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Advisory Council Minutes
January 2004 (historical)
Minutes of the 52nd meeting
January 29, 2004
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 52nd meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council was held on January 29, 2004, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 10. 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 McIntire
Mr. Robert Miranda-AcevedoMs. Rachel Moore
Dr. Michael Morse
Dr. Alan Moshell
Ms. Melinda Nelson
Dr. Teresa Nesbitt
Dr. Glen Nuckolls
Dr. James Panagis
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. Larry Raisz
Ms. Susan WhittierOther NIAMS staff members and guests also were present. Dr. Steven Hausman, Deputy Director of NIAMS, chaired the meeting until Dr. Katz, Director of NIAMS, arrived.
CONSIDERATION OF THE MINUTES
A motion was made to accept the minutes of the 51st Council meeting, held in September 2003, with no corrections. The motion was seconded and unanimously approved.
FUTURE COUNCIL DATES
Future Council meetings are planned on the following dates:
June 3, 2004
September 21, 2004
February 8, 2005
June 14, 2005
September 13, 2005Dr. Hausman noted that dates for 2006 would be available in the near future and would be distributed to Council members via e-mail.
REVIEW OF MEMORANDUM OF UNDERSTANDING FOR COUNCIL OPERATIONS
Dr. Hausman brought Council members' attention to the Memorandum of Understanding (MOU) between NIAMS staff and the NIAMS Advisory Council, which was included in the meeting materials. This document represents the annual assessment of the Council's operations. The first section of the MOU indicates the applications required to be called to the attention of the Council. These include any application: (1) with a concern identified by an initial review group (IRG) in the areas of animal welfare, human subjects, ethical issues, recombinant DNA, potential biohazards, MERIT awards, and/or the inclusion of women and minorities in clinical research; (2) from a foreign institution for which an award is planned; (3) recommending support of $500,000 or more direct costs in any year; (4) identified by members of the Council to be of special concern or as posing special policy issues; (5) previously deferred for additional information or for re-review by Council; and (6) identified by NIAMS staff as requiring special consideration or discussion by the Council.
Options generally available to the Council for each application that is identified for individual discussion include:
- Concurrence with an IRG recommendation
- Non-concurrence with an IRG recommendation based on scientific/technical merit
- Non-concurrence with an IRG recommendation based on other than scientific/technical merit considerations
- Recommendation of high program priority
- Recommendation of low program priority
- Deferral to obtain additional information for Council consideration at a subsequent meeting.
Dr. Hausman further explained that actions that do not require Council review or advice include the approval of: (1) domestic applications with primary or secondary assignment to NIAMS and recommended direct costs of $50,000 or less; (2) Scientific Review and Evaluation Awards for the support of NIAMS review committees in amounts and for periods of time determined by staff; (3) additional support to meet the increased cost of maintaining the level of research previously recommended, or to accommodate activities judged by staff to be within the scope of the previously peer-reviewed research project; (4) the appointment of a new Principal Investigator (PI) or Program Director to continue an active research or training project at the same institution; (5) the transfer of a project grant when the PI moves to another location; and (6) administrative actions resulting from communications with PIs prior to, or shortly after, the Council meeting and for which authority for resolution rests with Institute staff. Examples of such actions include amendment of the record, budgetary adjustments, and changes in the length of award.
NIAMS also has developed a procedure for expedited en bloc concurrence for applications with IRG recommendations. This process can expedite funding actions by the Institute because awards can be made as soon as an en bloc concurrence is obtained. The new procedure has the following parameters:
- The Chair of the Council will select one or more Council members each year to provide the Council en bloc concurrence.
- Awards can be made as soon as an en bloc concurrence has been obtained.
- All applications are eligible for inclusion in the en bloc concurrence action, although specific limitations may be instituted for any specific Council round.
- If a Council member acting for the Council wants an application to come to the full Council for discussion or not to be expedited, they simply have to indicate this fact.
- All Council members will have access to the information provided to the designated Council members.
A motion was made to accept and support the MOU for another year. The motion was seconded and unanimously approved.
- Concurrence with an IRG recommendation
REPORTS OF RECENT MEETINGS
Overviews of four recent scientific meetings were presented at this Council meeting. These meetings were: (1) Lupus Federal Working Group, (2) Consensus Development Conference on Total Knee Replacement, (3) Vitamin D and Health in the 21st Century: Bone and Beyond, and (4) First International Symposium on Osteopetrosis: Biology and Therapy. Because the Report of the Director, NIAMS, was postponed until the arrival of Dr. Katz, Dr. Lester was asked to brief the Council on the Vitamin D and Health in the 21st Century: Bone and Beyond Meeting.
Vitamin D and Health in the 21st Century: Bone and Beyond
Dr. Lester noted that this well-attended meeting was held on October 9-10, 2003, on the NIH Campus. NIAMS Council member Dr. Bess Dawson-Hughes spoke at the meeting, which addressed issues related to the current Recommended Dietary Allowance (RDA) for Vitamin D. At the meeting, many researchers in this field expressed the opinion that the current RDA for Vitamin D is too low for the general population. Presentations during the 2-day meeting related to deficiencies in Vitamin D. There was a strong emphasis on deficiencies in dark-skinned individuals and the fact that levels in these individuals tend to be much lower. It was suggested that the dietary levels may need to be adjusted for dark-skinned individuals to improve their Vitamin D health. Abstracts from this meeting were included in Council members' meeting packets. Dr. Lester noted that NIAMS provided funding to support the meeting.
DIRECTOR'S REPORT AND DISCUSSION
Dr. Katz apologized for arriving late to the meeting, noting that he was attending the bi-monthly NIH Steering Committee Meeting for Institute Directors. He reminded Council members that the January 2004 NIAMShorttakes was included in their meeting materials. The NIAMShorttakes addresses issues of importance to the Institute to enhance its transparency to the various communities interested in NIAMS activities. The January 2004 NIAMShorttakes focuses on the assessment of the Specialized Centers of Research (SCOR) Program.
Dr. Katz noted that although nominations for new Council members were submitted early, there has been an unforeseen delay in the approval process. Therefore, no new Council members attended this meeting. New appointees have been identified, however, and will be joining the Council pending approval. Dr. Katz thanked outgoing Council members Mr. Allen and Ms. Mandeville for their service to the NIAMS Advisory Council and for attending this meeting.
Personnel Changes
Dr. Katz announced several personnel changes at NIH. Dr. Norka Ruiz Bravo has been appointed as NIH's Deputy Director for Extramural Research. Most recently, Dr. Ruiz Bravo served as the Associate Director for Extramural Activities at the National Institute of General Medical Sciences. She may be asked to speak at a future Council meeting on issues related to NIAMS. Dr. Belinda Seto, following a nearly 1-year tenure as Acting Deputy Director for Extramural Research at NIH, has been named as the Deputy Director of the National Institute of Biomedical Imaging and Bioengineering. Dr. Claude L'Enfant, former Director of the National Heart, Lung, and Blood Institute, has retired, and there is a search underway to find a replacement. Similarly, NIH is searching for a Director of the National Institute of Environmental Health Sciences, as well as a Director for the Center for Scientific Review.
Within NIAMS, there is an active search underway for an Executive Officer. The application deadline for this position has closed, and applications are currently being reviewed. Dr. Katz mentioned one new addition to NIAMS' staff, Dr. Yan Wang, a former Research Associate at Johns Hopkins University School of Medicine, who is now a Health Science Administrator in the NIAMS Review Branch.
Update on Budget and Congressional Activity
With regard to the Fiscal Year (FY) 2004 budget, President Bush has signed the omnibus spending bill, which includes the appropriation for Labor/HHS. The net amount for NIH following rescissions and other adjustments is $27.7 billion; the amount for NIAMS is $501.1 million, representing a 3 percent increase over FY 2003. A certain amount of this money is dedicated to NIH Roadmap activities. NIAMS' FY 04 budget will allow for funding an estimated 202 new and competing research project grants (RPGs), which is a lower amount than in recent years. NIAMS staff will be re-evaluating the payline based on the final appropriations. Dr. Katz added that information on the President's FY 05 budget request will be made public on February 2, 2004.
Dr. Katz also highlighted Congressional activities related to provisions of the Children's Health Act of 2000. The Secretary, DHHS, established a Pediatric Research Initiative in the Office of the Director, NIH. NIH also has established the Inter-Institute Committee on Pediatric Research to encourage the development of new initiatives for pediatric research conducted and supported by its Institutes. The purposes of the Initiative are to increase support for pediatric biomedical research within NIH, enhance collaborative activities within NIH, and increase the number of pediatric clinical drug trials. The ultimate goal is to promote safer and more effective use of drugs in children.
During the week before this Advisory Council meeting, Dr. Katz along with NIH Director Dr. Elias Zerhouni and others testified at a Senate hearing entitled "Avoiding Conflict of Interest Issues at the NIH." Copies of Dr. Katz's written remarks from this hearing were sent to Council members in advance of this Advisory Council meeting. His remarks also are available to non-Council members upon request; the hearing is available on the Internet via Webcast for those who are interested. Dr. Katz emphasized that NIH is committed to ensuring that its conflict of interest policies and practices are completely transparent and that the NIH is conducting collaborations and partnerships in ways that benefit science and public health, but are above conflict of interest concerns. Dr. Zerhouni has created a blue ribbon panel to examine the guidelines governing the consulting activities of NIH.
Recent Scientific Advances
Dr. Katz highlighted several recent scientific advances. A very productive collaboration in the form of a Cooperative Research and Development Agreement involving NIAMS, Pfizer, and Stanford University has resulted in a paper published in the journal Science. The study focuses on a new immunosuppressive drug that was developed based on the identification of an enzyme called Jak 3, which is found only in immune cells. The study involved identification of compounds that would specifically block the action of the Jak 3 molecule.
Another study, conducted by University of Oklahoma investigators and funded largely by NIAMS, indicated that people diagnosed with lupus have autoantibodies in their blood years before symptoms appear. A greater specificity of the identified antibody system was achieved as the time of symptom onset approached. The study was able to access and take advantage of a large Army serum bank-Dr. Katz noted that serum banks such as these represent extraordinary resources for investigators studying antibody systems. Dr. Katz commented that this has been a very productive time for lupus research. He briefly mentioned a group of lupus studies-particularly cardiovascular lupus studies-recently published in The New England Journal of Medicine. Another recent study published in The Journal of Clinical Investigation showed that use of anti-CD40 ligand in patients can block B cell activation.
A group of researchers at Stanford University found that the average disability levels in patients with rheumatoid arthritis have declined by 40 percent since 1977. It is helpful to have these new data on long-term trends in disability showing that interventions in the last 25 years are improving disability levels at an average rate of 2 percent per year.
Upcoming Retreat
At the end of March, NIAMS will be holding its annual scientific retreat for the Institute's extramural program. At this retreat, areas of scientific opportunity, primarily focused on 2006, will be discussed. A report on the retreat will be given at the next NIAMS Advisory Council Meeting.
REVIEW OF NIAMS SPECIALIZED CENTERS OF RESEARCH PROGRAM
Dr. Sue K. Donaldson, Chair of the NIAMS SCOR Program Review Committee and former NIAMS Advisory Council member, called Council members' attention to the Report of the NIAMS Specialized Centers of Research Program Review Committee: Recommendations for the Future. The Committee included experts in the disease and basic science areas that are reflected in the SCOR Program. In preparing the report, the Committee was instructed to: (1) consider the current direction of NIAMS and its funding opportunities for translational research in the context of NIAMS priorities and the NIH Roadmap, (2) evaluate the NIAMS SCOR as a program for the advancement of translational research and make recommendations on the future of the SCOR Program, and (3) recommend new funding mechanisms for the advancement of basic to clinical research translation and clinical innovations.
Dr. Donaldson provided a brief overview of the current SCOR Program. She reminded Advisory Council members that the purpose of the SCOR Program is to expedite the development and application of new knowledge related to a specific disease. There are five disease-specific foci of the Program (osteoarthritis, rheumatoid arthritis, osteoporosis, lupus, and sclerodoma), which was designed to develop innovative approaches to understanding the mechanism and treatment of disease, elaborate new and significant hypotheses, and elucidate disease mechanisms and new treatment strategies. A key component is the basic-clinical matching of projects and investigators to create a synergy and collaboration. SCORs were designed to serve as national resources at major medical centers-each SCOR must include at least three separate but interrelated research projects focused on the specific disease-one of the projects must be a basic research project and another must be a clinical research project.
As part of the review of the SCOR Program, past and present SCOR Directors were asked to complete a survey and provide an assessment of their thoughts on the Program. A total of 14 past and present Directors completed and returned the survey. The Directors strongly advocated keeping a disease focus, and noted that the combination of basic and clinical projects and researchers stimulated scientific advances and multidisciplinary collaborations. These Directors indicated that the basic and clinical research requirement is unique to SCOR (at least with regard to NIAMS), and that the structure of the SCOR Program brought together scientists from disparate fields and across departmental boundaries to create a multidisciplinary team focused on the same disease. In addition, the Directors emphasized that the SCORs Administrative Core was essential to the coordination of scientists, scientific interactions, and research progress, and the Scientific Core served as an asset that attracted additional scientists as collaborators (the SCORs were viewed as prestigious by the home institution). One surprising finding of the survey was that the Directors felt that the SCORs changed the research culture of the home institution.
In evaluating the SCOR Program as a mechanism for translation, the Committee asked Directors what they thought should be changed. The Directors responded with mixed reactions. Comments included: (1) the 5-year award period is too short for outcomes, (2) there is uneven current knowledge across the diseases NIAMS supports, and (3) the current funding cap ($750,000) is too low for translational research. The Directors suggested increasing the award amount to attract the best scientists and increase the number of applications, adding flexibility to the SCORs for taking translational research risks by including a mechanism for pilot projects, and improving the review process.
The Committee concluded that basic-to-clinical research translation was not the primary aim or the major scientific contribution of SCOR. The Program has a well-established identity that would be difficult to change, and it has lost much of its appeal as a funding mechanism for the best scientists. For these reasons, the Committee decided not to amend the SCOR Program, but rather to move toward a completely new Centers mechanism-the Centers of Research Translation (CORT).
Dr. Donaldson presented the model of translational research used by the Committee in developing the new CORT mechanism, noting that the translational process can be defined as transforming knowledge from its context in basic science through directed basic research, translational applied research, and translational clinical research, toward the long-term goal of improving human health.
Dr. Donaldson explained that many of the features of CORT capture the positive or beneficial features of the SCOR Program. For example, there is an administrative unit headed by the PI as well as a Scientific Advisory Group (SAG) comprised of external scientists who oversee the rigor and conduct of the research. A minimum of three research projects are recommended for CORT (one directed basic research project and two clinical research projects). The Committee's vision of CORT is that each CORT would have a specific disease focus, similar to the SCOR Program. One major difference, however, is the addition of another administrative group, the Translation Advisory Group (TAG).
The TAG will have similar functions to the SAG (e.g., oversight, coordination, and communication), but they apply to the translational process and progress. The TAG will be composed of individuals who are lay persons who represent or are individuals affected by the disease, advocacy group representatives, etc. The intent is to provide a perspective from outside the scientific community into what the disease means for people who have it. TAG members could be scientists or health care professionals, but first and foremost they must be very familiar with what it is like to live with and cope with the disease. It is planned to have the TAG for each CORT meet at least once per year. The TAG will have well-defined goals and ways to measure progress, so that it can hold the CORT to its goals of innovative translation research and so that the knowledge is directly put into a clinically useful form.
Another departure from the SCOR Program is the addition of pilot projects that can quickly collect enough data so that larger grants, such as R01s, can be sought. These pilot projects will be internally funded at a level of about $50,000 per project per year for up to 2 years. Potential pilots will be approved by the SAG, and the TAG will select which projects to move forward. Innovative, spinoff research projects also are envisioned.
Dr. Donaldson summarized the recommendations/comments of the Committee as follows:
- Discontinue NIAMS SCOR at the end of its current funding cycle (the Committee recommended funding through the full award period of currently funded SCORs).
- Create a new research center mechanism specifically for translation and consistent with the CORT model.
- Institute 5-year award periods for CORT with competitive review criteria that take into account progress in the direction of translation.
- The time period for significant translation is likely to be more than 5 years.
- Identify and use short-term goals for basic-to-clinical research translation as the basis for renewals of CORT.
- The time period for significant translation is likely to be more than 5 years.
- Create a mechanism for sharing translational progress across funded CORTs and adaptation of CORTs over time.
- Create flexibility in the implementation of the CORT TAG.
- Provide adequate funding for CORTs.
- Minimum of $1 million direct costs for each CORT, with additional funding for pilot projects.
- Each CORT should be eligible for an additional $200,000 in direct costs per grant year to internally fund pilot projects ($50,000 per year for up to 2 years per pilot).
- The TAG must be fully implemented before CORTs become eligible to fund pilot projects.
- Minimum of $1 million direct costs for each CORT, with additional funding for pilot projects.
- Create a special review process for CORTs that weighs the quality of the overall translational plan as the highest priority, recognizing that research projects must be scientifically sound.
- Foster partnerships between CORTs and lay/advocacy groups and foundations invested in the disease-specific translation.
Discussion
Before Dr. Katz opened the discussion, he noted that the Institute of Medicine's (IOM) report on Centers of Excellence will be presented to the Senate on the Tuesday following this meeting. The report will be posted on IOM's Web Site, and Council members will be sent the executive summary and full content of that report.
Turning the discussion to the presentation by Dr. Donaldson, Dr. Katz asked who would be responsible for identifying the specific diseases on which CORTs will focus. Dr. Donaldson replied that there is no formal recommendation from the Committee on that matter; however, there should be some flexibility allowed so that diseases are not neglected. Input may come from individual investigators as well as NIAMS.
Dr. Andersson noted that the current SCOR Program focuses on some specific diseases, thereby eliminating others; the Committee's recommendations open the door for other diseases to be examined. Dr. Teitelbaum agreed, noting that the payoff in other diseases will come from the best translational research that is available and that this CORT model may represent the best possibility of bringing the science to the patients. He asked about the funding mechanism, particularly about what happens during the first few years when there will not be a clinical component. Dr. Donaldson replied that there are effective clinical projects that could start in the near term, and CORTs will not necessarily have to wait for the basic science to be developed from scratch in every case.
Dr. Teitelbaum suggested implementing a sequential funding mechanism in which the clinicians become part of the project later in its development. With regard to the TAG, he stressed the need to include disciplined individuals who understand how to conduct scientific projects and to ensure that the choice of project is not driven exclusively by emotion. Dr. Donaldson agreed, noting that the TAG will not select a project until after it has been cleared scientifically by the SAG.
Dr. Frank commented that it is appropriate that the TAG have a significant amount of input into the process. However, he expressed concern that the likelihood of success and completion of projects may not be as clear to TAG members. He suggested that at the time pilot projects are chosen, a few members of the SAG be present to provide expertise and assist in the decision making process. He cautioned that it may be difficult to integrate the TAG and SAG. Dr. Andersson explained that these groups will not be working in isolation, and commented that the existence of the TAG is an excellent approach to gaining another input into the process.
Dr. Donaldson noted that in terms of funding CORTs and replacing the SCOR Program, CORTs will cost more than SCORs, which currently represents less than 3 percent of NIAMS' budget. She also noted that the SCOR Program was never asked to be translational in nature. In response to another question, Dr. Donaldson explained that the interactions between and sequential nature of the three major projects of CORTs were left flexible. Depending on the state of knowledge, they might be tightly coordinated. With all three projects ongoing concurrently, those three PIs should interact closely because they are at the scientific heart of the synergy and translational aspects of the project. CORT pilot projects could be tied directly to these three projects, or could be spinoffs in other areas while still tied to the specific disease. In the discussion, it was recommended that NIAMS bring together CORT leaders at least once a year to promote cross-fertilization of ideas.
Dr. Moxley asked about the dynamics of the TAG group with the SAG and how the pool of TAG members would be identified. Dr. Donaldson explained that the Committee did not have enough time to discuss exactly how the TAG would be put together. In response to another question from Dr. Moxley, she noted that there is an opportunity to marry existing registries to CORTs. CORTs also could become a mechanism to help the registries link with one another and encourage cooperation across advocacy groups for which there currently is no incentive. She added that every patient advocacy group has boards and advisory groups, and that these bodies potentially could be tapped for TAG members.
Dr. Katz emphasized the need for the Committee to be explicit about where CORTs will be in 5 years. Dr. Donaldson agreed, adding that identifying achievable goals and aims as well as ways to objectively measure them are requirements of CORTs. As part of the flexibility of CORTs, it may be feasible to allow investigators who are applying for R01 grants or other types of similar awards to identify CORTs as a resource. The resources in CORTs as well as their translational impetus are very important, and other researchers might want to link with them.
Dr. Frank suggested that CORTs have a mechanism established at their onset to determine whether or not they are accomplishing the goals that have been set forth. Ms. Terry added that this mechanism should encourage public-private partnerships, involve industry, and possibly appeal to foundations for additional resources. She noted that exit strategies at the end of 5 years could include industry partners picking up a successful project and marketing it.
Dr. Lipsky closed this discussion session by commenting that implementing the CORT mechanism will require intensive education of the reviewers. This training will be essential; otherwise, CORTs may become just another mechanism for program project grants.
- Discontinue NIAMS SCOR at the end of its current funding cycle (the Committee recommended funding through the full award period of currently funded SCORs).
UPDATE OF THE NIAMS STRATEGIC PLAN
Ms. Helen Simon discussed updating the NIAMS Strategic Plan. She briefly outlined the current NIAMS strategic plan as a frame of reference. The current plan is for FY 2000-2004, and the framework included introductory information as well as a number of major crosscutting areas. Across programs, there are a number of disciplines and issues that affect every one of NIAMS' programs. Rather than framing the plan by crosscutting areas, it was decided to organize the narrative and goals by program structure.
In developing NIAMS' FY 2000-2004 Strategic Plan, six panels of approximately 12 individuals each were assembled in July 1999. Panel members were asked to think broadly; poll their community; and bring concerns, suggestions, and opportunities to their respective panels. Each panel included basic and clinical scientists as well as lay members. A draft plan was developed, posted on NIAMS Web Site, underwent a comment period, and then was submitted to NIH in December 1999.
Ms. Simon highlighted reasons for developing the new NIAMS Strategic Plan, including:
- Time-the current plan only extends through 2004. It is time for a longer range plan to be developed.
- NIAMS' budget, although experiencing substantial increases in recent years, will not always do so, and in light of recent budget projections, it is anticipated that research will be much more limited in coming years. Therefore, it is critical to ensure that the Institute is funding the highest quality research in areas of greatest opportunity and need.
- The NIH Roadmap involves a funded infrastructure that is under development. Developing NIAMS' strategic plan can help to determine how the Institute's communities can best use this infrastructure.
- Strategic planning is a healthy process for any organization to undertake when looking at its programs and long- and short-range goals.
Discussion
Dr. Katz noted that most of what is included in NIAMS' Strategic Plan for 2000-2004 is already being done or pursued in one way or another by the Institute. NIAMS staff are preparing to go through the Plan in detail to determine what has and has not been addressed. Because of the funding increases experienced by NIAMS and other NIH Institutes in recent years, it was possible to pursue many clinical research programs that NIAMS would not have been able to conduct otherwise. Dr. Katz further explained that updating the Strategic Plan is a high priority for the Institute. One approach is to ask various appropriate communities for input in identifying areas of opportunity or areas of real need. Then, scientific leaders, subject matter experts, and members of the lay community could be solicited for their input as well. In addition to identifying needs and opportunities, it will be important to discern what the realities are in terms of addressing them.
Dr. Moxley asked if there was flexibility within the government to allow NIAMS to play some formal role in other funding-related questions and how to define the potential resources that NIH Institutes, the Centers for Disease Control and Prevention (CDC), and other organizations might have. It may be important to fit in a number of other areas within the government because social and/or political measures likely should be funded using some bridge that utilizes other federal funds in addition to NIAMS resources. Dr. Katz agreed that making these types of decisions is critical in updating the Institute's Strategic Plan, and it is the responsibility of NIAMS staff to identify sources of additional federal-and nonfederal-sources of funding to complement NIAMS dollars. He added that NIAMS has to collaborate with other government agencies and does not necessarily have to share funds with these organizations, but should make every effort to share resources when appropriate.
Dr. Frank asked about the importance of setting goals in developing and updating NIAMS' Strategic Plan. Dr. Katz explained that goal setting and development are important, and flexibility is needed in these areas. He added that the current Strategic Plan covers a 5 year period, and that discussions have been held with NIAMS Program Directors to determine how to best develop the next strategic plan. It is likely that there will be a community comment period for the upcoming draft Strategic Plan. Dr. Katz assured Council members that the community will continue to have input in the NIAMS planning process.
Ms. Mandeville asked about using Requests for Applications (RFAs) to stimulate research in areas that are not as well developed at NIAMS. Dr. Katz responded that in the past, most RFAs were in areas that the Institute felt needed encouragement. He predicted that fewer RFAs will be released by the Institute in the future. When NIAMS does issue RFAs, it signals the community that those represent areas in need of more research. The Institute trusts the scientific community to push it in the appropriate directions.
In response to another question, Dr. Katz explained that NIAMS has maintained the RPG pool-not only R01s but also program projects as well-at 65-67 percent of the Institute's total budget. Some NIH Institutes (e.g., the National Cancer Institute [NCI]) maintain the RPG pool at 55 percent of the budget. One significant future challenge will be coping with changes in funding, particularly the deceleration in funding increases. NIAMS staff anticipated this deceleration and have been employing accelerated funding strategies to ease the impacts of these new budget realities.
- Time-the current plan only extends through 2004. It is time for a longer range plan to be developed.
NIH ROADMAP UPDATE
Dr. Katz briefed Council members on the NIH Roadmap, which is available online at http://www.nihroadmap.nih.gov. The Roadmap represents an infrastructure and framework of priorities that NIH has designed to optimize its research portfolio. The Roadmap contains a set of initiatives that are central to the study of the quality of healthy people in this country and is a vision for more efficient and productive biomedical research. Dr. Katz explained that the Roadmap positions NIH to address evolving public health challenges and is meant to accelerate the pace of discoveries.
The Roadmap was developed through extensive consultations with stakeholders that revolved around the scientific challenges of today, roadblocks and barriers to progress, needs for overcoming these roadblocks/barriers, and identifying activities that cannot be accomplished by any single Institute but rather are the responsibility of NIH as a whole. Criteria for inclusion in the Roadmap used by Institute Directors in developing it revolved around the following questions: (1) Is it transforming? (2) Would its outcome enhance the ability of all Institutes/ Centers (I/Cs) to achieve their missions? (3) Can NIH afford not do it? (4) Does it address key issues of interest to stakeholders (especially the public)? and (5) Is it something that no other entity can or will do?
Dr. Katz noted that three themes emerged:
- New pathways to discovery. This includes several initiatives, such as nanomedicine, computational biology, bioinformatics, molecular libraries, and building blocks/metabolomics and pathways.
- Developing research teams of the future. This includes establishing interdisciplinary research teams and more public/private partnerships, and is intended to facilitate development. It is envisioned that various groups will be able to utilize NIH as a resource for how to form these research teams.
- Reengineering the clinical research enterprise. This includes many initiatives in terms of moving information from the bedside to patient populations and practice. Harmonization of clinical research and regulatory issues is one of the highest priority initiatives in this area. Others include forming integrated clinical research networks, clinical research informatics, and training and career development.
Dr. Katz discussed reengineering the clinical research enterprise in more detail-he was involved in helping develop the NIH Roadmap in this area. One initiative in this area is the development of regional translational clinical research centers designed to promote an infrastructure that can be utilized by many investigators in various academic centers to conduct clinical research. Translational research also will be enhanced by promoting tools for translational research, that is, providing tools for investigators in areas such as preclinical drug synthesis and toxicity testing. This initiative is similar to NCI's Rapid Access to Intervention Development (RAID) Program and would help take individual investigator's fundamental ideas to the next step (e.g., the development of good laboratory manufacturing, toxicity testing, etc.). Without programs similar to RAID, investigators often turn to industry because federal funds and infrastructure are not available.
Another area of translational research found in the NIH Roadmap is enabling technologies for improved assessment of clinical outcomes. In essence, the goals are to improve and validate quality-of-life measures and improve the validation of surrogate markers of disease outcomes. Possible areas of focus include pain, fatigue, and other topics of common interest across the Institutes.
The integration of clinical research networks also is another Roadmap initiative. Dr. Katz explained that every time a clinical study is set up at NIAMS, infrastructure must be built. If all of NIH looks to integrate and expand clinical research networks, this would not be necessary, because the infrastructure already will exist. This initiative is meant to link existing networks so that clinical studies and trials can be conducted more effectively and to ensure that patients, physicians, and scientists form true communities of research. In lieu of the traditional NIH network involving academic health center sites and a data coordinating center, it is hoped that interoperable networks can be formed at NIH so that there can be shared sites, shared data, and wider utilization.
The Roadmap also will foster career development in terms of translational research. Much work already has been done in this area (e.g., K23, K24, and K30 Programs); however, these efforts need to be enhanced to attract more researchers to take training in this area. NIH already has an intramural clinical research training program, and that is being expanded because of a large amount of interest. Dr. Katz noted that there also have been discussions of whether there should be an M.D./Ph.D.-like program in clinical research to include experts who know all of the dimensions of and challenges associated with clinical trials. More recently, the TransNIH Multidisciplinary K12 Career Development Program has been established; its goals are to promote the development of investigators from a variety of disciplines in clinical research to be trained in multidisciplinary team settings to enhance clinical research.
Another Roadmap area that is being examined is the feasibility of whether NIH can utilize physicians in a program as National Clinical Research Associates to link with communities, with a specific focus on outcomes of comparative studies that NIH or other health agencies want to use. The question of feasibility arises because physicians already are tired, overworked, and burdened by too much paperwork. Dr. Katz explained that a think tank is being formed to discuss the barriers and realities of creating a network of National Clinical Research Associates.
Dr. Katz commented that harmonization and simplification of clinical research regulatory processes are among the easiest Roadmap initiatives for people to embrace. The goal is to harmonize and simplify requirements for clinical research in ways that enhance public trust. This already is being done to a very limited extent with adverse event reporting. Dr. Zerhouni appears ready to champion this initiative in terms of human subjects protection, the role of Data and Safety Monitoring Board-Institutional Review Board (IRB) interactions, the issue of having central IRBs, and consent procedures. All of these are practical issues that clinical researchers have to deal with and can discourage young investigators who may consider clinical research as a career.
As part of the Roadmap, NIH is building an inventory of networks and identifying best practices. The inventory includes networks at NIH as well as other federal agencies, academic centers, foundations, and industry. All of these stakeholders stand to gain considerably from a more efficient and effective clinical research enterprise.
In terms of funding NIH Roadmap activities, Dr. Katz explained that all I/Cs are committed to investing jointly in a pool of resources to support current and future Roadmap initiatives. In FY 2004, the budget for Roadmap activities is $128 million, in FY 2005 it is projected to be $260 million. Cumulative funding for the Roadmap from FY 2003 through FY 2009 will be approximately $2 billion (Dr. Katz reminded Council members that Roadmap initiatives are not set in stone, and some depend on feasibility). Dr. Katz identified members of the Roadmap Coordination Team, noting that NIH is actively recruiting a Senior Advisor for Clinical Research Reengineering Activities.
Dr. Katz closed his remarks by explaining that the Roadmap is grounded in broad-based input from many individuals across disciplines and is a work in progress. He stressed that it is incumbent upon NIAMS to identify how it can best utilize the resources and infrastructure being developed as a result of NIH Roadmap activities.
Discussion
In response to concerns about how the Roadmap addresses a lack of understanding of NIH's goals and public perception, Dr. Katz agreed that a significant portion of the population does not know what NIH does. NIH needs to do a better overall job of selling itself to the public and explaining its activities and how they are informing the science. NIH's Communications Office has developed a plan to better inform the public as well as elected officials about these issues. Dr. Katz explained that the Roadmap itself does not help inform in this way. Rather, it was developed to inform the scientific community and those interested in advocacy that NIH is trying build an infrastructure that various communities will be able to utilize over the long run to be more efficient and effective. Furthermore, it is envisioned that this infrastructure will lead to significant cost savings.
Ms. Replogle noted that one advantage of having patient and advocacy groups informed of the NIH Roadmap is that they can help NIH promote it to the larger community. Dr. Katz agreed, noting that these groups complement NIH's communication efforts to a great extent, although there still is much work to do in this regard. Dr. Teitelbaum explained that NIH also has to act as the "National Institutes of Science." NIH has made significant contributions and has been the catalyst for the development of the biotechnology industry, which in turn has made great contributions to translational research. He commented that translation only occurs as the result of good basic science research.
Ms. Kalabokes described a proposal that would create a communication network of all public advisory group members from NIH Institutes to discuss the various ways information is given to the public. Although it is important that NIH receive public input, it is equally critical that NIH fulfill its role in disseminating information to the public, and this is a significant challenge, particularly because of inconsistencies and constraints associated with IRBs.
Dr. Stanley cautioned that the term "roadmap" implies that all NIH-sponsored research is moving in a certain direction, and does not necessarily convey the fact that the NIH Roadmap is primarily establishing infrastructure. Dr. Katz explained that he recently had a conversation with Dr. Zerhouni regarding this issue, and agreed that the term "roadmap" could be misinterpreted as meaning that NIH is going to orchestrate research from the top down, but this is not true. He emphasized that the infrastructure being developed through Roadmap activities is intended to help facilitate the science. The term "roadmap" in this context is not meant to represent an orchestration of research.
Dr. Teitelbaum expressed concern that although many facets of the infrastructure will be helpful, some Roadmap initiatives may overlap with activities being conducted by other organizations. For example, one Roadmap initiative-creating molecular libraries-already is extensively being done by industry.
Dr. Katz agreed, noting that constant evaluation of the Roadmap is needed to ensure that it is promoting appropriate activities in support of NIH.
- New pathways to discovery. This includes several initiatives, such as nanomedicine, computational biology, bioinformatics, molecular libraries, and building blocks/metabolomics and pathways.
REPORTS OF RECENT MEETINGS (CONTINUED)
Lupus Federal Working Group
Dr. Serrate-Sztein reported on the recently created Lupus Federal Working Group, noting that establishing such a group has been an NIH objective for some time. One important reason for the creation of the Lupus Federal Working Group is the significant proliferation of organizations that are involved in research and education on lupus in addition to the increased number of clinical trials on lupus that are being conducted.
The Lupus Federal Working Group is comprised of invited representatives from DHHS agencies as well as the Department of Education, Department of Defense, and private foundations and industries involved in lupus research. The Working Group held its first meeting in October; Dr. Serrate-Sztein reported that this meeting was very successful.
The group is envisioned as providing a forum for the exchange of information and coordination of activities, starting with simple activities such as the organization of meetings and providing information on what other organizations are planning with regard to lupus. The group may evolve into coordinating more detailed initiatives as well. At least two meetings per year are planned.
Consensus Development Conference on Total Knee Replacement
Dr. Panagis reported on the Consensus Development Conference on Total Knee Replacement, which was held in December 2003. The Conference was intended to address the current state-of-the-science regarding total knee replacement (TKR). Conference sponsors included NIAMS, the NIH Office of Medical Applications of Research (OMAR), National Institute of Child Health and Human Development, NIH Office of Research on Women's Health, U.S. Food and Drug Administration, and the National Institute of Standards and Technology.
After an initial planning meeting to identify key issues and controversies, a series of questions were developed to be addressed by the Consensus Development Conference Panel. These questions involved the current indications and outcomes of TKR; identifying specific characteristics of TKR patients; the type of material used to make the prosthesis and the type of prosthetic design; specific surgical factors that ultimately may affect short- and long-term outcomes; and assessing whether there are steps that can be taken before, during, and after surgery to enhance outcomes. The Panel also was asked to consider approaches and outcomes for primary knee replacements that fail and have to be redone, identify whether there were factors that could explain disparities in utilization of TKR, and ultimately, provide recommendations for future research directions.
Dr. Panagis noted that these meetings are funded by the government, and Panel members are not federal employees. As part of the Consensus Development Conference process, an evidence-based literature review and report are generated, under the auspices of the Agency for Healthcare Research and Quality (AHRQ). Dr. Panagis drew Council members' attention to the Panel's draft statement, which was included in the meeting materials. A draft copy also is available on OMAR's Web Site. AHRQ is working to release their evidence-based report.
The panel concluded that TKR is a very successful procedure for patients who have symptomatic, painful end-stage arthritis. Approximately 90 percent of patients reported improved quality-of-life, and 85 percent reported satisfaction with the procedure. Some patients do not necessarily fare as well and may be at risk for a revision procedure. Young, overweight, especially active males are at risk for revision, as are patients who have comorbid conditions. Dr. Panagis reported that the Panel also found that surgeons and hospitals who carry out more of these procedures tend to have better outcomes, so surgical expertise clearly is a factor. One critical component of TKR is correct placement of the implant, and there are opportunities for computer-assisted technologies to help surgeons with placement. The Panel also found that use of antibiotics prior to or during surgery, aggressive postoperative pain management, and other factors improve patient outcomes following TKR.
Although few studies compare the success rates of different prosthetic designs, the Panel concluded that the durability and success rates appear to be similar. The effectiveness of anticoagulation therapy for pulmonary embolism prophylaxis is unclear. Furthermore, there is not a sufficient science base to recommend the most effective pre- and postoperative rehabilitation strategies.
Revision, or second, knee replacements tend to be less successful than primary knee replacements; these procedures also are more difficult and more extensive. Persistent infection and poor bone quality, limited quadriceps function, poor skin coverage, and poor blood supply are relative contraindications for a revision procedure. For those revisions that fail, there are successful salvage procedures (e.g., taking out the implant and leaving the joint as is with a soft tissue spacer).
Dr. Panagis noted that it is clear that there are racial/ethnic and gender disparities in TKR. Surprisingly, these do not seem to relate to economics or access to care. One study reviewed by the Panel found that despite the high success of the procedure, only 13 percent of women and 9 percent of men are willing to undergo TKR.
Discussion
Dr. Katz noted that even though $3.2 billion is spent on TKR and hip replacement procedures in the United States, TKR is an underutilized procedure. Dr. Serrate-Sztein, also noted that in some cases, the data from TKR studies are less than ideal because they come from surgeons and surgical institutions that are collecting the data. Therefore, these are convenience samples, and it is difficult or impossible to determine what happened to patients lost to followup or who went elsewhere for followup care. She commented that one other recommendation from the Panel was consideration for forming a national registry of TKR patients that collects certain information so that it can be shared.
Dr. Panagis closed the discussion session by noting that one of the benefits of the Consensus Development Conference was that it showcased research that NIAMS and others have supported. Furthermore, proposals for future studies can point to the evidence-based report generated from the Conference and refer to it for justification or validation of the need for future studies in this area.
First International Symposium on Osteopetrosis: Biology and Therapy
Dr. Sharrock reported on the First International Symposium on Osteopetrosis: Biology and Therapy, explaining that this was the first time that there was a serious effort to bring together basic scientists and clinicians to examine the state of knowledge on osteopetrosis, a rare genetic disorder with a great deal of variation in severity from benign to lethal cases. This group of disorders is characterized by a deficiency of osteoclastic bone resorption, which in severe cases could lead to immune deficiency. Over the years, researchers have found osteopetrosis to be poorly understood and refractory to treatment.
Dr. Sharrock noted that it was made clear at this meeting that understanding of the underlying mutations associated with osteopetrosis has improved markedly over the last few years. Most cases have been identified as mutations in genes or proteins that are involved in the generation of transport of protons across the osteoclast membranes and the acidification of the resorption space, which is crucial for bone resorption. One report discussed at the meeting showed promising results by treating patients with gamma interferon, which appears to improve their immune response to some degree. There also was a promising report on bone marrow transplantation, but this does not appear to have been as successful. Pulmonary hypertension was identified as a significant factor associated with morbidity in these patients.
Dr. Sharrock concluded that this was a much-needed meeting. It was organized primarily by Dr. Paul Orchard of the University of Minnesota and supported by a conference grant that was cofunded by NIAMS, the NIH Office of Rare Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases.
ADJOURNMENT
The 52nd 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.
CONSIDERATION OF APPLICATIONS
The Council reviewed a total of 561 applications in closed session requesting $123,778,994 and recommended for $123,620,354.
I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.
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Cheryl A. Kitt, Ph.D. |
Stephen I. Katz, M.D., Ph.D. |
