September 18-19, 2008
Department of Health and Human Services
Public Health Service
National Institutes of Health
National Institute of Mental Health
The National Advisory Mental Health Council (NAMHC) convened its 219th meeting in closed session to review grant applications at 1 p.m. on September 18, 2008, at the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 5:15 p.m. (see Appendix A: Review of Applications). The NAMHC reconvened for an open session on the following day, September 19, 2008, in Building 31C, National Institutes of Health, from 8:30 a.m. until adjournment at 12:35 p.m. In accordance with Public Law 92-463, the open policy session was open to the public. Thomas R. Insel, M.D., Director, National Institute of Mental Health (NIMH) chaired the meeting.
Council Members Present at the Grant Review and/or Open Policy Sessions
(See Appendix B: Council Roster)
Chairperson: Thomas R. Insel, M.D.
Executive Secretary: Jane A. Steinberg, Ph.D.
Carl C. Bell, M.D.
Glorisa J. Canino, Ph.D.
Elizabeth Childs, M.D., M.P.A.
Jonathan D. Cohen, M.D., Ph.D.
Robert Desimone, Ph.D.
Daniel H. Geschwind, M.D., Ph.D.
Raquel E. Gur, M.D., Ph.D.
Peter J. Hollenbeck, Ph.D.
Dilip V. Jeste, M.D.
Ira Katz, M.D.
Jeffrey A. Kelly, Ph.D.
Norwood Knight-Richardson, M.D., M.B.A.
Helena C. Kraemer, Ph.D.
Pat R. Levitt, Ph.D.
David A. Lewis, M.D.
John S. March, M.D., M.P.H.
Enola K. Proctor, Ph.D.
Carol Alter, Academy of Psychosomatic Medicine
Andrea Barnes, National Federation of Families for Children’s Mental Health
Andrea DeSanti, Social and Scientific Systems, Inc.
Reuven Ferziger, Johnson & Johnson
Marci Giang, Council on Social Work Education
Bryan Goodman, Children and Adults with Attention-Deficit/Hyperactivity Disorder
Elizabeth Hoffman, American Psychological Association
Ann Michaels, National Foundation on Mental Health
Eve Moscicki, American Psychiatric Institute for Research and Education
Anand Pandya, National Alliance on Mental Illness
Jim Payne, National Education Alliance for Borderline Personality Disorder
Laurel Cargill Radley, American Occupational Therapy Association
Stephanie Reed, American Association for Geriatric Psychiatry
Bette Runck, Science Writer
Angela Sharpe, Consortium of Social Science Associations
Jean Shin, American Sociological Association
Solomon Snyder, Johns Hopkins University School of Medicine
Andrew Sperling, National Alliance on Mental Illness
Audrey Spolarich, Health Policy and Social Marketing
Allison Trepod, SRI International
Stacy Weiner, Mental Health America
Jill Wetzel, Infinity Conference Group
Joan Levy Zlotnik, Institute for the Advancement of Social Work Research
Open Policy Session: Call to Order and Opening Remarks
NIMH Director, Dr. Thomas R. Insel, called the open policy session to order, welcoming all in attendance.
Approval of the Minutes of the Previous Council Meeting
Turning to the minutes of the May 2008 Council session, Dr. Insel asked if Council members had revisions or comments on the minutes. Hearing none, the minutes were unanimously approved.
NIMH Director's Report
The NIH Roadmap for Medical Research, launched in 2004, is the NIH-wide effort intended to accelerate translation of research to improvements in public health. The Molecular Libraries Program, one of the largest Roadmap projects, is now moving into its production phase with the establishment of the Molecular Libraries Probe Production Centers Network. In this new phase, a network of nine centers will use technologically advanced methods to screen a library of more than 300,000 small molecules maintained in the Program’s repository. The Program is led by NIMH and the National Human Genome Research Institute (NHGRI) under the leadership of NIMH’s Linda Brady, Ph.D.
Roadmap 1.5, launched in 2007, includes the epigenome and microbiome programs, is soliciting projects relevant to NIMH. Roadmap 2.0 will receive $25 million from the NIH Common Fund to support transformational science in behavior change, the mitochondriome function, pain, pharmacogenomics, protein capture, and 3-D tissue models. One large-scale Request for Applications (RFA) will be issued covering all of these topics. In addition, NIMH and NHGRI are leading a new Roadmap initiative in the genetics of tissue expression. This effort will relate genomic sequence variation to variation in messenger ribonucleic acid (mRNA) expression within 30 tissues taken from a large population. The purpose of this effort is to provide a database of functional variants in the human genome. The focus of 2009 is to establish the database and then complete pilot studies in 2010-2011.
Enhancing Peer Review
NIH has been deeply involved in an assessment of its peer review system. A Peer Review Oversight Committee and three subgroups consisting of NIH program, review, policy, grants management, and evaluation staff have developed an initial implementation timeline for enhancing peer review. The recommendations being implemented are based on the results of the diagnostic phase and significant dialogue with both internal and external communities regarding enhancements to the peer review system. Although the subgroups are continuing to work out specific details of the implementation plans, the priority areas for the implementation plans for the 2009 through 2010 calendar years are as follows:
Priority Area 1 – Engage the Best Reviewers
- Improve Reviewer Retention: In 2009, reviewers will be given additional flexibility regarding their tour of duty, and other efforts will be undertaken to improve retention of members of standing review committees.
- Recruit the Best Reviewers: A toolkit, incorporating best practices for recruiting reviewers, will be made available to all Institutes and Centers in 2009.
- Enhance Reviewer Training: In Spring 2009, training will be available to reviewers and Scientific Review Officials related to the changes in peer review.
- Allow Flexibility through Virtual Reviews: Pilots will be conducted in 2009 on the feasibility of using high-bandwidth support for review meetings to provide reviewers greater flexibility and alternatives for in-person meetings.
Priority Area 2 – Improve the Quality and Transparency of Review
- Improve Scoring Transparency and Scale: Review by criteria-based scoring on a new scale commences in May 2009. Reviewers will provide feedback through scores and critiques for each criterion in a structured summary statement.
- Provide Scores for Streamlined Applications: In 2009, streamlined applications will receive a preliminary score on each of the five review criteria.
- Shorten and Restructure Applications: Shorter (12-page research plan) R01 applications (with other activity codes scaled appropriately) will be re-structured to align with review criteria for January 2010 receipt dates.
Priority Area 3 – Ensure Balanced and Fair Reviews across Scientific Fields and Career Stages, and Reduce Administrative Burden
- Fund the Best Science Earlier and Reduce Need for Re-submissions: To ensure that the largest number of high-quality and meritorious applications receive funding earlier and to improve system efficiency, new application submitted after January 2009 will be allowed only one re-submission (amended application).
- Review Similar Applications Together: NIH is establishing an Early Stage Investigator (ESI) designation. In 2009, NIH will evaluate clustering ESI applications for review. The same approach will be considered for clinical research applications.
NIMH Strategic Plan
NIMH released its new Strategic Plan in August. This Plan, which includes a new vision and mission statement for the Institute, describes the agenda for research in mental health over the next 5 years. The plan was developed over the course of a full year of meetings between the Institute and its many stakeholders. Dissemination and implementation of the Plan will be a major focus of the next several months, as funding increasingly shifts towards the major objectives of the Plan. Dr. Insel asked for Council’s advice on methods to solicit more applications that are relevant to the major objectives of the Plan. One option might be to use RFAs as a means of soliciting applications in the areas of science emphasized in the Plan. Dr. Insel also suggested that as Council members review applications, they might ask program staff how each contributes to the goals of the Strategic Plan.
The NIMH budget was approximately $1.4 billion in 2008, which represented a 0.8 percent increase over the budget in 2007. With the inflation rate of about 3.4 percent, this represented a 2.6 percent decrease in purchasing power. The fiscal year 2009 budget has not yet been approved by Congress and the President, but it appears that it will not be substantially different from the 2008 budget. This would be the sixth year of having a subinflationary increase in the budget, which represents an actual reduction in purchasing power of about 14 percent since 2003.
In fiscal year 2007, NIMH funded 620 new research project grants (RPGs), whereas so far in 2008 the number is 571; the 2007 figure was higher than usual because money set aside for the Roadmap was returned to the Institute and was used to fund additional RPGs. Funded noncompeting grants numbered 1,553 in 2007 and 1,609 in 2008. The average cost of grants continues to creep up, and with tight budget restraints, this will require careful monitoring. The success rate–meaning the number of grants funded versus all of the applications that come in–was 21 percent in 2007, 19 percent in 2008. In terms of new investigators, NIMH funded a total of 98 new investigators in 2007 and 95 in 2008. That number may be appropriate, although more analysis is needed to ensure that early-stage investigators are adequately represented.
Dr. Insel announced that Richard Nakamura, Ph.D., NIMH Deputy Director since 1997, has accepted the position as the new Scientific Director of the NIMH Division of Intramural Research Program (DIRP). In addition, Maryland Pao, M.D., has accepted the position of Clinical Director of the DIRP, a position most recently occupied by Donald Rosenstein, M.D. Other recent additions to the NIMH staff include program officers Drs. Andrew Rossi, David Panchision, Julia Zehr, Marjorie Garvey, and Charles Sanislow. Dr. Insel announced that searches are currently underway to appoint a new Deputy Director of the Institute and a new Director for the Office of Special Populations.
Dr. Insel highlighted a few of the many recent scientific breakthroughs in the science supported by NIMH. Robert G. Robinson, M.D. and colleagues at the University of Iowa found that preventive treatment with an antidepressant medication or problem-solving talk therapy can significantly reduce the risk or delay the onset of depression following an acute stroke when compared with placebo. This finding is significant because depression is a very high risk factor for subsequent medical morbidity and these findings differ from past studies attempting to prevent post-stroke depression.
Results from the NIMH-funded 6-year multisite Treatment of Early Onset Schizophrenia Study (TEOSS) found no significant differences in outcomes with first- or second-generation antipsychotic medications. There was a striking difference in side effects, but there was no evidence that any of the medications was the best choice for the entire group of people being treated. Similar results were obtained in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, the Cost Utility of The Latest Antipsychotics in Severe Schizophrenia (CUtLASS) trial from the United Kingdom, and the large-scale Veterans Administration trial. Despite the lack of a clear superiority in overall effectiveness of the second-generation drugs, they account for more than 90 percent of the market and cost about 20 times more than the first-generation compounds.
Findings in psychiatric genetics reported over the last 4 months have spurred the field to look more deeply at single nuclear-type polymorphisms and have pointed to other kinds of variations in the genome that may be relevant to mental illness. Recent articles published in Science, Nature Genetics, and the New England Journal of Medicine suggested a higher prevalence of genetic structural variance in mental illnesses–a tenfold greater rate in autism and schizophrenia. In the next year or two, much more will be learned about the biological relevance of and the mechanisms by which these duplications and deletions increase the risk for these disorders.
Using novel techniques to identify new HIV infections and a broader range of infections, the Centers for Disease Control and Prevention recently reported that the number of new cases is about 40 percent higher than was obtained with old methods. Instead of 40,000 new cases of HIV a year, the number is reported as 56,300. Also of concern is the demographic distribution of the new cases: 73 percent are in men, 53 percent in men who have sex with men, 45 percent in African Americans, and 17 percent in Hispanics. As the testimony at a recent congressional hearing made clear, the public health community is still not very good at identifying who is infected. It is likely that 25 percent of those who are infected do not know they are infected, and these individuals are thought to account for about 67 percent of future new infections. Knowing one’s infection status is one of the most powerful interventions for reducing transmission.
Dr. Bell asked what methods might be used to infuse the Strategic Plan’s clear vision into the grant review process. Dr. Insel noted that it is important to communicate the Institute’s goals to grantees at an early stage in the grant application process. Dr. Insel has talked about the strategic plan with the NIMH-chartered review committees; however, only approximately 25 percent of applications are reviewed by NIMH committees. The remainder is reviewed by the NIH Center for Scientific Review (CSR), where many of the meetings review applications from multiple ICs and therefore they are not able to focus on the strategic plan of any one institute. In addition to early communication, Dr. Insel suggested that the Council help to assess how well an application meets the NIMH goals after it has been reviewed for scientific merit. That process, along with disseminating information to grantees, will help to ensure that the Strategic Plan is implemented.
In response to Dr. Insel’s comments about an emphasis on RFAs to implement the Strategic Plan, Dr. Desimone observed that the probability of success of a grant application submitted through an RFA is often less than one submitted as a standard R01. Because of this, Dr. Desimone suggest that in order to achieve the goals of the Plan, NIMH might consider issuing a few larger-scale RFAs such that the pool of money is larger and there is a greater chance of success. Dr. Insel said that the Institute’s leadership has come to a similar conclusion and has proposed having RFAs that are broader and with a larger set-aside amount than is common now. NIMH does want to steer the research community, and RFAs may be a way to do so, especially if unsolicited applications do not adequately address the Institute’s objectives.
Comments from Retiring Council Members
Dr. Insel acknowledged the contributions of Council members whose Council tenure ends on October 1: Drs. Jonathan Cohen, Raquel Gur, Peter Hollenbeck, Jeffrey Kelly, Helena Kraemer, and Suzanne Vogel‑Scibilia. As a token of appreciation, Dr. Insel presented each departing member with a plaque, an NIMH T-shirt, and a letter from the Secretary of the Department of Health and Human Services, Michael Leavitt. Dr. Insel invited the departing members to address the Council. Drs. Cohen and Vogel Scibilia were unable to attend this portion of the Council meeting and therefore did not provide any comments.
Dr. Raquel Gur
Dr. Gur titled her talk “My Journey with NIMH” because her personal and professional life is tightly linked to NIMH. She said that she has been driven by a personal commitment to schizophrenia research and to trying to make what she does in the laboratory improve the lives of patients with schizophrenia and their family members. Her association with NIMH has been partly responsible for her commitment to integrating the goals of her work to the life of a single patient, a single family with severe mental illness.
Dr. Gur went on to describe her work on schizophrenia and described how her work can be translated to patients. Dr. Gur illustrated how deficits in social cognition create difficulties for individuals with schizophrenia. She demonstrated that people with schizophrenia are less accurate and slower in reading emotion expression on the faces of others. Patients with schizophrenia are more easily distracted. Dr. Gur also demonstrated trait differences in emotional processing in the brain’s limbic structures. Her genetic studies, which involve thousands of people across the country, have shown that individuals with schizophrenia have significant impairment in emotional processing, whereas their unaffected relatives are somewhat impaired when compared with controls.
The challenge for the future, Dr. Gur said, is both to “zoom in” and “zoom out” when studying mental illness. She encouraged continued emphasis on interdisciplinary collaboration both between and within intramural and extramural research communities.
Dr. Helena Kraemer
Dr. Kraemer said that she, like other biostatisticians working in biomedical research, has tried to prevent unknowingly false results from being published in the medical literature. During her tenure on the Council, she has repeatedly stressed the need for care in the design and interpretation of studies. Dr. Kraemer pointed out that research by its nature is a process of trial and error, a condition that necessarily results in some errors.
Dr. Kraemer called for careful attention by peer review to the distinction between hypothesis-testing studies, which are by nature designed to test a specific hypothesis for which there is a theoretical rationale and justification, and hypotheses-generating studies, which are designed to generate the information necessary to design very powerful cost-effective type studies. The NIMH needs both types, and they need to be reviewed using different standards. Dr. Kraemer called for further clarification with the review committees regarding pilot studies. Originally a pilot study was meant to serve as a small preliminary study to a hypothesis-testing study to test feasibility of the research tactics, not to get the answers to the research questions. It appears that review committees often apply hypothesis-testing criteria to evaluate these studies as well, and this is where the peer review process may break down.
Dr. Kraemer turned her attention to the need for data sharing. Researchers working in genetics and imaging routinely share data, whereas those who conduct clinical trials or do epidemiological studies do not. She suggested that NIMH should require, as a condition of funding, that the data underlying a published study be made available to reviewers when a paper is submitted and to other experts after publication. A benefit of such a requirement is that it would provide an immediate check on the internal validity of results. In addition, the entire dataset from the study should be available in some reasonable time after the end of the funding period. Data sharing would improve the quality of future research, because the shared data would likely facilitate future hypothesis generating at little to no cost to NIMH. Such sharing would promote stronger hypotheses and better designs to test those hypotheses. In addition, it would improve the quality of the original study because the investigators would be much more careful about documenting, organizing, and analyzing their data.
Dr. Jeffrey Kelly
Dr. Kelly began his talk by complimenting the NIMH program staff. He said that he has been amazed by the staff’s depth of knowledge about the applications under review each Council round.
His own background as a clinical psychologist and AIDS researcher has led him to consider several issues. The first issue is health disparities. Whether it is AIDS or mental illness, it is clear that the neighborhood in which one lives, one’s income, and one’s race are significant determinants of one’s vulnerability to mental health problems and certain HIV risks. The mental health field needs to dedicate itself and its resources to reducing these disparities. The NIH has taken one major step in requiring researchers to include minority participants in funded research projects, but Dr. Kelly stated that the NIH also needs research to address why disorders are disproportionally affecting minorities in this country.
Dr. Kelly called attention to the need for researchers/scientists to not only publish research findings in journals read by other scientists but also make greater efforts to communicate research findings to practitioners, community members, and persons affected by the illnesses. By way of example, 96 percent of HIV infections occur outside of North America with the vast majority occurring in countries where people have no access to scientific journals or an adequate current literature. Other dissemination vehicles are needed; otherwise, researchers are engaging primarily in an academic exercise.
Dr. Kelly stressed the importance of integrated models. Clinical trials should test real- world populations rather than screen out many potential participants, such as those with comorbid conditions. By controlling every variable except the intervention of interest the science may be accurate, but it may not be applicable in the lives of patients. Research on interventions in the mental health field largely consists of efficacy trials, i.e., well‑controlled randomized trials. Dr. Kelly called for more effectiveness trials that might more accurately demonstrate how interventions are used in the real world, where there is a lot more noise and more heterogeneity, not only in the recipients of interventions but also in the delivery of them.
Finally, Dr. Kelly asked Council to strive for balance among genetic, physiological, and psychosocial factors in the research related to mental illness. Everyone’s lives, including those touched by mental disorder, are influenced by their life experiences, as well as their biological makeup.
Dr. Peter Hollenbeck
Dr. Hollenbeck echoed Dr. Kelly’s comments. He added that his own basic neuroscience research has been influenced by his experience on the Council. He added that, like Dr. Kelly, he has been impressed with NIMH staff members–with their intellect, motivation, and hard work.
Recommendations of Council Workgroup on Research Training
Dr. Dilip Jeste, Chair of the NAMHC Workgroup on Research Training reminded Council that an essential component of the NIMH mission is to promote the training of investigators who will conduct research into the causes and treatment of mental illness. The NAMHC Workgroup on Research Training was charged with advising the Council on NIMH’s investment in research training and to provide strategic recommendations about how NIMH could better achieve its goals in recruiting, training, and retaining a workforce capable of integrating novel technologies and approaches across multiple levels of analysis in its NIMH-relevant research. The workgroup met several times over the past 8 months and has developed a set of recommendations to present to Council for approval. Dr. Jeste summarized the workgroup’s recommendations:
- Maintain the NIMH budget for research training and career development. Despite targeted reductions in support for research training and career development, NIMH continues to be among the top ICs in terms of percent of extramural research budget devoted to research training and career development. NIMH was ranked fourth in fiscal year 2007.
- Build a strong pipeline of trainees who are focused on mental health-relevant research careers.
- Develop national mentoring networks. Mentoring is an essential component of effective research training. The workgroup recommends that national mentoring networks be developed, with an initial focus on individuals from diverse groups. These networks would assist at critical transitions points along the career path and would be integrated with NIMH-supported research training programs.
- Capitalize on the outstanding interdisciplinary research environments at NIMH-supported centers and expand support for systematic research training and education in these rich environments. In 2007, NIMH supported 49 research centers at an annual cost of $74 million.
- Implement efforts to span critical transition points in the career pipeline. The workgroup recommended two initial efforts, a match-making system and a diversity training merit program, emphasizing individuals from diverse groups.
- Retain M.D./Ph.D.s in mental health-related research by expanding research training options during residency and beyond.
- Implement best practices for management of institutional training programs at NIMH.
- Encourage ongoing program monitoring and assessment, including a comprehensive data collection effort that would allow for data-driven policy modifications.
- Strengthen dissemination and communication with the extramural research community to facilitate awareness of NIMH-funded training and education programs so that interested scientists would be aware and able to participate.
In summary, the workgroup’s recommendations provided NIMH with possible implementation strategies to enhance existing training efforts and investments and to develop new initiatives addressing current areas of need. Because science is becoming increasingly interdisciplinary, basic scientists and clinician-scientists are essential to achieving the NIMH mission. The Institute is encouraged to pursue an evidence-based approach to its support for research training and career development.
After thanking Dr. Jeste and the workgroup, Dr. Insel opened the discussion of the recommendations among the Council members. Dr. March agreed with the recommendations of the report; however, he noted that the report did not appear to comment on the need for infrastructure support for an investigator transiting to the mid‑career stage. This is a point of transition where a mentee becomes a mentor. The mechanism that is currently available is the K24; however, its use might be clarified so that it emphasizes mentoring in support of this transition.
Dr. Geschwind asked whether the workgroup was recommending a research- or academic-track residency for those in M.D./Ph.D. programs. Dr. Geschwind underlined the problem of integrating the clinical and research training components. A trainee goes from the laboratory, to the clinic, to a 4-year residency that involves seeing patients full time, and then returns to research. The report recommends Pioneer-like Awards for M.D./Ph.D.s to do mental health-related research and become the scientific leaders of the future. Such awards may have their greatest impact at the early stages of a scientific career. Dr. Insel said the practice of “capturing” someone who is just finishing an M.D. /Ph.D. program and going into a residency has been tried in a pilot program in the NIMH IRP. The candidates continue to obtain clinical training through a residency, but they are given the opportunity to do research throughout the residency because it is extended from 4 to 6 years. Dr. Insel suggested identifying five or six institutions that might offer different tracks so that enough M.D./Ph.D.s would be trained to meet future needs.
Dr. Bell praised the attention that the report gave to issues of underrepresented minorities both in terms of training needs and in representation in the workforce. He cautioned the workgroup against the bias that training underrepresented minorities in scientific pursuits would lead to more research into problems experienced by underrepresented minorities. Dr. Insel agreed that it was important not to conflate the issue of health disparities and to have a research program that addresses workforce diversity. It would be a mistake to assume that every minority trainee would do research on minority mental health. In response to another comment from Dr. Bell regarding the difficulties of assigning credit in interdisciplinary research, Dr. Insel said that the culture of science does need to change. It will require a shift in thinking by promotion committees and helping people to understand what a unique contribution someone can make within a team. At present, the scientific culture is largely based on individual accomplishment, even though everyone talks a lot about the importance of team science.
Following the discussion, the Council voted to approve the workgroup’s report.
Recommendations of the NIMH Intramural Research Program (IRP) Blue Ribbon Panel
NIMH, at the request of the NIH Director, Elias Zerhouni, M.D. convened a Blue Ribbon Panel (BRP) of distinguished experts to review the general organization, operation, and administration of the NIMH IRP. The Panel was co-chaired by Solomon Snyder, M.D., Department of Neuroscience at Johns Hopkins School of Medicine, and Carol Tamminga, M.D., Department of Psychiatry at the University of Texas, Southwestern Medical Center. The report of the BRP has been presented to Dr. Zerhouni and was approved by the Advisory Committee to the Director of NIH on June 6, 2008. (See the agenda or the meeting summary .) Dr. Insel welcomed Dr. Snyder to the meeting and thanked him for his work on the BRP and for presenting to the Council.
Dr. Snyder reviewed the charge to the BRP by Dr. Zerhouni, which included consideration of the following points:
- NIMH needs to recruit a new Scientific Director (SD) for the IRP and the BRP should identify characteristics to seek in a SD.
- Innovation and nimble adaptability are essential qualities for research programs to excel. How can NIMH IRP become more innovative and adaptable?
- NIMH IRP has many new research programs, in part in response to the suggestions from the previous BRP report in 1997. Are the current programs effective? How could they be improved?
- What is the appropriate balance between related programs at other NIH IRPs and that within NIMH's IRP? Is anything underrepresented or overrepresented in NIMH's IRP?
- NIH seeks ways in which to strengthen collaborative efforts between IRP scientists and extramural researchers.
The panel reviewed the previous BRP report and the accomplishments of the IRP since that report in 1997. These accomplishments include the recruitment of a cadre of experienced and talented physician scientists, the enhancement of brain imaging and nuclear medicine capabilities within the IRP, the strengthening of the response to the Board of Scientific Counselors (BSC) recommendations based upon annual reviews of the productivity of tenured IRP investigators, and the capacity of the IRP to play a central role in responding to new and emerging mental health needs in the United States, including the programs examining the subtypes of autism and defining new and better treatments, tailored to clinical needs.
In its review of the IRP, the BRP made several recommendations, including:
- Appoint a Scientific Director of world-class stature as a scientist and administrator: Since the BRP was presented to Dr. Zerhouni, Dr. Richard Nakamura has been appointed as the Scientific Director of the IRP.
- NIMH IRP as an incubator: The IRP should be an environment that fosters innovation and adaptability where scientists can participate in high-risk research and work in an environment with unique resources (i.e., the NIH Clinical Center).
- Exit strategy: The IRP would provide support to investigators leaving the IRP, to encourage the transition to the extramural research community.
- Structure and linkage of IRP basic and clinical neuroscience—Importance of Investigator Independence: The BRP suggests that the IRP be structured as a collaboration of independent teams rather than large groups with a single leader. The IRP clinical and basic researchers should be closely linked to facilitate the translational goals of understanding disease mechanisms and developing novel therapies. The BRP recommends that the IRP strengthen its emphasis on developmental neuroscience as there is an increasing realization that major mental illnesses have a strong developmental component.
- The need for additional laboratory research space: Completion of Phase II of the Porter Neuroscience Research Center is critical.
- The fluidity of IRP funding–discretionary funds: The Scientific Director should reserve a larger discretionary fund to facilitate nimble responses to new research opportunities.
- Future recruiting of scientists should be driven by the research needs identified in the NIMH Strategic Plan with particular focus on genetics, epigenetics, bioinformatics, developmental neurobiology, biomarker development, and therapeutics development.
Upon presenting the recommendations, Dr. Snyder opened the discussion among Council members. Dr. Nakamura noted that the BRP recommended increasing IRP and extramural interactions and collaborations. IRP scientists need to feel comfortable in both the extramural and the intramural worlds; for example, receiving training in how to write NIH grant applications.
Dr. Jeste, alum of the IRP, described it as unique, a place where one has the luxury of having great research resources without the commitments of academia, such as teaching and clinical work. Dr. Snyder elaborated on the uniqueness of the IRP. One reason for having such a program is that it is possible to do ambitious, often high-risk research because of guaranteed funding. The concentration of scientists and resources encourages large-scale collaborative efforts. Major efforts with large teams, similar to what physicists do, are possible in the IRP, although they are balanced against individual scientists working independently. Dr. Insel added that IRP makes it possible to recruit and assemble enough patients to study rare diseases. An example of this is IRP scientist Dr. Karen Berman’s work with patients who have Williams Syndrome. Dr. Insel, an IRP alum as well, said that the IRP also makes it possible for individuals to change directions, citing himself as a prime example.
Dr. March noted that during the panel’s lively discussions, the emphasis was on doing the best possible science, science that can't easily be done even in the best universities. For that to happen, the program has to be nimble, able to change. It is necessary to bring in new people, set up new alliances, reconfigure individuals, and change the direction of scientific research. In addition to the issue of moving people in and out of the IRP, the panel considered how to give the SD the budgetary flexibility and space to drive the science forward.
Dr. Insel closed the discussion of the panel’s report by crediting Susan Koester, Ph.D. Deputy Director of the Division of Neuroscience and Basic Behavioral Science (DNBBS), who organized the panel’s meetings and the materials for the report. He also thanked Dr. Snyder for his leadership.
Leveraging Health Care Networks to Transform Effectiveness Research
David Chambers, D. Phil. Chief of the Services Research and Clinical Epidemiology Branch within the Division of Services and Inventions Research, discussed an initiative aimed at stimulating research that will allow for the use of existing health care databases for conducting effectiveness trials.
Very large, well-characterized, and representative clinical samples are necessary to pursue many mental health research questions rapidly and cost effectively, including tests of effective treatments within large patient populations, implementation of systemic interventions (e.g. collaborative care interventions) within large health care systems, and methods for delivering personalized care. Health care networks with searchable medical records offer potential platforms for recruiting appropriate samples of patients, clinicians, and health care clinics. This initiative encourages information technology bridges among existing health care networks with the goal of reengineering mental health effectiveness and services research. The intent is to examine the feasibility of linked networks for identifying thousands of suitable case and control subjects for basic and applied investigations of mental illness in practice settings.
Dr. Chambers emphasized that the initiative is intended to leverage existing networks rather than create new networks. The goal is to stimulate research projects that demonstrate the linking of existing health care delivery system networks to perform efficient large-scale trials targeting improved quality of care and patient outcomes. The interest is in the effectiveness of strategies aimed not only at the patient level but also at the provider and clinic levels. In addition to the primary goals of the initiative, such a network could lead to rapid identification of subjects for trials; modeling of the impact of implementing interventions across different systems; specifically targeted studies to determine demand for interventions; and gathering of biomarker or genome data.
Dr. Jeste asked if the proposed initiative is restricted to people with mental illness or whether it can include those who may be particularly vulnerable to developing mental illness in the future; those individuals may be helped to improve their quality of life and functioning and possibly prevent the appearance of the illness. Dr. Chambers said that a health care network would make it possible to gain access to a broad population.
Dr. Geschwind emphasized the opportunity for banking biological data; most of these networks have amazing phenotype databases. Dr. Chambers said that was part of the plan.
Dr. Proctor said she thought it is important to capture provider- and system-level data and to recognize how difficult it is for current existing datasets to be cross-referenced. They often have very different architecture and context, particularly around the characterization of interventions and settings. It may be important to provide an opportunity to enhance data that already exist in some nonacademic settings with underdeveloped infrastructures.
Dr. Kraemer suggested including a provision for evaluating the quality of the data in a clinical database before it is incorporated into a network. This issue has been discussed, Dr. Chambers said. Dr. Insel acknowledged that it will be necessary to build quality control into the announcement.
Exploratory Studies of Induced Pluripotent Stem Cells from Healthy and Patient Population
David M. Panchision, Ph.D., Chief of the Developmental Neurobiology Program within DNBBS described an initiative to support exploratory studies to generate and characterize induced pluripotent (iPS) cells from healthy and/or mental health patient populations. The goal is to further our understanding of the basic cellular mechanisms underlying disease states and the variability in illness characteristics between patients.
Studies of thought, mood and social disorders currently suffer from a gap in understanding fundamental molecular and cellular defects and the role of altered developmental processes in these disorders. The ability to generate animal models, which could address this gap, is hindered by the absence of an obvious human lesion or single gene defect that can be replicated in animals. The recent development of iPS cells may provide a unique opportunity to resolve this experimental dilemma. iPS cells are similar to embryonic stem (ES) cells in that they exhibit pluripotency, the ability to generate all body cell types—including neurons and glia. However, they differ from ES cells in that somatic cells from an adult can be readily induced to pluripotency by in vitro genetic manipulation, thereby generating an individualized tool to study (and perhaps eventually treat) a patient’s disorder. For this relatively new area, it is recognized that the scientific community is essentially in the discovery phase and there is substantial basic research that remains to be done. An emphasis should be placed on appropriate validation of iPS cells and their derivatives, evaluating the hetero/homogeneity of cell populations to be screened and comparison of results with predicted biological outcomes relevant to brain function and mental disorders.
Dr. March said he is concerned that small biotechnology companies are rushing to patent iPS cells and that it would be desirable to have “whole panoplies” of these tools and technologies in the public domain sooner rather than later. Dr. Panchision said that NIMH will encourage the sharing of reagents and optimization of induction techniques that don’t involve genetic manipulation. The NIMH program foresees a resource-sharing system in which fibroblasts would be banked and readily available for these purposes.
Dr. Geschwind said that it would be useful to have the actual iPS lines from any NIMH-supported project. A researcher doing pharmacogenomics may be getting fibroblasts at the expense of considerable effort. If those lines were widely available, other research would be facilitated.
Dr. Insel welcomed the suggestions, since the technique has only been available for less than a year. No applications using the technique have been submitted as yet to NIMH. This initiative might generate interest in the community and bring in people working on schizophrenia, bipolar disorders, or autism. The first report on a clinical condition, amyotrophic lateral sclerosis, using the technique was published in Science in August. The opportunities offered by this technique impel NIMH to move quickly.
Dr. Insel pointed out that this strategy is reverse translation in its ultimate form. The researcher begins with patients who have the disease—for example, twins who are discordant for autism or schizophrenia—and ends up with disease-specific stem cells that can be studied, an accomplishment that could not have been imagined a year or two ago; now, such work could develop into the bench science that is much more closely related to the cellular mechanisms of disease. Dr. Panchision reiterated that the technique may be useful in developing individualized assays for treatment response, as well as in understanding the developmental course of mental illness.
Following the discussion, the Council voted unanimously to approve both concept clearances.
Joan Zlotnik, Ph.D., ACSW, Executive Director of the Institute for the Advancement of Social Work Research, commented on the importance of the recommendations from the NAMHC Workgroup on Research Training. The Consortium of Social Science Associations conducted a survey of more than 250 professional associations and scientific societies. This effort, together with a national meeting last February, created a collaborative for enhancing diversity in science. Dr. Zlotnik emphasized the breadth of the associations involved in the planning and noted that their report will be released soon. Some of the issues discussed related to undergraduate mechanisms for getting students into the pipeline leading to a Ph.D. or M.D. and a career in science. She said she would like to see the training priorities extended beyond neuroscience to include other sciences related to mental health as well.
Dr. Zlotnik said she was also interested in the Council’s discussion of HIV and AIDS and issues related to services and implementation, issues that extend beyond the discovery of the molecular involvement in mental illness.
Dr. Insel reminded Council members that the next meeting would be held February 12-13, 2009. With that, he adjourned the meeting.
Dr. Insel adjourned the 219th meeting of the NAMHC at 12:35 p.m. on September 19, 2008.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Thomas R. Insel, M.D., Chairperson
Appendix A: Review of Applications
Summary of Primary MH Applications Reviewed
Council: September 2008
|Scored #||Scored Direct Cost $||Not Scored (NRFC)#||Not Scored (NRFC) Direct Cost $||Other #||Other Direct Cost $||Total #||Total Direct Cost $|
Appendix B: Council Roster
(Terms end 9/30 of designated year)
|Thomas R. Insel, M.D.|
National Institute of Mental Health
|Jane A. Steinberg, Ph.D.|
Division of Extramural Activities
National Institute of Mental Health
|Carl C. Bell, M.D. (11)|
President and CEO
Community Mental Health Council and Foundation, Inc.
Glorisa J. Canino, Ph.D. (09)
Director, Behavioral Sciences Research Institute
University of Puerto Rico
Medical Sciences Campus
San Juan, PR
Elizabeth Childs, M.D., P.C. (10)
Jonathan D. Cohen, M.D., Ph.D. (08)
Eugene Higgins Professor of Psychology
Director, Princeton Neuroscience Institute
Robert Desimone, Ph.D. (11)
Director, McGovern Institute for Brain Research
Massachusetts Institute of Technology
Daniel H. Geschwind, M.D., Ph.D. (11)
Director and Professor
University of California, Los Angeles
Los Angeles, CA
Raquel E. Gur, M.D., Ph.D. (08)
Director, Neuropsychiatry Section
University of Pennsylvania Medical Center
Peter J. Hollenbeck, Ph.D. (08)
Professor of Biological Sciences
Department of Biological Sciences
West Lafayette, IN
Dilip V. Jeste, M.D. (10)
Ester and Estelle Levi Chair in Aging
Distinguished Professor of Psychiatry and Neurosciences
University of California, San Diego
VA San Diego Healthcare System (116A-1)
La Jolla, CA
Jeffrey A. Kelly, Ph.D. (08)
Professor of Psychiatry and Behavioral Medicine
Director, Center for AIDS Intervention Research (CAIR)
Medical College of Wisconsin
Norwood Knight-Richardson, M.D., M.B.A. (09)
Vice Chairman of Department of Psychiatry
Director of the Public Psychiatry Training Program
Director of Oregon Health and Science University Neuropsychiatric Institute
Oregon Health and Science University
|Helena C. Kraemer, Ph.D. (08)|
Department of Psychiatry and Behavioral Sciences
Pat R. Levitt, Ph.D. (09)
Professor, Department of Pharmacology
and Director, Vanderbilt Kennedy Center for Research on Human Development Vanderbilt University
David A. Lewis, M.D. (11)
Director, Translational Neuroscience Program
University of Pittsburgh
John S. March, M.D., M.P.H. (10)
Professor and Chief
Department of Psychiatry
Child and Adolescent Psychiatry
Duke University Medical Center
Enola K. Proctor, Ph.D. (10)
Frank J. Bruno Professor of Social Work Research
Washington University in St. Louis
St. Louis, MO
Suzanne E. Vogel-Scibilia, M.D. (08)
Beaver County Psychiatric Services
Ex Officio Members
Office of the Secretary, DHHS
Michael O. Leavitt
Department of Health and Human Services
National Institutes of Health
Elias A. Zerhouni, M.D.
National Institutes of Health
Ira Katz, M.D., Ph.D.
Department of Veterans Affairs
Office of Mental Health Services
A. Kathryn Power, M.Ed.
Director, Center for Mental Health Services