including the role of probiotics), and (6) the role of the NIH and NIAMS in facilitating microbiome research. Needs and opportunities related to the human microbiome were identified and include standardization in terms of techniques and protocols, cross-disciplinary training and collaboration, and communicating with (and educating) the scientific and lay communities.

   Therapeutic uses of oligonucleotides (strings of nucleic acids, usually no larger than 30 base pairs) include modifying pre-RNA splicing to mature mRNA, interfering with protein translation by preventing initiation, and disrupting protein-nucleic acid binding. A number of synthetic oligonucleotides were discussed. These are used for personalized treatments, generally involve costly chemistry, must be delivered directly into the cell, carry potential off-target effects, are resistant to endogenous nucleases, and do not evoke an interferon response. Retreat discussion topics related to oligonucleotide therapeutics included: (1) examples of diseases within the NIAMS mission (e.g., Duchene muscular dystrophy, epidermolysis bullosa, osteogenesis imperfecta); (2) exon-skipping oligonucleotides and Duchenne muscular dystrophy (particularly with regard to preclinical studies and clinical studies to address exon 51 defects); and (3) research challenges (including variable phenotypes of single-gene diseases, gain-of-function vs. loss-of-function diseases, drug delivery, and manufacturing costs).

   Discussion

   Dr. O�Keefe noted that at the last Council meeting, there was a presentation on the Patient-Reported Outcomes Measurement System (PROMIS). He asked, within the context of clinical trials, whether there was any mention of incorporating PROMIS into these topics as well as the potential for rehabilitation and injury prevention. Dr. Kronenberg noted that there was a great deal of retreat discussion on patient involvement in trial development, but did recall whether PROMIS was specifically discussed. Dr. Katz commented that there is an active, ongoing discussion on PROMIS across the NIAMS and the NIH overall.

7. THE NIAMS NATIONAL MULTICULTURAL OUTREACH INITIATIVE

   Dr. Carter explained the three goals of the NIAMS National Multicultural Outreach Initiative:

   • To improve the availability of and access to research-based and culturally relevant health information for racial, ethnic, and underserved populations
   • To emphasize that research is the foundation for progress in achieving better bone, joint, muscle, and skin health
   • To support and involve community, voluntary, and professional organizations and other governmental agencies in multicultural outreach.

   The Initiative�s target audiences include African Americans, Hispanics/Latinos, American Indians, Alaska Natives, Native Hawaiians, and Asians and Pacific Islanders. The Initiative was formed based on the simple fact that health disparities exist within diseases under the NIAMS mission. Dr. Carter cited examples from the NIAMS Health Disparities Strategic Plan in the areas of lupus (more common in women of African American, Hispanic, Asian, and Native American descent); scleroderma (affects members of all ethnic groups, but is particularly prevalent in certain Native American populations); osteoarthritis (African Americans have a higher risk of both knee and hip osteoarthritis than Caucasians); and keloids (seen predominantly in African American individuals).

   Another impetus for the Initiative is the lack of easy-to-read, culturally appropriate health information. Dr. Carter commented that the availability of more meaningful and relevant information will allow for an increased awareness and education, which is a precursor to improved health behaviors and behavior change. Dr. Carter reviewed the NIAMS National Multicultural Outreach Initiative�s accomplishments to date. A substantial amount of background research was conducted through an environmental scan to ascertain available data, a publication planning survey, and cultural profiles of racial and ethnic populations. Additional efforts have resulted in meetings with NIH Communications Directors, participation in a NIAMS Coalition Stakeholders meeting, the creation of an Initiative leadership group, and the creation of four Initiative work groups.

   The NIAMS National Multicultural Outreach Initiative will work with its partners to: (1) select and develop cross-cutting, research-based health messages and materials tailored for racial and ethnic populations; (2) deliver the messages and materials to racial and ethnic populations through trusted community sources; and (3) build and maintain a network of organizations to collaborate on outreach to racial and ethnic populations.

   Dr. Janet Austin described the Initiative�s current and future operation within the context of the health communications program process, which is widely used and involves four phases: planning and strategy development; concept, message and materials development, and pretesting; program implementation; and program assessment and improvements.

   She closed the presentation by acknowledging NIAMS staff and Council members who are helping to lead the Initiative.

   Discussion

   Dr. Katz opened the discussion by emphasizing the need for evaluating these types of programs to ensure that they are progressing effectively.

   Dr. Klippel asked about plans to engage voluntary groups and other agencies. Dr. Austin explained that a representative from the Centers for Disease Control and Prevention has been working closely with Initiative leadership as the program was being developed. There are existing partnerships between the voluntary organizations and the NIAMS� Health Partnership Program; the Initiative is looking to expand and broaden these relationships. In response to another question, Dr. Austin explained that NIAMS staff regularly receives comments from members of the NIAMS Coalition emphasizing the need for multicultural and easy-to-read information. The NIAMS Coalition groups share their literature with the Initiative, but there is a gap in providing these materials at the national level.

   Dr. Katz noted that although there are certain groups that know how to reach their constituencies effectively, this remains a significant challenge and one that the Initiative will have to overcome.

   Dr. Betty Diamond, a member of the Council and Chief of the Laboratory of Autoimmune Diseases at The Feinstein Institute of Medical Research at North Shore Health System, expressed concern that the presentation did not include mention of the fact that there is more than $1.5 million in HHS funding allocated to examining minority disparities associated with lupus. This effort is focused on professional education, whereas the Initiative is much more focused on patient education—it is difficult to do one without the other, and coordination between these efforts is warranted. Dr. Austin noted that the Initiative, since its inception, has been working closely with the ORWH on the lupus campaign and with other organizations and agencies to ensure there are consistent messages and to prevent duplicative efforts.

   In response to a question from Mr. Stephenson, Dr. Katz noted that the NIAMS has discussed the use of different media (e.g., print, radio, Internet, television) for disseminating information. He also noted that some media (e.g., the Internet) may not be the most effective for some underserved populations.

8. NEW NIAMS-ADMINISTERED INITIATIVE: NIH INDUCED PLURIPOTENT STEM CELL CENTER (NiPSC)

   Dr. O�Shea briefly reviewed the history of stem cells and pluripotency, from 1908 to the present. Progress in this field, which has advanced rapidly in recent years, has tremendously significant impacts as cells and tissues can now be used as medicine. There are many ways induced pluripotent stem (iPS) cells can be used therapeutically, and they can be used to help understand disease pathogenesis as well. iPS cells can also be used to develop assays to correct the abnormal phenotype of disease cells in high throughput settings. Eventually, iPS cells may be differentiated into different fates and used as restorative therapy; doing so safely will be a challenge.

   Dr. O�Shea noted that there is a great deal of misinformation being disseminated to the public related to stem cell therapy (e.g., using stem cells to stop aging or cure back pain). Many companies are taking advantage of uninformed or misinformed patients. It is incumbent upon the research community to develop and use stem cell therapies in a safe and effective manner. iPS cells present the opportunity to develop in vitro models of research tools for disease mechanisms and for drug screening. Their use may also allow development of cell-based therapies, although there are significant safety issues associated with these approaches. Cell-based therapies may carry the potential for oncogenicity and will require advances in reprogramming/differentiation, non-viral vectors, and extensive characterization.

   In December 2009, the NiPSC initiative was endorsed at an NIH Scientific Directors retreat following a challenge from Dr. Collins to consider high risk/large impact trans-NIH initiatives with clinical applicability. An iPSC workshop was held in January 2010, which was led by NIAMS and resulted in the submission of an application to the Common Fund to consider clinical applications in the areas of liver regeneration, hematopoietic uses of stem cells, ophthalmologic uses of stem cells, and non-weight bearing bone repair. The proposal was subsequently approved, and the NiPSC was established.

   iPS initiatives include: (1) establishing a state-of-the-art iPS facility to serve as a resource for Intramural Research Program and extramural partners to enable clinical applications using the NIH Clinical Center; (2) establishing an Intramural Research Program laboratory for the iPS Director; and (3) providing seed money for pilot projects that promote the clinical applications of iPS technologies.

   Housing the iPS program within the Intramural Research Program offers a number of advantages, including access to the NIH Clinical Center, which has well-characterized clinical cohorts and a GMP cell processing facility. Additional advantages include a high-throughput screening facility, existing scientific infrastructure, and long-term stable funding, all of which provide an ideal environment and culture for high-risk, high-impact clinical projects.

   The immediate goals of the program are to:

   • Fund timely and appropriate Intramural Research Program projects. Dr. O�Shea noted that a solicitation released in April 2010 resulted in 71 applications received. Projects are currently being selected for funding (Dr. Katz added that the success rate of these applications is expected to be no more than 20 percent).
   • Provide iPS training courses.
   • Recruit a Director. This process is ongoing; Council members were asked to suggest any individuals who have an interest consistent with the NIAMS mission.

   Discussion

   In discussion, Mr. Stephenson asked about the budget for this initiative and specifically for the applications that were submitted. Dr. O�Shea indicated that the budget is $52 million over the first 5 years (through the Common Fund). For this year, the budget is $3 million; $2 million is expected to fund the projects in the Intramural Program. Dr. Katz added that at its optimal level, the annual budget is projected to be approximately $18 million.

   Dr. Kronenberg commented that the Intramural Research Program is ideally suited for this type of work. Coordinating this relatively small enterprise with much larger extramural efforts will be critically important. Dr. O�Shea agreed on the importance of this coordination. Dr. Katz added that part of this initiative may involve developing a resource that will be utilized by the Extramural Research Program.

   Dr. O�Keefe asked about integration with a GMP facility and the surrounding infrastructure. Dr. O�Shea commented that there are a number of clinical trials planned on bone marrow, some of which have already started, that are taking advantage of this facility.

   Dr. Dietz asked for more detail on the scope of the mission for the NiPSC and whether all of the downstream applications are anticipated to be conducted outside the Center. Dr. O�Shea indicated that this is not the case, and that ideally, the new Director will have a clear clinical vision for the applicability of this technology and be able to create partnerships to advance this work.

   Council member George Beach, Chairman and CEO of Beach Creative Communications, asked about public opinion of the initiative. Dr. O�Shea commented that in terms of NIH scientists, there is tremendous excitement. In terms of the lay community, it is unclear what the prevailing opinion is. A Web site to start publicizing the NiPSC is being developed. iPS cells have an advantage over stem cells in terms of ethical considerations because they involve taking a cell from any part of the body and, in principle, turn it into any other cell. Dr. O�Shea noted that the Catholic Church has sponsored an iPS center at the University of Maryland.

9. CONCEPT CLEARANCE

   NIAMS Advisory Council Executive Secretary Dr. Laura K. Moen, Director of the NIAMS Division of Extramural Research Activities, explained that Council members would be presented with two concept clearances for consideration, one on a clinical study section concept, and one related to the Small Business Innovation Research Program (SBIR) and clinical trials.

   Dr. Charles Rafferty, Chief of the NIAMS Scientific Review Branch, explained that the first concept is to create a new standing study section for the review of clinical trail and clinical trial-related applications by the NIAMS Scientific Review Branch. Members would typically serve 4-year terms and meet three times per year. The study section would review clinical trial planning grant applications (R34/U34), clinical trial development/pilot project applications (R21), single and multisite clinical trial applications (R01/U01), multi-site clinical laboratory test development applications (R01), and future NIAMS RFAs related to clinical trials such as ancillary studies to existing clinical trials (R01/R21).

   The rationale for creating this study section is to enhance the quality of the initial review of clinical trial grant applications by improving expertise in NIAMS disease areas, expertise in clinical trial and biostatistics methodology, consistency of advice, oversight and coordination by the NIAMS, and the recruitment and retention of the best reviewers. It is expected that the study section will include 20 permanent members and will be augmented as needed by temporary members. Technical representation would include leaders in the field of clinical trials research in the areas of rheumatic diseases, skin diseases, orthopaedic diseases, muscle diseases, bone diseases, behavioral medicine and pain, clinical methodology and design, biostatistics, and biological mechanisms. A lay community member also will be included.

   Next steps include: (1) concept clearance by the NIAMS Advisory Council, (2) concept clearance by the NIH Office of Federal Advisory Committees, (3) submission of a memo from the NIAMS Director to the NIH Deputy Director requesting approval of the new study section, (4) the recruitment of permanent members, and (5) implementation of the standing study section for the May 2011 Council reviews.

   Discussion

   Dr. Weinstein suggested that bioinformatics, one of the most expensive components of a clinical trial, be represented on the standing study section. Dr. Rafferty indicated that consideration will be given to including this expertise on the study section. Council member Dr. Cliff Rosen, Director of Translational Research at Maine Medical Center, asked about how the NIH Center for Scientific Review (CSR) would be involved. He also asked if those who serve on this proposed study section would have the same privileges as those who serve on regular NIH study sections. Dr. Rafferty explained that any member of a chartered or standing study section can benefit from the continuous submission policy. Dr. Katz noted that other NIH ICs have pulled out of CSR for this type of review, and the NIAMS� goal in moving in this direction is to increase the breadth and depth of its reviews.

   Dr. Dietz noted that often the design for trials of rare disorders in small populations are not well aligned with the priorities of the FDA and asked if it would be possible to have FDA representation on the study section, not as a voting member but as a source of information and feedback. Dr. Katz explained that the FDA is present for a number of Institute discussions, but it would be difficult for the FDA to be involved in this process. In general, the FDA is reluctant to provide an opinion on the proximal phases of any study. Dr. Katz indicated that the NIAMS would consider whether and how best to involve the FDA. Dr. Joan McGowan, Director of the NIAMS Division of Musculoskeletal Diseases, noted that the proposed study section would be reviewing investigator-initiated trials for the most part and could recommend that the investigators contact the FDA directly. Dr. Rafferty noted that according to Committee Management rules, there is nothing that prohibits an FDA scientist from being appointed to this panel, although it is unclear whether the FDA would allow it.

   Dr. Weinstein suggested that this study section might also review potentially large database trials and large cohorts followed in databases across systems if the appropriate expertise is present. Dr. O�Keefe commented that the study section needs to have broad expertise but recognize that they are judging the science, not representing their constituencies. Dr. Katz agreed and indicated that through this process, applications will be judged on the merit of the science.

   Dr. Kronenberg commented that this is an extremely important initiative and asked about the definition of the term clinical trial as it is being used in this context. Dr. Carter indicated that the NIH definition of a clinical trial is being used.

   Following this discussion, Dr. Carter discussed the second concept clearance item: the use of the SBIR mechanism to support clinical trials. Currently, there are two ways that for-profit companies can apply to the NIH for support of clinical trials. One way is to apply through NIH�s SBIR/STTR Program; the other is to submit an R01 application. NIAMS currently has three active clinical trials being managed through the SBIR program. The concept for Council discussion was to consider disallowing SBIR applications to contain clinical trials and require for-profit institutions that want to apply for clinical trials funding to do so through the R01 mechanism; there are other NIH Institutes that have already done this. The new policy would mean that both for-profit and non-profit institutions would enter the system through the same mechanism and be reviewed by the same study section. The advantages to this approach would be that the NIAMS would have the expertise to ensure that all of the trials are properly reviewed, and the NIAMS leadership feels it is the best stewardship of public funds. It provides a level playing field for all institutions to be reviewed as well as continuity through a standing study section with regular members. In addition, this approach carries with it the advantage of providing the study section with institutional memory over time of what projects are being reviewed.

   Dr. Carter emphasized that the Institute is not discouraging for-profit companies or institutions from submitting clinical trial applications. The approach would change how the clinical trials previously conducted through the SBIR Program affect the Institute�s budget. Currently, the SBIR/STTR Program is a mandated percentage of the NIAMS budget. Switching to the proposed approach would result in for-profit companies competing through the standard R01 pool.

   Dr. Kronenberg noted that the SBIR Program budget is fixed, and if clinical trials are no longer funded through that mechanism, something else will have to be. He commented that it would be useful to have all clinical trials reviewed by the proposed study section. One possible consequence of this change may be that there will be the same amount of money for small businesses, but fewer of them will be getting funding from the NIH for clinical trials. Dr. Katz explained that at the NIAMS, the paylines for SBIR grants are much more stringent than they are at most other ICs.

   Dr. Diamond expressed concern that at a previous Council meeting, there was discussion that the mandated SBIR funding was not being used as effectively as possible. The proposed approach may remove projects that would represent a good use of SBIR Program funding. Dr. Katz clarified that SBIR applications are reviewed by an SBIR study section and that the Institute cannot modify that process. The discussions related to the SBIR Program that took place at the previous Council meeting focused on creating an RFA for SBIR applicants in certain targeted areas and whether the NIAMS was using the SBIR Program effectively in areas of interest to the Institute.

   Dr. Kronenberg asked about the potential for small businesses interested in obtaining NIH funding for clinical trials to challenge the proposed change because they may perceive this as requiring them to apply through a more rigorous process than the SBIR study section. Dr. Katz responded that there is a precedent for this change—the National Institute of Allergy and Infectious Diseases currently funds small businesses conducting clinical trials in this manner.

   Dr. Diamond suggested that the Institute review the applications and determine the available study section expertise before shifting the application of clinical trials from small businesses out of the SBIR study section and over to the R01 mechanism.

   In response to a question about cost, Dr. Rafferty indicated that the NIAMS clinical trials study section approach would involve an additional cost, primarily associated with the three annual in-person meetings and the fact that there will be more work associated with an increase in applications.

   Dr. Katz asked for the Council to vote on the concept clearance for creation of an NIAMS Arthritis and Musculoskeletal and Skin Diseases (AMS) Clinical Trials Review Committee.

   • The Council voted unanimously in favor of the creation of an NIAMS Arthritis and Musculoskeletal and Skin Diseases (AMS) Clinical Trials Review Committee.

   Dr. Katz indicated that in a future closed session of the Council, additional data and specific information would be presented to Council members related to the potential shift in how small businesses apply for funding for clinical trials.

10. CONSIDERATION OF APPLICATIONS

    This portion of the meeting occurred during closed session.

11. PORTFOLIO ANALYSIS

    This portion of the meeting occurred during closed session.

12. CONSIDERATION OF APPLICATIONS

    The Council reviewed a total of 785 applications in closed session requesting $861,632,420 and recommended 785 for $861,632,420.

13. ADJOURNMENT

    The 71st National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 2:30 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.