Skip to content

NAMHC Minutes of the 226th Meeting

NAMHC Minutes of the 226th Meeting
September 23-24, 2010

Department of Health and Human Services
Public Health Service
National Institutes of Health
National Institute of Mental Health

Introduction

The National Advisory Mental Health Council (NAMHC) convened its 226th meeting in closed session to review grant applications at 11 a.m. on September 23, 2010, at the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 5 p.m. (see Appendix A: Review of Applications). The NAMHC reconvened for an open policy session on the following day, September 24, 2010, in Building 31C, National Institutes of Health (NIH), from 8:30 a.m. until adjournment at approximately 12:45 p.m. In accordance with Public Law 92-463, the 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.

David G. Amaral, Ph.D.
Carl C. Bell, M.D.
Elizabeth Childs, M.D., M.P.A.
Robert Desimone, Ph.D.
Ralph J. DiClemente, Ph.D.
Howard B. Eichenbaum, Ph.D.
Daniel H. Geschwind, M.D., Ph.D.
Dilip V. Jeste, M.D.
David A. Lewis, M.D.
Roberto Lewis-Fernandez, M.D.
John S. March, M.D., M.P.H.
Thomas H. McGlashan, M.D.
Steven M. Paul, M.D.
Enola K. Proctor, Ph.D.
Rhonda Robinson Beale, M.D.

Ad Hoc Member: Carla Shatz, Ph.D.

Ex Officio Members:
Francis S. Collins, M.D., Ph.D., National Institutes of Health
Ira Katz, M.D., Ph.D., Department of Veterans Affairs

Liaison Representative at the Open Policy Session:
Elizabeth Lopez, Ph.D., Center for Mental Health Services, Substance Abuse and Mental Health Services Administration (SAMHSA)

Others Present at Open Policy Session:
Caitlin Annand-Baechtel, American Foundation for Suicide Prevention
Robi Blumenstein, CHDI Foundation
Nicole Cardarelli, American Foundation for Suicide Prevention
Danielle Coppola, Johnson & Johnson
Llewellyn Cornelius, Society for Social Work & Research
Yoshie Davidson, American Academy of Child & Adolescent Psychiatry
Debra Derr, Executive Court Reporters
Daniel Gage, American Academy of Pediatrics
Kathi Hanna, Transcriber
Ronald Honberg, National Alliance on Mental Illness
Julie Jolly, Lewis-Burke Associates
John Madigan, American Foundation for Suicide Prevention
Harry Mayfield, Lewis-Burke Associates
Ann Michaels, National Foundation on Mental Health
Enrique Michelotti, National Human Genome Research Institute
Nancy Moy Yven, SRI International
Emanuel Perry, American Foundation for Suicide Prevention
Darrel Regier, American Psychiatric Association
Kevin Roy, IKON Public Affairs
Angela Sharpe, Consortium of Social Science Associations
Natallia Sianko, American Orthopsychiatric Association
Andrew Sperling, National Alliance on Mental Illness
Karen Studwell, American Psychological Association
Jill Wetzel, Infinity Conference Group

Open Policy Session: Call to Order and Opening Remarks

NIMH Director Thomas R. Insel, M.D., called the open policy session to order and welcomed all in attendance. Dr. Insel specifically welcomed Carla Shatz, Ph.D., and noted her expertise in developmental neurobiology and neuroimmnunology.

Approval of the Minutes of the Previous Council Meeting

Turning to the minutes of the May 2010 Council meeting, Dr. Insel asked if Council members had any revisions or comments. Hearing none, the minutes were unanimously approved.

NIMH Director’s Report

Dr. Insel reviewed several ongoing activities at the Department of Health and Human Services (HHS) and NIH levels as well as recent scientific advancements in mental health.

HHS Activities

Cross-HHS Workgroup on Behavioral Health
A new cross-HHS coordinating committee on behavioral health is being co-led by Pamela Hyde, J.D., the Administrator of the Substance Abuse and Mental Health Services Administration (SAMHSA) and Howard Koh, M.D., M.P.H., the Assistant Secretary for Health. This committee will work to be coordinate behavioral health activities across the Department. Five subcommittees have been created to address: early intervention; prescription drug abuse; teenage drinking; integrating behavioral health care with primary care; and, behavioral health communications. Dr. Insel co-chairs the communications subcommittee along with the Deputy Assistant Secretary for Public Affairs at HHS. The subcommittee has already undertaken several activities. Marina Volkov, Ph.D., Acting Director of the NIMH Office of Science Policy, Planning and Communications, has been actively involved in this effort. Dr. Insel noted that children’s mental health is a key area for strategizing effective communications.

Gulf Coast Oil Spill
Dr. Insel explained that the Gulf Coast oil spill has been a major focus for the Department over the past few months and will result in initiatives guided by the National Institute of Environmental Health Sciences. Farris Tuma, Sc.D., Chief of the NIMH Traumatic Stress Research Program, will assist in addressing the mental health challenges facing residents and health care providers, as well as in studying the consequences of that disaster.

Interagency Autism Coordinating Committee (IACC)
The IACC is a Federal advisory committee mandated by Congress to coordinate autism spectrum disorder (ASD)-related activities across HHS. Through its inclusion of both Federal and public members, the IACC helps to ensure that a wide range of ideas and perspectives are represented and discussed in a public forum. With ASD prevalence estimates increasing, ASD represents a major public health concern. Dr. Insel chairs the committee, and NIMH is the lead NIH Institute for ASD activities. Dr. Insel noted that there has been an update of the annual IACC Strategic Plan for ASD Research, which guides ASD research for NIH, the Centers for Disease Control and Prevention (CDC), and other components of HHS. There has been increased focus on adults with ASD—an area of significant need for both science and service provision. ASD presents an interesting paradigm for research, Dr. Insel said, because as a developmental brain disorder, it helps inform the way one thinks about schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD), and a number of other disorders.

National Action Alliance for Suicide Prevention
In September 2010, the National Action Alliance for Suicide Prevention (The Alliance) was established to promote research, policies, and practices that reduce suicide. An executive committee was convened by SAMHSA and chaired by former Senator Gordon Smith, who lost his son to suicide, and who has championed the cause of suicide prevention among youth and college students. The group met recently to launch this effort. The Secretary of the Army, John McHugh, NAMHC member Carl Bell, M.D., several directors of Federal agencies, as well as a number of distinguished public members serve on the Alliance. The Alliance will initially update the National Strategy for Suicide Prevention, and then will work to develop a broad and aggressive effort to address this public health challenge, with the priority of advancing prevention among high-risk groups.

Suicides continue to exceed 34,000 a year in the United States—twice the number of homicides and more than the number of traffic fatalities—with a rising rate in the Army. In June 2010, there were a record 32 suicides in the Army. A recent report from the Secretary of the Army described suicide as an urgent problem that requires action. The Army Study to Assess Risk and Resilience in Service Members (Army STARRS) is the largest study of mental health risk and resilience ever conducted among military personnel. The study is a direct response to the Army's request to NIMH to enlist the most promising scientific approaches for addressing the rising suicide rates among soldiers. Study investigators aim to move quickly to identify risk and protective factors for suicide among soldiers and to provide a science base for effective and practical interventions to reduce suicide rates and associated mental health problems.

NIH Activities

Patient-Centered Outcomes Research Institute (PCORI)
PCORI was established by Congress as part of the Patient Protection and Affordable Care Act of 2010 to assist patients, clinicians, purchasers, and policymakers in making informed health decisions by carrying out research projects that provide quality and relevant evidence on how diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed. Francis Collins, M.D., Ph.D., NIH Director, will serve as a member of the Board of Governors for PCORI.

NIH Scientific Management Review Board (SMRB)
SMRB was authorized by the NIH Reform Act of 2006 to advise the NIH Director on organizational and other issues. At a recent meeting, SMRD members discussed NIH’s role in drug development and discovery; how NIH should conduct translational science; and the merits of creating a new institute focusing on substance use, abuse, and addiction research and related public health initiatives. The SMRB voted in favor of creating a new entity that would integrate the relevant portfolios of the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and other Institutes and Centers, including the National Cancer Institute’s (NCI) work on tobacco addiction and potentially NIMH research focusing on gambling and addictive disorders. The vote represents a recommendation to the NIH Director and is not a final decision. If the Director decides to accept the recommendation, it goes forward to the HHS Secretary, and if she accepts it, the recommendation goes forward to Congress for consideration. The NIH Director has formed a small internal committee to consider the recommendation, and Lawrence A. Tabak, D.D.S., Ph.D., the newly appointed NIH Principal Deputy Director, will work with Dr. Collins to consider the recommendation and its implications.

Common Fund
The NIH Common Fund supports cross-cutting, trans-NIH programs and new initiatives, and NIMH is participating in the following collaborative research initiatives:

  • Health Economics Program, launched in the wake of national health care reform, aims to support research on how specific features of the structure or organization of health care delivery organizations and reimbursement systems influence how health care technologies are adopted and combined by health care providers, how they are applied or used for specific patients, and how those features could be modified to enhance efficiency. NIMH is leading this effort along with the National Institute on Aging (NIA).
  • HMO Collaboratory program was created to speed efficiency, generate faster evidence, take advantage of high-throughput technologies and leverage known economies of scale across health maintenance organizations (HMOs) affiliated with the HMO Research Network to establish a research framework for conducting mega-epidemiology studies and clinical trials in priority disease areas. NIMH, along with the National Center for Complementary and Alternative Medicine (NCCAM), is co-leading the HMO Collaboratory program.
  • The NIH Director’s Early Independence Award is a $60 million, 5-year initiative to support junior investigators in independent academic positions immediately following completion of their graduate research degrees and prior to initiation of their postdoctoral work.

NIMH Activities

Biosignatures Initiative
The Council’s workgroup report, “From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses,” described a series of recommendations to provide the foundation for the next generation of mental health interventions development research, especially those that are preventive and personalized. One of the major areas considered in the report is how biomarkers or biosignatures can be used to individualize interventions, including preemptive interventions. The Establishing Moderators/Mediators for a Biosignature of Antidepressant Response in Clinical Care Study (EMBARC) is a collaborative effort to identify integrated panels of potential biomarkers (i.e., biosignatures) that are predictive of treatment outcomes in major depressive disorder (MDD). EMBARC employs a simple trial design comparing treatment response to a selective serotonin reuptake inhibitor (SSRI) versus placebo in 400 people with MDD. The study also assesses a number of moderator and mediator measures within the first week of the treatment initiation and is designed to develop a standardized set of measures across many different sites. The ultimate goal is to identify predictors of response and adverse events that will help clinicians tailor treatments for people with MDD.

Global Mental Health
NIMH is increasing its commitment to global mental health. NIMH will lead a Grand Challenge project with the Global Alliance for Chronic Disease to identify the highest priority opportunities in global mental health research. Pamela Collins, M.D., M.P.H., Director of the NIMH Office for Research on Disparities and Global Mental Health (ORDGMH), and her team are heading this project. The project represents a call to action in the area of global mental health. Along with the United Nations Millennium Project, the timing is right to ensure that this issue receives broad attention.

Budget Summary Report
Dr. Insel commented that the fiscal year (FY) 2011 budget remains unclear. The President’s budget has been presented, but the actual 2011 budget has not been finalized. He noted that the number of new and competing NIMH grant awards made over the past 5 years has consistently stayed between 550 and 600 grant awards per year. The goal is to maintain this level of support and a success rate of about 20 percent. However, if the number of applications increases greatly in 2011—after funding from the American Recovery and Reinvestment Act of 2009 (Recovery Act) ends—it may be difficult to maintain the 20 percent success rate. Another priority is the commitment to keep funding for early stage investigators or new investigators on par with that for established investigators.

Dr. Insel noted that although scientific opportunities are tremendous at this time, many challenges are ahead that will involve careful stewardship of funds. Providing advice on making these difficult decisions is the role of Council, and Dr. Insel concluded by recognizing the contributions made by Council members, Elizabeth Childs, M.D., M.P.A., John March, M.D., M.P.H., and Enola Proctor, Ph.D., whose terms on Council are ending. Dr. Insel also acknowledged the contributions of Council member Dilip Jeste, M.D., who was unable to attend the Open Session, but whose tenure on Council is also ending. Dr. Insel then introduced NIH Director Dr. Francis Collins.

NIH Director's Report

Dr. Collins thanked Dr. Insel for his dedicated leadership of NIMH and his contributions to trans-NIH efforts. Dr. Collins noted that although NIH is facing difficult budgetary circumstances, current scientific opportunities are exceptionally exciting. He referred to an article published in Science last January, Opportunities for Research and NIH,which identified five promising areas for major scientific advances: high throughput technologies, translational medicine, benefiting health care reform, focusing more on global health, and reinvigorating and empowering the biomedical research community.

Before turning to specifics regarding promising areas of science, Dr. Collins described the recent court ruling that resulted in a preliminary injunction issued on August 23, 2010, blocking Federal funding for human embryonic stem cell research. Just as scientists are gaining momentum, the injunction threatens to stop the progress in one of the most encouraging areas of biomedical research. He stated that the injunction could cause irreparable damage and delay potential breakthroughs to improve care for people living with serious diseases and conditions. NIH is, he continued, hopeful that this will be resolved in the coming months.

Updated On NIH Supported Research Activities

P7C3
Dr. Collins noted that Steven McKnight, Ph.D., Professor and Chair of the University of Texas Southwestern Medical Center’s Biochemistry Department, recently published a paper in Cell that describes an unprecedented screen carried out on mice involving in vivo testing of 1,000 small molecules, in an effort to identify compounds that help newborn neurons grow into mature brain cells. Because P7C3 results appears to serve that function, this discovery has electrified the field of neuroscience and provided hope that this research may provide a path forward for neurodegenerative conditions, such as Alzheimer’s disease. P7C3 has some interesting pharmacological properties: it rapidly crosses the blood-brain barrier, is well tolerated by mice, and produces some amelioration of cognitive decline in rats. Interestingly, P7C3 is structurally similar to the antihistamine Dimebon that has been used in Russia for the treatment of Alzheimer's disease, although there has been controversy over its efficacy. The target of P7C3 is not yet known. This work was supported both by a Transformative R01 from NIMH and a Pioneer Award to Dr. McKnight.

Depression
Dr. Collins discussed NIMH’s efforts to identify faster-acting antidepressants and improved therapeutic agents, including exploring the promise and limitations of ketamine. An August 2010 article in Science by Ron Duman, Ph.D., and his team reported that a low dose of ketamine rapidly activates a synapse-producing enzyme (mTOR) that produces proteins forming the connections between neurons or synapses in the prefrontal cortex of rats. This research is important as it identified the key cellular signaling pathway by which ketamine works, and may stimulate future research on the brain pathway that would lead to the identification of new active agents for the treatment of depression.

Development of New Therapeutics
Dr. Collins indicated that there is an increased emphasis on the development of new therapeutics at NIH. He said that although many assume that investments in developing therapeutics generally come from the private sector (once one gets beyond the basic science observations), it is clear that, especially for neurological and psychiatric disorders, those investments may be diminishing. Biotechnology companies are facing difficult times with the lack of access to venture capital, yet at the same time a remarkable proliferation of discoveries is occurring—discoveries that are leading to new ideas about drug targets. The molecular basis for thousands of rare diseases is being uncovered, which might be interpreted as the discovery of new targets for those diseases, perhaps with implications for common illnesses as well. He commented that genome-wide association studies have led to almost 1,000 well-validated variants that are associated with common diseases.

Much of the proliferation of basic discoveries of new targets has been through work supported by NIH. With the question of how to move forward in the development of therapeutics, NIH has been investing in some of the pieces that would be necessary to empower academic researchers to play a more integral role in this effort, especially in turning a target discovery into an assay that could be used in high-throughput screening. With funding from the Common Fund, NIH now supports four high-throughput screening centers that collectively have the capacity of a mid-sized pharmaceutical company. Work at these centers has resulted in the discovery of more than 100 valuable research probes. Half of these probes may represent reasonable starting points for moving into the preclinical space. Dr. Collins commented that the Molecular Libraries Initiative has changed the landscape for many academic investigators by providing them with the infrastructure needed for developing compounding libraries, robotics technology and other resources. Many academic investigators, he noted, are excited about the possibility of blending their knowledge of biology and genetics with chemistry in an effort to discover the next generation of treatments for mental disorders.

The Therapeutics for Rare and Neglected Diseases Program (TRND) is a new congressionally mandated program that performs preclinical and early clinical development of new drugs for rare and neglected diseases that primarily affect individuals from developing countries. The program also develops new technologies and paradigms to improve the efficiency of therapeutic development. The operational model of TRND is collaboration between intramural NIH drug development scientists and partners in the public and private sectors who have promising leads and disease/target knowledge, but lack the expertise or resources to develop these projects into clinical stage programs attractive to pharmaceutical or other suitable organizations. Dr. Collins indicated that there is no intention for NIH to become a drug development company and compete with the private sector, but rather to ‘de-risk’ projects to make them more attractive for commercial investment.

Currently, TRND supports five pilot projects with the goal of bringing a compound to the point of a Food and Drug Agency (FDA) Investigational New Drug (IND) application and then moving this into Phase I, II, and III trials, and, ultimately, FDA review and approval. For projects that are not attractive to the commercial sector, NIH has the capacity to conduct Phase I and II trials at the NIH Clinical Center and at its clinical and translational science award centers around the country. In an effort to address the barriers to moving a novel compound through the regulatory process, the NIH-FDA Joint Leadership Council was established, under the leadership of Margaret Hamburg, M.D., Commissioner of Food and Drugs, and Dr. Collins, to help ensure that regulatory considerations form an integral component of biomedical research planning, and that the latest science is integrated into the regulatory review process. The effort will combine NIH's experience in supporting and facilitating new discoveries in the laboratory and clinic with FDA’s experience and knowledge in regulating and approving drugs, biologics, and medical devices.

Cures Acceleration Network
Dr. Collins said that health care reform has added another important dimension to NIH’s therapeutic development plan through the Cures Acceleration Network (CAN)—a bold program to increase NIH resources and flexibility to advance the development of treatments and cures. CAN will be overseen by the NIH Director in collaboration with a review board, which will be established to advise and provide recommendations to the NIH Director on policies, programs, and procedures for overcoming barriers to the successful translation of basic science into clinical application. The NIH Director is authorized to spend $500 million per year to promote innovation in technologies supporting advanced research and development and production of high-need cures, through the development of medical products and behavioral therapies. CAN provides flexibility for NIH to enlist project managers who would have considerable authority to move resources around rapidly to speed up a project that has identified a new opportunity or to end a project that is missing milestones. One of NIH’s high priorities is to move the deluge of basic scientific discoveries into developing therapeutics rapidly, thus reducing the traditionally long waiting periods for a new treatment to reach clinical practice.

NIH Budget
Dr. Collins presented a graph showing the NIH base appropriation since FY 1998 and noted the additional $10 billion added by Recovery Act funding ($5 billion per year for FY 2009 and 2010). The President’s budget for FY 2011includes an increase of $1 billion, which approximates inflationary costs as calculated by the Biomedical Research and Development Price Index; however, it results in a net decrease in NIH funding over the current level since Recovery Act funding will no longer be available. As Dr. Insel noted, the final FY 2011 budget has not yet been determined.

Dr. Collins presented historical information on the overall success rate across NIH (the percentage of reviewed grant applications that are funded). He said that with the flat budgets that followed the post-doubling era, the success rate declined to about 20 percent. He projected that for FY 2011, the success rate will likely decline even further given the anticipated increase in the number of submitted grant applications and the end of Recovery Act funding.

Dr. Collins said that this stress on the system will make it difficult for many grantees to continue their work and that this will require thoughtful leadership, making priority decisions, and supporting productive research to ensure that the most innovative agenda is being pursued. He said that the best case for advocating the value of medical research is to continue to push the agenda of innovation. This will help to promote the scientific discoveries that excite supporters, Congress, and the public and will also benefit the economy.

Discussion

Robert Desimone, Ph.D., asked how expectations would be managed regarding the accelerated cure process for promising therapeutics, considering statistics in the pharmaceutical industry about how many targets enter the development pipeline and move into preclinical and clinical trials.

Dr. Collins said that it is important to manage expectations and that a mix of projects at various stages will be reviewed. There may be, for rare diseases in particular, some projects that are fairly far along in the preclinical space. As part of this process, there is a chance to look at the pipeline itself in a new way—an opportunity for process engineering. That is, the CAN program presents an opportunity in a more open atmosphere to assess both what works and what does not work and to learn from that experience over time.

Dr. Shatz asked if NIH is working on ways to try to improve the probability of success for particular drug candidate as they move along the pipeline.

Dr. Collins said that drug development begins with choosing the right target and ensuring that it is relevant to humans. He noted that we are in a better position to do this now compared to five or six years ago, because many of the targets that are emerging are coming out of human genetics research. However, animal testing must be done, and going beyond mice to non-human primates immediately becomes very expensive—and often there is no good model of the disease to be treated. He noted that NIH wants to work with the FDA regarding the degree to which a very large amount of animal model data is needed before asking for a small Phase I trial, or even a Phase 0 trial.

Steven Paul, M.D., commented that there is a need to obtain sufficient safety data in animals to be able to go into humans thoughtfully and safely, and that biomarkers are incredibly important for getting an early read on whether an effort is going in the right direction mechanistically.

Rhonda Robinson Beale, M.D., noted that from the standpoint of the lay public, there are questions about practices at pharmaceutical companies as well as at the FDA. She asked if this partnership with the FDA and the proposed infrastructure might strengthen the public’s trust.

Dr. Collins responded that he would expect that the closer relationship will have such benefits and heighten the sensitivities of the agencies to each other’s positions. The FDA has limited resources to handle an incredible array of safety questions and clearly the agency has limited resources that preclude it from moving as quickly as it would like.
Dr. Collins commented that he is hopeful that NIH can work with the FDA in terms of providing the kind of scientific input needed to judge some of the more innovative clinical trial designs being reviewed for rare diseases, for combination therapies, and for circumstances in which a diagnostic and a therapeutic are being linked. In turn, the FDA can help NIH move into this therapeutic area more intentionally without making mistakes—such as not collecting the right data at the right time.

Partnerships with pharmaceutical companies are essential to developing the next generation of effective therapies, noted Dr. Collins. He emphasized that NIH has rigorous rules in place for intramural scientists, in terms of collaborations with pharmaceutical companies, to guard against conflict of interest, and similarly rigorous rules are forthcoming with regard to extramural scientists. With those rules in place and rigorously enforced, scientific relationships can be formed with pharmaceutical companies that are above reproach. Ultimately, he said, the research enterprise will be judged by whether it helps people by curing disease; however, it is important to recognize that it will take sufficient time to allow for that judgment.

Examining How We Work Together To Develop Therapies

Stephen Friend, M.D., Ph.D., CEO of Sage Bionetworks, said he would be talking about existing approaches and issues in drug discovery, including the cost and time it takes to bring a therapeutic to market and the low percentage of therapies in Phase I trials that make it through to approval. He commented that there is a real need to develop better disease maps and models of human disease, to examine how scientists work together and share data, and to discuss possible solutions, one of which involves the power of building a pre-competitive commons for evolving generative models of disease.

Dr. Friend reviewed how his experiences have informed his perspective and said that there is some denial about the currently poor representations of disease. Dr. Friend also emphasized that it is important to acknowledge how poorly many approved drugs are working. Many drugs that make billions of dollars in sales benefit only a small number of patients. An example is statins, which lower cholesterol in 40 percent of those who take them and of that 40 percent, only 40 percent experience a health benefit. He said that costs for developing a new medication are exceptionally high because of the high failure rates throughout the entire drug developmental process (e.g., 10 percent of therapies in Phase I trials will lead to approval).

Dr. Friend said that human disease is incredibly complex, that the biochemical maps being used to study disease are not sufficient. There is a lack of adequate molecular physiologic models. The data that are now coming out at the DNA level, the metabolite level, the protein level, and the transcript level are one-dimensional views of the story.

Dr. Friend reviewed a five-year Merck project that began in 2003, called the Rosetta Integrative Genomics Experiment, which involved the generation, assembly, and integration of data to build models that predict clinical outcome. At a cost of between $150-$200 million, the project was designed to generate data needed to build bionetworks; assemble other available data useful for building networks; integrate and build models; test predictions; develop treatments; and, design predictive markers. Genomic data are used to understand biology by taking standard DNA variation approaches—genome-wide association approaches—combined with profiling to use an integrated genetics approach. The approach provides an unbiased view of molecular physiology as it relates to disease phenotypes and insights into mechanisms, helps illuminate causal relationships, and allows for predictions.

Dr. Friend commented that rather than the bottom-up classic systems biology, this approach is top-down network biology driven, and there are about five or ten groups around the world that are becoming leaders in this area. He discussed the work of five large modeling groups that will share all of their data, models, and tools in an effort to use bionetwork-based data-rich approaches. He said that humans are the best model organism and that money should be put into this effort now that there is the ability to generate the data. This effort will require massive resources and many decades to achieve.

He reviewed the work of Sage Bionetworks, a nonprofit foundation with a vision to create a commons where integrative bionetworks are evolved by contributor scientists with a shared vision to accelerate the elimination of human disease. Sage is based at the Fred Hutchinson Cancer Research Center, with a hub in China, and currently has $25-$30 million in funding from a number of sources, including the government, foundations, and pharmaceutical companies. One year after the completion of a project, all data will go into the public domain. Dr. Friend provided examples of Sage’s work in Alzheimer's disease, Huntington’s disease, and schizophrenia. He also reviewed a project Sage was involved in with the Genetic Alliance.

Dr. Friend focused on the importance of sharing data, noting that even when clinical trial data are published, they often are not publicly accessible; not generated in a way that allows sharing; and are in silos (i.e., not integrated). He contrasted this with the open access system used by physicists and the work of the Structural Genomics Consortium, which in 5 and a half years has published 50 percent of all the crystal structures that are in the public domain with no intellectual property (IP) rights associated with them.

He also emphasized that the existing reward structure with its institutional rules is not in the best interest of getting patients the therapies they need, and noted that the entire reward system needs to be examined, including publication, because it is not in the interest of publishers to have an open access system. Common standards for clinical data are needed that will take privacy and IP issues into consideration.

The real puzzle that scientists need to explore, he said, is how to move from patient data and samples to therapies. In addition, work is needed on how to ensure recognition, not just for those who publish, but also for those who build models. Dr. Friend noted that the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Hughes Foundation have been helping Sage determine how to work with international data, sharing across borders.

Discussion

Daniel Geschwind, M.D., Ph.D., talked about some of the differences between biology and the physical sciences. He commented that biology is not a mature science in some ways, because of the lack of fundamental laws (other than evolution). He commented that some of the greatest discoveries in physics over the last 200 years have consisted of analyses of other people’s experiments, but that this is not the culture of neuroscience research. Journals often do not consider analyses worthy of publication—only experiments. He stressed that the field of neuroscience has to reconsider issues surrounding the ownership of data, address the lack of appreciation of the importance of data analysis, and promote the assembly of large datasets. It is important, Dr. Geschwind emphasized, to get to the point where scientists determine how to differentiate good data from bad and begin to trust data and use them appropriately.

Dr. Shatz agreed with the importance of and need for data to be made more accessible. She commented that more focus may be needed on the effect of the environment. She commented that there is the notion that environmental influences can perturb datasets and alter them in ways that make it difficult to determine which one should be used.

Dr. Friend responded by noting that the effect of the environment may be more important than genetics, and he wondered what technologies are available to capture this effect. He also said that many times when experiments do not replicate a particular result, it is because the context or environment has changed. Thus, taking into account the real complexity involved goes beyond genetics and into the complexities of the environment.

Dr. March commented that academic partnerships need to go beyond Phase IIa trials because currently, the clinical team takes a good idea that has come out of fundamental biology and sends it to an outsourcing group, which then sends it to a clinical research organization. By that point, the clinical trial is long divorced from the academic setting in which the experiment began.

Dr. Geschwind commented that dealing with model organisms, network biology and other approaches can help in gaining an understanding of why animal models fail sometimes and what the appropriate animal models would be for certain diseases.

Dr. Robinson Beale commented on the barriers that exist regarding the intermingling of private datasets, including health care datasets.

NINDS Common Data Elements—Streamlining Clinical Research

Dr. Insel introduced Petra Kaufmann, M.D., M.Sc., Director of the Office of Clinical Research at the National Institute of Neurological Diseases and Stroke (NINDS), noting that she has been instrumental in the Institute’s effort to streamline clinical trials and data collection.

Dr. Kaufmann commented on the pragmatic approach NINDS has initiated through the Common Data Elements (CDE) project, which was designed to facilitate the highest quality research and streamline data collection. She said that generating clinical research datasets requires significant time and resources, and that investigators know that it can take 5 to 10 years to conduct a clinical trial or epidemiological study. Moreover, Dr. Kaufmann noted the importance of always being mindful of the time and burden on patients to participate in clinical trials. The resulting datasets are very valuable and create important scientific opportunities that can accelerate research. She said that NINDS wants to help realize the full value of these datasets and make them rapidly accessible and useful to a broader community.

Dr. Kaufmann discussed the importance of meta-analyses and of combining data across studies to advance science. She noted that in this era of health care reform with a focus on personalized medicine, subgroup analyses are a critical tool for determining if an intervention was useful to smaller subsets of individuals. Clinical trials must be set up with a consideration of how the data will be collected to ensure that sufficient information will be available for later subgroup analyses. These analyses may provide answers to questions that single studies may not be powered to address and thus help to maximize these valuable clinical trial datasets.

There are many challenges to the conduct of clinical trials, including a lack of widely used data standards in clinical research. Creating data collection instruments for each new project slows progress overall; conducting a meta-analysis across studies then requires extensive data reformatting; and a multitude of data formats creates barriers to data sharing. Often insufficient information and data are collected to make it possible to combine certain variables.

The CDE initiative is a pragmatic way to address the barriers to data sharing and thus increase the efficiency of the research enterprise by: (1) reducing start-up time and the cost of developing data collection tools; (2) avoiding the situation where different groups of investigators spend scarce research funding on similar databases that are being created over and over again for each new project; and, (3) helping new investigators get started by allowing them to use this free resource and pull down data collection instruments and definitions that were developed through expert consensus. The same benefits would be available for investigators in developing countries who also would have access to this free resource and immediately be more connected to the rest of the research community. Other goals are to improve data quality by promoting data collection in a consistent manner and to facilitate international research efforts involving rare diseases.

The CDE web site serves as a repository and dissemination tool for investigators to utilize in both planning trials and ongoing research. The web site provides access to common data elements used in clinical research and presents them in a standard format. It also allows access to common data definitions; standardizing case report forms and other instruments; and, information regarding database development, all in an effort to grant researchers easy access to information that is designed to streamline and enhance their research activities.

There are barriers to data sharing, especially when many clinicians and investigators have collected unique data suited for their individual study. To address this barrier, a process is used that involves experts in the scientific community identifying, vetting, and developing common data elements. NINDS provides continuous review, oversight, and updates but has a hands-off approach in development. The initiative seeks to find common ground by identifying data elements that transcend studies and disease areas and are found in most if not all studies. These are referred to as general common data elements (general CDEs) and include demographics, adverse event reporting, and medical history, which can be accomplished in a harmonized and uniform manner. The Institute also looks to see if there is common ground across trials and to identify common data elements used in NIH studies as well as those in the greater clinical research community.

Dr. Kaufmann presented a slide with a diagram that showed how the common data elements for a disease can be classified, represented as concentric circles. At the core or in the center were general CDEs: those that would be relevant across clinical neuroscience research. The next layer included CDEs that should be collected for a given disease and that were considered by the experts to be core elements. The next layer included supplemental disease-specific elements that are common to a specific disease area but that are not required. The outer layer indicated exploratory disease-specific data elements that represent novel outcomes that are not yet validated or that are under development. Dr. Kaufman said that the center of the graphic included a biorepository at the Coriell Institute for Medical Research, where specimens from the trials are often placed or submitted. The biorepository data are linked with the phenotypic or clinical data.

Next steps, Dr. Kaufmann said, include expanding to additional diseases, testing and improving CDEs, disseminating CDEs and encouraging their use, and developing and implementing a proactive data sharing process. The vision is that future NINDS-funded trials, as well as neuroscience clinical trials in general, will use these CDEs or be CDE-compatible, and that observational clinical studies would be linked more easily to trial datasets. The goal also is to enable new investigators to build on consensus data elements and to facilitate start-up for multicenter and international clinical research efforts. The overall hope is that clinical research progress will be accelerated through data harmonization and easier data access.

Discussion

Dr. March commented that the design and operational implementation of explanatory trials and pragmatic trials, or trials that look at mechanisms versus those that will test moderator variables that stratify patients in subgroups, are different; thus, having common data elements or core datasets or processes would require having to scale across this explanatory pragmatic dimension. He also said that new instruments are needed in neuroscience.

Dr. Kaufmann said that NINDS started by focusing on clinical trials but want to expand to facilitate more pragmatic trials. She also noted that this initiative is not about developing better outcome measures per se, but is meant to stimulate the process.

Dr. Bell commented that he appreciated this systemic and thoughtful effort to move away from “boutique science.”

Roberto Lewis-Fernandez, M.D. commented on the multiple difficulties of measurement that plague psychometrics, including the problem that people answer scales completely differently.

Dr. Kaufmann agreed that the situation is complex and does not solve all problems, and that even within one population, there will be psychometric differences across groups.

Comments From Retiring Council Members

Dr. Insel again acknowledged the contributions of Council members whose tenure ends on October 1, 2010: Elizabeth Childs, M.D., M.P.A., John March, M.D., M.P.H., and Enola Proctor, Ph.D. Dr. Insel invited the departing members to address the Council.

Dr. Childs said that it has been an honor to serve on the Council and thanked members for their best collective thinking on behalf of adults and children afflicted with mental illness and emotional disturbance. She offered three clinical and public policy observations. First, prevention is a prominent and critical piece of health care reform. However, prevention must be balanced with treatment; individuals who fall through the prevention net should not be further stigmatized as untreatable. Advances in treatment are necessary and critical to eradicate mental illness successfully, and NIMH is well-positioned to prioritize the development of more effective treatments for mental illness. Dr. Childs urged a continued focus on this course. Second, individuals with mental illness die younger of preventable and treatable cardiac, pulmonary, and cancer illnesses and suicide, and this health care disparity must be addressed, with a focus on the engagement of these individuals regarding treatment options and on provider education. Third, mental illnesses are exceedingly complex, with long courses and deterioration of functioning in all domains of life when left inadequately treated. The provider community, including clinicians and health care systems, has failed to develop effective, complex disease management models, not because of a lack of effort but because it is difficult to implement integrated care models in the context of this great complexity. It is easy to talk about collaboration, but as soon as implementation begins, the efforts to retain existing enterprises, perspectives, and positions result in limited integration.

Synthesis of this highly complex information and data is critical to the integration of clinical services and treatment, and help is needed from every part of the collective mental health community to solve this problem. Traditional models of primary care do not work for many with mental illness, and medical approaches must look different for these individuals with this level of complexity. Synthesis of large amounts of complex information is best done by sophisticated clinicians who know what they do not know and who seek genuine collaboration in these efforts.

Dr. Childs noted that individuals with mental illness and substance abuse disorders make up the largest group of the Medicaid expansion population in the health care reform. Thus, she said, it is important to get this right, not only for their well-being but also to maximize the overall social benefit of this expanded funding. NIMH does understand how complex and serious these illnesses are, and this clarity is essential in attempting to develop the better service models that patients desperately need and to train sophisticated clinicians to do this work.

Dr. March said that during his time on the Council there have been two important pivots that grew out of the investment in fundamental neurobiology (the decade of the brain). The first was the turn toward developmental neuroscience, and Dr. March commented on the privilege of participating in the workgroup report that helped NIMH turn toward this world of developmental neuroscience. The second area is the movement toward early-phase clinical pharmacology to take advantage of the investment in discovery and translational neuroscience.

It will be important, he said, for NIMH to develop a spectrum of research that extends from Phase I to Phase IV or explanatory trials out to pragmatic trials. Furthermore, although it is appropriate to focus at this point on the earlier phases, down the road it will be important to conduct Phase III trials and then effectiveness trials that will help further an understanding of whether these treatments are working in practice settings with real doctors and real patients. For this to happen, it would be helpful for the Institute to think about developing the structures, such as networks, that are needed to nurture successive generations of clinical trialists who can work in the various phases of intervention development. It also is important to think about how the Institute will nurture successive generations of clinical trialists.

Dr. March concluded by commenting that although it has been difficult making all these transitions and pivots, NIMH today is a much more vibrant place than it was five years ago.

Dr. Proctor said that she has learned much about the breadth and scope of NIMH’s research and commented that the Council is a remarkable group, conducting path-breaking science and delivering state-of-the-art services and passionate advocacy for people who suffer from mental illness. Dr. Proctor commented that most people with mental illness do not receive any services and that those who do often receive sub-standardized service. Furthermore, not only does it take 10 to 17 years to roll out a new treatment, but the system itself is a patchwork of fragmented, loosely collected services; it is a maze that people must navigate when they are desperate and do not know where else to turn. This system of care is filled with providers who want to do the right thing and who wait for discoveries to produce better cures; however, clinics struggle to realign and reconfigure their services to take advantage of the new treatments and discoveries that the researchers bring forth. Dr. Proctor said she hopes NIMH will be a leader in providing the critical information for closing this quality gap.

Dr. Proctor said that in addition to working for discoveries for tomorrow’s treatments, she hopes there will be discoveries regarding how to break through the barriers of providing good care, and discoveries in the science of service delivery. Scientific study is needed on how to change provider behavior, how to create and tailor health promotion messages and communication, how to eliminate stigma, how to help providers change outmoded ways of treating patients and embrace and deliver new discoveries, and how to reengineer the system of care. Only about 1 percent to 2 percent of Federal research dollars are dedicated to implementation science, she noted, but this science is essential to realize a return on the investment in basic and clinical, efficacy, and effectiveness research.

Research is needed to discover and rigorously test implementation strategies. Currently, most implementation work is dominated by treatment developers who create architectures to support the dissemination and implementation of a single treatment at a time. But the reality is that we have to manage, knit together, and seamlessly integrate many new discoveries to reap the benefits of this science. Dr. Proctor also said she hopes there will be support for science on the economics of implementation. She said there is a lack of a common language in this field, including the lack of a nomenclature for the outcomes of implementation. She urged the use of available tools, and said that it is important to begin to examine how to overcome the implementation gap in public settings of care where the need is the greatest. She said she thought it would be impossible for NIMH to realize Strategic Objective 4 without this kind of science.

A New Approach To Psychiatric Classification—The NIMH Research Domain

Dr. Insel said that increasingly, the clinical research community is asking for more thought about pathophysiology and the way that the nosology was built to describe psychopathology. The way forms of psychopathology are being classified, whether through International Classification of Diseases (ICD) or Diagnostic and Statistical Manual (DSM), is not working well in the research setting. Thus, NIMH has decided to go forward with the Research Domain Criteria Project (RDoC), and Bruce Cuthbert, Ph.D., Director of the NIMH Division of Adult Translational Research and Treatment Development, has taken the lead. Dr. Insel said he thought it would become an increasingly important part of what NIMH does over the next few years, and he introduced Dr. Cuthbert.

Dr. Cuthbert began by reviewing some of what has been learned during the “decade of the brain,” regarding what the brain does and how it does it. In genetics and behavioral neuroscience, he commented, much has been learned about what functions the brain carries out and how the brain implements these functions. However, much of what has been learned is not reflected in psychiatric nosology. Unfortunately, he continued, the disorders were defined long before this knowledge of the brain came into being; thus, these disorders were defined by clusters of signs and symptoms—essentially clinical phenomenology—and not by primary aspects of behavior or brain functioning.

It is now known that there can be many different brain mechanisms involved in one disorder; it also is known that a single mechanism can be involved in many different disorders. For example, anterior cingulate and other regulatory circuits that regulate impulsivity or disinhibition are related variously to ADHD, conduct disorder, antisocial behavior, and substance abuse, and the fear circuit is relevant to virtually all of the anxiety disorders.

Another problem with the current system is that as categories are over-specified in an effort to make increasingly tight diagnoses, the inclusion criteria become ever more restrictive, which results in an increase in the categories of “not otherwise specified,” or NOS diagnoses. In some areas, such as eating disorders, this is in fact the most common diagnosis. This represents a public health problem; a large number of people are excluded from clinical trials because usually such trials are conducted only on well-specified disorders such as MDD and post-traumatic stress disorder (PTSD). The result is that it becomes difficult to relate diagnoses to genes, particular brain circuits, or basic behavioral mechanisms.

Dr. Cuthbert reviewed the composition of the RDoC workgroup and said that there are three differentiating principles that set the RDoC apart: it is a dimensional approach, involving the translation of basic functional dimensions; it uses different units of analysis that can be independent variables; and, it is agnostic to current DSM/ICD categories. It is not intended to be a competitor to the DSM or the ICD; that is, the project is not aiming to cover all the disorders that are listed in the DSM or the ICD. Furthermore, RDoC is not intended to be used for clinical diagnosis at this time. Rather, it is a research framework to lay out what is known about these mechanisms.

Dr. Cuthbert reviewed the RDoC Draft Research Domain Criteria Matrix, noting that workshops will be held to consider each domain and then fill in each of the matrix cells with state-of-the-art elements. The main point is to ascertain samples in a very different way than is done now. Major changes are anticipated in the composition of patient groups, consistent with the statement of the goal. The idea is to give the investigators flexibility in pursuing their understanding of these mechanisms by being much less stringent in the exclusion criteria and by maintaining a focus on overt psychopathology, while including subjects along the full range of the dimension under study.

Dr. Cuthbert noted that developmental aspects are extremely important and this could be thought of as a third dimension in the matrix. And, in fact, many of the listings of our constructs emerge from developmental temperament studies. Similarly, the environmental effects of these large constructs could be thought of as the fourth dimension in the matrix. This is critical regarding how the organism develops and for the development of risks in both children and adults for different kinds of anxiety, post-traumatic stress disorders and depression.

Dr. Cuthbert explained that a Request for Information (RFI, a formal solicitation for comments from the field) is soon to be released. The RFI will be posted in the NIH Guide for Grants and Contracts and will allow investigators to comment on the matrix.

Following the RFI, a workshop will be held for each of the five domains to clarify each domain and its constructs and to identify particular targets and systems. Each workshop will be preceded by a survey sent to a large number of relevant researchers in the field, asking them for their comments about the domain and the particular constructs listed. This will be followed by continuing commentary on the Web; online criterion specification for each domain and construct; and work to define a mechanism and criteria for changes to the domain specifications. The major elements of the project will be completed within two years.

Dr. Cuthbert commented that this is a translational approach that will link basic mechanisms and psychopathology. RDoC aims to create a framework to study mechanisms and circuits that cut across traditional disorders by classifying on the basis of these mechanisms. The goal is to develop a much deeper understanding of these mechanisms as they cut across disorders, which will help in the development of new treatment targets.

Discussion
Dr. Robinson Beale said that clinicians will applaud this project. She also noted that although environmental factors are mentioned, it is not clear how those factors fit into the domains.

Dr. Cuthbert responded that any given study might look at the effects of a particular environmental influence on a circuit or on a behavior. For example, one might look at the events of early life stress on hypothalamic-pituitary-adrenal axis activity. Researchers can specify the kind of environmental effect that they want to examine as a part of neuroresearch design. In that sense, it would not be much different from what is done now, but the patients would be classified in a different way. In other words, rather than using a DSM or ICD diagnosis, the patient would be classified on the basis of some dimension that is of particular interest.

Dr. Robinson Beale asked how they will test this construct to see if it is correct.

Dr. Cuthbert said that construct validation has been considered, and that part of what is done is to assemble sets of measures that adequately describe the construct. All of the measures that address the construct of interest should converge (i.e., convergence validity). On the other hand, it is understood that perfect correspondence is not expected. He explained some of the complexities involved in construct validation.

Dr. Robinson Beale asked if they are incorporating into this construct an individual’s response to treatment, as a way of building the validity of this approach.

Dr. Cuthbert said that this could be consistent with an etiological approach that involves studying more about the mechanism or trying to understand how it relates to other measures better. For example, in developing new drug treatments for cognition and serious mental illness, patients with working memory dysfunction might be selected, rather than patients with schizophrenia. Schizophrenia is a heterogeneous disorder, and not all patients show massive deficits in working memory and other cognitive functions. The hope is to get a better effect size by selecting patients on the basis of their initial deficits in working memory, and not by whether they had schizophrenia, but it might be necessary to include some patients who may have another diagnosis.

Dr. Insel clarified that the uptake of RDoC ultimately will depend on what its implications are for treatment. Because many of the behavioral and pharmacological treatments are targeting specific brain systems, perhaps this approach will result in improved predictive value.

Dr. Paul commented that this is a real advance and that he appreciated the dimensional approach as opposed to the categorical approach. He advocated caution in developing this approach because a lot is unknown, for example, in the matrix Dr. Cuthbert provided, in terms of specifying genes, cells, and circuits. The approach could be conceived as a roadmap to indicate what NIMH should be doing over the next few years to fill in the current gaps in our understanding of the disorders.

Dr. Insel commented that the term “framework” has been used because it is a framework for the future, which is why Dr. Cuthbert is providing 5- to 10-year timelines; the entire matrix may never be filled in. But this approach helps to define what should be funded, with the idea that if those major dependent and independent variables can be identified—which are not simply coming out of ICD or DSM—it would change how mental health research is approached.

Dr. March said that this is a wonderful initiative that is, in some ways, long overdue. He noted the importance of educating review committee members about this process and asked if it would be possible to begin these diagnosis-independent projects soon, rather than waiting another five to seven years.

Dr. Cuthbert said that they are hoping to put out a notice for the community in general to indicate that this is the direction in which efforts are moving, and he hopes that this notice may help ease the review process. When funding opportunities are initiated, the early rounds of applications will be reviewed by NIMH special emphasis panels, which should begin to change the zeitgeist and help inform the Center for Scientific Review about the new approach.

Thomas McGlashan, M.D., asked what kind of cross talk, if any, will occur with DSM-V.

Dr. Cuthbert responded by saying that the RDoC team has maintained productive relationships with DSM staff, including working with them on the DSM-V revision process, and these relationships also have been established with the ICD staff as they work on the revision of ICD-11.

Dr. Proctor asked how they are thinking about functional impairment in this system.

Dr. Cuthbert explained how functional impairment would be measured, referring back to the relevant parts of the matrix shown earlier, to include behavior, self-, and clinical reports. There is more of a focus on how to relate the dimensions of performance in the laboratory to dimensions of functioning in the real world.

Dr. Childs commented that even though this initiative is set in a research context at this time, it is not at all contradictory to the complexity involved in thinking as a clinician, which involves considering the different symptoms a patient has that do not fall into the categories used in current diagnostic classification systems. The approach also allows more flexibility on the clinician’s part and avoids certain problems that are involved in using diagnostic categories. In addition, this complementary approach encourages paying attention to the nuances and addressing them individually.

David Amaral, Ph.D., said that he wanted to get more of a sense of the long-term vision, and he wondered how this project will change the world of research, particularly translational research, five to ten years from now. He commented that it is estimated that anywhere from 30 percent to 85 percent of people with autism also have anxiety disorders, but it is not clear what the motivation will be to evaluate anxiety in autism. Will it be to understand more about autism, with the research therefore focusing on dimensions of anxiety disorder within the context of autism? Or, will it be to look at anxiety disorders, with a sample that includes individuals who have autism and others who have anxiety without autism?

Dr. Cuthbert discussed the importance of sample heterogeneity, for example, in studying the fear circuit and anxiety disorders. But if a sample becomes so broad that it includes people with, for example, schizophrenia, substance abuse, or autism, it could become too heterogeneous. On the other hand, the approach taken is often too homogeneous with regard to the sample.

Dr. Insel commented that the current problem is that not enough is known to provide a definition of some disorders, except in a very global way. For example, the term “autism spectrum disorders” is nonspecific and may include a large number of different disorders. He noted that this new project will help in trying to find a way to provide categories of function that have more specificity.

Dr. Amaral said that ultimately many of the terms that that have been in use may go by the wayside. But autism spectrum disorders have some unifying characteristics that make them different from other psychiatric and mental health disabilities. He commented that it is difficult to envision what the result may be, and it is possible that this approach would result in an enormous number of different disorders because each would have different genetic risk factors, different anatomical patterns, and different temperamental patterns.

Dr. Insel commented that there are precedents for this approach in medicine, particularly in cancer. He noted said that Council will continue to discuss this project at future meetings and that by the time of the next meeting, RDoC version 1.1 may be available and include many changes. He said that Council members will continue to be part of discussions about the project and ways to refine it.

Public Comment

Dr. Insel welcomed members of the public to address the Council. No comments were voiced. With that Dr. Insel reminded all that the next meeting is scheduled for January 13-14, 2011.

Adjournment

Dr. Insel adjourned the meeting at approximately 12:45 p.m.

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

Summary of Primary MH Applications Reviewed September 2010

Category IRG Recommendation
  Scored # Scored Direct Cost $ Not Scored (NRFC)# Not Scored (NRFC) Direct Cost $ Other # Other Direct Cost $ Total # Total Direct Cost $
Research 599 $589,295,924.00 478 $499,298,714.00 6 $1,435,945.00 1083 $1,090,030,583.00
Research Training 0 $0.00 0 $0.00 0 $0.00 0 $0.00
Career 70 $49,621,202.00 17 $11,208,069.00 0 $0.00 87 $60,829,271.00
Other 0 $0.00 0 $0.00 0 $0.00 0 $0.00
Totals 669 $638,917,126.00 495 $510,506,783.00 6 $1,435,945.00 1170 $1,150,859,854.00

Appendix B
National Institutes of Health
National Institutes of Mental Health
National Advisory Mental Health Coucil

(Terms end 9/30 of designated year)

Chairperson Executive Secretary
Thomas R. Insel, M.D.
Director
National Institute of Mental Health
Bethesda, MD
Jane A. Steinberg, Ph.D.
Director
Division of Extramural Activities
National Institute of Mental Health
Bethesda, MD
Members

David G. Amaral, Ph.D. (12)
Professor
Department of Psychiatry
The M.I.N.D. Institute
University of California, Davis
Sacramento, CA

Carl C. Bell, M.D. (11)
President and CEO
Community Mental Health Council and Foundation, Inc.
Chicago, IL

Elizabeth Childs, M.D., M.P.A. (10)
Private Practice
Brookline, MA

Robert Desimone, Ph.D. (11)
Director, McGovern Institute for Brain Research
Massachusetts Institute of Technology
Cambridge, MA

Ralph J. DiClemente, Ph.D. (12)
Candler Professor
Department of Behavioral Sciences and
Health Education
Rollins School of Public Health
Emory University
Atlanta, GA

Howard B. Eichenbaum, Ph.D. (12)
Professor and Director
Center for Memory and Brain
Department of Psychology
Boston University
Boston, MA

Daniel H. Geschwind, M.D., Ph.D. (11)
Gordon & Virginia MacDonald
Distinguished Chair in Human Genetics
Professor of Neurology & Psychiatry
University of California, Los Angeles
Los Angeles, CA

Portia E. Iversen (12)
Co-Founder
Cure Autism Now Foundation and
Autism Genetic Resource Exchange
Los Angeles, CA

Kay Redfield Jamison, Ph.D. (13)
Professor
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University School of Medicine
Baltimore, MD

Dilip V. Jeste, M.D. (10)
Estelle and Edgar Levi Chair in Aging
Distinguished Professor of Psychiatry and
Neuroscience
Stein Institute for Research on Aging
University of California, San Diego
La Jolla, CA

David A. Lewis, M.D. (11)
Director, Translational Neuroscience Program
University of Pittsburgh
Pittsburgh, PA

Roberto Lewis-Fernandez, M.D. (13)
Director, Hispanic Treatment Program
New York State Psychiatric Institute
Associate Professor of Clinical Psychiatry
Columbia University
New York, NY

John S. March, M.D., M.P.H. (10)
Professor of Psychiatry and Behavioral Sciences
Director, Division of Neurosciences Medicine
Duke Clinical Research Institute
Duke University Medical Center
Durham, NC

Thomas H. McGlashan, M.D. (12)
Professor
Department of Psychiatry
Yale University School of Medicine
New Haven, CT

Steven M. Paul, M.D. (12)
Executive Vice President
Science and Technology
President, Lilly Research Laboratories
Eli Lilly and Company
Indianapolis, IN

Enola K. Proctor, Ph.D. (10)
Frank J. Bruno Professor of Social Work Research
Washington University in St. Louis
St. Louis, MO

Rhonda Robinson Beale, M.D. (13)
Chief Medical Officer
Optum-Health Behavioral Solutions
Glendale, CA

Carl Shatz, Ph.D. (Adhoc)
Director, Bio-X
Professor of Biology and Neurobiology
James H. Clark Center
Stanford, CA

Ex Officio Members

Office of the Secretary, DHHS
Kathleen Sebelius
Secretary
Department of Health and Human Services
Washington, DC

National Institutes of Health
Francis Collins, M.D., Ph.D.
Director
National Institutes of Health
Bethesda, MD

Veterans Affairs
Ira Katz, M.D., Ph.D.
Department of Veterans Affairs
Office of Mental Health Services
Washington DC

Department of Defense
John A. Ralph, Ph.D.
Commander, U.S. Navy
National Naval Medical Center
Bethesda, MD

Liaison Representative

A. Kathryn Power, M.Ed.
Director, Center for Mental Health Services
Rockville, MD