The 115th Meeting
January 24–25, 2012
- REVIEW OF APPLICATIONS
- CALL TO ORDER
- REPORT: Task Force on Minority Aging Research
- REPORT: Working Group on Program
- PRESENTATION: NIA-AoA Collaboration
- PRESENTATION: Managing NIH in an Era of Diminished Expectations
- PROGRAM HIGHLIGHTS
- INTRAMURAL PROGRAM REPORT
The 115th meeting of the National Advisory Council on Aging (NACA) was convened on Tuesday, January 24, 2012, at 3 p.m. in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, Maryland. Dr. Richard J. Hodes, Director, National Institute on Aging (NIA), presided.
In accordance with the provisions of Public Law 92–463, the meeting was closed to the public on Tuesday, January 24, from 3 p.m. to 5 p.m. for the review, discussion, and evaluation of grant applications in accordance with the provisions set forth in Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Public Law 92–463.1 The meeting was open to the public on Wednesday, January 25, from 8:00 a.m. to 2:00 p.m.
Dr. Norman Anderson
Dr. Robert Califf
Dr. Dennis Choi
Dr. Ana Maria Cuervo
Dr. Hugh C. Hendrie
Dr. Andrea LaCroix
Dr. Victor Molinari
Dr. Richard Morimoto
Dr. Lennart Mucke
Dr. Eliseo Perez-Stable
Mr. Daniel P. Perry
Dr. Ronald C. Petersen
Dr. Arlan G. Richardson
Ms. June Simmons
Dr. Jonathan Skinner
Dr. Terrie F. Wetle
Dr. Stephanie Studenski
Ex Officio Participants:
Mr. Robert Hornyak, Administration on Aging
Mr. James Wren, Administration on Aging
Absent Ex Officio Participants:
Dr. Kenneth G. Pugh, National Naval Medical Center
Dr. James F. Burris, Department of Veterans Affairs
The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as attachment A.
In Addition to NIA Staff, Other Federal Employees Present:
Dr. Andrea Baruchin, Foundation for the National Institutes of Health
Dr. Kathy Greenlee, Administration on Aging
Dr. Deborah Olster, Office of Behavioral and Social Sciences Research, NIH
Dr. Sally Rockey, Office of Extramural Research, NIH
Members of the Public Present:
Mr. James Appleby, Gerontological Society of America
Dr. Christopher M. Callahan, Indiana University School of Medicine
Ms. Pat Kobor, American Psychological Association
Dr. Rose M. Li, Rose Li and Associates, Inc.
Dr. Jens Ludwig, University of Chicago
Ms. Molly Maguire, Lewis-Burke Associates, LLC
Dr. Frances McFarland Horne, Rose Li and Associates, Inc.
Ms. Michelle Rodrigues, SRI International
This portion of the meeting was closed to the public, in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix).2
A total of 894 applications requesting $1,310,681,224 for all years underwent initial review. The Council recommended 464 awards for a total of $868,957,808 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.
Dr. Hodes welcomed members to the open session of the 115th NACA meeting and called the meeting to order at 8:00 a.m. on Wednesday, January 25, 2012.
Director’s Status Report
Dr. Hodes reported that a FY2012 appropriation for NIH was signed into law on December 23, 2011. This legislation sets an NIH budget of approximately $30.7 billion, which is $299 million above the FY2011 budget and $758 million below the President’s request. Language within the legislation also eliminates the National Center for Research Resources (NCRR) and officially establishes the National Center for Advancing Translational Sciences (NCATS), which will house many components from NCRR. The primary component will be the Clinical and Translational Science Award program (CTSA), funded at approximately $487.8 million as requested by the President. Funding for the NIH Common Fund remains flat, at approximately $546 million, and overall federal discretionary programs including NIH have received a “haircut” of 0.189 percent. However, language in the FY2012 appropriation strongly urges NIH to maintain a funding level for extramural research at 90 percent of its budget. Dr. Hodes noted that a presentation explaining NCATS and its potential relevance to NIA could be given as early as the May Council meeting.
An appropriation for FY2013 is scheduled to be announced on February 13, 2012. However, Dr. Hodes reminded Council members of the Budget Control Act of 2011, which imposes across-the-board cuts to discretionary spending if the “Super Committee” failed to reach consensus on a plan for deficit reduction. He noted the possibility that NIH and other agencies would begin FY2013 under a continuing resolution in this election year. Coupled with the possibility of across-the-board cuts, NIH leadership is exploring its options. Dr. Hodes also noted the continuing decline in constant dollars and reported the current NIH funding levels represent a 19 percent decrease in purchasing power since 2003.
How NIA spends its budget has changed little since FY2011. Research project grants (RPGs) constitute approximately two-thirds of the NIA budget, which is above the NIH average, and the Intramural Research Program (IRP) represents another 11 percent, which matches the NIH average. The proportions of the NIA budget devoted to administration and management, research and development contracts, and centers are all below the NIH average at 4 percent, 6 percent, and 8 percent, respectively. Dr. Hodes also noted that estimated RPG paylines remain the same as for FY2011, but he reminded the Council that the paylines differ between awards less than $500,000 and those of $500,000 or more. The R01 payline also differs depending on the principal investigator’s career stage, with slightly higher paylines for early-stage and other new investigators.
Dr. Hodes pointed out that the success rate for R01 applications to NIA in FY2011 was equal to the median value across all NIH ICs. However, rumors and misleading information still abound that NIA has the lowest success rate, and these rumors may discourage investigators from applying. NIA continues to reach out to the scientific community to communicate that although this is not an easy time for research; the success rate at the Institute is not lower than most NIH institutes.
A search is under way for a new director for the Center for Scientific Review (CSR). Dr. Hodes noted that this is an unusual search, because NIH is not necessarily looking for someone with expertise in a particular subject, but someone who is dedicated, understanding, and committed, and who understands the needs and policies of CSR and peer review, and who will implement changes as needed.
Another piece of legislation, the National Alzheimer’s Project Act (NAPA), sets research goals to prevent and/or effectively treat Alzheimer’s disease (AD) by 2025, optimize care quality and efficiency, expand patient and family support, enhance public awareness and engagement, and track progress and drive improvement. The advisory council for NAPA is chaired by NACA member Ronald Petersen. A framework for NAPA has been released and is open for public comment. To further inform the process of identifying opportunities and priorities, NIA will host an AD research summit on May 14–15, 2012. The ability to implement the NAPA research plan will depend on its budget.
Dr. Hodes reported that NIA has a new website that is more user friendly; he invited Council members to provide feedback. He also announced that the Summer Institute on Aging Research will be held July 7–13, 2012, and that applications are due March 9. The site for the Summer Institute has not yet been determined.
Dr. Hodes closed by welcoming three new Council members:
- Dr. Ana Maria Cuervo, of the Albert Einstein College of Medicine
- Dr. Jonathan Skinner, of Dartmouth College
- Dr. Dennis Choi, a neurologist at the Simons Foundation, on leave from Emory University.
In response to questions from Dr. Norman Anderson, Dr. Hodes noted that a misperception by some of a low success rate for NIA arose because the FY2010 payline was at the eighth percentile and because of confusion about funding decisions for specific mechanisms such as program projects (P01s); NIA established two paylines and stopped using a percentile payline for P01s. The funding picture has eased a bit, but the perception that applications to NIA are less likely to be funded than applications to other Institutes and Centers (ICs) seems to persist. In response to other questions from Dr. Choi, Dr. Robin Barr reported that NIH is starting to look at R01 applications success rates for second R01s, because policies to give advantage to new investigator began in 2007, and that data would be available within the next 18 months.
Dr. Marie Bernard, NIA Deputy Director, emphasized NIA’s interest in having trainees from all aging-related disciplines participate in the Summer Institute. Brochures will be sent to T32 trainees and directors. Dr. Bernard noted that Dr. Cuervo is a graduate of the Summer Institute.
Dr. Petersen emphasized that the NAPA framework is open for feedback and that a first draft of a research plan will be generated in February and posted for feedback for 30 to 60 days. Although this plan will be posted before the AD research summit, it is expected to be revised each year, and it is likely that recommendations from the summit will be incorporated into that revision. Dr. Hodes added that the initial plan will likely be general but that implementation of the plan will involve input from experts. He commended Dr. Petersen on his performance as NAPA advisory council Chair.
Dr. Richard Suzman, Director of the NIA Division of Behavioral and Social Research (DBSR), welcomed Amy Mistretta, who has joined DBSR as a Research Program Analyst. He also noted that Dr. Sidney Stahl has announced that he will retire.
A binder containing media coverage was circulated among Council members. In response to requests from Council members, Dr. Barr noted that NIA would send them information on the NIA paylines to share with their communities.
Future Meeting Dates
May 22–23, 2012 (Tuesday and Wednesday)
September 18–19, 2012 (Tuesday and Wednesday)
January 29–30, 2013 (Tuesday and Wednesday)
Consideration of Minutes of the Last Meeting
The minutes of the September 2011 meeting were considered. A motion was made, seconded, and passed unanimously to approve the minutes.
Dr. Chyren Hunter, Deputy Director of the Division of Extramural Activities, began her presentation by announcing that Dr. J. Taylor Harden had retired and that she, Dr. Hunter, would now serve as NIA liaison to the Task Force. Dr. Hunter also announced that Dr. Terri Wetle had retired as Task Force Chair and that Dr. Eliseo Perez-Stable is the new Chair.
Dr. Hunter reported on a presentation by Dr. Jerry C. Johnson, principal investigator of a Resource Center for Minority Aging Research (RCMAR) award at the University of Pennsylvania. This RCMAR, called Minority Aging Research for Community Health (MARCH), is a joint effort of the schools of medicine and nursing. MARCH focuses on community-based clinical, social, and behavioral interventions; conducts primary and secondary analyses with the potential to change policy or promote new methods and models of health care delivery; conducts studies exploring interactions among individual, provider, systems, policy, environmental, and community factors; and employs a broad focus to address a spectrum of health and illness and to foster the maximal development of diverse scientists in aging research. The center focuses predominantly on African Americans.
The cores within MARCH have been vital to its accomplishments. Through its Community Core, MARCH has built a sustainable and comprehensive approach to community engagement, including health education symposia, an advisory board, the interactions of faculty with the advisory board and community, and learning experiences for trainees. With this approach, MARCH has accomplished such activities as the Older Adult Research Connection Registry, which now includes almost 600 adults aged 55 years and older. The Investigator Development Core has been instrumental in fostering significant minority leadership and mentoring, through partnerships with disciplines such as nursing, epidemiology, ethnography, and statistics. Investigators engaged with MARCH receive comprehensive mentoring and consulting, with a strong emphasis on a development plan, and they are exposed to community-based research and participate in outreach efforts. Other cores include the Measurement and Methods Core, which assists with study design, and the Community Liaison core.
During the past 4 years, Penn MARCH has had 15 scholars, many of whom have received external funding in the form of K awards, R21s, and R01s. Seven of these scholars are from underrepresented minority groups.
Dr. Hunter concluded her report with several announcements:
- A new R25 funding opportunity, Advancing Diversity in Aging Research Through Undergraduate Education, aims to increase the pipeline of individuals going into aging and geriatrics research. This program seeks applications for novel programs to increase the engagement of undergraduates in medicine, science, technology, engineering, and mathematics.
- A new funding opportunity announcement (FOA) provides stipend and research funding for graduate students at the dissertation stage of their education.
- The Summer Institute on Aging Research will be held July 7–13, 2012.
- An NIA Grants Technical Workshop will be held November 12–13, 2012, in San Diego, California.
The Task Force forwarded a motion for a Council resolution thanking Dr. Harden for her service to NIA. The motion was seconded and passed unanimously.
The Task Force also forwarded a motion for a program-level review of health-disparities research and opportunities for training minority researchers in aging research. Dr. Anderson noted that the Task Force needs data to aid in its goal to provide advice to the Institute, and Dr. Eliseo Perez-Stable noted discussions at the September 2011 Council meeting regarding diversity supplements and their outcomes. Dr. Hodes noted that some Council members had already volunteered to serve on the review committee, but he invited others to join and suggested that the committee identify materials it would need to aid in its review. It is expected that the bulk of the work will begin in May and that a presentation will be given at the September Council meeting. The motion passed unanimously. This review will postpone the review of the Division of Neuroscience (DN) to January 2013.
Dr. Richard Morimoto chair of the Working Group on Program noted that the Council must vote on the Statement of Understanding, which outlines where the Council facilitates the decision making of NIA staff, for example with respect to expedited funding. A motion was forwarded, seconded, and passed unanimously to approve the Statement of Understanding.
Dr. Barr noted that because of the late date at which the FY2012 budget passed, NIA decisions on requests for applications (RFAs) were delayed. As a result, several RFA concepts will be brought to the May Council meeting for clearance. Because of the number of concepts, Dr. Barr suggested that two or three Council members look at each concept and lead discussions at the May meeting.
Dr. Barr also called attention to the Annual Data report, noting that the increased success rate in 2011 was the first increase in 6 years and that the average cost of awards has fallen during the past 2 years.
Ms. Kathy Greenlee, Assistant Secretary for Aging, began her presentation by emphasizing her desire to reinvigorate the partnership between the Administration on Aging (AoA) and NIA. The mission of AoA is to help older people maintain health and independence in their homes and communities through a comprehensive, coordinated, and cost-effective system of long-term care across the United States. AoA was established in 1965 under the Older Americans Act, one of three programs signed into law to address the needs of older Americans. Unlike Medicare and Medicaid, however, The Older Americans Act was not designed to be an entitlement program and thus has undergone a different development trajectory. AoA emphasizes chronic disease management and provides preventive services, with the belief that Medicare and Medicaid costs can be defrayed by helping individuals delay entry into those systems until absolutely necessary.
AoA, which became an independent agency under the Department of Health and Human Services in 1992, is structured differently from many other federal agencies, with a broad base. The AoA sends money directly to the States, which organize themselves into service areas, area agencies, and contracts. Services include senior centers, the meals program, transportation, personal care assistance, support for caregivers, and case management. Older adults do not receive an entire bundle of services, as is the case with Medicare or Medicaid. Rather, older adults access AoA services as they need them. Thus the package of services provided by AoA is tailored to each adult.
Ms. Greenlee emphasized the relationship between researchers and the network of community service providers, noting that she often confers with researchers and tries to determine how to translate their work to the community. AoA has spent more than a decade focusing on evidence-based practice and is committed to strong fundamental science. She expressed her desire to engage with NIA not only on its research programs, but also on its interactions with other NIH ICs, other Federal agencies, and private partners. Such interactions can facilitate work across domains and speed the translation of emerging science into changes in practice. Examples of evidence-based programs include Resources for Enhancing Alzheimer’s Caregiver Health II, funded by NIA; the Fit and Strong program, also funded by NIA; Tai-Chi Moving for Better Balance, funded by the Centers for Disease Control and Prevention (CDC); and the Chronic Disease Self-Management Program, funded by the Agency for Healthcare Research and Quality. As the Older Americans Act comes up for reauthorization, AoA is proposing to fund only evidence-based programs.
The renewed partnership between AoA and NIA has resulted in a funding opportunity to support translational research to help older adults maintain health and independence. The two agencies also have signed a Memorandum of Understanding (MOU) to support translational research on aging with disability. AoA staff also have talked with the Christopher and Dana Reeve Foundation about translating knowledge gained from Foundation-supported research to benefit AoA programs, and Ms. Greenlee noted that this discussion has helped the AoA review its own processes in translating research results into services. AoA also has established an MOU with the U.S. Department of Education’s National Institute for Disability and Rehabilitation Research to look at the impact and burden of disability, and it is working with the Institute of Medicine and Health and Aging Policy Fellows.
At the end of her presentation, Ms. Greenlee noted that AoA has never changed the size of its investments; thus the size of social services is dwarfed by the medical system in every State and city. Ms. Greenlee expressed concern that with increasing demands to find alternatives to costs in the acute-care system, and with the transition to Medicare- and Medicaid-based systems in many areas, medical facilities will try to take on social services and thus duplicate facilities already in place. She suggested that improved integration among the AoA, Medicare, and Medicaid systems, not a medicalization of community services, is likely to address increasing health costs while promoting health and independence. She concluded with a call for NIA and AoA to work together on translation by trying evidence-based programs and determining what works in practice, as well as by involving people who can translate conversations, understand that some services can be provided in a non-medical but scientific way, and identify ways the medical community can build upon existing programs rather than duplicating them.
In response to questions from Dr. Victor Molinari, Ms. Greenlee noted that AoA has always conducted program evaluations and has moved from measuring outputs to measuring outcomes. She pointed to the Meals program as an example. AoA can show how many meals it has served, but it also is revising its evaluation standards to assess, for example, the impact of these meals on recipients’ health and ultimately on cost savings. Ms. Greenlee acknowledged that such a transition has not been easy, however, because the level of granularity needed for such an evaluation was not known when the national system was created.
Referring to a map that Ms. Greenlee presented for the Chronic Disease Self-Management Program, Dr. Skinner asked why some areas had services while others did not and whether differences in availability of services would be reflected in differences in health outcomes. Mr. James Wren responded that AoA received $30 million under the American Recovery and Reinvestment Act (ARRA) and disbursed the funds in the form of State grants; the States decided how to deploy these funds. Although AoA will not track comparisons in outcomes under the ARRA funding, it will disseminate a new survey. For this project, AoA has hired the investigator who designed the original survey showing that older adults who engage with AoA programs had better health status, fewer hospital stays, and more interactions with health professionals. AoA also is working with Medicare and attempting to link a subset of its survey sample so that it can compare its participants with Medicare beneficiaries who have not used AoA services.
Dr. Choi commended AoA on its approach in advancing community-based translation and asked whether it is working with other ICs on key topics that affect the elderly community. Ms. Greenlee noted that AoA also is working with the National Cancer Institute and the National Institute of Nursing Research and suggested that AoA’s partnership with NIA could serve as a front door to interactions with other ICs. Dr. Bernard added that NIA has had ongoing discussions with other ICs, such as the National Institute of Mental Health, and that it is working with AoA to include as many ICs as possible.
Dr. Perez-Stable noted Ms. Greenlee’s concerns about duplication in services and observed two trends. Health plans and accountable-care organizations will focus on what happens when chronic care patients return to their primary care physicians following hospitalization. Coordination with health plans will be essential because many older patients have multiple conditions and are on multiple medications. In addition, as state budgets continue to be crunched during the economic downturn, in-home support services have increasingly lost support. Dr. Perez-Stable suggested that AoA find ways to address that trend in light of its key goal of supporting older adults to remain in their homes and communities. Ms. Greenlee acknowledged that this is a dynamic time for AoA; it must consider its role in light of current trends and be realistic about how it can partner with public and private health plans and how it can advise facilities within its network. Dr. Perez-Stable and Ms. June Simmons agreed that the work and leadership of AoA will continue to be important as areas transition toward Medicare- and Medicaid-managed systems.
Ms. Greenlee also clarified that AoA focuses on primary prevention in older adults and on prevention across the lifespan, with interests in such areas as medication management and the prevention of falls. It therefore does not adhere strictly to the typical division of preventive medicine strategies into primary, secondary, and tertiary prevention levels. Ms. Greenlee called for the inclusion of older adults at all levels of discussions regarding prevention and related research.
Dr. Suzman indicated that NIA-supported behavioral research could increase knowledge about cost-effective ways to change health-related behaviors. He invited AoA to partner with BSR and perhaps hold a joint workshop to explore additional research directions. Dr. Molinari noted the science behind interdisciplinary care and pointed out that the American Psychological Association has published brochures on how such care can improve outcomes. Ms. Greenlee noted geriatricians’ excitement about these brochures and expressed interest in exploring this information further.
Dr. Sally Rockey, Deputy Director for Extramural Research, reiterated that NIH appropriations have remained flat since 2003 and that, as a result, actual buying power and grant success rates have declined. NIH has employed several approaches to address these challenges. All ICs have reevaluated their research portfolios and scrutinized scientific priorities, and NIH overall has rigorously evaluated its entire portfolio to eliminate duplication, decrease support for less innovative research, and increase its support where possible for highly innovative research. Maintaining the system as it stands will likely result in a Darwinian approach, or “survival of the fittest” investigators, with success rates continuing to fall as the number of applications continues to rise. On the basis of the FY2010 budget and the number of applications, a 10 percent reduction in the RPG budget would push the success rate down to 12.3 percent, and a 20 percent reduction would result in a success rate of 4.1 percent, assuming no reductions in non-competing costs. Other approaches are under consideration, and Dr. Rockey reviewed the potential consequences of each.
Principal investigators on average hold one to two NIH grants at a time, and the majority holds only one grant. However, 20 percent of principal investigators receive about 50 percent of grant funds, either because they have more than the average number of grants or because they hold larger grants. In addition, 120 institutions throughout the United States receive 80 percent of NIH grant funds. NIH could limit the number of awards per principal investigator, but it would have to limit that number to two per investigator to have any kind of effect. This would make possible 1,000 new awards but would limit the number of great ideas coming from investigators.
On the basis of FY2010 numbers, if NIH were to reduce the average size of an award by $25,000, it would save $232 million. NIH would be able to increase the number of awards and thus the overall success rate, but it is not clear that investigators would receive enough funds to meet the objectives of their grants. Limiting the amount of funds per principal investigator might achieve some cost-savings, but again, the number of good ideas might be curtailed.
Limiting the amount of salary paid by a grant also has been discussed, particularly among the public and Congress. Increasingly the salary of tenured faculty at institutions is coming from NIH. However, it is difficult for NIH to determine just how much funding goes to institutions in the form of salaries. Even if it uses percentage effort as a proxy for salary, limiting the salary goes to the heart of how institutions manage their research portfolios and would thus take time to achieve.
Dr. Rockey closed this part of her presentation by inviting Council members and others to submit comments and feedback about these ideas. She also reported that NIH has talked with professional societies about ways to address NIH’s budget challenges.
NIH continues to be concerned about the future of the biomedical workforce and has established a working group of the Advisory Council to the NIH Director to develop a model for a sustained and diverse biomedical research workforce. Chaired by Dr. Rockey and Dr. Shirley Tilghman of Princeton University, the working group will advise on ways to train the optimal number of people for the types of positions that will advance science and promote health. Part of the group’s work will involve gauging the nature of support from private industry.
Dr. Rockey reminded the Council that since 2007 NIH has concentrated a large amount of effort in supporting new investigators. These efforts have included basing new investigator support on the average number of new investigators supported in previous years, equalizing success rates between new investigators and established investigators with new ideas, and reviewing the career pipeline and how and where new scientists are engaged. As a result of these efforts, the number of new investigators has increased dramatically. NIH is now assessing how well its policies have worked and their potential as a long-term strategy. With respect to education and training, the investigator population remains the same, with the majority being PhDs. It is not yet clear how the population will change in light of recent emphasis on translational research.
Although many graduate programs are now dominated by women, the proportion of women among principal investigators has grown slowly, to about 30 percent. Women competing for their first grant have about the same success rate as men, but they return less often with a renewal application, and when they do, their success rate is lower. The reason for this discrepancy is not clear. Even more concerning is the continuing low representation of racial and ethnic minorities among principal investigators. Although 10 percent of the United States population is African American, 12.5 percent Hispanic, and 3.6 percent Native American, based on 2008 Census data, only 1.2 percent of principal investigators in 2009 were African American, 3.4 percent were Hispanic, and 0.4 percent were Native American. Even among medical school faculty, representation of these groups is low. Moreover, a paper published by Ginther et al. (Science 19 August 2011, Vol.333 (6045): 1015-1019) showed that among PhDs, African Americans and Asians were less likely than Whites to receive new research grant funding. In response, NIH has established two high-level groups to advise on ways to increase diversity among the staff and biomedical workforce. NIH also has funded extramural grant programs to assess interventions to strengthen the pipeline to improve workforce diversity, and it has implemented an early reviewer program to increase the exposure of investigators from diverse institutions to peer review. In addition, NIH will employ efforts within the review process, such as de-identifying applications, testing the ability of reviewers to detect applicants’ race, and assessing training against bias, to determine whether bias exists.
Dr. Rockey reminded Council that even though the bulk of NIH-supported training occurs at the graduate or medical school level, the pipeline begins long before graduate student training. A large number of talented individuals are supported by National Research Service Award grants, but the number of these grants has remained relatively flat. The number of graduate students supported by training grants has increased, but it is not clear whether and how training for these students differs from that for students on research grants or fellowships. A similar trend can be seen for postdoctoral fellows, despite the continuing large need for postdocs. Moreover, about 65 percent of postdocs supported by NIH research grants comes from other countries, and among all postdocs, there is a feeling of isolation and lack of support.
Dr. Rockey concluded her presentation by noting that the results of an NIH request for information are now available on the Office of Extramural Research website. She invited Council members and others to visit the website and her Rock Talk blog for more information; Dr. Rockey also can be followed on Twitter.
In response to questions from Dr. Morimoto about measurement of impact factors, i.e., the possible relationship between the amount of money invested and scientific impact, Dr. Rockey noted that this is a difficult but important question. She agreed with Dr. Morimoto that a discussion of impact is needed in determining how to control the number and size of grants, and noted that CSR has looked at a measure of impact on study sections. Dr. Morimoto added that NIH has successfully managed its relationship with the Howard Hughes Medical Institute (HHMI), which uses an impact factor of accomplishment in funding decisions, but not every outstanding investigator receives support from HHMI. He wanted to avoid large discrepancies where one investigator receives large amounts of funding from multiple sources while another might be restricted, yet both are subject to indistinguishable accomplishment and quality measures.
Dr. Skinner argued against restrictions on multiple grants in part because it is easy to shuffle principal investigators, thus likely making cost savings elusive. He suggested instead making reviewers aware of the portfolio of closely related NIH-funded projects to help them better assess the marginal gains expected from the application under review. There also was some discussion about the impact of a 20 percent funding cut on success rates and whether ICs might have to caution non-competing awardees that out-year commitments could be revisited in order to fund more new grants. In response to questions from Dr. Robert Califf, Dr. Rockey noted that the biomedical workforce has seven times as many postdocs as faculty but that postdocs are finding positions in industry and elsewhere. NIH is trying to determine what these positions are. In addition, although the length of a postdoctoral position is shorter than it was during the 1990s, many institutions have renamed these positions. A recent survey by NIH revealed approximately 1,000 different descriptors for postdoctoral positions. Meanwhile, staff scientists at NIH, who are assigned to senior investigators, work in continued appointments and generally report satisfaction with their jobs.
Dr. Morimoto commented that any discussion of pipeline also must address the fact that many graduate programs continue to accept students because they need people to conduct the science. Although unemployment is low among scientists, whether and how scientists are underemployed is not clear. Nor is it clear whether NIH should play a role in training individuals for various career tracks.
- Division of Geriatrics and Clinical Gerontology: Aging and the Clinical Trials Enterprise
As medicine moves toward systems biology and a personalized approach, clinical recommendations must move beyond a one-size-fits-all approach to one that accounts for biological, environmental, and social factors. In addition, with the Internet and social networking, physicians and patients are overwhelmed by a deluge of medical information. Yet many clinical recommendations, particularly for older Americans, are not based on high-quality evidence. The current portfolio of clinical trials, and the U.S. clinical trials enterprise in general, will not fix this problem. Clinical trials are expensive, complex, and burdensome, with long, drawn-out timelines. More than 90 percent of clinical trials are delayed because of overambitious timelines and difficulties with enrollment. Clinical trials in the United States have the highest dropout rates and the lowest rates of protocol adherence, and despite their high cost, their quality is often poor.
Dr. Califf described work reviewing the clinical trials enterprise, particularly with respect to older patients. He and his colleagues have developed an analyzable database based on clinicaltrials.gov, with the goal of helping to inform policy and budgetary decision making. Overall, Dr. Califf and colleagues have found that although NIH-supported trials are more likely to be high quality, as illustrated by randomization, blinding, and data monitoring, the majority of trials are not. In addition, most clinical trials are small, with fewer than 100 research participants, and therefore not powered to answer their research questions. Many trials also are taking place in other countries.
Of approximately 120,000 intervention trials deposited in clinicaltrials.gov since 2007, only 140 focus exclusively on older patients, and of those, only 12 focus on patients older than 75. These studies are more likely to examine supportive care and prevention and less likely to focus on treatment. They more often have a parallel design, and the proportion of trials with randomization, blinding, and data monitoring is no different from that seen in trials including younger participants. Half of them are single-center studies funded neither by industry, nor NIH, and the majority of them are conducted in Europe. Dr. Califf pointed out that correct drug doses for patients older than 70 are not known, and virtually no trials are exploring pharmacology in older patients.
Clinical trials must be done more efficiently and cost-effectively. Efforts are under way to develop a sentinel system of millions of electronic health records that can be used at least to track adverse events, and federated data marts are under development. At NIH, elements are in place for a national clinical research network, with millions of research participants and electronic health records, but more work is needed to develop common informatics and terminology. Dr. Califf expressed the hope that the new National Center for Advancing Translational Science (NCATS) could transform existing Clinical and Translational Science Awards (CTSA) from internally focused academic medical centers to a true research network. In addition, thinking only about clinical trials in the United States is shortsighted, particularly in light of communications technologies that make it easier to transmit data. Global networks are needed to explore “rare” diseases, which are usually rare only in the United States. Dr. Califf closed his presentation by calling for regulatory reform and fixes to clinicaltrials.gov, to create an interface between that database and practitioners to facilitate learning.
In light of the current financial constraints, Dr. Perez-Stable suggested investing in establishing better health system data to allow researchers to identify the best doses for older adults. In response, Dr. Califf observed that although a small clinical trial may not be expensive on its own, a cluster of small clinical trials can be expensive collectively, and a lot of research dollars are supporting studies that focus on the wrong question, and are being conducted without sufficient attention to a portfolio view. He noted that reliable answers could be achieved by inserting randomization into integrated systems of electronic health records. However, such a process runs the risk of amplifying bias. More work is needed to determine where best to apply randomization.
Dr. Anderson expressed surprise that a higher percentage of randomized clinical trials are conducted in behavioral research than in biomedical research, particularly when the research community often calls for more behavioral research. Dr. Califf suggested that many behavioral studies might not have been registered as interventional studies because behavioral scientists are more sensitive about bias and randomization, whereas other researchers might not be as concerned because they believe they can tell whether a treatment is working.
- Division of Neuroscience: Alzheimer’s Disease Cost and Transitions Study
In a clinical study done 5 years ago, Dr. Christopher Callahan and colleagues, of the Indiana University School of Medicine, found that Alzheimer’s disease (AD) patients and caregivers benefit when AD care is provided in primary care settings. Although such findings might suggest that such care could delay placement of patients in nursing homes, Dr. Callahan’s group is not convinced that delaying nursing home placement is the best way to reduce costs. Patients at home might be more likely to go to the hospital, and contrary to popular perception, the regression of AD patients from independent living to nursing home care is not linear. Instead, many patients move back and forth among different models of care.
Dr. Callahan described a cohort of 4,000 Indianapolis adults who were screened for cognitive impairment and followed for 5 years. These adults were patients in a single, large, multi-site primary care practice and thus had electronic health records, which Dr. Callahan’s group linked with Indiana Medicare and Medicaid data, as well as with a minimal dataset including diagnoses and functional status and data on home health care. Dementia cases were identified from the electronic health record and Medicare claims data. As expected, Dr. Callahan and his colleagues found that patients with dementia were older, had more comorbidities, used more hospital and home health care, and were more likely to die. Dementia was a large driver of nursing home care; both short- and long-term nursing home care use were higher among these patients. Short-term stays were paid for by Medicare as an extension of recent hospitalizations, with the expectation that patients would return home. However, long-term nursing home stays were not that long, and many patients placed in long-term care eventually returned home for a while.
On the basis of the dates of transitions, Dr. Callahan and colleagues mapped how patients moved across sites of care and found that compared with 42 percent of patients without dementia, only 13.7 percent of patients with prevalent dementia and 9 percent of those with incident dementia had no transitions from home. Dementia patients who lived at home with no services were most likely to go to the hospital for care, patients who lived at home with services were most likely to lose their services, and patients in the hospital were most likely to move on to the nursing home or back home with no services. Likewise, patients in nursing homes were more likely to move back home or to the hospital. The majority of patients with dementia arrived at the nursing home through hospitalizations, partly because of the rules under which Medicare will pay for nursing home care. However, many patients in nursing homes were sent back to the hospital for 30 days, and patients with dementia were most likely to die at home. Thus the majority of care for patients with dementia takes place in the community, with a high burden of transitions across care sites. Moreover, Medicare hospital costs account for the largest proportion of total costs for patients with dementia.
The majority of discussion focused on technical aspects of the work described. Dr. Callahan noted that whether a patient in a nursing home returns home without services or goes back to the hospital depends on the nursing home, and he acknowledged that data on Medicare reimbursement rates might actually underestimate the true costs associated with dementia care. Dr. Callahan pointed to the electronic health record as an opportunity to look further into what happens to patients during hospitalization. Council members also noted that the Program of All-Inclusive Care for the Elderly, which bundles Medicare and Medicaid payments to provide care in the community, might serve as a starting point for a broader care model for patients with dementia. Although the cost-savings of the program are unclear, it is popular among families.
- Division of Behavioral and Social Research: Moving to Opportunity: Neighborhoods, Obesity, and Diabetes
Health outcomes vary dynamically across communities of varying socioeconomic status, and some evidence suggests that the community environment itself might play a role in health outcomes. Peer influences on health-related behaviors, stressors such as crime, and aspects of the physical environment, such as toxins or air quality, have all been suggested as mechanisms mediating the impact of the community environment. Some data have shown negative health effects associated with moving down in income level, and likewise, theoretical work predicts that moving to a less-disadvantaged neighborhood could improve health.
Dr. Jens Ludwig, of the University of Chicago, described Moving to Opportunity (MTO), a Department of Housing and Urban Development (HUD) program in which families who lived in the most economically disadvantaged census tracts were given an opportunity to move to less distressed communities. To be eligible, families had to have children and live in public housing, project-based assisted housing, or neighborhoods with a poverty rate of 40 percent or greater. Approximately 4,600 families who volunteered from 1994 to 1998 were randomly assigned to remain eligible for existing project-based housing assistance (control), receive conventional Section 8 vouchers, or receive mobility counseling and vouchers to move to communities with poverty rates less than 10 percent (eligibility). Almost all families were headed by unmarried women in their mid-30s, many of whom were high school dropouts. About 75 percent of the families were on welfare; two-thirds were African American, and one-third Hispanic.
At baseline, safety was the most common reason for moving; many households wanted to get away from gangs, drugs, and crime, and almost half reported being victims of crime. Half of the families in the experimental group and about 60 percent of the families in the Section 8 group successfully used their vouchers to relocate. At 1 year after baseline, geographic dispersion was wider in the experimental group than in the Section 8 or control groups. Although the MTO intervention generated little racial integration, it resulted in massive changes in economic integration. Although differences between experimental and control neighborhoods differed because of improvements in the controls, MTO appeared to reduce neighborhood poverty by 18 percent. The prevalence of extreme obesity (defined as body mass index [BMI] of 35 or higher) was reduced by 40 percent in the experimental group (New England Journal of Medicine 20 October 2011; 365:1509-1519). Similar results were seen for diabetes. The effects of moving to a low-poverty neighborhood were larger than those seen with the Diabetes Prevention Program, a large study that enrolled a different population, reduced diabetes incidence by 34 percent, and reduced diabetes medication by 18 percent.
These findings suggest a provocative hypothesis to explain why the prevalence of obesity has doubled since 1980. Neighborhood income segregation has been increasing since the 1970s, and the number of people living in high-poverty neighborhoods might also be increasing. The large increase in obesity and diabetes prevalence might result in part from growing population exposure to high-poverty neighborhoods. In addition, minorities are more likely to live in high-poverty neighborhoods, which might explain in part the disparities seen in obesity and diabetes prevalence. Five-year follow-up data suggest reductions in the prevalence of BMIs of 30 or more in the experimental group, but more work is needed to analyze changes in more detail.
In response to questions from Dr. Califf about the implications of such a study, Dr. Ludwig acknowledged that in the current political climate, further efforts to move poorer families to low-poverty neighborhoods is unlikely. However, he pointed out that he and his colleagues saw health benefits even among the conventional Section 8 group. He further noted that MTO is helping to further pinpoint mechanisms of action, which could facilitate the design of a community-wide intervention in lieu of moving families. Dr. Ludwig also pointed out that the MTO study has proven exciting for both HHS and HUD, two Departments that have not historically worked together.
- Division of Aging Biology: Resveratrol in Animal Models, and Aging Disease Update from the Intramural Research Program
Resveratrol, a compound found in grapes, has been shown in mice to extend lifespan. It also has been associated with fatty liver protection and increased insulin sensitivity, cataract reduction, improved bone health, reduced damage and stress in vascular tissue, and increased treadmill performance. In addition, in mice fed a high-fat diet, resveratrol has been associated with a gene expression profile similar to that seen in mice on a standard diet. Since the publication of these findings in Nature and Cell Metabolism, Dr. Rafael de Cabo, of the NIA Intramural Research Program, has been interested in the effects of resveratrol on muscle and bone atrophy during aging and in the role of Sirt1 in muscle atrophy. Middle-aged mice treated with resveratrol appear to preserve muscle, and in a hindlimb suspension model, resveratrol is associated with improved bone health.
Dr. de Cabo and colleagues also have developed models in rhesus macaque and squirrel monkeys to test the effects of resveratrol on sarcopenia. In a study of 10 monkeys on a high-fat, high-sugar diet, resveratrol had no effect on the increased body weight induced by this diet, and Dr. de Cabo and colleagues only saw a trend toward improvement of insulin sensitivity. However, treatment with resveratrol appeared to reverse the effects of a high-fat, high-sugar diet on the islet cells in these monkeys. Resveratrol also improved pulse wave velocity, a marker of arterial stiffening; reversed plaque deposits in the aorta, and improved inflammation, as demonstrated by reduced macrophage markers. In addition, microarray analysis showed a reversal of gene expression changes induced by the high-fat, high-sugar diet in almost every tissue tested. Further study showed that resveratrol significantly changed the levels of Sirt1 protein and pro-inflammatory cytokines in abdominal adipose tissue, suggesting that adipocytes mediate the anti-inflammatory effects of resveratrol in adipose tissue. Resveratrol also showed anti-inflammatory effects in cerebrospinal fluid and the temporal cortex of the brain. Dr. de Cabo’s group is now working to identify the molecular targets of resveratrol.
Dr. de Cabo closed his presentation by noting that this project has created a wide array of intramural and extramural collaborations, along with an abundance of tissue and resources. He also noted a recent study showing that low-dose resveratrol supplementation for 30 days confers calorie-restriction-like effects in middle-aged, healthy obese adults. Dr. de Cabo also discussed a recent pilot study showing that resveratrol improves insulin sensitivity in patients with impaired glucose transport.
Dr. Califf noted that resveratrol appears to affect all cell types and asked whether any toxicities have been found. Dr. de Cabo acknowledged new reports on toxicities to the kidney at doses of 3 grams per day or higher. In response to questions from Dr. Cuervo, Dr. de Cabo reported that the Intramural Program is still working to understand when and how best to use resveratrol, especially in models of long-term stress. He also noted studies that had shown no lifespan effects of resveratrol, but he pointed out that these studies had not looked at health span.
In response to questions from Dr. Morimoto, Dr. de Cabo expressed concern about the availability of resveratrol as a nutraceutical. He noted that resveratrol appears to work through many possible pathways and that how it interacts with other pharmaceuticals is not known. Dr. de Cabo further expressed doubt that resveratrol could be developed into a pharmaceutical because of its many non-specific targets.
Laboratory of Neurogenetics
The Laboratory of Neurogenetics (LNG) aims to understand the genetic basis of age-related neurological disorders; understand the etiology of disease; help intramural and extramural colleagues with critical projects and methods; make data and resources publicly available, often before findings are published; and recruit, train, and develop first-class scientists. The scientists in LNG interact extensively with each other, with other NIA laboratories, with laboratories in other NIH ICs, and with international research groups. The bulk of LNG work focuses on Parkinson’s disease, AD and related dementias, and amyotrophic lateral sclerosis (ALS). Dr. Andrew Singleton, LNG Chief, summarized recent work:
- Over the past 8 years, LNG has cloned several genes and mutations related to Parkinson’s disease, ataxia, and frontotemporal dementia (FTD). Most recently, a collaboration between the Neuromuscular Disease Research Unit and other consortia led to the identification of a large, hexanucleotide repeat that causes a large proportion of ALS and FTD and is seen in about 1 percent of clinical AD cases.
- LNG has developed a program in genetics of complex traits, focusing on disease-based genome-wide association studies (GWAS), epidemiological cohorts, and analytical leadership in statistics and computational biology. LNG has led the way in GWAS since 2006, and its most recent publication describes a mega analysis of 17 genetic loci. Since this publication, LNG has expanded this list to 140 loci and is leading replication efforts.
- In functional genomics, LNG has combined high-throughput technologies and assayed 400 brains to look at the effects of variant gene expression and methylation. These data are available in the database of Genotypes and Phenotypes (dbGAP). In generating these data, LNG has built a resource to look at the effects of GWAS hits, for example in a project examining risk alleles for Parkinson’s disease. LNG was the first laboratory to show that the kinase activity of one Parkinson’s-associated protein, Lrrk2, is required for its toxic associations with other mutations. Preliminary work with protoarrays is under way to identify proteins that interact with Lrrk2.
Dr. Singleton closed his presentation by noting LNG’s success in identifying gene mutations and risk factors; the new insights yielded by work integrating genetics, expression analysis, and epigenetics; and significant impacts of LNG discoveries on the field of neurogenetics. He noted that LNG now has a clear route to understanding the genetics of primary diseases, that it is working to be comprehensive and global, and that animal models remain key to in vivo testing and translation of the laboratory’s findings. Dr. Singleton reported that the interactive, close-knit nature of the laboratory is central to its successes.
During discussion, Dr. Singleton indicated that LNG also is looking for common factors across diseases, which is relatively easy from the genetic perspective but more difficult from the functional perspective. LNG is starting to look at different cell types and achieve more granularity in the biological effects it observes. In response to questions from Dr. Morimoto, Dr. Singleton noted that LNG conducts its functional genomics work partly to find ways to translate GWAS results biologically. LNG is working to identify molecular genetic networks in a disease, with the hope of perturbing nodes within those networks to learn more about disease biology. However, Dr. Singleton also expressed doubt that the complete complexity of a disease can be captured in an animal model.
Laboratory of Neurosciences
Scientists working on neurodegenerative diseases aim to understand how molecular abnormalities lead to neuronal dysfunction and degeneration, with the hope that drugs can be developed to block those abnormalities. However, cells and neurons have several natural pathways that are routinely activated to help them cope with stress and resist disease. One area of study in the Laboratory of Neuroscience (LNS) concerns the impacts of dietary restriction, exercise, and intellectual challenge on the brain. Over the past 10 years, LNS has discovered evidence of common mechanisms, such as upregulation of neurotrophic factors, that protect against the cytotoxicity of metabolic stress.
Dr. Mark Mattson, LNS Chief, cited work in mouse models as an example. In a stroke model, LNS scientists have found that intermittent fasting in young animals, but not in middle-aged or older animals, significantly upregulates brain-derived neurotrophic factor (BDNF), a neuroprotective factor. Using other models, the laboratory also has found that intermittent fasting reduces the local inflammation seen in AD, Parkinson’s disease, and other neurodegenerative diseases but that the ability to modulate inflammation with diet declines with age. In other work, LNS has shown that psychotropic drugs can protect neurons with adaptive stress responses in a mouse AD model, that dietary modifications can improve autonomic nervous system abnormalities in Parkinson’s disease, and that BDNF signaling in the brainstem enhances cholinergic drive to the heart. Moreover, translational work by LNS scientist Josephine Egan, in collaboration with Dr. Nigel Greig, suggests that glucagon-like protein 1 (GLP-1) and exendin-4, which are involved in glucose control, has neuroprotective effects and perhaps cognitive benefits through the Kreb and BDNF pathways. A clinical trial is under way to explore the use of exendin-4 in treatment of early AD.
Discussion focused on technical aspects of and speculation related to the work Dr. Mattson described.
The open session of the 115th meeting of the National Advisory Council on Aging adjourned at 2:00 p.m. on January 25, 2012. The next meeting is scheduled for May 22–23, 2012.
I hereby certify that, to the best of my knowledge, the foregoing minutes and attachments are accurate and complete.3
Richard J. Hodes, M.D.
Chairman, National Advisory Council on Aging
Director, National Institute on Aging
Prepared by Robin Barr, D.Phil.
With assistance by Rose Li and Associates, Inc.
- For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to “en bloc” actions. (Back to text.)
- For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to “en bloc” actions. (Back to text.)
- These minutes will be approved formally by the Council at the next meeting on May 22–23, 2012, and corrections or notations will be stated in the minutes of that meeting. (Back to text.)
NATIONAL ADVISORY COUNCIL ON AGING
NATIONAL INSTITUTE ON AGING
(Terms end December 31)
(* WGoP Member)
(** TFMAR Member)
(*** provisional member appointment not yet approved)
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
9000 Rockville Pike
Building 31, RM 5C35
Bethesda, MD 20892
Norman B. Anderson, Ph.D. (2014)
Chief Executive Officer and Executive Vice Chair
American Psychological Association
Washington, DC 20002
Robert M. Califf, M.D. (2013)
Vice Chancellor and Professor
Department of Medicine
Duke University Medical Center
Durham, NC 27710
***Dennis W. Choi, Ph.D., M.D. (2015)
New York, NY 10010
Ana M. Cuervo, Ph.D., M.D. (2015)
Albert Einstein College of Medicine
Department of Development and Molecular Biology
**Hugh C. Hendrie, DSC, Ph.D. (2013)
Professor of Psychiatry
Indiana University School of Medicine and Regenstrief Institute, Inc.
Indiana University Center on Aging Research
Indianapolis, IN 46202
**Andrea Z. LaCroix, Ph.D., MPH (2012)
Fred Hutchinson Cancer Research Center
Women’s Health Initiative Clinical Coordinating Center
Seattle, WA 98109
Victor A. Molinari, Ph.D. (2012)
University of South Florida
Department of Aging & Mental Health
Louis De la Parte Florida Mental Health Institute
Tampa, FL 33612
*Richard I. Morimoto, Ph.D. (2014)
Bill and Gayle Cook Professor of Biology
Departments of Biochemistry, Molecular, and Cell Biology
College of Arts and Sciences
Evanston, IL 60208
*Lennart Mucke, M.D. (2012)**
Department of Neurology
University of California, San Francisco
San Francisco, CA 94141
**Eliseo J. Perez-Stable, M.D. (2014)
Department of Medicine
University of California, San Francisco
School of Medicine
San Francisco, CA 94143
Daniel P. Perry (2013)
Alliance for Aging Research
Washington, DC 20006
Ronald C. Petersen, Ph.D., M.D. (2013)
Professor of Neurology
Cora Kanow Professor of Alzheimer’s Disease Research
Director, Mayo Alzheimer’s Disease Research Center
Director, Mayo Clinic Study of Aging
Rochester, MN 55905
Arlan G. Richardson, Ph.D. (2013)
Barshop Institute on Longevity and Aging Studies
University of Texas Health Science Center
San Antonio, TX 78245
June Simmons (2012)
Chief Executive Officer
Partners in Care Foundation
San Fernando, CA 91340
Jonathan S. Skinner, Ph.D. (2015)
Professor of Community and Family Medicine
Department of Economics
Institute for Health Policy and Clinical Practice
Lebanon, NH 03755
Stephanie A. Studenski, MPH, M.D. (2014)
Department of Medicine
University of Pittsburgh
Pittsburgh, PA 15213
**Terrie F. Wetle, Ph.D. (2013)
Associate Dean and Professor
Brown University Medical School
Providence, RI 02912
EX OFFICIO MEMBERS
Department of Health and Human Services
Hubert H. Humphrey Building
Washington, DC 20202
Francis S. Collins, Ph.D., M.D.
National Institutes of Health
Public Health Service
Building 1, Room 126
Bethesda, MD 20892
James F. Burris
Office of Research and Development
Department of Veterans Affairs
Washington, DC 20420
Office of Program Development
U.S. Administration of Aging
Washington, DC 20020
Kenneth G. Pugh, LCDR, MC
Department of Medicine
National Naval Medical Center
Bethesda, MD 20889
Robin A. Barr, D.Phil
Director, Office of Extramural Activities
National Institute on Aging
Bethesda, MD 20892