You are here:
News & Events
Advisory Council Minutes
September 2003 (historical)
Minutes of the 51st meeting
September 25, 2003
8:30 a.m. to 4:00 p.m.
Department of Health and Human Services
Public Health Service
National Arthritis and Musculoskeletal
and Skin Diseases Advisory Council
CALL TO ORDER
The 51st meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council was held on September 25, 2003, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 6. The meeting began at 8:30 a.m.
Attendance
Council members present
Dr. Graciela Alarcon
Mr. Chris Allen
Dr. Gunnar Andersson
Dr. John P. Atkinson
Dr. Paul R. Bergstresser
Dr. Bess Dawson-Hughes
Dr. Michael Frank
Ms. Victoria Kalabokes
Dr. Cato T. Laurencin
Ms. Jean Mandeville
Dr. Richard T. Moxley
Dr. Robert J. Oglesby (Ex Officio)Dr. Francesco B. Ramirez
Ms. Mary Elizabeth Replogle
Dr. Randy N. Rosier
Dr. John R. Stanley
Dr. Steven L. Teitelbaum
Ms. Sharon F. Terry
Dr. Oretta Mae Todd
Dr. Charles S. Via (Ex Officio)Staff and Guests
The following National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) staff and guests attended:
Staff
Dr. Deborah Ader
Dr. Janet Austin
Mr. Melvin Broadus
Ms. Anne Connors
Mr. Ray Fleming
Dr. Julia B. Freeman
Dr. Elizabeth Gretz
Ms. Lisa Hill
Dr. Steven J. Hausman
Ms. Jane Hymiller
Dr. Stephen I. Katz
Dr. Cheryl A. Kitt
Dr. Charisee Lamar
Dr. Gayle Lester
Ms. Anita Linde
Dr. Peter Lipsky
Dr. Richard W. Lymn
Dr. Joan A. McGowan
Ms. Leslie McIntireMr. Robert Miranda-Acevedo
Ms. Rachel Moore
Dr. Michael Morse
Dr. Alan Moshell
Ms. Melinda Nelson
Dr. Teresa Nesbitt
Dr. Glen Nuckolls
Dr. James Panagis
Ms. Christine Pellerin
Ms. Wilma Peterman
Dr. Susana A. Serrate-Sztein
Dr. William Sharrock
Ms. Helen Simon
Ms. Robyn Strachan
Dr. Bernadette Tyree
Dr. Fei Wang
Ms. Eileen Webster-CisselGuests
Mr. Gary Barron
Ms. Roberta Biegel
Mr. Kevin Brennan
Dr. Jennifer Burnelle
Ms. Janet Craigie
Ms. Melanie Gray
Ms. Gail Hardy
Ms. Joellen Harper
Dr. Scott Jenkins
Ms. Donna Kohli
Dr. Sergio Jimenez
Dr. David Lovett
Ms. Linda A. Payne
Dr. Lawrence Raisz
Ms. Susan WhittierOther NIAMS staff members and guests also were present. Dr. Katz, the Director of NIAMS, chaired the meeting.
CONSIDERATION OF THE MINUTES
The minutes of the 50th Council meeting, held in May 2003, were accepted with the one correction on page 4, under section IV: For Dr. Rosier, after "University of Rochester," remove "Minnesota" and replace with "Rochester, New York."
FUTURE COUNCIL DATES
Future Council meetings are planned on the following dates:
January 29, 2004
June 3, 2004
September 21, 2004
February 8, 2005
June 14, 2005
September 13, 2005DIRECTOR'S REPORT AND DISCUSSION
Dr. Katz thanked the following outgoing Council members: Mr. Allen, Drs. Atkinson and Bergstresser, and Ms. Mandeville. Dr. Katz also welcomed incoming Council member Dr. Stanley, who was not present at the May 2003 Council meeting.
Personnel Changes
Dr. Katz announced several personnel changes at NIH. Dr. Story Landis was appointed Director of the National Institute of Neurological Disorders and Stroke (NINDS) on September 1, 2003. Dr. Landis has been the Scientific Director of the NINDS Intramural Program since 1995. Dr. Jeremy Berg was appointed Director of the National Institute of General Medical Sciences (NIGMS). Dr. Berg formerly was Director of the Department of Biophysics and Biophysical Chemistry at The Johns Hopkins University School of Medicine. Dr. Elvera Ehrenfeld, Director of NIH Center for Scientific Review (CSR), will leave this position on September 30, 2003. Dr. Ehrenfeld will continue in her position as Chief of the Picornavirus Replication Section in the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID). Dr. Brent Stanfield was named Acting Director of the CSR.
At NIAMS, Dr. Glen Nuckolls is a new Scientific Review Administrator in the Review Branch. Dr. Nuckolls joined NIAMS' Intramural Research Program (IRP) in 1995 and the Cartilage Biology and Orthopaedics Branch in 2000. His research focused on the regulation of cartilage development and achondroplastic ossification and osteoarthritis by fibroblast growth factor signaling.
Update on Budget and Congressional Activity
Congress is working to finalize the Fiscal Year (FY) 2004 Appropriations Bill for the Departments of Labor, Health and Human Services (HHS), and Education. The Bill passed by the House of Representatives provides $27.6 billion for NIH and about $503 million for NIAMS. The Senate Bill provides $27.9 billion for NIH and about $505 million for NIAMS.
Recent Scientific Advances
Dr. Katz highlighted several recent scientific advances. The most recent issue of The New England Journal of Medicine published two studies on combination treatments for low bone mineral density (BMD). The first study, coordinated by Dr. Dennis Black and colleagues at the University of California at San Francisco and carried out at 4 centers, examined 238 postmenopausal women with low hip or spine BMD. This study was funded by NIAMS and Dr. McGowan was a coauthor of the publication. The second study, conducted by Dr. Joseph Finklestein and colleagues at a NIAMS Specialized Center of Research, attempted to optimize osteoporosis treatment and increase BMD in 83 men, aged 46-85 years. Both studies found that bone-building parathyroid hormone alone increased BMD at least as well as combination therapy with a drug that slows bone loss. Another interdisciplinary team of researchers at the University of Arizona, led by Dr. Timothy Lohman, found that a combination of weight-bearing and resistance exercises and intake of calcium citrate over 1 year period significantly improved BMD at specific bone sites in postmenopausal women, regardless of whether or not the women used hormone replacement therapy (HRT). The intensity of weight-bearing workout and level of resistance training had the greatest impact on BMD.
Another study published in the Arthritis Care Journal, led by Dr. Laura Schanberg and Dr. Frank (a member of the NIAMS Advisory Council) at Duke University, found that increased pain in children with juvenile arthritis led to reduced participation in school and social activities. The reduced participation was related to increased anxiety. Comprehensive treatment combined with aggressive palliative care increased the children's ability to participate in activities.
The NIAMS and the Department of Veteran Affairs collaborated on a study of a self-management education program to improve the quality of life for low-income patients residing in the inner city who experience acute lower back pain. The self-management program was shown to improve quality of life for this group of patients. Dr. Teresa Damush and other researchers at the Indiana University School of Medicine led this study.
A study by Drs. Matthew Liang, Elizabeth Karlson, and Lisa Mandl at Harvard Medical School examined the importance of various risk factors, including body mass index (BMI), use of HRT, age, physical activity, alcohol consumption, and tobacco use for requiring hip replacement surgery. Only BMI and age were related to the need for hip replacement. This is one of the first long-term, prospective studies to show an association between a modifiable risk factor (BMI) and osteoarthritis.
Recent Activities and Plans for the Future
Dr. Katz discussed recent NIH and NIAMS activities and plans for the future. These activities included: (1) the National Academy of Sciences (NAS) Report entitled "Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges," (2) the new NIH Steering Committee, (3) NIH Muscular Dystrophy research and education, (4) a planned U.S. Surgeon General's Report on osteoporosis and bone health, (5) the Lupus Federal Working Group, (6) the outcomes of the annual Scientific Retreat of the NIAMS Extramural Research Program, and (7) the Consensus Development Conference on Total Knee Replacement.
NAS Report on NIH Organization
A National Academy of Sciences expert panel recently released the report "Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges." Congress mandated the development of this report 1 year after the new Director, Dr. Elias Zerhouni, was appointed. Early in September 2003, Dr. Zerhouni and his senior staff met with Institute and Center directors at an annual NIH Leadership Forum to discuss the recommendations of "Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges." Dr. Zerhouni planned to discuss his response to these recommendations with NIH reauthorizing committees at a joint House and Senate hearing. Drs. Harold Shapiro and Harold Varmus also will testify at this hearing.
NIH Steering Committee
Dr. Zerhouni recently formed and will chair an NIH Steering Committee that includes nine Institute and Center directors. This Steering Committee will be a policymaking group for the NIH. Five working groups also were formed to examine different areas of management and policy concern, including intramural research, extramural research, information technology, facilities planning, and management and budget. Dr. Katz was asked to serve on the Steering Committee and as co-chair of the Management and Budget Working Group.
NIH Muscular Dystrophy Research and Education Activities
Dr. Katz has been involved in several Congressional briefings regarding muscular dystrophy. He noted that NIAMS, NINDS, National Institute of Child Health and Human Development (NICHD), and the Muscular Dystrophy Association are collaborating to fund cooperative research centers devoted to muscular dystrophy. These centers also will offer muscular dystrophy training opportunities. In addition, NIH formed a Muscular Dystrophy Research Task Force.
As part of the Muscular Dystrophy Care Act (MD-CARE Act), an interagency Muscular Dystrophy Coordinating Committee was established to develop a muscular dystrophy research and education plan. Dr. Katz was appointed to chair this Committee for its first 2 years. Members of this Committee include representatives from three NIH Institutes, other HHS components, the Departments of Defense and Education, and muscular dystrophy voluntary organizations and patient advocates. As part of this Committee's efforts, the NIH will host a meeting of muscular dystrophy scientific and clinical experts on October 8-9, 2003. The purpose of this meeting is to identify the key components of a muscular dystrophy research and education plan. The plan will be reviewed and approved by the full Committee before being submitted to Congress in the summer of 2004.
Planned U.S. Surgeon General's Report on Osteoporosis and Bone Health
Drs. McGowan and Raisz are working with the U.S. Surgeon General to develop a report on osteoporosis and bone health. The report is expected to be released in the summer of 2004. It is anticipated that the U.S. Surgeon General will publicize the need for greater public awareness of osteoporosis.
Lupus Federal Working Group
The Secretary of HHS, Mr. Tommy Thompson, has asked NIAMS to lead the formation of a Lupus Federal Working Group. Drs. Katz and Serrate-Sztein will cochair this group. The first meeting of this group is scheduled for October 21, 2003, and will involve representatives from the U.S. Food and Drug Administration (FDA) and from other interested Institutes, Federal agencies, and voluntary organizations.
Outcomes of the Annual Scientific Retreat of the Extramural Research Program
NIAMS staff discussed several new initiatives at the annual Scientific Retreat of the Extramural Research Program held in April 2003. The outcome of this Retreat was a set of proposed initiatives for FY 2005, which were discussed in the closed portion of this Council meeting.
Consensus Development Conference on Total Knee Replacement
A Consensus Development Conference on Total Knee Replacement is scheduled for December 8-10, 2003. Dr. Panagis is working with the NIH Office of Medical Applications in of Research, is organizing this conference. Dr. Katz explained that Consensus Development Conferences identify areas of research need. A past Consensus Development Conference, for example, led to a large epidemiological study of osteoporotic fractures.
INFORMATION DISSEMINATION PROGRAM
NIAMS' Office of Communications and Public Liaison recently launched a Spanish-language home page on NIAMS' Web Site. NIAMS is one of the first NIH Institutes to develop a translation of its home page in Spanish. Dr. Alarcon reviewed and assisted in the translation of several documents for this Spanish-language home page.
Mr. Miranda-Acevedo, who directed the development of NIAMS' Spanish-language home page, delivered a brief presentation of this Web page. The link to the Spanish-language home page is included on the English-language home page. This link brings users to the same home page and links, translated into Spanish.
Discussion
Dr. Atkinson asked whether NIAMS' Spanish-language Web page includes tools to determine its utility (e.g., tools that track number of hits, obtain user feedback, etc.). Mr. Miranda-Acevedo responded that the Spanish-language home page contains the same "Contact Us" button that is included in the English-language home page. The number of hits to NIAMS' Web Site is tracked, but currently no mechanism exists for separately tracking hits to the English- and Spanish-language Web pages. Council members agreed that the Office of Communications and Public Liaison should investigate the possibility of incorporating such a mechanism.
Ms. Replogle asked about NIAMS' capabilities for tracking the type of information sought on the Web Site by Spanish-speaking users. The Office of Communications and Public Liaison plans to track the type of Spanish-language information sought and plans to develop several new Spanish-language publications over the next 2 years. Dr. Katz suggested comparing the number of Spanish-language inquiries to number of English-language inquiries.
In response to a question from Dr. Bergstresser, Dr. Alarcon agreed to investigate the accessibility of NIAMS' Spanish-language Web page via an Internet search. Spanish-speaking individuals residing outside the United States may provide an important target audience for NIAMS' Spanish-language Web page.
NIAMS MERIT AWARD RENEWAL PROCESS
Dr. Moshell presented a proposed process for renewing NIAMS' MERIT (Method to Extend Research in Time) Awards. A subgroup of NIAMS staff and Council members (comprised of Drs. Bergstresser, Moshell, Teitelbaum, and Tyree) recommended that NIAMS consider and, when appropriate, award second as well as repeat MERIT Awards. Second MERIT Awards may be repeat awards for the same project for which a prior MERIT Award was issued. The subgroup recommended only two review cycles for this type of second MERIT Award (compared to three for initial review). A second MERIT Award also may be provided to investigators who previously received a MERIT Award for another project but have changed the primary direction of their research. This type of second MERIT Award would not be considered until at least 5 years have passed since the initial MERIT Award. The review process for this type of second MERIT Award would be the same as for an initial award. Initial MERIT Awards normally are issued for 10 years, and a second MERIT Award would be issued for another 5 years. A maximum of nine investigators would qualify for second MERIT Awards over the next 4 years. The Council approved the proposed process for reviewing and renewing NIAMS' MERIT Awards.
CONSIDERATION OF A PROCESS FOR APPLICATIONS OVER $500,000
Dr. Kitt presented a new policy being considered by NIAMS regarding the acceptance of unsolicited clinical research and program project applications for $500,000 or more in direct costs. A new policy for accepting these large applications is needed because:
- Budget increases are expected to be less than in the past.
- The number of applications received, particularly R01 applications, is increasing.
- The cost of conducting research is increasing.
NIH policy requires that all Institutes make decisions regarding whether or not to accept large applications at least 6 weeks prior to their submission deadline. The current process for reviewing applications for large clinical research and program projects at NIAMS is:
- Administrative review of unofficial letters of intent. These letters are expected to include detailed information about the budget for and purpose of the proposed research.
- NIAMS Director and staff review letters of intent presented at weekly meetings. Factors that affect NIAMS' decision to consider a planned application include its relevance to NIAMS' mission, balance of grants addressing the proposed topic within the program, program interests and priorities, and cost. The quality of the planned application is not considered at this point.
Dr. Kitt explained that, because of the increasing volume of applications reduced budget, large applications that are received near the end of the fiscal year might not be funded. Therefore, a new process should be developed to ensure adequate scientific and budgetary planning for large clinical and program project applications so that high-quality, large applications can be funded. The proposed process is to accept and review new and revised applications for large clinical research and program projects only once a year.
Dr. Kitt examined how other NIH Institutes prioritize and accept large applications for review. She noted that most large applications are for clinical research, which was discussed by Dr. Hausman at the last Council meeting. Most Institutes do not accept unsolicited R01 applications for funding for more than $500,000.
The National Heart, Lung, and Blood Institute (NHLBI) Director must approve all applications for $500,000. The Division Director, Institute Director, and a panel of Institute officials review applications above the P01 cap, and a letter is sent to the Principal Investigator (PI) regarding their decision. Like NIAMS, NHLBI reviews all applications on a rolling basis, depending on the number received annually.
NIGMS uses a process similar to NHLBI, but makes decisions to accept or reject large applications 8 weeks prior to the submission deadline. NIGMS also requires investigators to include with the letter of intent an abstract of and specific aims for the planned research along with a budget. The Program Director reviews letters of intent and sends a memo to senior staff (Division and Institute Directors) stating whether or not the proposed research fits program objectives, whether any special circumstances exist to account for a large budget, and the type of application (including scores of previous applications if it is a Type 2 application).
At the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the Program Director, Division Director, and Institute Director examine each application as it arrives in relation to the Institute's current research priorities and other projects. Investigators frequently are asked to provide a detailed budget, particularly if a large amount of funding is requested. The Institute Director makes the final decision regarding whether to accept the application.
NINDS has a separate fund for large grants so that applications for these grants do not compete with smaller project grant applications. A NINDS Council subcommittee reviews all clinical trial applications for $1 million dollars and over make a recommendation to accept or reject the application. The recommendation is based on community and scientific need for the proposed research and whether NINDS already is supporting this type of research.
Discussion
Dr. Dawson-Hughes expressed concern about applications that may be cofunded by multiple Institutes. NIAMS program directors normally identify potential cofunding opportunities prior to applicants submitting a large application for approval by the Institute. Dr. Katz noted that most Institutes would not commit to funding applications before they go through the review process. For this reason, NIAMS may not be able to commit to funding very large applications. Dr. McGowan added that cofunding commitments are easier to obtain when applicants approach NIAMS during the planning phase of their proposed research (usually months rather than 6-8 weeks before the application is submitted). Other Institutes that provide cofunding want to be involved in the planning phase of an application. Investigators also need to know the requirements of all potential funding Institutes while planning their research.
Dr. Rosier encouraged NIAMS to continue to accept unsolicited, large applications because this promotes new ideas that the Institute may not have considered. He also supported Dr. McGowan's suggestion that the deadline for letters of intent for large applications be more than 8 weeks before the application submission date. Dr. Rosier further suggested that NIAMS, like some other Institutes, request more detailed information in the letter of intent so that disparate types of research projects can be adequately compared. Dr. Katz agreed that NIAMS could better define the criteria for information to be included in letters of intent. In response to a question from Dr. Rosier, Dr. Katz noted that about 2.5 percent of NIAMS Research Project Grants are program projects, which translates into about 8 percent of noncontract funding dollars. Some Institutes have as much as 15 percent of their noncontract funding dollars allocated to program projects. Although the proportion of NIAMS funding allocated for program projects has declined over time, increasing this proportion would significantly reduce the number of investigator-initiated grants that NIAMS could fund. Dr. Katz communicated a commitment to maintain the current NIAMS success rate for investigator-initiated applications. He added that many large clinical trials are funded through contracts.
Dr. Andersson noted the possibility that investigators applying for renewal of a project may experience a lapse in funding if applications only are reviewed once a year. Large clinical studies are particularly vulnerable to lapses in funding because, unlike program projects, gaps in funding cannot be filled with R01 grants. Dr. Katz responded that exceptions could be made for certain renewal applications.
Dr. Andersson also inquired about the proportion of large clinical studies that NIAMS plans to fund relative to program projects in the future. Dr. Katz indicated that the criteria for funding all types of research will become more specific and will focus more on the impact that a proposed study is expected to have on clinical outcomes than on the research methodology.
Dr. Frank recommended that NIAMS not allocate set amounts of funding for specific types of research. Dr. Katz agreed that funding decisions should continue to be based on the need for the proposed research, rather than on the type of study. He emphasized the importance of considering research portfolio balance and development when making funding decisions. Dr. Frank also recommended reviewing letters of intent for large funding applications twice a year rather than once a year. The practice of carrying applications over to the next year complicates the budgetary planning process. Dr. Katz agreed, however, to examine the feasibility of conducting biannual reviews of letters of intent for large applications. One approach recommended by Dr. Frank, which Dr. Katz agreed to consider if biannual reviews are feasible, is to select outstanding applications during the first annual review session and then consider all remaining applications during the second annual review session.
Dr. Ramirez recommended that, if plans for large applications are reviewed only annually, they should be evaluated more stringently so that investigators do not waste time resubmitting applications that are not likely to be funded. He further recommended that applicants be given no more than one opportunity to resubmit and that resubmissions be evaluated in an expedited fashion. Applications for P01 funding often are for studies that are difficult to initiate 1 year after the research plan was developed.
Mr. Allen asked whether the NIH is considering developing a standard process for reviewing large research applications across Institutes. Dr. Katz replied that a standard review process is difficult to establish because of the diversity of science addressed by the various Institutes and programs. The NIH Office of Research on Women's Health (ORWH), however, developed a successful, standardized, Web-based process for reviewing Specialized Programs of Research Excellence applications. This process incorporated review of budget, project need, and scientific merit. Dr. Katz agreed that the timelines and general review criteria probably could be standardized across Institutes.
In general, the Council members agreed that a streamlined process is needed for NIAMS to review large applications. The CSR may be asked to reduce the review burden on NIAMS staff by reviewing some program project applications for program relevance, need, and budget, as well as for scientific merit.
In response to a question from Dr. Dawson-Hughes, Dr. Katz noted that, for at least 8 years, prior approval has been required before applications for $500,000 or more are accepted by an NIH Institute. Some Institutes, however, allow program directors to make funding decisions about applications for less than $1 million.
In response to a question from Ms. Kalabokes, Dr. Kitt noted that applications likely would be due in August and letters of intent would be due a minimum of 3 months prior to the application due date. She added that limiting Institute review of all large applications to once or twice a year should significantly reduce the burden for reviewers and allow them to come better prepared to review sessions.
In response to Ms. Mandeville's question, Dr. Katz noted that prioritization of proposed studies is complicated by the fact that the burden of a disease or condition can be measured in many ways (e.g., impact on the quality of life of the individual with the illness, economic impact on society, mortality rate, etc.).
- Budget increases are expected to be less than in the past.
REPORTS OF RECENT MEETINGS
Overviews of three recent scientific meetings were presented at this Council meeting. These meetings were:
(1) Lupus Today: Research Into Action,
(2) NIAMS Bone Quality Investigators Meeting, and
(3) Conference on Immunomodulatory Drugs in the Treatment of Skin Diseases.
Lupus Today: Research Into Action
Dr. Gretz reported on the "Lupus Today: Research Into Action" Conference held on September 5-6, 2003, which she organized with Dr. Serrate-Sztein. This conference was a collaboration between the Office of Women's Health in the Office of the Secretary of the HHS; the NIH ORWH; NIAMS and seven other NIH Institutes; the NIH National Center on Minority Health and Health Disparities; the Centers for Disease Control and Prevention's (CDC) Office of Women's Health; the Offices of Women's Health at the FDA and at the Health Resources and Services Administration (HRSA); and several advocacy groups (including the Alliance for Lupus Research, American Autoimmune Related Diseases Association [AARDA], Arthritis Foundation, Lupus Clinical Trials Consortium, Inc., Lupus Foundation of America, Lupus Research Institute, and The S.L.E. Foundation, Inc.).
The HHS originally requested that NIH's ORWH develop a scientific conference on lupus. The NIH ORWH collaborated with NIAMS to develop the agenda for this conference, which ultimately became a science conference for the public (including voluntary organization representatives, lupus patients and their families, and health care providers) as well as for the scientific community. Eleven travel grants were awarded that allowed patients to attend the conference. Conference presentations were tailored to lay audiences. The agenda also was revised to ensure a high degree of interaction between the presenters and the audience. To increase interaction between participants, the agenda permitted long breaks. A coffee break room with discussion tables and information about lupus also facilitated informal discussions and networking at the conference. Presentation topics items included:
- A lupus primer, an overview of lupus, lupus research, and treatment.
- Six presentations on cutting-edge research regarding basic mechanisms of lupus and how this research can be translated into treatment. Topics included the reproductive years and the pregnant patient and her infant, health disparities in lupus, and selected major organs targeted by lupus (kidney, heart, and brain).
- A dinner panel discussion that presented perspectives of different stakeholders (e.g., patients, family members, physicians, NIH representatives, and advocates) on how lupus affects patients and how patients cope with it.
- A session on novel diagnostics.
- A session on investigator- and industry-initiated clinical trials.
- A luncheon panel discussion of future research from patients', the FDA's, industry's, and scientists' perspectives.
A total of 235 people attended the "Lupus Today: Research Into Action" Conference. The conference is available on NIH Videocast.
NIAMS Bone Quality Investigators Meeting
Dr. Lester provided an overview of the NIAMS Bone Quality Investigators Meeting held on August 18, 2003. This meeting was organized for seven Principal Investigators who received R01 and R21 grants through a NIAMS Request for Applications (RFA) to examine tools and methods for better assessing BMD. Investigators were asked to share information on their research projects and preliminary results at this meeting. Clinical experts also were invited to present at the meeting along with five other investigators who are examining alternative methods for assessing bone quality. About 60 people attended the meeting from NIAMS; other NIH components (including The National Institute on Aging [NIA], National Institute of Dental and Craniofacial Research [NIDCR], and ORWH); CDC; FDA; the American Society for Bone and Mineral Research (ASBMR); and several pharmaceutical companies (including Roche, Wyeth, Proctor and Gamble, Novartis, Lilly, Merck, Aventis, and GlaxoSmithKline).
The goals of the NIAMS Bone Quality Investigators Meeting included:
- Develop approaches for standardizing and evaluating new measurements of bone quality (BMD).
- Determine the status of current methods for measuring bone quality to assess the risk of osteoporosis and fractures, diagnose osteoporosis, and assess treatment response.
- Determine how to foster the development of new methods.
- Stimulate crossdisciplinary interaction and collaboration between participating organizations in the areas of biomechanics, bone imaging, and clinical medicine.
- Determine the need for a large bone quality workshop that would be linked to the 2004 or 2005 ASBMR Meeting.
Participants concluded that no methods have been identified for measuring bone quality that are significantly superior or additive to dual-energy x-ray absorptiometry (DXA). Some promising alternative methods for measuring bone quality, however, are being developed. These methods include structural analysis, microcomputed tomography (CT), and micro-CT with finite element analysis.
As a followup to the NIAMS Bone Quality Investigators Meeting, the Institute plans to:
- Prepare a meeting summary and post it on NIAMS' Web Site.
- Publish a perspective article in the Journal of Bone and Mineral Research that will summarize the meeting and present research challenges and future directions.
- Conduct a minisymposium at the 2004 ASBMR Conference.
Discussion
In response to a question from Dr. Raisz, Dr. Lester indicated that methods exist for measuring architectural bone defects, including micro-CT and magnetic resonance imaging (MRI). At least two NIAMS-supported studies are using CT to assess trabecular structure. Studies are needed that examine the efficacy of these methods as compared to DXA in examining fracture risk.
Dr. Rosier noted that data on the relative value of CT and MRI for determining fracture risk might be missing because of the unavailability of these technologies for use in large clinical trials. Dr. Lester indicated that the Bone Quality Investigators Meeting might promote collaboration between the investigators of bone quality measurement methods and clinical investigators.
Conference on Immunomodulatory Drugs in the Treatment of Skin Diseases
Drs. Stanley and Moshell discussed the Conference on Immunomodulatory Drugs in the Treatment of Skin Diseases held in September 2003. The focus of this Conference was how immunomodulatory drugs may help scientists understand the pathophysiology of skin disease. The Conference included presentations on:
- Immunobiology.
- Immunomodulatory drugs currently used to treat skin diseases (e.g., atopic dermatitis, psoriasis, rheumatic diseases with skin effects, cutaneous T-cell lymphoma, and a number of rare diseases). The mechanism by which immunomodulatory drugs affect certain rare diseases is not well understood, but the fact that these drugs impact these diseases suggests areas for further investigation of the pathophysiology of skin disease.
- Immune pathophysiology of skin diseases.
- Current and future treatments.
- Common problems with the use of immunomodulatory drugs to treat skin disease.
- New data regarding skin diseases that may be treatable with immunomodulatory drugs.
- Immune modulation in the treatment of metastatic melanoma.
Conclusions resulting from the Conference on Immunomodulatory Drugs in the Treatment of Skin Diseases included:
- Many skin diseases develop through multiple pathways that may involve T-cell activation, cytokines, chemokines, antibody production, dendritic cell biology, cell signaling, and transcription of DNA.
- Experience has shown that basic research is needed to identify pathways for disease.
- Methods for identifying possible pathways for a disease include:
- Examining gene arrays of individuals with and without the disease to identify secondary pathways.
- Using clinical knowledge of a disease and efficacious treatments as well as knowledge of secondary pathways to determine candidate pathways.
- Testing the effect of drugs on candidate pathways.
- Examining gene arrays of individuals with and without the disease to identify secondary pathways.
- Serendipitous discoveries that certain drugs cause particular diseases to improve suggest multiple points in pathways that could be modulated to treat various diseases with similar pathways.
Scientists now need to identify points in pathways where specific diseases are triggered so that more targeted treatments for these diseases can be developed.
Discussion
Ms. Kalabokes added that the National Alopecia Areata Foundation benefited from this Conference because no drugs have been approved to treat the skin effects of alopecia areata. The Foundation has succeeded in partnering with Biogen to conduct clinical research at four sites to study the use of immunomodulatory drugs to treat alopecia areata. Dr. Katz noted that studies of this type are eligible for the NIH Hyperaccelerated Award/Mechanisms in Immunomodulation Trials.
Dr. Teitelbaum added that the study of immunomodulatory drugs and disease pathways is important to osteoimmunology (e.g., T-cells have been shown to play a key role in the development of osteoporosis).
- A lupus primer, an overview of lupus, lupus research, and treatment.
NIAMS CONTRACT CONCEPT CLEARANCE
Dr. Moshell presented a proposal for a contract requesting a survey of tools used to measure the burden of skin disease. This proposal is the outcome of a Congressional mandate and recommendations from a subsequent workshop on the burden of skin disease. Dr. Moshell distributed a handout that provided a description of the purpose, scope, objectives, need, and relevance of the proposed Request for Proposals (RFP). Specifically, the proposed RFP would solicit proposals for:
(1) surveying databases that contain information on the burden of skin disease;
(2) surveying instruments to collect relevant data on the burden of disease in general, skin disease as a whole, and specific skin diseases;
(3) arraying instruments in a matrix against personal, family, and societal impact;
(4) identifying gaps in available data and data collection instruments; and
(5) prioritizing missing data and data collection instruments so that subsequent initiatives can address these deficiencies.
The majority of Council members agreed that NIAMS should move forward in the development of an RFP for a survey of tools used to measure the burden of skin disease.
Discussion
Dr. Andersson recommended that the quality of the identified databases and instruments also be evaluated. Dr. Moshell agreed that the identified databases and instruments should be examined to determine whether they contain and can generate reliable information about the burden of skin disease.
Dr. Stanley suggested that a stronger rationale might be needed for examining the burden of skin disease. He also questioned what would be compared to a measure of the burden of skin disease. Dr. Moshell explained that Congress is interested in determining the burden of all diseases, and the burden of skin diseases would be compared to the burden of other diseases. In the case of the proposed initiative, databases and instruments for more extensively studied diseases such as arthritis may be compared to those for skin diseases.
Ms. Terry recommended that the proposed RFP request that the contractor compare instruments that examine only the burden of skin disease to instruments that examine the overall burden of disease. She also recommended examining the ability of these instruments to provide reliable information about systemic diseases that cause some skin diseases. Dr. Moshell indicated that these recommendations could be incorporated into the contract.
Drs. Bergstresser and Moxley expressed support for the proposed RFP and agreed that there is need to examine data about and measures of the burden of skin disease. Dr. Moxley added that the initiative to measure the burden of skin disease provides an opportunity for NIH and NIAMS, specifically, to set the agenda for examining this issue.
Ms. Mandeville pointed out that Congress wants to examine the burden of disease so that budgetary priorities for funding medical research can be set. She cautioned that burden of disease should be considered not only in terms of the number of people affected, but also the degree to which individual lives are affected (as with rarer diseases).
In response to a question from Dr. Andersson, Dr. Moshell noted that the RFP would request that the contractor examine both primary skin diseases and skin diseases secondary to another condition.
NIAMS INTRAMURAL RESEARCH PROGRAM SCIENTIFIC DIRECTOR'S REPORT
Dr. Katz introduced a representative from the Board of Scientific Counselors (BSC), Dr. Sergio Mendez, prior to Dr. Lipsky's update on NIAMS' IRP. The Office of Science and Technology (OST) and the Clinical Program provide infrastructure and resources for the IRP, other components of NIH, and researchers around the country.
Eight scientists within the OST manage the eight sections or facilities with complex technologies/equipment that are accessible to investigators. These sections or facilities include a Light Imaging Section (with confocal microscopes), Flow Cytometry Facility, Biodata Mining and Discovery Section (computer modeling and analysis of data, including microarrays), Scientific Interchange Section (develops collaborations with other NIH IRPs and extramural researchers), Laboratory Animal Care and Use Section (which includes 80 separate strains of animals), Macromolecular Biophysics Section, X-ray Crystallography Facility (collaborates with other such facilities to produce protein crystals), and a Career Development Section (also provides didactic education). The OST appears to be successful in enabling science that now is resulting in some published papers. The BSC also will review the OST.
The Clinical Program has 30 active protocols, and this number is increasing. These protocols focus on adult lupus, adult rheumatoid arthritis, and genetic diseases of children (particularly inflammatory and immunodeficiency diseases such as chronic juvenile arthritis). Although the Clinical Program is seeking a new director, it has been able to recruit several key staff members over the past year. For example, Dr. Michael Ward recently was recruited to the IRP. He has been with NIAMS for 6 months and already has established a program in outcomes research with three active protocols. Dr. Ildy Katona also has been recruited to head the Pediatric Rheumatology Program, and Dr. Rafael Casellas was recruited to work in the Molecular Immunology and Inflammation Branch. In addition, the Cartilage Biology Program hired Dr. David Hall. The new Clinical and Investigative Orthopaedic Section recently recruited Dr. Benjamin Alman, a highly regarded pediatric orthopaedic surgeon at Toronto Children's Hospital, to head this Section. Dr. Alman eventually is expected to establish a Clinical Center within the Clinical and Investigative Orthopaedic Section. The IRP Laboratory of Skin Biology currently has no director due to the recent death of Dr. Peter Steinert. The IRP is in the process of determining the best approach for continuing its Skin Biology Program.
Some recent important accomplishments of IRP staff include:
- Dr. Daniel Kastner, Head of the Genetics and Genomics Branch, previously identified the gene (named pyrin) that causes familial Mediterranean fever. Dr. Kastner and staff have developed genetic engineered pyrin mice. The knockout mouse produces many of the symptoms seen in human patients with familial Mediterranean fever and therefore provides a good model for testing new therapies. This research recently was published in Molecular Cell.
- Dr. Rocky Tuan is developing a project that examines the chondrogenesis of stem cells. Some of the findings of this project recently were published in the Internet Journal of Biologic Chemistry.
- Dr. Vittorio Sartorelli in the Laboratory of Muscle Biology has identified a molecule that influences muscle gene development and cell differentiation. His research recently was published in Molecular Cell.
- Dr. Robert Horowits, also in the Laboratory of Muscle Biology, identified a novel protein in heart muscle that is linked to the association of several other muscle framework proteins. This research was published in the Journal of Cell Science.
- Dr. Mustapha Mallah, a fellow working under Dr. Raphaela Goldbach-Mansky in the Clinical Center, found that the same cryopyrin mutation related to familial urticaria is related to neonatal onset multisystem inflammatory disease (NOMID). Dr. Mallah's hypothesis is that cryopyrin/pyrin work together to control the signaling mechanism that generates active IL1. This research was published in Arthritis & Rheumatism.
- Dr. John O'Shea previously discovered the enzyme Jak3. Genetic mutations in Jak3 are responsible for a form of severe combined immunodeficiency syndrome. In collaboration with Pfizer (using a Cooperative Research and Development Agreement [CRADA]), Dr. O'Shea developed a specific Jak3 inhibitor, which was tested in several immunologic models. Dr. O'Shea found that blocking Jak3 and signaling through cytokines such as IL2 leads to a potent and specific inhibition of transplant rejection in mice and nonhuman primates. This study recently was accepted for publication in Science.
Discussion
In response to a question from Dr. Teitelbaum, Dr. Katz explained that the scientists that manage the eight OST sections/facilities are not PIs, but staff scientists/clinicians. Their performance evaluations are based on how much science they enable rather than on how much science they initiate.
Dr. Stanley asked about collaboration between NIAMS' IRP Skin Biology Section and the National Cancer Institute's (NCI) Dermatology Branch. Dr. Lipsky has been speaking to Dr. Mark Udey of NCI's Dermatology Branch about opportunities for collaboration. One possible opportunity for NIAMS may be to assist with studies of inflammatory diseases. NCI's Dermatology Branch, in turn, could provide access to its large clinical training program. Dr. Lipsky added that discussions between research programs at NIAMS and NCI have focused on the development of corresponding laboratories without establishing new laboratories or otherwise duplicating efforts.
Dr. Bergstresser inquired about the extent to which investigators in other Institutes want to use IRP resources and facilities. Dr. Lipsky responded that investigators at other Institutes might use these resources and facilities when collaborating with a NIAMS investigator. In general, similar resources are available at other Institutes so that investigators outside of NIAMS do not need to use NIAMS' IRP resources. If an investigator from another Institute needs access to a resource that only is provided by NIAMS' IRP, NIAMS is willing to discuss the possibility of providing this investigator with access to the resource. For example, NIAMS has developed contracts with other Institutes to provide them access to NIAMS' facilities in exchange for the other Institute covering some of the cost of maintaining the facility.
- Dr. Daniel Kastner, Head of the Genetics and Genomics Branch, previously identified the gene (named pyrin) that causes familial Mediterranean fever. Dr. Kastner and staff have developed genetic engineered pyrin mice. The knockout mouse produces many of the symptoms seen in human patients with familial Mediterranean fever and therefore provides a good model for testing new therapies. This research recently was published in Molecular Cell.
CONSIDERATION OF APPLICATIONS
The Council reviewed a total of 569 applications in closed session requesting $130,717,786 and recommended for $126,133,364.
ADJOURNMENT
The 51st National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 4:00 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.
|
Cheryl A. Kitt, Ph.D. |
Stephen I. Katz, M.D., Ph.D. |
