Forum on Neuroscience and Nervous System Disorders: 2013 Annual Report (2014)

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BOARD ON HEALTH SCIENCES POLICY Forum on Neuroscience and Nervous System Disorders 2013 Annual Report 

About the Neuroscience Forum The Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders was established in 2006 to bring together government, industry, academia, patient advocacy orga- nizations, and other interested parties. The Forum meets three times per year and provides its members with a structured, neutral venue for exchanging information, ideas, and differing points of view. At its meetings, the Forum examines significant—and some- times contentious—issues concerning science, priority setting, and policy related to neuroscience research, nervous system disorders, and the development, regulation, and clinical use of interventions for the nervous system. Based on such discussions, the Forum sponsors workshops (symposia), workshop summaries, and com- missioned papers as an additional mechanism for informing its membership, other stakeholders, and the public about emerging issues and matters deserving scrutiny. Information about past and upcoming meetings is available at the Forum’s website, www.iom. edu/neuroforum. Cover Image Credits Left: Greg Hood, John Burkardt, and Greg Foss, Pittsburgh Supercomputing Center Right: Paul Thompson and Arthur Toga, UCLA 

Message from the Chair The IOM Forum on Neuroscience and Nervous System Disorders brings together the private sector; federal agencies that serve as research sponsors and regulators; the nonprofit sector, including foundations and groups focused on nervous system disease; and the academic community to consider shared approaches to pressing issues. Through its meetings and public workshops, the Forum provides a venue for its members, other neuroscience leaders, government officials, and members of the public to have rich and candid discussions about issues of mutual interest. In 2013, discussions included diverse topics such as challenges associated with providing evidence-based psychosocial treatments to patients in need; opportunities based on emerging neuroscience technologies to speed potential treatments into first-in- human trials; mechanisms to standardize data analysis in diffusion magnetic reso- nance imaging (dMRI) to enhance its potential for research and clinical use; and opportunities created by the federal BRAIN Initiative. Looking ahead to 2014, the Forum plans an array of activities on topics such as • S  trategies for strengthening the connections between basic neuroscientists and translational researchers working on diagnostics and therapeutics; • R  egulatory trends and opportunities to increase private-sector investment in central nervous system (CNS) research and development; • I mproving access to essential medicines for mental, neurological, and substance use disorders in sub-Saharan Africa; • E  xamining current practices for training scientists and identifying opportunities for improving training programs in the neurosciences; and • O  pportunities to improve the research community’s access to large basic datasets. I look forward to another productive year for the Forum. Steve Hyman Chair 

Reflecting Back Forum Activities in 2013 Accelerating Therapeutic Development for Nervous System Disorders Toward First-in-Human Trials Although there is a high burden associated with nervous system disorders, development of new therapeutics remains stagnant. Current data suggest that a high percentage of drugs intended for nervous system disorders fail in clini- cal trials. Moreover, for drugs that are eventually marketed, development, from the start of a discovery program to regulatory approval, can take an average of 12 to 15 years. Among the obstacles to successful drug discovery and devel- opment are the limitations of current animal models. The Forum hosted a workshop to examine opportunities to accelerate early phases of drug devel- opment for nervous system disorders. Participants discussed approaches to using animal models more effectively, emerging uses of in vitro technolo- gies for therapeutics research using human cells reprogrammed into neu- rons, and how to enable faster entry of potential treatments into first-in- human trials. The workshop explored how new and emerging tools, technol- ogies, and techniques may improve the efficiency of research and considered mechanisms to facilitate a more effective and efficient development pipeline. NEURO FORUM TIMELINE 2006 2007 2006 Oct 4–5 2007 1st meeting 

Reflecting Back: Forum Activities in 2013 Developing Standards for Diffusion Magnetic Resonance Imaging There is strong interest across many organizations to make faster progress in detecting and monitoring progression of brain injuries, neurodevelopmen- tal disorders, and neurodegenerative diseases. Although the use of diffusion magnetic resonance imaging (dMRI) tools offers great promise, its utility has been held back by a lack of shared standards and clinical validation. Multiple platforms with little, or no, ability to compare results makes it challenging to incorporate dMRI into basic studies of disease and clinical trials. Given the pressing need for better tools, the Forum, together with experts in the field and key stakeholders from both public and private groups, discussed oppor- tunities for developing standards for dMRI that would advance the field without slowing innovation. Feb 27 Apr 18 2nd meeting Autism & Environment Workshop Feb 26 Jul 30–31 Oct 24–25 2008 Biomarkers Workshop 3rd meeting 4th meeting 

Looking Forward Forum Activities in 2014 Managing and Sharing Large Basic Research Datasets Neuroscience and allied areas of science are generating ever larger, richer, and more complex datasets. There is tremendous potential for these datasets to improve understanding of the nervous system and the biology of disease and to aid in the development of therapeutics. Data collected from imaging, genomics, and circuitry all highlight the opportunities that might arise from greater understanding and sharing of basic data. However, infrastructure and policies have not been firmly established to ensure successful management, sharing, and sustainability of data- bases within the global neuroscience community. The Forum will host an activity to address challenges and examine potential opportunities that would facilitate better management and greater sharing of large basic research datasets. Improving Access to Essential Medicines for Mental, Neurological, and Substance Use Disorders in Sub-Saharan Africa Sub-Saharan Africa (SSA) has one of the world’s largest treatment gaps for mental, neurological, and substance use (MNS) disorders, causing a substantial burden for the continent’s population. Improving access to essential medicines has been identi- fied as a critical component of reducing the treatment gap for MNS disorders. In an effort to achieve reliable, sustainable access to essential medicines, the Forum will host a meeting that will bring together key stakeholders to discuss opportunities for providing access to essential medicines for MNS disorders. Specifically, participants will examine successful models in a variety of disease areas and in low- and middle- income countries outside SSA. Because of the complex and multifaceted nature of this topic, the meeting will also focus on determining the specific steps and partner- ships needed to make drugs accessible. Jun 25 Molecules to Mind: Oct 15–16 Grand Challenges Workshop 7th meeting 2008 2009 2008 Jan 30 Jun 24 Oct 3 2 5th meeting 6th meeting Venture Philanthropy Strategies Workshop 

Looking Forward: Forum Activities in 2014 Non-Invasive Devices for the Treatment of Nervous System Disorders Based on advances in biotechnology and neuroscience, and given the interest of the federal BRAIN Initiative, non-invasive neuromodulation devices are poised to gain clinical importance in coming years and to be of increasing interest to industry. Emerging evidence suggests that the potential uses of neuromodulation are broad and might expand beyond move- ment disorders, depression, obsessive-compulsive disorder, epilepsy, and pain to an array of additional conditions, includ- ing memory loss, rehabilita- tion after stroke, addictive dis- orders, and others. However, along with opportunities, there are challenges, including ques- tions of risk-benefit for invasive devices and ethical questions which extend to the possibility of enhancement (e.g., of mood states or memory) in individuals who are not impaired at baseline. The Forum will host a series of activities to examine opportunities and risks and discuss appropriate regulatory regimes and the concerns of both developers and payers. Aug 4–5 Nov 9 Feb 25 Jun 17 Sub-Saharan Africa Animal Law 8th meeting 9th meeting Workshop Workshop 2009 Jun 16 Nov 3 Suicidality Workshop 10th meeting 

Training the Next Generation of Neuroscientists From its very beginnings, neuroscience has been fundamentally interdisciplinary. As a result of rapid technological advances and the advent of large collaborative projects, however, neuroscience is expanding well beyond its traditional subdisciplines and intel- lectual boundaries to include more engineering, computer science, and applied math- ematics. Revolutionary tools, such as optogenetics and genome engineering tools like CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are quickly being incorporated into the work of some labs. However, the importance and rapid prolifera- tion of mission-critical technologies raises important questions about how to train the next generation of neuroscientists, not only to use particular tools, but to be prepared for a changing technological landscape. In addition, the advent of new types of data and the growing important of large datasets raise additional questions about how to train the next Jun 17 Jun 22 Jul 12 9th meeting Glutamate Workshop ADNI-2 Workshop 2010 2011 2010 Mar 8–9 Jun 23 Dec 10 2011 Sex Differences Workshop 11th meeting 12th meeting 

Looking Forward: Forum Activities in 2014 generation in approaches to data standardization and sharing and proper analysis. These concerns dovetail with the need to teach improved scientific practices rang- ing from experimental design (powering of studies, appropriate blinding) to greater sophistication in statistics. Given the changing landscape resulting from techno- logical advance and the growing importance of interdisciplinary and collaborative science, the Forum will host a workshop to explore future workforce needs and consider the needs of training programs. Current and new components of training programs will be discussed in order to identify methods for enhancing data han- dling and analysis capabilities, increasing scientific rigor, and improving research practices. Finally, the roles of mentors, mentees, training program administrators and funders in the development and execution of revised training programs for new and current researchers will be explored. Mar 2–3 Jul 26–27 Neuroscience and the Law Workshop Animal Regulations Workshop 2012 Feb 2 Jul 18 Aug 10 Nov 30 2012 13th meeting AAIC 2011 Session 14th meeting 15th meeting 

Working Groups The Forum has created a series of working groups to provide an opportunity for subsets of the broader group to work together on selected topics. Workshop topics often result from these groups and are organized by an independently appointed workshop planning committee. Mental Health, Neurological, and Substance Use Disorders in Sub-Saharan Africa In collaboration with the World Health Organization’s mental health Gap Action Programme, the Forum is continuing to explore additional opportunities to build on its 2009 Mental Health and Neurological Disorders in Sub-Saharan Africa workshop. The working group is focused on identifying innovative solutions to enhance care for MNS disorders in SSA. Special attention is being paid to finding solutions to increase human and financial resources to support current and future efforts. Translational Neuroscience The translational neuroscience working group was established to identify areas of synergy where public- and private-sector stakeholders can work together to improve the efficiency and effectiveness of drug discovery and development for neurological and mental disor- ders. The group is currently addressing barriers to repurposing and reusing existing com- pounds. In addition, the working group is discussing strategies to increase communication and information sharing among pharmaceutical and diagnostic developers and academic researchers. The aim of such communication is to inform researchers about how they can contribute to partnerships in a meaningful way, with the goal of improving the neuroscience translational therapeutic development pipeline. Mar 28 Jul 11 Sep 4–5 Nov 28 Mar 5 16th meeting 17th meeting SSA Workshop 18th meeting 19th meeting 2013 Mar 28–29 May 10–11 Oct 4–5 Animal Models Workshop Neurodegeneration Workshop Sharing Clinical Research Data Workshop 

Working Groups Enabling Neuroscience Research and Development The Forum is establishing a working group that will explore potential financial incentives that could spur additional investment from the private sector in translational neuroscience research and development. To begin this effort, the Forum expects to commission a paper that will perform a financial analysis of two or three incentives that could lead to significant reinvestment by large pharmaceutical companies in CNS disorders. This analysis would include the cost to society and how much it would cost payers if a therapeutic drug were delayed from transitioning to a generic. Apr 8–9 Aug 22 Jan 13-14 Accelerating Therapeutic Meeting on Developing SSA Essential Development Workshop dMRI Standards Medicines Workshop 2014 Dec 2 Feb 18 20th meeting 21st meeting 

2013 Publications Improving the Utility and Neurodegeneration: Translation of Animal Exploring Commonalities Models for Nervous Across Diseases – System Disorders – Workshop Summary Workshop Summary June 17 Oct 28 22nd meeting 23rd meeting 2012 Nov 15 Meeting on Dry AMD 

Sharing Clinical Strengthening Human Resources Through Research Data – Development of Candidate Core Competencies Workshop Summary for Mental, Neurological, and Substance Use Disorders in Sub-Saharan Africa – Workshop Summary 

Forum Members (as of December 2013) Steven Hyman (Chair) Thomas Insel Joanne Tornow Broad Institute of the Massachusetts National Institute of Mental Health National Science Foundation Institute of Technology and Harvard Phillip Iredale Nora Volkow Susan Amara Pfizer, Global Research and National Institute on Drug Abuse Society for Neuroscience Development Kenneth Warren Mark Bear Daniel Javitt National Institute on Alcohol Abuse Massachusetts Institute of Columbia University and Alcoholism Technology Frances Jensen David Wholley Katja Brose University of Pennsylvania Health Foundation for the National Institutes Cell Press System of Health Daniel Burch Story Landis John Williams Pharmaceutical Product National Institute of Neurological Wellcome Trust Development, Inc. Disorders and Stroke Stevin Zorn Maria Carrillo Alan Leshner Lundbeck USA Alzheimer’s Association American Association for the Charles Zorumski Advancement of Science C. Thomas Caskey Washington University School of Baylor College of Medicine Husseini Manji Medicine Johnson & Johnson Pharmaceuticals Timothy Coetzee FastForward of the National Multiple David Michelson Sclerosis Society Merck Research Laboratories Emmeline Edwards Richard Mohs IOM Staff Bruce Altevogt, Ph.D. National Center for Complementary Eli Lilly and Company Project Director and Alternative Medicine Jonathan Moreno Martha Farah University of Pennsylvania School of Diana Pankevich, Ph.D. University of Pennsylvania Medicine Program Officer Daniel Geschwind Atul Pande Sheena Posey Norris, M.S. University of California, Los Angeles GlaxoSmithKline Research Associate Hank Greely Steven Paul Rachel Kirkland, M.A. Stanford University Weill Cornell Medical College Senior Program Assistant Magali Haas Todd Sherer Andrew M. Pope, Ph.D. One Mind for Research The Michael J. Fox Foundation for Director, IOM Board on Health Parkinson’s Research Sciences Policy Richard Hodes National Institute on Aging Paul Sieving National Eye Institute Stuart Hoffman Department of Veteran Affairs 

Sponsors Forum Members and Sponsorship (as of December 2013) Financial support for the Forum is derived from federal agencies, patient advocacy organizations, industry, and a nonprofit membership society. Alzheimer’s Association Department of Veterans Affairs Nonprofit Foundation for the National Institutes of Health GlaxoSmithKline 11% Johnson & Johnson Pharmaceuticals Lilly Research Laboratories Lundbeck USA Federal Merck Research Laboratories 53% The Michael J. Fox Foundation for Parkinson’s Research 36% National Eye Institute Industry National Institute on Aging National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse National Institute of Mental Health National Institute of Neurological Disorders and Stroke National Institutes of Health Blueprint for Neuroscience Research National Multiple Sclerosis Society National Science Foundation One Mind for Research Pharmaceutical Product Development, Inc. Pfizer, Global Research and Development Society for Neuroscience Wellcome Trust 

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