The 91st meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December 1–2, 2005. NIH Director Elias A. Zerhouni, M.D., welcomed the ACD members, presenters, and guests. He remarked on his attendance that morning at a White House event to recognize World AIDS Day. The NIH has played a strong role in fighting AIDS, especially through the National Institute of Allergy and Infectious Diseases and the Office of AIDS Research.
Dr. Zerhouni continued his update by discussing the NIH effort to pursue a multi-pronged strategy on the research front to prepare for a potential bird flu pandemic, supporting basic science, modeling programs, and the development of surveillance systems. Pierre Noel, M.D., of the Warren Grant Magnuson Clinical Center, has been assigned to serve as coordinator for the NIH's efforts for emergency preparedness in the event of an avian flu outbreak.
During the past summer, the NIH announced new, final conflict-of-interest rules for NIH employees. The rules balance the need for standards on divestiture and disclosure with the need to allow researchers to remain on the cutting edge of science, including participation in outside activities such as teaching.
Dr. Zerhouni characterized the fostering of young scientific investigators as paramount among NIH priorities. For this reason, the meeting featured a report on the work of the NIH New Investigators Committee, by Story C. Landis, Ph.D., Director of the National Institute of Neurological Disorders and Stroke (NINDS), and a presentation about a novel program at Princeton University to encourage students to pursue the biological sciences, by David Botstein, Ph.D.
Dr. Zerhouni recognized retiring ACD members Thomas J. Ansfield, M.D., Steven M. Paul, M.D., Larry L. Smarr, Ph.D. He also announced that regretfully Senator Connie Mack has resigned from the Committee due to other commitments. He expressed a debt of gratitude to Dushanka V. Kleinman, D.D.S., Deputy Director of the National Institute of Dental and Craniofacial Research, for her work in guiding the NIH Roadmap for Medical Research. He thanked Jeremy M. Berg, Ph.D., Director of the National Institute of General Medical Sciences, (NIGMS), and Judith H. Greenberg, Ph.D., Director, Division of Genetics and Developmental Biology at NIGMS for managing the second year of the NIH Director's Pioneer Award Program, which funded 13 awards.
Elizabeth G. Nabel, M.D., Director of the National Heart, Lung, and Blood Institute (NHLBI), reviewed opportunities, challenges, and activities of the Institute. She cited the NHLBI's research agenda and public outreach activities. The NHLBI is developing a translational research agenda that fosters clinical communications, stimulates the development of new tools, and trains the clinical workforce.
Antonio Scarpa, M.D., Ph.D., Director of the Center for Scientific Review (CSR), reviewed the Center's history and current activities. The CSR's mission is to ensure that NIH grant applications receive fair, independent, expert, and timely reviews — free from inappropriate influences — so that the NIH can fund the most promising research. It is well on the way toward instituting a totally electronic application process. Dr. Scarpa and the ACD members discussed ideas for improving the peer review process in the future.
Story C. Landis, Ph.D., Director of the National Institute of Neurological Disorders and Stroke (NINDS), presented background on the NIH Neuroscience Blueprint and an update on its progress. The Blueprint, which involves 16 NIH institutes and centers, has developed strategies and ideas for projects, such as graduate courses in the neurobiology of disease, a neuroscience information database, a neuroscience microarray consortium, and neuroscience training programs.
Dr. Landis also presented an interim report on the progress of the New Investigators Committee, which is addressing the problem of the increasing age of recipients of first-time RO1 awards. She reviewed the committee's development of action items for NIH consideration, as ways to better balance the age of investigators in the NIH portfolio.
Barbara M. Alving, M.D., Acting Director of the National Center for Research Resources (NCRR), reported on the Clinical and Translational Science Awards, which are part of the NIH Roadmap for Medical Research. The awards program is an attempt to develop an academic home for research in the clinical and translational sciences.
The Congress and Administration recently approved the NIH's Office of Portfolio Analysis and Strategic Initiatives (OPASI), the new office for analyzing the NIH research portfolio and determining how to best use resources to maximize the investment in science. Raynard S. Kington, M.D., Ph.D., NIH Deputy Director, provided an update on the OPASI.
ACD member David Botstein, Ph.D., described the development of a curriculum for undergraduate students at the Lewis-Sigler Institute for Integrative Genomics at Princeton University. The series of integrated introductory courses can prepare students for majors in any science. A hope is that the curriculum's introduction of modern ideas and techniques will encourage original research.
Timothy C. Hays, Ph.D., of the Office of Extramural Research, provided an update on the public access initiative, which is developing and offering access to published research funded by the NIH.
ACD member Joan Y. Reede, M.D., provided an update on the Outside Awards for NIH Employees initiative, which has been developing a list of bona fide awards that NIH employees may receive. Dr. Reede presented the ACD members with a list of 17 additional bona fide awards that have been reviewed.
Marc Smolonsky, Associate Director of the Office of Legislative Policy and Analysis, Office of the Director, reported on recent NIH budget deliberations by Congress and other Congressional activities that involve the NIH, such as hearings and briefings involving NIH scientists and staffs, and the draft legislation to reauthorize the NIH.
Wendy Chaite, J.D., the NIH Director's Council of Public Representatives' liaison to the ACD reported on the Council's recent meeting.
The 91st meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held December 1-2, 2005, on the NIH campus in Bethesda, Maryland, and Webcast globally. The next meeting is tentatively scheduled for June 2, 2006.
NIH Director Elias A. Zerhouni, M.D., welcomed the ACD members and other participants and guests. He remarked on the White House event to recognize World AIDS Day that prevented him from joining the group at the beginning of the meeting. A notable aspect of the United States' effort to combat AIDS is the difficulty of delivering therapy to developing countries. The pandemic continues to be a global challenge. The NIH has played a strong role in fighting AIDS, especially through the Office of AIDS Research and the National Institute of Allergy and Infectious Diseases.
Dr. Zerhouni reviewed the day's agenda. This included a report on the Clinical and Translational Science Award program, which is part of a large effort to create an intellectual home that will support clinical research on translational science. Also on the agenda was an update on the NIH Neuroscience Blueprint initiative efforts to identify cross-cutting, multi-institutional areas of research that need support.
Dr. Zerhouni characterized the fostering of young scientific investigators as paramount among NIH priorities. The age at which investigators receive their first RO1 grants has risen steadily in recent years. Furthermore, a flat NIH budget in the years to come will disproportionately affect young researchers. It will become increasingly difficult for new investigators to achieve independence. Story C. Landis, Ph.D., and Norka Ruiz Bravo, Ph.D., reported on the work of the NIH New Investigators Committee, which formed about one year ago to identify ways in which the NIH could help young investigators flourish. David Botstein, Ph.D., described a novel program at Princeton University to encourage students to pursue the biological sciences.
Dr. Zerhouni stated that it was important for the ACD members to meet new NIH Institute and Center directors. For this reason, Elizabeth G. Nabel, M.D., Director of the National Heart, Lung, and Blood Institute, and Antonio Scarpa, M.D., Ph.D., Director of the Center for Scientific Review, made presentations at the meeting.
Raynard S. Kington, M.D., Ph.D., NIH Deputy Director, presented progress in developing and preparing to launch the new NIH Office of Portfolio Analysis and Strategic Initiatives (OPASI). The OPASI will continuously analyze the NIH research portfolio and seek to fund new science (such as in emerging fields) that otherwise might not be funded. It will create a dialogue about cross-cutting areas of science and will help the NIH provide leadership in the scientific community.
Timothy C. Hays, Ph.D., of the NIH Office of Extramural Research, reported on the new public access policy, which involves an electronic compendium of NIH-funded research that is searchable and linked to sources and other databases. The policy will provide the public with a window into NIH-supported research.
Marc Smolonsky, the NIH's Associate Director for Legislative Policy and Analysis, reviewed recent Congressional activities pertaining to the NIH. Dr. Zerhouni reported that the Senate and House of Representatives held a conference in which President Bush's budget for the NIH was adopted. The bill then failed in the House, leading to a continuing resolution to fund the NIH at the 2005 level (until December 17). In light of the chance that the budget will remain flat, the NIH has attempted to be a good steward of available funds. It will fund all programs at 80 percent during the first quarter of 2006 and adjust funding when Congress establishes 2006 levels.
Dr. Zerhouni expressed a debt of gratitude to Dushanka V. Kleinman, D.D.S., for her work in guiding the NIH Roadmap for Medical Research (she has returned to her position as Deputy Director at the National Institute of Dental and Craniofacial Research). Lisa J. Colpe, Ph.D., M.P.H., has taken the position of Acting Assistant Director for Roadmap Coordination.
Dr. Zerhouni thanked Jeremy M. Berg, Ph.D., Director of the National Institute of General Medical Sciences, (NIGMS), and Judith H. Greenberg, Ph.D., Director, Division of Genetics and Developmental Biology at NIGMS for managing the second year of the NIH Director Pioneer Award. Seven institutes volunteered to fund 13 Pioneer Awards in the second year. In time, the Pioneer Award program will allow the NIH to identify, based on the cohort of applicants, research ideas that have had difficulty finding support.
The NIH is pursuing a multi-pronged research strategy to prepare for the potential bird flu pandemic, including support of basic science, modeling programs, and the development of surveillance systems. The efforts are national and international. A candidate vaccine is currently being tested. The NIH, the U.S. Department of Health and Human Services (HHS), and the White House are working together to create a coordinated plan to respond to the threat administratively. Pierre Noel, M.D., of the Warren Grant Magnuson Clinical Center, is serving as coordinator of the efforts at NIH for preparedness in the event of an outbreak.
During the past summer, the NIH announced revised conflict-of-interest rules for NIH employees. The period of comment and revision resulted in final rules that reflect a greater need for standards on divestiture and disclosure among NIH employees who play decision-making roles. The rules balance this need with the need to allow researchers to remain on the cutting edge of science, including participation in outside activities such as teaching opportunities. The NIH continues to encourage interaction with the private industry, including public-private partnerships. Dr. Zerhouni thanked Dr. Kington for leading the efforts on the ethics issue.
Dr. Zerhouni recognized retiring ACD members, and thanked them for their years of service. These included Thomas J. Ansfield, M.D., Steven M. Paul, M.D., Larry L. Smarr, Ph.D. He also announced that Senator Connie Mack regretfully resigned from the Committee. Dr. Kington noted that the following ACD members were unable to attend this meeting: Nancy E. Adler, Ph.D., Lee C. Bollinger, J.D., Alexander R. Lerner, Christine E. Seidman, M.D., and Phillip L. Williams.
Discussion
The ACD members considered whether the NIH Director's Pioneer Award program and the OPASI program might be integrated in some way. Dr. Kington suggested that some new research needs identified by the OPASI might become Pioneer Award projects. Dr. Berg noted that some candidates applying for the Pioneer Award had histories of unsuccessful grant applications. Analysis of such candidates could lead to the identification of areas in need of support. Dr. Botstein stated that many research applicants do not enjoy the proposal process and that some sense biases in the reviewing. He suggested that the NIH offer more aid in learning and using the process.
Institute Director's Report: National Heart, Lung, and Blood Institute
Elizabeth G. Nabel, M.D., Director of the National Heart, Lung, and Blood Institute (NHLBI), reviewed opportunities, challenges, and activities of the Institute. The NHLBI supports basic research, clinical investigations, population studies, training, and more. Its operations have four main themes:
Stimulating the discovery of the causes of disease.
Speeding the translation of discoveries to clinical applications.
Facilitating communication between scientists and physicians.
Communicating advances to the public.
Areas in which discovery is stimulated include systems biology, nanotechnology, proteomics, genomics, genotyping, pharmacogenetics, and imaging. Single investigators and small groups of basic researchers produce most of the unanticipated and major scientific discoveries.
The NHLBI seeks to provide national leadership in taking risks, capturing research opportunities, and developing an innovative research portfolio that includes emerging fields. The NHLBI is developing a translational research agenda that fosters clinical communication, stimulates the development of new tools, and trains the clinical workforce. It seeks to focus on scientists within collaborative research teams to advance communication between scientists and physicians. It is creating mechanisms that facilitate interdisciplinary research and has developed a new RO1 expedited grant mechanism to facilitate first-time awards.
The NHLBI communicates scientific advances to the public in part by forming strong partnerships with professional organizations and patient advocacy groups. The education of the public in preventing heart, lung, and blood diseases is among our highest priorities. Large public awareness campaigns have included the HeartTruth campaign, which targets women and heart disease, and the We Can! Campaign, which targets childhood obesity.
The NHLBI is developing a strategic plan to devise a scientific blueprint for the next decade. This will be a bottom-up approach to a series of scientific and operational questions (opportunities and challenges, obstacles to progress, operational needs). The Institute will identify scientific areas to which it is well positioned to contribute, evaluate mechanisms of research support, and increase inclusiveness.
The strategic process will begin in 2006 with a series of meetings and workshops to develop themes, including NIH-wide cross-cutting topics. A strategic plan will be drafted in late 2006 and will be reviewed, revised, and finalized by spring 2007. Dr. Nabel looks forward to working with NHLBI constituencies to develop an innovative research portfolio.
Discussion
J. Michael Bishop, M.D., encouraged Dr. Nabel to include the topic of prevention in the NHLBI's list of areas targeted by basic research. Dr. Nabel agreed with the importance of prevention and noted the NHLBI's rich history of work in this area and its application to such problems as obesity. Dr. Landis encouraged the NHLBI to integrate with other institutes in planning research on stroke. Dr. Vijayanagar mentioned the great recent advancements in fighting cardiovascular disease and wondered whether statin drugs would be emphasized in new research. Dr. Nabel noted ongoing clinical trials on new statin drugs and research on the mechanisms of cholesterol.
David B. Abrams, Ph.D., Director of the Office of Behavioral and Social Sciences Research (OBSSR) stated that his office was participating in a cross-institutional effort to examine mechanisms of behavioral change, an issue relevant to prevention. This is a basic-science focus.
Dr. Botstein mentioned the overlap of the NHLBI portfolio with those of the neurobiology and endocrinology research communities. He encouraged the institutes to consider jointly funded programs.
The ACD members lauded the NHLBI's effort to support young researchers. Dr. Ruiz Bravo noted her subcommittee's work to evaluate what each of the institutes and centers was doing to support young researchers. Dr. Bishop encouraged the NIH to go beyond the issue of new investigators to consider the research ideas contained in proposals that are nearly (but not) accepted. Joan Y. Reede, M.D., reminded the group of the need to target women and minorities when supporting young investigators. Dr. Ruiz Bravo responded that her subcommittee had not yet performed a full analysis of women and minorities, but that early indications were that female young investigators were successfully obtaining funding.
NIH Director's Council of Public Representative (COPR) Liaison Report
Wendy Chaite, J.D., the COPR's liaison to the ACD, reported on the COPR's October meeting. At that meeting, the Council members witnessed presentations on the Clinical and Translational Science Awards, the efforts to reengineer the clinical research enterprise, the NIH Public Trust Initiative, the OPASI, and the Trans-NIH Communications Initiative on Clinical Research. They discussed those issues and more, including the possibility of incorporating public representatives into the NIH peer review process.
The COPR meeting followed a new format, in which a work session was held the day before, rather than after the formal meeting. This new approach produced a productive discussion of issues in the formal meeting and allowed Dr. Zerhouni to respond immediately to a number of new ideas.
The COPR members made many suggestions, including the following:
Consider ways in which the public can contribute to OPASI.
Educate scientists about the role of the public in research, perhaps using a standard curriculum.
Involve communities in reengineering the clinical research enterprise.
Consider new models for bringing clinical/translational science to rural settings, for example, by using mobile research centers.
The COPR members agreed that public participation in the peer review process would be most beneficial if employed at particular places in the review cycle. Dr. Zerhouni asked the COPR members to reach out to the public representatives at the NIH and to identify additional opportunities for more public participation. Public participation should be made integral to the fabric of the NIH research enterprise. The COPR members also heard about progress in the efforts of two of their work groups. The first group has been developing a process for assessing the usefulness and effectiveness of COPR activities. The second identified areas that the NIH should target to strengthen its communications, including the NIH identity, congressional contacts, and public outreach. All persons associated with the work of the NIH should consider communication as part of what they do on a daily basis.
Ms. Chaite recognized the work and support of Dr. Ansfield, who served as the ACD's liaison to the COPR. Dr. Ansfield responded by offering his appreciation for the strides that the COPR has made.
Story C. Landis, Ph.D., Director of the National Institute of Neurological Disorders and Stroke, presented background on the NIH Neuroscience Blueprint and an update on its progress. She described the Blueprint as a "Roadmap" type of initiative for the nervous system. One reason for development of the Blueprint is that no NIH institute or center takes the lead in diseases of the nervous system, which include devastating conditions such as Alzheimer's disease, schizophrenia, autism, and addictions. Nevertheless, most of the institutes consider aspects of nervous system disorders, such as addictions, blindness, and autism.
The Neuroscience Blueprint involves 16 NIH institutes and centers (ICs), with the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS) playing lead roles. The initiative is guided by the following three themes that permeate the work of most institutes:
Many diseases share underlying mechanisms that involve the nervous system (e.g., neurodegeneration).
Problems with neural development underlie many diseases, and repair of the nervous system would be facilitated if we could reactivate developmental mechanisms.
The brain can adapt and remodel.
Dr. Zerhouni initiated the Blueprint in February 2004, when 14 IC directors met to begin planning to work together. The group inventoried major NIH neuroscience efforts and convened meetings with consultants identified by the ICs. The consultants met in a large gathering in August 2004 and developed outreach to societies and advocates. The public launch of the NIH Neuroscience Blueprint occurred in October 2004.
The Blueprint group has developed strategies and ideas for projects, including graduate courses in the neurobiology of disease, a neuroscience information database, a neuroscience microarray consortium, an interdisciplinary center (resources and facilities), neuroscience training programs, and a toolbox for the assessment of neurological and behavioral function. The development of these strategies is under way. Future ideas include initiatives within the themes of neurodegeneration (2007), development (2008), and plasticity (2009). Blueprint initiatives are supported by a common fund created by contributions from participating ICs ($7 million for 2005). Some key functions, such as sharing best practices and developing common policies, might not require funding. Information is available at http://www.neuroscienceblueprint.nih.gov/. Ideas may be sent to blueprint@mail.nih.gov.
Discussion
Tadataka Yamada, M.D., proposed that the development of the toolbox (biomarkers, etc.) feature the involvement of industry. In developing the microarray consortium, the Blueprint group should seek to avoid redundant efforts and to increase productivity. Dr. Landis noted that the National Center for Research Resources (NCRR) has taken the lead in supporting imaging studies and collecting results in databases. Its work could be considered a good starting point for such studies relevant to the Neuroscience Blueprint.
Dr. Paul wondered whether the Blueprint lacked a focus on the genome, which is needed. Dr. Landis recognized that need, noting that the Blueprint was required to set priorities in light of limited funding. Many of the institutes have initiatives relating to gene discovery. Dr. Botstein proposed that the National Human Genome Research Institute (NHGRI) be invited to join the Blueprint group. Collaborative efforts (including groups outside the NIH) could lead to reduced genotyping costs. The complexity and scope of genome research might suggest a need for a future "Roadmap" initiative for this area itself. The need for collaborative efforts in the Blueprint raises issues such as the social engineering of researchers and the fact that the NIH funding structure encourages individual achievement. Dr. Ruiz Bravo cited one response to these issues-an effort within the Blueprint to credit researchers as principal investigators. Ms. Chaite suggested that the OPASI consider the Neuroscience Blueprint as a model for other NIH efforts.
Barbara M. Alving, M.D., Acting Director of the NCRR, reported on the Clinical and Translational Science Awards (CTSAs), which are part of the NIH Roadmap for Medical Research. The request for applications for this award will be issued annually. This program will develop academic homes (centers, departments, or institutes) for clinical and translational science throughout the country. These CTSAs are designed to transform clinical and translational research in the United States; their ultimate purpose is to ensure that new treatments and improved understanding of disease can be developed and delivered more efficiently and quickly to patients and the general public.
A new integrated environment for clinical and translational researchers will involve support for bioinformatics, clinical trial design, protocol preparation, regulatory compliance, and ethics.. The CTSAs are designed to train and develop the workforce of the future and will therefore offer advanced degrees in clinical and translational research. The awards encourage partnerships with industry and other nonfederal as well as federal agencies.
Domestic institutions, universities, and academic health centers are eligible for CTSAs. Each institution may be part of only one application for an award and is encouraged to provide examples of interdisciplinary collaborations that will be developed through the award.
By providing opportunities for original research in clinical and translational science, the program will help to establish a distinct discipline to work toward discovery and improved patient care. A CTSA award may be for up to $6 million in total costs per year (usually less) and will be for a 5-year period. The program has $30 million to support from four to -seven awards during FY 2006.
The NIH intends to expand the program to about 60 awards by 2012, funded in part by the NIH Roadmap for Medical Research. The first round of applications are due in the summer of 2006, to be funded beginning in September 2006. A trans-NIH committee will oversee the program. Further information is available at http://nihroadmap.nih.gov.
Discussion
Dr. Yamada suggested creation of an RO1-styled program to accompany the CTSA, and tailored for young researchers who, based on their expertise, have difficulty finding an academic home. The CTSA program will also likely need to consider the problems of promotion and tenure that can occur in the clinical environment. Dr. Alving expressed the hope that the degree-granting aspect of the program could create forces that would mitigate such difficulties. Dr. Zerhouni emphasized the intention of having science drive the program. The RO1 formula does not necessarily promote the asking of bold questions. Dr. Yamada added the suggestion of incorporating clinical/translational ideas into medical school curricula.
C. Martin Harris, M.D., suggested beginning an evaluation program to uncover areas where best practices might be shared. Dr. Alving expressed the hope that such a program could address issues of intellectual property and produce standards that could apply to protocols. Dr. Zerhouni noted that the level of sophistication needed for translational science was usually lacking. The CTSA could lead to a critical mass of sophistication at a reasonable cost. The program likely will involve international cooperation over time. Pharmaceutical firms will not be program applicants, although they could partner with program applicants. Dr. Abrams welcomed the possibility of bringing behavioral, social, and biomedical sciences together in this program.
Princeton Interdisciplinary Undergraduate Biology Program
Dr. Botstein described the development of a curriculum for undergraduate students at the Lewis-Sigler Institute for Integrative Genomics at Princeton University. In response to a diminished interest of students in biology and a trend away from teaching quantitative aspects of biology, a group of educators created an introductory science curriculum that integrates biology with other areas. The curriculum is intended to supplement rather than replace standard curricula. It teaches quantitative aspects by introducing them as they are needed, but stressing fundamental ideas.
Other features of the Princeton curriculum are the use of modern tools (computers, computer languages, algorithms, numerical methods) and heuristics (as opposed to rigorous calculations). Senior faculty in physics, chemistry, computer science, molecular biology, and ecology and evolutionary biology teach the 2-year curriculum (6 semesters total). Student fellowship winners teach the laboratory classes.
A key principle of the curriculum is to teach all ideas from a modern viewpoint, using new technologies and eliminating or at least reducing teaching from history. Dr. Botstein expressed the opinion that integrated introductory courses, using computation from the start, can prepare students for majors in any science. Introducing modern ideas and techniques early in a student's curriculum can encourage original research.
Discussion
Dr. Botstein stated that the school does not intend to apply such a curriculum on the graduate level, because students at that point have made choices that would reduce the course's effectiveness. Dr. Smarr expressed concern about how the students would integrate into upper-level undergraduate courses after experiencing the special curriculum. Dr. Botstein reported that the students, who are high achievers, have integrated well so far. Nevertheless, the molecular biology department is developing a new course that might help to accommodate these students.
Dr. Yamada expressed concern that such a curriculum does not affect the problem of losing science students in secondary school. Also, it might simply attract students who are well motivated. Dr. Zerhouni cautioned that the curriculum might be experiencing success at present because of its small size, drawing on the small number of good students. Dr. Botstein stated that engineering departments have been conservators of science culture for the past quarter century. This new curriculum brings together biology and chemical engineering in a non-engineering environment. The value of the program for the graduate teaching assistants (labs) has yet to be assessed. The laboratory portions of the curriculum are to be published in book form in 2006.
Dr. Landis presented an interim report on the progress of the New Investigators Committee, which comprises institute directors, training program directors, and others.
The committee has been studying the problem of the increasing age of first-time RO1 award recipients. It developed action items for NIH consideration aimed at better balancing the age of investigators in the NIH portfolio. One goal is to ensure that investigators spend a good amount of their careers as independent researchers. The committee recently studied published reports on investigators and their independence. It considered a series of topics, including the following:
Definitions of predocs, postdocs, and first-time investigators. " Systems to track them.
Best practices for research training.
Encouraging research institutes to offer postdocs training in grant writing, project management, and mentoring.
Training opportunities for non-U.S. citizens.
Expanded NIH funding strategies.
In particular, the committee proposed that the NIH develop a Career Transition Award Program to promote independent research careers. In the program, a first phase of 1 to 2 years of mentored support would be funded by a K mechanism. A second phase of 3 years of independent research (faculty position) would be funded by an R mechanism. The Steering Committee is considering the proposal.
Dr. Landis noted additional IC-specific practices that are serving to foster new investigator independence, such as special attention at Council, increased paylines (RO1) for new investigators, funding RO1 applications for new investigators to achieve designated success rates rather than a specific payline, and compressed review cycles for new investigators. The National Institute of Environmental Health Sciences (NIEHS) has created an RO1 pilot program for first-time applicants only.
Discussion
Dr. Botstein advised against eliminating elasticity in the definitions ("postdocs," etc.) that allows certain international investigators to work in the United States. There is also a need for flexibility in budgets. It was noted that the nature of science today might be what accounts for the rarity of an investigator being prepared for an RO1 at an early point.
Dr. Zerhouni expressed enthusiasm for the proposed Career Transition Awards, which would be welcomed by deans at research institutions. Such an award would give the young investigator "credentials." Dr. Bishop agreed and encouraged the NIH to apply a fast-track approach in its review of RO1s for first-time investigators. Dr. Landis noted that NIH would have to encourage program directors not to reduce funding in transition years. It should also evaluate the program to determine whether it leads to an increase in new investigators.
Publicity and marketing could be important to the program's success. Dr. Reede encouraged the NIH to track the success of women and minorities in the program. Dr. Landis stated that the committee has not determined whether the Career Transition Awards should be reviewed by the ICs or the CSR (they will comprise a mix of K and R awards). One idea is to create special study sections for the program. However, as Dr. Zerhouni noted, the ICs must be involved to ensure that the most relevant research is supported.
Office of Portfolio Analysis and Strategic Initiatives
Dr. Zerhouni reported that Congress and the Administration had approved the OPASI, the new office for evaluating the NIH portfolio and determining how to best use resources to maximize the investment in science.
Dr. Kington, who has led the development of OPASI, provided an overview of how it will function and why it has been created. The mission of OPASI includes the following:
To provide the ICs and NIH as a whole with methods and the information necessary to improve management of their portfolios.
To identify important areas of emerging scientific opportunities and health challenges.
To assist in accelerating investments in those areas, especially involving multiple ICs.
To coordinate and make more effective the use of the NIH evaluation process.
The OPASI will be an intellectual home for new techniques. It will feature transparent, systematic processes for coding the funding of research on diseases and conditions, for assessing scientific opportunities and public health needs, and for coordinating the funding of research that cuts across or falls between NIH institutes and centers. It will continually evaluate NIH research investments and be responsive to emerging scientific demands and opportunities.
Dr. Kington presented a schematic of the structure of OPASI, featuring three levels. The NIH Director will oversee the office. A second level will include an OPASI Director who will coordinate with a steering committee. A third level will comprise a Division of Resource Development and Analysis (DRDA), a Division of Strategic Coordination (DSC), and a Division of Evaluation and Systematic Assessments (DESA). As an example, the DRDA will employ computerized methods for scanning documents, developing "fingerprints" to reveal themes and relationships that can identify relevant, needed research.
Sources for the identification and nomination of topics for OPASI will range widely and include IC directors, stakeholders, evaluation processes, programmatic offices, and more. Topics will be vetted by a Council of Councils (public and NIH representatives), by the IC directors, and by the ACD. The OPASI will assign approved topics to a lead IC or combination of ICs. Each approved program will have a 5-year cycle, with an opportunity to be renewed for an additional 5 years (for a maximum of 10 years). The programs will be supported by a common fund comprising set-asides by the ICs (a total of 1.1 percent of the NIH budget for FY 2006). Future growth of the common fund will depend on identified trans-NIH scientific opportunities and public health needs.
Discussion
Dr. Bishop applauded the OPASI for providing more opportunities for trans-NIH dialogue, decision making, and funding. . He wondered how NIH would coordinate suggestions for OPASI programs/initiatives. Dr. Kington responded that many ideas would come from the Roadmap process. Dr. Zerhouni responded that many ideas would come from the ICs and their scientific constituencies. Prioritization will be driven by the IC directors and the OPASI staff and steering committee. Many early initiatives of the NIH Roadmap for Medical Research were driven by pent-up demand, and this could happen with OPASI at first. A goal is to eventually generate completely novel ideas. Outside participation will be encouraged. Dr. Zerhouni expressed the hope that the OPASI program will help some researchers bypass NIH process hurdles and better support new ideas.
Dr. Smarr encouraged the NIH to continue to take advantage of the massive amounts of scientific data that it generates. This data pool can be considered a conceptual map that can guide the NIH and researchers in management and planning (and that can inform OPASI). Dr. Ansfield cited the Obesity Initiative as an example of the sort of barrier-breaking process that the OPASI might undertake as it streamlines methodologies and helps agencies to work together.
Dr. Kington stated that the OPASI has been announced in the Federal Register and the NIH is seeking an acting director. The program should be up and running in January 2006. Dr. Zerhouni stated three governing ideas for the OPASI:
Minimize the OPASI infrastructure.
Allow the ICs to perform the management of projects (OPASI should not become another institute).
Maintain time limits on projects.
The OPASI organizers have already begun talking about time frames for future projects, including the creation of a fast-track system for rapid response (for example, to address an epidemic). Dr. Smarr encouraged the OPASI to keep the ICs involved in projects continually, so that methods and successes can be picked up by them rather than lost.
Timothy C. Hays, Ph.D., of the Office of Extramural Research, provided an update on the public access initiative, which is developing and offering access to archives of publications funded by the NIH. The goals of the policy are as follows:
To establish a central archive of NIH-funded research publications.
To create an information resource that helps scientists mine research publications and helps the NIH manage its research investment.
To provide general electronic access to NIH-funded research publications.
Dr. Hays reviewed milestones in the initiative, leading to the current effort to add progress report functionality to the system and (in February) batch uploading by publishers. The progress of the new policy will be reported to Congress on March 1, 2006.
Participation in the system by authors, which is voluntary, has been low. Nearly 200 journals provide all of their articles to PubMed Central, and this represents about 8 percent of all eligible documents that could be submitted to the public access manscript submission system. NIH found that the time required for authors to submit articles varied, but two thirds of submitters took less than 13 minutes to submit. Submission time decreases for an author making multiple submissions.
A recent survey of health sciences libraries revealed anecdotal reasons for the low participation rate. In this study, most librarians and senior faculty stated that they were aware of the policy. The major reason for limited participation is time. Other concerns include confusion over copyrights and version control. Congress directed the NIH to develop an aggressive education and outreach initiative to inform grant recipients of the policy as a way to increase participation. Dr. Hays reported a series of outreach efforts that have focused on both the public and NIH staff.
The Public Access Policy Working Group, comprising investigators, publishers, and library representatives, met on November 15, 2005, and discussed three questions: Should participation in the policy be voluntary or mandatory? What should be the length of the embargo period before public access is permitted? What is the best version to display? Most of the group members stated that for the policy to be effective (e.g., have a large percentage of submissions) the policy would need to be mandatory for NIH-funded investigators. Opinions on an embargo period varied (mainly 6 or 12 months). Display of the publishers' final copyedited versions of articles was strongly preferred.
Dr. Hays stated that his group would continue efforts in outreach and evaluation. The Public Access Policy Web site is at http://publicaccess.nih.gov/.
Discussion
In response to the idea that agreements with main science publishers would increase participation, Dr. Hays noted that a large number of articles are published in small not-for-profit journals. The NIH's relationship is with the funded investigators rather than the publishers. Concerns of publishers include the length of time for the NIH's use of articles and their format (publishers prefer that their PDF version of an article not be altered). Dr. Smarr wondered whether financial incentives could make publishers more willing to contribute to the program. Dr. Hays responded by noting that publishers who are part of PubMed Central have had increased traffic to their Web sites. Reduced revenues from article reprints appear to be minimal. Dr. Smarr recalled similar issues and arguments surrounding Science magazine's creation of an X-ray crystallographic database, which, in the end, had a positive result.
Dr. Hays cited copyright issues. Journals have identified articles posted in PubMed Central that have violated copyright, and the NIH has removed them. The NIH will repost the article when the author and publisher resolve the copyright question. Dr. Bishop encouraged the NIH to solve such problems by dealing with the publishers rather than the authors, because copyright law is complex. Dr. Zerhouni cited additional complexities of the archiving process (possible linkages, limited-access archives) and concluded that having a process in place (Public Access) can lead to resolution.
The ACD members wondered about the possibility of offering article digests or abstracts that are friendly to non-scientists. .Dr. Smarr suggested a potential profit for publishers who offer lay-targeted digests of articles, for example, through a Web link from the archive to the journal site.
Institute Director's Report: Center for Scientific Review
Dr. Scarpa, Director of the Center for Scientific Review, described peer review as the heart and soul of the NIH, adding that it has provided an incredible value for the country and the world. The CSR has historically processed huge numbers of grant applications in its offices outside Washington, D.C. However, it is now well on the way to becoming an all-electronic process. The NIH processes about 80,000 grant applications per year, and about two-thirds of those are handled by the CSR (the others are handled by the ICs).
The CSR's mission is to ensure that NIH grant applications receive fair, independent, expert, and timely reviews — free from inappropriate influences — so that the NIH can fund the most promising research. The culture of science is changing as a result of profound trends such as increase in chronic diseases, multi-organ diseases, and shifts in the practices of medical schools and hospitals. The CSR needs to respond to these changes by increasing communications, uniformity, and efficiency, and by better facilitating the work of the IC program staff.
Changes at CSR that are under way or being planned include shortening the review cycle, improving the evaluation of clinical research, improving the assessment of high-risk/high-reward research, and recruiting more high-quality reviewers. For most research grants, the CSR now posts summary statements within 1 month after a study section meeting, rather than 2 to 3 months. A pilot study to speed up the review process for new investigators seeks to allow them to revise and resubmit an application in a subsequent review cycle 4 months earlier. The NIH Director's Pioneer Award is a good model for improving the assessment of innovative research; however, the CSR would have to modify such a program to process more applicants.
The need for more reviewers has lowered the pool's average age. One strategy for increasing the number of reviewers is the use of electronic technology, such as video-teleconferences, in which whole study sections participate. Another is the use of Web-based sites to allow asynchronous participation by study section reviewers.
Dr. Scarpa offered the possibility of creating, well into the future, a completely new system to replace the traditional study-section review of applications (a process that has not changed substantially in 50 years). Various features could be questioned and changed. These might include the number of deadlines during a year, the length of the applications, the number of reviewers for each application, and methods of scoring. Ultimately, the value of peer review lies in its ability to ensure the best biomedical research and the discovery of new cures.
Discussion
Dr. Zerhouni thanked Dr. Scarpa for bringing a scientific approach to his leadership of the peer-review system. Ms. Chaite proposed that the CSR include the word "diverse" in its stated goal to recruit high-quality reviewers (in particular, referring to diverse scientific skills).
The ACD members discussed the issue of the length of an application, recognizing that this could vary by necessity. An alternative strategy (as used in the Pioneer Awards) is to call for an initial brief application/proposal, then request a subsequent longer version for projects deemed most promising. Such a strategy might stimulate researchers to propose riskier ideas.
Dr. Reede welcomed the trend of more junior faculty as reviewers. Dr. Scarpa added that study sections have also witnessed increases in the numbers of minorities and women-and the CSR is sensitive to the issue of young researchers spending too much time working in study sections. Ms. Chaite noted that the COPR had discussed public participation in peer review, concluding that this should occur in certain cases — for example, clinical studies — and at certain points in the process.
Work Group Report On Outside Awards for NIH Employees
Dr. Reede reported that the Work Group on Outside Awards for NIH Employees had responded to issues that were making the process of reviewing candidate awards inefficient — such as being submitted for consideration at unpredictable moments. The awards have been reviewed by the ethics office staff, by Dr. Kington, and by Dr. Reede to determine whether they meet the criteria for acceptability for NIH employees (made by a clearly established entity or organization, represent an ongoing program, and have clear selection criteria).
Dr. Reede presented the ACD members with a list of 17 awards that have been reviewed and are ready to be added to the list of bona fide awards that NIH employees may receive. The work group will present this list of additional awards to the ACD (a quorum) electronically, which will vote to add them to the full list of bona fide awards. Dr. Reede stated that she would forward the full list of awards to the ACD members. Dr. Kington offered to provide an analysis of awards that have or have not been won by NIH employees.
Mr. Marc Smolonsky reported on recent Congressional activity pertinent to the NIH, citing 34 hearings, 75 briefings by NIH scientists and staffs, and 17 visits to the NIH by members of Congress and their staffs. The legislators have been particularly interested in the potential pandemic flu.
President Bush had requested a FY 2006 NIH budget of $27.9 billion, and a House/Senate conference agreed on a budget of about that amount (a 0.3 percent increase over FY 2005). However, the House of Representatives defeated the measure in a vote, and the conferees will meet again December 12-13, with instructions to increase the amount.
Mr. Smolonsky reviewed the process of reauthorization of the NIH. The authority of the NIH derives from the Public Health Service Act of 1944, and, in fact, the NIH need not be reauthorized and can continue to operate as long as funds are appropriated. The House Committee on Energy and Commerce and the Senate Committee on Health, Education, Labor, and Pensions became interested in reviewing the NIH at the completion of the NIH's budget doubling. The committees held nine hearings between June 2002 and July 2005, surveyed NIH stakeholders, reviewed the IOM report on the NIH, interviewed IC directors, and circulated a draft reauthorization bill in July 2005.
Representative Joseph Barton, Chair of the House Committee on Energy and Commerce, has been the driving force in the NIH's reauthorization. He seeks to expand the authority of the NIH director to improve portfolio management and facilitate trans-NIH research. He seeks to realign budget authorities to foster collaboration, and he wants to streamline and improve public reporting of research results. Mr. Smolonsky listed provisions in the draft reauthorization legislation, emphasizing that it is only a draft. In response, Dr. Zerhouni has cited the importance of the OPASI as a new tool for NIH, has agreed on the need for more flexibility in allocating the NIH budget and for cross-cutting research, and has recognized difficulties in setting NIH priorities. We must preserve the peer-review process, maintain the emphasis on investigator-initiated research, continue the policy of minimal congressional directives, maintain general research authorities, and enhance scientific freedom. Mr. Smolonsky stated that the chances of reauthorization moving forward in the near future are slight.
Discussion
Dr. Bishop noted that some scientists were consulted early in the development of the reauthorization draft legislation. At that time, the Congressional staff revealed a strong understanding of NIH issues. The subsequent political process that led to the draft appears to have produced a result not consonant with those early discussions. Mr. Smolonsky suggested that the draft's call for a cap on the number of institutes was an attempt to restrain Congress from expanding the NIH unreasonably. Dr. Smarr characterized the near future as one of flat NIH budgets, emphasizing a need for the NIH to seek efficiencies. Dr. Zerhouni responded that demonstrating greater efficiency could be difficult. He proposed creating better decision-support mechanisms and a rapid funding system that would allow for the adaptability of an institution. This could lead to new intelligence in light of changing issues.
Ms. Chaite proposed increasing awareness of what the NIH does. Yet the NIH currently expends much effort to educate the legislators about NIH activities. Dr. Smarr wondered whether the discussion with Congress could be shifted to describe the different types of medical problems and distinguish between different ways in which they yield to research. The analyses performed by OPASI could support such a discussion. One problem is that many people are familiar with the histories of simple cures — expecting the investment of the NIH to produce such — and do not understand complex medical problems. Dr. Zerhouni agreed that the NIH must address such expectations and must also maintain the integrity of its research practices.
Another strategy is for members of the NIH's extramural community to get involved in educating the Congress. One-on-one interactions with legislators can be very valuable. Dr. Zerhouni stressed the need to eliminate the disconnect between the reality of medical science research and the expectations for curing diseases.
Dr. Zerhouni thanked the ACD members and other participants and adjourned the meeting.
Summary and Conclusions
The Advisory Committee to the Director of the National Institutes of Health convened on December 1–2, 2005, to receive updates on the NIH Neuroscience Blueprint, the Clinical and Translational Science Awards Program, and the work of the New Investigators Committee to encourage young researchers; to learn about activities of the National Heart, Lung, and Blood Institute and the Center for Scientific Review; to hear about progress in the new Office of Portfolio Analysis and Strategic Initiatives; to learn about further development of a list of bona fide awards that NIH employees may receive; to receive an update on the publicly accessible archive of articles published by investigators who receive NIH funding; to learn about a new multidisciplinary undergraduate biology program at Princeton University; and to receive an update on legislative matters.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
