NAMHC Minutes of the 244th Meeting

February 4, 2016

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 244th meeting in open policy session at 8:00 a.m. on February 4, 2016 at the Neuroscience Center in Rockville, Maryland, to review the report from the Board of Scientific Counselors, the group that provides scientific oversight for the NIMH Division of Intramural Research Programs (IRP). This portion of the meeting recessed at approximately 9:00 a.m. The NAMHC then reconvened in open session at 9:15 a.m. and adjourned at approximately 1:00 p.m. In accordance with Public Law 92-463, the policy session was open to the public. The NAMHC reconvened for a closed session to review grant applications at 2:00 p.m. on February 4, 2016, at the Neuroscience Center in Rockville, Maryland, until adjournment at approximately 5:00 p.m. Bruce Cuthbert, Ph.D., Acting Director, National Institute of Mental Health (NIMH) presided.

Council Members Present at the Grant Review and/or Open Sessions

(See Appendix B: Council Roster)

Chairperson

• Bruce Cuthbert, M.D.

Executive Secretary

• Jean Noronha, Ph.D.

Council Members

• Patricia Areán, Ph.D.
• Deanna M. Barch, Ph.D.
• David A. Brent, M.D.
• Benjamin G. Druss, M.D., M.P.H.
• Hakon Heimer, M.S.
• Michael F. Hogan, Ph.D.
• Richard L. Huganir, Ph.D.
• Marsha M. Linehan, Ph.D. (via telephone)
• Maria A. Oquendo, M.D.
• Gene E. Robinson, Ph.D.
• Mary Jane Rotheram, Ph.D.
• J. David Sweatt, Ph.D.
• Hyong Un, M.D.

Ad Hoc Consultants

• Rhonda Robinson Beale, M.D.
• John Krystal, M.D.
• Christopher A. Walsh, M.D.

Ex Officio Members

• John W. Davison, M.B.A., Ph.D. Department of Defense
• Theresa Gleason, Ph.D., Department of Veterans Affairs

Liaison Representative

• Paolo del Vecchio, M.S.W., Center for Mental Health Services, Substance Abuse and Mental Health Services Administration (SAMSHA)

Others Present at the Open Policy Session

• Annie Allen, Transcriber
• Pritty Dwivedy, Cure Alliance, GMU Chapter
• Florence Fee, No Health without Mental Health (NHMH)
• Craig Fisher, American Psychological Association
• Samanza Hussain, Cure Alliance, GMU Chapter
• Dytrea Langon, Synergy Enterprises, Inc.
• Joyal Mulheron, Evermore
• Ami Murray, Sign Language Interpreter
• Laura Sherman, SAMHSA
• Andrew Sperling, National Alliance on Mental Illness
• Taylor Swankie, RTI International
• Lori Whitten, Science Writer
• TaRaena Yate, Synergy Enterprises

Open Policy Session Call to Order and Opening Remarks

NIMH Acting Director Bruce Cuthbert, Ph.D., called the open policy session to order and welcomed all in attendance. He noted that the meeting was unique, because members of NIMH’s Board of Scientific Counselors were in attendance. Dr. Cuthbert welcomed members of the public attending via videocast. Each member of the Council and Board of Scientific Counselors briefly introduced themselves and described their backgrounds.

Approval of Minutes of the Previous Council Meeting

Turning to the minutes of the September 2015 Council meeting, Dr. Cuthbert asked whether Council members had any comments, revisions, or questions. Receiving none, the Council unanimously passed the motion to approve the minutes.

NIMH Director’s Report

Dr. Cuthbert reviewed the agenda for the open policy session and provided an update on activities related to NIMH.

The NIH fiscal year (FY) 2016 budget is $32.3 billion, which represents an increase of more than $2 billion from FY 2015. The FY 2016 budget for NIH includes funding for special initiatives, such as the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative , Alzheimer’s research, and the Precision Medicine Initiative . Dr. Cuthbert noted that the President’s Budget for FY 2017 is expected to be released on February 9, 2016. The FY 2017 budget may influence how institutes allocate their FY 2016 funds.

NIH has developed overarching AIDS research priorities indicating high-priority areas of study for the next 3 to 5 years. Those priorities include reducing the incidence of AIDS (including through the use of vaccines), developing the next generation of HIV therapies with better safety and ease of use, supporting research toward a cure, and decreasing HIV-associated comorbidities and co-infections. The United Nations and other organizations have set the 90-90-90 AIDS target for 2020—that is, 90 percent of people living with HIV will know their HIV status, 90 percent of those with diagnosed HIV will receive sustained anti-retroviral therapy (ART), and 90 percent of those receiving ART will exhibit viral suppression.

Taking into account new NIH AIDS Research Priorities and Guidelines , which align with the 90-90-90 AIDS target, NIH conducted an AIDS portfolio review in the fall of 2015. Dr. Cuthbert briefly described the scope and results of the AIDS portfolio review. The overall conclusion of the review was that there was a high concordance in priority ratings between the NIH Office of AIDS Research and Institute and Center staff members, so the process can differentiate the relevance of research projects.

NIH will continue to review its AIDS research over the next 3 to 4 years to further align its program with new, overarching priorities. This will include a more comprehensive review of the intramural program. NIH will also consider revising its priorities in FY 2017 and beyond to reflect emerging scientific opportunities, the changing dynamics of the epidemic, and the most recent scientific advances. NIH will clearly communicate its research priorities and portfolio review processes to the scientific community, research advocates, and other stakeholders. Dr. Cuthbert commented that this last point is critical, as investigators need to be able to shift in response to the new priorities. He added that the NIMH Division of AIDS Research, led by Dianne Rausch, Ph.D., has a very active research portfolio.

The BRAIN Initiative emphasizes tool development, circuits and networks, and measurement of fluctuating electrical and chemical patterns within circuits. The BRAIN Initiative’s FY 2016 budget is $150 million, an $85 million increase from FY 2015. The year 2017 will be a churn year for the BRAIN Initiative—that is, funding for FY 2014 projects will expire, and the money will go back into the competitive pool for new projects. Dr. Cuthbert remarked that the BRAIN Initiative is a massive undertaking, with many NIH staff members at multiple Institutes and Centers working on it in addition to their usual job responsibilities.

Turning to NIMH news, Dr. Cuthbert noted that the search for a new NIMH Director closes February 8. Walter Koroshetz, M.D., Director of the National Institute of Neurological Disorders and Stroke, and Nora Volkow, M.D., Director of the National Institute on Drug Abuse, are leading the search committee. There is a desire to name a new NIMH Director prior to the 2016 election.

Some NIMH staff members have transitioned to new positions. Shelli Avenevoli, Ph.D., is serving as Acting Deputy Director. Sarah Morris, Ph.D., is serving as Acting Head of the Research Domain Criteria (RDoC) Unit as well as the Acting Head of the Division of Translational Research Adult Psychopathology Branch. Tracy Waldeck, Ph.D., serves as Acting Deputy Director of the Division of Extramural Activities. Joel Sherrill, Ph.D., is now Deputy Director of Services and Intervention Research. Dr. Cuthbert thanked Kevin Quinn, Ph.D., for many years of service and wished him all the best in retirement which is planned for the end of March 2016.

Council Workgroup Updates

The Opportunities and Challenges of Developing Information Technologies on Behavioral and Social Science Clinical Research Workgroup of the NAMHC was formed to review the opportunities and challenges of using new information technologies to study human behaviors relevant to the NIMH mission. The Workgroup will address the following questions:

• What technologies need to be developed to understand the life course and etiology of mental disorders in terms of their developmental trajectory, course, and epidemiology?
• How can these new technologies be used to predict and prevent mental illness?
• How can these new technologies be used to achieve more efficient and effective diagnoses and treatments of mental illnesses?
• How can these new technologies be used to improve quality in mental health practice?
• How can these new technologies enable new questions to be asked, enable research to move more rapidly and to become more nimble?

Dr. Cuthbert thanked Patricia Areán, Ph.D., and Alan Leshner, Ph.D., for co-chairing the Workgroup. He reviewed the Workgroup roster and meeting schedule. The Workgroup plans to give an update to Council at the September 2016 meeting.

Dr. Cuthbert announced the formation of another Council Workgroup. This Workgroup arose from a recent RDoC concept clearance. The Workgroup is charged with developing a set of recommendations for a compilation of tasks and measures relevant to each of the RDoC constructs, and with developing a list of recommended measures for each construct that can serve as Common Data Elements for studies. Dr. Cuthbert thanked Deanna Barch, Ph.D., and Maria Oquendo, Ph.D., for co-chairing the Workgroup. He remarked that the efforts of the Workgroup will be important for data sharing and big data. Dr. Cuthbert asked for volunteers from Council and noted that Workgroup members will also be drawn from the research community. The Workgroup will address the following questions:

• How strong is the evidence that the task provides a valid measure of the RDoC construct?
• Can the task be used (or adapted for use) with children or other special populations?
• Does the task have good psychometric properties?
• Is the task currently in wide usage, or is its use limited to particular research groups?
• To what extent is the task (or differing versions) suitable for use across lab-based studies, clinical trials (as a measure of target engagement or clinical outcome), and high-throughput screening settings?

Dr. Cuthbert next briefly reviewed major scientific findings from NIMH-funded research. In the area of brain connectivity and behavior, scientists have found a clustering of connectivity in the sensory motor and attention regions as well as between the default mode and subcortical regions. Moreover, this connectivity was correlated with functioning on various measures (e.g., education, intelligence, etc.; see PMID: 26414616 ).

Research from the NIMH-funded Recovery After an Initial Schizophrenia Episode project indicates that patients have better outcomes with coordinated specialty care for first episode psychosis compared with usual care. Patients in the study typically had a duration of untreated psychosis of 74 weeks, which is the median in the United States. The research found that comprehensive care for first episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. The effects were more pronounced for those with a shorter duration of untreated psychosis (see PMID: 26481174 ).

The proposed Early Psychosis Intervention Network (EPINET) aims to establish a national learning health care network among early psychosis clinics and to standardize measures of clinical characteristics, interventions, and early psychosis outcomes. Other goals of EPINET are to adopt a unified informatics approach to study variations in treatment quality, clinical impact and value, and to cultivate a culture of collaborative research participation in academic and community early psychosis clinics. Dr. Cuthbert remarked that EPINET represents a significant strategic direction for NIMH and that the institute will invest resources in the network reflective of its promise.

A recent study elucidates a genetic mechanism of schizophrenia risk (see PMID: 26814963 ). Variants of the complement component 4 (C4) gene are important for pruning synapses during adolescence. The research found that excessive pruning related to this gene may confer risk for schizophrenia. These findings are consistent with those of research on the schizophrenia prodrome conducted in the North American Prodrome Longitudinal Study (NAPLS II). This research found a reduction in cortical thickness among people with active psychosis (see PMID: 23043872 . The NAPLS III project will test this hypothesis more rigorously. Additionally, other findings suggest psychosis biotypes related to cognitive control and sensorimotor reactivity. Researchers have found that the extent of gray matter loss varies by biotype (see PMID: 26651391 ). Dr. Cuthbert commented that this is exciting research and NIMH is looking forward to the results of follow-up studies in this area.

A recent study elucidates a genetic mechanism of schizophrenia risk (see PMID: 26814963 ). Variants of the complement component 4 (C4) gene are important for pruning synapses during adolescence. The research found that excessive pruning related to this gene may confer risk for schizophrenia. These findings are consistent with those of research on the schizophrenia prodrome conducted in the North American Prodrome Longitudinal Study (NAPLS II). This research found a reduction in cortical thickness among people with active psychosis (see PMID: 23043872 . The NAPLS III project will test this hypothesis more rigorously. Additionally, other findings suggest psychosis biotypes related to cognitive control and sensorimotor reactivity. Researchers have found that the extent of gray matter loss varies by biotype (see PMID: 26651391 ). Dr. Cuthbert commented that this is exciting research and NIMH is looking forward to the results of follow-up studies in this area.

Discussion

Tirin Moore, Ph.D., asked whether the NAPLS project collects measures related to biotypes. Dr. Cuthbert noted that this is a good question. Although the project probably does not collect biotype information specifically, it is harmonizing data with international prodrome efforts.

Rhonda Robinson Beale, M.D., asked whether private payers are involved in the RAISE expansion. Although the states and Medicaid are involved, with the Affordable Care Act, patients are seeking care in the private market. She inquired about the presence of a virtual quality tool so that learning can be passed to others across the country to teach providers about new treatments. Dr. Cuthbert responded that although few private payers are currently covering coordinated specialty care, interest in doing so will probably increase. Robert Heinssen, Ph.D., Director of the NIMH Division of Services and Interventions Research, remarked that the process is still unfolding. Early in the process, NIMH engaged the Centers for Medicare & Medicaid Services (CMS). CMS accepted the data as sufficient for support of coordinated care for schizophrenia through Medicaid. With that foundation in place, now is a good time to start conversations with private payers. The virtual component of EPINET will be driven by data analysis and feedback to clinics. An associated national organization of providers and scientists are interested in applying this research to improve the quality of care. Steven Adelsheim, M.D., of Stanford University leads that group, which will disseminate the information and create a knowledge network.

Marsha Linehan, Ph.D., wondered whether there is any research on patients who show brain patterns related to psychosis but do not display psychotic behaviors. Dr. Cuthbert commented that this question relates to the cognitive reserve hypothesis and that there are researchers examining interventions to prevent or delay the onset of psychosis. Dr. Heinssen added that bringing the data from this research together will allow scientists to address this question. Research from the Human Connectome Project  also points to neuroplasticity and the possibility that cognitive control and inhibition could be modulated among this population. Across several areas, the research on schizophrenia is promising.

Overview of the Division of Intramural Research Programs (IRP)

Susan Amara, Ph.D.
Scientific Director
IRP, NIMH

Dr. Amara commented that she was pleased to talk about IRP, which has undergone many changes during past few years. She briefly described the NIMH extramural and intramural research programs. The NIMH IRP comprises clinical and basic research programs housed on the NIH campus. IRP research spans many levels of analysis—from genes to cells and from systems to behavior. The IRP receives approximately 11 percent of NIMH’s budget, representing about $140 million in FY 2015, with 70 percent allocated to applied research and 30 percent to basic research. The IRP has 40 Principal Investigators, approximately 260 trainees at all levels, as well as 355 scientific, clinical, and administrative staff members. 

The NIMH IRP has unique capabilities to conduct high-risk, high-impact research with a longer time horizon than conventional grant cycles. IRP researchers can provide a rapid response to emerging needs—including pediatric disorders, autism, suicide in the military, diagnosis/biomarkers, and drug discovery. The Clinical Center is the world’s largest research hospital and has training programs for clinicians and scientists, which is critical to the IRP’s work. The IRP also houses major national resources—including tissue, cell, and gene repositories—as well as databases, tools, and techniques. The IRP has eight core facilities in the areas of neurophysiology imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, magnetoencephalography, scientific and statistical computing, transgenic research, instrumentation, and the NIMH human brain collection.

The goals for the IRP are to nurture the most creative science that uses cutting-edge, cross-disciplinary approaches to explore how genes, cells, circuits, and systems operate in the healthy brain and how they are altered in mental illnesses. The IRP also aims to address critical areas and gaps in basic and clinical research that would be hard to address without stable long-term funding. Other IRP goals include advancing common themes and coordinating mechanisms between clinical and basic research efforts, as well as ensuring that an outstanding and diverse group of young scientists and clinicians are inspired to continue to undertake high-risk, innovative research. Finally, the NIMH IRP aims to encourage collaborative science and the exchange of ideas by facilitating partnerships with researchers everywhere.  The work of the IRP is designed to complement, not duplicate, that of the NIMH extramural program. Naturally, the two programs should interact, for example, by sharing data and forming partnerships.

Dr. Amara highlighted new additions to the IRP faculty and briefly described their research programs. She also highlighted IRP faculty achievements. Zheng Li, Ph.D., has been awarded tenure, and Mortimer Mishkin, Ph.D., was awarded the 2016 award in Neurosciences by the National Academies of Science. Carlos Zarate, M.D., delivered the annual Astute Clinical Award Lecture, which is selected by the NIH Clinical Center, and Karen Berman, M.D., received the NIH Graduate Partnerships Program Outstanding Mentor Award. Dr. Amara also highlighted newsworthy IRP research and scientific advances.

Dr. Amara emphasized the IRP’s efforts to foster collaborative science and reviewed various mechanisms for intramural-extramural interactions (e.g., cooperative agreements, Lasker Scholar Awards). In FY 2015, each IRP faculty member had eight external collaborations, on average. The IRP’s clinical program has launched new efforts to address critical areas and gaps in clinical research—including the neurobiology of suicide, non-invasive neuromodulation, interventions for adolescent depression, and sleep/circadian rhythm regulation across the lifespan. To meet the challenges of training translational scientists, the IRP has initiated the “Labs to Life” monthly patient interviews. These interviews enable basic researchers to gain a deeper understanding of the heterogeneity of human mental illnesses. The IRP is actively training the next generation of clinician scientists, with eight current fellows and four new clinical fellows to start in July 2016. Dr. Amara reviewed aspects of IRP training, which is led by Janet Clark, Ph.D., and highlighted the array of professional development opportunities available. 

The IRP strives to enhance scientific synergy or convergence among its researchers. The NIMH IRP has formed committees in an effort to enhance scientific endeavors within the division. The Scientific Organization Committee’s goal is to evolve common themes and boarder collaborative efforts between research groups at the IRP. The purpose is to spark collaborations within the NIMH IRP and to increase interactions between basic and clinical researchers. Dr. Amara reviewed various activities designed to promote scientific convergence and noted that there are early signs of success (e.g., launching of a cross-species hub on irritability).

The goal of the Translational Neuropsychopharmacology Task Force, led by Dr. Clark, is to re-invigorate psychiatric drug discovery by facilitating the discovery of novel targets or development of repurposed compounds. This effort will enable the IRP to invest in projects that will have the highest probability of success (i.e., medications that make it to patients). Dr. Amara remarked that colleagues from industry are excited about this effort and have provided thoughtful input.

Dr. Amara commented that the IRP has developed various policies and plans concerning data sharing. It has shared this guidance—covering genomic, neuroimaging, and human data—with researchers at the IRP. The IRP’s data sharing policies also cover data repositories.

She highlighted the IRP’s accomplishments during 2015. In 2015, the IRP recruited six new Principal Investigators, reorganized lab structures and enhanced scientific synergies within the Program, and implemented new IRP genomic and human data sharing policies. The IRP also created a new NIMH core facility (rodent behavior), established a IRP Employee Advisory Committee, expanded training programs, and reinstated the Annual Fellows’ Scientific Training Day. Other accomplishments include establishing the NIMH IRP Translational Neuropsychopharmacology Task Force and creating a new Technology Transfer Office within NIMH.

Discussion

Benjamin Druss, M.D., M.P.H., remarked on the wide spectrum of research at the IRP and asked how the Division is addressing questions related to the social and individual levels of analyses. He also wondered about the IRP’s long-term investments. Dr. Amara responded that the IRP’s clinical program is committed to developing treatments and understanding the underpinnings of diseases. She asked Council for suggestions on including the social and individual levels of research in the IRP portfolio. Perhaps reviewing the IRP’s portfolio in greater detail with Council might point to opportunities to strengthen research on the social level, perhaps through collaboration.

Gene Robinson, Ph.D., asked whether there are parallel efforts to find scientific convergence between NIMH IRP researchers and those at other NIH institutes that address neuroscience. Dr. Amara noted that IRP recruitments are often combined across institutes. The institutes do communicate with each other, particularly since they moved into the Porter Neuroscience Research Center. It is possible for the NIMH IRP to build on the strength of other institutes, and the neuroscience clinical programs across institutes have a retreat to coordinate research and avoid duplicative efforts. Additionally, the IRP core facilities are joint efforts with other institutes.

John Krystal, M.D., remarked that the range of psychiatric disorders covered in the research portfolio seems fairly narrow. Dr. Amara commented that the IRP portfolio cannot cover all disorders and that a task force helps the Division evaluate its range of research. Strategic collaborations may be one way to help expand the range of psychiatric disorders covered. Mechanisms are in place for such collaborations, and the IRP has started the process of initiating these efforts.

Mary Jane Rotheram, Ph.D., commented on the IRP’s narrow focus, which has not traditionally included social and services research. She suggested that Council discuss the current burden of disease in the area of mental health so the group can determine the best way to address this level of research, including a possible role for the IRP. Dr. Areán added that this topic is not specific to the IRP, but is a general question about where social and services research fits into NIMH’s overall program. Dr. Cuthbert said he understood and noted that he would ask Council members how to frame discussion on this topic for a future NAMHC meeting. The discussion will be timely, as the institute is preparing a list of priorities for the new NIMH Director. Dr. Linehan suggested that NIMH reach out to universities and the mental health field to keep them apprised of the institute’s initiatives and opportunities for collaboration.

Global Mental Health Update

Pamela Collins, M.D., M.P.H.
Director, Office for Research on Disparities & Global Mental Health
Director, Office of Rural Mental Health Research
NIMH

Dr. Collins commented that NIMH’s Office for Research on Disparities and Global Mental Health addresses equity and disparities, women’s mental health, rural mental health, workforce diversity, and global mental health. She focused on global mental health efforts—including research, research capacity building, and outreach and collaboration—during the past 5 years. NIMH has supported international research for many years. Currently, the majority the global mental health portfolio represents awards to research projects with foreign components. Most of these projects are located in high-income countries and span a range of science. NIMH also makes extramural awards directly to foreign institutions, mostly in high-income countries. By FY 2014, NIMH had shifted more awards to low- and middle-income countries, some of whom were working with high-income countries.

To understand the global mental health context, one must acknowledge the overall shortage of outpatient mental health care in low-income countries. Psychiatric patients may have no place to go but jail. The problem is compounded by the mental health problems of refugees fleeing chaotic countries. Globally, there are only nine mental health workers per 100,000 people. Most mental health workers are concentrated in high-income countries, and the shortage in other nations will not improve without direct action. In sub-Saharan Africa, for example, experts estimate that an additional 216,600 mental health care providers will be needed by 2050. However, a shortage of mental health care providers is also a problem in many high-income countries—including the United States, which has more than 4,000 areas with a shortage of these clinicians. Low- and middle-income countries allocate very limited expenditures on mental health despite the fact that mental disorders are the leading causes of disability globally.

Research is integral to selecting ways to address these critical global mental health challenges. It is important to set an agenda and establish priorities for global mental health research, allocate resources and invest in research and research capacity building, and engage partners within and outside the research community with shared goals.

NIMH has set several directions to address global health disparities. By focusing on equity, NIMH addresses the treatment gap in low- and middle-income countries and learns lessons to address mental health care disparities in the United States. NIMH strives to anticipate and respond to global public health trends, including demographic and epidemiological transitions. It is also important to integrate mental health into global platforms of care to address the combined mental health and general health needs of people with mental illnesses. NIMH supports research capacity building in global mental health, which will bolster efforts to diversify the U.S. scientific workforce.

A commentary to engage the worldwide community in the grand challenges related to global mental health (see PMID: 21734685 ) identified multiple priorities for research that will make an impact on the lives of people living with mental, neurological, and substance use disorders. More than 400 people from 60 different countries are now engaged in this important endeavor. Dr. Collins focused on one of these goals: building human resource capacity. The challenge for this goal is to increase capacity in low- and middle-income countries by creating regional centers for mental health research, education, training, and practice that incorporate the views and needs of local people. To meet this goal, NIMH has established collaborative hubs for international research in mental health. Five global hubs conduct research on using providers with abbreviated training to extend the workforce (task sharing), building research capacity for a region, collaborating with end-users of the research, and networking the research to learn from the health system and contextual diversity. Examples of task sharing include using technology and nurse-supported care for depression, diabetes, and hypertension in Peru and Brazil, as well as training community health workers to manage maternal depression in South Africa.

This research has great potential to generate knowledge about extending mental health human resources. Trials to test these approaches are ongoing, but the research has already provided some important lessons. The hubs are integral to building research capacity, and there is an emerging network of scientists in the next generation of awardees. Dr. Collins reviewed the global mental health training paths for non-U.S. investigators in low- and middle-income countries, which are supported by NIMH and the Fogarty Center. NIMH is also engaging other funders—for example, Grand Challenges Canada and the Global Alliance for Chronic diseases, which involves multiple countries.

There has been an intensification of research in global mental health during the past 5 years, and NIMH aims to scale up effective approaches (RFA-MH-16-350 ). Policy actions and collaborative activities for reducing the treatment gap are helping to support the World Health Organization’s Mental Health Action Plan (2013-2020). It is a very active time in global mental health research. Advocates for global mental health research are using the evidence base to make the case for mental health investment at the World Bank, which is attending to this topic for first time.

Discussion

Dr. Robinson asked whether there are ways to compare and contrast effective approaches examined by global and domestic research programs. Dr. Collins agreed that innovations from low-income countries are ripe for implementation in low-resource contexts in the United States. Dr. Cuthbert thanked Dr. Collins for updating the group on this exciting area of research. 

Update on NIMH Clinical Trial Effort

Shelli Avenevoli, Ph.D.
Acting Deputy Director, NIMH 

Dr. Cuthbert explained that in 2014, NIMH launched a pilot project reflecting a new approach to funding clinical trials. This experimental therapeutics approach emphasizes engagement of a specific target. NIMH also set standards and criteria for proper monitoring, reporting, transparency, and efficiency in clinical trials. The institute also announced that it would not support clinical trials under the traditional R01 parent grant announcement. Rather, clinical trial applications must come in under very specific funding opportunity announcements. This approach has now been in effect for several funding cycles. Dr. Cuthbert introduced Dr. Avenevoli, Acting Deputy Director at NIMH, who shared lessons learned with the Council as well as future directions in the NIMH clinical trial efforts. He thanked Dr. Avenevoli for the superlative job she has done on this effort.

Dr. Avenevoli acknowledged colleagues who have helped with this effort. NIMH has a robust program for developing and testing interventions, but the institute revised its approach to maximize investments in this area. Based on the 2008 NIMH Strategic Plan, one of the institute’s strategic objectives is to develop new and better interventions that incorporate the diverse needs and circumstances of people with mental illnesses.

The mental health field is characterized by the therapeutic paradox in which there is increased treatment (as measured by epidemiology, prescriptions, and expense), but not a significant decrease in morbidity and mortality. Two reasons underlying the therapeutic paradox are: (1) current treatments are not effective enough to influence public health outcomes; and, (2) there are no new therapeutics (e.g., medications, devices, and psychosocial interventions).

After Council discussions on the interventions objective of the 2008 Strategic Plan, the NAMHC Workgroup report, From Discovery to Cure, laid the foundation for developing the next generation of interventions for mental disorders. The report especially focused on the need to develop interventions that are tailored to the individual and that prevent the damaging consequences of these illnesses. NIMH has shifted away from the traditional approach to intervention development and testing, in which researchers study the clinical effect of an intervention. The traditional approach has several problems. For example, failure to replicate a positive result in larger trials is costly. Additionally, it is difficult to determine the reason for negative results, and researchers gain a limited understanding about the mechanism underlying the disorder. Finally, the traditional approach is inconsistent with the Council Workgroup’s emphasis on personalized and pre-emptive interventions.

Based on these recommendations, NIMH took an experimental therapeutics approach, in which the intervention is used as a tool to validate or engage the target, which is then examined for its effect on clinical symptoms. The test of target engagement informs a “Go/No Go” decision whether to examine clinical effects. A fully powered and expensive test of efficacy is not pursued without target engagement and a preliminary signal of efficacy. This approach optimizes the value of clinical trials regardless of clinical outcomes. The results of early-stage trials provide initial signs of potential failure or success and help inform whether later-stage trials should be considered. A negative result suggests that attention should be focused on other, more promising targets. The selection of intervention doses is based on the adequacy of target engagement, and a careful selection of treatment groups enables testing of the intervention’s proposed mechanism of action in humans.

Targets exist at many different levels in the experimental therapeutic approach. Examples of targets include molecular entities proposed for pharmacologic agents; synaptic- and circuit-level regions or networks proposed for devices; cognitive, emotional, behavioral, or interpersonal processes and/or their underlying neural circuits for psychotherapeutic interventions; and consumer behavior, provider behavior, or system-level factors that can be modified to improve access, engagement, quality, or outcomes of treatments and services.

Upon developing this new approach to clinical trials, NIMH began advertising to let the field know about these changes. The institute conveyed its new approach to the field through updated strategic research priorities, Director’s Blogs, and by publishing new clinical trial Funding Opportunity Announcements (FOAs). New FOAs issued in early 2014 were mapped to the clinical pipeline. These FOAs replaced almost all other mechanisms for clinical trial funding at NIMH.

Dr. Avenevoli focused on preliminary data from 2015 regarding this new approach, as NIMH is still finalizing funding decisions for 2016. At this point, it is difficult to measure the impact of the institute’s new approach. However, NIMH has received applications consistent with the experimental therapeutics paradigm. Over cycles, the number of applications that had to be returned because they did not respond appropriately to the Request for Applications (RFA) has declined. As expected, there was a decrease in the number of applications, but the number of funded applications has been stable across three cycles. It is not yet possible to measure the impact of the new approach on the quality of applications.

NIMH staff members have reported their observations on applicant misperceptions. Misperceptions include that NIMH is not interested in funding clinical trials, is only interested in biological targets (not psychosocial interventions), and that there is no interest in optimizing current therapies. Other staff observations note that over time, applicants and reviewers better understand the paradigm. In addition, they noted that combining intervention modalities (e.g., drug and devises with psychosocial interventions) in a single RFA was confusing to applicants; and reviewers have difficulty assessing target and target engagement in psychosocial intervention studies. NIMH staff members wonder whether the institute is being overly prescriptive and whether there is a sufficient number of novel targets available for testing. Also of concern to staff is whether the institute is meeting immediate clinical needs for optimizing new therapies and whether NIMH is sufficiently integrating RDoC into its clinical trials. Moving forward, NIMH plans to maintain the experimental therapeutics approach, will consider developing separate drug/device and psychosocial intervention FOAs, and will consider companion FOAs to fill gaps. NIMH plans to improve communication and outreach in this area by providing webinars and conference presentations for applicants, and will strive to ensure a consistent understanding of the approach by reviewers.

Discussion

David Brent, M.D., remarked that RDoC could help identify viable and reliable targets for clinical trials. This would be particularly useful for new investigators. Dr. Barch thanked Dr. Avenevoli for the great summary. To help reduce the misperception that NIMH is not interested in developing and testing psychosocial interventions, the institute should present at large conferences to re-engage the field. Dr. Barch expressed concern that target development for psychosocial interventions (particularly for children) may be inhibited by the lack of a funding mechanism specifically for this purpose. Investigators need information on psychometrics and reliability related to targets for psychosocial interventions. This is a gap that NIMH needs to fill. David Sweatt, Ph.D., agreed and noted that Dr. Barch’s suggestion might help investigators interested in a target that is not identified on a standard list.

Dr. Areán remarked that studies to test services interventions can be difficult to do with the amount of money allocated by R34 grants. She suggested that NIMH have a well-resourced companion FOA for services development. Studies to test service interventions must be conducted in a region rather than a single clinic, and they require resources. Michael Hogan, Ph.D., added that the number of funded grants on services is not enough given the public health needs. He suggested that the institute think more broadly about how its research can address unmet public health needs. A bright spot is that actions to address suicide are beginning to take on a broader perspective.

Dr. Krystal wondered about the change in the number applications and funded grants after implementing the new approach. Dr. Avenevoli responded that the number of applications has decreased and asked the Council members to identify other appropriate metrics. The applications might be of a higher quality, but it is too early to determine. Dr. Krystal noted that the long-term goal is generating a new treatment, but that would take many years to determine.

Dr. Heinssen remarked that RAISE did not target the duration of untreated psychosis specifically. RAISE illustrates a particular type of study in which the assessment approach was dense enough to look at factors affecting the success of treatment and revealed a legitimate target for further public health efforts. RAISE was designed prior to NIMH’s shift to the experimental therapeutics approach. Results from RAISE suggest that, at the front end of the process, the experimental therapeutics approach has potential. The RAISE study illustrates the importance of optimizing treatment, enhancing practice standards, and improving the outcomes with available treatments. At the same time, it is important to develop new interventions and cures. Dr. Heinssen stressed the importance of getting the balance right and asked for Council members’ feedback on this issue.

Dr. Brent commented that there seems to be an imbalance at the moment. He wondered whether it would be possible to optimize available treatments within the experimental therapeutics approach or whether another mechanism was needed. It is critical to improve available treatments. Dr. Cuthbert clarified that NIMH does make an exception to the experimental therapeutics approach if researchers are examining specific modifiers for current treatments or the effect of the therapy in a particular subgroup; the institute will accept such applications. Prior to adopting the experimental therapeutics approach, NIMH had many applications that were adaptations of current treatments, representing small extensions rather than transformative research.

Dr. Robinson Beale applauded NIMH for its efforts in experimental therapeutics, as it is a difficult task. She suggested that the institute consider the scope of topics studied in clinical trials and the depth of answers. That knowledge must be translated into practice so payers can cover the intervention. Interventions must be reproducible so payers know they are effective. Researchers should also identify the effective dosage, frequency, and duration of the intervention’s effect. These are all critical pieces for payment, not only by insurance companies but also by Accountable Care Organizations.

Dr. Krystal agreed that NIMH should not focus on incremental studies. He remarked that other NIH Institutes are also likely considering ways to advance and optimize clinical trials. Perhaps current funding mechanisms are not encouraging novel treatments. He asked about the limiting factors for good clinical trials. Perhaps NIMH could map out resources and determine where investment might help advance the development of novel treatments.

Dr. Linehan commented that she supports the new approach to clinical trials at NIMH. Researchers want to develop a treatment, but they sometimes do not specify the problem solved by the intervention. Dr. Linehan also remarked that many are concerned about the cost of treatments for mental disorders. This criticism may not be made about other areas of medicine. Society must balance the cost of not treating people over the long term with the cost of intervention.

Dr. Rotheram remarked that little innovation has occurred in treatment development. Huge data sets—for example, from insurance companies or the U.S. Department of Veterans Affairs—might help advance treatment development. In the past, data from economists has been helpful, as huge samples enable the examination of relationships. She suggested that NIMH consider partnerships to make these datasets available and establish funding mechanisms for data analysis. Dr. Robinson Beale agreed and noted that partnerships are starting to form to answer these questions. She added that some databases are limited to claims information data and, in general, the data require more standardization on diagnosis, treatment rendered, and other factors. She also noted that, while these databases should be made available, a great deal of work is required for this to happen. Many states have data exchanges so they can pool data, but these efforts are in the early stages and concerns about access, privacy, purposes of data use, and other issues must be addressed. Nevertheless, there is movement in this area. Hyong Un, M.D., remarked that the quality of these datasets is improving. Insurance companies have both claims and provider-generated data, which helps create more useful datasets. However, corporate entities and academic institutions have different cultures, which present a challenge to these efforts. NIMH will need to address the funding mechanism for researchers and the business case for insurance companies.

Dr. Sweatt commented that Dr. Avenevoli’s presentation has crystallized the immediate key decisions that need to be made. Dr. Sweatt suggested that it may be helpful to address practical issues by holding a workshop with researchers who have, and have not, been funded to conduct clinical trials. Issues uncovered by such a workshop might help set the institute’s direction in this area for new NIMH Director.

Big Data to Knowledge (BD2K) Multi-Council Working Group Update

Gene Robinson, Ph.D.
University of Illinois at Urbana-Champaign

Dr. Robinson focused on the human resources and training aspects of BD2K . Existing programs address various audiences of all types of biomedical scientists. The goal is to provide training opportunities at all levels—from undergraduate to senior faculty—so individuals can work with big data. The BD2K initiative has proposed new training programs for FY 2017 to consolidate and fill gaps, including open educational resources and short courses. These programs will help scientists who are already trained and will promote data science, a new area of science within biomedicine. A collective aim of the BD2K initiative is to create data scientists.

At the September NAMHC meeting, Dr. Sweatt suggested that the BD2K initiative engage scientists in analyzing existing datasets. BD2K Centers of Excellence are one way to do this, as these 11 facilities provide resources to scientists across the country. Dr. Robinson added that online resources on big data are available to researchers. Large databases are coming to the fore at NIH. Members of the BD2K Workgroup are examining potential funding models to use in the future.

Discussion

Dr. Sweatt commented that the BD2K focus on the big data workforce pipeline is appropriate, as experts in this area are rare and in great demand. Dr. Amara added that providing established scientists with training so they can conduct research with big data will enhance the rigor of experimental approaches.

Dr. Robinson noted that institutes have not always tracked the types of data available and that data is often in different formats; the data landscape is complex. David Van Essen, Ph.D., remarked that it is challenging to make a database that is useful to neuroscience. Putting data in one place is not sufficient, and he emphasized the importance of training experts in big data who can be integrated into laboratories and other scientific contexts.

Greg Farber, Ph.D., who leads NIMH informatics, noted that the Institute has been at the forefront of aggregating human subject’s data at NIH. At this point, all researchers who conduct human subject’s studies are expected to deposit the data into a designated archive. This archive is linked with other relevant databases (e.g., Connectome. Large datasets with information from more than 100,000 subjects are available. It can be challenging to search through the data collection instruments used by researchers to determine individual questions and measures. NIMH is looking for help to improve this, and Dr. Farber said he would be happy to report more fully to Council about the data available in the NIH archive and in other data repositories.

Dr. Cuthbert commented that for many years, NIH’s policies have required investigators to include a data sharing plan in their applications, but did not necessarily require them to share the data. Dr. Farber led the way in transforming the NIMH culture toward data sharing. NIMH’s approach to data sharing has been collaborative and aimed at helping investigators archive their data in a clean and standardized way. This effort has required NIMH resources; and has helped investigators in the long run. Data sharing has required a shift in how NIH thinks about the human subject’s research enterprise. Each subject represents a great investment, so institutes need to consider this and maximize their use of the data.

Edwin (Ted) Abel, Ph.D., suggested that NIMH consider metrics for investigator productivity and success related to data sharing. Researchers tend to not share their data because publication is the metric of professional success. There needs to be a way to include sharing as part of the promotion process. Dr. Farber noted that NIH has considered the professional credit and promotion system and is working to modify it. One mechanism would be to give credit to the researchers who collected the data each time it is used. This can be achieved by linking an investigator identifier to his or her dataset, which is not technically difficult and could be in place in a couple of years.

Public Comment

Dr. Cuthbert invited members of the audience to make any comments to the Council. Florence C. Fee, J.D., Founder and Executive Director of No Health Without Mental Health, a nonprofit organization that focuses on the integration of medical and behavioral health care, noted that most people with behavioral health issues present in primary care. Moreover, many patients with severe mental illness visit primary care settings. She remarked that the Federal government is interested in chronic medical conditions, comorbidities, and health care costs and outcomes. There is a great need for integration of care and attention to chronic conditions. Identifying and treating patients with behavioral health conditions in primary care can reduce the number of complex patients with comorbid conditions seeking care at community mental health clinics. This issue is receiving attention in Congress. Ms. Fee asked whether NIMH could serve as a convener to summarize the lessons learned about the best models for integrating primary care and behavioral health. As the field needs guidance on integrated care delivery models, it would be helpful to gather researchers and clinicians to discuss this issue. Such a discussion would also be helpful to patient advocacy organizations.

Dr. Cuthbert commented that the integration of primary care and behavioral health is an important issue that can affect health and health care costs. Dr. Hogan added that there is a good deal of information available on integration, but it is not often applied. This issue is salient, as many people with behavioral health conditions have moved into mainstream health plans, and there have been changes in payment. The environment is dynamic, so this is a great opportunity to discuss the issue. Paolo del Vecchio, M.S.W., remarked that the U.S. Preventive Services Task Force  recently made recommendations on screening for depression in primary care, which presents an opportunity for integrating behavioral health into this setting. Dr. Cuthbert thanked participants for their comments and added that NIMH will discuss this issue.

Hearing no further comments from the public, Dr. Cuthbert adjourned the meeting at approximately 1:00 p.m.

Appendix A

Summary of Primary MH Applications Reviewed

February 2016

Category	IRG Recommendation
	Scored #	Scored Direct Cost $	Not Scored (NRFC) #	Not Scored (NRFC) Direct Cost $	Other #	Other Direct Cost $	Total #	Total Direct Cost $
Research	571	$769,670,240.00	395	$471,462,356.00	10	$4,594,356.00	976	$1,245,726,952.00
Research Training	23	$37,135,704.00	12	$18,940,590.00	0	$0.00	35	$56,076,294.00
Career	65	$45,389,628.00	36	$26,501,375.00	0	$0.00	101	$71,891,003.00
Other	1	$998,000.00	0	$0.00	0	$0.00	1	$998,000.00
Totals	660	$853,193,572.00	443	$516,904,321.00	10	$4,594,356.00	1113	$1,374,692,249.00

Appendix B

Department of Health and Human Services
National Institutes of Health
National Institute of Mental Health
National Advisory Mental Health Council

(Terms end 9/30 of designated year)

Chairperson

• Bruce N. Cuthbert, Ph.D.
  Acting Director
  National Institute of Mental Health
  Bethesda, MD

Executive Secretary

• Jean Noronha, Ph.D.
  Director
  Division of Extramural Activities
  National Institute of Mental Health
  Bethesda, MD

Members

• Patricia A. Areán, Ph.D. (16)
  Professor
  Director of Targeted Treatment Development
  University of Washington
  Department of Psychiatry and Behavioral Sciences
  Seattle, WA
• Deanna M. Barch, Ph.D. (16)
  Gregory B. Couch Professor of Psychiatry
  Department of Psychology, Psychiatry and Radiology
  Washington University
  St. Louis, MO
• David A. Brent, M.D. (17)
  Academic Chief
  Child & Adolescent Psychiatry
  Endowed Chair in Suicide Studies
  Professor of Psychiatry, Pediatrics and Epidemiology
  Director, Services for Teens at Risk
  University of Pittsburgh School of Medicine
  Pittsburgh, PA
• BJ Casey, Ph.D. (16)
  Sackler Professor
  Department of Psychiatry and Neuroscience
  Sackler Institute for Developmental Psychobiology
  Weill Medical College of Cornell University
  New York, NY
• Benjamin G. Druss, M.D., M.P.H. (18)
  Rosalynn Carter Chair in Mental Health and Professor
  Department of Health Policy and Management
  Rollins School of Public Health
  Emory University
  Atlanta, GA
• Hakon Heimer, M.S. (16)
  Founding Editor
  Schizophrenia Research Forum
  Brain and Behavior Research Foundation
  Providence, RI
• Michael F. Hogan, Ph.D. (18)
  Consultant and Advisor
  Hogan Health Solutions LLC
  Delmar, NY
• Richard L. Huganir, Ph.D. (17)
  Professor and Director
  Department of Neuroscience
  Investigator, Howard Hughes Medical Institute
  Co-Director, Brain Science Institute
  The Johns Hopkins University School of Medicine
  Baltimore, MD
• John H. Krystal, M.D. (19)
  Robert L. McNeil, Jr. Professor of Translational Research
  Chair, Professor of Neurobiology
  Chief of Psychiatry, Yale-New Haven Hospital
  Department of Psychiatry
  Yale University School of Medicine
  New Haven, CT
• Marsha M. Linehan, Ph.D. (17)
  Professor and Director
  Behavioral Research and Therapy Clinics
  Department of Psychology
  University of Washington
  Seattle, WA
• Maria A. Oquendo, M.D. (17)
  Vice Chair for Education
  Professor of Psychiatry
  Department of Psychiatry
  Columbia University
  New York State Psychiatric Institute
  New York, NY
• Gene E. Robinson, Ph.D. (16)
  Director, Institute for Genomic Biology
  Swanlund Chair
  Center for Advanced Study Professor in Entomology And Neuroscience
  University of Illinois at Urbana-Champaign
  Urbana, IL
• Rhonda Robinson Beale, M.D. (19)
  Senior Vice President and Chief Medical Officer
  Blue Cross of Idaho
  Meridian, ID
• Mary Jane Rotheram, Ph.D. (16)
  Bat-Yaacov Professor of Child Psychiatry And Behavioral Sciences
  Director, Global Center for Children and Families
  Director, Center for HIV Identification Prevention And Treatment Services (CHIPTS)
  Semel Institute and the Department of Psychiatry, University of California, Los Angeles
  Los Angeles, CA
• J. David Sweatt, Ph.D. (16)
  Professor
  Evelyn F. McKnight Endowed Chair
  Department of Neurobiology
  Director, McKnight Brain Institute
  University of Alabama at Birmingham
  Birmingham, AL
• Hyong Un, M.D. (17)
  Head of EAP & Chief Psychiatric Officer
  AETNA
  Blue Bell, PA
• Christopher A. Walsh, M.D. (19)
  Chief, Division of Genetics and Genomics
  Boston Children’s Hospital
  Bullard Professor of Pediatrics and Neurology
  Harvard Medical School
  Boston, MA

Ex Officio Members

Office of the Secretary, DHHS

• Sylvia M. Burwell
  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

Department of Veterans Affairs

• Theresa Gleason, Ph.D.
  Deputy, Chief Research & Development Officer
  Office of Research & Development
  Department of Veterans Affairs
  Washington DC

Department of Defense

• John W. Davison, M.B.A., Ph.D.
  Chief, Conditioned-Based Specialty Care Section
  Clinical Support Division
  Defense Health Agency
  Department of Defense
  Office of the Chief Medical Officer (OCMO)
  TRICARE Management Activity, OASD (HA)
  Falls Church, VA

Liaison Representative

• Paolo del Vecchio, M.S.W.
  Director
  Center for Mental Health Services
  Rockville, MD